|Year : 2018 | Volume
| Issue : 11 | Page : 902-908
|Date of Web Publication||29-Nov-2018|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Thoracic Oncology. J Can Res Ther 2018;14, Suppl S4:902-8
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Brain metastases in ALK-mutation positive NSCLC: A distinct entity
Vedanta Ray, Naveen Mummudi, Anil Tibdewal, Amit Janu1, Rajiv Kumar2, J. P. Agarwal
Departments of Radiation Oncology,1 Radio-Diagnosis and2 Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
Aims/Objectives: Patients with driver mutation NSCLC (EGFR and ALK mutation) have a better survival compared to wild type NSCLC; several studies have shown that these patients have higher incidence of brain metastases (BM both at presentation and during treatment. We aim to study the pattern of BM in a cohort of NSCLC patients with ALK mutations. Materials and Methods: We retrospectively analyzed the electronic medical records and imaging studies and selected 63 patients with histologically proven NSCLC (32 patients with and 31 patients without ALK mutation), who were diagnosed with brain metastases and had treatment at our institution between January 2014 and September 2018. MRI of the brain was available for re-assessment in all these patients. Patients were studied for EGFR/ALK mutation using FISH/IHC studies. Statistical analyses was performed using SPSS; overall survival was censored at death or last follow up. Results: Mean age at presentation of the entire cohort was 49.8 years (range 26-80 years). ALK mutated patients were more likely to be never smokers than non-mutated patients (68 vs 45%; p = 0.05). A similar number of patients presented with BM at diagnosis (44%) and on disease progression (56%). Average GPA score of the ALK-mutated and –non-mutated cohorts were significantly different, 2.0 and 1.5 respectively (p = 0.02). ALK-mutated patients were more likely to have their primary and predominant BM lesions on the same side (66 vs 39%; p <0.05); more than a third of ALK-mutated patients presented with miliary BM lesions (p <0.05). Regardless of ALK status, BM exhibited similar MR features – iso- to hypo-intense on T1 sequence, hyper-intense on T2 and FLAIR sequences. ALK-mutated BM were more likely to have ring enhancement (78% vs 45%, p<0.05), were less likely to have nodular enhancement (9% vs 35%, p<0.05), were three times more likely to be cystic (28% vs 9%, p = 0.06), have minimal or no perilesional edema (50% vs 3%, p = 0.06) and have no restriction of ADC values on DWI (88% vs 68%, p = 0.056) compared to non-ALK mutated patients. At a median follow up of 20 months, ALK-mutation positive patients had a median survival of 12.5 months since diagnosis of BM (range 0-40 months). In addition to systemic therapy, whole brain RT was delivered in 92% patients; 4 patients were kept on close observation. Four patients with ALK-mutation received a second course of whole brain RT for CNS disease progression. Conclusion: In addition to features like young age at presentation, non-smoker status and female predilection, ALK-mutation positive patients may have a distinct radiological appearance of BM that may prove to be an additional tool for the oncologist in prognosticating patients. We intend to study these features and validate in a larger sample.
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Definitive chemo radiation in non small cell carcinoma lung-a tertiary cancer centre experience
P. N. Shoaib Nawaz, Geetha Muttath, N. V. Vinin, Joneetha Jones, K. E. Greeshma, Nabeel Yahiya E.K, Arun Narendran
Department of Radiation Oncology, Malabar Cancer Centre, Kannur, Kerala, India
Aims/Objective: To find progression free interval in non small cell carcinoma lung patients treated with definitive chemoradiation at Malabar cancer from 1st January 2016 to 31st December 2016. Materials and Methods: This study is a retrospective analysis of non small carcinoma lung cases treated with definitivechemo radiation between January 2016 and December 2016 in the department of radiation oncology at Malabar cancer centre. Data was collected from medical records division of the institute. All non small cell carcinoma patients who received chemo radiation with or without noeadjuvant chemotherapy are included in the study. All patients were treated to a dose of 60 Gy in 30 fractions by 3DCRT or VMAT or hybrid technique. For those patients, which were unlikely to get normal organ constraints due to bulkiness of the tumour, neo adjuvant chemotherapy was given with paclitaxel and carboplatinfor 2-3 cycles. After completion of chemotherapy, concurrent chemo radiation was started after three weeks. Patients were followed up at 1month post treatment and then 3monthly for 3 years. Imaging was done only if clinically suspicious. Results: A total of twenty patients were studied. All of them were males. Mean age was 58.3 years. Squamous -55%, adeno- 35% and poorly differentiated carcinoma- 10%.45% had stage 3adisease, 35% had stage 3b, 10% had stage 2b and 10 % stage 2a. 50% patients underwent neoadjuvant chemotherapy with paclitaxel and carboplatin due to bulky tumour and the rest 50% underwent upfront chemoradiation. Mean number of chemo cycles was 3. All patients who took chemotherapy had partial response as per RECIST criteria. All patients except one completed chemoradiation. Only one patient developed brain metastasis during the course of treatment and was stopped in between.3 patients were lost to follow up. Median follow up period is 24 months (range 32-16). Median progression free survival is 20.5 months and median overall survival is 24 months. Conclusions: Concurrent chemoradiation with or without neoadjuvant chemotherapy in locally advanced non small cell carcinomas of lung is well tolerated by our population of patients. Progression free survival and overall survival is better than the literature data. Further larger studies in this aspect can throw more light in this area.
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Factors affecting the risk of brain metastases after definitive chemoradiation for locally advanced nonsmall-cell lung carcinoma
Mohammed Harris, Giridharan
Purpose: As therapy for locally advanced non–small-cell lung carcinoma (NSCLC) improves, brain metastases becomes a greater problem. We analyzed our chemoradiation experience for patients at highest risk for the brain as the first failure site. Methods: Records for 150 consecutive patients with stage II/III NSCLC treated definitively with chemoradiation in our institute were reviewed. Most patients (89%) received cisplatin, paclitaxel, or both. All had negative brain imaging before treatment. Post treatment brain imaging was performed for suspicious symptoms. Incidence of BM was examined as a function of age, sex, histology, stage, performance status, weight loss, tumor location, surgery, radiation dose, initial radiation field, chemotherapy regimen, and chemotherapy timing. Results: Crude and 2-year actuarial rates of BM were 19% and 30%, respectively. Among pre-treatment parameters, stage IIIB was associated with a higher risk of BM versus stage II/IIIA. Examining treatment-related parameters, crude and 2-year actuarial risk of BM were 27% and 39%, respectively, in patients receiving chemotherapy before radiotherapy and 15% and 20%, respectively, when radiotherapy was not delayed. Conclusion: Patients with later stage, non squamous NSCLC, particularly those receiving induction chemotherapy, have sufficiently common BM rates.
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Dosimetric robustness of motion inclusive strategies (mid P and internal target volume techniques) in lung stereotactic ablative radiation therapy
Ashish Bhange, V. Shankar, A. Karuppusamy, K. P. Bhaskar, T. Basu, U. Saxena, G. Ponmani, S. Mourya, D. Sen, T. B. Sebin, S. Sebastian
Department of Radiation Oncology, HCG Cancer Center, Mumbai, Maharashtra, India
Aim: Motion management is one of the crucial aspect of lung stereotactic ablative radiation therapy (SABR). Various modalities of motion management have been established such as motion inclusive and exclusive techniques. The motion inclusive SABR can be done either with estimation of position of tumor in which tumor is at least distance from tumor centroid (Mid P) or with estimation of Internal target volume (ITV) encompassing range of tumor motion during respiration. We intended to study the dosimetric discrepancies in both of these modalities of motion inclusive techniques. Materials and Methods: Five patients with inoperable early stage lung cancer were included. 4D CT was done using Varian RPM gating device. All the bins of respiratory phases were transferred to MIM software. The gross target volume (GTV) was contoured on one of the 10 bins of 4D CT. The contours were deformed on rest of the bins and Mid P bin was calculated using the inbuilt workflow in MIM software. ITV was estimated using all the bins of 4D-CT. GTV was drawn on Mid P bin (TV Mid P) and ITV volume was expanded over GTV (TV itv). PTV margin of 3 mm was expanded over TV Mid P and TV itv. Two set of target volumes and OARs were planned on Monaco TPS version 5.11. The dosimetric analysis including target coverage, high dose spillage (V105% prescription dose), intermediate dose spillage (D2cm-maximum dose in 2cm volume around PTV and V50% prescription dose/PTV volume), low dose spillage (opposite lung dose) and rest OAR doses was done for both the plans. Statistical comparison was done using paired t test in SPSS software Version 21. Result: Mean tumor volume was 13.02cc and 7.56cc in ITV and Mid P bin respectively. Target coverage parameters (Conformity and heterogeneity index) was satisfied in both the plans. High dose spillage was limited to PTV in both the plans. Mean D2cm was 17.68 Gy (Range:13.48-20.9Gy) and 15.69Gy (Range:12.47 – 17.9Gy) in ITV and Mid P respectively (P=0.023). Mean V50%/PTV was 3.35 and 3.57 in ITV and Mid P respectively (P=0.18). Mean Dmax of opposite lung, heart, chest wall, vessels and liver was 4.79, 6.98, 30.62, 14.89, 3.01Gy and 4.098, 5.68, 26.87, 13.17, 2.6 Gy in ITV and Mid P technique respectively (P=significant in all except liver). Conclusion: Mid P technique offers superior dosimetric robustness for target and OAR doses as compared to ITV technique. Hence Mid P is preferred technique of motion inclusion in lung SABR given the advantage of target delineation offsetting 4D data artefacts, plan robustness with uncompromised target coverage due to sufficient penumbra and accurate image registration with time weighted average sequence of 4D CBCT giving better understanding on baseline shifts.
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Stereotactic body radiation therapy for central early nonsmall cell lung cancers-yes! It's possible
Ritika Harjani Hinduja, Jack Zheng, Graham Cook, Robert M. MacRae, Jason Pantarotto
Purpose/Objectives: Stereotactic Body Radiation Therapy(SBRT) is a standard treatment for early non small cell lung cancers. Concerns exist about its use in centrally located tumours. RTOG 0813 demonstrated the efficacy and tolerability of SBRT in centrally located tumours. However, there is a reluctance in many institutions regarding its widespread adoption into clinical practice. We report our institutional experience with treatment of central tumors. Materials and Methods: We retrospectively reviewed consecutive medically inoperable early central NSCLC patients treated with SBRT in an ethics approved study. All tumours were biopsy proven and adequately staged by Positron Emission Tomography (PET) scan. The end points of interest were Local Recurrence Free Survival (LRFS) and Overall Survival (OS). The outcomes were compared based on ECOG status, left versus right sided tumours, histology, age adjusted Charlson Comorbidity index, SUVmax and pre-treatment Hemoglobin and Poly-Morpho-Nuclear (PMN) leucocytes. Results: 92 patients who underwent SBRT for centrally located lung tumours were eligible. The median age was 75 years, (56 to 90 years). 40(43.5%) were males. The median age adjusted comorbidity index was 5. 86% were current/former smokers. 28, 34, 27 and 3 patients had ECOG 0, 1, 2 and 3 respectively. 52.2% had left and 47.8 % had right sided tumours. 28.3% were squamous cell carcinomas, 50% were adenocarcinomas and remaining 21.7% included large cell and NSCLC-NOS. All patients were PET staged and the median SUVmax was 6.85. The most common dose schedule was 60Gy in 8 fractions. The dose fractionation was increased in 14 patients to deliver treatment in 15-20 fractions. The median BED was 105Gy. The median OS was 47 months as compared to 53 months for peripheral tumours in the database(p-0.08). The median local recurrence free survival (LRFS), Regional recurrence free survival (RRFS) and Distant relapse free survival (DRFS) was 40 months, 47 months and 45 months, respectively. Lower ECOG score patients had better OS as compared to higher ECOG score (median OS- 42, 61, 35 and 18 months, respectively p-0.05) and a trend towards better LRFS (P-0.07). Patients with pre-treatment hemoglobin >130g/L and PMN leucocyte count > 5*109/L were associated with improved OS (p- 0.03 and p- 0.003 respectively). Adenocarcinomas had a higher LRFS and OS as compared to squamous cell carcinomas, however this was not statistically significant (median OS- 65 and 47 months respectively, p- 0.2), (median LRFS of 47 and 35 months respectively, p- 0.10). There was no difference in LRFS or OS when stratified by age adjusted Charlson comorbidity score, SUVmax or location of left/right side. Conclusion: SBRT for centrally located tumours is feasible with outcomes comparable to published literature. Lower ECOG performance score, pre treatment hemoglobin > 130, PMNs > 5 and adenocarcinoma histology have a better outcome.
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Prospective Comparative Study of Dosimetric Parameters in 3D versus 4D CT Image Acquisition in Conformal Radiotherapy of Carcinoma Lung
Pallavi Nair, Arun Sankar, Saju Bhasi, Roshni Syam, Geethi M.H, A. Sajeed, Mithun Sajeev, C. D. Sivanandan
Department of Radiation Oncology, Regional Cancer Centre, Trivandrum, Kerala, India
Aim: The aim of this study was to compare the planning parameters in three dimensional versus four dimensional image acquisition in conformal radiotherapy of carcinoma lung. Materials and Methods: Fifteen patients with carcinoma lung, who were planned for radical chemoradiation and who were registered at our institution from January 2016 to August 2018 were selected. A Conventional CT simulation was done followed by a 4DCT. Images were taken at 10 phases of respiration in each slice and images at each phase were compiled together to 10 bins. A 3DCRT plan(PlanA) was first generated based on the conventional CT images using Departmental protocols. The Gross target volume(GTV) was first contoured followed by the Clinical target volume(CTV). The PTV was contoured with a margin of 1.5cm in the superior and inferior direction and 1cm all around the CTV. A 4DCT plan(Plan C) was then generated from the 4D data set. IGTV was contoured using the maximum intensity projection(MIP) followed by an ICTV. IPTV was contoured with a margin of 1cm in all direction. Another Plan(Plan B) was generated by copying the 4DCT volumes to the 3DCRT plan(Plan A). The GTV/IGTV, CTV/ICTV and PTV/IPTV volumes were compared. The Plan B and Plan C were compared in terms of the volume of IGTV receiving 100% of dose(ITV V100), volume of ICTV receiving 100% and 98% of dose(ICTV V100, V98) and volume of IPTV receiving 100% and 95% of dose(IPTV V100, V95). The Dose volume histogram(DVH) of the organs at risk(OAR) in Plan A and Plan C was compared. Results: Nine patients(60%) had left sided tumors. Eleven patients(73%) had upper lobe tumors and 4(27%) had lower lobe tumors. Six patients(40%) had stage IIA tumors, 2(13.3%) had stage IIB, 4 (26.7%) had stage IIIA and 3 (20%) had stage IIIB tumors. Thirteen patients had adenocarcinoma and only 2 had squamous cell carcinoma. The GTV was significantly smaller than the IGTV(p=0.005) with a mean difference of 13.9cm3 and the PTV was significantly larger than the IPTV(p=0.002) with a mean difference of 81cm3. The ITV V100, ICTV V100, V98 and the IPTV V100, V95 had significantly better coverage in the 4DCT plan compared to the conventional plan. The lung volume receiving 20Gy and 5Gy(V20, V5) and the mean lung dose(MLD) was significantly reduced in Plan C. The heart volume receiving 30Gy and 40 Gy(V30, V40) were significantly reduced in Plan C. The dose to the spinal cord(maximum dose) and esophagus(mean dose) were less in a Plan C(p=insignificant). These results were correlated with the site of tumor, the Tumor stage and the nodal stage. The difference between the PTV and IPTV was found to have a significant correlation with the site of the tumor with upper lobe tumors showing the maximum difference. Conclusions: This study demonstrated that 4DCT helped to delineate the GTV in all phases of respiration and thereby reduce the PTV. This in turn led to reduction in the doses received by the OARs.
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Dosimetric evaluation of three different image datasets in lung stereotactic body radiation therapy planning
Nishtha Sehra, Naveen Mummudi, Anil Tibdewal, Yogesh Ghadi, J. P. Agarwal
Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
Aims and Objectives: To investigate and compare the dosimetric difference between Average Intensity projection (AIP), Maximum Intensity Projection (MIP) and free-breathing (FB) CT image datasets used in Stereotactic Body Radiation Therapy (SBRT) for Lung cancer. Materials and Methods: We retrospectively studied ten patients who underwent SBRT for lung cancer at our institution. All patients had undergone a planning free-breathing and 4DCT scan; a motion encompassing technique was performed, by registering the ITV generated from the MIP onto FB CT; planning target volume (PTV) was generated and dose calculation performed. MIP and AIP images sets were generated on the Eclipse External beam planning workstation (v13.5). The PTV based on FBCT was copied to MIP and AIP CT sets. All treatment beams and optimized MLC fluences of plan based on FB CT were copied to MIP and AIP CT sets with the same iso-center. Dose calculation was performed using the same Monitor units. Dosimetric parameters for target volumes and organs at risk were compared between the three datasets; Statistical analyses was performed using SPSS. Results: Dosimetric differences between FB and AIP/MIP datasets were seen in the doses to PTV and OARs. Better target coverage was seen with AIP plans; lung dosimetric features favored FB CT, likely because of the larger lung volume in FB CTs. No difference between the plans were seen for dose characteristics pertaining to heart, spinal cord and esophagus. See [Table 1] and [Table 2]. Conclusion: MIP CT is helpful in generating ITV; however inherent imaging artifacts limits its role in dose calculation. FB CTs allow performing a contrast study and is a useful fail-safe option in patients with difficulty completing a 4DCT; else, AIP CT dataset may be a viable alternate for dose calculation and may obviate the need for a separate FB planning CT scan. The clinical significance of these minimal dosimetric differences are unknown.
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To study the dosimetric benefit of adaptive radiotherapy in carcinoma lung treated at a regional cancer centre
C. K. Fareena Taj, N. P. Jayashree, Sweta Kumari, Vezokhoto, Ibrahim Khaleel, Siddanna Palled, H. B. Govardhan, Kurian Puttur
Aims/Objectives: To evaluate the dosimetric benefits of adaptive radiotherapy in carcinoma lung treated at a regional cancer centre. Materials and Methods: A total of 15 locally advanced non-small cell lung cancer (NSCLC) planned for definitive curative chemo radiation were prospectively recruited for this study. All patients underwent a base line and a mid-treatment CT scan (breath hold CT). Two sets of breath hold CT acquired one each at end inspiration, and end expiration to estimate tumor motion to account for ITV. A free breathing CT scan is acquired for planning and contouring. Contouring was done for heart, lungs, spinal cord and target volumes according to RTOG contouring guidelines. GTV delineation was done on CT images for both primary and significant lymph nodes. CTV for both primary and nodes were grown by adding a margin of 6-8mm, ITV of estimated tumour motion was grown, PTV of 5mm as per the institutional protocol for set up uncertainties. IMRT plan was done on Eclipse planning system for a total dose 66 Gy in 33 fractions. Phase I RT was delivered for 46 Gy in 23 fractions. Mid treatment CT simulation was done after phase I RT. Planning for phase II RT was done on mid treatment CT simulation scans for a dose of 20 Gy in 10 fractions. Volumetric and dosimetric changes of target volumes and critical structures were assessed between the two plans, plan 1 of (66 Gy) n plan 2 (46Gy+20Gy). Appropriate statistical tests were used for the study. Results: The mean volumes of GTV, CTV, ITV, PTV for phase I was 185.14cc, 430.18cc, 837.07cc, 1112.8cc respectively. And the mean volumes GTV, CTV, ITV, PTV in phase II was 106.7cc, 315.86cc, 556.86cc, 700.6cc respectively. The mean volume reduction for GTV, CTV, ITV, PTV was 42.9%, 27.2%, 33.4%, 37% respectively. The mean of Dmean for plan I was 37.8Gy, 9.82Gy, 19.7Gy for ipsilateral lung, contralateral lung and heart respectively. For plan 2, mean of Dmean was 35.7Gy, 8.64Gy, 17.5Gy respectively. The mean Dmax of spinal cord in plan 1 was 46Gy and in plan 2 was 40 Gy. Mean of D10, D20, D50, D100 for ipsilateral lung was 64.6Gy, 63,5Gy, 41.28Gy, 1.9 Gy for plan 1; and 63Gy, 61Gy, 39.19Gy, 1.71Gy for plan 2. Mean of D10, D20, D50, D100 for contralateral lung was 17.6Gy, 13.5Gy, 6.4Gy, 0.8Gy for plan1; and 17.2Gy, 12.5Gy, 6.0Gy, 0.6Gy for plan2. Mean of D10, D20, D50, D100 for heart was 42.7Gy, 34.4Gy, 13.47Gy, 1.3Gy for plan 1; and 41.2Gy, 33.9Gy, 12.8Gy, 1.15Gy for plan2. Conclusions: There was a significant reduction in the target volumes and dose to OAR in Plan2 when compared to Plan 1, with significant increase in normal lung volume. Hence adaptive RT in CA Lung can be safely used. And clinical follow up data awaited.
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Role of neutrophil lymphocyte ratio and platelet lymphocyte ratio as predictor of stage in lung cancer
P. K. Naseef, Manoj Gupta, Rajesh Pasricha, Sweety Gupta, Ajay S. Krishnan, Muddabhaktuni B. Minu Chandra, Nidhi Sharma, T. S. Aathira, Ajas Ibrahim
Background: Lung cancer is the most common cancer in the world for several decades. Out of this 58% occur in the developing world. Indian subcontinent due to many variations in genetic, socioeconomic and tobacco smoking practices, the standard predictive and prognostic markers approved as a part of standard of care in Europe and United states may not be well fitting into the context. At this juncture a search for an easily accessible and inexpensive strategy to predict and prognosticate the stage in carcinoma lung was made. As hemogram is the most easily accessible and less expensive investigation, which can be done in any nook and corner of the country, we tried to use different permutations and combinations of this basic information to analyse if it was following any trend with the disease process. Aim: To evaluate the predictive value of Neutrophil lymphocyte ratio(NLR) and platelet lymphocyte ratio(PLR) in base line stage and histology of lung cancer. Methods: 57 biopsy proven patients of lung cancer were analysed in the dept of radiotherapy and oncology, AIIMS Rishikesh from February 2018 to September 2018. All patients who had diabetes mellitus, thyroid dysfunction, obvious signs of infection were excluded. Analysed patients baseline hemogram was used for calculation of any statistical trends. Result: The baseline characteristics were similar between the two groups. The sample was divided based on histology into NSCLC(Non small cell lung cancer) and SCLC(Small cell lung cancer). On analysis of the 2 different subsets, the mean value of PLR was high with SCLC(Mean + 1 SD :268 + 213) when compared to NSCLC (Mean + 1 SD :189 + 96). But the difference in means were not found to be statistically significant (p Value-0.19). On analysis of NLR(Neutrophil lymphocyte ratio), it did not show a marked difference between the NSCLC and SCLC [Median 3.89 (IQR – 3.09) and 4.29 (IQR – 5.36)]respectively. The sample was evaluated based on stage. PLR showed a small difference in mean between Stage 3 and Stage 4 (Mean + SD : 194 + 94 and 228 + 163). NLR however, did not show much difference between the stage groups (Median (IQR) : 3.83 (2.9) and 3.89 (3.69) respectively). We further found that none of the differences observed here were statistically significant. Conclusion: The PLR appears to have some predictive role in the stage and histology. However, statistical significance could not be established in our study due to the small sample size. A conclusive statement on basic haematological parameters predicting or prognosticating the disease could be established or rejected only after analysing an adequate sample.
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Three arm retrospective study comparing gefitinib alone, cisplatin and etoposide or combination of both in advance nonsmall cell lung cancer
D. Kumar, A. K. Arya, I. Yadav
Aims: To find out viability for use of Gefitinib alone or in combination with Cisplatin-based chemotherapy in patient of advanced non-small cell lung cancer. Materials and Methods: 103 Patients who were diagnosed from January 2012 to march 2018 were considered for evaluation. 13 Patients were excluded who defaulted after registration without receiving any treatment. 44 patients those who lost to follow-up and were not available for evaluation. 46 patients were found evaluable for analysis. As per their treatment received, they were distributed in three arms. 16 patients in Arm-A, those who received Cisplatin 80 mg/m2 iv on day one and Etoposide 100 mg/m2 iv on day-1 to day-3 for two cycles followed by Radiotherapy to thoracic region. 14 patients in Arm-B, those who received same chemotherapy regimen along with Tab Gefitinib 250mg daily from day one of enrolment followed by Radiotherapy to thoracic region. 16 patients in Arm-C, who received only Tab Gefitinib 250 mg daily from day one of enrolment along with Radiotherapy to thoracic region. All patients had received palliative Radiotherapy in form of 30Gy/ 10 fractions at the rate of 300cGy per fraction. Response of treatment was evaluated by chest X-ray. Symptomatic improvement on follow-up, evaluated according to the clinical judgment and KPS scoring. Results: The mean age of patients was 59 years (range 39-71 year). Out of 46 patients there were 34 (73.91%) men and 12 (26.08%) women. The most common histopathology type was Squamous cell carcinoma (52.2%), followed by (47.8%) adenocarcinoma. 7 Out of 46 patients, were non-smoker. Mean year of smoking was 25.4yrs. Arm-A: Mean progression free survival (PFS) was 113 days (range 65-267 days). The most common haematological toxicities were neutropenia and leukopenia in this group. Arm-B: Mean progression free survival (PFS) was 143 days (range 98-386 days). The most common haematological toxicities were neutropenia and leukopenia. Patients also developed skin rashes (28.6%) up to grade 2 attributed to Gefitinib. Arm-C: Mean progression free survival (PFS) was 132 days (range 72-306 days). The most common toxicity in patients was skin rash (36%) up to grade 2. Gefitinib was well tolerated and without any life-threatening toxicities. One-year survival for Arm-A, Arm-B and Arm-C was 43.75%, 78.57% and 68.75% respectively. Conclusions: In most of the literatures EGFR mutation-positive show a strong correlates with a favourable response in case of Non-small cell lung cancer. EGFR mutation status should be done in all patients of non-small cell lung cancer, but in resource-limited institutions, the test is not easily available. In case of advanced Non-small cell lung cancer patients, treatment with Gefitinib is still a good option. Tab Gefitinib therapy of 250 mg/day either given alone or in combination of cisplatin and etoposide is having better response rate, good safety profile and is well manageable.
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Clinical outcomes of stereotactic body radiotherapy for early stage lung cancer at a tertiary care center: A retrospective analysis
M. P. Aparna, S. Roshni, Arun Sankar, A. Sajeed, M. H. Geethi, A. L. Lijeesh, Saju Bhasi1, K. M. Jagath Nath Krishna2, C. D. Sivanandan
Departments of Radiation Oncology,1 Medical Physics and2 Biostatistics and Epidemiology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
Aims/Objectives: To estimate the relapse free survival after 12 months of SBRT. To estimate the rates of toxicity one year from the start of SBRT. Materials and Methods: We reviewed the records of ten patients treated with SBRT for stage I non-small cell lung carcinoma (NSCLC) during the period of January 2015 to April 2017 at RCC, Trivandrum and was followed up till September 2018. All patients underwent 4DCT simulation with free breathing technique. Area of maximum intensity projection was recorded using 10 phases of respiratory cycle. The planning target volume (PTV) equaled gross tumor volume (GTV) plus internal target volume (ITV) plus 3-4 mm margin. Planning was done with Volumetric-modulated arc therapy (VMAT) technique in all patients using semi arcs including 2 non coplanar beams. A dose of BED >100 Gy was planned to PTV prescribed to the 100 % isodose line covering at least 95% of the PTV. Delivery of each fraction of treatment was done with Image-guided radiation therapy (IGRT) technique using cone beam CT. Results: Meta-analysis of studies on SBRT based on biological effective dose has shown a statistically significant overall survival benefit and loco regional control at 2 years with confidence interval 0.701 (0.648–0.753) and 0.942 (0.901–0.982) respectively in the treatment of Stage I NSCLC with the delivery of BED >100 Gy. In our study relapse free survival at 12 months was found to be 90%. Tumor control was excellent when PTV volume was less than 75 cm3. In field recurrences happened in 2 patients and one patient had nodal relapse. There were no grade III acute or chronic toxicities. Conclusions: SBRT was emerged as an adaptation of principles from SRS in early 1990, s. It allows the delivery of high doses of radiation therapy using hypo fractionated regimens using multiple co-planar and non-coplanar beams and has got radiobiological advantage. Most of our patients were elderly with multiple comorbidities, active breath holding technique and tumor tracking system was not available in our center and our results shows that SBRT using VMAT technique in free breathing set up is safe and effective for medically inoperable stage I non-small cell lung carcinoma patients in resource limited setting.
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Analysis of outcomes in patients with locally advanced nonsmall cell lung stage III treated with chemoradiation
V. Gowthami, I. Monica, Syed Fayaz Ahmed, V. Deepthi
Aims/Objectives: The objective of this paper is to analyze clinical profile and the survival outcomes of patients with locally advanced non-small cell lung cancer treated with definitive chemoradiation. Background: Lung cancer is the leading cause of cancer-related mortality. Understanding patient attributes that enhance survival is necessary to individualize treatment options. Materials and Methods: Medical records of locally advanced non-small cell lung cancer (NSCLC) patients treated with chemo radiation (CTRT) from 2013 to 2017 at our institute were reviewed. The patients had unresectable tumor limited to one hemithorax and no evidence of distant metastases. Data analysis was done using SPSS v20. Kaplan-Meier estimates wereused to estimate survival. Results: 36 patients with non-small cell lung cancer -stage IIIA/IIIB, treated with 3D-CRT from 2013 to 2017 were available for analysis. Male to female ratio was 5:1. Mean age at diagnosis is 59 years(range 41-82 years). The predominant histological type wasadenocarcinomain 21(58%) followed by squamous cell carcinomas(SCC) in15 (42%) cases. Most of the patients presented with stage-IIIB (81%). Right lung was involved in 19(52.8%) cases, left lung in 17(47.2%) cases. Cough and dysnoea (26%), chest pain (23.8%), hoarseness of voice (9.5%) were common presenting symptoms. The radiotherapy dose was 60Gyin 30 fractions. 77% were treated concurrently and 23% received sequential chemotherapy. Concurrent chemoradiation was given with two cycles of etoposide plus cisplatin. Sequential therapy consisted of six cycles of sequential chemotherapy with platinum-based doublets. The median OS of all patients was 16 months: One and two-year OS was70% and 38% respectively. The median OS rates of patients under and over 57 years were 14 and 17months, respectively (p=0.388). The median OS rates of patients with squamous cell carcinoma (SCC) and non- SCC lung cancer were 17 and 16 months, respectively (p=0.795). The median OS rates of patients treated with concurrent chemotherapy and sequential chemotherapy was 14 and 16 months respectively (p=0.373).17 % of patients had progressive disease-4 patients had metastasis to brain, 1 with metastasis to bone and 1 had local recurrence on follow up. Conclusions: The predominant histology was adenocarcinoma and its variants followed by squamous cell carcinoma. Definitive CRT, sequence being individualized depending on performance status and disease stage at presentation, is a feasible and effective treatment modality for locally advanced NSCLC patients.
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A prospective, comparative, randomized study of concurrent chemoradiation with weekly carboplatin versus weekly gemcitabine in locally advanced non-small cell carcinoma of lung
Azizul Purkait, Biswamit Bhattacharya, Diptimay Das, Sanatan Banerjee
Department of Radiotherapy, Burdwan Medical College and Hospital, Burdwan, West Bengal, India
Introduction: Most of the patients with non small cell carcinoma of lung (NSCLC) present with locally advanced disease with tumor being non-resectable because of either loco-regional invasion or lymph nodal metastasis. The standard treatment for this patient is concurrent chemoradiation with platinum based therapy. Gemcitabine is an active chemotherapeutic agent in NSCLC and is a potent radio-sensitizer. Comparative study of gemcitabine versus carboplatin in concurrent chemoradiation of locally advanced NSCLC has not been investigated in much detail earlier. The aim of this study is to evaluate the toxicity and efficacy of concurrent chemoradiation with weekly gemcitabine compared to the widely accepted concurrent chemoradiation with weekly carboplatin in management of locally advanced NSCLC. Methods: Total sixty patients (n=60) were enrolled in this study. Thirty patients were assigned in each arm (n=30) in a randomized manner. All patients received thoracic external beam radiation of 60 Gy in 30# in 6 wks by telecobalt machine in parallel opposed AP/PA technique. In control arm, patients received weekly carboplatin (AUC= 2) and in study arm patients received weekly gemcitabine (150 mg/m2) during the course of radiation. CECT thorax was done after 6 week of radiation and response evaluation was done by RECIST criteria. Toxicities were assessed by CTCAE criteria (Version 4.03). The two groups were comparable in terms of age distribution, sex distribution, performance status, stage and histological grade. Results: 50% patients achieved partial response (PR) in the control arm while 63% patients achieved PR in the study arm, but the difference was not significant statistically (P=0.087). Gemcitabine had better disease control rate than Carboplatin (87% versus 80%), but the difference was not significant statistically (P=0.253). Median progression free survival in both arms were comparable (4.5 month versus 4.25 month). Gemcitabine had increased rate of radiation pneumonitis (33% versus 47%), esophagitis (23% versus 43%), anemia(43% vs 63%) and neutropenia (53% vs 63%). Carboplatin had increased rate of thrombocytopenia (47% vs 30%). Other treatment related complications were same in both arms. Conclusion: Concurrent chemoradiation with weekly gemcitabine had better disease control rate than carboplatin at the cost of increased toxicities. So, gemcitabine may be used in concurrent chemoradiation of locally advanced NSCLC patients who have contraindication to platinum compound or as an alternative to carboplatin in patients with good performance status. Further multi-centric studies involving greater number of patients are required to confirm the results.
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Locally advanced carcinoma lung- best supportive care or short course palliative radiotherapy
Anil Khurana, Shiely Arora, Paramjeet Kaur, Om Parkash, Ashok K. Chauhan
Aim: To evaluate the effectiveness of palliative radiotherapy and best supportive care in locally advanced carcinoma lung and to analyze the risk factors which help in decision making. Materials and Methods: Retrospective analysis of 100 patients from January 2015 to June 2018 registered at PGIMS Rohtak with histopathological proof of carcinoma lung. Treatment given was different hypofractionated radiation regimes with or without concurrent chemotherapy or best supportive care. 8 Gy in single fraction, 20 Gy in 5 fractions over 5 days and 30 Gy in 10 fractions over 2 weeks regimens were used. They were compared with respect to survival, symptom palliation and quality of life. The risk factors assessed were performance status (PS), histopathology, stage and continuation of smoking. Lost to follow up and time of death was taken as end point. Results: Median survival was 6 months amongst our set of patients however there were 26 patients who survived less than 2 months, even prior to the effect of radiation. All of these 26 patients presented with poor PS (ECOG 4 and above) and amongst rest 74 patients had PS between 2 to 4. Only 5 patients with ECOG 4 survived for 3 to 8 months. Symptom palliation was achieved in all the three regimes of radiation. Conclusions: All parameters should be assessed prior to treatment commencement. Best supportive care as an option should be offered to the patient/attendants who are with poor PS but its recommendation as a guideline must be validated by randomized controlled trial. Short course palliative Radiotherapy is good option in terms of symptom palliation in patients with life expectancy more than 2 months.
| > Thorax: 16|| |
A radical conformal radiotherapy and concurrent chemotherapy in locoregionally advanced and medically inoperable early stage non-small cell lung cancer: A single institution experience
C. D. Sivanandan1, Sajeed Abdul Rahuman1, S. Roshni1, Arun Sankar1, A. L. Lijeesh1, K. M. Jagathnath Krishna2, M. H. Geethi1
1Departments of Radiation Oncology and2 Biostatistics and Epidemiology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
Aims/Objectives: Primary: Response rate. Secondary: (1) Patterns of failure, (2) Failure free survival, (3) Overall survival, (4) Prognostic factors, (5) To assess treatment related toxicity. Materials and Methods: This is an interim analysis of prospectively collected data of patients who underwent radical chemoradiation for non-small cell lung cancer between the period 1st December 2013 and 30th April 2016 in Regional Cancer Centre Trivandrum. Patients were selected for radical chemoradiation if there was cytological or histological diagnosis of NSCLC, stage IIIA, stage I or II disease who were unfit or unwilling for surgery, ECOG performance status 0 to 2 and normal blood counts and biochemical parameters. Selected stage IIIB cases were also included. Radiotherapy planning was done according to three dimensional conformal radiotherapy (3D CRT) technique. Intensity modulated radiotherapy (IMRT) was considered if the dose distribution with 3D CRT was not satisfactory. Dose prescribed was 60-64 Gy to PTV in 2 Gy per fraction, 5 fractions a week. Concurrent chemotherapy consisted of cisplatin 75 mg/m2 day 1 and 29, and etoposide 70 mg/m2 day 1 to 3 and day 29 to 31 of radiotherapy. Results: Total number of patients was 25. Median age was 58 years (range 39 to 72). There were 3 females and 22 males. Pathological diagnosis were adenocarcinoma in 12 patients, squamous cell carcinoma in 10, NSCLC not otherwise specified in 2 and poorly differentiated carcinoma in 1. One patient had stage I disease, 6 had stage II, 14 had IIIA and 4 had IIIB. The response rate (complete and partial) was 68%, six (24%) complete and 11 (44%) partial. Median failure free survival was 26 months. Thirteen (52%) patients failed. 4 (16%) failed loco-regionally and 9 (36%) systemically. Median overall survival was 25 months. Planning target volume (PTV), response to treatment and T status of the primary tumor had prognostic significance, but none had significance in multivariate analysis. Two patients died during treatment, one due to febrile neutropenia and other due to renal failure. Five patients (20%) had >10% weight loss. Thirteen (52%) and 7 (28%) patients had grade 3 or above leucopenia and thrombocytopenia respectively. Conclusions: Radical conformal radiotherapy along with concurrent cisplatin and etoposide produced impressive response rate and survival in early and locally advanced non-small cell lung cancer. However it was associated with significant toxicity. Majority of failures occurred systemically.
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Recurrences after stereotactic body radiation therapy for medical inoperable early nonsmall cell lung cancers-salvage remains challenging
Ritika Harjani Hinduja, Jack Zheng, Jason Pantarotto, Robert MacRae
Purpose/Objectives: Stereotactic Body Radiation Therapy (SBRT) is an accepted standard treatment for treatment of stage I medically inoperable non-small cell lung cancers (NSCLC). The most common mode of failure for these patients is distant failure. Among the few percentage of patients who fail locally or regionally, salvage treatment options are limited in this frail population. We aim to evaluate our experience in salvage treatments at local or regional isolated failures after SBRT. Materials and Methods: We retrospectively reviewed failure patterns and subsequent treatments for our early NSCLC patients treated with SBRT/ hypo-fractionated radiation therapy between 2009 and 2015 in a research ethics board approved study. Local and regional recurrences were noted and then were categorized into isolated local/regional /loco-regional versus widespread progression (along with distant metastases). Salvage treatments offered to loco-regional recurrences were reviewed. Results: 511 patients who received SBRT/hypo-fractionated radiation therapy were eligible for the study. 475 (92.95%) of the tumours were treated with SBRT. 395 (77.6%) were peripheral tumours and 114 (22.4%) were central. The median BED was 132Gy. With a mean follow up of 4.5 years, 47(9.2%), 47 (9.2%) and 85 (16.7%) experienced local, regional and distant failures respectively. Of these, 38 patients experienced isolated local and/or regional failure (21- local, 11- regional and 6 local and regional failure; with no distant failure). 21.05% (8) tumours received salvage treatment with modalities like RFA (3), re-irradiation with or without chemotherapy (5). Of the non-salvaged tumours (30), 16 (53.33%) received palliative treatments (7- palliative radiation, 9- palliative chemotherapy). The most common reason for non-salvaged tumors was poor performance score (Eastern Co-operative Oncology Group score 3 or 4), followed by dearth of local options. 13 additional patients developed loco regional failure with time- separated distant metastases (with distant failure at minimum 3 months after loco-regional failure), of which 6 were salvaged locally. Conclusions: Although, the outcomes for stage I medically inoperable patients are impressive with the advent of stereotactic body radiation therapy, management of local and regional recurrences remains a dilemma owing to poor performance status and overall frailty of this population.
[Table 1], [Table 2]
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