Publications by authors named "George Rodrigues"

220 Publications

Predicting pathological complete response (pCR) after stereotactic ablative radiation therapy (SABR) of lung cancer using quantitative dynamic [F]FDG PET and CT perfusion: a prospective exploratory clinical study.

Radiat Oncol 2021 Jan 13;16(1):11. Epub 2021 Jan 13.

Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, 1151 Richmond St N, London, ON, N6A 5C1, Canada.

Background: Stereotactic ablative radiation therapy (SABR) is effective in treating inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. This prospective study aimed to develop a predictive model for true pathologic complete response (pCR) to SABR using imaging-based biomarkers from dynamic [F]FDG-PET and CT Perfusion (CTP).

Methods: Twenty-six patients with early-stage NSCLC treated with SABR followed by surgical resection were included, as a pre-specified secondary analysis of a larger study. Dynamic [F]FDG-PET and CTP were performed pre-SABR and 8-week post. Dynamic [F]FDG-PET provided maximum and mean standardized uptake value (SUV) and kinetic parameters estimated using a previously developed flow-modified two-tissue compartment model while CTP measured blood flow, blood volume and vessel permeability surface product. Recursive partitioning analysis (RPA) was used to establish a predictive model with the measured PET and CTP imaging biomarkers for predicting pCR. The model was compared to current RECIST (Response Evaluation Criteria in Solid Tumours version 1.1) and PERCIST (PET Response Criteria in Solid Tumours version 1.0) criteria.

Results: RPA identified three response groups based on tumour blood volume before SABR (BV) and change in SUV (ΔSUV), the thresholds being BV = 9.3 mL/100 g and ΔSUV = - 48.9%. The highest true pCR rate of 92% was observed in the group with BV < 9.3 mL/100 g and ΔSUV < - 48.9% after SABR while the worst was observed in the group with BV ≥ 9.3 mL/100 g (0%). RPA model achieved excellent pCR prediction (Concordance: 0.92; P = 0.03). RECIST and PERCIST showed poor pCR prediction (Concordance: 0.54 and 0.58, respectively).

Conclusions: In this study, we developed a predictive model based on dynamic [F]FDG-PET and CT Perfusion imaging that was significantly better than RECIST and PERCIST criteria to predict pCR of NSCLC to SABR. The model used BV and ΔSUV which correlates to tumour microvessel density and cell proliferation, respectively and warrants validation with larger sample size studies.

Trial Registration: MISSILE-NSCLC, NCT02136355 (ClinicalTrials.gov). Registered May 8, 2014, https://clinicaltrials.gov/ct2/show/NCT02136355.
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http://dx.doi.org/10.1186/s13014-021-01747-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805034PMC
January 2021

Is SABR Cost-Effective in Oligometastatic Cancer? An Economic Analysis of the SABR-COMET Randomized Trial.

Int J Radiat Oncol Biol Phys 2021 Apr 10;109(5):1176-1184. Epub 2020 Dec 10.

London Health Sciences Centre, London, Canada; Schulich School of Medicine & Dentistry, Western University, London, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address:

Purpose: The phase 2 randomized study SABR-COMET demonstrated that in patients with controlled primary tumors and 1 to 5 oligometastatic lesions, SABR was associated with improved progression-free survival (PFS) compared with standard of care (SoC), but with higher costs and treatment-related toxicities. The aim of this study was to assess the cost-effectiveness of SABR versus SoC in this setting.

Methods And Materials: A Markov model was constructed to perform a cost-utility analysis from the Canadian health care system perspective. Utility values and transition probabilities were derived from individual-level data from the SABR-COMET trial. One-way, 2-way, and probabilistic sensitivity analyses were performed. Costs were expressed in 2018 CAD. A separate analysis based on US payer's perspective was performed. An incremental cost-effectiveness ratio (ICER) at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was used.

Results: In the base case scenario, SABR was cost-effective at an ICER of $37,157 per QALY gained. This finding was most sensitive to the number of metastatic lesions treated with SABR (ICER: $28,066 per QALY for 2, increasing to $64,429 per QALY for 5), difference in chemotherapy use (ICER: $27,173-$53,738 per QALY), and PFS hazard ratio (HR) between strategies (ICER: $31,548-$53,273 per QALY). Probabilistic sensitivity analysis revealed that SABR was cost-effective in 97% of all iterations. Two-way sensitivity analysis demonstrated a nonlinear relationship between the number of lesions and the PFS HR. To maintain cost-effectiveness for each additional metastasis, the HR must decrease by approximately 0.047. The US cost analysis yielded similar results, with an ICER of $54,564 (2018 USD per QALY) for SABR.

Conclusions: SABR is cost-effective for patients with 1 to 5 oligometastatic lesions compared with SoC.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.001DOI Listing
April 2021

American Radium Society Appropriate Use Criteria: Radiation Therapy for Limited-Stage SCLC 2020.

J Thorac Oncol 2021 01 6;16(1):66-75. Epub 2020 Nov 6.

Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.

Introduction: Combined modality therapy with concurrent chemotherapy and radiation has long been the standard of care for limited-stage SCLC (LS-SCLC). However, there is controversy over best combined modality practices for LS-SCLC. To address these controversies, the American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) Committee have developed updated consensus guidelines for the treatment of LS-SCLC.

Methods: The ARS AUC are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for LS-SCLC. Agreement or consensus was defined as less than or equal to 3 rating points from the panel median. The consensus ratings and recommendations were then vetted by the ARS Executive Committee and subject to public comment before finalization.

Results: The ARS Thoracic AUC committee developed multiple consensus recommendations for LS-SCLC. There was strong consensus that patients with unresectable LS-SCLC should receive concurrent chemotherapy with radiation delivered either once or twice daily. For medically inoperable T1-T2N0 LS-SCLC, either concurrent chemoradiation or stereotactic body radiation followed by adjuvant chemotherapy is a reasonable treatment option. The panel continues to recommend whole-brain prophylactic cranial irradiation after response to chemoradiation for LS-SCLC. There was panel agreement that prophylactic cranial irradiation with hippocampal avoidance and programmed cell death protein-1/programmed death-ligand 1-directed immune therapy should not be routinely administered outside the context of clinical trials at this time.

Conclusions: The ARS Thoracic AUC Committee provide consensus recommendations for LS-SCLC that aim to provide a groundwork for multidisciplinary care and clinical trials.
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http://dx.doi.org/10.1016/j.jtho.2020.10.020DOI Listing
January 2021

Is hypofractionated whole pelvis radiotherapy (WPRT) as well tolerated as conventionally fractionated WPRT in prostate cancer patients? The HOPE trial.

BMC Cancer 2020 Oct 9;20(1):978. Epub 2020 Oct 9.

Division of Radiation Oncology, London Regional Cancer Program, 800 Commissioners Road East, London, Ontario, N6A 5W9, Canada.

Background: Patients with high-risk prostate cancer are at increased risk of lymph node metastasis and are thought to benefit from whole pelvis radiotherapy (WPRT). There has been recent interest in the use of hypofractionated radiotherapy in treating prostate cancer. However, toxicity and cancer outcomes associated with hypofractionated WPRT are unclear at this time. This phase II study aims to investigate the impact in quality of life associated with hypofractionated WPRT compared to conventionally fractionated WPRT.

Methods: Fifty-eight patients with unfavourable intermediate-, high- or very high-risk prostate cancer will be randomized in a 1:1 ratio between high-dose-rate brachytherapy (HDR-BT) + conventionally fractionated (45 Gy in 25 fractions) WPRT vs. HDR-BT + hypofractionated (25 Gy in 5 fractions) WPRT. Randomization will be performed with a permuted block design without stratification. The primary endpoint is late bowel toxicity and the secondary endpoints include acute and late urinary and sexual toxicity, acute bowel toxicity, biochemical failure-, androgen deprivation therapy-, metastasis- and prostate cancer-free survival of the hypofractionated arm compared to the conventionally fractionated arm.

Discussion: To our knowledge, this is the first study to compare hypofractionated WPRT to conventionally fractionated WPRT with HDR-BT boost. Hypofractionated WPRT is a more attractive and convenient treatment approach, and may become the new standard of care if demonstrated to be well-tolerated and effective.

Trial Registration: This trial was prospectively registered in ClinicalTrials.gov as NCT04197141 on December 12, 2019.
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http://dx.doi.org/10.1186/s12885-020-07490-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547418PMC
October 2020

American Radium Society Appropriate Use Criteria on Radiation Therapy for Extensive-Stage SCLC.

J Thorac Oncol 2021 01 1;16(1):54-65. Epub 2020 Oct 1.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Introduction: The standard-of-care therapy for extensive-stage SCLC has recently changed with the results of two large randomized trials revealing improved survival with the addition of immunotherapy to first-line platinum or etoposide chemotherapy. This has led to a lack of clarity around the role of consolidative thoracic radiation and prophylactic cranial irradiation in the setting of chemoimmunotherapy.

Methods: The American Radium Society Appropriate Use Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with the application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for extensive-stage SCLC.

Results: Current evidence supports either prophylactic cranial irradiation or surveillance with magnetic resonance imaging every 3 months for patients without evidence of brain metastases. Patients with brain metastases should receive whole-brain radiation with a recommended dose of 30 Gy in 10 fractions. Consolidative thoracic radiation can be considered in selected cases with the recommended dose ranging from 30 to 54 Gy; this recommendation was driven by expert opinion owing to the limited strength of evidence, as clinical trials addressing this question remain ongoing.

Conclusions: Radiation therapy remains an integral component in the treatment paradigm for ES-SCLC.
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http://dx.doi.org/10.1016/j.jtho.2020.09.013DOI Listing
January 2021

Does adding local salvage ablation therapy provide survival advantage for patients with locally recurrent prostate cancer following radiotherapy? Whole gland salvage ablation post-radiation failure in prostate cancer.

Can Urol Assoc J 2021 Apr;15(4):123-129

Departments of Urology and Oncology, Western University, London, ON, Canada.

Introduction: Some men who experience prostate cancer recurrence post-radiotherapy may be candidates for local salvage therapy, avoiding and delaying systemic treatments. Our aim was to assess the impact of clinical outcomes of adding salvage local treatment in prostate cancer patients who have failed radiation therapy.

Methods: Following radiation biochemical failure, salvage transperineal cryotherapy (sCT, n=186), transrectal high intensity focused ultrasound ablation (sHIFU, n=113), or no salvage treatment (NST, identified from the pan-Canadian Prostate Cancer Risk Stratification [ProCaRS] database, n=982) were compared with propensity-score matching. Primary endpoints were cancer-specific survival (CSS) and overall survival (OS).

Results: Median followup was 11.6, 25.1, and 14.3 years following NST, sCT, and sHIFU, respectively. Two propensity score-matched analyses were performed: 1) 196 NST vs. 98 sCT; and 2) 177 NST vs. 59 sHIFU. In the first comparison, there were 78 deaths and 49 prostate cancer deaths for NST vs. 80 deaths and 24 prostate cancer deaths for sCT. There were significant benefits in CSS (p<0.001) and OS (p<0.001) favoring sCT. In the second comparison, there were 52 deaths (31 from prostate cancer) for NST vs. 18 deaths (nine from prostate cancer) for sHIFU. There were no significant differences in CSS or OS possibility attributed to reduced sample size and shorter followup of sHIFU cohort.

Conclusions: In select men with recurrent prostate cancer post-radiation, further local treatment may lead to benefits in CSS. These hypothesis-generating findings should ideally be validated in a prospective clinical trial setting.
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http://dx.doi.org/10.5489/cuaj.6676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021422PMC
April 2021

A review of ongoing trials of stereotactic ablative radiotherapy for oligometastatic disease in the context of new consensus definitions.

Ann Palliat Med 2020 Aug 7. Epub 2020 Aug 7.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

The characterization and treatment of oligometastatic disease (OMD) are rapidly growing areas of research. Consensus statements have recently been developed by European Society for Radiotherapy and Oncology (ESTRO)/American Society for Radiation Oncology (ASTRO) and ESTRO/European Organization for Research and Treatment of Cancer (EORTC) in an effort to harmonize terminology describing OMD. The purpose of this study was to assess patient populations eligible for ongoing clinical trials evaluating stereotactic ablative radiotherapy (SABR) in OMD in the context of key definitions from both statements. Using the clinicaltrials.gov database, a search of ongoing OMD clinical trials evaluating the use of SABR was performed from inception to January 2020, using the keywords "oligometastasis", "stereotactic radiotherapy", and related terms. Results were independently reviewed by two investigators, with discrepancies settled by a third. Information from these trials including study design, population criteria, and primary endpoints were extracted. OMD was defined in general as a limited number of metastases that could be safely treated with metastasis-directed therapy. States of OMD were broadly categorized into de novo, repeat, and induced, with synchronous and metachronous being subsets of de novo. The initial search strategy identified 293 trials, of which 85 met our eligibility criteria. Phase II trials were by far the most common (n=46, 52%). Most trials had a single treatment arm (n=43, 51%), and 31 (36%) were randomized. The majority of trials (n=65, 76%) had populations that included all three subsets of OMD. Notably, 70 trials (82%) also included oligoprogressive disease, which is debatably a distinct entity from OMD. Progressionfree survival was the most common primary endpoint (n=31, 36%), followed by local control (n=17, 20%), toxicity (n=14, 16%) and overall survival (n=7, 8%). Although the use of SABR for OMD is an active area of prospective clinical trial research, ongoing studies include mixed populations as defined by new consensus statements. Therefore, the applicability of results from these trials should be considered within relevant OMD scenarios.
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http://dx.doi.org/10.21037/apm-20-847DOI Listing
August 2020

Is prostate brachytherapy a dying art? Trends and variation in the definitive management of prostate cancer in Ontario, Canada.

Radiother Oncol 2020 11 24;152:42-48. Epub 2020 Jul 24.

Division of Radiation Oncology, Department of Oncology, London Health Sciences Centre, London, Canada.

Background And Purpose: Declining prostate brachytherapy utilization has been reported in several studies, despite strong evidence for efficacy and safety compared to alternatives. We sought to evaluate contemporary trends in brachytherapy, external beam radiotherapy (EBRT) and prostatectomy utilization in a publicly funded healthcare system.

Materials And Methods: Men with localized prostate cancer diagnosed and treated between 2006 and 2017 in Ontario, Canada were identified using administrative data. Men received EBRT, brachytherapy (monotherapy or boost) or prostatectomy as initial definitive management. Multivariable logistic regression evaluated patient-, tumour-, and provider-factors on treatment utilization.

Results: 61,288 men were included. On multivariable regression, the odds of receiving brachytherapy boost increased 24% per year (odds ratio [OR]:1.24, 95% CI 1.22-1.26, p < 0.01), brachytherapy monotherapy increased 3% per year (OR:1.03, 95% CI:1.02-1.04, p < 0.01), and prostatectomy declined by 6% per year (OR:0.94, 95% CI 0.93-0.95, p < 0.01). Treatment year was not significant on multivariable modelling of EBRT. In a separate multivariable model limited to those who received radiotherapy, if the first radiation oncologist seen performed brachytherapy, the OR of receiving brachytherapy monotherapy over EBRT was 5.66 (95% CI: 5.11-6.26, p < 0.01) and 2.88 (95% CI: 2.60-3.19, p < 0.01) for brachytherapy boost over EBRT alone. Substantial geographic, provider and patient variation in treatment receipt was observed.

Conclusion: We found increasing brachytherapy utilization, largely driven by increasing utilization of brachytherapy boost. To our knowledge, this is the first report of increasing brachytherapy use in the era of dose escalated EBRT.
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http://dx.doi.org/10.1016/j.radonc.2020.07.036DOI Listing
November 2020

Does ADT benefit unfavourable intermediate risk prostate cancer patients treated with brachytherapy boost and external beam radiotherapy? A propensity-score matched analysis.

Radiother Oncol 2020 09 30;150:195-200. Epub 2020 Jun 30.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address:

Purpose: To investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost.

Material And Methods: Data from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan-Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups.

Results: A total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4-6) and delivered a median time of 2.7 months (IQR: 1.7-4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS.

Conclusion: Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.
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http://dx.doi.org/10.1016/j.radonc.2020.06.039DOI Listing
September 2020

Practice Recommendations for Lung Cancer Radiotherapy During the COVID-19 Pandemic: An ESTRO-ASTRO Consensus Statement.

Int J Radiat Oncol Biol Phys 2020 07;107(4):631-640

Division of Radiation Oncology, Western University, London, Canada.

Background: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic.

Methods: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC.

Results: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided.

Conclusion: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.ijrobp.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836268PMC
July 2020

Is There a Role for Hypofractionated Thoracic Radiation Therapy in Limited-Stage Small Cell Lung Cancer? A Propensity Score Matched Analysis.

Int J Radiat Oncol Biol Phys 2020 11 13;108(3):575-586. Epub 2020 Jun 13.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. Electronic address:

Purpose: Various radiation schedules are used in concurrent chemoradiation therapy for limited-stage small cell lung cancer (LS-SCLC). Since there is currently no randomized evidence comparing hypofractionated radiation therapy (HFRT) and conventionally fractionated radiation therapy (CFRT), the aim of this study was to compare overall survival (OS), progression-free survival (PFS), and toxicity of HFRT and CFRT in LS-SCLC.

Methods And Materials: Patients with LS-SCLC treated between 2000 and 2013 with HFRT (40 Gy/15 fractions, 45 Gy/15 fractions, 45 Gy/20 fractions) or CFRT (60 Gy/30 or 66 Gy/33 fractions) were included. Propensity scores were generated using a multivariable logistic regression model. Patients were matched on a 1:1 ratio with a caliper distance of 0.20. OS and PFS were estimated by the Kaplan-Meier method and compared using log-rank tests. As a sensitivity analysis, univariable and multivariable Cox regression was performed including all patients without matching. Logistic regression was performed to identify predictors of pulmonary and esophageal adverse events.

Results: In the overall group of 117 patients, there were significant baseline differences between the HFRT and CFRT cohorts. Patients who received CFRT were older, more often smoked concurrently with treatment, had higher Eastern Cooperative Oncology Group performance status, different T and N stage patterns, and more commonly received concurrent chemoradiation therapy and prophylactic cranial irradiation. After propensity score matching for these differences, 72 patients were included, 36 in the HFRT and CFRT cohorts, respectively. There was no difference in OS (P = .724), PFS (P = .862), or any pulmonary (P = .350) or esophageal (P = .097) adverse events between cohorts. Skin adverse events were significantly higher for CFRT (41.7%) compared with HFRT (16.7%, P = .020). Multivariable Cox regression also revealed no differences in OS (P = .886) or PFS (P = .717) between all HFRT and CFRT patients, without matching. No grade 5 adverse events were observed.

Conclusions: In LS-SCLC patients, HFRT was associated with comparable survival and toxicity outcomes and may be considered as an alternative to CFRT, should its efficacy be confirmed in prospective studies.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293491PMC
November 2020

Are Female Radiation Oncologists Still Underrepresented in the Published Literature? An Analysis of Authorship Trends During the Past Decade.

Adv Radiat Oncol 2020 May-Jun;5(3):325-332. Epub 2019 Sep 13.

Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada.

Purpose: We examined whether female authorship, traditionally underrepresented in the radiation oncology (RO) literature, has improved during the past decade, and whether the introduction of double-blind peer review (where reviewers are blinded to author names and vice-versa) improved female authorship rates.

Methods: We analyzed authorship lists during a 10-year period (2007-2016) from the 2 highest impact-factor RO journals: (IJROBP) and (R&O). From each journal, 20 articles per year were randomly selected. Gender trends of the first, second, last, and collaborating authors (defined as all other positions), were analyzed. A one-sample proportion test was used to compare US female senior authorship (2012-2016) with the 2015 benchmark for female US academic radiation oncologists (30.6%).

Results: Across 400 articles, the mean ± standard deviation percentage of female authors was 30.9% ± 22.0% with 34.8% of first, 36.7% of second, and 25.4% of last authors being female. The total percentage of female authors per year increased from 2007 to 2016 ( = .005), with no significant increase in the percentage of first ( = .250), second ( = .063), or last ( = .213) female authors. Double-blind peer review was associated with an increase in the mean percentage of female authors (2007-2011: 27.4% vs 2012-2016: 34.0%; = .012). The proportion of US female senior authors in the latter period (27.6%) and the proportion of female US academic radiation oncologists (30.6%) were not significantly different ( = .570).

Conclusions: Although the percentage of female authors in RO has increased during the past decade, this did not correspond to a higher representation of women in high-profile authorship positions. Introduction of double-blind peer review was associated with a rise in female authorship. The proportion of female US senior authors and academic radiation oncologists is similar, suggesting that senior authorship rates are approaching appropriate levels in the United States.
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http://dx.doi.org/10.1016/j.adro.2019.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276664PMC
September 2019

Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial.

J Clin Oncol 2020 09 2;38(25):2830-2838. Epub 2020 Jun 2.

Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Purpose: The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data that test this paradigm are lacking.

Methods: We enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 4-5) and randomized in a 1:2 ratio between palliative standard-of-care (SOC) treatments (arm 1) and SOC plus SABR (arm 2). We used a randomized phase II screening design with a primary end point of overall survival (OS), using an α of .20 (wherein < .20 indicates a positive trial). Secondary end points included progression-free survival (PFS), toxicity, and quality of life (QOL). Herein, we present long-term outcomes from the trial.

Results: Between 2012 and 2016, 99 patients were randomly assigned at 10 centers internationally. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Median follow-up was 51 months. The 5-year OS rate was 17.7% in arm 1 (95% CI, 6% to 34%) versus 42.3% in arm 2 (95% CI, 28% to 56%; stratified log-rank = .006). The 5-year PFS rate was not reached in arm 1 (3.2%; 95% CI, 0% to 14% at 4 years with last patient censored) and 17.3% in arm 2 (95% CI, 8% to 30%; = .001). There were no new grade 2-5 adverse events and no differences in QOL between arms.

Conclusion: With extended follow-up, the impact of SABR on OS was larger in magnitude than in the initial analysis and durable over time. There were no new safety signals, and SABR had no detrimental impact on QOL.
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http://dx.doi.org/10.1200/JCO.20.00818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460150PMC
September 2020

Is lung stereotactic ablative radiotherapy safe after pneumonectomy?-a systematic review.

Transl Lung Cancer Res 2020 Apr;9(2):348-353

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Patients treated with surgery for lung cancer are at risk of second primary lung cancers (SPLCs), which when localized, may be amenable to radical treatment. Treatment options, however, are limited due to reduced cardiopulmonary reserve and competing mortality risks. The aim of this study was to perform a systematic review of publications examining treatment planning considerations, clinical outcomes, and toxicity rates of stereotactic ablative radiotherapy (SABR) in patients who have previously undergone pneumonectomy. A systematic review of the literature was conducted in accordance with PRISMA guidelines using PubMed and EMBASE from inception to July 2018. Articles were limited to those published in the English language. Non-review articles with patients who received exclusively lung SABR post-pneumonectomy were included. Two reviewers independently performed abstract and full-text review, with discrepancies settled by a third reviewer. Of the 215 articles identified by the initial search, 6 articles comprising 53 patients who received lung SABR post-pneumonectomy met inclusion criteria. The mean age was 68, and most patients were male (73.7%). The mean time to pneumonectomy was 6.5 years. The mean biologically effective dose was 115 Gy, and the most common dose fractionation schemes were 54 Gy in 3 fractions, 48 Gy in 4 fractions, and 50 Gy in 5 fractions. The mean follow-up was 25.4 months. The mean 1-year overall survival and 2-year local control rates were 80.6% and 89.4%. Grade 3 or higher toxicity was reported in 13.2% of patients. SABR appears to be a safe and feasible option for SPLCs in patients with prior pneumonectomy. Multi-institutional and/or prospective studies would be helpful to determine the true risk and appropriateness of SABR in this high-risk patient population.
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http://dx.doi.org/10.21037/tlcr.2020.01.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225144PMC
April 2020

Beyond Oligometastases.

Int J Radiat Oncol Biol Phys 2020 06;107(2):253-256

Division of Radiation Oncology, Western University, London, Canada.

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http://dx.doi.org/10.1016/j.ijrobp.2019.12.023DOI Listing
June 2020

Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement.

Radiother Oncol 2020 05 6;146:223-229. Epub 2020 Apr 6.

Division of Radiation Oncology, Western University, London, Canada.

Background: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic.

Methods: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC.

Results: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided.

Conclusion: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.radonc.2020.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252074PMC
May 2020

A Primer on Interstitial Lung Disease and Thoracic Radiation.

J Thorac Oncol 2020 06 24;15(6):902-913. Epub 2020 Feb 24.

Departments of Radiation Oncology and Respirology, London Health Sciences Centre, London, Ontario, Canada. Electronic address:

Interstitial lung disease (ILD) is a term used to describe a heterogeneous group of lung disorders with characteristic clinical and imaging features. Patients with ILD are at an increased risk of developing NSCLC, which is frequently medically comorbid, often precluding operative management. In this scenario, radiotherapy (RT) is generally recommended; however, ILD is known to increase the risk of RT-related toxicity. Recommendations for treatment with appropriately individualized risks and benefits are thus dependent on integration of patient-, ILD-, and cancer-specific factors. We aim to provide an overview of ILD for the thoracic oncologist, an assessment of risk of thoracic RT in patients with ILD, and evidence-based recommendations for treatment in a variety of clinical scenarios.
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http://dx.doi.org/10.1016/j.jtho.2020.02.005DOI Listing
June 2020

Predictors of Survival Benefit From Immune Checkpoint Inhibitors in Patients With Advanced Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis.

Clin Lung Cancer 2020 03 3;21(2):106-113.e5. Epub 2020 Jan 3.

Division of Medical Oncology, Department of Oncology, London Regional Cancer Program, Western University, London, ON, Canada.

Randomized trials showed inconsistent survival benefit with immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer with low programmed death-ligand 1 (PD-L1) tumors (< 1%) and in elderly patients (> 65 years old) and never-smokers. We conducted a systematic review and meta-analysis to assess the efficacy of single agent ICIs in these pre-defined subgroups. The electronic databases PubMed and EMBASE were searched for relevant randomized trials. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were meta-analyzed using the generic inverse variance method. Nine studies were included. Compared with chemotherapy, the use of single agent ICIs in the second-line setting reduced the risk of death independent of PD-L1 expression (HR, 0.79; 95% confidence interval [CI], 0.66-0.96 and HR, 0.75; 95% CI, 0.61-0.85 for patients with PD-L1-negative and -positive tumors, respectively). Yet, a PFS benefit was only seen in patients with PD-L1-positive tumors. Similarly, an OS benefit was seen in patients independent of age (HR, 0.79; 95% CI, 0.69-0.89 and HR, 0.76; 95% CI, 0.66-0.88 for elderly and non-elderly patients, respectively). Conversely, an OS benefit was only seen in ever-smokers (HR, 0.78; 95% CI, 0.68-0.89) and a detrimental effect on PFS in never-smokers (HR, 1.68; 95% CI, 1.07-2.63). Patients with advanced non-small-cell lung cancer derive a survival benefit from ICIs independent of tumor PD-L1 expression and age, particularly in the second line, whereas never-smokers do not. Caution should be exercised when offering single-agent ICIs to elderly patients in the first line, and other treatment options should be considered in never-smokers.
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http://dx.doi.org/10.1016/j.cllc.2019.11.004DOI Listing
March 2020

A Phase II Multi-institutional Clinical Trial Assessing Fractionated Simultaneous In-Field Boost Radiotherapy for Brain Oligometastases.

Cureus 2019 Dec 16;11(12):e6394. Epub 2019 Dec 16.

Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, CAN.

Purpose/Objective Published preclinical and phase I clinical trial data suggest that fractionated lesional radiotherapy with 60 Gy in 10 fractions can serve as an alternative approach to single fraction radiosurgical boost for brain oligometastases.  Methods and Materials A phase II clinical trial (NCT01543542) of a total of 60 Gy in 10 fractions of lesional (one to three) radiotherapy (given simultaneously with whole-brain helical tomotherapy with 30 Gy in 10 fractions) was conducted at five institutions. We hypothesized that fractionated radiotherapy would be considered unsuitable if the median overall survival (OS) was degraded by two months or if six-month intracranial control (ICC) and intracranial lesion (ILC) were inferior by 10% compared with the published RTOG 9508 results. Results A total of 87 patients were enrolled over a 4.5-year accrual period. Radiological lesion and extralesional central nervous system progression were documented in 15/87 (17%) and 11/87 (13%) patients, respectively. Median OS for all patients was 5.4 months. Six-month actuarial estimates of ICC and ILC were 78% and 89%, respectively. However, only the ILC estimate achieved statistical significance (p=0.02), demonstrating non-inferiority to the a priori historical controls (OS: p=0.09, ICC=0.31). Two patients developed suspected asymptomatic radionecrosis. Conclusions The phase II estimates of ILC were demonstrated to be non-inferior to the results of the RTOG 9508.
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http://dx.doi.org/10.7759/cureus.6394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959838PMC
December 2019

Assessment of precision irradiation in early non-small cell lung cancer and interstitial lung disease (ASPIRE-ILD): study protocol for a phase II trial.

BMC Cancer 2019 Dec 11;19(1):1206. Epub 2019 Dec 11.

Department of Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, British Columbia, V5Z 1M9, Canada.

Background: Stereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD.

Methods: ASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1-2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy or 217 Gy), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy or 133 Gy) and 45 Gy in 15 fractions daily (58 Gy or 90 Gy). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR.

Discussion: ASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD.

Trial Registration: Clinicaltrials.gov identifier: NCT03485378. Date of registration: April 2, 2018.
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http://dx.doi.org/10.1186/s12885-019-6392-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905060PMC
December 2019

A Phase I/II Trial of Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy for High-Risk Prostate Cancer (FASTR-2): Preliminary Results and Toxicity Analysis.

Adv Radiat Oncol 2019 Oct-Dec;4(4):668-673. Epub 2019 Jul 16.

Division of Radiation Oncology, Department of Oncology, London Health Sciences Centre and Western University, London, Ontario, Canada.

Purpose: FASTR was designed to provide a compact treatment course for high-risk prostate cancer patients but was discontinued because of excess toxicity. We present the results of FASTR-2, which used a lower dose to the prostate (35 Gy vs 40 Gy), smaller posterior PTV margin (4 mm vs 5 mm) and omitted nodal radiation to lower the volumes of rectum receiving high and intermediate doses compared with FASTR. Gastrointestinal (GI) and genitourinary (GU) toxicities at baseline, 6 weeks, 6 months, and 1 year and biochemical control rates are presented.

Methods And Materials: Eligibility included high-risk prostate cancer (cT3/4, prostate-specific antigen >20 or Gleason Score ≥8), age ≥70 or refused standard treatment, and no evidence of metastatic disease. Patients received 18 months of androgen deprivation therapy starting 2 months before radiation. Clinical target volume was defined as prostate plus proximal 1-cm seminal vesicles. PTV was a nonuniform expansion around clinical target volume (4 mm posteriorly, 5 mm in all other directions). Volumetric arc therapy was used for treatment delivery (35 Gy delivered in 5 weekly fractions of 7 Gy each), and cone beam computed tomography with soft tissue matching (no fiducial placement) was used for daily image guidance. Toxicity was assessed at 6 weeks, 6 months, and 1 year according to Common Toxicity Criteria.

Results: In the study, 30 patients were enrolled in FASTR-2 between 2015 and 2017. Two patients were withdrawn owing to ineligibility after enrollment. One patient (3.7%) reported grade 2 GI toxicity at 6 weeks. There was no reported grade ≥2 GI toxicity at 6 months or 1 year. There were no reported episodes of rectal bleeding. Four patients (14.8%), 5 patients (17.9%), and 5 patients (21.7%) reported grade 2 GU toxicity at 6 weeks, 6 months, and 1 year, respectively. There were no reported cases of grade ≥3 GU toxicity. The most common toxicities were nocturia and urinary frequency or urgency.

Conclusions: FASTR-2 was more tolerable than FASTR, with no grade ≥3 toxicities reported, in keeping with expectations based on our previous FASTR analysis. Long-term follow-up is necessary to ensure disease control and toxicity outcomes are comparable to conventional high-risk treatment paradigms.
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http://dx.doi.org/10.1016/j.adro.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817718PMC
July 2019

Intraluminal Superior Vena Cava Invasion.

J Thorac Oncol 2020 01 9;15(1):144-145. Epub 2019 Oct 9.

Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2019.09.010DOI Listing
January 2020

Quality of Life Outcomes After Stereotactic Ablative Radiation Therapy (SABR) Versus Standard of Care Treatments in the Oligometastatic Setting: A Secondary Analysis of the SABR-COMET Randomized Trial.

Int J Radiat Oncol Biol Phys 2019 12 27;105(5):943-947. Epub 2019 Aug 27.

London Health Sciences Centre, London, Ontario, Canada.

Purpose: Randomized data assessing the longitudinal quality of life (QoL) impact of stereotactic ablative radiation therapy (SABR) in the oligometastatic setting are lacking.

Methods And Materials: We enrolled patients who had a controlled primary malignancy with 1 to 5 metastatic lesions, with good performance status and life expectancy >6 months. We randomized in a 1:2 ratio between standard of care (SOC) treatment (SOC arm) and SOC plus SABR to all metastatic lesions (SABR arm). QoL was measured using the Functional Assessment of Cancer Therapy-General. QoL changes over time and between groups were assessed with linear mixed modeling.

Results: Ninety-nine patients were randomized. Median age was 68 years (range, 43-89), and 60% were male. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Most patients (n = 92) had 1 to 3 metastases. Median follow-up was 26 months. Because of the previously reported inferior survival of the SOC arm, the time for attrition in QoL respondents to <10% of subjects was shorter in the SOC versus SABR arm (30 vs 42 months). In the whole cohort, QoL declined over time after randomization: There were significant declines in total Functional Assessment of Cancer Therapy-General score over time compared with baseline (P < .001) owing to declines in physical and functional subscales (both P < .001), with no declines in social and emotional subscales. However, the magnitudes of decline were small, and clinically meaningful changes were not seen at most time points. Comparison between arms showed no differences in QoL between the SABR and SOC arms in total score (P = .42) or in the physical (P = .98), functional (P = .59), emotional (P = .82), or social (P = .17) subscales.

Conclusions: For patients with oligometastases, average QoL declines slowly over time regardless of treatment approach, although the changes are small in magnitude. The use of SABR, compared with SOC, was not associated with a QoL detriment.
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http://dx.doi.org/10.1016/j.ijrobp.2019.08.041DOI Listing
December 2019

Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial.

BMC Cancer 2019 Aug 19;19(1):816. Epub 2019 Aug 19.

Department of Radiation Oncology, Amsterdam UMC Vrije Universiteit Amsterdam Radiation Oncology, Cancer Center Amsterdam, Amsterdam, The Netherlands.

Background: Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control for primary tumors or metastases. A recent randomized phase II trial evaluated SABR in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4-10 metastatic cancer lesions.

Methods: One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival.

Discussion: This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with 4-10 oligometastatic lesions.

Trial Registration: Clinicaltrials.gov identifier: NCT03721341 . Date of registration: October 26, 2018.
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http://dx.doi.org/10.1186/s12885-019-5977-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699121PMC
August 2019

A Review of Ongoing Trials of Stereotactic Ablative Radiotherapy for Oligometastatic Cancers: Where Will the Evidence Lead?

Front Oncol 2019 21;9:543. Epub 2019 Jun 21.

Division of Radiation Oncology, London Regional Cancer Program, London, ON, Canada.

The oligometastatic state is a proposed entity between localized cancer and widely metastatic disease, comprising an intermediate subset of metastatic cancer patients. Most data to support locally-directed treatment, such as stereotactic ablative radiotherapy (SABR), for oligometastases are from retrospective institutional reports. Following the success of a recently completed and reported phase II trial demonstrating important clinical outcomes, herein we review the current landscape of ongoing clinical trials in this context. A review of currently activated and registered clinical trials was performed using the clinicaltrials.gov database from inception to February 2019. A search of actively recruiting trials, using the key words oligometastases, SABR, and various related terms was performed. Search results were independently reviewed by two investigators, with discrepancies settled by a third. Data abstracted from identified studies included study type, primary disease site, oncologic endpoints, and inclusion/exclusion criteria. Of the initial 216 entries identified, 64 met our review eligibility criteria after full-text review. The most common study type was a phase II clinical trial ( = 35, 55%) with other study designs ranging from observational registry trials to phase III randomized controlled trials (RCTs). A minority of trials were randomized in design ( = 17, 27%). While most studies allowed for metastases from multiple primary disease sites ( = 22, 34%), the most common was prostate ( = 13, 15%), followed by breast, gastrointestinal, non-small cell lung cancer (NSCLC), and renal ( = 6, 9% each). In studies with a solitary target site, the most common was liver ( = 6, 9%) followed by lung ( = 3, 5%). The most common primary endpoints were progression-free survival (PFS) ( = 20, 31%) and toxicity ( = 10, 16%). A combined strategy of systemic therapy and SABR was an emerging theme ( = 23, 36%), with more recent studies specifically evaluating SABR and immunotherapy ( = 9, 14%). The safety and efficacy of SABR as oligometastasis-directed treatment is increasingly being evaluated within prospective clinical trials. These data are awaited to compliment the abundance of existing observational studies and to guide clinical decision-making.
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http://dx.doi.org/10.3389/fonc.2019.00543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598429PMC
June 2019

Radical radiotherapy for locally advanced non-small cell lung cancer-what's up with arm positioning?

J Thorac Dis 2019 May;11(5):2099-2104

Department of Radiation Oncology, London Health Sciences Centre, London, ON, Canada.

Radical thoracic radiotherapy is ideally delivered in the arms-up (AU) position; however, patient comfort may only allow for arms-down (AD) positioning to be feasible. Objectives of this study were (I) to evaluate the dosimetric impact of changing arm position during treatment and (II) to compare plan quality for optimization in AU AD positions. In this retrospective planning study, stage III lung cancer patients (n=10) who received 60 Gy in 30 fractions using volumetric modulated arc therapy (VMAT) were identified. To simulate AD treatment, a PET/CT (acquired AD) was registered to the planning CT (acquired AU) for arm delineation. The clinically delivered plan (AU) was recalculated with a density override to 1 g/cm for one or both arm contours (AD). Plans were also re-optimized for the AD position. Dose-volume parameters were compared for each scenario. Moving from AU to AD without re-optimization resulted in a mean 3.7% reduction in PTV D95; in all cases, this caused 95% of the PTV to receive ≤57 Gy. The mean arms D2cc were 23.1 and 4.0 Gy for the ipsilateral and contralateral, respectively. Dosimetric consequences of ipsilateral arm only were similar to both AD, whereas contralateral arm only had less than 1% effect on PTV D95. Re-optimizing to account for both AD recovered PTV D95 coverage with acceptable doses to all organs at risk. Arm D2cc were also decreased to 5.5 and 2.3 Gy for ipsilateral and contralateral, respectively. There was a significant difference in heart V25 and mean heart dose (P<0.001), but the magnitude was small at 4.1% for V25 and 1.7 Gy for mean heart dose and the plans still met institutional dose constraints. This planning study suggests that it is feasible to plan radiotherapy for locally advanced lung cancer patients in the AD position using VMAT, when necessary, with only a modest dosimetric impact.
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http://dx.doi.org/10.21037/jtd.2019.05.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588765PMC
May 2019

Analysis of Pathologic Complete Response 10 Weeks After Radiotherapy-A Radiobiological Sin-In Reply.

JAMA Oncol 2019 Jul 3. Epub 2019 Jul 3.

Department of Oncology, Western University, London Health Science Centre, London, Ontario, Canada.

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http://dx.doi.org/10.1001/jamaoncol.2019.1901DOI Listing
July 2019

Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial.

Lancet 2019 05 11;393(10185):2051-2058. Epub 2019 Apr 11.

Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Background: The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions.

Methods: This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0-1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1-3 vs 4-5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744.

Findings: 99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group. Median overall survival was 28 months (95% CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30-1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5-34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group.

Interpretation: SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit.

Funding: Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.
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http://dx.doi.org/10.1016/S0140-6736(18)32487-5DOI Listing
May 2019

Adjuvant Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (TKIs) in Resected Non-Small Cell Lung Cancer (NSCLC): A Systematic Review and Meta-analysis.

Am J Clin Oncol 2019 05;42(5):440-445

London Regional Cancer Program, Department of Oncology, Division of Medical Oncology.

The role of adjuvant tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) is not well defined. Recent randomized controlled trials showed a disease-free survival (DFS) benefit in patients harboring an epidermal growth factor receptor (EGFR) mutation. Yet, older trials on patients with any EGFR status did not demonstrate the same benefit. We aimed to assess the efficacy and safety of adjuvant TKIs in NSCLC patients. The electronic databases Medline (PubMed) and EMBASE were searched for relevant randomized controlled trials. Random effect models were used. The primary outcome was DFS measured as hazard ratio (HR). The secondary outcomes were overall survival (OS) measured as HR, 2-year DFS and toxicity expressed as risk ratio and odds ratio (OR), respectively. Subgroup analyses assessed DFS by trial design. Six trials incorporating 1860 patients were included. In patients harboring an EGFR mutation, adjuvant TKIs decreased the risk of disease recurrence by 48% (HR: 0.52, 95% confidence interval [CI]: 0.35-0.78), improved 2-year DFS (HR: 0.53, 95% CI: 0.43-0.66) but did not improve OS (HR: 0.64, 95% CI: 0.22-1.89). The risk of developing ≥grade 3 skin toxicity (OR: 6.07, 95% CI: 4.34-8.51) and diarrhea (OR: 4.05; 95% CI: 2.44-6.74) was increased. In subgroup analyses, the DFS benefit was more pronounced in trials using TKIs over chemotherapy compared with trials using TKIs postchemotherapy. In conclusion, adjuvant TKIs decrease the risk of recurrence in NSCLC patients harboring an EGFR mutation but do not improve OS. Longer follow-up is needed for a definitive assessment of OS and to define the role of adjuvant TKI for NSCLC in the clinical practice.
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http://dx.doi.org/10.1097/COC.0000000000000533DOI Listing
May 2019

Effect of Chemotherapy With Docetaxel With Androgen Suppression and Radiotherapy for Localized High-Risk Prostate Cancer: The Randomized Phase III NRG Oncology RTOG 0521 Trial.

J Clin Oncol 2019 05 12;37(14):1159-1168. Epub 2019 Mar 12.

6 Cedars-Sinai Medical Center, Los Angeles, CA.

Purpose: Radiotherapy (RT) plus long-term androgen suppression (AS) are a standard treatment option for patients with high-risk localized prostate cancer. We hypothesized that docetaxel chemotherapy (CT) could improve overall survival (OS) and clinical outcomes among patients with high-risk prostate cancer.

Patients And Methods: The multicenter randomized NRG Oncology RTOG 0521 study enrolled patients with high-risk nonmetastatic disease between 2005 and 2009. Patients were randomly assigned to receive standard long-term AS plus RT with or without adjuvant CT.

Results: A total of 612 patients were enrolled; 563 were evaluable. Median prostate-specific antigen was 15.1 ng/mL; 53% had a Gleason score 9 to 10 cancer; 27% had cT3 to cT4 disease. Median follow-up was 5.7 years. Treatment was well tolerated in both arms. Four-year OS rate was 89% (95% CI, 84% to 92%) for AS + RT and 93% (95% CI, 90% to 96%) for AS + RT + CT (hazard ratio [HR], 0.69; 90% CI, 0.49 to 0.97; one-sided = .034). There were 59 deaths in the AS + RT arm and 43 in the AS + RT + CT arm, with fewer deaths resulting from prostate cancer in the AS + RT + CT arm versus AS + RT (23 16 deaths, respectively). Six-year rate of distant metastasis was 14% for AS + RT and 9.1% for AS + RT + CT, (HR, 0.60; 95% CI, 0.37 to 0.99; two-sided = .044). Six-year disease-free survival rate was 55% for AS + RT and 65% for AS + RT + CT (HR, 0.76; 95% CI, 0.58 to 0.99; two-sided = .043).

Conclusion: For patients with high-risk nonmetastatic prostate cancer, CT with docetaxel improved OS from 89% to 93% at 4 years, with improved disease-free survival and reduction in the rate of distant metastasis. The trial suggests that docetaxel CT may be an option to be discussed with selected men with high-risk prostate cancer.
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http://dx.doi.org/10.1200/JCO.18.02158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506419PMC
May 2019