|Year : 2022 | Volume
| Issue : 3 | Page : 740-746
To evaluate the use of tandem and cylinder as an intracavitary brachytherapy device for carcinoma of the cervix with regard to local control and toxicities
Irfan Rasool Gadda1, Nazir Ahmad Khan1, Shaqul Qamar Wani1, Misba Hamid Baba2
1 Department of Radiation Oncology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
2 Department of Radiological Physics, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
|Date of Submission||09-Feb-2021|
|Date of Decision||04-Mar-2021|
|Date of Acceptance||05-Mar-2021|
|Date of Web Publication||28-Jan-2022|
Misba Hamid Baba
Room No. 254, Department of Radiological Physics and Bio-Engineering, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar - 190 011, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
Introduction: Brachytherapy always remains a keystone in the treatment of gynecological carcinoma for both definitive and adjuvant treatments. Due to the rapid fall-off nature of brachytherapy, the target gets a high dose with a low dose to the normal organs nearby and thereby increasing the tumor control probability.
Aims and Objectives: This study aims at the evaluation of local control and toxicities in the carcinoma of the cervix using tandem and cylinder as brachytherapy applicator.
Materials and Methods: The study was conducted between January 2014 and December 2018 in a tertiary care hospital. Thirty-one patients who fulfilled our set criterion of Clinical stage IB3–IVA, Performance status Eastern Cooperative Oncology Group 0–2 were selected. All patients were treated initially with external beam radiotherapy and later by high dose rate intracavitary brachytherapy after completion of external beam radiation therapy (EBRT). A dose of 18–21 Gy was delivered to the residual disease in three sessions with a 1-week interval between each session. The dose was optimized in such a way that the organs at risk (OAR), namely bladder and rectum received doses within their tolerance levels. The patients were continuously monitored using Common Terminology Criteria for Adverse Events version 5.0 for both acute and late toxicities and by imaging for local control. Statistical analysis using SPSS Version 20.0 (SPSS Inc., Chicago, Illinois, USA) was used to evaluate the results. Continuous variables were expressed as mean ± standard deviation, and categorical variables were summarized as frequencies and percentages.
Results: Out of the 31 patients, 5 (16.1%) experienced radiation-induced Grade 1 skin changes which were due to EBRT, 1 (3.2%) had Grade 1 G. I. T toxicity, 1 (3.2%) had Grade 1 radiation-induced vaginal mucositis after brachytherapy. At 6–8-week follow-up, all the patients showed no evidence of disease on radiological imaging. At 3 months of follow-up, 1 (3.2%) patient had radiation-induced proctitis of Grades 2 and 3 (9.7%) had radiation-induced cystitis of Grades 1 and 1 (3.2%) had Grade 2 cystitis. At 6 months of follow-up, 1 (3.2%) had Grade 1, 1 (3.2%) had Grade 2, and 1 (3.2%) had Grade 3 radiation-induced proctitis. At 3 months of follow-up, 29 (93.5%) patients had no evidence of disease, while 2 (6.5%) were having residual disease on imaging. At 6 months of follow-up, all the patients were disease-free. At 12 months of follow-up, 26 (83.9%) patients were disease-free, 1 (3.2%) had local recurrence, 2 (6.5%) had distant metastasis, and 2 (6.5%) had expired. At 24 months of follow-up, 26 patients were disease-free. Acute and late toxicities were similar to those used in the treatment of carcinoma cervix by standard brachytherapy applicators. Local control was achieved in 83.87% of cases. Two-year survival was 93.5%.
Conclusion: We observed that the tandem and cylinder applicator is an acceptable applicator to be used for intracavitary brachytherapy. It is safe and simple besides this; the toxicities and local control are similar to the other standard applicators used in brachytherapy in carcinoma cervix. However, the required dose prescription to point A was not possible in all the patients due to limitations of OARs. Furthermore, long-term follow-up is needed to see the patterns of failure, recurrence-free survival, overall survival, and long-term toxicities in the treated patients.
Keywords: Carcinoma, brachytherapy tandem, and cylinder, common terminology criteria for adverse events, dose-volume histogram, intracavitary, toxicity
|How to cite this article:|
Gadda IR, Khan NA, Wani SQ, Baba MH. To evaluate the use of tandem and cylinder as an intracavitary brachytherapy device for carcinoma of the cervix with regard to local control and toxicities. J Can Res Ther 2022;18:740-6
|How to cite this URL:|
Gadda IR, Khan NA, Wani SQ, Baba MH. To evaluate the use of tandem and cylinder as an intracavitary brachytherapy device for carcinoma of the cervix with regard to local control and toxicities. J Can Res Ther [serial online] 2022 [cited 2022 Aug 10];18:740-6. Available from: https://www.cancerjournal.net/text.asp?2022/18/3/740/351881
| > Introduction|| |
Cervical cancer is one of the most common gynecologic cancers worldwide. There were an estimated 530,000 cases of cervical cancer and 275,000 deaths from the disease in 2018. It is the third most common female cancer ranking after breast (1.38 million cases) and colorectal cancer (0.57 million cases). The incidence of cervical cancer varies widely among countries. Cervical cancer is the leading cause of cancer-related death among women in Eastern, Western, and Middle Africa; Central America; and South-Central Asia. India is the country with the highest disease frequency with 134,000 cases and 73,000 deaths. Cervical cancer affects women <45 years. India also has the highest age-standardized incidence of cervical cancer in South Asia at 22, compared to 19.2 in Bangladesh, 13 in Sri Lanka, and 2.8 in Iran. Disparities of health and poverty play a major role in this high mortality rate, whereas routine Papanicolaou and human papillomavirus testing have dramatically reduced cervical cancer deaths in developed countries. However, in developing countries without proper infrastructure facilities and medical training, the rates of cervical cancer will remain high. Only 5% of women in these regions have been screened for cervical diseases in the past 5 years. Cervical cancer as per hospital-based cancer registration data in our institution is not common cancer in our region. The incidence varies from 18 to 30 cases per year. Cervical cancer treatment depends on the cancer stage and its spread in and around the cervix. There are multiple modalities to treat cervical cancer, but the common treatment techniques are surgery, radiation therapy, chemotherapy, and targeted therapy. Although surgery is the treatment of choice in cervical carcinoma, the majority of patients present with locally advanced diseases, so these patients are treated by concurrent chemoradiation. Radiation therapy is the main component in the management of cervical cancer treatment. Radiation therapy is generally used in combination with chemotherapy for cervical cancer treatment. Cervical cancer can be treated with external beam radiation therapy (EBRT) alone or a combination of EBRT and brachytherapy or brachytherapy alone depending upon tumor stage and extent of the diseases. Various brachytherapy applicators such as tandem and ovoid, tandem and ring, or tandem and cylinder are used to place the radioactive source in the uterus and near the cervix as per the bulk of the disease and stage. Tandem and ovoid are used to treat barrel-shaped cervix using large ovoids to cover cervix, uterus, medial parametrium, and upper 1–2 cm vagina, tandem, and ring for shallow fornices, and tandem and cylinder for upper vaginal stenosis or narrowing and a superficial disease in lower vagina. In the current study, we used tandem and cylinder applicator for the delivery of high dose rate brachytherapy (HDR) for the treatment of cervical cancer patients, due to nonavailability of standard applicator at our institute and assessed the patients for local control and toxicities related to HDR brachytherapy. Although it is not an ideal applicator to treat all the stages of cervical carcinoma and literary indications for this type of applicator are less, due to nonavailability of standard applicator in centers catering to patients of low socioeconomic status, rural population, and refusal by the patient for referral, it always stands as an alternative, although a compromise is often made between an optimal dose distribution and an ideal dose distribution. Many authors have suggested the use of tandem and cylinder brachytherapy at times when either the resources are limited or when patient anatomy prohibits the use of traditional applicators, rather than refusing the treatment.
| > Materials and Methods|| |
This study was conducted in a tertiary care hospital. It was an observational study conducted between January 2014 and December 2018. This study was approved by the ethical committee of the institute. A total number of 144 carcinoma cervix patients was registered at the Regional Cancer Centre of our institute during the study period. 31 patients who fulfilled the inclusion criteria, i.e., clinical stage of IB3–IVA carcinoma cervix and performance status Eastern Cooperative Oncology Group (ECOG) (0–2) were included in this study. The patients who underwent surgery, prior pelvic radiotherapy, and performance status ECOG >2, stage IVB (distant metastasis) were excluded from the study. Written consent for treatment was taken from every patient. After a staging workup, all patients were treated initially with external beam radiotherapy. EBRT of 45 Gy was planned at 1.8 Gy per fraction 5 days a week for 5 weeks concurrent with weekly cisplatin. The cisplatin was given at a dose of 40 mg/m2 intravenously for 3 h every week. Patients were assessed for intracavitary brachytherapy (ICBT) in the last week of EBRT. In our study, all the selected cases were treated using a tandem and cylinder applicator. The majority of patients were treated under intravenous analgesics except one who received spinal anesthesia. All of the cases received three ICBT treatment sessions with a 1-week interval between each session. Patients were given lithotomy position in a procedure room for examination and assessment of the primary disease under all aseptic precautions. All patients were catheterized, and the Foley balloon was inflated with 7 cc contrast material for the localization of the bladder wall. After per vaginal and per rectal examination for the disease assessment, Sims speculum and vulsellum were inserted to make growth accessible and visible. Then, cervical dilatation was done with cervical dilators, and then, the uterine sound was inserted to check for the length of the uterine cavity. Assessment for the proper cylinder dimensions was also done after cervical dilatation. Tandem was then inserted into the uterine cavity slowly while holding vulsellum and Sims in place and was followed by insertion of the cylinder making sure that the tip of the cylinder is touching the OS. To minimize applicator movement, gauze was used to hold the applicator in place wrapped around the abdomen. The same procedure was repeated for the rest of the sessions. After intracavitary applicator placement, all patients were subjected to pelvic computed tomography (CT) scan. Once CT scanning was completed, the attending radiation oncologist then reviewed the applicator position to ensure that the tandem and cylinder were at the proper place anatomically. If any variation was observed in applicator positioning, it was rectified by readjusting the applicator and a rescan was done to confirm the position of the applicator. If everything was within the satisfaction of the treating physician, then the CT data set was exported to the treatment planning system in DICOM format through institution network. BrachyVisionTM Treatment Planning (Version 11), Varian Medical Systems Palo Alto, CA, USA system was used for treatment planning of all patients. Patients were then shifted to the treatment room. After segmentation of the target and organs at risks (OARs), i.e., bladder, rectum, and sigmoid, the reference points were defined (Reference point A: Left and Right) and the dose of 6–7 Gy was prescribed at point A [Figure 1]. The dose optimization was done so that the OARs received the doses within the tolerance limit and the target receives the prescribed dose as per the standard guidelines. After the evaluation of the plan, the dose coverage to the target and dose-volume histogram for the OAR doses was checked thoroughly [Figure 2]. Once dose volume histogram for OAR's was within prescribed limits, the dosimetric plan was approved and treatment was executed. Nine patients received 6 Gy dose only because the organ at risk, i.e., the rectal dose was getting beyond the tolerance limits. Patients were followed weekly, during treatment with CBC and KFT, and after completion of treatment; patients were followed for 2 years. Clinical evaluation, gynecological checkups, and imaging were done 6–8 weeks after completion of ICBT. The same was repeated at 3 months, 6 months, 1 year, and 2 years. The patients were monitored using Common Terminology Criteria for Adverse Events, version 5.0 for toxicities (acute and late toxicities) and by radiological imaging for local control. The recorded data were compiled edited using SPSS Version 20.0 (SPSS Inc., Chicago, Illinois, USA). Continuous variables were expressed as mean ± standard deviation, and categorical variables were summarized as frequencies and percentages. Graphically, the data were presented by bar, pie, and Kaplan–Meier Survival diagrams.
|Figure 1: Representative dose in color wash for 7 Gy prescription to point A in multiplanar view and three-dimensional view|
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|Figure 2: DVH-Rectum (2cc) and Representative isodose cloud for 7 Gy prescription to point A|
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| > Results|| |
The total number of cancer patients registered in our hospital was 22,180 between 2014 and 2018, out of these 144 were carcinoma cervix patients (0.64%). A total of 31 patients were enrolled in the study. Patients were treated with EBRT concurrent with chemotherapy followed by a supplementary dose of brachytherapy using tandem and cylinder. Patients belonged to the age group 30–70 years. The majority of the patients were in the age group 50–59 (38.7%). The majority of patients had Stage IIB (18 patients, 58.1%) at presentation. Maximum patients 22 (71.0%) received 21 Gy and 9 (29%) patients received only 18 Gy of brachytherapy boost in addition to EBRT dose of 45 Gy [Figure 3]. The first response assessment was done at 6–8 weeks posttreatment completion; all the patients were disease-free on radiological imaging. At 3 months of follow-up, 29 (93.5%), patients had no evidence of disease, while 2 (6.5%) were having residual diseases on radiological imaging [Figure 4]. At 6 months, the majority of patients were disease-free [Figure 5]. At 12 months of follow-up, 26 (83.9%) patients were disease-free, 1 (3.2%) had local recurrence, 2 (6.5%) had distant metastasis, and 2 (6.5%) expired [Figure 6]. By the end of 2 years, 26 patients were disease-free on evaluation, and out of two patients, who had distant metastasis at 12 months, one expired and the other lost the follow-up. One patient with local recurrence at 12 month followup was referred to surgical department for possible salvage did not report back and lost follow up. Acute toxicities were radiation-induced skin changes of Grade 1 in five patients post-EBRT. GI toxicity in the form of vomiting during the first session of brachytherapy with Grade 1 severity was seen in one patient. Similarly, one patient developed vaginal mucositis of Grade 1 severity [Figure 7]. At 3 months of follow-up, one patient had radiation-induced proctitis of Grade 2 and three had radiation-induced cystitis of Grade 1 and one had Grade 2 [Figure 8]. At 6 months of follow-up, three patients had radiation-induced proctitis of Grades 1, 2, and 3 in severity [Figure 9]. [Figure 10] and [Figure 11] show the late toxicity in percentage after 3 and 6 months of ICBT and disease control post-ICBT. At 2 years of follow-up, no toxicities were observed. Survival analysis was done using SPSS Version 23.0 (SPSS Inc., Chicago, Illinois, USA). The follow-up period was 66 months (maximum for patients taken for ICBT in 2014). The overall survival was 93.5% after 66 months with a mean of 61.210 months (95% confidence interval, 54.715–67.705), [Figure 12].
|Figure 5: At 6 months of follow-up postintracavitary brachytherapy, the majority of patients were disease-free|
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|Figure 10: Late toxicity in percentage after 3 and 6 months of intracavitary brachytherapy|
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| > Discussion|| |
Cervical cancer is one of the most common gynecologic cancers worldwide. Treatment for cervical cancer depends on how far cancer has spread. Cervical cancer if diagnosed early is curable. Treatment options are surgery, chemotherapy, radiation, and targeted therapy. Surgery is done for early cervical cancer. An important component of the treatment of cervical carcinoma in the early stages is adding radiation therapy in situations at high risk for local or systemic recurrence. However, the majority of patients present with locally advanced disease at presentation, therefore the addition of concurrent chemoradiation with cisplatin improves overall and progression-free survival and reduces local and distant recurrence., Brachytherapy is a key component of radiotherapy treatment for cervical cancer, so the addition of brachytherapy after concurrent chemoradiation or EBRT alone serves to boost the gross tumor and improves local control and disease-free survival with acceptable toxicities., During 2014–2018, out of 144 carcinoma cervix patients who were registered at our institution, 31 patients were enrolled in our study, assessed, and taken for brachytherapy using tandem and cylinder applicator. Out of 31 patients, 71.0% received 21 Gy, i.e., 7 Gy per fraction and 29.0% received 18 Gy, i.e. 6 Gy per fraction once a week for 3 weeks [Figure 3]; similar doses were also used by other clinicians, namely Ahmed et al. Out of 31 patients, post-EBRT treatment 16.1% developed Grade 1 skin toxicity and during brachytherapy, 3.2% developed gastrointestinal toxicity of Grade 1, and 3.2% developed Grade 1 vaginal mucositis [Figure 7] which is compatible with a study conducted by Sahil N et al. who observed the same toxicities. At 6–8 weeks, posttreatment assessment, all patients were diseases free on radiological imaging. At 3 months of follow-up, 3.2% had Grade 1 proctitis and 9.7% had Grade 2 cystitis [Figure 8] which is compatible with the study conducted by Kara D Romano who observed the same toxicities. At 6 months of follow-up, 3.2% had Grade 1 proctitis, 3.2% had Grade 2, and 3.2% had Grade 3 proctitis, and no genitourinary toxicity was observed in any patient [Figure 9] which is compatible with the study of Mazeron R Fokedal et al. Three patients who had Grade 1, Grade 2, and Grade 3 proctitis underwent colonoscopy. The patient who had Grade 1 proctitis had a normal colonoscopic report but the patients who had Grade 2 proctitis had a radiation-induced ulcer and the patient who had Grade 3 proctitis had developed a fistula. These two patients were initially managed conservatively, but they did not respond to treatment and underwent diverting colostomy. At 3 months of follow-up, 93.5% were disease-free while 6.5% had the residual disease [Figure 4] and were given chemotherapy. After 6 months of follow-up, all the patients were diseases free [Figure 5]. After 1 year of follow–up, 83.9% of patients were alive and diseases free, 3.2% had local recurrence while 6.5% developed distant metastasis, and 6.5% of patients expired due to posttreatment complications [Figure 6]. By the end of 2 years, 26 patients were disease-free on evaluation, and out of two patients, who had distant metastasis at 12 months, one expired and the other lost to follow-up. One patient with local recurrence at 12 month followup was referred to surgical department for possible salvage did not report back and lost follow up. The overall survival was 93.5% after 66 months (for patients treated in 2014) with a mean of 61.210 months (95% confidence interval, 54.715-67.705). Local control and toxicities as seen in our study were similar to other studies that used traditional applicators such as tandem and ovoid or Fletcher-Suit Delclos, namely Toita et al. These results are also compatible with the study conducted by Ahmed et al. who used tandem and cylinder where Fletcher-Suit Delclos was not feasible due to anatomical geometry. Another study conducted in this context was by Barney et al. who concluded that patients treated by tandem and cylinder have similar outcome and toxicities as patients treated with tandem and ovoid or Fletcher-Suit Delclos and their data supported the fact that this treatment modality represents an acceptable alternative for patients with disease extension to the distal third of the vagina or with obliteration of vaginal fornices or where nonideal anatomy or tumor characteristics prohibiting tandem and ovoid brachytherapy.
| > Conclusion|| |
This study concludes that although the local control and toxicities with brachytherapy using tandem and cylinder were comparable to standard Fletcher-Suit applicators, the required dose prescription to point A was not possible in all the patients due to limitations of OARs. As tandem and cylinder was the only available applicator at out hospital we optimized the dose such that the target receives prescribed dose and spare OARs to maximum possible although tandem and cylinder may not be one of the ideal applicators in locally advanced carcinoma cervix. Furthermore, long-term follow-up is needed to see the patterns of failure, recurrence-free survival, overall survival, and long-term toxicities in the treated patients.
The drawback of our study is that the sample size was small and it was not a comparative study. We recommend a study on a larger sample size to be conducted for establishing the use of tandem and cylinder as brachytherapy applicators in the management of carcinoma cervix.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12]