Dr. Bindu Musunuru headshot

Hima Bindu Musunuru, MBBS, MRCP-UK, FRCR-UK

Eric Wolfe Clinical Research Fellow

Department of Human Oncology

I am the Eric Wolfe Clinical Research Fellow in the Department of Human Oncology. My work focuses on advancing clinical research and developing clinical protocols. I collaborate with DHO faculty on projects focused on improving treatment and outcome for a variety of disease sites, including brain, head and neck, breast and lung. My work leverages opportunities afforded by the department’s ViewRay MRIdian radiation therapy system. This advanced system uses real-time magnetic resonance imaging to enable clinicians to monitor tumors and normal tissues in real time during the delivery of radiation. This is quite new in the world of radiation oncology and offers unique opportunities to achieve greater precision in daily treatments. When I complete the Wolfe Fellowship, I plan to pursue a position in academic medicine. In the meantime, I’m excited about this opportunity to further develop my skills and advance cancer research.


Fellow, University of Toronto, Prostate SABR and Brachytherapy (2015)

Resident, Humber and Yorkshire Deanery, Clinical Oncology (2013)

FRCR-UK, Royal College of Radiology, Radiation Oncology (2012)

Resident, Leeds General Infirmary, Internal Medicine (2008)

MRCP-UK, Royal College of Physicians, Internal Medicine (2007)

Resident, Huddersfield General Infirmary, Cardiology (2006)

Resident, St. James's University Hospital, Renal and Geriatric Medicine (2005)

Intern, Siddhartha Medical College and Hospital, (2003)

MB, BS, Siddhartha Medical College, NTR University of Health Sciences, (2003)

Selected Honors and Awards

Frank Ellis RCR Medal for best contribution to Clinical Oncology (2014)

ESTRO Young Scientist (2012)

Best oral presentation at the UK and Ireland Brachytherapy conference (2012)

Dr. P. Siva Reddy Endowment Medal in Ophthalmology (2002)

Boards, Advisory Committees and Professional Organizations

Canadian Association of Radiation Oncology

American Society for Radiation Oncology

American Society of Clinical Oncology

  • Reduction of cardiac dose using respiratory-gated MR-linac plans for gastro-esophageal junction cancer. Med Dosim
    Lee SL, Mahler P, Olson S, Witt JS, Musunuru HB, Rajamanickam V, Bassetti MF, Yadav P
    2020 Oct 20; :
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      Treatment of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) with chemoradiation may be associated with high rates of symptomatic cardiac toxicity. Large margins are typically required to ensure coverage of GEJ tumors with free-breathing volumetric modulated arc therapy (VMAT) radiotherapy. The purpose of this study is to determine whether treatment with tighter margins enabled by maximum-inhalation breath hold (MIBH)-gated intensity modulated radiation therapy (IMRT) on an integrated MRI-linear accelerator system (MR-linac) can decrease radiation doses to the heart and cardiac substructures. Ten patients with locally advanced GEJ adenocarcinoma underwent both free breathing 4-dimensional computed tomography (4DCT) and MIBH MRI simulation scans. MR-linac IMRT plans were created with a 3 mm clinical target volume (CTV) to planning target volume (PTV) isotropic margin and 4DCT VMAT plans were created with a 11, 13, and 9 mm CTV to PTV anisotropic margins in the left-right, cranial-caudal, and anterior-posterior directions according to GEJ-specific PTV expansion recommendations by Voncken et al. Prescription dose to PTV was 50.4 Gy in 28 fractions. Dosimetry to the heart and cardiac substructures was compared with paired t test; p < 0.05 was considered significant. Mean PTV on the MR-linac IMRT plans was significantly smaller compared to the 4DCT VMAT plans (689 cm3vs 1275 cm3, p < 0.01). Mean dose to the heart and all cardiac substructures was significantly lower in the MR-linac IMRT plans compared to the 4DCT VMAT plans: heart 20.9 Gy vs 27.8 Gy, left atrium 29.6 Gy vs 39.4 Gy, right atrium 20.5 Gy vs 25.6 Gy, left ventricle 21.6 Gy vs 29.6 Gy, and right ventricle 18.7 Gy vs 25.2 Gy (all p values <0.05). MIBH-gated MR-linac IMRT treatment of locally advanced GEJ adenocarcinoma can significantly decrease doses to the heart and cardiac substructures and this may translate to reduced rates of cardiac toxicity.

      View details for PubMedID 33097372
  • A Feasibility Study on the Role of Ultrasound Imaging of Bladder Volume as a Method to Improve Concordance of Bladder Filling Status on Treatment with Simulation. J Med Imaging Radiat Sci
    Nathoo D, Loblaw A, Davidson M, Musunuru HB, Khojaste A, Ravi A
    2018 Sep; 49 (3): 277-285
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      PURPOSE: Accurate positioning of the prostate is of paramount importance to ensure optimal target coverage and normal tissue sparing in stereotactic ablative body radiation when large doses per fraction are delivered with tight margins around the prostate. Bladder and rectal filling play an important part in controlling the accuracy of a patient's setup and therefore the overall toxicities and outcomes. The aim of this study was to establish the value of characterizing patients' bladder filling kinetics at the time of simulation with ultrasound scans so that a predictive model can be used to ensure that a bladder volume at treatment would match at simulation.

      METHODS: A prospective trial was conducted in unfavorable risk prostate cancer patients to evaluate the utility of ultrasound bladder monitoring. Thirty patients (n = 30) were enrolled in this study. Patients were required to void before simulation and then were given 500 mL of fluids to drink. Ultrasound measurements of the bladder were documented at 15-minute intervals for up to four measurements before simulation. On treatment, bladder volumes were measured at a single time point; typically, half an hour after the patient voided and consumed 500 mL of fluids. The kinetic model was then used to predict the optimal time to set up the patient for treatment such that the bladder volume at treatment would match the volume at simulation. Every patient had a cone beam computed tomography scan before each fraction to ensure accurate patient positioning before dose delivery. Bladder volumes at treatment were measured and compared with those at simulation on the cone beam computed tomography data sets using MIMVISTA software.

      RESULTS: Of 30 patients, 26 were analyzed. The comparison of the bladder contours at treatment compared to simulation yielded a DICE coefficient (similarity) of 0.76 ± 0.11. The largest variation in bladder size was seen in the anterior-posterior direction.

      CONCLUSIONS: This study demonstrated that ultrasound monitoring of the bladder status was a valuable tool in ensuring reproducible bladder filling on treatment. The bladder kinetic model indicated the general time required to achieve optimal bladder filling was 60 minutes after voiding and drinking 500 mL of water.

      View details for PubMedID 32074054
  • Evaluating the tolerability of a simultaneous focal boost to the gross tumour in prostate SABR: a toxicity and quality of life comparison of two prospective trials. Int J Radiat Oncol Biol Phys
    Alayed Y, Davidson M, Liu S, Chu W, Tseng CL, Cheung P, Vesprini D, Chung H, Morton G, Musunuru HB, Ravi A, Korol R, Deabreu A, Ho L, Commisso K, Bhounr Z, D'Alimonte L, Mittmann N, Dragomir A, Zhang L, Loblaw DA
    2020 Jan 24; :
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      PURPOSE: Dose-escalated XXXX to the whole prostate may be associated with better outcomes, but at a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on MRI. We report the toxicity and quality of life (QOL) outcomes of two phase II trials of prostate and pelvic XXXX, with or without a simultaneous DIL boost.

      METHODS: The first trial treated patients with high-risk prostate cancer (PCa) to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk PCa to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities and QOL were assessed.

      RESULTS: 30 patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 GI or GU toxicity between the two trials, or cumulative worst late GI or GU toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the two trials.

      CONCLUSIONS: Prostate and pelvic XXXX with a simultaneous DIL boost was feasible. Acute grade ≥2 toxicity, late toxicity, and QOL seems to be comparable to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes, and randomized data is required to confirm these findings.

      View details for PubMedID 31987962
  • Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy. Radiother Oncol
    Alayed Y, Davidson M, Quon H, Cheung P, Chu W, Chung HT, Vesprini D, Ong A, Chowdhury A, Liu SK, Panjwani D, Helou J, Musunuru HB, Pang G, Korol R, Ravi A, McCurdy B, Zhang L, Mamedov A, Deabreu A, Commisso A, Commisso K, D'Alimonte L, Ho L, Bhounr Z, Loblaw A
    2019 Dec 03; 144: 135-140
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      PURPOSE: SABR offers an effective treatment option for clinically localized prostate cancer. Here we report the dosimetric predictors of late toxicity and quality of life (QOL) in a pooled cohort of patients from four phase II trials.

      METHODS: The combined cohort included all three prostate cancer risk groups. The prescription dose was 35-40 Gy in 5 fractions. Toxicity (CTCAE) and QOL (EPIC) were collected. Multiple dosimetric parameters for the bladder, rectum and penile bulb were collected. Univariate (UVA) followed by multivariate (MVA) logistic regression analysis was conducted to search for significant dosimetric predictors of late GI/GU toxicity, or minimal clinically important change in the relevant QOL domain.

      RESULTS: 258 patients were included with median follow up of 6.1 years. For QOL, bladder Dmax, V38, D1cc, D2cc, D5cc and rectal V35 were predictors of urinary and bowel MCIC on UVA. On MVA, only bladder V38 remained significant. For late toxicity, various parameters were significant on UVA but only rectal Dmax, V38 and bladder D2cc were significant predictors on MVA.

      CONCLUSIONS: This report confirms that the high-dose regions in the bladder and rectum are more significant predictors of late toxicity and QOL after prostate SABR compared to low-dose regions. Caution must be taken to avoid high doses and hotspots in those organs.

      View details for PubMedID 31809979
  • Impact of adjuvant fractionated stereotactic radiotherapy dose on local control of brain metastases. J Neurooncol
    Musunuru HB, Witt JS, Yadav P, Francis DM, Kuczmarska-Haas A, Labby ZE, Bassetti MF, Howard SP, Baschnagel AM
    2019 Oct 12; :
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      PURPOSE: The aim of this study was to determine whether a higher biological effective dose (BED) would result in improved local control in patients treated with fractionated stereotactic radiotherapy (FSRT) for their resected brain metastases.

      METHODS: Patients with newly diagnosed brain metastases without previous brain radiotherapy were retrospectively reviewed. Patients underwent surgical resection of at least one brain metastasis and were treated with adjuvant FSRT, delivering 25-36 Gy in 5-6 fractions. Outcomes were computed using Kaplan-Meier survival analysis and univariate analysis.

      RESULTS: Fifty-four patients with 63 post-operative cavities were included. Median follow-up was 16 months (3-60). Median metastasis size at diagnosis was 2.9 cm (0.6-8.1) and median planning target volume was 19.7 cm3 (6.3-68.1). Two-year local control (LC) was 83%. When stratified by dose, 2 years LC rate was 95.1% in those treated with 30-36 Gy in 5-6 fractions (BED10 of 48-57.6 Gy10) versus 59.1% lesions treated with 25 Gy in 5 fractions (BED10 of 37.5 Gy10) (p < 0.001). LC was not associated with resection cavity size. One year overall survival was 68.7%, and was independent of BED10. Symptomatic radiation necrosis occurred in 7.9% of patients and was not associated with dose.

      CONCLUSION: In the post-operative setting, high-dose FSRT (BED10 > 37.5 Gy10) were associated with a significantly higher rate of LC compared to lower BED regimens. Overall, 25 Gy in 5 fractions is not an adequate dose to control microscopic disease. If selecting a 5-fraction regimen, 30 Gy in five fractions appears to provide excellent tumor bed control.

      View details for PubMedID 31606876
  • Dosimetric study for spine stereotactic body radiation therapy: magnetic resonance guided linear accelerator versus volumetric modulated arc therapy. Radiol Oncol
    Yadav P, Musunuru HB, Witt JS, Bassetti M, Bayouth J, Baschnagel AM
    2019 Sep 24; 53 (3): 362-368
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      Background Stereotactic body radiation therapy (SBRT) given in 1-5 fractions is an effective treatment for vertebral metastases. Real-time magnetic resonance-guided radiotherapy (MRgRT) improves soft tissue contrast, which translates into accurate delivery of spine SBRT. Here we report on clinical implementation of MRgRT for spine SBRT, the quality of MRgRT plans compared to TrueBeam based volumetric modulated arc therapy (VMAT) plans in the treatment of spine metastases and benefits of MRgRT MR scan. Patients and methods Ten metastatic lesions were included in this study for plan comparison. Lesions were spread across thoracic spine and lumbosacral spine. Three fraction spine SBRT plans: 27Gy to planning target volume (PTV) and 30Gy to gross tumor volume (GTV) were generated on the ViewRay MRIdian Linac system and compared to TrueBeamTM STx based VMAT plans. Plans were compared using metrics such as minimum dose, maximum dose, mean dose, ratio of the dose to 50% of the volume (R50), conformity index, homogeneity index and dose to the spinal cord. Results MRIdian plans achieved equivalent target coverage and spinal cord dose compared to VMAT plans. The maximum and minimum PTV doses and homogeneity index were equivalent for both planning systems. R50 was lower for MRIdian plans compared to VMAT plans, indicating a lower spread of intermediate doses with MRIdian system (5.16 vs. 6.11, p = 0.03). Conclusions MRgRT can deliver high-quality spine SBRT plans comparable to TrueBeam volumetric modulated arc therapy (VMAT) plans.

      View details for PubMedID 31553704
  • Pre-treatment serum bicarbonate predicts for primary tumor control after stereotactic body radiation therapy in patients with localized non-small cell lung cancer. Radiother Oncol
    Sebastian N, Wu T, Driscoll E, Willers H, Kelly S, Musunuru HB, Mo X, Tan Y, Bazan J, Haglund K, Xu-Welliver M, Baschnagel AM, Ju A, Keane F, Williams TM
    2019 Jun 05; 140: 26-33
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      BACKGROUND: Tumor aggressiveness and hypoxia are linked to acidosis in the tumor microenvironment (TME). We hypothesized that low pre-treatment serum bicarbonate, potentially correlating with an acidic and hypoxic TME, predicts for poor outcomes after stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC).

      METHODS: We included patients with localized NSCLC treated to a biologically effective dose (BED) ≥ 100 Gy, with available pre-treatment bicarbonate values within 3 months of treatment. We used receiver operating characteristic analysis to determine the bicarbonate concentration optimally predicting for primary tumor recurrence, and evaluated its association with recurrence and survival. We validated our findings in an independent cohort of patients from three collaborating institutions.

      RESULTS: A total of 110 patients and 114 tumors were included in the training cohort, with median follow-up of 15.0 months. Bicarbonate < 26 mEq/L was associated with primary tumor recurrence on univariate (HR = 5.92; 95% CI 1.69-24.88; p = 0.005) and multivariate analysis (HR = 5.48; 95% CI 1.37-25.19; p = 0.020). The validation cohort consisted of 195 patients and 208 tumors with median follow-up of 27.5 months. In the validation cohort, bicarbonate < 26 mEq/L was again associated with primary tumor recurrence on univariate (HR = 3.38; 95% CI 1.27-9.37; p = 0.015) and multivariate analysis (HR = 3.33; 1.18-10.07; p = 0.023).

      CONCLUSIONS: Pre-treatment bicarbonate predicts for primary tumor control in NSCLC treated with SBRT and may be useful for risk stratification. These findings should be confirmed prospectively.

      View details for PubMedID 31176206
  • SABR in high risk prostate cancer: outcomes from two prospective clinical trials with and without elective nodal irradiation. Int J Radiat Oncol Biol Phys
    Alayed Y, Cheung P, Vesprini D, Liu S, Chu W, Chung H, Musunuru HB, Davidson M, Ravi A, Ho L, Deabreu A, D'Alimonte L, Bhounr Z, Zhang L, Commisso K, Loblaw A
    2018 Nov 13; :
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      PURPOSE: There is limited data on SABR in high-risk prostate cancer (PCa) especially regarding the role of elective nodal irradiation (ENI). This study compares two prospective phase II trials using SABR in high-risk prostate cancer, with and without ENI.

      METHODS: Patients had high-risk PCa. Trial1 received 40Gy/5 to the prostate and 30Gy/5 to the seminal vesicles. Trial2 received 40Gy/5 to the prostate and 25Gy/5 to the pelvis and seminal vesicles. CTCAE toxicities were collected. Biochemical failure (BF) was defined as nadir+2 and 4-year PSA response rate (4yPSARR) was < 0.4 ng/ml.

      RESULTS: 60 patients were included (trial1, n=30; trial2, n=30). Median follow-up was 5.6y and 4.0y. Median nPSA was 0.02ng/ml for both. Six patients had BF, all from trial1. The BF rate was 14.6% at 5y in trial1and 0% in trial2. 63% of patients in trial1 and 93% in trial2 had a 4yPSARR. Two patients died in trial1, one from metastatic disease. One patient in trial2 died from other causes. No other patients developed metastatic disease, and one patient in trial1 had CRPC. OS at 5y was 93.2% and 96.7% (p=0.86). There was significantly worse late GI and sexual toxicity in trial1, but no difference in late GU toxicity.

      CONCLUSIONS: SABR in high-risk prostate cancer yields biochemical control rates that may be comparable to other radiotherapy modalities. ENI using SABR is feasible and may lead to a significant improvement in biochemical control as well as in 4yPSARR, without an increase in late GI or GU toxicity. Longer follow-up would provide a better assessment of biochemical control. Well conducted phase III trials are needed to fully establish the role of SABR as well as ENI in high-risk prostate cancer.

      View details for PubMedID 30445172
  • Large volume re-irradiation for recurrent meningioma with pulsed reduced dose rate radiotherapy. J Neurooncol
    Witt JS, Musunuru HB, Bayliss RA, Howard SP
    2018 Nov 03; :
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      PURPOSE: Meningiomas comprise up to 30% of primary brain tumors. The majority of meningioma patients enjoy high rates of control after conventional therapies. However, patients with recurrent disease previously treated with radiotherapy have few options for salvage treatment, and systemic interventions have proven largely ineffective. The aim of this study was to determine whether pulsed reduced dose rate radiotherapy (PRDR) was well tolerated in a small cohort of patients with recurrent meningioma.

      METHODS: We retrospectively identified eight patients with recurrent intracranial meningioma treated with PRDR from April 2013 to August of 2017 at a single institution. All patients had radiographic and/or pathologic evidence of progression prior to treatment and had previously completed conventional radiotherapy. Acute and late toxicities were graded based on CTCAE 4.0.

      RESULTS: Of eight patients, six had histologically confirmed atypical meningiomas upon recurrence. All patients were re-treated with IMRT at an apparent dose rate of 0.0667 Gy/min. Median time between radiation courses was 7.7 years. Median PRDR dose was 54 Gy in 27 fractions to a median volume of 261.6 cm3. Two patients (25%) had in field failure with a median follow up of 23.3 months. PFS at 6 months was 100%. All but one (87.5%) patient was still alive at last follow up. No patient experienced grade ≥ 2 acute or late toxicities.

      CONCLUSIONS: PRDR re-irradiation was well tolerated and appeared effective for a small cohort of patients with recurrent meningioma previously treated with radiotherapy. A phase II trial to assess this prospectively is in development.

      View details for PubMedID 30392090
  • Phase I/II Study of Stereotactic Ablative Radiotherapy Including Regional Lymph Node Irradiation in Patients with High-Risk Prostate Cancer (SATURN): Early Toxicity and Quality of Life. Int J Radiat Oncol Biol Phys
    Musunuru HB, D'Alimonte L, Davidson M, Ho L, Cheung P, Vesprini D, Liu S, Chu W, Chung H, Ravi A, Deabreu A, Zhang L, Commisso K, Loblaw DA
    2018 Jul 30; :
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      Two-year toxicity and quality of life (QOL) results are reported from a dose-escalated prostate SABR study for high-risk prostate cancer. Prostate, seminal vesicles, and pelvic lymph nodes were treated using a dose-painting schema up to 40Gy and 25Gy in 5 fractions, respectively, delivered weekly, in combination with androgen deprivation therapy. No grade 3 or higher CTCAE v 3.0 toxicity was noted. EPIC quality of life in all 4 domains was comparable to baseline at 24 months.

      View details for PubMedID 30071295
  • Dose escalation for prostate stereotactic ablative radiotherapy (SABR): Late outcomes from two prospective clinical trials. Radiother Oncol
    Alayed Y, Cheung P, Pang G, Mamedov A, D'Alimonte L, Deabreu A, Commisso K, Commisso A, Zhang L, Quon HC, Musunuru HB, Helou J, Loblaw DA
    2018 Mar 24; :
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      PURPOSE: Optimal prostate SABR dose-fractionation is unknown. This study compares long-term outcomes from two prospective trials.

      METHODS: Study1 patients had low-risk PCa and received 35 Gy/5. Study2 patients had low/intermediate-risk PCa and received 40 Gy/5. Biochemical failure (BF) was defined as nadir + 2.

      RESULTS: 114 patients were included (study1, n = 84; study2, n = 30). Median follow-up was 9.6 years and 6.9 years. Median nPSA was 0.4 and 0.1 ng/ml. Nine patients had BF (8 in study1, 1 in study2); two were managed with ADT and four had local salvage. The BF rate was 2.5% and 12.8% at 5 and 10 years for study1 and 3.3% at 5 years for study 2. BF probability was 0% if PSA <0.4 at 4 years, and 20.5% at 10 years if PSA ≥0.4 (p = 0.02). Nine patients died, none of PCa. No patient has metastases or castrate-resistance. At 10 years, OS and CSS were 90.4% (p = 0.25) and 100%.

      CONCLUSIONS: Dose-escalated prostate SABR was associated with lower nPSAs but no difference in BF, OS, CSS or MFS. PSA <0.4 at 4 years was a predictor of biochemical control. Half of patients with BF were successfully salvaged. Given that this is a favorable-risk cohort, longer follow-up will be needed to see if the lower nPSA translates into lower BF rates.

      View details for PubMedID 29588072
  • Stereotactic Body Radiotherapy versus Low Dose Rate Brachytherapy for Localised Prostate Cancer: a Cost-Utility Analysis. Clin Oncol (R Coll Radiol)
    Helou J, Torres S, Musunuru HB, Raphael J, Cheung P, Vesprini D, Chung HT, D'Alimonte L, Krahn M, Morton G, Loblaw A
    2017 Nov; 29 (11): 718-731
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      AIMS: To conduct a cost-utility analysis comparing stereotactic body radiotherapy (SBRT) with low dose rate brachytherapy (LDR-BT) for localised prostate cancer (PCa).

      MATERIALS AND METHODS: A decision-analytic Markov model was developed from the healthcare payer perspective to simulate the history of a 66-year-old man with low-risk PCa. The model followed patients yearly over their remaining lifetimes. Health states included 'recurrence-free', 'biochemical recurrence' (BR), 'metastatic' and 'death'. Transition probabilities were based on a retrospective cohort analysis undertaken at our institution. Utilities were derived from the literature. Costs were assigned in 2015 Canadian dollars ($) and reflected Ontario's health system and departmental costs. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios. A willingness-to-pay threshold of $50 000/QALY was used.

      RESULTS: SBRT was the dominant strategy with 0.008LYs and 0.029QALYs gained and a reduction in cost of $2615. Under base case conditions, our results were sensitive to the BR probability associated with both strategies. LDR-BT becomes the preferred strategy if the BR with SBRT is 1.3*[baseline BR_SBRT] or if the BR with LDR-BT is 0.76*[baseline BR_LDR-BT]. When assuming the same BR for both strategies, LDR-BT becomes marginally more effective with 0.009QALYs gained at a cost of $272 848/QALY.

      CONCLUSIONS: SBRT represents an economically attractive radiation strategy. Further research should be carried out to provide longer-term follow-up and high-quality evidence.

      View details for PubMedID 28916284
  • Dose-Escalated Stereotactic Body Radiation Therapy for Prostate Cancer: Quality-of-Life Comparison of Two Prospective Trials. Front Oncol
    Quon HC, Musunuru HB, Cheung P, Pang G, Mamedov A, D'Alimonte L, Deabreu A, Zhang L, Loblaw A
    2016; 6: 185
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      INTRODUCTION: The optimal prostate stereotactic body radiation therapy (SBRT) dose-fractionation scheme is controversial. This study compares long-term quality of life (QOL) from two prospective trials of prostate SBRT to investigate the effect of increasing dose (NCT01578902 and NCT01146340).

      MATERIAL AND METHODS: Patients with localized prostate cancer received SBRT 35 or 40 Gy delivered in five fractions, once per week. QOL was measured using the Expanded Prostate Cancer Index Composite at baseline and every 6 months. Fisher's exact test and generalized estimating equations were used to analyze proportions of patients with clinically significant change and longitudinal changes in QOL.

      RESULTS: One hundred fourteen patients were included, 84 treated with 35 Gy and 30 treated with 40 Gy. Median QOL follow-up was 56 months [interquartile range (IQR) 46-60] and 38 months (IQR 32-42), respectively. The proportion of patients reporting clinically significant declines in average urinary, bowel, and sexual scores were not significantly different between dose levels, and were 20.5 vs. 24.1% (p = 0.60), 26.8 vs. 41.4% (p = 0.16), and 42.9 vs. 38.5% (p = 0.82), respectively. Similarly, longitudinal analysis did not identify significant differences in QOL between treatment groups.

      CONCLUSION: Dose-escalated prostate SBRT from 35 to 40 Gy in five fractions was not associated with significant decline in long-term QOL.

      View details for PubMedID 27622157
  • Active Surveillance for Intermediate Risk Prostate Cancer: Survival Outcomes in the Sunnybrook Experience. J Urol
    Musunuru HB, Yamamoto T, Klotz L, Ghanem G, Mamedov A, Sethukavalan P, Jethava V, Jain S, Zhang L, Vesprini D, Loblaw A
    2016 Dec; 196 (6): 1651-1658
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      PURPOSE: To assess the applicability of active surveillance in patients with intermediate risk prostate cancer, we compared the survival outcomes of patients with low risk and intermediate risk disease.

      MATERIALS AND METHODS: Active surveillance was offered to all patients with low risk (cT1-T2b and Gleason score 6 and prostate specific antigen 10 ng/ml or less) and select intermediate risk disease (age greater than 70 years with cT2c or prostate specific antigen 15 ng/ml or less, or Gleason score 3+4 or less). Data from November 1995 to May 2013 were extracted from a prospectively collected database. The primary outcome was metastasis-free survival, and secondary outcomes were overall survival, cause specific survival and treatment-free survival.

      RESULTS: A total of 213 intermediate risk and 732 low risk cases were identified. Median age was 72 years (IQR 67.3, 76.8) in the intermediate risk cohort and 67 years (IQR 60.6, 71.9) in the low risk group. Median followup was comparable (6.7 years for intermediate risk vs 6.5 years for low risk). Gleason 7 disease comprised 60% of the intermediate risk cohort. The 15-year metastasis-free, overall, cause specific and treatment-free survival rates were inferior in the intermediate risk group (metastasis-free survival HR 3.14, 95% CI 1.51-6.53, p=0.001, 82% for intermediate risk vs 95% for low risk). On further evaluation the estimated 15-year metastasis-free survival for cases of Gleason 6 or less with prostate specific antigen less than 10 ng/ml was 94%, Gleason 6 or less with prostate specific antigen 10 to 20 ng/ml was 94%, Gleason 3+4 with prostate specific antigen 20 ng/ml or less was 84% and Gleason 4+3 with prostate specific antigen 20 ng/ml or less was 63%.

      CONCLUSIONS: These data support the use of active surveillance in low risk and intermediate risk cases of Gleason 6 but not Gleason 7 prostate cancer. Multiparametric magnetic resonance imaging and novel biomarkers might be vital in detecting favorable Gleason 7 disease.

      View details for PubMedID 27569437
  • Predictive Parameters of Symptomatic Hematochezia Following 5-Fraction Gantry-Based SABR in Prostate Cancer. Int J Radiat Oncol Biol Phys
    Musunuru HB, Davidson M, Cheung P, Vesprini D, Liu S, Chung H, Chu W, Mamedov A, Ravi A, D'Alimonte L, Commisso K, Helou J, Deabreu A, Zhang L, Loblaw A
    2016 Apr 01; 94 (5): 1043-51
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      PURPOSE: This study identified predictors of high-grade late hematochezia (HH) following 5-fraction gantry-based stereotactic ablative radiation therapy (SABR).

      METHODS AND MATERIALS: Hematochezia data for 258 patients who received 35 to 40 Gy SABR in 5-fractions as part of sequential phase 2 prospective trials was retrieved. Grade 2 or higher late rectal bleeding was labeled HH. Hematochezia needing steroid suppositories, 4% formalin, or 1 to 2 sessions of argon plasma coagulation (APC) was labeled grade 2. More than 2 sessions of APC, blood transfusion, or a course of hyperbaric oxygen was grade 3 and development of visceral fistula, grade 4. Various dosimetric and clinical factors were analyzed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis and recursive partitioning analysis were used to determine clinically valid cut-off points and identify risk groups, respectively.

      RESULTS: HH was observed in 19.4%, grade ≥3 toxicity in 3.1%. Median follow-up was 29.7 months (interquartile range [IQR]: 20.6-61.7) Median time to develop HH was 11.7 months (IQR: 9.0-15.2) from the start of radiation. At 2 years, cumulative HH was 4.9%, 27.2%, and 42.1% in patients who received 35 Gy to prostate (4-mm planning target volume [PTV] margin), 40 Gy to prostate (5-mm PTV margin), and 40 Gy to prostate/seminal vesicles (5-mm PTV margin), respectively (P<.0001). In the ROC analysis, volume of rectum receiving radiation dose of 38 Gy (V38) was a strong predictor of HH with an area under the curve of 0.65. In multivariate analysis, rectal V38 (≥2.0 cm(3); odds ratio [OR]: 4.7); use of anticoagulants in the follow-up period (OR: 6.5) and presence of hemorrhoids (OR: 2.7) were the strongest predictors. Recursive partitioning analysis showed rectal V38 < 2.0 cm(3), and use of anticoagulants or rectal V38 ≥ 2.0 cm(3) plus 1 other risk factor resulted in an HH risk of >30%.

      CONCLUSIONS: Rectal V38 and 2 clinical factors were strong predictors of HH following 5-fraction SABR. Planning constraints should keep rectal V38 below 2.0 cm(3).

      View details for PubMedID 27026311
  • Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials. Radiother Oncol
    Musunuru HB, Quon H, Davidson M, Cheung P, Zhang L, D'Alimonte L, Deabreu A, Mamedov A, Loblaw A
    2016 Jan; 118 (1): 112-7
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      PURPOSE: To compare biochemical outcome and toxicities of two prospective 5-fraction stereotactic ablative radiotherapy (SABR) studies in prostate cancer.

      MATERIALS AND METHODS: 84 patients in pHART3 received 35 Gy, 30 patients in pHART6 received 40 Gy in 5-fractions to the prostate alone, once weekly. 4mm and 5mm PTV margins were used, respectively. Biochemical outcome, acute, late and cumulative genitourinary (GU)/gastrointestinal (GI) toxicities were compared.

      RESULTS: Median follow-up was 74 and 36 months, respectively. Median prostate specific antigen nadir was 0.4 ng/ml and 0.3 ng/ml. 2-, 4- and 6-year biochemical relapse-free survival (bRFS-2+nadir) was 100%, 98.7% and 95.9% in pHART3; 100%, 100% and not reached in pHART6 (p=0.91). There was one acute grade 3 GU (retention) and late grade 4 GI (fistula) toxicity in pHART3, none in pHART6. One patient in each study had persisting grade 2+ toxicity at the last follow-up. pHART6 patients had a greater grade 2+ cumulative GU (5% versus 24.2%) and GI (7.6% versus 26.2%) toxicities.

      CONCLUSIONS: Patients receiving dose-escalated SABR had slightly lower PSA nadir and similar bRFS, longer follow-up is needed to better estimate biochemical outcomes. There was a greater risk of grade 2 toxicity in pHART6 but not grade 3+ toxicities. Persisting toxicity at the last follow-up is similar.

      View details for PubMedID 26796591
  • Lung stereotactic ablative radiotherapy (SABR): dosimetric considerations for chest wall toxicity. Br J Radiol
    Murray L, Karakaya E, Hinsley S, Naisbitt M, Lilley J, Snee M, Clarke K, Musunuru HB, Ramasamy S, Turner R, Franks K
    2016; 89 (1058): 20150628
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      OBJECTIVE: To investigate chest wall pain in patients with peripheral early stage lung cancer treated with stereotactic ablative radiotherapy (SABR), and to identify factors predictive of Common Terminology Criteria of Adverse Events Grade 2 + chest wall pain.

      METHODS: Patients who received 55 Gy in five fractions were included. A chest wall structure was retrospectively defined on planning scans, and chest wall dosimetry and tumour-related factors recorded. Logistic regression was performed to identify factors predictive of ≥Grade 2 chest wall pain.

      RESULTS: 182 patients and 187 tumours were included. There were 20 (10.9%) episodes of ≥Grade 2 chest wall pain. Multivariate logistic regression demonstrated that the maximum dose received by 1 cm(3) of chest wall (Dmax1 cm(3)) and tumour size were significant predictors of ≥Grade 2 chest wall pain [Dmax1 cm(3) odds ratio : 1.104, 95% confidence interval : 1.012-1.204, p = 0.025; tumour size (mm) odds ratio : 1.080, 95% confidence interval : 1.026-1.136, p = 0.003]. This model was an adequate fit to the data (Hosmer and Lemeshow test non-significant) and a fair discriminator for chest wall pain (area under receiver-operating characteristic curve: 0.74). Using the multivariate logistic regression model, parameters for Dmax1 cm(3) are provided, which predict <10% and <20% risks of ≥Grade 2 chest wall pain for different tumour sizes.

      CONCLUSION: Grade 2+ chest wall pain is an uncommon side effect of lung SABR. Larger tumour size and increasing Dmax1 cm(3) are significant predictors of ≥Grade 2 chest wall pain. When planning lung SABR, it is prudent to try to avoid hot volumes in the chest wall, particularly for larger tumours.

      ADVANCES IN KNOWLEDGE: This article demonstrates that Grade 2 or greater chest wall pain following lung SABR is more common when the tumour is larger in size and the Dmax1 cm(3) of the chest wall is higher. When planning lung SABR, the risk of chest wall pain may be reduced if maximum doses are minimized, particularly for larger tumours.

      View details for PubMedID 26760508
  • Hybrid (CT/MRI based) vs. MRI only based image-guided brachytherapy in cervical cancer: Dosimetry comparisons and clinical outcome. Brachytherapy
    Choong ES, Bownes P, Musunuru HB, Rodda S, Richardson C, Al-Qaisieh B, Swift S, Orton J, Cooper R
    2016 Jan-Feb; 15 (1): 40-8
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      PURPOSE: Limited access to MRI has restricted implementation of MRI-based image-guided brachytherapy (IGBT) in line with GEC-ESTRO guidelines in many centers. This work reports our experience using an alternative CT/MRI based (hybrid) approach for IGBT, dosimetry comparisons, and its impact on long-term clinical outcome and major toxicity.

      METHODS AND MATERIALS: Seventy-six patients diagnosed with locally advanced cervical cancer between May 2008 and May 2012 treated with IGBT were analyzed. The hybrid approach is the default IGBT approach during this study period. Forty-nine had hybrid approach and 27 patients had "3-fraction conformal MRI" approach (17 within EMBRACE study). Treatment consisted of 48 Gy in 24 fractions of conformally planned external beam radiotherapy with weekly cisplatin followed by three weekly fractions of brachytherapy to high-risk clinical target volume (HR-CTV). All patients have a prebrachytherapy MRI 4 days before treatment and with the applicators in place on Fraction 1. MRI only or CT is used for subsequent fractions. Using image registration techniques and the assumption that the HR-CTV is fixed with respect to the applicator, the HR-CTV from MRI at Fraction 1 is transferred onto subsequent fraction CT image sets for the hybrid approach.

      RESULTS: Median follow-up was 41 months (range, 23-71 months). Excellent 3-year local control, overall progression-free survival, and overall survival of 92.6%, 78.8%, and 77.7% were seen with the hybrid approach and 92.2%, 66.3%, and 69.6% with a 3-fraction conformal MRI approach, respectively. Dosimetry achieved and late toxicity rates were comparable in the two groups.

      CONCLUSIONS: Hybrid IGBT in locally advanced cervical cancer offers an alternative approach when access to MRI restricts implementation of IGBT.

      View details for PubMedID 26602964
  • Stereotactic Ablative Radiotherapy (SABR) in Patients with Medically Inoperable Peripheral Early Stage Lung Cancer: Outcomes for the First UK SABR Cohort. Clin Oncol (R Coll Radiol)
    Murray L, Ramasamy S, Lilley J, Snee M, Clarke K, Musunuru HB, Needham A, Turner R, Sangha V, Flatley M, Franks K
    2016 Jan; 28 (1): 4-12
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      AIMS: To report outcomes for the first UK cohort treated for early stage peripheral lung cancer using stereotactic ablative radiotherapy (SABR).

      MATERIALS AND METHODS: Patients were included who received SABR between May 2009 and May 2012. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Patients were treated according to the UK SABR Consortium Guidelines. Univariate and multivariate Cox regression was used to determine factors that influenced overall survival and local control.

      RESULTS: In total, 273 patients received SABR for 288 lesions in the time period examined. The median follow-up was 19.7 months. The median overall survival for all patients was 27.3 months, with 1, 2 and 3 year overall survival of 78.0, 54.9 and 38.6%, respectively. The 1, 2 and 3 year rates of local control were 98.2, 95.7 and 95.7%, respectively. All patients completed the planned course of treatment and rates of Common Toxicity Criteria grade 3+ toxicity were low. On multivariate analysis, patients with Medical Research Council (MRC) breathlessness scores of 3-5 had worse overall survival compared with patients with scores of 1-2 (hazard ratio: 2.10; 95% confidence interval: 1.25-3.59) and the presence of histological diagnosis conferred improved overall survival (hazard ratio: 0.54; 95% confidence interval: 0.31-0.93), probably reflecting that patients who are considered well enough to undergo biopsy are generally fitter overall. No factors were identified that significantly influenced local control.

      CONCLUSIONS: SABR is an effective and well-tolerated treatment option for patients with early stage peripheral lung cancer who are not suitable for surgery. No patient cohort was identified in whom SABR was considered inappropriate. This series adds to the existing positive data that support SABR for this patient group.

      View details for PubMedID 26474546
  • Clinical trials of stereotactic ablative radiotherapy for prostate cancer: updates and future direction. Future Oncol
    Musunuru HB, Loblaw A
    2015; 11 (5): 819-31
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      Stereotactic body radiotherapy, also known as stereotactic ablative body radiotherapy (SABR), is an emerging treatment option for lung, prostate, liver and other tumors. Key factors in SABR are delivery of a high-dose radiation per fraction, proper patient positioning and target localization. Our review details the various radiotherapy techniques, dose fractionation schedules and toxicities for prostate SABR. Ongoing Phase II/III SABR studies across various risk groups have been included. It also discusses the role of conscientious focal dose escalation of the dominant intraprostatic nodule, integrating multiparametric MRI into radiotherapy protocols and finally cost-effectiveness of SABR.

      View details for PubMedID 25757684
  • A comparative study of quality of life in patients with localized prostate cancer treated at a single institution: stereotactic ablative radiotherapy or external beam+high dose rate brachytherapy boost. Radiother Oncol
    Helou J, Morton G, Zhang L, Deabreu A, D'Alimonte L, Elias E, Musunuru HB, Mamedov A, Ravi A, Chung H, Cheung P, Loblaw A
    2014 Dec; 113 (3): 404-9
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      PURPOSE: To compare the quality of life (QOL) in patients treated with stereotactic ablative radiation therapy (SABR) alone or high dose rate (HDR) brachytherapy+hypofractionated external beam radiotherapy (EBRT).

      METHODS AND MATERIALS: Patient self-reported QOL was prospectively measured among patients from two sequential phase 2 clinical trials: 1-SABR 35Gy/5fractions/5 weeks, 2-15Gy HDR 1 fraction, followed by EBRT 37.5Gy/15 fractions/3 weeks. The expanded prostate cancer index composite was assessed at baseline and q6 monthly up to 5 years. Urinary, bowel and sexual domains were analyzed. A minimally clinical important change (MCIC) was defined as 0.5*standard deviation of the baseline for each domain. Fisher exact test and general linear mixed model were used (p<0.05).

      RESULTS: 84 and 123 patients were treated on the SABR and HDR boost studies, with a median follow up of 51 and 61 months respectively. There was a significant difference in MCIC between treatments in the urinary function and bother (p<0.0001), the bowel function (p=0.0216) and the sexual function (p=0.0419) and bother (p=0.0290) domains in favor of the SABR group. Of patients who reported no problem with their sexual function at baseline, 7% and 23% respectively considered it to be a moderate to big problem on follow up (p=0.0077).

      CONCLUSION: Patients treated with HDR-boost reported deterioration of QOL particularly in sexual domains in comparison with SABR.

      View details for PubMedID 25466371
  • Evolution of hypofractionated accelerated radiotherapy for prostate cancer - the sunnybrook experience. Front Oncol
    Musunuru HB, Cheung P, Loblaw A
    2014; 4: 313
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      Stereotactic ablative body radiotherapy (SABR) is a newer method of ultra hypo fractionated radiotherapy that uses combination of image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT), to deliver high doses of radiation in a few fractions to a target, at the same time sparing the surrounding organs at risk (OAR). SABR is ideal for treating small volumes of disease and has been introduced in a number of disease sites including brain, lung, liver, spine, and prostate. Given the radiobiological advantages of treating prostate cancer with high doses per fraction, SABR is becoming a standard of care for low and intermediate-risk prostate cancer patients based upon the results from Sunnybrook and also the US-based prostate SABR consortium. This review examines the development of moderate and ultra hypo-fractionation schedules at the Odette Cancer centre, Sunnybrook Health Sciences. Moderate hypo-fractionation protocol was first developed in 2001 for intermediate-risk prostate cancer and from there on different treatment schedules including SABR evolved for all risk groups.

      View details for PubMedID 25452934
  • Assessment of uterus position as a surrogate for high-risk clinical target volume with respect to the applicator position for multiple fractions of brachytherapy in cervical cancer. Arch Gynecol Obstet
    Cooper R, Brearley E, Hurmuz P, Musunuru HB, Richardson C, Swift S, Orton J, Bownes P
    2014 Dec; 290 (6): 1201-5
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      AIM: Hybrid magnetic resonance imaging/computerized tomography (MRI/CT) planning for high-dose-rate (HDR) brachytherapy in cervical cancer with MR/CT fusion for the first fraction followed by CT for fraction 2 and 3 is used at our center. The aim of this study is to evaluate the position of applicator intrauterine tube (IU) in relation to uterine serosa with each fraction of intracavitary high-dose-rate brachytherapy.

      METHODS: Position of the applicator relative to uterus was measured from tip of the applicator (IU) to the top of uterus in the plane of IU and perpendicular to IU in anterior, posterior, left and right directions at the tip of IU, mid-point of the IU and 1 cm from the surface of vaginal ring. The mean absolute difference (±95 % confidence interval) between these positions at fraction 2 and 3 was calculated with fraction one as reference.

      RESULTS: The mean absolute difference (±95 %) of the applicator relative to uterus was 2.7 ± 0.5 mm at the tip, 1.5 ± 4 mm at mid-point and 1.1 ± 0.3 mm at 1 cm from the surface of the ring.

      CONCLUSION: This study shows that there is consistency in inter-fraction applicator position relative to uterus apart from at the tip and, therefore, in situations where high-risk clinical target volume (HRCTV) extends towards uterine fundus, MRI should be used for each fraction of brachytherapy planning to accurately define HRCTV.

      View details for PubMedID 25001571

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