|Year : 2014 | Volume
| Issue : 6 | Page : 5-16
|Date of Web Publication||29-Oct-2014|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Awards. J Can Res Ther 2014;10, Suppl S2:5-16
A prospective, randomized trial showing impact of neoadjuvant chemotherapy on downstaging tumours, comparing anthracycline based versus taxane based regime in locally advanced carcinoma breast in female
MBBS, MD PGT, Department of Radiotherapy, R. G. Kar Medical College and Hospital 1, Khudiram Bose Sarani , Kolkata - 700004, West Bengal, India
Introduction: Locally Advanced Breast Cancer (LABC) (AJCC TNM stage group IIIA, IIIB, IIIC) is associated with high risk for distant relapse compared to earlier-stage cancers, despite modern multimodality therapy. Neoadjuvant chemotherapy (NACT) plays an important role in downstaging initially unresectable tumours to operable disease. Although, anthracycline remains the cornerstone for NACT in LABC, the efficacy of non anthracycline based regimes in this setting have seldom been studied. We therefore designed this study to compare taxane based (non-anthracycline) versus anthracycline based CT in LABC with special emphasis on tumour downstaging. Aims and Objectives: To compare the efficacy of two chemotherapy regimens (anthracycline based vs. taxane based) on tumour downstaging in LABC. Material and Methods: In this prospective, randomized, single-institutional, crossover phase II study, between Jan 2013 to Mar 2014, 60 patients of biopsy proven LABC without any evidence of distant metastasis and with normal baseline haematological, biochemical and cardiological parameters (LVEF ≥ 50%) and ECOG PS 0-1 were randomised into two arms (30 in each arm) by computer generated random number sequencing to receive either Inj Doxorubicin (60mg/m 2 ) and Inj Cyclophosphamide (600mg/m 2 ) (Arm A; AC; Control) or Inj Paclitaxel (175 mg/m 2 ) and Inj Cyclophosphamide (600mg/m 2 ) (Arm B; PC; Study) every 3 weeks for 3 cycles. After completion of 3 cycles of NACT response and toxicity were assessed clinically and radiologically and the patients having CR or PR were sent for MRM. After MRM patients were treated by three more cycles of adjuvant chemotherapy with patients on AC arm receiving PC and vice versa (crossover design). Adjuvant External Beam Radiotherapy (50 Gy/25 #/5 weeks) and/or adjuvant endocrine therapy were administered if indicated. Results: 60 patients were analysed to compare the response to NACT. The baseline characteristics were comparable in both the arms and median age of the patients were 47.5 yrs, 45% patients were premenopausal and 56.67% were ER (+). Tumour downstaging after NACT was similar in between the two arms with ycCR 13.3% vs. 10%; P = 0.687; PR 76.7% vs. 66.67%; P = 0.573; SD 6.67% vs. 10% P = 0.640; and PD 6.67% vs. 13.33% P = 0.389; in Arm A and Arm B respectively. There was also no significant difference in ypCR between the two arms (16.67% vs. 10% in Arm A and Arm B, P = 0.448). Significantly more haematological toxicities were in Arm A (74.67% total; 16.67% Grade 3) (P = 0.004) and neuropathy in Arm B (83.3% total; 16% Grade 3) (P = 0.017). Conclusion: Although this study suffers from low sample size and short follow up, it demonstrates that non anthracycline based NACT can be a viable alternative option in patients with LABC.
Clinico-morphological profile and receptor status in breast cancer patients in a South Indian institution
GSL Medical College and General Hospital
Background: Breast cancer is the most common malignancy in women worldwide and the second most common cancer in women in India. Hence, clinico-morphological parameters and receptor status in breast cancer patients were studied in a South Indian institute. Objective: To analyse and correlate the clinical and morphological parameters with receptor status in breast carcinoma patients in a tertiary care institution in Southern India. Materials and Methods: This is a retrospective study done among 320 patients of breast cancer diagnosed in an oncology hospital over a period of 3 years. Statistical Analysis: Data was analysed by using SPSS Version 21. Results: In our study, 60.6% patients of breast carcinoma belonged to the age group of 40 to 60 years. Most common histological type of breast cancer was infiltrating ductal carcinoma, not otherwise specified, consisting of 84.4% patients. On immunohistochemistry, estrogen receptor (ER) and progesterone receptor (PR) were expressed in 56.25% and 53.1% of our patients respectively. Conclusion: Breast cancers in developing countriesoccur in younger women and tend to be more aggressive with lower rates of ER and PR expression and higher histological tumor grades. Both ER and PR status of the tumors had a significant association with the age of the patient, pathological TNM stage and histological tumor grade.
Hypofractionated Radiotherapy in postoperative breast carcinoma patients-a hit and run regimen
2 nd year PG resident, Mahatma Gandhi Memorial Medical College, Indore, Madhya Pradesh. E-mail: firstname.lastname@example.org
Introduction: Hypofractionation has long been the common practice in countries such as the UK and Canada, where a lower total dose using fewer, larger fractions (hypofractionation) is often used. Data are now available from hypofractionated trials in breast cancer that a smaller number of fractions could offer similar rates of tumor control and normal tissue damage as the standard fractionation schedule of 50Gy in 25 fractions. Aims and Objectives: 1) To analyse the efficacy, safety, benefits of hypofractionated radiotherapy 2) To study tolerance of patients, response and complications 3) to analyse local recurrence and distant metastases. Materials and Methods: Retrospective study of '50' patients with operated breast cancer who received 17#x270cGy RT at GCH, Indore, between October 2012 to October 2013. Results: The locoregional relapse was 6%. 22% patients developed metastatic disease. Gr I/II skin toxicities in 8%. Lymphedema in 8%. No cardiac toxicity and 6% GrI/II pulmonary toxicity. 28% of GrI/II pain. Conclusion: Hypofractionated RT schedule has good locoregional disease control and toxicity profile when compared to conventional RT regimen. Further hypofractionated RT schedule helps in reducing workload and therefore can be safely recommended for routine clinical use.
Can we predict molecular subtypes of medulloblastoma based on MRI? Encouraging data from a blinded study
Archya Dasgupta, Tejpal Gupta, Sona Pungavkar, Amit Janu,
Neelam Shirsat, Girish Chinnaswamy, Rakesh Jalali
Department of Radiation Oncology and Medical Physics, Tata Memorial Centre, Mumbai
Background: Recent investigations on medulloblastoma has revealed at least 4 different subgroups with diverse clinical, demographic profiles rendering better insight in understanding the heterogenous entity of the disease. Aims and objectives: The study deals with the radiogenomics as an attempt of unifying the molecular subgrouping obtained from biological material with the radiological features obtained through the MRI scans of the patients. Methods and Materials: After obtaining the IEC approval the pre-operative scans of 35 patients were collected with due consent or assent. Interpretation was done on a set of 22 prefixed radiological parameters based on our previous experience and few other recent studies Molecular subgrouping into either of the four groups- WNT, SHH, group 3 or group 4 was done based on miRNA profiling of a set of 9 genes. The scans were discussed in the institutional joint meeting of neuro-oncology group comprising of specialists from each of neuroradiology, radiation oncology, neurosurgery, pediatric oncology, who were blinded to the results regarding the molecular groups. Based on the features studied and our previous experience a provisional diagnosis was given predicting the molecular subgroups. In cases of controversy, a second probable diagnosis was also noted. Statistical analysis was done using IBM SPSS software (V20). Pearson's chi square test was used for finding the correlation between the variables and the molecular groups. Cohen's kappa test was used to find out the agreement for prediction. Results: Patients ranged from 2 years to 36 year (mean-13 years) and 22 of 30 were male. RT-PCR based miRNA profiling revealed 6 patients to be in WNT, 12 in SHH, 5 in group 3 and 7 in group 4 molecular subtypes. Radiological assessment analysis revealed 75% of SHH tumors to have lateralized location with less propensity for involving dorsal brainstem. Presence of perifocal edema and a trend for higher association with macrocyst was also highrer in SHH. Features suggestive of WNT subtype were midline location or involvement of C-P angle, homogenous contrast enhancement in more than 80% areas and presence of intratumoral hemorrhage. All group 3/group 4 tumors had midline position and higher chances for epicentre of the tumor being located inferiorly (NS). Group 3 tumors were showing heterogenous patchy contrast enhancement whereas calcification was a significant finding for group 4 tumors. Cross tab analysis revealed four distinct radiological features, viz horizontal tumor location (P-0.001), involvement of dorsal brainstem (P-0.032), perifocal edema (P-0.02), intratumoral calcification (p-0.002) significantly predictors of accurate molecular subtype. A separate analysis was done for WNT, SHH and combining the group 3/group 4 tumors, as per recent international norms. Three more features in the form of pattern of contrast enhancement (P-0.05), T2W homogeneity (P-0.027) and intratumoral hemorrhage (P-0.017) were found to be significantly predictive, as well. Overall, the prediction was correct for 20/30 (66%) taking 2 nd prediction into account with kappa correlation coefficient for agreement being 0.43 (moderate agreement). Conclusion: We have demonstrated significant correlation between sets of certain radiological parameters with the molecular subgroups in medulloblastoma, which can have important implications in our clinical practice. These features need to be confirmed in the ongoing study and in an independent cohort of patients.
Epworth Sleepiness Scale- a novel tool to assess somnolence syndrome post radiotherapy to brain.
Ritika Harjani*, Janaki M. G.*, Uma Maheshwari#, Ram C. Alva*,
Arul Ponni T. R.*, Kirthi Koushik T. S.*, Mohankumar S.*
*Department of Radiotherapy, #Department of Chest Medicine, M S Ramaiah Medical College, Bangalore
Introduction: Radiation to brain causes early, early-delayed and delayed side effects. 1 Although early and delayed effects are well studied, there is paucity of literature regarding early-delayed effects like somnolence syndrome. The existing studies use general symptom assessment and visual analog scales. 2 Epworth Sleepiness Scale is a time tested tool to assess daytime sleepiness in various conditions. 3 This study is an attempt to determine the presence of somnolence in our patients using this novel scale. It is a simple questionnaire and we expect this will be able to grade the severity of somnolence. This is the first study to our knowledge to determine post radiation somnolence using Epworth Sleepiness Scale. Objective: To study the incidence of somnolence syndrome in patients receiving radiotherapy to brain. Materials and methods: 23 patients with primary brain tumor or metastases to brain were the subjects of the study. Patient demographics and tumor type- primary or metastatic along with grade was noted. Patients with Karnofsky performance status less than 70 and those with pre-existing sleep disorders were excluded from the study. Patients were treated with palliative whole brain radiation for brain metastases and conformal adjuvant radiotherapy for primary brain tumors as per standard guidelines. Patients were subjected to Epworth Sleepiness Scale3 at baseline, thereafter every week during radiation; also continuing weekly after cessation of radiation until 6 weeks post treatment. Results: All 23 patients (median age 50 years) completed the planned questionnaires until 6 weeks post radiation. 20 had primary brain tumors whereas 3 had metastatic lesions in brain. Of the 23 patients, 14 patients (60.86%) had abnormal or increased daytime sleepiness; of which 3 had ESS scores greater than 16. Conclusion: Somnolence occurred in 60.86% of the patients who underwent radiation treatment for brain tumors, which is in accordance with existing literature. 4,5 Epworth Sleepiness Scale is an effective tool to detect and quantify somnolence, however it does not consider other symptoms of somnolence syndrome and hence should be combined with visual analog scale to get complete information.
Efficacy and tolerability of alternate weekly regimen of temozolomide concurrent and adjuvant to radiotherapy in high grade glioma
Richa Tiwari, Pramod K. P. R., Lokesh V., Naveen T., Siddanna P., Sridhar P.
3 rd year MDRT student at Kidwai memorial institute of oncology in Bangalore. E-mail: email@example.com
Introduction: One hurdle to successful treatment of high grade glioma is resistance to alkylating agents. The cytotoxic activity of temozolomide is by forming O6 methylguanine DNA adducts. Consequently, the mechanism of resistance to this drug is repair of these adducts by DNA repair enzyme MGMT (O6 methyl guanine methyl transferase) which fortunately is a one action enzyme. So, theoretically, it is possible to overcome resistance by overwhelming MGMT enzyme by increasing the rate of DNA alkylation more than formation of DNA adducts. This study explores the alternate dosing regimen of temozolomide to provide optimum antitumor activity with acceptable toxicity. Materials and Method: 31 Histologically proven GBM and grade 3 astrocytoma post maximal safe resection were recruited and treated with conformal radiotherapy 60Gy/30fr with concurrent and adjuvant temozolomide 150mg/m2 week on and week off. Toxicity was recorded in accordance with CTCAE version 4.0 and radiological response evaluated at 1, 3, 6 mnth and 1yr and 6 monthly thereafter using Macdonald's and RANO (radiological assessment in neuro oncology) criteria. Results: Total 31 patients -GBM- 51.61%(16pts), AA- 25.8% (8 pts), OA- 22.58%(7pts) were recruited. CTCAE Grade 3,4 hematoxicity manifesting as thrombocytopenia 6.4% (2 pts) and lymphopenia was observed in 9.6% (3pts). Mean follow up was 12.35months. Progression free survival observed was 80.64% (GBM- 68%, AA-76%, OA- 100%). MGMT promoter methylation in tumor tissue subset analysis revealed 51.6%(16) pts to have methylated MGMT and 48.28%(15) unmethylated MGMT gene and 1yr progression free survival in methylated gene was 84.48% and in unmethylated gene carriers 76.8%. Conclusion: This study demonstrates that alternating weekly high dose regimen of temozolomide given concomitant and adjuvant to radiotherapy in high grade glioma is safe and effective and shows promising results even in patients with tumor lacking promoter methylation. Though, larger randomized studies are needed to verify the same.
Dosimetric analysis of external beam radiotherapy plus HDR brachytherapy boost vs. external beam radiotherapy alone (IMRT) in intermediate and high risk prostate cancer: Early results of biologically equivalent dose-volume parameters from a randomized control trial
Manikandan A., Laviraj M. A., Haresh K. P., Sharma D. N., Gupta S., Mallick S., Julka P. K., Rath G. K.
Department of Radiation Oncology, AIIMS, New Delhi, India, E-mail: firstname.lastname@example.org
Introduction: Radical radiation with neo adjuvant, concurrent and adjuvant hormonal therapy is considered the standard for intermediate and high risk prostate. The radiation can be delivered with Intensity modulated radiotherapy (IMRT) alone or in combination with brachytherapy. Aims and objectives: In this prospective randomized study we compared dose conformity between two modalities HDR Brachytherapy and IMRT to deliver a boost to the prostate after External beam Radiotherapy (EBRT). Materials and Method: Patients with localized adeno carcinoma of prostate were randomized to receive either IMRT alone or IMRT plus brachytherapy. After randomization all patients received EBRT 45Gy/25#/5 weeks by IMRT in phase I. In phase II patients received either HDR brachytherapy 19Gy/2# (Arm A) or EBRT 29Gy/15#/3 weeks (Arm B). In phase II EQD2-DVH parameters were calculated for comparison. EQD2 calculated with a prostate a/b ratio of 1.5 and 3 Gy and a/b ratio of 3Gy for organ at risks. The IMRT planning was done in ADAC Pinnacle version 8.0M and treated with Synergy S. The brachytherapy was planned in Oncentra-brachy version 4.3. Results: We randomized 12 patients to Arm A and Arm B. The median age of the cohort was 68.9 years (Range 60-78). The stage distribution was T2b-T3b. Median Gleason 7 (Range 6-8), Median PSA 32.7ng/ml (Range 4.8-92.3). The median prostate volume was 45.8cc (27.1-60.9). All patients received 45Gy/25#/5 weeks in phase I by IMRT. The HDR BT delivered higher mean doses to PTV compared with IMRT plan. In phase II, the mean EQD2 of 95% of the prostate volume was 48.6Gy in HDR BT whereas 27.2Gy in IMRT. The EQD2 of 33% of rectal volume received mean dose of 6.5Gy and Dmean of rectum was 6.8 Gy with HDR BT. In comparison doses delivered with IMRT were 18.1Gy and 12Gy respectively. EQD2 of Dmean to bladder in HDR BT and IMRT were 4.1Gy and 13.5Gy respectively. Conclusion: HDR BT produced more conformal plan for the boost to the prostate. With brachytherapy the doses to the OAR are lower than IMRT. Dose escalation for prostate tumors is easily achievable with brachytherapy than with IMRT alone. Therefore, brachytherapy might be the preferred modality to achieve further dose escalation.
BOOST PHASE Arm A Arm B
EQD2 for 95% of PTV (a/b: 1.5Gy) 48.6Gy 27.2Gy
EQD2 for DMEAN to PTV (a/b: 1.5Gy) 47.5Gy 29.5Gy
EQD2 for 95% of PTV (a/b: 3Gy) 39.1Gy 27.5Gy
EQD2 for DMEAN to PTV (a/b: 3Gy) 38.3Gy 29.6Gy
EQD2 for DMEAN to Rectum 6.8Gy 12Gy
EQD2 for 33% of Rectum 6.5Gy 18.1Gy
EQD2 for DMEAN to Bladder 4.1Gy 13.5Gy
EQD2 for 50% of Bladder 2.9Gy 12.6Gy
EQD2 for 1cc of Bladder 15.5Gy 30Gy
To compare the effect of bone marrow sparing intensity modulated radiotherapy (BMS-IMRT) vs non bone marrow sparing intensity modulated radiotherapy (NBMS-IMRT) on acute hematological parameters in carcinoma prostate: A randomized study
Introduction: Pelvic radiotherapy (RT) is associated with significant dose to active bone marrow and subsequent hematological toxicity (HT). Fall in hemoglobin can be also contributed by androgen deprivation therapy in addition to radiation. Anemia may have a negative impact on outcome as shown in some studies, although it is not conclusively proven in prostate cancer. IMRT, which is the standard of care for delivering radical RT doses to prostate, can be further optimized to decrease dose to pelvic marrow. This may translate into lesser decline in hemoglobin and better clinical outcome. Aims and Objectives: To compare the effect of bone marrow sparing intensity modulated radiotherapy (BMS-IMRT) on volume of bone marrow irradiated and its effect on acute hematological parameters in carcinoma prostate in a randomized study. Methods and Materials: 17 patients of carcinoma prostate planned for radical radiotherapy were prospectively analysed. They were randomly allocated to group A comprising of BMS-IMRT and group B comprising of non-BMS IMRT. An extra dose constraint for bone marrow was planned in group A. All patients received neo-adjuvant androgen-deprivation therapy followed by radical radiotherapy with IMRT. All patients underwent weekly hemogram during treatment to assess for effects of radiation on hematological parameters including hemoglobin (Hb), total leucocyte counts (TLC), platelets (Plt). Volume of pelvic marrow receiving 5, 10, 20, 30 and ≥ 40 Gy (V5, V10, V20, V30, and V40 respectively) was calculated. Acute HT was graded as per the Radiation Therapy Oncology Group system. Means of various hematological parameters were compared at baseline and at weekly intervals between the two groups. Results: There was a significant reduction in volume of marrow irradiated at doses of 30-40 Gy. There was no statistical difference between means of Hb, TLC and platelets at baseline in the two groups. Group A had significantly higher mean platelets and TLCs during RT. There was no significant difference between grade of acute HT or Hb levels during RT between the two groups. Conclusions: There was significant difference in V30 and V40 with BMS-IMRT. This neither translated into lesser grades of acute HT nor lesser decline in hemoglobin with BMS-IMRT. However there was significant difference between mean platelet levels and mean TLCs during various weeks of radiotherapy. Larger studies are required to evaluate the impact of reducing bone marrow doses on hematological parameters, especially hemoglobin in carcinoma prostate. Its relevance in terms of clinical outcome in Indian scenario also needs to be studied.
Comparison of dose-volume parameters, tumor response and toxicity in two different schedules of 3D-image based high-dose rate intracavitary brachytherapy using cobalt-60 source in the treatment of locally advanced carcinoma of cervix
R.G. Kar Medical College & Hospital, Kolkata. E-mail: email@example.com
Introduction: There is no established time, dose, fractionation schedule in High dose rate (HDR)-Intracavitary Brachytherapy (ICBT) for the treatment of locally advanced carcinoma cervix 1. At our institution these patients are treated with 3 weekly fractions of 7Gy (7Gyx 3#) HDR-ICBT schedule abiding the recommendation of American Brachytherapy Society. Studies based on X-ray based point dosimetry have shown that 2 weekly fractions of 9Gy (9Gyx 2#) HDR-ICBT is safe and effective in terms of local control and toxicity and of particular importance in cost-constraint setting.Clinical feasibility of HDR-ICBT using 60Co has been shown previously4. Here, we report a prospective randomized clinical trial comparing dose- volume (DVH) parameters tumor response and toxicity in 7 Gyx 3# versus 9 Gyx 2# using CT based 3D treatment planning using 60Co HDR remote afterloading device. Aims and Objective: Comparison of DVH parameters, tumor response and and toxicity between the two arms. Materials and Methods: Between January 2013 to March 2014, 60 eligible locally advanced cervical carcinoma patients were randomized into two arms (30 in each arm) to receive either 7Gyx 3# (Control: Arm A) or 9Gyx 2# (Study: Arm B) after completion of EBRT (50.4Gy/28 fractions in 5.3 weeks) with concurrent weekly cisplatin. During brachytherapy CT scan based contouring and plan optimization was done using 3D treatment planning software. DVH parameters of target i.e. High risk clinical target volume (HRCTV), Intermediate risk clinical target volume (IRCTV) and organ at risk (OAR) i.e. bladder, rectum and sigmoid colon were assessed. Equivalent dose in 2Gray/fraction (EQD2) was calculated summing EBRT and all ICBT doses (considering a/b of tumor and OARs are 10 and 3 respectively). Patients were followed up for tumor response and toxicity. RTOG criteria were used for toxicity scoring. Results: EQD2 D90HRCTV in Arm A (93.99 14.19Gy) and Arm B (100.42 13.75Gy) were comparable (P = 0.108). EQD2 D90IRCTV in Arm A and B are 70.36 8.23Gy and 67.49 5.96 Gy respectively (P = 0.16).EQD2 D2cc bladder was 83.48 9.63Gy and Arm B was 79.50 5.96Gy (P = 0.077). EQD2 D2cc rectum in Arm A was 63.15 4.75Gy and Arm B was 62.56 4.72Gy (P = 0.661).EQD2 D2cc sigmoid colon in Arm A was 67.05 5.13Gy and in Arm B was 65.15 5.81Gy (P = 0.228). Median follow up time in Arm A was 10 months (range 6 to 18 months) and in Arm B was 11 months (range 5 to 15 onths).Complete response (CR) at last follow up in two arms (Arm A vs. Arm B) was 82.6% vs. 85.7%, partial response (PR) was 8.7% vs. 10.7%, stable disease was 4.3% vs. 0% and progressive disease was 4.3% vs. 3.6%. No grade 3 acute hematological, gastrointestinal, skin or genitourinary toxicity was observed in either arm. Late grade 2 proctitis/proctosigmoiditis was 4.3% in Arm A and 10.7% in Arm B (P = 0.617). No late bladder toxicity was noted in either arm. Conclusion: In spite of the small sample size and short follow up duration the study shows that 9Gyx 2# is equivalent to 7Gyx 3# of HDR-ICBT in terms of DVH parameters, tumor response and toxicity using 60Co HDR source.
An interindividual comparison of prone and supine positioning for radiotherapy in patients with cancer cervix.
Suchandana Bhaumik, Lokesh Vishwanath, K. P. Jagannath,
Uday Krishna A. S., Shwetha B. and Sathian
Kidwai Memorial Institute of Oncology, Bangalore.
Introduction: Pelvic irradiation in cervical cancers is associated with both acute and chronic gastrointestinal and genitourinary toxicities.The volume of small bowel, bladder and rectum and the radiation dose are the main factors behind this. Due to the mobility of the small intestine, a variety of noninvasive techniques manoeuvring the small bowel out of the field have been reported. The prone position with the Belly Board Device provides an easy, economical, comfortable and non-invasive gravity oriented technique. Also distended bladder helps in sparing bowel volume by pushing it away from the high dose region in the pelvis. Availability of facility for virtual simulation and 3D planning system allows proper quantification of volume of normal tissue irradiated and clinical correlation with the acute toxicities seen during the course of radiotherapy in prone or supine patient position. Aims and Objective: To study the anticipated quantitative reduction in small bowel irradiated in prone or supine position during pelvic radiotherapy. Materials and Method: In twenty histologically proven carcinoma cervix patients (stage II - IIIB) scheduled for definitive external beam radiotherapy of the pelvis, treatment planning CT scans were performed in supine and prone (belly board) positions. Patients were randomly allocated to two arms one being treated in prone and the other in supine position in linear accelerator along with concurrent weekly CDDP @ 40 mg/m2 followed by HDR brachytherapy. After volume delineation of target and organs at risk, treatment plans were calculated applying the four-field box technique. The dose-volume histograms of organs at risk were compared. Patients were assessed weekly with clinical examinations during the treatment for acute and subacute toxicities of skin, bladder and bowel using RTOG/CTC criteria and also at the end of first, second, th ird and sixth month. Results: The average small bowel volume in the treatment volume was 215cc (+/-112.8cc) in supine position and 129.3cc (+/-97.7cc) in prone position (P < 0.002). The volume of small bowel in the radiotherapy field was significantly reduced in prone position. Conclusion: Treatment of cervical cancer patients in the prone position using a bellyboard reduces the volume of irradiated small bowel. Therefore for pelvic radiotherapy in patients with cervical malignancy, prone position with belly board device should be used.
Comparision of local control and rectal toxicity in carcinoma cervix stage III using x-ray based vs mri based hdr brachytherapy
Background: Cervical cancers accounts for about 20% cancer cases among females in India and 60-80% present with locally advanced disease. Concurrent radiation therapy with chemotherapy is the mainstay for advanced diseases. Brachytherapy is the integral component of radical radiotherapy and the pelvic controls rates and complications (acute and late) of radical radiotherapy to a large extent depend on dose delivered by brachytherapy. Aim: To compare the local control in carcinoma cervix stage III using conventional X-Ray based brachytherapy (2D) and MRI based brachytherapy (3D). This study also intends to assess the rectal toxicity in both groups. Methods: 30 patients with carcinoma cervix stage III were included in study with 15 patients in each group. All patients were treated with definitive radiotherapy with cisplatin chemotherapy. Patients in 3D group were treated with brachytherapy as per GEC ESTRO guidelines. Median age was 53 years. Total prescribed dose was 75-80 Gy (total biologically equivalent dose in 2 Gy fractions). The response to treatment and toxicity was assessed clinically after 1, 3, and 5 months of treatment. Rectal toxicity was graded as per LENT SOMA scoring system. Results: Out of 30 patients, only 28 patients were available for the analysis, 2 patients were defaulted after EBRT. The complete remission was achieved in 96% (26/28 patients). Local control rates were 85.6% in 3D group and 78.6% in 2D group. Grade II rectal toxicity was only 6.7% in each group i.e. 2/28 patients (one in each group) seen over a period of 10 months in 2D group and 12 months in 3D group. Compared to 2D group, 3D group showed an increase in local control rates without any statistical significance. Conclusion: MRI guided brachytherapy in locally advanced cervical cancers shows promising results in future as a better tool for escalating dose so as to achieve a better local control rates and reduced toxicity rates. However, it is practicable with minimal logistic issues.
Nab-paclitaxel in recurrent ovarian cancer: An institutional based retrospective study
Vamsi Raj Kota
Indira Gandhi Institute of Medical Sciences
Background: Nab-paclitaxel is a novel Cremophor free nanoparticle of albumin-stabilized paclitaxel. We evaluated the efficacy and toxicity of the nab-paclitaxel in recurrent ovarian cancer patients. Methods: 17 patients of recurrent epithelial ovarian cancer with platinum and taxane resistance defined by persistent or progressive disease following recurrence within six months of treatment completion and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) or elevated CA-125 (≥70 U/mL) in patients without measurable disease. Patients treated with nab-paclitaxel between Jan 2012 to Mar 2014, dose of 260 mg/m2 administered intravenously for 30 minutes on day 1 of a 21-day cycle for six cycles or until disease progression. Results: Median age of patients was 62 years; 76% of patients had stage IIIC or IV disease, 82% had Eastern Cooperative Oncology Group performance status of 0, and 88% had prior surgery. For assessable patients, the objective response rate (ORR) was 58% (6 complete responses [CR] and 4 partial responses [PR] among 17 assessable patients). In patients evaluated with RECIST only, the ORR was 44.4% (one CR and three PR of 9 patients). In patients with only elevated CA-125, ORR was 75% (5 CRs and 1 PRs of 8 patients). Median time to response was 1.3 months (range 0.5 to 4.8 months). Estimated median progression-free survival was 8.5 months. The most frequent grade 3 to 4 treatment-related toxicities were neutropenia (35%) and neuropathy (11%). Conclusion: Nab-paclitaxel as a single agent in patients with recurrent epithelial ovarian cancer seems to be well tolerated and effective in patients who are previously treated with paclitaxel or platins.
Role of HDR Brachytherapy using MUPIT (Martinez Universal Perineal Interstitial Template) in locally advanced gynaecological malignancies
Rahul Misra, Dimpal, U. Suryanarayana, Ankita Parekh, R. K. Vyas, GCRI, Ahmedabad
Introduction: Gynaecological cancers are among the most common cancers affecting females in developing countries like India. Majority of patients come in advanced stages which are treated largely by external beam radiotherapy followed by brachytherapy in form of central vaginal cylinder or intracavitary brachytherapy which has advantage of optimal dose distribution to the volume of interest without jeopardizing the tolerance of normal structures (i.e. bladder and rectum) and compliance of patients. But those cases with extensive pelvic and vaginal diseases which are expected to get suboptimal dose distribution by ICR should be considered for interstitial brachytherapy. Material and Methods: Between Jun2011 and June 2013, a total of 71 patients with histologically confirmed cases of either locally advanced or recurrent malignancies of cervix (11), vault (54) and vagina (6) were treated by a combination of external beam radiotherapy using megavoltage irradiation to pelvis upto 40 to 50 Gy followed by Interstitial Brachytherapy using MUPIT with a dose of 16-24 Gy in 4-6 fractions. Patients were treated with 400cGy/fraction with two fractions a day at a minimum gap interval of 6 hours on microHDR. Results: In this study, 71 patients of locally advanced gynaecological cancers were studied retrospectively. Among these 7 patients were lost to follow-up, they were excluded from the study. The age of the patients ranged from 34-65 yrs. At 6 months, 46 patients (71.8%) had complete local control, 10 patients (15.6%) had partial response and 8 patients (12.5%) had no response. overall complication rate were 9.3% Conclusion: Intracavitary brachytherapy has known to be the most efficient form of brachytherapy but when performed with accurate technique Interstitial Brachytherapy using MUPIT has better dose distribution for larger tumour volumes with good local control rate and acceptable complication rate.
Management of early stage Endometrial Cancer, single institute experience
Purpose: Endometrial cancer is second most common gynaecological cancers in developed countries. Its incidence in India is about 10.5 per 100,000 women with an overall 5 year survival for all stages are around 80%. This study retrospectively analysed clinicopathological factors contributing to the disease control, local recurrence and overall survival in patients diagnosed to have endometrial cancer. Methods: Patients diagnosed to have carcinoma Endometrium from 2009 to 2013 were retrospectively analysed and clinical data collected. A total number of 55 patients were included in the study. The details of the surgery, histopathological findings of the surgical specimen, external beam radiation therapy and Brachytherapy details were noted. The data was analysed using SPSS software. Results: A total of 55 patients were included in the study. Among them 43% of the patients were found to have age more than 60yrs. All patients underwent total abdominal hysterectomy. 76% of the patients had adequate lymph node staging during surgery while the rest didn't. 49% of the patients were found to have grade I well differentiated adenocarcinoma, while 30.9% of the patients had grade II or moderately differentiated and 5.4% of the patients had grade III or poorly differentiated cancer. 27% of the patients had less than half the myometrium involved while 50.9% of the patients had more than half the myometrium involved. Cervical stromal involvement was found to be in 20% of the patients. 25% of the patients had presence of lymph vascular space invasion. Majority of the patients were diagnosed to have stage IB followed by stage IA and followed by stage II. 50% of the patients received radiation therapy with EBRT and 80% of the patients received mould Brachytherapy. Till the time of analysis only 1 patient had local recurrence and died and 2 patients developed distant metastasis giving an overall survival rate of 98%. Conclusions: Early endometrial cancer has an overall good response as evident from the study; however consensus regarding the optimum management in this group is yet to arrive. The treatment is mostly risk adaptive. Adjuvant radiotherapy is justified after assessing the risk factors like grade of the tumor, percentage of myometrial involvement and age more than sixty years.
Head and Neck
Impact of Molecular Profiling on the Response Rates in Head and Neck cancer Patients - An Observational Study
Arvind S., Kirthi Koushik A. S., Mangala Gowri*, Janaki M. G., Arul Ponni T. R., Ram Charith Alva
Department of Radiation Oncology, M.S.Ramaiah Medical College, Bangalore. *Department of Pathology, M.S.Ramaiah Medical College, Bangalore. E-mail: firstname.lastname@example.org
Introduction: Squamous cell carcinoma of head and neck region account for more than 25% of male and more than 10% of female cancers in India (1). Head and neck cancer treatment includes a multidisciplinary approach involving all specialties. Concurrent chemo-radiation is the standard of care in most of the subsites (2). Inspite of the multi-disciplinary approach, a plateau has been reached in terms of results with 5 year survival of locally advanced disease of around 30%(3). In order to improve outcomes, there has been considerable interest in molecular profiling of head and neck cancers (4-10). However there is still significant paucity in terms of Indian data, hence the need for the study. Objectives: •To Assess the HPV-p16, EGFR and p53 status
•To Correlate HPV-p16, EGFR and p53 status with the response rates
•To Correlate HPV-p16, EGFR and p53 status with other factors like age, sex, tobacco use.
Methods and Materials: 25 consecutive cases of histopathologically proven head and neck cancers were accrued. All patients were treated with external radiation to a dose of 66Gy in 33 fractions along with concurrent weekly cisplatin chemotherapy at a dose of 40mg/sqm. HPV-p16, EGFR and p53 mutation analysis was done on paraffin embedded histopathological blocks.PCR technique used for HPV-p16, EGFR and p53 status detection. Response assessment was done based on RECIST Criteria. Correlation of HPV, EGFR and p53 status on Response was done.
Results: •Mean Age of the study population: 59 years
- Sex: 76% Male and 24% Female
- Stage: I-8%, II-4%, III-36%, IV-52%
- Tobacco Use: 92% were tobacco consumers either in the smoke or smokeless form and 8% were non-tobacco users
- The EGFR positivity rate was 84%
- The p53 positivity rate was 76%
- The HPV p-16 positivity rate was 28%
- Out of 25 patients, 13 (52%) had Complete Response, 7 (28%) had Partial Response, 3 (12%) had Stable Disease and 2 (8%) had Progressive Disease.
- On correlation of molecular profile with response, there was no statistical significance between EGFR status and response (P 0.5) or HPV-p16 and response (P 0.8).However, p53 positivity was significantly associated with good response (P 0.03)
- Among other factors there was significant correlation between smoking and HPV status (P 0.01). However there was no significant correlation between other factors like age, sex and socio-economic status.
Conclusion: The HPV, EGFR and p53 positivity rates were in concordance with hitherto published literature. The HPV and EGFR did not have significant impact on response rate however p53 positivity was associated with higher percentage of complete response rate which was statistically significant.
Patterns of failure after intensity modulated radiotherapy for nasopharyngeal cancer
Avinash Pilar, Sarbani Ghosh Laskar, JaiPrakash Agarwal, Ashwini Budrukkar, Tejpal Gupta, Vedang Murthy
Purpose: To evaluate the patterns of failure, clinical outcomes and factors affecting these outcomes in patients of nasopharyngeal cancer (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods and Materials: One hundred and thirteen patients of non- metastatic NPC treated radically with IMRT between 2008 -2013 were included in the study. All patients had been treated with 7-9 field LA-based IMRT/tomotherapy. Prescribed dose was 66Gy/30# to high risk PTV (primary and involved lymph node regions with margins) and 54Gy/30# was delivered to the uninvolved neck. One hundred and four patients (92%) completed the planned radiotherapy. One hundred and eleven patients (98%) received concurrent chemoradiotherapy. Hundred patients (88%) also received Neoadjuvant chemotherapy prior to chemo- radiation. Results: The median age was 46 years (range: 18-85yrs). Undifferentiated Carcinoma was the most common histology (95%). Seventy nine percent patients were in stage III/IV. At a median follow-up (FU) of 27 months (range: 6-78months), 86 patients were alive at last FU. The 3 year local (LC) and regional control (RC) rates were 86% and 85%, respectively. Freedom from distant metastases (DMFS), progression-free survival (PFS), and overall survival (OS) at 3 years were 81%, 65%, and 87%, respectively. The LC for Stage I/II disease was 91%, compared to 84% for III/IV disease (P = 0.23). RC for stage II disease was 100% while for stage III/IV it was 81% (P = 0.035). Estimated 3 year OS for stage I/II was 96% and stage III/IV was 87% (P = 0.31). Nodal stage had a significant impact on DMFS, early nodal stage (N0-N2) had 3 year DMFS of 84% as compared to N3 which had 3 year DMFS of 69%. (P = 0.04). Nodal stage also had a significant impact on RC with early stage (N0-N1) having a 3 year RC of 97.6% v/s 77% for N2-N3. (P = 0.009). Nodal stage influenced PFS with 3 year estimate being 75% for N0-N1 and 57% for N2-N3 disease. (P = 0.03). T stage influenced only the DMFS with T1-T3 showing a 86% 3 year DMFS while T4 had a 63%, 3 year DMFS. Age, gender and endemicity had no influence on the LC, RC, DMFS or OS. There were 35 failures of which 3 (8.5%) were at primary site alone, 6 (17%) were nodal failures, 8 (23%) failed both at primary and nodal sites and 18 patients (51.5%) had distant metastases. Median time to failure was 4 months (Range 0-38months). All the primary and nodal failures were inside the high dose region (66Gy/30#) with exception of 1 patient (failed at edge of high dose volume). 9 of the 35 patients who failed were effectively salvaged (n = 4 solitary distant metastases, n = 5 nodal recurrences) and remain controlled at last FU. Conclusions: IMRT results in high locoregional control in NPC. The predominant site of locoregional failure is within the high dose region. Despite a good locoregional control, distant failure remains a common problem and is influenced by nodal stage.
A comparative study of hypofractionated versus conventional radiotherapy in terms of toxicities and treatment outcome in early stage glottic cancer
Monidipa Mondal, Arnab Adhikary, Shyamal Kumar Sarkar
Radiotherapy Dept, Medical College, Kolkata. E-mail:email@example.com
Introduction: Radiotherapy is the treatment of choice in early stage glottis cancer because it provides excellent local control rate along with a good preservation of the voice. A range of radiation fractionation schedules exists for the treatment of early glottic cancer. Several studies have shown that hypofractionated radiotherapy with short overall treatment time provides better local control and survival than conventional radiotherapy. In our institution, both of the radiation fractionation schedules are practised. We therefore conducted a comparative retrospective analysis of the two fractionation schedules. Aims and Objectives: The aim of the study was to compare the two radiation fractionation schedules - hypofractionation and conventional fractionation in terms of treatment outcome and treatment related toxicities in patient of early glottis carcinomas. Primary objectives were (1) to compare the response rates after radiation in two treatment groups, (2) to compare acute and late radiation toxicities in between the two groups and (3) to compare 3-year local control rates and loco-regional recurrence free survival in between the two groups. Materials and Method: Between January 2009 and December 2012, 78 patients of newly diagnosed, biopsy proven, early stage (stage I and II) squamous cell carcinoma of glottis treated in Radiotherapy Department of our Institution were retrospectively analyzed. Two fractionation groups were identified with respect to daily fraction size and overall treatment time. Arm A consisted of 38 patients who received radiation dose of 60 GY at 2.5Gy per fraction, 5 days a week for a total of 24 fractions over 32 days (5 weeks). Arm B consisted of 40 patients who received radiation dose of 66 GY at 2 Gy per fraction, 5 days a week for a total of 33 fractions over 46 days (7 weeks). All patients were treated with EBRT using conventional planning in cobalt-60 teletherapy machine. Response to radiation was assessed at 6 weeks after completion of therapy by RECIST Criteria version 1.1. Acute and Late toxicities of Radiation were recorded according to RTOG Acute and Late Radiation Morbidity Scoring Criteria. 3-year local control and loco-regional recurrence free survival were analyzed using the Kaplan-Meier method. Results: Median follow-up was 37 months. After completion of radiotherapy, patients treated in Arm A had a complete response rate of 91.8% vs 87.5% in Arm B (P = 0.71), partial response rate of 8.2% vs 12.5%, respectively. There was no treatment interruption due to toxicity. No statistically significant difference in acute and late toxicity rates were found in the two treatment group. The 3-year Loco-regional Control rates (LRC) were 86% for the entire study population, 91.4% in Arm A and 81.1% Arm B. No significant differences in the 3-year LRC rates were detected between treatment groups. (P = 0.20, log rank test). Conclusions: Hypofractionated radiotherapy has the same response rate and local control rate as that of conventional radiotherapy without significance increase in toxicity in early stage glottic cancer.
Objective assessment of swallowing dysfunction and aspiration after chemoradiation for head and neck cancer with its impact on quality of life
Nithin Bhaskar V., Iqbal Ahmed, Rajesh J., Chendil V., Amruth Kadam
Bangalore Medical College and research institute.
Background/Objective: To assess the prevalence, severity and morbidity of dysphagia following concurrent chemo-radiation for head and neck cancer. Materials and Methods: Between November 2012 and October 2014, 20 patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx were studied. All patients received conventional EBRT on Telecobalt to a total dose of 66-70 Gy (by shrinking field technique) with concurrent weekly cisplatin 40 mg/m 2 . All patients were given symptomatic care in the form of analgesics, antiemetic. Patients were evaluated before and after RT to assess the swallowing dysfunction by nasopharengeal larygoscopy. Results: Flexible endoscopy was performed pre-therapy in 22 patients, early post treatment in 17 patients and late post-therapy in 12. Post therapy dysfunction was characterized by pooling of food in and around pyriform sinus. Defective swallowing characterized by pooling of liquids/solids was noticed in 15 patients (68%) in the early post-therapy period and nine patients (41%). Aspiration noted in the post therapy period was mostly silent aspiration eliciting no cough reflex. Post-therapy aspiration was noticed in 11 patients (50%) out of which 10 patients (45%) had silent aspiration. 8 patients were diagnosed of pneumonia and required admission and i.v antibiotics. 2 patients expired in the early post treatment time due to pneumonia. One patient was lost to follow-up in the early post treatment period and four in the late post treatment periods. Conclusions: After concurrent chemo-radiotherapy, significant objective swallowing dysfunction is prevalent. It promotes aspiration, which may not elicit a cough reflex and can contribute to pneumonia.
Three weekly versus weekly concomitant chemoradiation with cisplatin in locally advanced head and neck cancer- a prospective, randomised study
Parna Basu*, Krishnangshu B Chowdhury*, Abhishek Basu*, Kazi S. Manir*, Partha Dasgupta*, Subir Gangopadhayay*
*Department of Radiotherapy, R.G.Kar Medical College and Hospital, Kolkata. E-mail: firstname.lastname@example.org
Background: Concurrent Cisplatin based chemoradiotherapy (CTRT) is now the standard of care for locally advanced head neck cancer patients (LAHNC). The most common chemotherapy regimen is high dose (100mg/m 2 ) three weekly Cisplatin with CTRT. This protocol is associated with significant acute and late toxicities which resuls in either early treatment termination or decrease in treatment compliance. Therefore splitting full dose three weekly Cisplatin as weekly Cisplatin schedule (30 mg/m 2 ) maintaining the dose intensity might decrease toxicity and increase compliance. Objectives: This prospective study compares the differences in response rate, acute toxicity and PFS outcomes between weekly Cisplatin and 3-weekly Cisplatin based concurrent chemotherapy (CTRT) regimens given to patients of Stage III/IV head and neck cancer. (T3-4b, N1-3) Methods: The study was designed as single institutional, open label, parallel 2 arm phase 3 randomized controlled clinical trial. LAHNC (squamous cell histology) patients with Eastern Co-operative Oncology Group (ECOG) performance status 0-2, normal hematological parameters, creatinine clearance > 50 ml/min, with no significant co-morbid conditions were randomized into 2 arms: Arm A was treated with weekly Cisplatin (30 mg/m 2 ) concomitantly with conventional RT and Arm B received 3 weekly Cisplatin (100 mg/m 2 ) for 3 intended cycles along with similar RT schedule, i.e.,66-70 Gy in conventional fractionation. The groups were compared for response rate (RECIST V1.1), acute toxicity (CTCAEv4) and progression free survival (PFS, Kaplan Meier Survival). The statistical analysis was done using two tailed tests with alpha < 0.05 statistical significant, SPSS v16, Chicago. Results: Initially 80 patients were recruited in study with 60 patients elgible for analysis for PFS (intention to treat). At median follow up period of 12 months (range 5- 19 months) the baseline parameters of demographic profiles and tumour characteristics were comparable in both arms. Majority of patients were in stage III, 20 (66.7%) and 14 (48.3%) for Arm A and B. Response rates at the end of 2 months post treatment were comparable in both arms Arm A (N = 27) patients and Arm B (N = 30) patients, with Complete Response in Arm A 17 (65.4%) vs 19 (63.3%) in Arm B, Partial Response 8 (30.8%) in Arm A vs 6 (20%) in Arm B and Progressive Disease 1 (3.8%) in Arm A vs 5 (16.7%) in Arm B, P value 0.248. Response at last follow up CR 15 (57.7%) in Arm A vs 17 (56.7%) in Arm B, and PD 10 (38.5%) in Arm A vs 9 (30%) in Arm B, P value 0.427. Majority of patients with oropharngeal subsite had local recurrence or progressive disease. Median PFS was 16 months (mean SE: 10.36 1.25 months; 95% CI 7.903, 12.81) in Arm A vs 14 months (mean SE: 12.15 0.74 months; 95% CI 10.70,13.60) in Arm B, log rank test 0.062. Weekly cisplatin arm was showing statistically significant toxicities in the form of dysphagia (Grade3- 36.7%); mucositis (Grade3-30%) and dermatitis (Grade 3- 13.3%). Among hematotoxicies, neutropenia was numerically more in Arm A and anemia and thrombocytopenia more in Arm B. Conclusion: In this study, Three weekly high dose Cisplatin treatment showed better locoregional response and lower acute toxicity compared to weekly low dose Cisplatin treatment.
Comparison of manual and inverse optimisation techniques in high dose rate intracavitary brachytherapy of cervical cancer: A dosimetric study
Ram Abhinav K.
M.S. Ramaiah Medical College
Background: Brachytherapy has been a standard component of definitive radiation therapy for cervical cancer.With advent of advanced imaging modalities, there has been a shift from conventional xray based planning to three dimensional planning. Manual optimisation is the one which is widely used across various institutions but it is time consuming and operator dependant. Inverse planning simulated annealing (IPSA) is now available in various brachytherapy planning systems. Similar to external beam radiation, there could be potential improvement in target volume coverage and reduction in planning time with the use of inverse planning. But there is a paucity of studies comparing manual optimisation and IPSA in the treatment of carcinoma cervix with intracavitary brachytherapy and hence this study. Aims and Objectives: To compare dosimetrically, manual optimisation with inverse planning simulated annealing using dose volume histograms (DVH) among patients treated for carcinoma of cervix with intracavitary brachytherapy. Materials and Methods: 15 consecutive patients treated between December 2013 to March 2014 with intracavitary brachytherapy for carcinoma of cervix were selected for this dosimetric study. All patients were initially treated with external beam radiotherapy to a dose 45Gy in 1.8 Gy per fraction followed by intracavitary brachytherapy to a dose of 26Gy in four equally divided fractions over two days. Manual optimisation was done by changing the active dwell weights, by clicking the isodose line and mouse dragging it to the desired location until a satisfactory plan was obtained with respect to target volume coverage and organ at risk (OARs). Inverse planning was done for the same fifteen patients who were treated previously after manual optimisation. Dose constraints were set to OAR's and target volume. IPSA was used to generate an inverse plan, which identifies the combination of dwell times that best conforms to dose constraints of target volumes and OARs. The dose volume histograms (DVH) were analysed for each group and were compared between the two groups using paired t test. The level of significance was set at 0.05. Results: There was a significant improvement in the HRCTV coverage, mean V100 of 88.52% and 83.67% (P = 0.03) and homogeneity inde Χ 0.42 and 0.39 (P = 0.04) for plans generated using IPSA and manual optimisation, respectively.D90 dose also showed a trend towards significance 6.4 Gy and 5.95 Gy (P = 0.07). There was no significant increase in the high dose volumes measured as V150, V200 and V300 between the two groups. Conformity index and dose to the OAR's remained similar between two groups. No difference in the volume of tissue covered by 100% (VPD) and 200% (V2PD) of the prescription dose was noted. Planning time for IPSA was around 5 minutes compared to 30-45 minutes in manual optimisation. Conclusion: The use of inverse planning in intracavitary brachytherapy of cervix has shown a significant improvement in the target volume coverage and homogeneity index when compared with manual planning, while volume of high dose region and doses to organ at risk remained similar between the two groups. Planning time also considerably decreased with the use of inverse planning.
Head and Neck
Metronomic Chemotherapy with oral Methotrexate and Celecoxib in Advanced/Recurrent/Residual Head and Neck Cancers not amenable to curative treatment: A Prospective Study
Akhil Kapoor, Daleep Singh, Shankar Lal Jakhar, Surender Beniwal 1 , Ashok Kalwar, Harvindra Singh Kumar
Department of Radiation Oncology, 1 Department of Medical Oncology, Acharya Tulsi Regional Cancer Treatment and Research Institute, Sardar Patel Medical College and Hospital, Bikaner, Rajasthan 334003. E-mail: email@example.com
Introduction: In every day-to-day practice in India, we encounter a lot of patients of recurrent/residual head and neck cancers who are not amenable to salvage surgery. Palliative chemotherapy is the most widely used option for such patients. However, many-a-times these patients have poor performance status or experience intolerable side effects to full blown palliative chemotherapy making it impossible to continue the treatment. Best Supportive care though a viable option, has limited survival and also brings a sense of nocebo to the medical science. Aims and Objectives: To evaluate the feasibility and efficacy of Metronomic chemotherapy (MC) with oral Methotrexate and Celecoxib in Advanced/Recurrent/Residual Head and Neck Cancers not amenable to curative treatment. Materials and Methods: We performed retrospective analysis of prospectively collected data of advanced/recurrent/residual head and neck cancer patients not amenable to curative treatment. Between January 2013 to June 2013, 121 patients were enrolled into the study and were treated with daily Celecoxib 400 mg in two divided doses along with weekly oral methotrexate 15mg/m 2 . Informed consent was obtained from the patients after clearly explaining all the alternative treatment options. The treatment was continued till progressive disease, intolerable side effects or the decision of patient or the family members. SPSS version 20.0 (Armonk, NY, IBM Corp.) was used for the statistical analysis. Progression free survival (PFS) was calculated from date of start of MC till the date of progression, or death due to any cause. Overall survival (OS) was calculated from date of start of MC to death. The Kaplan Meier method was used for estimation of survival. Results: The median age of the study patients was 50 years (Standard deviation: 12.79) with male: female ratio of 4:1. 61.2% patients had Eastern Cooperative Oncology Group performance status > 2. 88.4% patients had received prior radiotherapy while 38.8% patients had received palliative intravenous chemotherapy before enrollment into the study. 34.7% patients had partial remission, 37.2% had stable disease before developing progressive disease or death, although no patient had complete remission. 47.9% patients reported subjective improvement in their symptoms at some point of the treatment. The median PFS was 4.0 months [95% confidence interval (CI): 3.59-4.40 months] and the median OS was 7.0 months (95% CI: 6.57-7.42 months). The MC was well tolerated with most frequent grade 3 toxicities included anemia: 9%, neutropenia: 7.4%, and oral stomatitis: 12%. There were no grade 4 toxicities and no episode of febrile neutropenia. Conclusions: Metronomic chemotherapy with oral methotrexate and celecoxib is an attractive treatment option in advanced/recurrent/residual Head and Neck Cancer patients who are not amenable to curative intent with minimal toxicities. There is need to conduct well-designed randomized controlled trials to evaluate the efficacy of metronomic chemotherapy over best supportive care or other palliative regimes.
A prospective randomised trial comparing Neoadjuvant Chemotherapy followed by concomitant chemoradiation versus concomitant chemoradiation alone in locally advanced Head and Neck Squamous Cell Carcinoma
R.G. Kar Medical College, Kolkta. E-mail: firstname.lastname@example.org
Introduction: Concurrent chemoradiotherapy (CTRT) is currently the standard of care for management of Locally Advanced Head and Neck Squamous Cell Carcinoma (LAHNSCC).  In this setting, taxane, platinum and 5-fluorouracil based Neoadjuvant Chemotherapy (NACT) has role in tumour downstaging facilitating organ preservation with potential to control distant metastasis albeit at the cost of increased toxicities [2-8] . However, the optimal sequencing of NACT and CTRT and the potential benefit of adding NACT to CTRT in LAHNSCC remains unanswered. Aims and Objectives: We designed this study to evaluate the role of NACT followed by conventional CTRT versus conventional CTRT alone in LAHNSCC to observe locoregional response, toxicities and Progression Free Survival (PFS). Materials and method: In this prospective, randomized, open label, single-institutional phase II study, done between Jan 2013 to Mar 2014, 70 patients of biopsy proven LAHNSCC (AJCC Stage Group III, IVA and IVB) with normal baseline haematological, biochemical parameters and ECOG PS 0-1 were randomised (using computer generated sequencing) into two arms (35 each) to receive either three cycles of NACT (with Inj. Paclitaxel 175 mg/m 2 and Inj. Carboplatin AUC 5 IV on day 1 every 3 weeks) followed by conventional CTRT (Arm A; NACT-CTRT; Study) or conventional CTRT alone (Arm B; CTRT; Control).CTRT was administered with Inj. Cisplatin 100mg/m2 IV on Day 1, 22 and 43 in both arms along with External Beam Radiation Therapy to a total dose of 70.2 Gy/39 #/7.5 weeks. CTRT started 3 weeks after last NACT. After completion of NACT Loco-regional Response (LRR, by RECIST v1.1) and toxicities (with CTCAE v4.0) were assessed in the Arm A. LRR was again assessed at the end of treatment in both arms (Primary Endpoint). Secondary endpoints were toxicities (acute and late) and PFS in the both arms. Results: At median follow up period of 12 months (range 5-19 months), 64 patients were evaluable (32 in each arm).Median age was 60 years in Arm A and 55 years in Arm B (P = NS).Baseline patient characteristics were comparable between the arms (P = NS). After NACT 65.62% of patients in Arm A achieved PR (CR = 6.25%, SD = 28.12%) with Grade ≥ 3 acute toxicities being Diarrhoea (3.1%), Anemia (9.7%), Neutropenia (3.1%) and Thrombocytopenia (3.1%). At the end of treatment, LRR were comparable between two arms. Grade ≥ 3 toxicities included numerically more haematotoxicities and neuropathy in Arm A and dermatitis in Arm B (statistically nonsignificant). Mean PFS (compared by Kaplan Meier Survival analysis) between these 2 arms were not statistically significant (Arm A 17 months vs 16 months in Arm B; log rank P = 0.839). There were 4 events in arm A (including two deaths - one due to disease progression and another due to toxicity) and 6 events in arm B (including 1 death due to disease progression). Conclusion: Although this study suffers from low sample size and short follow up, it demonstrates that paclitaxel and carboplatin based NACT can be of some potential benefit before CTRT in patients with LAHNSCC.
Comparison of concomitant chemoradiotherapy with weekly cisplatin against weekly cisplatin and 5-fluorouracil in loco-regionally advanced oropharyngeal cancer
Introduction: Oropharyngeal cancers account for 25% of the head and neck squamous cell carcinomas and most are locally advanced at presentation. Concurrent chemoradiotherapy is a standard organ preservation approach for locally advanced oropharyngeal cancers. The optimal chemotherapy regimen is still debated and the unresolved issue remains whether to use single agent chemotherapy or a combination of two or more agents. Aims and Objectives: This prospective randomised study aims to compare the efficacy and toxicity of weekly cisplatin against weekly cisplatin and 5-fluorouracil given concomitantly with radiotherapy in loco-regionally advanced oropharyngeal cancer. Methods: In this prospective study, 50 patients with histologically proven Stage III - IVB oropharyngeal cancer were randomly assigned to one of the two chemoradiotherapy regimens, either weekly cisplatin (40 mg/m 2 ) alone or weekly cisplatin (40 mg/m 2 ) and 5-fluorouracil (350mg/m 2 ). All patients received radiotherapy to 66-70 Gy in 33-35 fractions over 6.5-7 weeks. Response, compliance and toxicity were investigated. Primary end points were (i) the responses (ii) toxicity profile and overall treatment time in the two groups. Study period was from June 2013 - July 2014. Results: 50 patients were randomly allocated to the study, 25 in Arm A (CRT with weekly cisplatin) and 25 in Arm B (CRT with weekly cisplatin and 5-fluorouracil). 24 patients in Arm A and 19 patients in Arm B could complete the planned treatment. Longer overall treatment time and treatment interruptions were associated with 14 patients in Arm A (58.3%) versus 16 patients in Arm B (84.2%). Complete response to treatment seen in 9 patients in Arm A versus 3 patients in Arm B (37.5% vs 15.7%). Partial response seen in 8 patients in Arm A versus 5 patients in Arm B (33.3% vs 26.3%). Grade III -IV mucosal toxicity seen in 15 patients in Arm A versus 16 patients in Arm B (62.5% vs 84.2%). Conclusion: Concomitant chemoradiotherapy with weekly cisplatin was found safe and superior to weekly cisplatin and 5-fluorouracil in locally advanced oropharyngeal cancer in this study. Addition of 5-fluorouracil resulted in prolongation of overall treatment time, increased mucosal toxicity and did not confer any benefit in tumour response.
Brain metastasis from Carcinoma base of tongue after nine years of disease free survival - A case report
Introduction: Head and neck carcinoma usually metastasizes to lungs, liver and bones. Brain metastasis after a disease free survival of nine years is a rare event. Aims and Objectives: To present a rare case of Carcinoma Base of tongue presenting with brain metastasis after a disease free survival of nine years. Methods and Materials: A 67 year old patient of Carcinoma base of tongue (T1N0M0) was managed with curative dose radiotherapy (66Gray/33#) in 2003.The patient was asymptomatic till 2012. In September 2012, the patient developed hemiplegia. CT Brain revealed a right fronto-parietal space occupying lesion. Craniotomy was done. The histo-pathological reports were in favour of metastatic squamous cell carcinoma. Immunohistochemistry was done which also suggested metastasis rather than a primary brain tumour. A PET scan was done to search for the primary but it was absolutely normal.Whole brain radiotherapy (30 Gray/10#) followed by an additional dose (20Gy/10#) to the tumour bed was administered.The patient was stable with all neurological functions intact at the time of discharge in December 2012. Result: The patient is on follow up for one year and eight months with all neurological functions intact. Conclusion: Brain metastasis can occur even after nine years of disease free survival with primary site under remission. The potential for developing a brain metastasis long after curative therapy argues for extended patient follow up.
Evaluation of volume changes in target tissues and organs at risk during the course of intensity modulated radiotherapy in head and neck cancers
E-mail: drsiva. email@example.com
Purpose: To evaluate the changes in treatment volumes of tumour and normal tissues during a course of IMRT in head and neck cancer patients and analyzing the dosimetric effects of these volume changes by comparing the initial and mid-course plans for Gross tumor volume, Clinical target volume and Organs at risk. Materials and Methods: A total of 12 oropharyngeal (11 patients) and hypopharyngeal (1 patient) patients were included in this study between march 2013 to june 2014. A CECT of head and neck was acquired. All patients were delineated for region of interest (ROI) and organ at risk (OAR) as per standard RTOG guidelines. SIB IMRT plan was made by prescribing dose of 66Gy, 60Gy and 54 Gy to PTV66, PTV60 and PTV54 respectively all in 30 fractions. After completion of 15 fractions a repeat ct scan is taken. Weight of the patient was also noted. In 2 nd ct scan again same structures were segmented and small volume changes in right and left parotid organs, GTV and CTV were also seen. A 2 nd SIB IMRT plan was made to the 2 nd ct. Patient was treated with 1 st plan for the entire fractions. In plan 2 same number of fields and constraints are tried to achieve. Optimization was done until the least possible dose to organs at risk (OAR) and at the same time target volumes were well covered. Results: The change in volume of right parotid was determined by wilcoxon signed rank test. The test came as significant volume change (P = 0.003). The change in left parotid volume was also significant (P = 0.002). Mean change in volume of right parotid was 3.88 cm 3 while that of left parotid was 2.83 cm 3 . Volume change in GTV was significant in day 15 CT scan (P = 0.002). Change in volume of CTV1 was also significant in day 15 ct compared to that of day 1 (P = 0.012). The dose received by right parotid from plan1 was not different from plan 2 statistically which was found from the same Wilcoxon signed rank test (P = 0.388). Also the dose received by the left parotid gland by plan 2 was not statistically different from plan 1 (P = 0.638).The dose received by GTV was not statistically different in plan 2 (P = 0.410). Similarly the dose received by CTV1 was also not statistically different (P = 0.084).There appears to be no role of taking repeat ct and replanning during the course of IMRT in head and neck cancers.
Study assessing feasibility of Electrochemotherapy using Bleomycin followed by pre-operative radiotherapy in locally advanced lip and buccal mucosa cancer
Vishal D. Manik
Madras Medical college, Chennai
Introduction: Lip and Buccal mucosa cancers are one of the most common malignancies in our practice. Some advanced cases can be technically difficult to operate upfront and are usually taken up for pre-operative chemo/radiotherapy. Tumouricidal doses of chemotherapy has its own systemic toxic effects. Electro-chemotherapy is a local treatment. Bleomycin (15IU/m 2 ) administered intravenously gets distributed in circulation over 8-10 minutes. Electrical impulses delivered to the tumour, open up the cell membrane channels temporarily resulting in drug concentration and improved cell kill. Added to this, radiotherapy results in good cytoreduction which in-turn improves the likelihood of negative margins and improved loco-regional control. Aims and Objectives: To assess the feasibility of treating locally advanced lip and buccal mucosa cancer with electro- chemotherapy using bleomycin followed by pre-operative radiotherapy. Materials and Methods: We selected 26 cases of squamous histology of oral cavity, stage IV, surgeon deemed inoperable. All patients were treated with electro-chemotherapy using intravenous bleomycin at a dose of 15IU/m 2 . Patients were assessed for toxicities and clinical response from electro chemotherapy two weeks after the procedure and were then proceeded to radiotherapy up to 50Gy (2Gy/#). Toxicities were re-assessed weekly during radiotherapy and at the end. Results: Males comprised 57.6% and age group 51-70 were 59%. Stage IVA cases were 88.4%. 53.8% had well differentiated histology. No procedure related complications observed. No patient developed systemic toxicity to bleomycin. Two weeks post procedure, electrode site skin scarring was observed in 76.9% cases, which reduced by end of radiotherapy to 19.2% cases. Toxicities like radiation mucositis-grade III (23%), post-RT hyperpigmentation (26.9%) and ulceration over treated site (15%) were observed. Partial response noted in all cases 2 weeks post electro-chemotherapy. Conclusion: Electro-chemotherapy with bleomycin followed by radiotherapy is feasible in carefully selected advanced cases of oral cavity. No cases reported any form of systemic toxicity. Local toxicity was manageable.
Advances in Radiation Treatment
Liver sbrt: Can it be truly non-invasive? A comparison between fiducials and anatomical surrogates for daily setup errors
Bharath C. Gurram
Introduction: With advances in modern imaging, treatment planning, respiratory motion management and treatment verification, Sterotactic body radiotherapy (SBRT) is rapidly evolving as the preferred option for liver tumours. But unlike other sites, cone beam CT (CBCT) has its limitations in identifying liver tumours as the electron density of the lesions and normal liver are not always different. Hence in practice, inert gold fiducials are implanted around the tumour for the purpose of image guidance. But this makes SBRT a partly invasive procedure like Radio Frequency Ablation (RFA). Hence to make out whether fiducials can be avoided for SBRT, we analyzed the set up variations using fiducial based matching and anatomical surrogates like, liver, ribs, and vertebra. Aim: To analyze the set up variation in x, y and z direction with the use of cone beam CT using different anatomical surrogates (liver, vertebra and ribs) versus fiducials. Materials and Methods: As part of prospectively planned SBRT treatment protocol for liver tumors all patients will be treated using active breath control technique with gold fiducials implanted near the tumor and a planning treatment volume (PTV) of 1 cm cranio-caudal and 0.5 cm radial margin is given. CBCT scans are taken prior treatment and in between the treatment to evaluate for errors. A total of 27 CBCT scans were prospectively analyzed. CBCT's were acquired and images were registered with planning CT scan. Setup errors were calculated after matching using anatomical surrogates and fiducials separately. Comparisons were made with the patient setup using fiducials versus anatomical surrogates (liver, vertebrae and ribs). Treatment was delivered after adjusting for the fiducial based matching. Results: The mean error in the x, y, z direction using fiducials were 1.5 mm, 6.3 mm and 1.5 mm with the standard deviation of 2.1 mm, 5.4 mm and 2.7 mm respectively. The Mean variation in x direction using liver, ribs and vertebra as surrogates was -1.2 mm, -1.8 mm and -1.6 mm respectively. The similar difference in y direction was 0.2 mm, 2.8 mm and 6.2 mm. The corresponding values in z direction were 0.19 mm, 0.9 and 0.07 mm respectively. Discussion: Our results show that the PTV margin of 5mm in the axial direction and 1 cm in cranio caudal direction is adequate when using an active breath coordinator for respiratory motion management and daily image guidance using cone beam CT. We found bony land marks like ribs and vertebra are quite unreliable for daily set up variation especially in the y direction. Liver was the most reliable anatomic surrogate with a difference of -1.2 mm, 0.2 mm and, 0.19 mm in x, y and z direction. Liver deformation during treatment is known and this must be taken into account before embarking on such a strategy. Increasing the PTV margin to account for errors due to anatomical surrogates may lead to increased toxicity. Conclusion: Fiducials placed around the tumour at least 2 weeks before the planning CT remain the most reliable strategy to guide radiation delivery in Liver tumours.
Early response to concurrent chemoradiotherapy in cervix and head and neck cancer- an observational study
Jyosthna Elagandula*, Janaki M. G., Arul Ponni T. R., Kirthi Koushik A. S., Ram Charith Alva, Mohan Kumar S.
*Post Graduate, Dept of Radiation Oncology, M. S. Ramaiah Medical College, Bangalore. E-mail: firstname.lastname@example.org
Introduction: Concurrent Chemoradiotherapy is definitive treatment for most of the squamous cell carcinoma of cervix and head and neck. We in our department treating most of these patients under government funded insurance scheme. As a part of this, CT scan of treated area is mandatory at the end of external beam radiotherapy before discharging patient. This study is an effort to assess early response to treatment. Objective: To assess radiological response at the end of external beam radiotherapy in squamous cell carcinoma of cervix and head and neck. Materials and Methods: 50 patients with squamous cell carcinoma of cervix and head and neck who were planned for radiotherapy between November 2013 to july 2014 were retrospectively analysed. CT scans were done once prior to start of radiotherapy and once on the last day of completion of external beam radiotherapy. Both were analysed for early response using RECIST criteria of response assessment. The response was correlated with initial tumour characteristics. Results: Following external beam radiotherapy, among 36 patients of cervix cancer 19 pts (52.77%) had partial response, 7 pts (19.43%) had complete response, 9 pts (25%) had stable disease and 1 pt (2.8%) had progressive disease and this was the response to external radiation and not at the end of brachytherapy. Among 14 patients of head and neck cancer 6 pts (42.9%) had partial response, 6 pts (42.9%) had complete response, 2 pts (14.2%) had stable disease and none had progressive disease. Conclusion: Early response was seen in squamous carcinoma of head and neck cancer patients. However long term follow up of these patients would help us to decide if doing the imaging so early is beneficial in either predicting the outcome or in tailoring the treatment in nonresponders. Doing a CT scan for cervical cancer patients at the end of external radiation and before brachytherapy is not necessary and is just an additional burden on the CT scan machine and should be avoided. This needs to be considered by the law makers.
Advances in Radiation Treatment
Dosimetric comparison of coplanar intensity modulated radiotherapy plans using target specific gantry angle versus equally spaced gantry angle in hypofractionated accelerated radiotherapy in patients of newly diagnosed glioblastoma
Ahitagni Biswas 1 *, Seema Sharma 1 , Pramod Kumar Julka 1 ,
Ashish Binjola 1 , Daya Nand Sharma 1 , Goura Kishor Rath 1
Department of Radiation Oncology 1 All India Institute of Medical Sciences, New Delhi, India. *corresponding author E-mail: email@example.com
Introduction: Glioblastoma (GBM) is the most aggressive malignant brain tumor with overall survival ranging from 12-15 months. Aims: We compared target coverage, conformity, homogeneity, normal tissue avoidance, irradiated body volume and treatment monitor unit in 2 sets of plan- intensity modulated radiotherapy (IMRT) with target specific gantry angle versus equally spaced gantry angle in 10 patients of newly diagnosed glioblastoma undergoing post-operative hypofractionated accelerated radiotherapy with concurrent and adjuvant Temozolomide. Methods: In a single arm phase II study, 25 patients of newly diagnosed, histologically proven GBM with age 18-70 years, Karnofsky performance scale (KPS) ≥70 and normal end-organ function were included. Four weeks after maximal safe surgery, patients underwent contrast enhanced planning CT scan. Gross tumor volume (GTV) was defined as enhancing tumor on T1-W post contrast MR or contrast enhanced CT images. High risk clinical target volume (CTV) included GTV with perifocal edema on T2-W/FLAIR MR images. Low risk CTV encompassed high risk CTV with isotropic expansion of 2 cm. Planning target volume (PTV) encompassed low risk CTV with 0.5 cm isotropic expansion. PTV boost was defined as GTV with 0.5 cm isotropic expansion. IMRT 60Gy/25fractions/5 weeks to PTV boost; 50Gy/25fractions/5 weeks to PTV was delivered by simultaneous integrated boost technique with 5-7 coplanar beams (Eclipse version 6.5/Pinnacle version 8.0 m). In 10 patients with lateralized tumor not crossing the midline and corpus callosum, a dosimetric comparison was done between 2 sets of dynamic IMRT plans using target specific gantry angle (Arm A) versus equally spaced gantry angle (Arm B) with respect to target coverage, conformity, homogeneity, normal tissue sparing, irradiated body volume (IBV) and total monitor unit (MU) by Wilcoxon paired test (MedCalc statistical software version 11.3.0). P value less than 0.05 was considered statistically significant. Results: The median values of D95PTV and VPTV95% were 98.74% and 97.86% of prescribed dose (P value 0.1602) and 99.67% and 99.06% (P value 0.1289) in arm A and B respectively. The median values of conformity index (treated volume/VPTV prescribed dose) were 1.07 and 1.04 (P value 0.6523) in arm A and B respectively. The median value of homogeneity index (D2/D98) were 1.1 and 1.11 (P value 0.4609) in arm A and B respectively. With regard to organ sparing, the median values of dose maximum to brainstem, optic chiasma, spinal cord, ipsilateral eye, ipsilateral optic nerve, ipsilateral temporal lobe and ipsilateral cochlea were 53.29Gy and 55.53Gy (P value 0.3223), 45.7Gy and 42.59Gy (P value 0.4316), 0.99Gy and 1.08Gy (P value 0.0117), 25.22Gy and 27.87Gy (P value 0.1055), 42.57Gy and 42.69Gy (P value 1), 63.88Gy and 64.06Gy (P value 0.0547), 23.12Gy and 21.99Gy (P value 0.7695) in arm A and B respectively. The median values of dose maximum to contralateral eye, optic nerve, temporal lobe and cochlea were 12.75Gy and 16.51Gy (P value 0.0098), 19.15Gy and 19.37Gy (P value 0.1309), 34.08Gy and 40.8Gy (P value 0.1055), 8.48Gy and 8.15Gy (P value 0.5566) in arm A and B respectively. With regard to low dose bath, the median values of IBV5Gy and IBV10Gy were 1936.55cc and 1909.05cc (P value 1), 1616.08cc and 1650.97cc (P value 0.0020). The median values of MU in arm A and B were respectively 701 and 688.5 (P value 0.6523). Conclusion: In patients of newly diagnosed GBM, postoperative hypofractionated accelerated IMRT with target specific gantry angle in comparison with equally spaced gantry angle, results in comparable target coverage, conformity, homogeneity with better sparing of critical organs at risk like spinal cord, contralateral eye and temporal lobe with simultaneous decrease of IBV at 10Gy. This may lead to enhanced therapeutic ratio in this potentially fatal tumor.
Quantification of set-up errors in patients receiving conformal radiotherapy using portal imaging- A prospective study
M.S. Ramaiah Medical College,Bangalore
Introduction: Radiotherapy forms one of the main modalities of treatment of cancer along with surgery and chemotherapy. The main aim of radiotherapy is to deliver high dose of radiation to tumor tissue and at the same time to keep the dose to the surrounding normal tissues to the minimum. Curative radiation is when the treatment is given for a period of 5 to 7 weeks where in everyday treatment accuracy and reproducibility of the initial treatment position is mandatory. Hence accurate patient positioning becomes necessary during daily treatment. Even with adequate immobilisation techniques, random set-up errors are likely to occur. This error beyond the specified limits will lead to geographical miss and increased dose to surrounding normal tissues leading to poor loco regional control and increased normal tissue side effects. The main aim of this study is to quantify the random errors occurring in our patients who are receiving conformal radiation therapy in head and neck, thoracic and pelvic malignancies using portal films during their treatment schedule. Objectives: 1) To verify the treatment fields in antero-posterior (Z), medio-lateral (X) and longitudinal (Y) directions using portal imaging. 2) To quantify the random setup errors. Materials and Methods: This is a prospective study. Thirty patients (10 patients in each site) with histologically proven head and neck, thorax and pelvic malignancies and undergoing radical treatment were taken up for the study. All patients underwent immobilisation with aquaplast cast and planning CT scan was done. The images were loaded onto the treatment planning system and contouring was done as per standard guidelines. The image on digitally reconstructed radiograph (DRR) served as reference image. Port films were obtained in orthogonal directions, initially for the first three days of starting treatment and later weekly till the completion of the treatment. The port films were compared with DRR and the variations were noted in X, Y and Z axes. Any variations above the prescribed limits were corrected accordingly. Results: Thirty patients (10 in each) were included in the study. In head and neck malignancy patients the mean value ranges from 0.12 to 0.20 cms in X axis, 0.11 to 0.15 cms in Y axis and from 0.10 to 0.25 cms in Z axis. The median value ranges from 0.10 to 0.20 cms in X axis, 0.10 cms in Y axis and 0.10 to 0.25 cms in Z axis while the mode had a value of 0.10 cms in head and neck irradiation. The maximum variation of 7 mm was seen in week 4 and week 6 of treatment for which the corrections were done accordingly. The ANOVA test is denoted by F value for which the P value was calculated for its significance. The P value is not significant on all the days of the treatment. Similarly for thorax malignancies the mean values varied from 0.25 to 0.49 cms in X axis, from 0.46 to 0.53 cms in Y axis and from 0.51 to 0.73 cms in Z axis. The median value varied from 0.25 to 0.75 cms in X, Y and Z axes. Mode had a value of 0.40 cms. The maximum value was 1.6 cms in Z axis in week 5. The F value of ANOVA was calculated. The P value came out to be significant in week 1, week 4 and week 5 of radiation treatment. For pelvis malignancies the mean value ranged from 0.14 to 0.26 cms in X axis, from 0.24 to 0.43 cms in Y axis and from 0.21 to 0.34 cms in Z axis. The median value ranged from 0.10 to 0.50 cms in X, Y and Z axes respectively. Mode had a value of 0.20 cms. The maximum value was 1.0 cms in Y axis. The F value was derived for ANOVA test. The P value was statistically significant in week 4 of radiation treatment. Conclusion: Port films form an easy and inexpensive method of treatment verification. The set-up errors for head and neck patients undergoing conformal radiation are within acceptable range which are verified using port films. For head and neck cases, it is reliable and comparable to EPID. For thorax and pelvis, the port films are inferior in terms of estimation of set-up errors as the variation is beyond the acceptable range. This is due to inferior contrast on imaging compared to EPID. Hence EPID forms a better alternative modality of portal imaging in thorax and pelvic malignancies.
Expression of immunohistochemical markers in locally advanced breast carcinoma and their use as predictors of pathological response (EXIPAR study): Initial results of a prospective analysis tertiary care centre database
Animesh Saha*, Sanjit Agarwal, Indu Arun, Rosina Ahmed, Sonali Susmita Nayek, Mayur Parihar, Deepak Dabkara, Subir Sinha, Sanjoy Chatterjee
Tata medical center, kolkata. E-mail: firstname.lastname@example.org
Introduction: Immunohistochemical (IHC) markers are important factors in determining the subtype of breast cancers and to formulate the most effective management plan, including the use of neoadjuvant chemotherapy (NACT). Patients who develop a pathological complete response (pCR) after NACT have better survival than those with residual disease (RD). Aims and Objectives: To compare the pCR between various molecular subtype of breast cancer, To findout the incidence of Febrile neutropenia and prophylactic use of Pegylated Granulocyte Colony Stimulating Factor (Peg GCSF) in locally advanced breast cancer (LABC) patients undergoing NACT, To correlate the pCR with dose intensity and regimen of chemotherapy used. Materials and Methods: We compared the pCR between various molecular subtypes of breast cancer when treated using a standard NACT regime in 156 LABC patients. We also analysed the tolerability and dose density, the incidence of Febrile neutropenia, treatment delay and use of prophylactic use of Peg GCSF in LABC patients undergoing NACT. Cases were classified into four subtypes: 1) Luminal A type (ER- and/or PR-positive, HER2-negative, and Ki-67 < 14%); 2) Luminal B type (ER- and/or PR-positive and either HER2- positive or Ki-67 ≥ 14%); 3) Her-2 rich type (HE) (ER- and PR-negative and HER2-positive); and 4) Triple Negative (TN) (ER-, PR-, and HER2-negative). Associations between the pCR and other categorical variables were assessed using the Chi-square tests. Associations between pCR and the Ki-67 index was assayed by using the independent Student t-test. Results: Median age of our patients was 48yrs. Grade 3 tumours had a higher pCR rate (27.4% vs16.9%, P = 0.19). There was no significant difference in pathological response with ER/PR or HER2 neu expression. HER2neu positive tumours who had received Trastuzumab had a higher pCR rate (35.7% vs 22.45%.). Patients with low KI67(<14%) had Pcr rate of 17.14% compared to high Ki 67(≥14%) patient with pCR rate of 23.07% (P = 0.36). LA subtype has lowest pCR rate of 13.64% and TN subtype had highest Pcr rate of 33.33%. LB and HE subtype had a Pcr rate of 24.36% and 26.31%. Patients with less than 10% dose reduction had higher Pcr rate (29.3%vs22%, P = 0.42). 24.49% patients received prophylactic Peg G CSF.8.84% patients developed febrile neutropenia requiring hospital admission., 9.52% patients had treatment interruption for more than 1 week. Patients with treatment interruption more than 1 week had a lower response rate (13.3% vs25.5%, P = 0.46). At a median follow up of 20 months 1.28% patient developed locoregional recurrence, 6.41%has developed distant metastases. Conclusion: To increase the pCR rate, it is reasonable to consider targeted approaches according to each subtype. Patients with LA subtype breast cancer had a poorer response to NACT may be considered for upfront surgery and endocrine therapy. NACT had a higher chance of downstagingTNBC patients and these cases should therefore get a routine pre NACT marker clip insertion to assist conservation surgery. No significant difference existed in pCR rates amongst Her 2 rich and Luminal B cases, mainly because majority of Her 2 rich patients couldn't afford Trastuzumab treatment. Use of Trastuzumab along with NACT provides better pCR rates in Her-2 positive cancers.
Clinical profile and outcomes in Medulloblastoma: An institutional experience
Pavan Kumar Lachi
Background: Medulloblastoma is a common malignancy in the pediatric population, accounting for 25% of all childhood brain tumours. This review was to investigate treatment outcome and prognostic factors after radiation therapy medulloblastoma. Methods and Materials: Fifty three patients with histological confirmed medulloblastoma cases were treated at our institute of between 2006 and 2012 were included in the study. Demographic variables, clinical variables, radiological findings and treatment details with respect to age, sex, signs and symptoms, location of tumor, extent of surgical resection, histopathology type, RT dose, follow up period and outcomes were recorded. Survival was analyzed by using these various parameters. Results: Thirty one (58.5%) patients were pediatric (<14 years), and 22 (41.5%) patients were adults (>=14 years). Duration of symptoms were less than three months in19 (36%) and more than three months in 34 (64%) patients. Tumor resection was performed in all patients and gross total resection in eight (15%) patients, near total resection in 34 (64%) patients and subtotal resection in 11 (21%) patients. All patients underwent postoperative craniospinal irradiation (CSI) delivering a median craniospinal dose of 36 Gy with additional boosts to the posterior fossa up to 54 Gy. Median overall survival was 50 months for the total group where as 36 months for pediatric age group and 70 months for adult group. Desmoplastic histology showed a improved outcome compared to other histologies with median survival 71 months compared to classical medulloblastoma histology median survival 36 and other histologies median survival 34 months. Other factors include durations of symptoms, sex, location of the tumor, extent of surgical resection were not effecting the survival. Conclusions: Treatment of medulloblastoma with surgery and craniospinal irradiation yields long survival rates in both children and adults. Adult age group and desmoplastic histology were associated with a favorable outcome.
Head and Neck
Necessity of replanning during the intensity modulated radiotherapy (imrt) for head and neck cancer, to ensure adequate coverage of target volume
Background: Radiation therapy (RT) plays a critical role in the current management of patients with head and neck (H and N) cancer. By generating steep dose gradients, intensity-modulated radiation therapy (IMRT) has the ability to conform the dose to target volumes with complex shapes, and to avoid organs at risk (OAR) to a much greater degree than it was possible to do with classical three-dimensional (3D) conformal RT. It is recognized that the location, shape, and size of disease and normal anatomy change significantly during a 6-7 week course of radiation treatment. Because of these changes, steep dose gradients with IMRT may move across target volume and critical structures resulting in under dose to the target volume and over dose to the critical structures. To address these issues, there is a necessity of re planning at mid treatment. Objectives of the study: The objectives of our study were to compare the coverage of target volume in the initial IMRT plan and at the end of 4 weeks and to quantify the dose to normal structures in these two sets of CT images. Materials and Methods: Patients with Stage III, IVA and IVB head and neck squamous cell carcinoma, in whom definitive/adjuvant radiotherapy with or without chemotherapy was planned were included for the study. 30 patients were selected for the study. All the patients included for the study underwent CT simulation and were treated with 3DCRT plan. IMRT plan was used for dosimetric comparison only. The IMRT plan was created on pre treatment planning study. Repeat CT simulation was done at the end of 40 Gy and fused with pre treatment CT. The coverage of PTV and doses to critical structures were compared for the repeat CT using the pretreatment IMRT plan. Statistical methods (student's paired t test) were applied. Results: In our study, both PTV coverage (V95 from 96.29 1.12 to 97.33 0.80) and dose (D95 from 66.64 0.87 to 67.57 0.74 (Average standard deviation) increased in repeat CT images, which can be attributed to shifting of volume more medially due to shrinkage in tumour/nodal volume and weight loss. Both Max dose and Mean dose increased for Brain stem and spinal cord. Also the mean dose to the parotid glands increased in repeat CT images compared to pre treatment images. All the increase in dose were statistically significant. Interpretation and Conclusion: Repeat CT imaging and planning is necessary during mid treatment in order to accommodate anatomical changes and its impact on dosimetry which take place during 6 to 7 weeks of radiation treatment. Otherwise actual delivered dose to critical structures would be higher than the planned dose.
Radiation Physics Award
Enhancing the longevity of 3D dose in a diffusion-controlled Fricke gel dosimeter
S. Ebenezer Suman Babu
Introduction: The principle of Fricke Gel Dosimeter is the oxidation of Ferric ion on exposure to radiation. The major limitation in using the Fricke Gel Dosimeter is the post irradiation diffusion of ferric ion which results in the destruction of spatial dose information. Aims and Objectives: The main objective of this study is to reduce diffusion of ferric ions after irradiation and enhance the stability of the dose information for an acceptable period within which the spatial dose information can be read out. Methods and Materials: In this work we propose a simple and novel method to achieve this aim by incorporation of an antioxidant in the present Fricke gel dosimeter. The final concentration of the Fricke gel dosimeter consisted of 50 mM Sulphuric acid, 0.15 mM Xylenol Orange, 0.5 mM Ferous ammonium Sulphate along with the addition anti oxidant. Various concentrations of antioxidants ascorbic acid and glycine were used in the preparation of the Fricke gel dosimeters. The gel samples were characterized dosimetrically with telecobalt, 6 MV, 15 MV beams and dose response was studied. Also observation of the post irradiation diffusion of dose was performed hourly for a minimum period of 6 hours. The irradiated gel samples were read out using a spectrophotometer at a wavelength of 585 nm. Large volume phantom (1 L) was also prepared to study the longevity of spatial dose with respect to time. An in-house optical CT scanner was used to acquire the 3D dose information from the phantom. Results: Glycine based Fricke gel dosimeter was found to be useful with both issues of auto oxidation and diffusion controlled, thereby enhancing longevity of 3D dose for 6 hours post irradiation. Ascorbic acid based Fricke gel dosimeter did not return the expected results as auto oxidation and diffusion could not be controlled. Conclusion: We conclude that the diffusion controlled, Glycine incorporated, performance enhanced Fricke gel dosimeter can be used for practical and convenient read out of 3D dose distributions.
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