Publications by authors named "Jolie Ringash"

181 Publications

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

Head and neck imaging surveillance strategy for HPV-positive oropharyngeal carcinoma following definitive (chemo)radiotherapy.

Radiother Oncol 2021 04 16;157:255-262. Epub 2021 Feb 16.

Department of Medical Imaging, University of Toronto, Canada; Department of Medical Imaging, Princess Margaret Cancer Centre, University of Toronto, Canada.

Purpose: To describe the utilization pattern of head and neck (HN) surveillance imaging and explore the optimal strategy for radiologic "residual" lymph node (LN) surveillance following definitive (chemo)radiotherapy (RT/CRT) in human papillomavirus (HPV)+ oropharyngeal carcinoma (OPC).

Methods: All HPV+ OPC patients who completed RT/CRT from 2012 to 2015 were included. Schedule and rationale for post-treatment HN-CT/MRI were recorded. Imaging findings and oncologic outcomes were evaluated.

Results: A total of 1036 scans in 412 patients were reviewed: 414 scans for first post-treatment response assessment and 622 scans for the following reasons: follow-up of radiologic "residual" LN(s) (293 scans/175 patients); local symptoms (227/146); other (17/16); unknown (85/66). Rate of scans with "unstated" reason varied significantly among clinicians (3-28%, p < 0.001) and none of them yielded any positive imaging findings. First post-treatment scans identified 192 (47%) patients with radiologic "residual" LNs. Neck dissection (ND) was performed in 28 patients: 16 immediately (6/16 positive), 10 after one follow-up scan (2/10 positive), and 2 after 2nd follow-up scan (1/2 positive). Thirty patients had >2 consecutive follow-up scans at 2-3-month intervals, and none showed subsequent imaging progression or regional failure.

Conclusions: Pattern of HN imaging utilization for surveillance varied significantly among clinicians. Imaging surveillance reduces the need for ND. However, routine HN-CT/MR surveillance without clinical symptoms/signs does not demonstrate proven value in identifying locoregional failure or toxicity. Radiologic "residual" LNs without adverse features are common. If two subsequent follow-up scans demonstrate stable/regressing radiologic "residual" LNs, clinical surveillance without further imaging appears to be safe in this population.
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http://dx.doi.org/10.1016/j.radonc.2021.02.005DOI Listing
April 2021

Presence and duration of feeding tube in a 5-year cohort of patients with head and neck cancer treated with curative intensity-modulated radiation therapy.

Head Neck 2021 May 13;43(5):1610-1620. Epub 2021 Feb 13.

Rehabilitation Sciences Institute, University of Toronto, Toronto, Ontario, Canada.

Background: Our study assessed post-radiation therapy (RT) G-tube presence, duration, and clinical predictors in patients with head and neck cancer (HNC).

Methods: We identified those 1-5-years post-RT with stage III/IV nasopharyngeal, oropharyngeal, hypopharyngeal, laryngeal, or unknown primaries. Logistic regression identified predictors of post-RT G-tube presence, Kaplan-Meier analysis estimated G-tube days, and log-rank test compared by tumor site.

Results: The 977 patients had mean age 60.6 ± 11.6 years, 804 (82.3%) male, 764 (78.2%) stage IV, and 618 (63.3%) oropharyngeal primaries. All patients received intensity-modulated RT (IMRT), 571 (58.4%) received chemotherapy, and 698 (71.4%) prophylactic G-tube. G-tube prevalence 1- and 5-years post-IMRT was 7.1% and 4.8%, respectively. Median post-IMRT G-tube days were overall 63 (95%CI: 56-70), nasopharynx 119 (95%CI: 109-131), oropharynx 57 (95%CI: 51-68), hypopharynx 126 (95%CI: 77-256), larynx 53 (95%CI: 21-63), unknown 30 (95%CI: 17-55), of which hypopharynx was highest p < 0.001.

Conclusions: At an institution offering prophylactic G-tube for patients with advanced HNC, no differences were found in yearly G-tube use 1-5 years post-IMRT. Across all patients, median post-IMRT days with G-tube was 63 day but those with hypopharyngeal tumors registered the most days.
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http://dx.doi.org/10.1002/hed.26638DOI Listing
May 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

Patient and family financial burden associated with cancer treatment in Canada: a national study.

Support Care Cancer 2021 Jan 5. Epub 2021 Jan 5.

DeGroote School of Business-Health Policy & Management, McMaster University, 4350 South Service Rd, Burlington, Ontario, L7L 5R8, Canada.

Goal: To determine patient-reported financial and family burden associated with treatment of cancer in the previous 28 days across Canada.

Methods: A self-administered questionnaire (P-SAFE v7.2.4) was completed by 901 patients with cancer from twenty cancer centres nationally (344 breast, 183 colorectal, 158 lung, 216 prostate) measuring direct and indirect costs related to cancer treatment and foregone care. Monthly self-reported out-of-pocket-costs (OOPCs) included drugs, homecare, homemaking, complementary/ alternative medicines, vitamins/supplements, family care, accommodations, devices, and "other" costs. Travel and parking costs were captured separately. Patients indicated if OOPC, travel, parking, and lost income were a financial burden.

Results: Mean 28-day OOPCs were CA$518 (US Purchase Price Parity [PPP] $416), plus CA$179 (US PPP $144) for travel and CA$84 (US PPP $67) for parking. Patients self-reporting high financial burden had total OOPCs (33%), of CA$961 (US PPP $772), while low-burden participants (66%) had OOPCs of CA$300 (US PPP $241). "Worst burden" respondents spent a mean of 50.7% of their monthly income on OOPCs (median 20.8%). Among the 29.4% who took time off work, patients averaged 18.0 days off. Among the 26.0% of patients whose caregivers took time off work, caregivers averaged 11.5 days off. Lastly, 41% of all patients had to reduce spending. Fifty-two per cent of those who reduced spending were families earning < CA$50,000/year.

Conclusions: In our Canadian sample, high levels of financial burden exist for 33% of patients, and the severity of burden is higher for those with lower household incomes.
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http://dx.doi.org/10.1007/s00520-020-05907-xDOI Listing
January 2021

Stereotactic body radiation therapy for hepatocellular carcinoma with Macrovascular invasion.

Radiother Oncol 2021 03 5;156:120-126. Epub 2020 Dec 5.

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

Background: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. The purpose of this study is to describe long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT).

Methods: Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were analyzed. Patients who had extrahepatic disease or previous liver transplant were excluded. Demographical, clinical, and treatment variables were analyzed.

Results: 128 eligible patients with HCC and MVI were treated with SBRT. Median age was 60.5 years (39 to 90 years). Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%. Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 5 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). Median overall survival (OS) was 18.3 months (95% CI 11.2 to 21.4 months); ECOG performance status > 1 (HR:1.85, p = 0.0138) and earlier treatment era (HR: 2.20, p = 0.0015) were associated with worsening OS. In 43 patients who received sorafenib following SBRT, median OS was 37.9 months (95% CI 19.5 to 54.4 months). Four patients developed GI bleeding possibly related to SBRT at 2 to 8 months, and 27% (31/112 evaluable patients) had worsening of CP class at three months after SBRT.

Conclusions: SBRT was associated with encouraging outcomes for patients with HCC and MVI, especially in those patients who received sorafenib after SBRT. Randomized phase III trials of SBRT with systemic and/or regional therapy are warranted and ongoing.
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http://dx.doi.org/10.1016/j.radonc.2020.11.033DOI Listing
March 2021

Healthcare resource utilization following unilateral versus bilateral radiation therapy for oropharyngeal carcinoma.

Radiother Oncol 2021 03 29;156:95-101. Epub 2020 Nov 29.

Department of Otolaryngology-Head & Neck Surgery/Surgical Oncology, Princess Margaret Cancer Centre/University of Toronto, Canada.

Purpose: To describe differences in healthcare resource utilization between patients treated with bilateral vs. unilateral neck radiation therapy (RT) for lateralized oropharyngeal cancer.

Methods: A propensity score matching strategy was used to identify two otherwise clinically similar cohorts of tonsillar cancer patients treated with either bilateral or unilateral neck RT. Cohorts were matched based on similar propensity scores for age, sex, ECOG performance status, pack-year smoking history, cT-category, cN-category, HPV-status, and use of concurrent chemotherapy. Short term (from start of RT to 3 months following end of RT) resource utilization included: 1) outpatient supportive care visits, 2) hospital admission, and 3) interventions (feeding tube insertion and outpatient intravenous hydration). Long-term resource utilization included feeding tube dependency at 1-year.

Results: Among 559 patients with tonsillar cancer treated between 2004-2017, propensity score matching identified a unilateral neck RT cohort (n = 81) and bilateral neck RT cohort (n = 81) with similar clinical and treatment characteristics. Bilateral neck RT was associated with a higher likelihood of hospitalization (33% vs 12%, p < 0.01), outpatient IV hydration (33% vs 17%, p = 0.03), and feeding tube insertion (33% vs 10%, p < 0.001); a greater number of total days of hospitalization (110 vs 47 days, p < 0.01) and outpatient IV hydration (135 vs 72 days, p = 0.02); and higher total number of supportive clinic visits (1226 vs 1053 days, p = 0.04). In the long-term, bilateral RT was associated with higher rate of feeding tube dependency at 1-year (7% vs 0%, p < 0.001).

Conclusion: Bilateral RT for tonsillar cancer resulted in significant increase in health resource utilization.
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http://dx.doi.org/10.1016/j.radonc.2020.11.028DOI Listing
March 2021

Needs assessment for a decision support tool in oral cancer requiring major resection and reconstruction: a mixed-methods study protocol.

BMJ Open 2020 11 23;10(11):e036969. Epub 2020 Nov 23.

Otolaryngology -- Head & Neck Surgery, University Health Network, Toronto, Ontario, Canada

Introduction: Advanced oral cancer and its ensuing treatment engenders significant morbidity and mortality. Patients are often elderly with significant comorbidities. Toxicities associated with surgical resection can be devastating and they are often highlighted by patients as impactful. Given the potential for suboptimal oncological and functional outcomes in this vulnerable patient population, promotion and performance of shared decision making (SDM) is crucial.Decision aids (DAs) are useful instruments for facilitating the SDM process by presenting patients with up-to-date evidence regarding risks, benefits and the possible postoperative course. Importantly, DAs also help elicit and clarify patient values and preferences. The use of DAs in cancer treatment has been shown to reduce decisional conflict and increase SDM. No DAs for oral cavity cancer have yet been developed.This study endeavours to answer the question: Is there a patient or surgeon driven need for development and implementation of a DA for adult patients considering major surgery for oral cancer?

Methods And Analysis: This study is the first step in a multiphase investigation of SDM during major head and neck surgery. It is a multi-institutional convergent parallel mixed-methods needs assessment study. Patients and surgeon dyads will be recruited to complete questionnaires related to their perception of the SDM process (nine-item Shared Decision-Making Questionnaire, SDM-Q-9 and SDM-Q-Doc) and to take part in semistructured interviews. Patients will also complete questionnaires examining decisional self-efficacy (Ottawa Decision Self-Efficacy Scale) and decisional conflict (Decisional Conflict Scale). Questionnaires will be completed at time of recruitment and will be used to assess the current level of SDM, self-efficacy and conflict in this setting. Thematic analysis will be used to analyse transcripts of interviews. Quantitative and qualitative components of the study will be integrated through triangulation, with matrix developed to promote visualisation of the data.

Ethics And Dissemination: This study has been approved by the research ethics boards of the Nova Scotia Health Authority (Halifax, Nova Scotia) and the University Health Network (Toronto, Ontario). Dissemination to clinicians will be through traditional approaches and creation of a head and neck cancer SDM website. Dissemination to patients will include a section within the website, patient advocacy groups and postings within clinical environments.
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http://dx.doi.org/10.1136/bmjopen-2020-036969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684801PMC
November 2020

Short-term and long-term unstimulated saliva flow following unilateral vs bilateral radiotherapy for oropharyngeal carcinoma.

Head Neck 2021 Feb 15;43(2):456-466. Epub 2020 Oct 15.

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

Background: We aimed to compare unstimulated saliva flow using 3-minute modified Schirmer test (MST) following bilateral vs unilateral radiotherapy (RT) in oropharyngeal carcinoma (OPC).

Methods: We reviewed OPC patients treated with definitive intensity-modulated radiation therapy (IMRT) between 2011 and 2017. MST was measured at baseline, 1-/6-/12-/24-month post-RT. MST values were compared between bilateral-RT vs unilateral-RT groups. Multivariable logistic regression analysis (MVA) identified predictors of hyposalivation (MST < 25 mm).

Results: Total 498 bilateral-RT and 36 unilateral-RT patients were eligible. The MST values at 1-/6-/12-/24-month post-RT were all significantly reduced from baseline for the entire cohort. Baseline unilateral-RT and bilateral-RT MST values (in mm) were similar (P = .2), but much higher for unilateral-RT 1-month (mean: 19.1 vs 13.0, P = .03), 6-month (20.5 vs 9.3, P < .001), 12-month (20.1 vs 11.9, P < .01), and 24-month post-RT (22.2 vs 13.9, P = .04). MVA confirmed that unilateral RT reduced the likelihood of hyposalivation vs bilateral RT (OR 2.36, P = .006).

Conclusion: Unilateral RT reduces unstimulated salivary flow in OPC patients.
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http://dx.doi.org/10.1002/hed.26496DOI Listing
February 2021

Chemoradiotherapy Using Carboplatin plus Paclitaxel versus Cisplatin plus Fluorouracil for Esophageal or Gastroesophageal Junction Cancer.

Oncology 2021 14;99(1):49-56. Epub 2020 Oct 14.

Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada,

Background: Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT.

Methods: A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis.

Results: Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (n = 67; 72%) or dCRT (n = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; p = 0.001; HR 3.1; 95% CI: 1.2-7.7) and DFS (0 vs. 41%; p = 0.004; HR 3.6; 95% CI: 1.4-8.9) on multivariable and IPTW sensitivity analyses.

Conclusions: TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.
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http://dx.doi.org/10.1159/000510446DOI Listing
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

Non-operative management for oral cavity carcinoma: Definitive radiation therapy as a potential alternative treatment approach.

Radiother Oncol 2021 01 28;154:70-75. Epub 2020 Aug 28.

Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada. Electronic address:

Purpose: To determine the outcomes of oral cavity squamous cell cancer (OSCC) patients treated with non-surgical approach i.e. definitive intensity-modulated radiation therapy (IMRT).

Methods: All OSCC patients treated radically with IMRT (without primary surgery) between 2005-2014 were reviewed in a prospectively collected database. OSCC patients treated with definitive RT received concurrent chemotherapy except for early stage patients or those who declined or were unfit for chemotherapy. The 5-year local, and regional, distant control rates, disease-free, overall, and cancer-specific survival, and late toxicity were analyzed.

Results: Among 1316 OSCC patients treated with curative-intent; 108 patients (8%) received non-operative management due to: medical inoperability (n = 14, 13%), surgical unresectability (n = 8, 7%), patient declined surgery (n = 15, 14%), attempted preservation of oral structure/function in view of required extensive surgery (n = 53, 49%) or extensive oropharyngeal involvement (n = 18, 17%). Sixty-eight (63%) were cT3-4, 38 (35%) were cN2-3, and 38 (35%) received concurrent chemotherapy. With a median follow-up of 52 months, the 5-year local, regional, distant control rate, disease-free, overall, and cancer-specific survival were 78%, 92%, 90%, 42%, 50%, and 76% respectively. Patients with cN2-3 had higher rate of 5-year distant metastasis (24% vs 3%, p = 0.001), with detrimental impact on DFS (p = 0.03) and OS (p < 0.02) on multivariable analysis. Grade ≥ 3 late toxicity was reported in 9% of patients (most common: grade 3 osteoradionecrosis in 6%).

Conclusions: Non-operative management of OSCC resulted in a meaningful rate of locoregional control, and could be an alternative curative approach when primary surgery would be declined, unsuitable or unacceptably delayed.
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http://dx.doi.org/10.1016/j.radonc.2020.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453211PMC
January 2021

Pre-treatment psychoeducational intervention and outcomes in head and neck cancer patients undergoing radiotherapy.

Support Care Cancer 2021 Mar 6;29(3):1643-1652. Epub 2020 Aug 6.

Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.

Background: To investigate the relationship between attendance to a pre-treatment psychoeducational intervention (prehab) with treatment outcomes and toxicities in patients receiving radiotherapy for head and neck cancers (HNCs).

Methods: Patients were included from prehab inception in 2013 to 2017, comparing overall survival (OS), locoregional recurrence-free survival (LRFS), and locoregional recurrence (LRR) between prehab attendees (PA) and non-attendees (PNA). Multivariable analysis was performed for OS and LRFS.

Results: Among 864 PA and 1128 PNA, 2-year OS was 88% vs 80% (p < 0.001), and LRFS was 84% vs 75% (p < 0.001). On multivariable analysis (MVA), OS and LRFS were independently and unfavourably associated with PNA. The PA cohort had a lower frequency of a "rocky treatment course" compared with the PNA cohort (52/150, 35% vs 71/150, 47%; p = 0.034).

Conclusions: Prehab at our institution is associated with improved long-term oncologic outcomes. Prospective data is needed to better understand this association.
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http://dx.doi.org/10.1007/s00520-020-05627-2DOI Listing
March 2021

Sexual satisfaction in nasopharyngeal carcinoma survivors: Rates and determinants.

Oral Oncol 2020 Jul 14;109:104865. Epub 2020 Jul 14.

Department of Radiation Oncology, Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada. Electronic address:

Objectives: Sexual health problems have been identified as an unmet need in head and neck cancer (HNC) survivors. In particular, little is known about such outcomes in survivors of nasopharyngeal cancer (NPC).

Materials And Methods: A cross-sectional study of NPC survivors with ≥4y follow-up was undertaken. Sexual satisfaction was assessed using the optional "I am satisfied with my sex life" item of the FACT-H&N. Other patient-reported outcomes measures were also captured including fatigue (FACIT-F), HNC symptom burden (MDASI-HN), emotional distress (HADS) and frontal function (FrSBE). Univariate and multivariate analyses were performed to determine factors influencing sexual satisfaction.

Results: The sexual satisfaction item was answered by 85/103 (83%) enrollees. Female (p < 0.001) and non-partnered (p = 0.0045) patients were more likely to abstain from answering. The distribution of responses were: "very much" (26%), "quite a bit" (21%), "somewhat" (20%), "a little bit" (13%) and "not at all" (20%). Sexual satisfaction was associated with multiple patient-reported measures on univariate analysis, including quality of life, fatigue, a priori selected HNC symptoms (pain, taste), emotional distress, frontal lobe function, body image and relationship strength. On multivariate analysis, only relationship strength and emotional distress remained significant. Sociodemographic factors (age, sex, marital status) and other selected orofacial toxicities were not significant.

Conclusions: Nearly half (47%) of our sample reported being in the higher satisfaction range. While reassuring in the context of comparative population level data, a number of factors including toxicity, psychological and social factors were associated with sexual satisfaction responses. Prospective evaluation of this unmet need is required.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104865DOI Listing
July 2020

Measuring financial toxicity incurred after treatment of head and neck cancer: Development and validation of the Financial Index of Toxicity questionnaire.

Cancer 2020 Sep 30;126(17):4042-4050. Epub 2020 Jun 30.

Department of Otolaryngology-Head and Neck Surgery, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

Background: The treatment of head and neck cancer (HNC) may cause significant financial toxicity to patients. Herein, the authors have presented the development and validation of the Financial Index of Toxicity (FIT) instrument.

Methods: Items were generated using literature review and were based on expert opinion. In item reduction, items with factor loadings of a magnitude <0.3 in exploratory factor analysis and inverse correlations (r < 0) in test-retest analysis were eliminated. Retained items constituted the FIT. Reliability tests included internal consistency (Cronbach α) and test-retest reliability (intraclass correlation). Validity was tested using the Spearman rho by comparing FIT scores with baseline income, posttreatment lost income, and the Financial Concerns subscale of the Social Difficulties Inventory. Responsiveness analysis compared change in income and change in FIT between 12 and 24 months.

Results: A total of 14 items were generated and subsequently reduced to 9 items comprising 3 domains identified on exploratory factor analysis: financial stress, financial strain, and lost productivity. The FIT was administered to 430 patients with HNC at 12 to 24 months after treatment. Internal consistency was good (α = .77). Test-retest reliability was satisfactory (intraclass correlation, 0.70). Concurrent validation demonstrated mild to strong correlations between the FIT and Social Difficulties Inventory Money Matters subscale (Spearman rho, 0.26-0.61; P < .05). FIT scores were found to be inversely correlated with baseline household income (Spearman rho, -0.34; P < .001) and positively correlated with lost income (Spearman rho, 0.24; P < .001). Change in income was negatively correlated with change in FIT over time (Spearman rho, -0.25; P = .04).

Conclusions: The 9-item FIT demonstrated internal and test-retest reliability as well as concurrent and construct validity. Prospective testing in patients with HNC who were treated at other facilities is needed to further establish its responsiveness and generalizability.
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http://dx.doi.org/10.1002/cncr.33032DOI Listing
September 2020

Design and Implementation of a Distant-Learning Clinical Research Mentorship Program: The Accra-Toronto Collaboration.

JCO Glob Oncol 2020 06;6:919-928

Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Purpose: For many oncology training programs in low- and middle-income countries, dedicated time for research education and mentorship of trainees is limited. Here, we report a 1-year-long collaboration between a cancer center in Canada and one in Ghana with the aim of imparting clinical research skills and mentoring the research of radiation oncology residents.

Methods: On the basis of a needs assessment conducted in Ghana, we designed a curriculum consisting of 13 weekly seminars delivered via videoconference, followed by a 1-year-long mentorship program to support research projects. The primary outcome was the feasibility of the program from seminars to manuscript preparation. We used multiple secondary outcomes to capture the learning experience with study-specific questionnaires. We evaluated critical thinking ability using the Berlin questionnaire. Funding was made available for research and travel to international conferences.

Results: Five Ghanaian trainees submitted research proposals. Nine Canadian faculty members delivered the seminars and two served as methodology mentors, and two Ghanaian faculty acted as local supervisors. Feedback questionnaires from all participants showed that they agreed strongly that they would recommend the sessions to another resident (75%), that the objectives were clear (71%), and that the topics were useful for their training (73%). At the end of the program, two Ghanaian trainees finalized their manuscripts and one was published.

Conclusion: Here, we report on the implementation of a mentorship program focused on research methods and evidence-based medicine in sub-Saharan Africa. The program was successful in the drafting and publication of abstracts and manuscripts by local trainees.
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http://dx.doi.org/10.1200/JGO.19.00240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328115PMC
June 2020

Quality of Life, Toxicity and Unmet Needs in Nasopharyngeal Cancer Survivors.

Front Oncol 2020 12;10:930. Epub 2020 Jun 12.

Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.

Concerted research efforts over the last three decades have resulted in improved survival and outcomes for patients diagnosed with nasopharyngeal carcinoma (NPC). The evolution of radiotherapy techniques has facilitated improved dose delivery to target volumes while reducing dose to the surrounding normal tissue, improving both disease control and quality of life (QoL). In parallel, clinical trials focusing on determining the optimal systemic therapy to use in conjunction with radiotherapy have been largely successful, resulting in improved locoregional, and distant control. As a consequence, neoadjuvant chemotherapy (NACT) prior to definitive chemoradiotherapy has recently emerged as the preferred standard for patients with locally advanced NPC. Two of the major challenges in interpreting toxicity and QoL data from the published literature have been the reliance on: (1) clinician rather than patient reported outcomes; and (2) reporting statistical rather than clinical meaningful differences in measures. Despite the lower rates of toxicity that have been achieved with highly conformal radiotherapy techniques, survivors remain at moderate risk of persistent and long-lasting treatment effects, and the development of late radiation toxicities such as hearing loss, cranial neuropathies and cognitive impairment many years after successful treatment can herald a significant decline in QoL. Future approaches to reduce long-term toxicity will rely on: (1) identifying individual patients most likely to benefit from NACT; (2) development of response-adapted radiation strategies following NACT; and (3) anticipated further dose reductions to organs at risk with proton and particle therapy. With increasing numbers of survivors, many in the prime of their adult life, research to identify, and strategies to address the unmet needs of NPC survivors are required. This contemporary review will summarize our current knowledge of long-term toxicity, QoL and unmet needs of this survivorship group.
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http://dx.doi.org/10.3389/fonc.2020.00930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303258PMC
June 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

Long term outcomes of stereotactic body radiation therapy for hepatocellular carcinoma without macrovascular invasion.

Eur J Cancer 2020 07 24;134:41-51. Epub 2020 May 24.

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

Background: Stereotactic Body Radiation Therapy (SBRT) is a non-invasive ablative treatment for hepatocellular carcinoma (HCC). This report aimed to address the limited availability of long-term outcomes after SBRT for HCC from North America.

Methods: Localized HCC patients without vascular invasion, who were ineligible for other liver-directed therapies and treated with SBRT at the University of Toronto or University of Michigan, were pooled to determine overall survival (OS), cumulative recurrence rates, and ≥ grade-3 toxicity. Multivariable analysis determined factors affecting OS and local recurrence rates.

Results: In 297 patients with 436 HCCs (42% > 3 cm), one-, three- and five-year OS was 77·3%, 39·0% and 24·1%, respectively. On Cox proportional hazards regression analysis, liver transplant after SBRT, Child-Pugh A liver function, alpha-fetoprotein ≤ 10 ng/ml, and Eastern Co-operative Oncology Group performance status 0 significantly improved OS (hazard ratio [HR] = 0·06, 95% confidence interval [CI- 0·02-0·25; p<0·001; HR = 0·42, 95% CI = 0·29-0·60, p<0·001; HR = 0·61, 95% CI- 0·44-0·83; p=0·002 and HR = 0·71, 95% CI = 0·51-0·97, p=0·034, respectively). Cumulative local recurrence was 6·3% (95% CI = 0.03-0.09) and 13·3% (95% CI = 0.06-0.21) at one and three years, respectively. Using Cox regression modelling, local control was significantly higher using breath-hold motion management and in HCC smaller than 3 cm (HR = 0.52, 95% CI = 0.58-0.98; p=0.042 and HR = 0.53, 95% CI = 0.26-0.98; p=0.042, respectively). Worsening of Child-Pugh score by ≥2 points three months after SBRT was seen in 15.9%.

Conclusions: SBRT confers high local control and long-term survival in a substantial proportion of HCC patients unsuitable for, or refractory to standard loco-regional treatments. Liver transplant should be considered if appropriate downsizing occurs after SBRT.
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http://dx.doi.org/10.1016/j.ejca.2020.04.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340168PMC
July 2020

Impact of cumulative cisplatin dose and adjuvant chemotherapy in locally-advanced nasopharyngeal carcinoma treated with definitive chemoradiotherapy.

Oral Oncol 2020 06 6;105:104666. Epub 2020 Apr 6.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada. Electronic address:

Background: Both adjuvant chemotherapy and higher cumulative cisplatin dose (CDDP-D) given as part of multimodality therapy for locally-advanced nasopharyngeal carcinoma (LA-NPC) have improved survival in Asian series. We evaluated their impact in a contemporary single-institution Canadian cohort of LA-NPC.

Methods: Patients with EBV-related stage II-IV LA-NPC by 7th edition TNM (TNM-7) treated with IMRT plus high-dose CDDP followed by adjuvant chemotherapy with CDDP/Carboplatin - 5-FU (maximum total/adjuvant CDDP-D = 540/240 mg/m) between 2003 and 2016 were analyzed. 5-year overall survival (OS) and recurrence-free survival (RFS) were calculated and compared using log-rank test by stage, adjuvant chemotherapy (yes/no) and total CDDP-D (>300 vs ≤300 mg/m). Multivariable analysis (MVA) was performed to identify survival predictors.

Results: A total of 312 patients were evaluated: TNM-7 stage II/III/IV = 2%/51%/47%; T4 = 36%; N3 = 17%; adjuvant chemotherapy = 83% (79% 21% CDDP/carboplatin); median total/adjuvant CDDP-D = 380/160 mg/m; median follow-up 76 years (range 06-149). 5-year OS differed by stage II-III vs IV (95% vs 80%, p < 0.001) and by total CDDP-D >300 (n = 210) vs ≤300 (n = 102) mg/m (89% vs 83%, p = 0.02). Adjuvant chemotherapy and total CDDP-D impacted on 5-year OS in stage IV but not stage II-III. 5-year RFS was higher in stage IV patients with total CDDP-D >300 vs ≤300 mg/m (74% vs 59%, p = 0.03), with a trend seen in locoregional (LRC) (91% vs 80%, p = 0.05) but not distant control (DC) (78% vs 72%, p = 0.36).

Conclusions: Adjuvant chemotherapy and total CDDP-D >300 mg/m improved OS and RFS in stage IV but not stage II-III LA-NPC, mainly due to effect on LRC rather than DC.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104666DOI Listing
June 2020

Patient-reported symptoms following diagnosis in esophagus cancer patients treated with palliative intent.

Dis Esophagus 2020 Aug;33(8)

Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, Canada.

The majority of patients with esophagus cancer have advanced-stage disease without curative options. For these patients, treatment is focused on improving symptoms and quality of life. Despite this, little work has been done to quantify symptom burden for incurable patients. We describe symptoms using the Edmonton Symptom Assessment System (ESAS) among esophagus cancer patients treated for incurable disease. This retrospective cohort study linked administrative datasets to prospectively collected ESAS data of non-curatively treated adult esophagus cancer patients diagnosed between January 1, 2009 and September 30, 2016. ESAS measures nine common cancer-related symptoms: anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and impaired well-being. Frequency of severe symptoms (score ≥ 7/10) was described by month for the 6 months from diagnosis for all patients and by treatment type (chemotherapy alone, radiotherapy alone, both chemotherapy and radiotherapy, and best supportive care). A sensitivity analysis limited to patients who survived at least 6 months was performed to assess robustness of the results to proximity to death and resulting variation in follow-up time. Among 2,989 esophagus cancer patients diagnosed during the study period and meeting inclusion criteria, 2,103 reported at least one ESAS assessment in the 6 months following diagnosis and comprised the final cohort. Patients reported a median of three (IQR 2-7) ESAS assessments in the study period. Median survival was 7.6 (IQR 4.1-13.7) months. Severe lack of appetite (53.1%), tiredness (51.1%), and impaired well-being (42.7%) were the most commonly reported symptoms. Severe symptoms persisted throughout the 6 months after the diagnosis. Subgroup analysis by treatment showed no worsening of symptoms over time in those treated by either chemotherapy alone, or both chemotherapy and radiation. Results followed a similar pattern on sensitivity analysis. Patients diagnosed with incurable esophagus cancer experience considerable symptom burden in the first 6 months after diagnosis and the frequency of severe symptoms remains high throughout this period. Patients with this disease require early palliative care and psychosocial support upon diagnosis and support throughout the course of their cancer journey.
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http://dx.doi.org/10.1093/dote/doz108DOI Listing
August 2020

Prognostic importance of radiologic extranodal extension in HPV-positive oropharyngeal carcinoma and its potential role in refining TNM-8 cN-classification.

Radiother Oncol 2020 03 8;144:13-22. Epub 2019 Nov 8.

Department of Neuroradiology and Head and Neck Imaging, Princess Margaret Cancer Centre/University of Toronto, Canada.

Purpose: This study examines outcome heterogeneity and potential to refine the TNM-8 cN-classification using radiologic extranodal extension (rENE) in a contemporary HPV-positive (HPV+) oropharyngeal carcinoma (OPC) cohort.

Methods: All HPV+ OPC treated with definitive IMRT from 2010-2015 were included. Pre-treatment CT/MR of cN+ cases were reviewed by a head-neck radiologist for rENE. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) vs rENE-negative (rENE-). Multivariable analysis (MVA) for OS confirmed the prognostic value of rENE. Refined cN-classifications for new TNM staging proposals were evaluated against TNM-8 using established criteria.

Results: A total of 517 cN+ (rENE+: 97; rENE-: 420) and 41 cN0 cases were identified. The rENE+ proportion increased with rising N-category (N1/N2/N3: 11%/19%/84%, p < 0.001). Median follow-up was 5.1 years. Compared to rENE-, rENE+ patients had a lower 5-year OS (56% vs 85%) and DFS (46% vs 83%) overall, and in N1 (OS: 57% vs 89%; DFS: 51% vs 87%) and N2 subsets (OS: 45% and 76%; DFS: 33% vs 74%) (all p < 0.001). MVA confirmed the prognostic value of rENE for OS (HR = 3.86, p < 0.001) and DFS (HR = 3.89, p < 0.001). We proposed two new cN-classifications: Schema1 reclassified any N_rENE+ as New_N3; Schema2 reclassified N1_rENE+ as New_N2 and N2_rENE+ as New_N3. Stage incorporating either Schema1 (ranked 1st) or Schema2 (ranked 2nd) cN-categories outperformed TNM-8.

Conclusion: This study confirms that rENE is prognostically important and facilitates understanding of known outcome heterogeneity within TNM-8 in HPV+ OPC patients. rENE is a promising parameter to refine the TNM-8 cN-classifications.
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http://dx.doi.org/10.1016/j.radonc.2019.10.011DOI Listing
March 2020

Re: Misuse of Quality of Life Evaluation in Oncology Studies.

Authors:
Jolie Ringash

Pract Radiat Oncol 2019 11;9(6):503

Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.prro.2019.07.016DOI Listing
November 2019

The Prevalence and Determinants of Return to Work in Nasopharyngeal Carcinoma Survivors.

Int J Radiat Oncol Biol Phys 2020 01 27;106(1):134-145. Epub 2019 Sep 27.

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

Purpose: To assess the employment status in working-age survivors of nasopharyngeal carcinoma (NPC) and explore clinical, treatment, and sociodemographic factors that may facilitate or impede successful return to work (RTW).

Methods And Materials: This Canadian study was part of a larger cross-sectional study assessing late toxicities in 107 disease-free survivors of NPC who received curative-intent intensity modulated radiation therapy ≥4 years earlier. For this substudy, eligible participants were employed at diagnosis and were of working age (<65 years) at study enrollment. Patient-reported work status (modified Radiation Therapy Oncology Group Work Status Questionnaire), quality of life (Functional Assessment of Cancer Therapy-Head and Neck questionnaire), symptom burden (MD Anderson Symptom Inventory for head and neck cancer), anxiety and depression (Hospital Anxiety and Depression Scale), neurobehavioral functioning (Frontal Systems Behavior Scale), and neurocognitive function (Montreal Cognitive Assessment) were assessed. Univariable and multivariable logistic regression models were used to explore the impact of variables on RTW status.

Results: Among 73 eligible patients, the median age was 53 years (range, 32-64) and median time from intensity modulated radiation therapy completion was 7.3 years (range, 4.2-11.1). At enrollment, 45 (62%) were working, of whom 14 (31%) had reduced work hours from diagnosis by a median of 12 h/wk (range, 4-30). Overall, mean work hours decreased from 41.6 to 37.8 h/wk (P = .005). Currently employed (vs unemployed) patients were younger (P = .017) and reported better performance status (P = .013). They had higher quality of life (P = .044), lower symptom burden (P = .03), less significant change from their baseline neurobehavioral function (P = .008), and disability (P = .0025) or private health benefits (P = .035). Anxiety, depression, occupation type, income, and Montreal Cognitive Assessment score were not significantly associated with RTW in the univariable analysis. Age, change in baseline neurobehavioral function, and having private health benefits were all independent predictors of RTW.

Conclusions: The majority of long-term survivors of NPC do RTW, although almost one-third report working fewer hours. Prospective research is needed to better understand and facilitate successful RTW in survivors of NPC.
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http://dx.doi.org/10.1016/j.ijrobp.2019.09.008DOI Listing
January 2020

Patient-Reported Symptoms for Esophageal Cancer Patients Undergoing Curative Intent Treatment.

Ann Thorac Surg 2020 02 21;109(2):367-374. Epub 2019 Sep 21.

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada. Electronic address:

Background: Esophageal cancer (EC) patients experience considerable symptom burden from treatment. This study utilized population-level patient-reported Edmonton Symptom Assessment System (ESAS) scores collected as part of standard clinical care to describe symptom trajectories and characteristics associated with severe symptoms for patients undergoing curative intent EC treatment.

Methods: EC patients treated with curative intent at regional cancer centers and affiliates between 2009 and 2016 and assessed for symptoms in the 12 months after diagnosis were included. The ESAS measures 9 common patient-reported cancer symptoms. The outcome was report of a severe symptom score (score ≥7 our of 10). Multivariable analyses were used to identify characteristics associated with severe symptom scores.

Results: A total of 1751 patients reported a median of 7 (interquartile range, 4-12) ESAS assessments in the year after diagnosis, for a total of 14,953 unique ESAS assessments included in the analysis. The most frequently reported severe symptoms were lack of appetite (n = 918, 52%), tiredness (n = 787, 45%), and poor well-being (n = 713, 41%). The highest symptom burden was within the first 5 months after diagnosis, with moderate improvement in symptom burden in the second half of the first year. Characteristics associated with severe scores for all symptoms included female sex, high comorbidity, lower socioeconomic status, urban residence, and symptom assessment temporally close to diagnosis.

Conclusions: This study demonstrates a high symptom burden for EC patients undergoing curative intent therapy. Targeted treatment of common severe symptoms and increased support for patients at risk for severe symptoms may enhance patient quality of life.
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http://dx.doi.org/10.1016/j.athoracsur.2019.08.030DOI Listing
February 2020

Treatment outcomes in oropharynx cancer patients who did not complete planned curative radiotherapy.

Oral Oncol 2019 10 11;97:124-130. Epub 2019 Sep 11.

Department of Radiation Oncology, University of Toronto, 106-150 College St, Toronto, ON M5S 3E2, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2M9, Canada. Electronic address:

Purpose: To evaluate outcomes in oropharyngeal cancer (OPC) patients who did not complete their planned curative radiation therapy (RT).

Methods: OPC Patients who received less than planned curative RT dose between 2002 and 2016 were identified for analysis. HPV status was assessed. Radiation dose was normalized for fractionation variations using biological effective doses assuming tumor α/β = 10 Gy [BED10]. Outcomes were compared using BED10. Multivariable and univariable analysis identified OS predictors.

Results: From a total of 80 patients who did not complete therapy, 64 patients were eligible for analysis. RT incompletion was due to: RT side effects (n = 23), patients' decision (n = 21), disease progression or metastases (n = 3), and other causes (n = 7). Median BED10 (Gy) was 56.2 for the HPV-positive and 58 for the HPV-negative. Three-year OS was 74% vs 13% (p < 0.001) for the HPV-positive (n = 29) and HPV-negative (n = 24), respectively. HPV-positive patients who received BED10 ≥55 had higher OS than those received BED10 <55 (94% vs 47%, p = 0.002) while no difference in OS by BED10 ≥55 vs <55 for the HPV-negative (12 vs 13%, p = NS). HPV-positive status was associated with a higher OS (HR 12.5, 95% CI, 4.54 to 33.3, p < 0.001). A total of 37 patients were available to estimate TD for local control assessment. TD (BED10) was estimated at 60.5 Gy for HPV-negative patients compared to 27.2 Gy for HPV-positive patients.

Conclusion: Overall, in patients with incomplete treatment, HPV-positive OPC patients demonstrated a better OS compared to HPV-negative patients. HPV-positive patients who received BED10 ≥55 have higher rates of OS.
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http://dx.doi.org/10.1016/j.oraloncology.2019.05.012DOI Listing
October 2019

Impact of cisplatin dose and smoking pack-years in human papillomavirus-positive oropharyngeal squamous cell carcinoma treated with chemoradiotherapy.

Eur J Cancer 2019 09 19;118:112-120. Epub 2019 Jul 19.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada. Electronic address:

Background: To evaluate the impact of cisplatin cumulative dose (CDDP-D) and smoking pack-years (PYs) on cause-specific survival (CSS) and overall survival (OS) in human papillomavirus-positive (HPV+) oropharyngeal carcinoma (OPSCC) using the eighth edition tumour-node-metastasis (TNM) staging classification (TNM8).

Patients And Methods: We reviewed patients with HPV+ OPSCC treated with high-dose CDDP and intensity-modulated radiotherapy between 2005 and 2015 at Princess Margaret Cancer Centre. CSS and OS were compared according to CDDP-D <200/=200/>200 mg/m stratified by TNM8.

Results: A total of 482 consecutive patients were evaluated (stage I/II/III: N = 189/174/119; CDDP-D <200/=200/>200 mg/m: N = 112/220/150). Median follow-up duration was 5.1 years (range: 0.6-12.8). Five-year CSS and OS differed by stages I/II/III: 96%/85%/88% (p=0.005) and 93%/84%/78% (p = 0.001), respectively. Five-year CSS by CDDP-D <200/=200/>200 mg/m was similar in stage I (98%/95%/95%, p = 0.74) and stage II (88%/84%/84%, p = 0.86) but different in stage III (76%/98%/84%, p = 0.02). Five-year OS by CDDP-D <200/=200/>200 mg/m did not differ significantly among stages. In the multivariable analysis, CDDP-D <200 mg/m did not influence CSS in the whole cohort versus = 200/>200 mg/m (p=0.53/0.79, respectively) but was associated with reduced CSS in stage III subgroup versus =200 mg/m (=200 mg/m versus < 200 mg/m hazard ratio [HR] = 0.08; 95% confidence interval [CI]: 0.01-0.67; p = 0.02). Higher smoking PYs had no effect on CSS (p = 0.34) but reduced OS in the whole cohort (HR = 1.14 [95% CI: 1.02-1.27], p=0.01).

Conclusion: CDDP-D correlated with neither survival nor disease-specific outcomes in this large and homogeneous HPV+ cohort, although reduced CSS was observed in stageIII HPV+ OPSCC receiving CDDP-D <200 mg/m. Smoking PYs were negatively associated with OS but not with CSS.
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http://dx.doi.org/10.1016/j.ejca.2019.06.019DOI Listing
September 2019

Readmission rates following esophageal cancer resection are similar at regionalized and non-regionalized centers: A population-based cohort study.

J Thorac Cardiovasc Surg 2019 09 3;158(3):934-942.e2. Epub 2019 May 3.

Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Objective: Readmission following esophagectomy affects the patient experience, has important economic implications, and can be tied to hospital reimbursement. Ontario has regionalized thoracic centers; regionalized surgery may lower the readmission rate. We investigated whether surgery at regionalized thoracic centers is associated with reduced readmission following esophageal cancer resection.

Methods: A retrospective, population-based cohort study (2002-2014) was conducted in Ontario, Canada (population 13.6 million). Adults with resected esophageal cancer were identified through the Ontario Cancer Registry. Multivariable regression was used to estimate the effect of surgery at a regionalized thoracic surgery center on readmission to any Ontario hospital within 90 days following discharge.

Results: Of 3670 patients, 27.9% were readmitted within 90 days of discharge (n = 1022). Median hospital length of stay was 12 days (interquartile range 9-20). The readmission rate at thoracic centers was similar to other hospitals (28.1% vs 27.1%, P = .57). The readmission rate did not change during the 13-year study period. Case-mix adjusted readmission rates varied from 17.6% to 35.2% even across thoracic centers and were not related to hospital volume or perioperative mortality. After adjusting for confounders, we found that surgery at a thoracic center was not significantly associated with readmission (odds ratio, 1.10; 95% confidence interval, 0.95-1.27, P = .22).

Conclusions: Surgery at a designated thoracic surgery center did not reduce the risk of 90-day readmission following esophageal cancer resection, and readmission rates varied significantly even across thoracic centers. Our results suggest that despite universal, regionalized esophageal cancer care, there appears to be a minimum readmission threshold following esophagectomy that may be clinically necessary.
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http://dx.doi.org/10.1016/j.jtcvs.2019.04.061DOI Listing
September 2019