Publications by authors named "Rahul Krishnatry"

47 Publications

Locoregional recurrence after cystectomy in muscle invasive bladder cancer: Implications for adjuvant radiotherapy.

Urol Oncol 2021 Feb 8. Epub 2021 Feb 8.

Department of Radiation Oncology, Tata Memorial Centre (TMH/ACTREC), Mumbai, India; Homi Bhabha National Institute (HBNI), Anushakti Nagar, Mumbai, India.

Purpose: We report the patterns of locoregional recurrence (LRR) in muscle invasive bladder cancer (MIBC), and propose a risk stratification to predict LRR for optimizing the indication for adjuvant radiotherapy.

Materials And Methods: The study included patients of urothelial MIBC who underwent radical cystectomy with standard perioperative chemotherapy between 2013 and 2019. Recurrences were classified into local and/or cystectomy bed, regional, systemic, or mixed. For risk stratification modelling, T stage (T2, T3, T4), N stage (N0, N1/2, N3) and lymphovascular invasion (LVI positive or negative) were given differential weightage for each patient. The cohort was divided into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the cumulative score.

Results: Of the 317 patients screened, 188 were eligible for the study. Seventy patients (37.2%) received neoadjuvant chemotherapy (NACT) while 128 patients (68.1%) had T3/4 disease and 66 patients (35.1%) had N+ disease. Of the 55 patients (29%) who had a recurrence, 31 (16%) patients had a component of LRR (4% cystectomy bed, 11.5% regional 0.5% locoregional). The median time to LRR was 8.2 (IQR 3.3-18.8) months. The LR, IR and HR groups for LRR based on T, N and LVI had a cumulative incidence of 7.1%, 21.6%, and 35% LRR, respectively. The HR group was defined as T3, N3, LVI positive; T4 N1/2, LVI positive; and T4, N3, any LVI. The odds ratio for LRR was 3.37 (95% CI 1.16-9.73, P = 0.02) and 5.27 (95% CI 1.87-14.84, P = 0.002) for IR and HR respectively, with LR as reference.

Conclusion: LRR is a significant problem post radical cystectomy with a cumulative incidence of 35% in the HR group. The proposed risk stratification model in our study can guide in tailoring adjuvant radiotherapy in MIBC.
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http://dx.doi.org/10.1016/j.urolonc.2021.01.015DOI Listing
February 2021

Safety and efficacy of concurrent carboplatin during full-dose craniospinal irradiation for high-risk/metastatic medulloblastoma in a resource-limited setting.

Pediatr Blood Cancer 2021 Feb 3:e28925. Epub 2021 Feb 3.

Department of Pediatric Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India.

Purpose: To assess the safety and efficacy of concurrent carboplatin during craniospinal irradiation (CSI) in high-risk/metastatic medulloblastoma defined as either residual tumor >1.5 cm or leptomeningeal metastases.

Methods: This single-arm combined prospective (2005-2011) and retrospective (2011-2019) study was undertaken at a tertiary care cancer center in India. Following surgery, patients with newly diagnosed high-risk/metastatic medulloblastoma received concurrent carboplatin (35 mg/m ) for 15 days (day 1 to day 15) during CSI plus posterior fossa/tumor bed boost, followed by six cycles of standard adjuvant chemotherapy.

Results: All 97 patients completed their planned course of radiotherapy without interruptions, except for two (2.1%) patients who had brief gaps due to treatment-related toxicity. Grade 3-4 anemia, neutropenia, thrombocytopenia, and febrile neutropenia were seen in four (4.1%), 41 (42.2%) 21 (21.6%), and 18 (18.6%) patients, necessitating packed cell transfusion, granulocyte colony-stimulating factor, and platelet support in five (5.1%), 41 (42.2%), and five (5.1%) patients, respectively, during the concurrent phase. Following myelorecovery, 92 (94.9%) patients completed the planned six cycles of standard adjuvant systemic chemotherapy. There were no treatment-related deaths during the concurrent chemo-radiotherapy phase, while three (3.1%) toxic deaths were ascribed to adjuvant chemotherapy-related complications. At a median follow-up of 82 months, the 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 60.2% and 62.1%, respectively. On univariate analysis, leptomeningeal metastases (M0/M1 vs. M2/M3) and histological subtype (large cell/anaplastic vs. others) emerged as significant prognostic factors for survival.

Conclusion: Addition of concurrent carboplatin to RT as radiosensitizing chemotherapy is a simple and effective way of treatment intensification in high-risk/metastatic medulloblastoma.
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http://dx.doi.org/10.1002/pbc.28925DOI Listing
February 2021

Clinical approach to re-irradiation for recurrent diffuse intrinsic pontine glioma.

Jpn J Clin Oncol 2021 Jan 30. Epub 2021 Jan 30.

Department of Radiation Oncology, Tata Memorial Centre (TMH/ACTREC), Mumbai, India.

Background: We present our institutional approach for re-irradiation in diffuse intrinsic pontine glioma and their outcomes.

Methods: Consecutive patients of recurrent diffuse intrinsic pontine glioma treated with re-irradiation (January 2015-September 2019) were reviewed retrospectively to describe the clinical-response-based approach followed for the dose and volume decision. Outcomes were defined with clinical and steroid response criteria and survival endpoints included progression-free survival and overall survival as cumulative(c) overall survival and re-irradiation overall survival (re-irradiation starting to death). The Kaplan-Meier method and log-rank test were used for survival analysis.

Results: Twenty-patient cohort with a median (m) age of 7.5 years, m-progression-free survival of 8.4 months and m-Lansky performance score of 50 received re-irradiation of which 17 (85%) were called clinical responders. The median re-irradiation-overall survival with 39.6-41.4, 43.2 and 45 Gy were 5.8, 7 and 5.3 months, respectively. One-month post-re-irradiation steroid independent status was a significant predictor of better survival outcomes (overall survival, P≤0.004). No ≥ grade 3 toxicities were noticed. Two patients succumbed to intra-tumoral hemorrhage.

Conclusions: Higher doses of re-irradiation based on a clinical-response-based approach show improvement in survival and steroid dependence rates with acceptable toxicity. Steroid independent status at 1-month post-re-irradiation predicts better outcomes. Prospective studies may validate this with quality of life data.
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http://dx.doi.org/10.1093/jjco/hyab006DOI Listing
January 2021

Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial.

J Clin Oncol 2021 Jan 26:JCO2003282. Epub 2021 Jan 26.

Department of Radiation Oncology, Tata Memorial Hospital and Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Homi Bhabha National Institute (HBNI), Mumbai, India.

Purpose: We report the clinical outcomes of a randomized trial comparing prophylactic whole-pelvic nodal radiotherapy to prostate-only radiotherapy (PORT) in high-risk prostate cancer.

Methods: This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%. Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to prostate, 50 Gy/25# to pelvic nodes, including common iliac) using computerized stratified block randomization, stratified by Gleason score, type of androgen deprivation, prostate-specific antigen at diagnosis, and prior transurethral resection of the prostate. All patients received image-guided, intensity-modulated radiotherapy and minimum 2 years of androgen deprivation therapy. The primary end point was 5-year biochemical failure-free survival (BFFS), and secondary end points were disease-free survival (DFS) and overall survival (OS).

Results: From November 2011 to August 2017, a total of 224 patients were randomly assigned (PORT = 114, WPRT = 110). At a median follow-up of 68 months, 36 biochemical failures (PORT = 25, WPRT = 7) and 24 deaths (PORT = 13, WPRT = 11) were recorded. Five-year BFFS was 95.0% (95% CI, 88.4 to 97.9) with WPRT versus 81.2% (95% CI, 71.6 to 87.8) with PORT, with an unadjusted hazard ratio (HR) of 0.23 (95% CI, 0.10 to 0.52; < .0001). WPRT also showed higher 5-year DFS (89.5% 77.2%; HR, 0.40; 95% CI, 0.22 to 0.73; = .002), but 5-year OS did not appear to differ (92.5% 90.8%; HR, 0.92; 95% CI, 0.41 to 2.05; = .83). Distant metastasis-free survival was also higher with WPRT (95.9% 89.2%; HR, 0.35; 95% CI, 0.15 to 0.82; = .01). Benefit in BFFS and DFS was maintained across prognostic subgroups.

Conclusion: Prophylactic pelvic irradiation for high-risk, locally advanced prostate cancer improved BFFS and DFS as compared with PORT, but OS did not appear to differ.
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http://dx.doi.org/10.1200/JCO.20.03282DOI Listing
January 2021

Clinico-radiological characteristics, histo-pathological features and long-term survival outcomes in central neurocytoma: A single-institutional audit.

J Clin Neurosci 2021 Feb 24;84:91-96. Epub 2020 Dec 24.

Department of Radiation Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India. Electronic address:

Central neurocytoma is a rare benign brain tumor that typically arises from the subependymal lining of the lateral ventricles in young adults and is generally associated with excellent survival following neurosurgical excision alone. This is a retrospective clinical audit of biopsy-proven neurocytoma registered between 2004 and 2019 at a single institution in India. All time-to event outcomes were analyzed using Kaplan-Meier method and compared with the log-rank test. Any p-value <0.05 was considered statistically significant. A total of 66 patients with neurocytoma were included in the descriptive analysis. Median age of study cohort was 31 years with equitable gender ratio. Majority (83%) of tumors were intraventricular, lateral ventricle being the commonest location. Following maximal safe resection, patients were generally kept on close clinico-radiological surveillance. Most patients (80%) had typical World Health Organization (WHO) grade II neurocytoma with remaining 20% showing histological atypia and/or high-grade features. Outcome analysis was restricted to 35 patients with relevant treatment details and adequate follow-up information. Six patients experienced recurrent/progressive disease with 2 documented deaths. At a median follow up of 52 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 93.3% and 96.8% respectively. Three patients developed delayed recurrence (>5-years after initial diagnosis) underscoring the importance of long-term follow-up. Atypical/high-grade histology was associated with inferior survival that may stand to benefit with upfront adjuvant radiotherapy. This represents the largest single-institution series of central neurocytoma and demonstrates excellent outcomes with adequate surgical resection alone, reserving radiotherapy for large residual tumor, recurrent disease, and/or atypical high-grade histology.
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http://dx.doi.org/10.1016/j.jocn.2020.11.051DOI Listing
February 2021

A randomized trial of stereotactic versus conventional radiotherapy in young patients with low-grade brain tumors: occupational therapy-based neurocognitive data.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa130. Epub 2020 Oct 1.

Neuro Oncology Disease Management Group, Tata Memorial Centre, Parel, Mumbai, India.

Background: Radiotherapy for brain tumors in young patients is not only associated with improved survival but also long-term neurocognitive sequelae. We aimed to compare group differences in the executive neurocognitive outcomes in young patients with low-grade brain tumors treated with stereotactic conformal radiotherapy (SCRT) and conventional RT (ConvRT) techniques.

Methods: This a phase 3 randomized trial that enrolled 200 young patients with benign brain tumors and low-grade gliomas. Patients were randomly allocated (1:1) to either SCRT or ConvRT arms and treated to a dose of 54 Gy in 30 fractions over 6 weeks. Lowenstein Occupational Therapy Cognitive Assessment battery was performed at preradiotherapy baseline, 6 months, and annually thereafter until 5 years. Executive functions measures included orientation, visual perception, spatial perception, motor praxis, visuomotor organization, thinking operations, and attention and concentration. The trajectory of these parameters was compared between the treatment arms over 5 years.

Results: Two hundred patients were enrolled in the study (SCRT: 104 and ConvRT: 96). The median age was 13 years (interquartile range: 9-17); mean total neurocognitive scores over 5 years were significantly superior in SCRT arm as compared to ConvRT (difference in slope: 2.27, = .024). Outcomes improved in the SCRT arm vis-à-vis ConvRT for the subdomain of visuomotor organization (difference in slope: 0.66, < .001). Visuomotor organization scores significantly improved in majority of the substratification groups. Spatial perception improved in craniopharyngioma patients with SCRT technique as opposed to ConvRT.

Conclusions: SCRT achieved superior outcomes compared to ConvRT in certain executive neurocognitive functional domains. We provide high level of evidence in favor of SCRT. ClinicalTrials.gov Identifier: NCT00517959.
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http://dx.doi.org/10.1093/noajnl/vdaa130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668487PMC
October 2020

Reactor produced [Cu]CuCl as a PET radiopharmaceutical for cancer imaging: from radiochemistry laboratory to nuclear medicine clinic.

Ann Nucl Med 2020 Dec 13;34(12):899-910. Epub 2020 Oct 13.

Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.

Objective: Copper-64 is a useful theranostic radioisotope that is attracting renewed interest from the nuclear medicine community in the recent times. This study aims to demonstrate the utility of research reactors to produce clinical-grade Cu via Cu(n,γ)Cu reaction and use it in the form of [Cu]CuCl as a radiopharmaceutical for PET imaging of cancer in human patients.

Methods: Copper-64 was produced by irradiation of natural CuO target in a medium flux research reactor. The irradiated target was radiochemically processed and detailed quality control analyses were carried out. Sub-acute toxicity studies were carried out with different doses of Cu in Wistar rats. The biological efficacy of the radiopharmaceutical was established in preclinical setting by biodistribution studies in melanoma tumor bearing mice. After getting regulatory approvals, [Cu]CuCl formulation was clinically used for PET imaging of prostate cancer and glioblastoma patients.

Results: Large-scale (~ 30 GBq) production of Cu could be achieved in a typical batch and it was adequate for formulation of clinical doses for multiple patients. The radiopharmaceutical met all the purity requirements for administration in human subjects. Studies carried out in animal model showed that the toxicity due to "cold" Cu in clinical dose of [Cu]CuCl for PET scans would be negligible. Clinical PET scans showed satisfactory uptake of the radiopharmaceutical in the primary cancer and its metastatic sites.

Conclusions: To the best of our knowledge, this is the first study on use of reactor produced [Cu]CuCl for PET imaging of cancer in human patients. It is envisaged that this route of production of Cu would aid towards affordable availability of this radioisotope for widespread clinical use in countries with limited cyclotron facilities.
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http://dx.doi.org/10.1007/s12149-020-01522-2DOI Listing
December 2020

Reverse swing-M, phase 1 study of repurposing mebendazole in recurrent high-grade glioma.

Cancer Med 2020 07 13;9(13):4676-4685. Epub 2020 May 13.

Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.

Background: Relapsed high-grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in-vitro and in-vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma.

Methods: We conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re-irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m day 1-5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination.

Findings: 11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%).

Interpretation: The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide-radiation combination while the dose of 800 mg TDS needs to be used with single-agent CCNU.
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http://dx.doi.org/10.1002/cam4.3094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333848PMC
July 2020

Study protocol of a randomised controlled trial of prostate radiotherapy in high-risk and node-positive disease comparing moderate and extreme hypofractionation (PRIME TRIAL).

BMJ Open 2020 02 28;10(2):e034623. Epub 2020 Feb 28.

Division of Uro-Oncology, Tata Memorial Centre, Mumbai, India.

Introduction: There has been an interest in studying the efficacy of extreme hypofractionation in low and intermediate risk prostate cancer utilising the low alpha/beta ratio of prostate. Its role in high-risk and node-positive prostate cancer, however, is unknown. We hypothesise that a five-fraction schedule of extreme hypofractionation will be non-inferior to a moderately hypofractionated regimen over 5 weeks in efficacy and will have acceptable toxicity and quality of life while reducing the cost implications during treatment.

Methods And Analysis: This is an ongoing, non-inferiority, multicentre, randomised trial (NCT03561961) of two schedules for National Cancer Control Network high-risk and/or node-positive non-metastatic carcinoma of the prostate. The standard arm will be a schedule of 68 Gy/25# over 5 weeks while the test arm will be extremely hypofractionated radiotherapy with stereotactic body radiation therapy to 36.25 Gy/5# (7 to 10 days). The block randomisation will be stratified by nodal status (N0/N+), hormonal therapy (luteinizing hormone-releasing hormone therapy/orchiectomy) and centre. All patients will receive daily image-guided radiotherapy.The primary end point is 4-year biochemical failure free survival (BFFS). The power calculations assume 4-year BFFS of 80% in the moderate hypofractionation arm. With a 5% one-sided significance and 80% power, a total of 434 patients will be randomised to both arms equally (217 in each arm). The secondary end points include overall survival, prostate cancer specific survival, acute and late toxicities, quality of life and out-of-pocket expenditure.

Discussion: The trial aims to establish a therapeutically efficacious and cost-efficient modality for high-risk and node-positive prostate cancer with an acceptable toxicity profile. Presently, this is the only trial evaluating and answering such a question in this cohort.

Ethics And Dissemination: The trial has been approved by IEC-III of Tata Memorial Centre, Mumbai.

Trial Registration Number: Registered with CTRI/2018/05/014054 (http://ctri.nic.in) on 24 May 2018.
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http://dx.doi.org/10.1136/bmjopen-2019-034623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050316PMC
February 2020

Extent of re-excision, sequence/timing of salvage re-irradiation, and disease-free interval impact upon clinical outcomes in recurrent/progressive ependymoma.

J Neurooncol 2020 Apr 18;147(2):405-415. Epub 2020 Feb 18.

Departments of Radiation Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Mumbai, Homi Bhabha National Institute (HBNI), Kharghar, Navi Mumbai, 410210, India.

Purpose: To report clinical outcomes of salvage re-irradiation (re-RT) in recurrent/progressive ependymoma.

Methods: Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive ependymoma were analyzed retrospectively. The linear-quadratic model was used to provide estimates of biologically effective dose (BED) of irradiation using an α/β value of 2 for late CNS toxicity for each course of irradiation and summated to derive cumulative BED without correcting for the assumed recovery.

Results: A total of 55 patients (median age 10 years at index diagnosis) treated with curative-intent re-RT between 2010 and 2018 were included. Median time to first recurrence was 29 months with an inter-quartile range (IQR) of 16-64 months. Majority (n = 46, 84%) of patients underwent surgical re-excision of recurrent disease. Median interval from first course of irradiation (RT1) to second course (RT2) was 35 months (IQR = 26-66 months) with a median re-RT dose of 54 Gy in 30 fractions (range 40-60 Gy), resulting in median cumulative equivalent dose in 2 Gy fraction (EQD2) of 106.2 Gy (range 92.4-117.6 Gy). Volume of re-RT was based on location and pattern of relapse, comprising uni-focal (n = 49, 89%), multi-focal (n = 3, 5.5%), or craniospinal irradiation (CSI) in 3 (5.5%) patients respectively. Thirty-six (66%) patients received platinum-based salvage chemotherapy either before or after RT2. At a median follow up of 37 months (range 6-80 months), the Kaplan-Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) for the entire study cohort were 40% and 51% respectively. Gross total resection at recurrence; early salvage re-RT (prior to chemotherapy, if any); and longer (> 2 years) disease-free interval (DFI) were associated with better survival outcomes. Salvage re-RT was generally well tolerated with only 3 (5.5%) patients developing symptomatic radiation necrosis necessitating corticosteroids.

Conclusion: Extent of re-excision, sequence/timing of re-RT, and DFI impact upon outcomes in curative-intent, multi-modality salvage therapy for recurrent ependymoma.
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http://dx.doi.org/10.1007/s11060-020-03434-7DOI Listing
April 2020

Late toxicity and quality of life with prostate only or whole pelvic radiation therapy in high risk prostate cancer (POP-RT): A randomised trial.

Radiother Oncol 2020 Apr 7;145:71-80. Epub 2020 Jan 7.

Department of Radiation Oncology, Tata Memorial Hospital and Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Homi Bhabha National Institute (HBNI), Mumbai, India.

Aim: To report toxicity and quality of life (QOL) outcomes from a randomised trial of prostate only versus whole pelvic radiotherapy in high risk, node negative prostate cancer.

Materials/methods: Patients with localised prostate adenocarcinoma and nodal involvement risk > 20%, were randomised to prostate only (PORT, 68 Gy/25# to prostate) and whole pelvis (WPRT, 68 Gy/25# to prostate and 50 Gy/25# to pelvis) arms with stratification for TURP, Gleason score, baseline PSA, and type of androgen deprivation therapy (ADT). Image guided intensity modulated radiotherapy (IG-IMRT) and two years of ADT were mandatory. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded using RTOG grading. QOL was assessed using EORTC QLQ-C30 and PR-25 questionnaire pre-treatment and every 3-6 months post RT.

Results: Total 224 patients were randomised (PORT 114, WPRT 110) from November 2011 to August 2017. Median follow up was 44.5 months. No RTOG grade IV toxicity was observed. Acute GI and GU toxicities were similar between both the arms. Cumulative ≥ grade II late GI toxicity was similar for WPRT and PORT (6.5% vs. 3.8%, p = 0.39) but GU toxicity was higher (17.7% vs. 7.5%, p = 0.03). Dosimetric analysis showed higher bladder volume receiving 30-40 Gy in the WPRT arm (V30, 60% vs. 36%, p < 0.001; V40, 41% vs. 25%, p < 0.001). There was no difference in QOL scores of any domain between both arms.

Conclusion: Pelvic irradiation using hypofractionated IG-IMRT resulted in increased grade II or higher late genitourinary toxicity as compared to prostate only RT, but the difference was not reflected in patient reported QOL. CLINICALTRIALS.GOV NCT02302105: Prostate Only or Whole Pelvic Radiation Therapy in High Risk Prostate Cancer (POP-RT).
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http://dx.doi.org/10.1016/j.radonc.2019.12.006DOI Listing
April 2020

Utility of flouro-deoxy-glucose positron emission tomography/computed tomography in the diagnostic and staging evaluation of patients with primary CNS lymphoma.

CNS Oncol 2019 12 29;8(4):CNS46. Epub 2019 Nov 29.

Department of Radiation Oncology, TMH/ACTREC, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai 400012, India.

To prospectively assess the clinical utility of pretreatment flouro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients with primary central nervous system (CNS) lymphoma (PCNSL). Patients with suspected/proven PCNSL underwent baseline whole-body 18F-FDG-PET/CT. Maximum standardized uptake value and tumor/normal tissue ratios were compared between CNS lymphoma and other histological diagnoses. The mean maximum standardized uptake value (27.5 vs 18.2; p = 0.001) and mean tumor/normal tissue ratio (2.34 vs 1.53; p < 0.001) of CNS lymphoma was significantly higher than other histologic diagnoses. Five of 50 (10%) patients with biopsy-proven CNS lymphomas had pathologically increased FDG-uptake at extraneuraxial sites uncovering systemic lymphoma. Pretreatment whole-body 18F-FDG-PET/CT provides valuable complementary information in the diagnostic and staging evaluation of patients with PCNSL to guide therapeutic decision-making.
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http://dx.doi.org/10.2217/cns-2019-0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912853PMC
December 2019

Cabergoline may act as a radioprotective agent in Cushing's disease.

Clin Endocrinol (Oxf) 2020 01 22;92(1):55-62. Epub 2019 Nov 22.

Department of Endocrinology, Seth G S Medical College & KEM Hospital, Mumbai, India.

Context: Conventional fractionated radiotherapy (CRT) achieves control of pathological hypercortisolism in 75%-80% of patients with persistent or recurrent Cushing's disease (CD), over a mean period of 18-24 months. Medical therapy is recommended as bridge therapy while awaiting RT effect.

Objective: To determine long-term outcome of CRT and its predictors in CD patients.

Design, Setting And Patients: This is a retrospective case record analysis of 42 patients with CD who received CRT as a treatment modality and had at least 12 months post-RT follow-up. The dose delivered was 45 Gy in 25 fractions over 5 weeks. Demographic details, hormonal evaluation and radiological data were extracted from case records. Dexamethasone suppressed cortisol at cut-off of 1.8 µg/dL was used to define remission or recurrence. Possible predictors for remission and recurrence were analysed.

Results: The mean age at the time of CRT administration was 23.7 ± 10.7 (range: 12-48) years. A total of 29 (69%) patients achieved remission 26.5 ± 28.5 (median: 18, range: 3-120) months after RT, while 13 (31%) patients had persistent disease at last follow-up. There were no significant predictors of disease remission after CRT. Six (20.7%) patients had recurrence after a documented initial remission. Recurrence occurred 66.6 ± 25.9 (median: 74; range: 18 to 90) months after documented remission. Recurrence of the disease was exclusively seen in patients who received peri-RT cabergoline. Peri-CRT use of cabergoline was significantly associated with increased recurrence rates (P = .016).

Conclusion: Use of cabergoline in the peri-CRT period did not affect initial remission after CRT but was associated with increased recurrence after initial remission in CD.
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http://dx.doi.org/10.1111/cen.14123DOI Listing
January 2020

Outcomes of salvage re-irradiation in recurrent medulloblastoma correlate with age at initial diagnosis, primary risk-stratification, and molecular subgrouping.

J Neurooncol 2019 Sep 24;144(2):283-291. Epub 2019 Jun 24.

Departments of Neurosurgical Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.

Purpose: To report outcomes of salvage re-irradiation (re-RT) in recurrent/progressive medulloblastoma (MB).

Methods: Medical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive MB between 2008 and 2018 were analyzed retrospectively.

Results: A total of 28 patients (median age 18 years at index diagnosis) were included. Molecular subgrouping was done using real-time reverse transcriptase polymerase chain reaction (RT-PCR) based on the differential expression of select set of 12 protein coding genes and 9 microRNAs. Fifteen of 17 (88%) patients with sonic hedgehog (SHH)-MB developed isolated local recurrence within the index tumor-bed, while 5 of 7 (72%) patients with Group 4 MB developed localized relapse outside the posterior fossa. Diffuse neuraxial dissemination was seen in 2 patients with SHH-MB, and one each of Group 4 and wingless (WNT)-MB. Molecular subgrouping was not known in 3 patients. The dose and volume of re-RT was based on site and patterns of relapse, comprising unifocal in 18 (64%), multi-focal in 3 (11%), and repeat craniospinal irradiation (re-CSI) in 7 (25%) patients. Median interval from primary irradiation to re-RT was 49.5 months (range 24-98 months) with median cumulative biologically effective dose of 117 Gy (range 78-132 Gy). All patients received platinum-based salvage chemotherapy either before or after re-RT. One patient developed symptomatic radiation necrosis following re-CSI. At a median follow-up of 24 months (range 6-84 months), 2-year post-re-RT progression-free survival (PFS) and overall survival (OS) was 46% and 51% respectively. Younger age (< 18 years) at index diagnosis, primary risk stratification (standard-risk) and molecular subgrouping (Group 4) were associated with significantly better post-re-RT outcomes.

Conclusion: Salvage re-RT provides good local control and encouraging survival outcomes with acceptable toxicity in selected patients with recurrent/progressive MB.
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http://dx.doi.org/10.1007/s11060-019-03225-9DOI Listing
September 2019

In Regard to Amsbaugh et al.

Int J Radiat Oncol Biol Phys 2019 06;104(2):467-468

Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

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http://dx.doi.org/10.1016/j.ijrobp.2019.02.038DOI Listing
June 2019

Safety of Prostate Stereotactic Body Radiation Therapy after Transurethral Resection of Prostate (TURP): A Propensity Score Matched Pair Analysis.

Pract Radiat Oncol 2019 Sep - Oct;9(5):347-353. Epub 2019 Apr 9.

Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Parel, Mumbai, India.

Purpose: To determine the genitourinary (GU) toxicity outcomes in prostate cancer patients treated with stereotactic body radiation therapy (SBRT) who have undergone a prior transurethral resection of prostate (TURP) and compare it to a similar non-TURP cohort.

Materials And Methods: Fifty prostate cancer patients who had undergone a single TURP, had a good baseline urinary function, and had been subsequently treated with SBRT were chosen from a prospectively maintained database. These were propensity score matched to a similar non-TURP cohort treated during the same period. Matching was done for diabetes mellitus and volume of radiation therapy. Acute GU and late GU toxicity were scored using the Radiation Therapy Oncology Group (RTOG) criteria. Stricture and incontinence were scored using Common Terminology for Common Adverse Events version 4.0.

Results: Median follow-up for the entire cohort was 26 months (non-TURP vs TURP, 30 months vs 22 months, P = .34). The median duration between TURP and start of SBRT was 10 months. There was no significant difference between non-TURP versus TURP cohort in terms of RTOG acute GU toxicities grade ≥2 (8% vs 6%, P = .45), RTOG late GU toxicities grade ≥2 (8% vs 12%, P = .10), stricture rates (4% vs 6%, P = .64), and incontinence rates (0% vs 4%, P = .15). The median duration of time to late toxicity was 16 months vs 10 months (P = .12) in non-TURP and TURP cohort, respectively.

Conclusions: Although modestly increased as compared with non-TURP patients, GU toxicities remains low with SBRT in post-TURP patients. SBRT can be safely performed in carefully selected post-TURP prostate cancer patients.
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http://dx.doi.org/10.1016/j.prro.2019.04.003DOI Listing
January 2020

Pediatric Patients With SHH Medulloblastoma Fail Differently as Compared With Adults: Possible Implications for Treatment Modifications.

J Pediatr Hematol Oncol 2019 11;41(8):e499-e505

Departments of Radiation Oncology.

Purpose: The purpose of this work was to study the diversity of sonic hedgehog (SHH) medulloblastoma across different age groups with an emphasis on patterns of relapse.

Methods: All data for the study were obtained through review of medical records, imaging, radiation charts, treatment planning, and chemotherapy details.

Results: Sixty-three patients with SHH medulloblastoma were identified from a prospectively maintained database and classified into 3 groups-infantile: ≤3 years (i-SHH, n=11); pediatric: >3 to <18 years (p-SHH, n=21); and adult: ≥18 years (a-SHH; n=31). Lateralized tumors were common with increasing age (81% a-SHH, 67% p-SHH, 27% i-SHH; P=0.01). Large cell anaplastic histology was relatively common for p-SHH (33%), while the nodular/desmoplastic variant was more frequent in i-SHH (64%) and adults (51%). Median follow-up was 38 months (range, 5 to 91 mo). Five-year event-free survival was 80%, 31%, and 52% for i-SHH, p-SHH, and a-SHH, respectively (P=0.001). Median time to failure for p-SHH and a-SHH were 12 and 36 months, respectively. For p-SHH, 83% were metastatic relapses compared with localized failure in 75% for a-SHH. Five-year overall survival for i-SHH, p-SHH, and a-SHH were 91%, 31%, and 70%, respectively (P=0.001). On univariate analysis, event-free survival was significantly worse for superiorly located tumors (P=0.01), nondesmoplastic histology (P=0.02), and histology alone for overall survival (P=0.04) (none on multivariate analysis).

Conclusions: SHH medulloblastoma demonstrates varied outcomes depending on age, with p-SHH associated with early and metastatic relapses, while for a-SHH it tends to be delayed and localized.
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http://dx.doi.org/10.1097/MPH.0000000000001484DOI Listing
November 2019

Bladder cancer demographics and outcome data from 2013 at a tertiary cancer hospital in India.

Indian J Cancer 2019 Jan-Mar;56(1):54-58

Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Background: Bladder cancer (BCa) is the ninth most common cancer accounting for 3.9% of all cancer cases as per the Indian Cancer Registry data. There is a scarcity of data on urinary Bca from India.

Aim: The aim of this study was to know demographic background, stage distribution, utilization of various treatment modalities, and oncological outcome in Indian patients presenting with bladder cancer to a tertiary care cancer center in Mumbai.

Methodology: We performed a retrospective audit of all patients registered as urinary BCa in our hospital from January 1, 2013 to December 31, 2013. Electronic medical records of these patients were checked for most of the information gathered.

Results: Median age of patients at presentation was 59 years with a range of 18-88 years. There were 84% male and 16% female patients. Forty seven percent of patients had nonmuscle invasive bladder cancer (NMIBC), 36% had muscle invasive bladder cancer and locally advanced disease, and 17% had metastatic disease. Eight patients were treated with trimodality bladder preservation protocol. Recurrence was seen in 38 (22.6%) patients with NMIBC. Out of them. 44.7% and 55.3% were in low- and high-grade tumors, respectively. Overall survival and disease-free survival estimated for 3 years were 63% and 57%, respectively.

Conclusion: Bladder cancer has a varied spectrum of presentation. Bladder cancer patients presenting to our hospital generally have a higher stage and grade of disease compared with that in the west.
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http://dx.doi.org/10.4103/ijc.IJC_351_18DOI Listing
August 2019

Kidney cancer demographics and outcome data from 2013 at a tertiary cancer hospital in India.

Indian J Cancer 2017 Oct-Dec;54(4):601-604

Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Introduction: The stage at diagnosis of renal cell cancer (RCC) in developed countries is lower due to increased utilization of routine health checkups by patients compared to developed countries. This study aims to determine the sociodemographic and clinical distribution of RCC in patients presenting to Tata Memorial Hospital (TMH).

Subjects And Methods: We performed a retrospective audit of all patients presenting to TMH with a diagnosis of RCC. Data were retrieved from our electronic medical record system from January 1, 2013 to December 31, 2013. The survival analysis was done by Kaplan-Meir analysis method of estimating survival. Log-rank test of comparison was applied to estimate the difference in the survival among the different stages of renal cancer.

Results: Of the 35,197 new registered patients at TMH, 338 were diagnosed with RCC. Most patients were in the 50-60 years age group, with 56.6 years being the median age at presentation. Among patients treated at TMH, 84 underwent surgery and tyrosine kinase inhibitor was given in 55 (16%) patients. The patients' characteristics, clinical characteristics of RCC, treatment modalities offered, and survival of patients treated for RCC are presented in this paper.

Conclusion: In the absence of robust Indian data on RCC, this audit provides baseline information on epidemiology, stage at presentation, and outcomes of RCC at our center compared with the West.
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http://dx.doi.org/10.4103/ijc.IJC_644_17DOI Listing
October 2018

Demographic profile, clinicopathological spectrum, and treatment outcomes of primary central nervous system tumors: Retrospective audit from an academic neuro-oncology unit.

Indian J Cancer 2017 Oct-Dec;54(4):594-600

Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Primary tumors of the central nervous system are relatively uncommon, comprising only 1%-2% of all neoplasms. However, they constitute the second most common type of malignancy in children (after leukemia) and the leading cause of cancer-related morbidity and mortality in children and young adults worldwide. Globally, there is substantial variability with nearly five-fold difference in incidence between various parts of the world. Brain tumors are quite heterogeneous with regard to histology, biological behavior, and prognosis mandating multidisciplinary therapeutic decision-making. This retrospective audit of all consecutive patients registered in a single calendar year (2013) in the neuro-oncology disease management group at Tata Memorial Centre is reflective of the ground reality and fair representation of outcomes in routine neuro-oncologic practice.
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http://dx.doi.org/10.4103/ijc.IJC_543_17DOI Listing
October 2018

Nomograms based on preoperative multiparametric magnetic resonance imaging for prediction of molecular subgrouping in medulloblastoma: results from a radiogenomics study of 111 patients.

Neuro Oncol 2019 01;21(1):115-124

Department of Radiation Oncology, Tata Memorial Hospital/Advanced Centre for Treatment, Research, & Education in Cancer, Tata Memorial Centre, Mumbai, India.

Background: Novel biological insights have led to consensus classification of medulloblastoma into 4 distinct molecular subgroups-wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. We aimed to predict molecular subgrouping in medulloblastoma based on preoperative multiparametric magnetic resonance imaging (MRI) characteristics.

Methods: A set of 19 MRI features were evaluated in 111 patients with histologic diagnosis of medulloblastoma for prediction of molecular subgrouping. MRI characteristics were correlated with molecular subgroups derived from tissue samples in 111 patients (WNT = 17, SHH = 44, Group 3 = 27, and Group 4 = 23). Multinomial logistic regression of imaging parameters was performed on a training cohort (TC) of 76 patients, representing two-thirds of randomly selected patients from each of 4 molecular subgroups, to generate binary nomograms. Validation of these nomograms was performed on the remaining 35 patients as the validation cohort (VC).

Results: Medulloblastoma subgroups could be accurately predicted by preoperative MRI features in 74% of cases. Predictive accuracy was excellent for SHH (95%), acceptably high for Group 4 (78%), modest for Group 3 (56%) and worst for WNT (41%) subgroup medulloblastoma. SHH-specific nomogram was associated with excellent correlation between TC and VC, with area under the curve (AUC) of 0.939 and 0.991, respectively. AUC for Group 4 was acceptable at 0.851 and 0.788 in TC and VC, respectively; however, these values were consistently suboptimal in WNT and Group 3 medulloblastoma.

Conclusion: The predictive accuracy of MRI-based nomograms was excellent for SHH and encouraging for Group 4 medulloblastoma. Further work is needed for Group 3 and WNT-pathway medulloblastoma.
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http://dx.doi.org/10.1093/neuonc/noy093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303469PMC
January 2019

Distinct demographic profile and molecular markers of primary CNS tumor in 1873 adolescent and young adult patient population.

Childs Nerv Syst 2018 08 5;34(8):1489-1495. Epub 2018 May 5.

Neuro-Oncology Disease Management Group, Tata Memorial Centre, 1129, Homi Bhabha Block, Parel, Mumbai, 400012, India.

Introduction: We present detailed demographic profile, tumor types, and their molecular markers in adolescent and young adult (AYA) patients of age group between 15 and 39 years with primary central nervous system (PCNS) tumors, and compare with pediatric and adult patient populations.

Methodology: Demographic- and disease-related information of 1873 PCNS tumor patients of age 15-39 years registered between 1 January 2011 and 31 December 2015 at our institution was analyzed with respect to their demographics and tumor subtypes. Various molecular markers for glial tumors and subgroup classification of medulloblastoma were evaluated for AYA, pediatric, and older adult patient populations.

Results: AYA constituted 27% of all PCNS. Median age was 29 years. Glial tumors (62.36%) comprised the largest tumor type with astrocytoma (38.55%) being the most common histology. Glioblastoma (51.52%) was the commonest astrocytic tumor with 74.67% of them being isocitrate dehydrogenase 1 (IDH1) negative and 41.38% with O (6)-methylguanine DNA methyltransferase (MGMT) promoter methylated. Diffuse astrocytoma and glioblastoma showed significantly higher IDH1 positivity and loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) for AYAs as compared to pediatric and adult patient populations (p < 0.0001). Medulloblastoma (73.8%) was the most commonly diagnosed embryonal tumor, with sonic hedgehog (SHH) being the commonest molecular subtype (48%). Younger patients among AYA population presents with pediatric type of tumor spectrum, while older ones present with more aggressive tumor subtypes.

Conclusion: This is among the few studies reporting spectrum of PCNS tumor in AYA population with distinct tumor subtypes and molecular profiles. AYA patient populations may need special attention with appropriately designed clinical trials.
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http://dx.doi.org/10.1007/s00381-018-3785-yDOI Listing
August 2018

Shadow study: randomized comparison of clinic with video follow-up in glioma undergoing adjuvant temozolomide therapy.

CNS Oncol 2018 04 30;7(2):CNS14. Epub 2018 Apr 30.

Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India.

Aim: This study was designed with a primary objective to study the rate of agreement in treatment plan and decisions between video follow-up (VF) and conventional clinic follow-up (CF).

Patients & Methods: Adult patients with intermediate- to high-grade glioma on adjuvant temozolomide (TMZ) with facilities for live video call were invited to participate in the study.

Results: The concurrence in decision of administering TMZ between VF and CF was 100% (p < 0.00). The median cost incurred in VF was US$58.15 while that incurred in CF was US$131.23 (p < 0.00).

Conclusion: VF can substitute CF during adjuvant TMZ administration (CTRI/2017/01/007626).
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http://dx.doi.org/10.2217/cns-2017-0024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977274PMC
April 2018

Magnetic Resonance Image Guided Adaptive Brachytherapy in Locally Advanced Cervical Cancer: An Experience From a Tertiary Cancer Center in a Low and Middle Income Countries Setting.

Int J Radiat Oncol Biol Phys 2017 11 20;99(3):608-617. Epub 2017 Jun 20.

Department of Radiation Oncology and Medical Physics, Tata Memorial Centre, Mumbai, India.

Purpose: To determine the clinical impact of magnetic resonance image guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC) (stages II and III) in a tertiary care cancer hospital in a low and middle income countries setting.

Methods And Materials: Ninety-four LACC patients enrolled in a prospective EMBRACE (An International Study on MRI-Guided Brachytherapy in Locally Advanced Cervical Cancer) protocol treated with external radiation therapy (45 Gy in 25 fractions) with or without weekly cisplatin, followed by magnetic resonance IGABT (4 fractions of 7 Gy), were analyzed in detail for dosimetric and clinical outcomes including late toxicities.

Results: The mean (± standard deviation) high-risk clinical target volume (HR-CTV) at the first session of brachytherapy and at the second session of brachytherapy for the current study cohort was 46.94 ± 24.6 cm and 42.7 ± 22.5 cm, respectively, with mean minimum dose received by 90% volume (D) of 88.3 ± 4.4 equivalent 2-Gy fractionation (Gy). At median follow-up (39 months), the local control rate (LCR) and overall progression-free survival rate were 90.1% ± 3.4% and 72.1% ± 4.8%, respectively, with grade 3 bladder toxicity in 3% of patients and rectum toxicity in 9%. The LCR at 39 months was significantly better in patients with stage IIB and IVA disease versus stage IIIB disease (100% vs 85%, P=.013). Local failures were limited to stage IIIB only and were associated with significantly larger HR-CTVs at brachytherapy (70 ± 25.7 cm vs 44.3 ± 21.9 cm, P=.01) but not with HR-CTV D doses (which were similar for patients who had local failures vs those who did not: 86.3 ± 3.9 α/β equal to 10 Gy (Gy) vs 88.5 ± 5 α/β equal to 10 Gy, P=.987).

Conclusions: IGABT leads to a significant improvement in LCR and overall progression-free survival in LACC and should be considered for wider implementation in developing countries to improve outcomes.
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http://dx.doi.org/10.1016/j.ijrobp.2017.06.010DOI Listing
November 2017

Effect of imaging frequency on PTV margins and geographical miss during image guided radiation therapy for prostate cancer.

Pract Radiat Oncol 2018 Mar - Apr;8(2):e41-e47. Epub 2017 Oct 7.

Department of Radiation Oncology, Tata Memorial Centre- Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, Maharashtra, India. Electronic address:

Background: The relationship between frequency of imaging during image guided radiation therapy (IGRT) and planning target volume (PTV) margin remains unclear. This issue is of practical significance given resource and time intensive nature of IGRT. The purpose of this study was to evaluate PTV margins with predefined and commonly used less-than-daily IGRT schedules using data obtained from patients treated with daily IGRT for prostate cancer.

Methods And Materials: Daily setup error and 3-dimensional daily alignment data for a total of 108 consecutive patients with prostate cancer treated with 2700 fractions of daily image guidance on tomotherapy were retrospectively analyzed. Five IGRT scenarios were simulated: alternate day, twice weekly, once weekly, first 3 days only, and no image guidance. The daily alignment data were modeled to simulate the 5 predefined scenarios by applying appropriate corrections to determine the PTV margin for each image guidance scenario. The data were also analyzed to predict possible geographical miss in any direction using 2 frequently used PTV margins of 7 and 5 mm for all the scenarios.

Results: Decreasing the frequency of image guidance increased the mean systematic error and the standard deviation of the systematic error. With decreased image guidance frequency, an increase in PTV margins was required to achieve adequate coverage of the clinical target volume. With reduction in image guidance from 50% to 12%, a gradual increase in percentage of fractions with predicted geographical miss using an isotropic PTV margin of 7 or 5 mm was seen. With every 15% decrease in imaging, a 5% increased risk of geographical miss was estimated.

Conclusions: The use of less-than-daily IGRT requires larger PTV margins for patients treated with intensity modulated radiation therapy for prostate cancer. With every 15% reduction, a 5% increased risk of geographical miss was estimated.
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http://dx.doi.org/10.1016/j.prro.2017.09.010DOI Listing
September 2018

Multiplex Detection of Pediatric Low-Grade Glioma Signature Fusion Transcripts and Duplications Using the NanoString nCounter System.

J Neuropathol Exp Neurol 2017 Jul;76(7):562-570

Department of Cancer and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Divisions of Pathology and Genome Diagnostics, Department of Paediatric Laboratory Medicine; and Division of Hematology and Oncology, The Division of Hematology and Oncology should be followed by Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada. Hospital for Sick Children, Toronto, Ontario, Canada; Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, India; and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

Previous studies identified recurrent fusion and duplication events in pediatric low-grade glioma (pLGG). In addition to their role in diagnosis, the presence of these events aid in dictating therapy and predicting patient survival. Clinically, BRAF alterations are most commonly identified using fluorescent in situ hybridization (FISH). However, this method is costly, labor-intensive and does not identify nonBRAF events. Here, we evaluated the NanoString nCounter gene expression system for detecting 32 of the most commonly reported fusion/duplication events in pLGG. The assay was validated on 90 pLGG samples using FISH as the gold standard and showed sensitivity and specificity of 97% and 98%, respectively. We next profiled formalin-fixed paraffin-embedded preserved biopsy specimens from 429 pLGG cases. 171 (40%) of the cases within our cohort tested positive for a fusion or duplication event contained within our panel. These events, in order of prevalence, were KIAA1549-BRAF 16;9 (89/171, 52.0%), KIAA1549-BRAF 15;9 (42/171, 24.6%), KIAA1549-BRAF 16;11 (14/171, 8.2%), FGFR1-TACC1 17;7 (13/171, 7.6%), MYBL1 duplication (5/171, 2.9%), KIAA1549-BRAF 18;10 (4/171, 2.3%), KIAA1549-BRAF 15;11 (2/171, 1.2%), FAM131B-BRAF 2;9 (1/171, 0.6%), and RNF130-BRAF 3;9 (1/171, 0.6%). This work introduces NanoString as a viable clinical replacement for the detection of fusion and duplication events in pLGG.
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http://dx.doi.org/10.1093/jnen/nlx042DOI Listing
July 2017

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.

J Clin Oncol 2017 Sep 20;35(25):2934-2941. Epub 2017 Jul 20.

Alvaro Lassaletta, Michal Zapotocky, Matthew Mistry, Vijay Ramaswamy, Marion Honnorat, Rahul Krishnatry, Ana Guerreiro Stucklin, Nataliya Zhukova, Anthony Arnoldo, Scott Ryall, Catriona Ling, Tara McKeown, Jim Loukides, James T. Rutka, Peter Dirks, Michael D. Taylor, Shiyi Chen, Ute Bartels, Annie Huang, Eric Bouffet, Cynthia Hawkins, and Uri Tabori, The Hospital for Sick Children, Toronto; Adam Fleming, McMaster Children's Hospital, McMaster University, Hamilton; Shayna Zelcer, Children's Hospital of Western Ontario, London, Ontario; David Eisenstat and Bev Wilson, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta; Anne Sophie Carret, Hospital Sainte Justine; Nada Jabado, McGill University, Montreal; Valerie Larouche, Centre Hospitalier Universitaire de Québec, Québec City, Quebec, Canada; Ofelia Cruz and Carmen de Torres, Hospital Sant Joan de Déu, Barcelona, Spain; Cheng-Ying Ho, University of Maryland School of Medicine, Baltimore, MD; Roger J. Packer, Children's National Health System, Washington, DC; Ruth Tatevossian, Ibrahim Qaddoumi, Julie H. Harreld, James D. Dalton, and David W. Ellison, St Jude Children's Research Hospital, Memphis, TN; Jean Mulcahy-Levy and Nicholas Foreman, Children's Hospital Colorado, Aurora, CO; Matthias A. Karajannis, Shiyang Wang, and Matija Snuderl, New York University Langone Medical Center, New York, NY; Amulya Nageswara Rao and Caterina Giannini, The Mayo Clinic, Rochester, MN; Mark Kieran and Keith L. Ligon, Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA; Maria Luisa Garre, Paolo Nozza, Samantha Mascelli, and Alessandro Raso, Istituto Giannina Gaslini, Genoa, Italy; Sabine Mueller and Theodore Nicolaides, University of California, San Francisco, San Francisco, CA; Karen Silva and Romain Perbet, Hospices Civils de Lyon; Alexandre Vasiljevic, Cécile Faure Conter, and Didier Frappaz, Institute of Pediatric Hematology and Oncology, Lyon, France; Sarah Leary and Courtney Crane, Seattle Children's Hospital, Seattle, WA; Aden Chan and Ho-Keung Ng, The Chinese University of Hong Kong, Hong Kong; Zhi-Feng Shi and Ying Mao, Huashan Hospital, Fudan University, Shanghai, People's Republic of China; Elizabeth Finch, University of North Carolina, School of Medicine, Chapel Hill, NC; Peter Hauser, Semmelweis University, Budapest, Hungary; and David Sumerauer and Lenka Krskova, University Hospital Motol, Charles University, 2nd Medical School, Prague, Czech Republic.

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively ( P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy.
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http://dx.doi.org/10.1200/JCO.2016.71.8726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791837PMC
September 2017

Income generated by women treated with magnetic resonance imaging-based brachytherapy: A simulation study evaluating the macroeconomic benefits of implementing a high-end technology in a public sector healthcare setting.

Brachytherapy 2017 Sep - Oct;16(5):981-987. Epub 2017 Jun 7.

Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, India.

Purpose: To estimate the difference in income generated if all women presenting in our institute over a 5-year period were treated with MRI-based image-guided brachytherapy (MR-IGBT) instead of conventional radiograph-based brachytherapy (CR-BT).

Methods And Materials: Outcome data from 463 patients (94 treated with MR-IGBT) treated in our institute was used to simulate cumulative women-days of work and cumulative income over 5 years for 5526 patients expected to be treated in this period. The average daily income for a woman was derived from the National Sample Survey Organization (NSSO) survey data. Outcomes from both unmatched and propensity score-matched data sets were simulated.

Results: The cumulative income in 5 years ranged between Rs 101-168 million if all patients presenting at our institute underwent MR-IGBT. The simulated excess income ranged from Rs 4-45 million after 5 years, which represented 6-66% of the expenditure incurred for acquiring the required equipment and manpower for practicing exclusive MR-IGBT.

Conclusions: Using outcome data from a prospective cohort of patients treated with MR-IGBT in our institute, we demonstrated that significant economic gains may be realized if MR-IGBT was used instead of CR-BT.
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http://dx.doi.org/10.1016/j.brachy.2017.05.003DOI Listing
April 2018

Survey of return to work of head and neck cancer survivors: A report from a tertiary cancer center in India.

Head Neck 2017 05 7;39(5):893-899. Epub 2017 Feb 7.

Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Background: The rates and factors associated with the return to work of head and neck cancer survivors from low- and middle-income countries, such as India, are largely unknown.

Methods: We conducted a preliminary cross-sectional survey of 250 consecutive eligible head and neck cancer survivors (age <60; ≥6 months posttreatment) to identify return to work rates and sociodemographic, clinical, and quality of life (QOL; European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions [EORTC-QLQ-C30] and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions [EORTC-QLQ-H&N35]) correlates.

Results: In our cohort, 92.4% of the patients were employed pretreatment, 65.6% and 81.2% returned to work at 6 months posttreatment and by the time of the survey (median follow-up 19 months), respectively. Family structure (<2 male children, p = .008; eldest child age <20 years, p = .04), a higher level of education (vocational or professional training, p = .013) and female sex (p = .001) were associated with higher return to work. Head and neck cancer survivors who returned to work had better global quality of life (QOL; p = .014) and less coughing (p = .001) but more problems related to sticky saliva (p = .004).

Conclusion: Further studies are needed to address the large unmet needs regarding identification and amelioration of barriers to return to work for head and neck cancer survivors in low- and middle-income countries, such as India. © 2017 Wiley Periodicals, Inc. Head Neck 39: 893-899, 2017.
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http://dx.doi.org/10.1002/hed.24703DOI Listing
May 2017