Clinical outcomes of adaptive intracavitary and interstitial brachytherapy technique in locally advanced cervical cancer: A real-world data.

PURPOSE: To evaluate clinical outcomes of CT-based adaptive intracavitary and interstitial brachytherapy (IC followed by IC-ISBT) in locally advanced cervical cancer (LACC) in resource-constrained settings. METHODS AND MATERIALS: LACC patients treated with adaptive brachytherapy techniques were analyzed to evaluate treatment characteristics and clinical outcomes. The Kaplan-Meier method was used for survival analysis, and the log-rank test for univariate analysis. RESULTS: Out of 141 eligible patients with LACC, 87 (61.7%) patients received external beam radiotherapy (EBRT) in referral hospitals, while 54 (38.3%) were treated at our center. We divided our cohort into two groups: poor EBRT responder group (n = 70 [49.6%]) where IC-ISBT was adapted to achieve optimum tumor doses and OAR optimization group 71 (50.4%) where IC-ISBT was performed to reduce OAR doses. Median HRCTV-D90 dose was 88 Gy (range 70-109 Gy) with median HRCTV volume 33cc (range 15-96). Median D2cc doses to OARs were 90 Gy (range 70-107), 71 Gy (range 55-105) and 70 Gy (range 47-90) to bladder, rectum and sigmoid, respectively. At median follow-up of 32 months, 3-year local control (LC), locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) were 83%, 75%, 64% and 72%, respectively. Subgroup analysis revealed significantly better outcomes for OAR optimization compared to poor EBRT responders, with 3-year LC (95% vs. 70.1%, p < 0.001), LRC (87.3% vs. 62.7%, p < 0.001), DFS (79.2% vs. 49.4%, p < 0.001), and OS (86.2% vs. 57.4%, p < 0.001) CONCLUSION: In resource-constrained settings, implementation of Adaptive IC-ISBT is a viable alternative for optimizing OAR doses in LACC. However proactive approach employing IC-ISBT for tumor dose-escalation from first fraction of BT is warranted for improving LC in poor EBRT responders.

Reirradiation with advanced brachytherapy techniques in recurrent GYN cancers.

PURPOSE: To evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique. METHODS AND MATERIALS: Seventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis. RESULTS: Median age at recurrence was 55 years (Range: 35-73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30-50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients. CONCLUSION: The use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers.

Transitioning India to advanced image based adaptive brachytherapy: a national impact analysis of upgrading National Cancer Grid cervix cancer guidelines.

Background: High-dose-rate image guided brachytherapy (IGBT) for cervical cancer leads to improved local control and reduced toxicity and is a critical component of treatment. However, transition to IGBT requires capacity upscaling. An institutional activity mapping and national impact analysis of such a transition were undertaken to understand feasibility. Methods: Between September 2020 and March 2021, activity mapping was conducted in a high-volume centre that triaged cervical cancer patients for brachytherapy into four workflows; A: two-dimensional (2D) X-Ray point A-based intracavitary brachytherapy, B: CT point A-based intracavitary brachytherapy, C: MRI/CT-volume based intracavitary brachytherapy, D: MRI/CT volume-based intracavitary +/- interstitial brachytherapy. Clinical process time mapping was performed, and case scenarios for transition were modelled at the institutional and national levels based on available incidence and infrastructure levels. Treatment capacity changes were calculated, and potential strategies for workflow reorganisation were proposed. Findings: Eighty-four patients were included in the study. The total time taken for the workflows A, B, C, and D were 176 min (57-208), 224 min (74-260), 267 min (101-302), and 348 min (232-383), respectively. The transition from workflow A to D through sequential steps led to 35%, 49%, and 64% loss of treatment capacity in the index institution. Solutions such as 10-hour or 12-hour overlapping shifts increased treatment capacity by 25% and 50% and performing single implants and delivering multiple fractions increased capacity by 100%. Twenty-three Indian states and Union Territories are predicted to be able to transition to advanced workflows. For four Indian states, it may be detrimental considering the current infrastructure level, and eight Indian states lacked brachytherapy access. Further financial investment is required in the latter 12 states for transition to advanced workflows. Interpretation: Our study demonstrates that unplanned transition to IGBT can lead to treatment capacity loss and increase in waiting lists to access treatment. The proposed solutions of workflow reorganisation, using strategies such as single brachytherapy applicator implant and delivering multiple treatment fractions can improve access to treatment for women with cervix cancer in resource-strained and high patient-volume settings. We recommend state-wise solutions for the upscale from conventional 2D workflows to IGBT, subject to the availability of skilled personnel, infrastructure and training. Financial investments may be needed in some states to achieve this goal. Funding: International Atomic Energy Agency (IAEA) supported the salary of VH through project E33042 that focussed on implementation strategies of image guided brachytherapy.

Early outcomes of abbreviated multi-fractionated brachytherapy schedule for cervix cancer during COVID-19 pandemic.

PURPOSE: Brachytherapy (BT) for cervix cancer was listed as a level I priority and reduced number of implants and multiple fractions were recommended during COVID-19 pandemic. We present early clinical outcome of this approach. METHODS AND MATERIALS: Patients treated with (chemo)radiotherapy and BT with single implant and multiple fractions BT were included. Treatment protocol included 3-5 fractions of 5-8.5 Gy with an aim to achieve point A dose of 70 Gy EQD210Gy (or HRCTV dose of >80 Gy EQD210Gy) in those undergoing intracavitary (IC) and HRCTV dose >85 Gy EQD2 10Gy in patients undergoing Intracavitary-Interstitial (IC/IS) whereas maintaining bladder (B2cc), rectum (R2cc), sigmoid (S 2cc) doses of 90, 75, and 75 Gy EQD23Gy. Time to event analysis was used to report oncological endpoints. Toxicity was reported using crude proportions. RESULTS: From April 2020 to March, 2021, 64 patients with stage IB2-IV received single implant and multi-fraction BT after external radiation of 45 Gy/25 fractions/5 weeks. Only 76.7% (n = 49) received concurrent chemotherapy. Median overall treatment time (OTT) was 56 days (38-131 days). Overall, 62.5% (n = 40) patients received IC and 37.5% (n = 24) received IC+IS. The median HRCTV was 34.7 cc (IQR 25-41). Median (IQR) point A dose, HRCTV D90, B2cc, R2cc, and S2cc for those undergoing IC was 74 Gy (71-78), 80 Gy (73-84), 86 Gy (82-89), 70 Gy (65-74), 65 Gy (59-73) respectively. For the IC+IS cohort, HRCTV D90, B2cc, R2cc, and S2cc was 84 Gy (78-89 Gy), 89 Gy (86-92), 70 Gy (67-74), 68 Gy (59-76). At a median follow-up of 16 months (5-27) the 2-year local control, pelvic control, cause specific and overall survival was 88%, 85.3%, 92.2%, and 81.3% respectively. Late gastrointestinal and genitourinary grade ≥III toxicities were 14% and 1.5% each. CONCLUSIONS: Abbreviated BT outcomes are encouraging for oncological outcomes despite delays in overall treatment time and omission of chemotherapy. Further mature follow up is needed.

Clinical outcomes of patients treated with template-based high-dose-rate interstitial brachytherapy boost for post-operative recurrent gynecological malignancies: A retrospective analysis.

Purpose: To report the clinical outcomes in patients treated with Martinez universal perineal interstitial template (MUPIT)-based interstitial brachytherapy boost for primary and recurrent vault and vaginal cancers, and to perform a comparative analysis with our previously published series of similar patients. Material and methods: One hundred and seventeen patients treated between January, 2009 and December, 2015 were evaluated. Descriptive statistics for the patterns of relapse, local recurrence-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and late toxicities were carried out. Kaplan-Meier curves were used for survival analysis. All variables with the potential to affect outcomes were tested using log-rank test for statistical significance. Results: At a median follow-up of 63 months, LRFS, DFS, and OS at 3/5 years were 77.1%/74.7%, 61%/52%, and 72.3%/63.1%, respectively. Overall treatment time (OTT) of 56 days did not affect outcomes. Bulky tumors and OTT > 63 days adversely affected LRFS. Overall treatment time also significantly impacted DFS and OS. Grade 3-4 late bladder toxicities were observed in 1.7% patients, and grade 3-4 late rectal toxicities in 5% patients. Compared to our previous series, the outcome in the current series is better in terms of severe late toxicities (5% improvement in rectal toxicity, and 2.7% improvement in bladder toxicity) and OS by 10%. This could be attributed to the increasing use of concurrent chemotherapy and relative optimization strategies for organs at risk. Conclusions: Patients with primary and recurrent vault and vaginal cancers treated with high-dose-rate interstitial brachytherapy boost using MUPIT resulted in modest clinical outcomes and acceptable late toxicities. OTT was the most important factor affecting the outcomes.

Effect of COVID-19 Pandemic on Gynecological Cancer Radiation During Complete Nationwide Lockdown: Observations and Reflections From Tertiary Care Institute in India.

PURPOSE: To report real-world compliance to radiation in gynecologic cancers during the complete lockdown phase of COVID-19 pandemic. METHODS AND MATERIALS: From March 23, 2020, until June 30, 2020, complete lockdown was imposed in India. During this period there was restructuring of cancer care and radiation oncology department due to operational policies prevalent in the institution, and the care for gynecological cancer was based on the evolving international recommendations. Institutional review board approval was obtained to audit patterns of care during the complete lockdown phase. Descriptive variables were used to report on patient characteristics, compliance, delays, toxicity, and observed deviations in recommended care. RESULTS: During the lockdown period spanning 100 days, treatment of 270 and telephonic follow-up of 1103 patients with gynecological cancer was undertaken. Of 270 new patients, due to travel restrictions, 90 patients were referred to the facilities in vicinity of their residence. Of the remaining 180 patients, 138 were planned for complete treatment at our institution and 42 were referred to our center for brachytherapy. Of 138 patients, only 106 (76%) completed the planned external radiation. Twenty-four (26%) patients completed full course of concurrent chemotherapy, 11 (12%) received chemotherapy dose reduction, and 57 (62%) received no concurrent chemotherapy. Treatment delay of up to 3 weeks was noted in 8.6% patients due to COVID-19 infection. No grade 4 to 5 acute sequelae were observed. No excess adverse effects were observed in high-risk population. Low rate of symptom burden was observed among 1103 patients on telephonic follow-up. With 100 (9.6%) patients reporting symptoms, among these, 54% (54 of 100) had complete resolution of symptoms within 4 weeks of teleconsultation, and 10% had disease progression. CONCLUSIONS: Low compliance with planned treatment was observed for radiation and concurrent chemotherapy due to lockdown and fear of contracting COVID-19 and will likely lead to increased risk of cancer-related mortality. Rapid restructuring of care is needed to prevent the same as COVID-19 pandemic further evolves.

Modified Houdek vault applicator for high-dose-rate brachytherapy: a technical report and case series.

PURPOSE: Treatment of isolated post-surgical vault recurrence of cervical and endometrial cancers in previously unirradiated patients includes external beam radiotherapy (EBRT) ± concomitant chemotherapy, followed by brachytherapy (BT) boost. Supra-vaginal component of vault disease often requires interstitial BT for optimal dose coverage. We describe technical details and preliminary case series using modified Houdek vault applicator (MHVA) developed at our institution for limited intra-cavitary plus interstitial high-dose-rate (HDR) vault BT. MATERIAL AND METHODS: Nineteen patients with vaginal vault recurrences received BT boost with MHVA between October 2015 and May 2018. All underwent BT application and CT-based BT planning after completion of EBRT ± concomitant chemotherapy. RESULTS: Median EQD2 of BT dose in patients with carcinoma cervix recurrence (n = 15, α/ß = 10) was 18.8 Gy, and in those with endometrial cancer recurrence was 22.08 Gy (n = 4, α/ß = 4.5). Median total EQD2 was 68.8 Gy and 72.08 Gy, respectively. Mean 2 cc of bladder, rectum, and sigmoid EBRT + BT doses (EQD2, α/ß = 3) were 65.38 Gy (±7.76), 63.37 Gy (±5.52), and 57.04 Gy (±4.45), respectively. At 6-8 weeks, 17 patients showed complete response (CR). With median follow-up of 20.5 months, 2-year overall survival was 95% (95% CI: 85.2-100.0%), and 2-year progression-free survival was 79.4% (95% CI: 61.0-97.8%). Late toxicities seen were grade 2 proctitis in 1 patient, grade 1 proctitis in 5, grade 2 urethritis in 1, grade 3 cystitis in 1, and recto-vaginal fistula in 1 patient (with disease controlled). Recurrence rate was 6.7 times higher in patients with post-EBRT disease greater than 10 mm (p = 0.01). CONCLUSIONS: MHVA is a simple solution for intra-cavitary and interstitial HDR-BT boost in isolated vault cancers post-surgery, achieving acceptable dosimetric parameters. Preliminary clinical outcomes and late toxicities are satisfactory.

Change of target volume and its dosimetric impact during the course of accelerated partial breast irradiation using intraoperative multicatheter interstitial brachytherapy after open cavity surgery.

PURPOSE: To investigate the change of clinical target volume (CTV) and its dosimetric impact during the course of accelerated partial breast irradiation (APBI) using intraoperative multicatheter interstitial brachytherapy after open cavity surgery. METHODS AND MATERIALS: Twenty-two patients of APBI with intraoperative placement of catheters underwent computed tomography scans for the treatment planning before the first (CT1) and the last (CT2) treatment fraction. Delineation of lumpectomy cavity and CTV was done consistently on both CT data sets by one of the coauthors. Optimum plan (PCT1) was made on CT1. PCT1 was manually reproduced in CT2 which yielded plan PCT2. Plans were compared using coverage index (CI), dose homogeneity index (DHI), external volume index (EI), overdose volume index (OI) and conformal index (COIN). RESULTS: The mean ± SD volume of lumpectomy cavity and CTV was 78.5 ± 40.7 cm3, 156.4 ± 69.0 cm3 for PCT1, and 84.7 ± 50.1 cm3 (p = 0.11), 165.7 ± 82.8 cm3 (p = 0.15) for PCT2, respectively. CTV volume increase by ≥ 10% was observed in 9 cases however decrease of ≥10% was observed in 5 cases. Mean (SD) of absolute pairwise difference in CTV volume was found to be 13.2 (6.7) %. For cases with increase in CTV volume, significant (p < 0.05) decrease of 8.4%, 12.2%, and 5.5% was observed in CI, EI, and COIN of CTV respectively. However for cases with shrinkage of CTV, significant (p = 0.004) increase of 45% in EI was observed, whereas COIN reduced significantly (p = 0.001) by 13.5%. Overall 22 cases showed significant decrease of 5.8% and 8.1% in mean CI and COIN, respectively. CONCLUSIONS: The change of CTV during the course of APBI using intraoperative multicatheter interstitial brachytherapy after open cavity surgery was found patient specific and showed a significant impact on coverage and conformity.

Clinical outcome of high-dose-rate interstitial brachytherapy in vulvar cancer: A single institutional experience.

PURPOSE: With an aim to evaluate and report high dose date interstitial brachytherapy (HDR-ISBT) in vulvar cancers, we undertook this retrospective analysis. METHODS AND MATERIALS: Histologically proven vulvar cancers treated with HDR-ISBT between 2001 and 2016 were analyzed. Radiotherapy details, clinical outcome in terms of local control rates, survivals, and toxicities were evaluated. RESULTS: A total of 38 patients received HDR-ISBT, with definitive radiation in 29 (76.3%), adjuvant postoperative in six (15.8%) and salvage radiation in three (7.9%) patients. Of them, 29 patients received brachytherapy boost and nine patients ISBT alone. BT procedure included freehand plastic tube technique in 23 (single [n = 5] or multiple plane [n = 18]), 13 patients with template based and two patients combined approach. Patients with brachytherapy alone received median EQD2 of 38.4 Gy10 (35.5-46.7 Gy10), as boost received median 23.3 Gy10 (13-37.3 Gy10). At 3-month post-treatment response evaluation, 30 patients achieved clinically complete response, two patients partial response and six maintained postoperative status. With a median follow-up of 30 months, 29 (76.3%) were disease free, and 9 (23.7%) patients had relapsed disease with four patients expired due to disease and two died of other causes. The 5-year overall survival, disease free survival, and local control rates were 82%, 51%, and 77%, respectively. CONCLUSIONS: HDR-ISBT in vulvar cancer is a feasible and a viable option with acceptable and comparable outcomes.