Publications by authors named "Aaron R Hansen"

84 Publications

Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium.

J Clin Oncol 2021 Apr 6:JCO2003296. Epub 2021 Apr 6.

University Department of Medical Oncology, Inselspital, University Hospital, University of Bern, Bern, Switzerland.

Purpose: The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990.

Materials And Methods: Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set.

Results: Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update).

Conclusion: The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.
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http://dx.doi.org/10.1200/JCO.20.03296DOI Listing
April 2021

The Future of Clinical Trial Design in Oncology.

Cancer Discov 2021 Apr;11(4):822-837

Division of Medical Oncology and Hematology, Drug Development Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.

Clinical trials represent a fulcrum for oncology drug discovery and development to bring safe and effective medicines to patients in a timely manner. Clinical trials have shifted from traditional studies evaluating cytotoxic chemotherapy in largely histology-based populations to become adaptively designed and biomarker-driven evaluations of molecularly targeted agents and immune therapies in selected patient subsets. This review will discuss the scientific, methodological, practical, and patient-focused considerations to transform clinical trials. A call to action is proposed to establish the framework for next-generation clinical trials that strikes an optimal balance of operational efficiency, scientific impact, and value to patients. SIGNIFICANCE: The future of cancer clinical trials requires a framework that can efficiently transform scientific discoveries to clinical utility through applications of innovative technologies and dynamic design methodologies. Next-generation clinical trials will offer individualized strategies which ultimately contribute to globalized knowledge and collective learning, through the joint efforts of all key stakeholders including investigators and patients.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1301DOI Listing
April 2021

Examining the ability of the Cancer and Aging Research Group tool to predict toxicity in older men receiving chemotherapy or androgen-receptor-targeted therapy for metastatic castration-resistant prostate cancer.

Cancer 2021 Apr 2. Epub 2021 Apr 2.

Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: Because multiple treatments are available for metastatic castrate-resistant prostate cancer (mCRPC) and most patients are elderly, the prediction of toxicity risk is important. The Cancer and Aging Research Group (CARG) tool predicts chemotherapy toxicity in older adults with mixed solid tumors, but has not been validated in mCRPC. In this study, its ability to predict toxicity risk with docetaxel chemotherapy (CHEMO) was validated, and its utility was examined in predicting toxicity risk with abiraterone or enzalutamide (A/E) among older adults with mCRPC.

Methods: Men aged 65+ years were enrolled in a prospective observational study at 4 Canadian academic cancer centers. All clinically relevant grade 2 to 5 toxicities over the course of treatment were documented via structured interviews and chart review. Logistic regression was used to identify predictors of toxicity.

Results: Seventy-one men starting CHEMO (mean age, 73 years) and 104 men starting A/E (mean age, 76 years) were included. Clinically relevant grade 3+ toxicities occurred in 56% and 37% of CHEMO and A/E patients, respectively. The CARG tool was predictive of grade 3+ toxicities with CHEMO, which occurred in 36%, 67%, and 91% of low, moderate, and high-risk groups (P = .003). Similarly, grade 3+ toxicities occurred among A/E users in 23%, 48%, and 86% with low, moderate, and high CARG risk (P < .001). However, it was not predictive of grade 2 toxicities with either treatment.

Conclusions: There is external validation of the CARG tool in predicting grade 3+ toxicity in older men with mCRPC undergoing CHEMO and demonstrated utility during A/E therapy. This may aid with treatment decision-making.
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http://dx.doi.org/10.1002/cncr.33523DOI Listing
April 2021

Transitions in oral and gut microbiome of HPV+ oropharyngeal squamous cell carcinoma following definitive chemoradiotherapy (ROMA LA-OPSCC study).

Br J Cancer 2021 Mar 10. Epub 2021 Mar 10.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

Background: Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and evaluated the impact of chemoradiotherapy (CRT).

Methods: Saliva, oropharyngeal swabs over the tumour site and stool were collected at baseline and post-CRT. 16S RNA and shotgun metagenomic sequencing were used to generate taxonomic profiles, including relative abundance (RA), bacterial density, α-diversity and β-diversity.

Results: A total of 132 samples from 22 patients were analysed. Baseline saliva and swabs had similar taxonomic composition (R = 0.006; p = 0.827). Oropharyngeal swabs and stool taxonomic composition varied significantly by stage, with increased oral RA of Fusobacterium nucleatum observed in stage III disease (p < 0.05). CRT significantly reduced the species richness and increased the RA of gut-associated taxa in oropharyngeal swabs (p < 0.05), while it had no effect in stool samples. These findings remained significant when adjusted by stage, smoking status and antibiotic use.

Conclusions: Baseline oral and gut microbiomes differ by stage in this HPV+ cohort. CRT caused a shift towards a gut-like microbiome composition in oropharyngeal swabs. Stage-specific features and the transitions in oral microbiome might have prognostic and therapeutic implications.
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http://dx.doi.org/10.1038/s41416-020-01253-1DOI Listing
March 2021

Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium.

J Clin Oncol 2021 Mar 17:JCO2003292. Epub 2021 Mar 17.

Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.

Purpose: The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium.

Materials And Methods: Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients.

Results: Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH.

Conclusion: PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.
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http://dx.doi.org/10.1200/JCO.20.03292DOI Listing
March 2021

Efficacy of immune-checkpoint inhibitors (ICI) in the treatment of older adults with metastatic renal cell carcinoma (mRCC) - an International mRCC Database Consortium (IMDC) analysis.

J Geriatr Oncol 2021 Mar 2. Epub 2021 Mar 2.

William Osler Health System, Brampton, ON, Canada. Electronic address:

Objective: Older adults with metastatic renal cell carcinoma(mRCC) are underrepresented in immune-checkpoint inhibitor(ICI) registration trials. Here we compare the efficacy of ICI treatments in older vs. younger adults with mRCC.

Methods: Using the International mRCC Database Consortium(IMDC), patients treated with a PD(L)-1 based ICI were identified. Older adult was defined as ≥70-years at the time of treatment. Descriptive statistics were summarized in means, medians, and proportions. Effectiveness endpoints included overall survival (OS), time-to-treatment failure(TTF), time-to-next treatment(TNT), and overall response rate(ORR). Hazards ratios were adjusted(aHR) for IMDC risk factors, histology, line of treatment and older age.

Results: Of 1427 included patients, 397(28%) were older adults. ICI was used as 1st line(1 L) in 40%, 2nd line(2 L) in 49% and 3rd line(3 L) in 11% of patients. In univariable analysis, older adults had inferior OS compared to younger adults(25.1 m vs. 30.8 m, p < 0.01). There were no significant differences in TTF (6.9 m vs. 6.9 m, p = 0.4) or TNT(9.1 m vs 10 m, p = 0.3) between groups. In multivariable analyses, older age was not independently associated with worse OS(aHR = 1.02, p = 0.8), TTF(aHR = 0.95, p = 0.6) or TNT(aHR = 0.93, p = 0.5). Older adults had a lower ORR compared to younger adults(24% vs. 31%, p = 0.01), which was mainly driven by responses in 1 L(31% vs. 44%, p = 0.02) and not observed in 2 L/3 L.

Conclusions: After multivariable analyses, older adults with mRCC treated with ICI had no difference in OS, TTF or TNT when compared to younger adults. Our data support that chronological older age should not preclude patients from receiving ICI based therapies.
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http://dx.doi.org/10.1016/j.jgo.2021.02.022DOI Listing
March 2021

Health-related quality-of-life assessment of patients with solid tumors on immuno-oncology therapies.

Cancer 2021 Mar 4. Epub 2021 Mar 4.

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

Immuno-oncology therapies have been approved for various solid tumors; however, the high cost of these treatments and their potential toxicities require a thorough assessment of their risks and benefits. Collection of data directly from patients through patient-reported outcome instruments can improve the precision and reliability of adverse event detection, assess tolerability of adverse events, and provide an evaluation of health-related quality of life (HRQOL) changes from immuno-oncology therapies. There is robust development in HRQOL tools specifically for patients treated with immuno-oncology agents. This review examines the history and basic concepts of HRQOL and patient-reported outcome assessments commonly used in oncological trials, highlighting the strengths and weaknesses of current approaches when applied to immunotherapies, as well as some of the current efforts to develop tools for this field and opportunities for future research. LAY SUMMARY: Immuno-oncology (IO) therapies are costly and carry potential toxicities known as immune-related adverse events. Evaluation of health-related quality of life (HRQOL) can impact the risk-benefit assessment of IO therapies. Integration of HRQOL end points and patient-reported outcome data for IO therapies are urgently needed. Ongoing robust development of patient-reported outcome tools specific to IO therapies are currently underway and will permit the evaluation of HRQOL for IO agents. Improvement in precision and reliability of HRQOL evaluation will enhance the ultimate true value of these expensive and effective drugs.
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http://dx.doi.org/10.1002/cncr.33457DOI Listing
March 2021

The Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Metastatic Testicular Cancer.

Curr Oncol 2020 Dec 21;28(1):107-114. Epub 2020 Dec 21.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON M5G 2C1, Canada.

We investigated the prognostic utility of pre-chemotherapy neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic germ cell tumors (GCTs) undergoing first-line chemotherapy. We utilized two institutional databases to analyze the pretreatment-derived NLR (dNLR). Predictive accuracy was evaluated using the Cox proportional hazard model adjusted for the international germ cell cancer collaborative group (IGCCCG) risk classification. Discriminatory accuracy was evaluated by determining the area under the receiver operating characteristic curve (AUROC). In total, 569 of 690 patients had available dNLR (IGCCCG: good, 64%; intermediate, 21%; poor, 16%). The 5-year and 10-year overall survivals (OSs) for good, intermediate, and poor risk groups were 96.2%, 92.8%, and 62.7% and 93.9%, 90.3%, and 62.7%, respectively. A dNLR of 2 provided the best discriminatory accuracy with an AUROC of 0.58 (95% CI: 0.52-0.65, = 0.01) for progression-free survival (PFS), whereas for OS, a dNLR of 3 provided the best discriminatory accuracy with an AUROC of 0.62 (95% CI: 0.53-0.70, < 0.01). A dNLR > 2 was associated with a hazard ratio (HR) of 1.99 (95% CI: 1.27-3.12, < 0.01) for PFS, which lost its effect after adjustment for IGCCCG (HR: 1.44, 95% CI: 0.90-2.30, = 0.13). For OS, a dNLR >3 was associated with an HR of 3.00 (95% CI: 1.79-5.01, < 0.01), but lost its effect after adjustment for IGCCCG. Systemic inflammation plays a role in metastatic GCT, but its prognostic utility beyond established algorithms is limited. The general prognostic value of NLR can be seen across a number of tumors, although the consistency and magnitude of the effect differ according to cancer type, disease stage, and treatment received. We identified that an elevated NLR was associated with an adverse PFS and OS, but not independent of the IGCCCG risk classification. dNLRs >2 and >3 were associated with an adverse PFS and OS, respectively, in patients with metastatic GCT receiving first-line chemotherapy, but not independent of the IGCCCG risk classification.
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http://dx.doi.org/10.3390/curroncol28010014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816171PMC
December 2020

Underreporting of symptomatic adverse events in phase I clinical trials.

J Natl Cancer Inst 2021 Feb 22. Epub 2021 Feb 22.

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Background: Clinician reporting of symptomatic adverse events (AEs) in phase I trials utilizes the Common Terminology Criteria for Adverse Events (CTCAE). The utility of the patient-reported outcomes (PRO) version of the CTCAE (PRO-CTCAE) in this setting is unknown. This prospective, observational study compared patient- and clinician-reported symptomatic-AEs in phase I patients.

Methods: Phase I study eligible patients at Princess Margaret were surveyed with the PRO-CTCAE full item library (78 symptomatic-AEs) at baseline (BL), mid-cycle 1 (C1) and mid-cycle 2 (C2). Patient and trial characteristics, best response, and survival data were collected. Presence/absence of patient- (PRO-CTCAE) or clinician-reported (CTCAEv4) symptomatic-AEs were compared (kappa) at defined timepoints and overall (BL+C1+C2).

Results: Of 292 patients approached from 05/2017-01/2019, 265 (90.8%) were consented, with 243 (91.7%) evaluable and 552 PRO-CTCAE surveys (completion rate = 98.7%) included in analyses. Evaluation of overall patient-reported symptomatic-AEs identified 50 PRO-CTCAE and 11 CTCAE items with ≥10% reporting frequency. 19 CTCAE items were reported at ≤ 1% despite matched PRO-CTCAE items with reporting ≥10%. Underreported categories included sexual health, bodily emissions, and cognition. Clinician- relative to patient-reporting frequency (ratio) demonstrated 9 symptomatic-AEs with a ≥ 50-fold lower clinician reporting rate. Overall patient-clinician agreement for individual symptomatic-AEs ranged from poor (kappa = 0.00-0.19) to moderate (kappa = 0.40-0.59) with discordance driven by lack of clinician reporting. Dyspnea (kappa = 0.54) and peripheral neuropathy (kappa = 0.63) at BL, and limb edema (kappa = 0.55) at C2 demonstrated highest patient-clinician agreement.

Conclusion: Poor to moderate patient-clinician agreement for symptomatic-AEs suggests clinician underreporting in phase I trials. Analyses of severity and interference PRO categories are ongoing.
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http://dx.doi.org/10.1093/jnci/djab015DOI Listing
February 2021

Prognostic value of clinical and radiologic extranodal extension and their role in the 8th edition TNM cN classification for HPV-negative oropharyngeal carcinoma.

Oral Oncol 2021 Mar 25;114:105167. Epub 2021 Jan 25.

Department of Radiation Oncology, The Princess Margaret Cancer Centre/University of Toronto, Canada; Department of Otolaryngology-Head & Neck Surgery, The Princess Margaret Cancer Centre/University of Toronto, Canada. Electronic address:

Background/objectives: We evaluate the performance between the TNM-8 versus TNM-7 cN-classification and explore the relative prognostic contribution of radiologic extranodal extension (rENE) for HPV-negative oropharyngeal cancer (HPV-OPC).

Materials/methods: All HPV- OPC treated with IMRT between 2005 and 2016 were included. cENE was defined as unambiguous "fixation" of a neck mass or "skin involvement" on clinical examination. rENE was recorded by re-reviewing pre-treatment CT/MR. Disease-free survival (DFS) stratified by cENE or rENE were compared. Multivariable analyses (MVA) calculated the adjusted hazard ratio (aHR) for the separate cENE and rENE attributes and their combination. A refined cN-category incorporating both cENE and rENE parameters was proposed. The performance of the revision was compared to TNM-8 and TNM-7.

Results: Of 361 HPV- OPC, 97 were cN0 and 264 were cN+ with 48 cENE+ and 72 rENE+ respectively. Median follow-up was 5.4 years. The 3-year DFS was lower in cENE+ vs cENE-negative (cENE-) (23% vs 45%; aHR = 1.68, p = 0.008) and rENE+ vs rENE-negative (rENE-) patients (29% vs 45%; aHR = 1.44, p = 0.037). The cENE+/rENE+ subset had the worse DFS vs cENE-/rENE+ or cENE-/rENE- (24%/37%/46%, p = 0.005). We propose a refined cN-category wherein any cENE-/rENE+ case is reclassified one N-stratum higher while any cENE+ case remains cN3b. The stage schema with the refined N-categorization outperformed TNM-8, and both outperformed TNM-7.

Conclusions: cENE and rENE are both prognostic but the cENE+/rENE+ subset has the worst outcome. The TNM-8 cN-categories improves outcome prediction compared to the TNM-7. Incorporation of rENE into TNM-8 cN-categories may further augment performance.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105167DOI Listing
March 2021

Pathologic concordance of resected metastatic nonseminomatous germ cell tumors in the chest.

J Thorac Cardiovasc Surg 2021 Mar 30;161(3):856-868.e1. Epub 2020 Nov 30.

Division of Thoracic Surgery, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Objective: Men with metastatic nonseminomatous germ cell tumors (NSGCTs) often present with residual chest tumors after chemotherapy. We examined the pathologic concordance of intrathoracic disease and outcomes based on the worst pathology of disease resected at first thoracic surgery.

Methods: A retrospective analysis was performed of consecutive patients undergoing thoracic resection for metastatic NSGCT in our institution between 2005 and 2018.

Results: Eighty-nine patients (all men) were included. The median age was 29 years (interquartile range [IQR], 23-35 years). Primary sites were testis (n = 84; 94.4%) and retroperitoneum (n = 5; 5.6%). Eighty-seven patients received chemotherapy before undergoing surgery. Nineteen patients (21.3%; group 1) had malignancy resected at first surgery (OR1), and the other 70 patients had benign disease at OR1 (78.7%; group 2). Concordant pathology between lungs was 85.2% in group 1 and 91% in group 2, and between lung and mediastinum was 50% in group 1 and 72.7% in group 2. Despite no teratoma at OR1, 3 patients (15.8%) in group 2 had resection of teratoma (n = 2) or malignancy (n = 1) at future surgery. After a mean follow-up of 65.5 months (IQR, 23.1-89.2 months) for group 1 and 47.7 months (IQR, 13.0-75.1 months) for group 2, overall survival was significantly worse for group 1 (68.4% vs 92.9%; P = .03).

Conclusions: The wide range of pathology resected in patients with intrathoracic NSGCT metastases requires careful decision making regarding treatment. Pathologic concordance between lungs is better than that between lung and mediastinum in patients with intrathoracic NSGCT metastases. Aggressive surgical management should be considered for all residual disease due to the low concordance between sites and the potential for excellent long-term survival even in patients with chemotherapy-refractory disease.
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http://dx.doi.org/10.1016/j.jtcvs.2020.10.158DOI Listing
March 2021

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults.

Curr Oncol 2021 Jan 15;28(1):523-548. Epub 2021 Jan 15.

Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON M5G 2C4, Canada.

The tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib were recently approved in Canada for the treatment of solid tumours harbouring neurotrophic tyrosine receptor kinase ( gene fusions. These gene fusions are oncogenic drivers found in most tumour types at a low frequency (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., secretory carcinoma of the salivary gland and of the breast). They are generally mutually exclusive of other common oncogenic drivers. Larotrectinib and entrectinib have demonstrated impressive overall response rates and tolerability in Phase I/II trials in patients with TRK fusion cancer with no other effective treatment options. Given the low frequency of TRK fusion cancer and the heterogeneous molecular testing landscape in Canada, identifying and optimally managing such patients represents a new challenge. We provide a Canadian consensus on when and how to test for gene fusions and when to consider treatment with a TRK inhibitor. We focus on five tumour types: thyroid carcinoma, colorectal carcinoma, non-small cell lung carcinoma, soft tissue sarcoma, and salivary gland carcinoma. Based on the probability of the tumour harbouring an gene fusion, we also suggest a tumour-agnostic consensus for gene fusion testing and treatment. We recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options.
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http://dx.doi.org/10.3390/curroncol28010053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903287PMC
January 2021

Significantly Minimizing Drug Wastage and the Cost of Cabazitaxel Used to Treat Metastatic Castration-Resistant Prostate Cancer.

Eur Urol 2021 Feb 21;79(2):177-179. Epub 2020 Oct 21.

Division of Medical Oncology, Department of Medicine, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Cabazitaxel is used to treat patients with metastatic castration-resistant prostate cancer progressing after docetaxel. It is prepackaged in 60 mg single-dose vials, a quantity much higher than the average prescribed dose, which leads to, substantial drug wastage (DW) and associated costs. To minimize DW we implemented a cost-saving, cohorting strategy where multiple patients scheduled to receive cabazitaxel (at a dose of 20mg/m every 3 wks) were cohorted and treated on a single weekday whenever possible. Excess drug from each vial was then saved and used for subsequent patients treated on the same day. The drug cost with cohorting was calculated from the actual number of vials used, and the drug cost without cohorting was estimated by assumingthat one vial was used per treatment. The cost of DW was determined based on the amount of drug that was discarded. All cost calculations also accounted for the discount incentives offered by Sanofi-Aventis. Over a 3-yr period, 74 patients received 402 treatments of cabazitaxel. Multiple patients were treated on 67.4% of the treatment days, and grouping of three patients on one day saved one vial. The estimated total drug cost saved was $394 536 CAD (21.1%). Pending further studies on safety and efficacy, this strategy could potentially be adopted to mitigate DW for cabazitaxel and similarly for other oncology drugs. This would significantly decrease the overall financial burden on patients, institutions, and stakeholders. PATIENT SUMMARY: Cabazitaxel chemotherapy is associated with substantial drug wastage and associated costs. By cohorting patients scheduled to receive cabazitaxel on a single weekday, the total drug cost was decreased by $394 536 CAD (21.1%) over a 3-yr period. Similar strategies could be considered to overcome the prohibitory costs associated with drug wastage for cabazitaxel and other cancer drugs.
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http://dx.doi.org/10.1016/j.eururo.2020.09.048DOI Listing
February 2021

Screening for Nasopharyngeal Cancer in High-Risk Populations: A Small Price to Pay for Early Disease Identification?

J Natl Cancer Inst 2020 Dec 21. Epub 2020 Dec 21.

Department of Medical Oncology, Princess Margaret Cancer Center, Toronto, Canada.

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http://dx.doi.org/10.1093/jnci/djaa199DOI Listing
December 2020

Predicting response and toxicity to PD-1 inhibition using serum autoantibodies identified from immuno-mass spectrometry.

F1000Res 2020 7;9:337. Epub 2020 May 7.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Validated biomarkers are needed to identify patients at increased risk of immune-related adverse events (irAEs) to immune checkpoint blockade (ICB). Antibodies directed against endogenous antigens can change after exposure to ICB. Patients with different solid tumors stratified into cohorts received pembrolizumab every 3 weeks in a Phase II trial (INSPIRE study). Blood samples were collected prior to first pembrolizumab exposure (baseline) and approximately 7 weeks (pre-cycle 3) into treatment. In a discovery analysis, autoantibody target immuno-mass spectrometry was performed in baseline and pre-cycle 3 pooled sera of 24 INSPIRE patients based on clinical benefit (CBR) and irAEs. Thyroglobulin (Tg) and thyroid peroxidase (TPO) were identified as the candidate autoantibody targets. In the overall cohort of 78 patients, the frequency of CBR and irAEs from pembrolizumab was 31% and 24%, respectively. Patients with an anti-Tg titer increase ≥1.5x from baseline to pre-cycle 3 were more likely to have irAEs relative to patients without this increase in unadjusted, cohort adjusted, and multivariable models (OR=17.4, 95% CI 1.8-173.8, p=0.015). Similarly, patients with an anti-TPO titer ≥ 1.5x from baseline to pre-cycle 3 were more likely to have irAEs relative to patients without the increase in unadjusted and cohort adjusted (OR=6.1, 95% CI 1.1-32.7, p=0.035) models. Further, the cohort adjusted analysis showed patients with anti-Tg titer greater than median (10.0 IU/mL) at pre-cycle 3 were more likely to have irAEs (OR=4.7, 95% CI 1.2-17.8, p=0.024). Patients with pre-cycle 3 anti-TPO titers greater than median (10.0 IU/mL) had a significant difference in overall survival (23.8 vs 11.5 months; HR=1.8, 95% CI 1.0-3.2, p=0.05). Patient increase ≥1.5x of anti-Tg and anti-TPO titers from baseline to pre-cycle 3 were associated with irAEs from pembrolizumab, and patients with elevated pre-cycle 3 anti-TPO titers had an improvement in overall survival.
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http://dx.doi.org/10.12688/f1000research.22715.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707117PMC
March 2021

Systematic Review and STARD Scoring of Renal Cell Carcinoma Circulating Diagnostic Biomarker Manuscripts.

JNCI Cancer Spectr 2020 Oct 8;4(5):pkaa050. Epub 2020 Jun 8.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

Background: No validated molecular biomarkers exist to help guide diagnosis of renal cell carcinoma (RCC) patients. We seek to evaluate the quality of published RCC circulating diagnostic biomarker manuscripts using the Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines.

Methods: The phrase "(renal cell carcinoma OR renal cancer OR kidney cancer OR kidney carcinoma) AND circulating AND (biomarkers OR cell free DNA OR tumor DNA OR methylated cell free DNA OR methylated tumor DNA)" was searched in Embase, MEDLINE, and PubMed in March 2018. Relevant manuscripts were scored using 41 STARD subcriteria for a maximal score of 26 points. All tests of statistical significance were 2 sided.

Results: The search identified 535 publications: 27 manuscripts of primary research were analyzed. The median STARD score was 11.5 (range = 7-16.75). All manuscripts had appropriate abstracts, introductions, and distribution of alternative diagnoses. None of the manuscripts stated how indeterminant data were handled or if adverse events occurred from performing the index test or reference standard. Statistically significantly higher STARD scores were present in manuscripts reporting receiver operator characteristic curves ( < .001), larger sample sizes ( = .007), and after release of the original STARD statement ( = .005).

Conclusions: Most RCC circulating diagnostic biomarker manuscripts poorly adhere to the STARD guidelines. Future studies adhering to STARD guidelines may address this unmet need.
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http://dx.doi.org/10.1093/jncics/pkaa050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583155PMC
October 2020

Activity of Platinum-Based Chemotherapy in Patients With Advanced Prostate Cancer With and Without DNA Repair Gene Aberrations.

JAMA Netw Open 2020 10 1;3(10):e2021692. Epub 2020 Oct 1.

Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.

Importance: DNA repair gene aberrations occur in 20% to 30% of patients with castration-resistant prostate cancer (CRPC), and some of these aberrations have been associated with sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition platinum-based treatments. However, previous trials assessing platinum-based treatments in patients with CRPC have mostly included a biomarker-unselected population; therefore, efficacy in these patients is unknown.

Objective: To characterize the antitumor activity of platinum-based therapies in men with CRPC with or without DNA repair gene alterations.

Design, Setting, And Participants: In this case series, data from 508 patients with CRPC treated with platinum-based therapy were collected from 25 academic centers from 12 countries worldwide. Patients were grouped by status of DNA repair gene aberrations (ie, cohort 1, present; cohort 2, not detected; and cohort 3, not tested). Data were collected from January 1986 to December 2018. Data analysis was performed in 2019, with data closure in April 2019.

Exposure: Treatment with platinum-based compounds either as monotherapy or combination therapy.

Main Outcomes And Measures: The primary end points were as follows: (1) antitumor activity of platinum-based therapy, defined as a decrease in prostate-specific antigen (PSA) level of at least 50% and/or radiological soft tissue response in patients with measurable disease and (2) the association of response with the presence or absence of DNA repair gene aberrations.

Results: A total of 508 men with a median (range) age of 61 (27-88) years were included in this analysis. DNA repair gene aberrations were present in 80 patients (14.7%; cohort 1), absent in 98 (19.3%; cohort 2), and not tested in 330 (65.0%; cohort 3). Of 408 patients who received platinum-based combination therapy, 338 patients (82.8%) received docetaxel, paclitaxel, or etoposide, and 70 (17.2%) received platinum-based combination treatment with another partner. A PSA level decrease of at least 50% was seen in 33 patients (47.1%) in cohort 1 and 26 (36.1%) in cohort 2 (P = .20). In evaluable patients, soft tissue responses were documented in 28 of 58 patients (48.3%) in cohort 1 and 21 of 67 (31.3%) in cohort 2 (P = .07). In the subgroup of 44 patients with BRCA2 gene alterations, PSA level decreases of at least 50% were documented in 23 patients (63.9%) and soft tissue responses in 17 of 34 patients (50.0%) with evaluable disease. In cohort 3, PSA level decreases of at least 50% and soft tissue responses were documented in 81 of 284 patients (28.5%) and 38 of 185 patients (20.5%) with evaluable disease, respectively.

Conclusions And Relevance: In this study, platinum-based treatment was associated with relevant antitumor activity in a biomarker-positive population of patients with advanced prostate cancer with DNA repair gene aberrations. The findings of this study suggest that platinum-based treatment may be considered an option for these patients.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.21692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593810PMC
October 2020

Dual Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancer: Just a Gambit or Real CheckMate?

Cancer Cell 2020 10;38(4):438-440

Princess Margaret Cancer Centre, Division of Medical Oncology, University Health Network, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada. Electronic address:

In this issue of Cancer Cell, Sharma et al. report that ipilimumab and nivolumab combination achieved impressive response rates in patients with metastatic castration-resistant prostate cancer (mCRPC). But this regimen produced high rates of toxicity, treatment-related discontinuation, and death. Tolerability needs improvement for this combination to benefit more men with mCRPC.
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http://dx.doi.org/10.1016/j.ccell.2020.09.009DOI Listing
October 2020

Clinical dilemmas in local and regional testis cancer.

Can Urol Assoc J 2021 Jan;15(1):E58-E64

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada.

At the Canadian Testis Cancer Workshop, the multidisciplinary management of testis cancer care was discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents, fellows, nurses, patients, and patient advocacy group members.This review summarizes the discussion regarding clinical dilemmas in local and regional testis cancer. We present cases that highlight the need for a coordinated approach to individualize care. Overarching themes include the importance of a multidisciplinary approach to testis cancer, willingness to involve a high-volume experienced center, and given that the oncological outcomes are excellent, a reminder that clinical decisions need to prioritize selecting a strategy with the least treatment-related morbidity when safe.
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http://dx.doi.org/10.5489/cuaj.6913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769526PMC
January 2021

Pre- and Post-Radiotherapy Radiologic Nodal Features and Oropharyngeal Cancer Outcomes.

Laryngoscope 2021 04 1;131(4):E1162-E1171. Epub 2020 Oct 1.

Department of Radiation Oncology, The Princess Margaret Cancer Centre/University of Toronto, Toronto, Ontario, Canada.

Objectives: To assess the prognostic value of pre-/post-radiotherapy (pre-/post-RT) radiologic lymph node (LN) features in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal carcinoma (OPC) patients treated with definitive (chemo-)RT.

Methods: Clinical node-positive OPCs treated from 2011 to 2015 were reviewed. Nodal features were reviewed by a radiologist on pre-/post-RT computed tomography (CTs). Univariable analysis calculated hazard ratio (HR) for regional failure (RF), distant metastasis (DM), and deaths. Multivariable analysis estimated adjusted HR (aHR) of significant nodal features identified in univariable analysis adjusting for confounders.

Results: Pre-RT CT was undertaken in 344 HPV-positive and 94 HPV-negative OPC patients, of whom 242 (70%) HPV-positive and 67 (71%) HPV-negative also had a post-RT CT. Median follow-up was 4.9 years. Pre-RT LN calcification (pre-RT_LN-cal) increased the risk of RF in HPV-negative (aHR: 5.3, P = .007) but not HPV-positive patients (P = .110). Pre-RT radiologic extranodal extension (pre-RT_rENE+) increased the risk of DM and death in both HPV-negative (DM: aHR 6.6, P < .001; death: aHR 2.1, both P = .019) and HPV-positive patients (DM: aHR 4.9; death: aHR 3.0, both P < .001). Increased risk of RF occured with < 20% post-RT LN size reduction in both HPV-negative (HR 6.0, P = .002) and HPV-positive cases (HR 3.0, P = .049). Post-RT_LN-cal did not affect RF, DM, or death regardless of tumor HPV status (all P > .05).

Conclusion: Pre-RT_LN-cal is associated with higher RF risk in HPV-negative but not in HPV-positive patients. Pre-RT_rENE increases risk of DM and death regardless of tumor HPV status. Minimal post-RT LN size reduction (< 20%) increases risk of RF in both diseases. Post-RT_LN-cal + has no apparent influence on outcomes in either disease.

Level Of Evidence: 4 (a single institution case-control series) Laryngoscope, 131:E1162-E1171, 2021.
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http://dx.doi.org/10.1002/lary.29045DOI Listing
April 2021

Long-term Surveillance of Patients with Complete Response Following Chemotherapy for Metastatic Nonseminomatous Germ Cell Tumor.

Eur Urol Oncol 2020 Sep 6. Epub 2020 Sep 6.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address:

Background: There is controversy regarding the management of patients with normal markers and residual masses (≤1 cm) after chemotherapy for nonseminomatous germ cell tumors (NSGCTs).

Objective: To determine long-term outcomes of a surveillance strategy in such patients.

Design, Setting, And Participants: A retrospective review of our multidisciplinary testicular cancer database was performed. All patients who underwent primary chemotherapy for metastatic NSGCTs were identified between 1981 and 2016. A complete response (CR) was defined as normalization of serum tumor markers and a ≤1 cm residual mass in the largest axial dimension following chemotherapy. All such patients were surveilled.

Outcome Measurements And Statistical Analysis: Outcome variables of interest were time to death, time to cancer-specific survival, and time to relapse. Overall survival and relapse-free survival were calculated using the Kaplan-Meier method, and the cumulative incidence of cause-specific survival rates was calculated using competing risk analysis. The impact of risk group and chemotherapy regimen on relapse-free survival was assessed using log-rank test.

Results And Limitations: During the study period, 1429 metastatic germ cell tumor patients were treated with primary chemotherapy. CR was achieved in 191 (18.5%) NSGCT patients. The median age at diagnosis was 27.4 yr, with a median follow-up of 81.1 mo. The majority had American Joint Committee on Cancer stage II at diagnosis (I: 23.8%; II: 49.2%; III: 27%) and International Germ Cell Cancer Collaborative Group good-risk disease (good: 78%; intermediate: 17.8%; poor: 4.2%). Of the 191 patients with a CR, 175 (91.6%) never relapsed and remain disease free. Sixteen (8.4%) patients relapsed after a median of 11.3 mo (range 1-332 mo), with over half (nine patients; 4.7%) relapsing in the retroperitoneum only and salvaged successfully with postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) alone. Of these nine patients, only two (1%) had viable disease in the PC-RPLND specimen. The remaining seven patients had relapses outside the retroperitoneum and received salvage chemotherapy ± postchemotherapy resection. Overall, nine (4.7%) patients have died, but only four (2.1%) from testis cancer.

Conclusions: Our data, the largest series to date, confirm that surveillance is safe and effective for men who achieve a CR following chemotherapy for metastatic NSGCTs.

Patient Summary: Surveillance is a safe strategy for patients who achieve a complete response following chemotherapy for metastatic testis cancer.
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http://dx.doi.org/10.1016/j.euo.2020.08.007DOI Listing
September 2020

Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment.

Epigenomics 2020 08 1;12(15):1317-1332. Epub 2020 Sep 1.

Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5G 1X5, Canada.

We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration-resistant prostate cancer (mCRPC) during treatment. Genome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Alterations in methylation states of genes previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression. Importantly, we also report that markers associated with a highly aggressive form of the disease, neuroendocrine-CRPC, were associated with a faster time to clinical progression. Our findings highlight the potential of monitoring the cfDNA methylome during therapy in mCRPC, which may serve as predictive markers of response to androgen-targeting agents.
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http://dx.doi.org/10.2217/epi-2020-0173DOI Listing
August 2020

An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors.

J Immunother Cancer 2020 08;8(2)

Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Purpose: To evaluate whether administration of the oral DNA hypomethylating agent CC-486 enhances the poor response rate of immunologically 'cold' solid tumors to immune checkpoint inhibitor durvalumab.

Experimental Design: PD-L1/PD-1 inhibitor naïve patients with advanced microsatellite stable colorectal cancer; platinum resistant ovarian cancer; and estrogen receptor positive, HER2 negative breast cancer were enrolled in this single-institution, investigator-initiated trial. Two 28 day regimens, regimen A (CC-486 300 mg QD Days 1-14 (cycles 1-3 only) in combination with durvalumab 1500 mg intravenous day 15) and regimen B (CC-486 100 mg QD days 1-21 (cycle 1 and beyond), vitamin C 500 mg once a day continuously and durvalumab 1500 mg intravenous day 15) were investigated. Patients underwent paired tumor biopsies and serial peripheral blood mononuclear cells (PBMCs) collection for immune-profiling, transcriptomic and epigenomic analyzes.

Results: A total of 28 patients were enrolled, 19 patients treated on regimen A and 9 on regimen B. The combination of CC-486 and durvalumab was tolerable. Regimen B, with a lower dose of CC-486 extended over a longer treatment course, showed less grade 3/4 adverse effects. Global LINE-1 methylation assessment of serial PBMCs and genome-wide DNA methylation profile in paired tumor biopsies demonstrated minimal changes in global methylation in both regimens. The lack of robust tumor DNA demethylation was accompanied by an absence of the expected 'viral mimicry' inflammatory response, and consequently, no clinical responses were observed. The disease control rate was 7.1%. The median progression-free survival was 1.9 months (95% CI 1.5 to 2.3) and median overall survival was 5 months (95% CI 4.5 to 10).

Conclusions: The evaluated treatment schedules of CC-486 in combination with durvalumab did not demonstrate robust pharmacodynamic or clinical activity in selected immunologically cold solid tumors. Lessons learned from this biomarker-rich study should inform continued drug development efforts using these agents.

Trial Registration Number: NCT02811497.
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http://dx.doi.org/10.1136/jitc-2020-000883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406114PMC
August 2020

Treatment implications of postoperative chemoradiotherapy for squamous cell carcinoma of the oral cavity with minor and major extranodal extension.

Oral Oncol 2020 11 29;110:104845. Epub 2020 Jun 29.

Department of Pathology, University Health Network, Toronto, Canada.

Objectives: To evaluate adjuvant chemoradiotherapy (CRT) for patients with oral cavity squamous cell carcinoma (OSCC) with minor or major extranodal extension (ENE).

Materials And Methods: Surgically resected OSCC with pathologically involved lymph node(s) (pN+) between 2006 and 2017. Sections of pN+ were re-reviewed and classified as no, minor (≤2 mm), or major (>2 mm) ENE. Patterns of failure and survival were compared between the groups and stratified by adjuvant treatment. Multivariable (MVA) analysis assessed the value of adjuvant treatment for minor and major ENE.

Results: Total of 384 patients, 62 had minor and 114 had major ENE. Adjuvant CRT was delivered in 32(15%), 21(34%), and 45(39%) of patients with no, minor and major ENE, respectively. Patients with minor ENE had similar 5-year loco-regional control (LRC) and distant control (DC) but lower disease-free survival (DFS) (38% vs. 51%, p = 0·02) compared to patients with no ENE, while patients with major ENE had marginally lower LRC (59% vs 74%, p = 0·07), lower DC (58% vs 82%,p = 0·005) and DFS (13% vs. 38%, p=·001) compared to those with minor. On MVA, adjuvant chemotherapy was associated with improved DFS for major ENE (adjusted HR = 0·49; 95% CI 0·29-0·85, p = 0·01) but not for minor ENE after adjusting for age, ECOG status, T-, N-category, margin status, and radiotherapy.

Conclusions: Adjuvant chemoradiotherapy improves outcomes in patients with major ENE, but the benefit is unclear in patients with minor ENE. Future trials should focus on intensification of treatment for patients with major ENE and alternative adjuvant strategies for patients with minor ENE.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104845DOI Listing
November 2020

Use of combined androgen deprivation therapy with postoperative radiation treatment for prostate cancer: Impact of randomized trials on clinical practice.

Urol Oncol 2020 11 16;38(11):848.e1-848.e7. Epub 2020 Jun 16.

Department of Radiation Oncology, University of Toronto, Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Canada; Techna Institute, University Health Network, Canada. Electronic address:

Purpose: To assess the impact of RTOG-9601 and GETUG-AFU-16 on the routine use of combination androgen deprivation therapy (ADT) with postoperative radiotherapy (PORT) for prostate cancer (CaP).

Material And Methods: Patients with localized CaP treated with radical prostatectomy (RP) and PORT with or without ADT at a comprehensive cancer center from January 2006 to June 2007 (Period 1 = P1), July 2011 to December 2012 (Period 2 = P2), and January 2017 to June 2018 (Period 3 = P3) were included. Clinicopathologic features and treatment characteristics were analyzed and compared. Multivariable logistic regression was used to assess prognostic factors and association with ADT use. Statistical tests were two-sided and a P value <0.05 was considered significant. To validate the findings, United States National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results (SEER) data were collected to assess rates of combined ADT and PORT from 2004 to 2015.

Results: Five hundred and two patients were included: 152 (P1), 185 (P2), and 165 (P3). PORT was most commonly delivered as early SRT (delivered >1 year post-RP with undetectable PSA or PSA >0.05 and ≤0.5 ng/ml) in all periods. The use of combination PORT and ADT increased over time: 14.5% (P1), 32% (P2), and 41% (P3) (P < 0.001). The proportion of patients that met eligibility criteria for either GETUG-AFU-16 or RTOG-9601 decreased from 47% (P1) to 35% (P3) (P = 0.04). International Society of Urological Pathology grade ≥4 (P < 0.002) and pre-PORT PSA >0.5 ng/ml (P < 0.001) were associated with use of ADT. Positive surgical margin status had a negative association (RR 0.5, P < 0.002). The NCDB demonstrated similar trends for use of combined ADT with PORT, increasing from 37% to 49% from 2004 to 2015.

Conclusion: The use of combined ADT with PORT increased over time. However, only a third of contemporary patients undergoing PORT are represented in the major trials supporting the evidence for combination treatment, highlighting the need to characterize the modern impact of this intensification strategy.
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http://dx.doi.org/10.1016/j.urolonc.2020.04.019DOI Listing
November 2020

Hypofractionated radiotherapy alone with 2.4 Gy per fraction for head and neck cancer during the COVID-19 pandemic: The Princess Margaret experience and proposal.

Cancer 2020 08 1;126(15):3426-3437. Epub 2020 Jun 1.

Department of Radiation Oncology, Princess Margaret Cancer Centre/University of Toronto, Toronto, Ontario, Canada.

Background: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT-hypo) during the COVID-19 pandemic.

Methods: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT-hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT-acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005-2017 were included. Locoregional control (LRC) and distant control (DC) after RT-hypo, RT-acc, and CCRT were compared for various subgroups.

Results: The study identified 994 human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT-hypo, RT-acc, and CCRT, respectively) and 1045 HPV- HNSCC cases (with 263, 451, and 331 receiving RT-hypo, RT-acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy-alone patients were older. The median follow-up was 4.6 years. RT-hypo, RT-acc, and CCRT produced comparable 3-year LRC and DC for HPV+ T1-2N0-N2a disease (seventh edition of the TNM system [TNM-7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1-T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1-2N2c/T3N0-N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT-hypo or RT-acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV- HNSCC, 3-year LRC and DC were similar with RT-hypo, RT-acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT-hypo and RT-acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT-acc (62%) but not RT-hypo (80%) or CCRT (92%; RT-hypo vs CCRT: P = .270; RT-acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT-hypo or RT-acc in stage IV (73%, 65%, and 66%; P = .336).

Conclusions: It is proposed that RT-hypo be considered in place of CCRT for HPV+ T1-T3N0-N2c (TNM-7) HNSCCs, HPV- T1-T2N0 HNSCCs, and select stage III HNSCCs during the COVID-19 outbreak.
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http://dx.doi.org/10.1002/cncr.32968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300809PMC
August 2020

A Canadian approach to the regionalization of testis cancer: A review.

Can Urol Assoc J 2020 Oct;14(10):346-351

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada.

At the Canadian Testis Cancer Workshop, the rationale and feasibility of regionalization of testis cancer care were discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents and fellows, and nurses, as well as patients and patient advocacy groups.This review summarizes the discussion and recommendations of one of the central topics of the workshop - the centralization of testis cancer in Canada. It was acknowledged that non-guideline-concordant care in testis cancer occurs frequently, in the range of 18-30%. The National Health Service in the U.K. stipulates various testis cancer care modalities be delivered through supra-regional network. All cases are reviewed at a multidisciplinary team meeting and aspects of care can be delivered locally through the network. In Germany, no such network exists, but an insurance-supported online second opinion network was developed that currently achieves expert case review in over 30% of cases. There are clear benefits to regionalization in terms of survival, treatment morbidity, and cost. There was agreement at the workshop that a structured pathway for diagnosis and treatment of testis cancer patients is required.Regionalization may be challenging in Canada because of geography; independent administration of healthcare by each province; physicians fearing loss of autonomy and revenue; patient unwillingness to travel long distances from home; and the inability of the larger centers to handle the ensuing increase in volume. We feel the first step is to identify the key performance indicators and quality metrics to track the quality of care received. After identifying these metrics, implementation of a "networks of excellence" model, similar to that seen in sarcoma care in Ontario, could be effective, coupled with increased use of health technology, such as virtual clinics and telemedicine.
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http://dx.doi.org/10.5489/cuaj.6268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716843PMC
October 2020