Publications by authors named "Andrew Hope"

215 Publications

Estimating the impact of Tiny Targets in reducing the incidence of Gambian sleeping sickness in the North-west Uganda focus.

Parasit Vectors 2021 Aug 18;14(1):410. Epub 2021 Aug 18.

Liverpool School of Tropical Medicine (LSTM), Pembroke Place, Liverpool, UK.

Background: Riverine species of tsetse (Glossina) transmit Trypanosoma brucei gambiense, which causes Gambian human African trypanosomiasis (gHAT), a neglected tropical disease. Uganda aims to eliminate gHAT as a public health problem through detection and treatment of human cases and vector control. The latter is being achieved through the deployment of 'Tiny Targets', insecticide-impregnated panels of material which attract and kill tsetse. We analysed the spatial and temporal distribution of cases of gHAT in Uganda during the period 2010-2019 to assess whether Tiny Targets have had an impact on disease incidence.

Methods: To quantify the deployment of Tiny Targets, we mapped the rivers and their associated watersheds in the intervention area. We then categorised each of these on a scale of 0-3 according to whether Tiny Targets were absent (0), present only in neighbouring watersheds (1), present in the watersheds but not all neighbours (2), or present in the watershed and all neighbours (3). We overlaid all cases that were diagnosed between 2000 and 2020 and assessed whether the probability of finding cases in a watershed changed following the deployment of targets. We also estimated the number of cases averted through tsetse control.

Results: We found that following the deployment of Tiny Targets in a watershed, there were fewer cases of HAT, with a sampled error probability of 0.007. We estimate that during the intervention period 2012-2019 we should have expected 48 cases (95% confidence intervals = 40-57) compared to the 36 cases observed. The results are robust to a range of sensitivity analyses.

Conclusions: Tiny Targets have reduced the incidence of gHAT by 25% in north-western Uganda.
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http://dx.doi.org/10.1186/s13071-021-04889-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371857PMC
August 2021

Development and Validation of a Good Manufacturing Process for IL-4-Driven Expansion of Chimeric Cytokine Receptor-Expressing CAR T-Cells.

Cells 2021 Jul 15;10(7). Epub 2021 Jul 15.

Guy's Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London, Great Maze Pond, London SE1 9RT, UK.

Adoptive cancer immunotherapy using chimeric antigen receptor (CAR) engineered T-cells holds great promise, although several obstacles hinder the efficient generation of cell products under good manufacturing practice (GMP). Patients are often immune compromised, rendering it challenging to produce sufficient numbers of gene-modified cells. Manufacturing protocols are labour intensive and frequently involve one or more open processing steps, leading to increased risk of contamination. We set out to develop a simplified process to generate autologous gamma retrovirus-transduced T-cells for clinical evaluation in patients with head and neck cancer. T-cells were engineered to co-express a panErbB-specific CAR (T1E28z) and a chimeric cytokine receptor (4αβ) that permits their selective expansion in response to interleukin (IL)-4. Using peripheral blood as starting material, sterile culture procedures were conducted in gas-permeable bags under static conditions. Pre-aliquoted medium and cytokines, bespoke connector devices and sterile welding/sealing were used to maximise the use of closed manufacturing steps. Reproducible IL-4-dependent expansion and enrichment of CAR-engineered T-cells under GMP was achieved, both from patients and healthy donors. We also describe the development and approach taken to validate a panel of monitoring and critical release assays, which provide objective data on cell product quality.
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http://dx.doi.org/10.3390/cells10071797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307141PMC
July 2021

Limited-stage small cell lung cancer: Outcomes associated with prophylactic cranial irradiation over a 20-year period at the Princess Margaret Cancer Centre.

Clin Transl Radiat Oncol 2021 Sep 8;30:43-49. Epub 2021 Jul 8.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.

Background & Purpose: Prophylactic cranial irradiation (PCI) is recommended for limited-stage small-cell lung cancer (LS-SCLC) patients with good response to concurrent chemoradiation. We report our institution's 20-year experience with this patient population and associated clinical outcomes.

Materials & Methods: A retrospective cohort of consecutive LS-SCLC patients treated with curative intent chemoradiation at our institution (1997-2018) was reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method, and significant covariates determined by the Cox proportional hazards model. Covariates predictive of PCI were determined using Fisher's exact test and the Mann-Whitney test. Brain failure risk (BFR) was calculated using the cumulative incidence method treating death as a competing event. Treatment cohorts (historic vs. contemporary) were stratified by the median year of diagnosis (2005).

Results: A total of 369 patients with LS-SCLC were identified, of which 278 patients were notionally PCI eligible. PCI was given to 196 patients (71%). Younger age was associated with PCI utilization (p < 0.001). PCI utilization rates did not change between the historic and contemporary treatment era (p = 0.11), whereas magnetic resonance imaging (MRI) use at baseline and follow-up became more prevalent in the contemporary era (p = <0.001). On multivariable analysis, PCI utilization was associated with improved OS (HR 1.88, 95% CI 1.32-2.69) and decreased BFR (HR 4.66, 95% CI 2.58-8.40). Patients who had MRI follow-up had a higher incidence of BFR (HR 0.35, 95% CI 0.18-0.66) in multivariable analyses.

Conclusions: For LS-SCLC patients at our institution, PCI is more frequently utilized in younger patients, and the utilization rate did not change significantly over the past 20 years. PCI was independently associated with improved OS and lower BFR. Omission of PCI in LS-SCLC patients should not be routinely practiced in the absence of further prospective data.
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http://dx.doi.org/10.1016/j.ctro.2021.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282904PMC
September 2021

A Comparison of Hypofractionated and Twice-Daily Thoracic Irradiation in Limited-Stage Small-Cell Lung Cancer: An Overlap-Weighted Analysis.

Cancers (Basel) 2021 Jun 9;13(12). Epub 2021 Jun 9.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.

Despite evidence for the superiority of twice-daily (BID) radiotherapy schedules, their utilization in practice remains logistically challenging. Hypofractionation (HFRT) is a commonly implemented alternative. We aim to compare the outcomes and toxicities in limited-stage small-cell lung cancer (LS-SCLC) patients treated with hypofractionated versus BID schedules. A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45 Gy/30 fractions) or HFRT (40 Gy/15 fractions) schedules from 2007 to 2019. Overlap weighting using propensity scores was performed to balance observed covariates between the two radiotherapy schedule groups. Effect estimates of radiotherapy schedule on overall survival (OS), locoregional recurrence (LRR) risk, thoracic response, any ≥grade 3 (including lung, and esophageal) toxicity were determined using multivariable regression modelling. A total of 173 patients were included in the overlap-weighted analysis, with 110 patients having received BID treatment, and 63 treated by HFRT. The median follow-up was 20.4 months. Multivariable regression modelling did not reveal any significant differences in OS (hazard ratio [HR] 1.67, = 0.38), LRR risk (HR 1.48, = 0.38), thoracic response (odds ratio [OR] 0.23, = 0.21), any ≥grade 3+ toxicity (OR 1.67, = 0.33), ≥grade 3 pneumonitis (OR 1.14, = 0.84), or ≥grade 3 esophagitis (OR 1.41, = 0.62). HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.
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http://dx.doi.org/10.3390/cancers13122895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229231PMC
June 2021

Outcome and treatment toxicity in east-indian versus white-canadian patients with oral cavity cancer following postoperative (chemo-)radiotherapy delivered under similar multidisciplinary care: A propensity-matched cohort study.

Oral Oncol 2021 Sep 25;120:105419. Epub 2021 Jun 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:

Purpose: We compare clinical behaviour of East-Indians and White-Canadians with oral cavity squamous cell carcinoma (OSCC) treated at a Western institution within a uniform health care system.

Materials/methods: Newly diagnosed OSCC patients who underwent postoperative (chemo-)radiotherapy (PORT/POCRT) between 2005 and 2017 were included. Data on ethnicity and other variables were extracted from patient-questionnaires, a prospective database and supplemented by chart review. Baseline characteristics were compared between East-Indian versus White-Canadian groups. A propensity-matched (1:1 ratio) of East-Indian versus White-Canadian cohorts was generated to compare locoregional control (LRC), distant control (DC), overall survival (OS), and acute and late toxicities.

Results: A total of 53 East-Indian and 467 White-Canadian OSCC patients were identified. Compared to White-Canadians, East-Indian patients were younger, had less exposure to smoking and alcohol (p < 0.001), but more chewed betel (areca) nut /tobacco (43% vs 0.2%, p < 0.001). Buccal/retromolar-trigone/lower gingiva primaries were more common in East-Indians (49% vs 25%, p < 0.001). Median follow-up was 5.0 years. Propensity-score paired analysis revealed inferior 3-year LRC (68% vs 81%, p = 0.030), non-significantly lower OS (61% vs 75%, p = 0.257), but similar DC (81% vs 87%, p = 0.428) in East-Indian versus White-Canadian patients. Actuarial rate of toxicities was higher in East-Indians vs White-Canadians: acute toxicity at 6 weeks: 47% vs 30%, p = 0.012; chronic trismus at 5-years: 16% vs 2%, p = 0.013.

Conclusion: East-Indian OSCC patients have a greater betel nut/ chewable tobacco exposure compared to White-Canadians and a different distribution of OSCC sites. Propensity-matched cohort analysis showed lower LRC and higher toxicities in East-Indian OSCC patients, suggesting a complicated interaction between genetic/biological and life-style factors.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105419DOI Listing
September 2021

Artificial Intelligence Applications to Improve the Treatment of Locally Advanced Non-Small Cell Lung Cancers.

Cancers (Basel) 2021 May 14;13(10). Epub 2021 May 14.

Department of Radiation Oncology (Maastro) GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, 6229 ET Maastricht, The Netherlands.

Locally advanced non-small cell lung cancer patients represent around one third of newly diagnosed lung cancer patients. There remains a large unmet need to find treatment strategies that can improve the survival of these patients while minimizing therapeutical side effects. Increasing the availability of patients' data (imaging, electronic health records, patients' reported outcomes, and genomics) will enable the application of AI algorithms to improve therapy selections. In this review, we discuss how artificial intelligence (AI) can be integral to improving clinical decision support systems. To realize this, a roadmap for AI must be defined. We define six milestones involving a broad spectrum of stakeholders, from physicians to patients, that we feel are necessary for an optimal transition of AI into the clinic.
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http://dx.doi.org/10.3390/cancers13102382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156328PMC
May 2021

Prediction of Human Papillomavirus (HPV) Association of Oropharyngeal Cancer (OPC) Using Radiomics: The Impact of the Variation of CT Scanner.

Cancers (Basel) 2021 May 8;13(9). Epub 2021 May 8.

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2CI, Canada.

Studies have shown that radiomic features are sensitive to the variability of imaging parameters (e.g., scanner models), and one of the major challenges in these studies lies in improving the robustness of quantitative features against the variations in imaging datasets from multi-center studies. Here, we assess the impact of scanner choice on computed tomography (CT)-derived radiomic features to predict the association of oropharyngeal squamous cell carcinoma with human papillomavirus (HPV). This experiment was performed on CT image datasets acquired from two different scanner manufacturers. We demonstrate strong scanner dependency by developing a machine learning model to classify HPV status from radiological images. These experiments reveal the effect of scanner manufacturer on the robustness of radiomic features, and the extent of this dependency is reflected in the performance of HPV prediction models. The results of this study highlight the importance of implementing an appropriate approach to reducing the impact of imaging parameters on radiomic features and consequently on the machine learning models, without removing features which are deemed non-robust but may contain learning information.
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http://dx.doi.org/10.3390/cancers13092269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125906PMC
May 2021

Determining the Impact of Thickened Liquids on Swallowing in Patients Undergoing Irradiation for Oropharynx Cancer.

Otolaryngol Head Neck Surg 2021 May 4:1945998211010435. Epub 2021 May 4.

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

The current standard for the treatment of oropharynx cancers is radiation therapy. However, patients are frequently left with dysphagia characterized by penetration-aspiration (impaired safety) and residue (impaired efficiency). Although thickened liquids are commonly used to manage dysphagia, we lack evidence to guide the modification of liquids for clinical benefit in the head and neck cancer population. The objective of this study was to assess the impact of slightly and mildly thick liquids on penetration-aspiration and residue in 12 patients with oropharyngeal cancer who displayed penetration-aspiration on thin liquid within 3 to 6 months after completion of radiotherapy. Significantly fewer instances of penetration-aspiration were seen with slightly and mildly thick liquids as compared with thin ( < .05). No differences were found across stimuli in the frequency of residue. Patients with oropharyngeal cancers who present with post-radiation therapy dysphagia involving penetration-aspiration on thin liquids may benefit from slightly and mildly thick liquids without risk of worse residue.
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http://dx.doi.org/10.1177/01945998211010435DOI Listing
May 2021

Importance of Margins, Radiotherapy, and Systemic Therapy in Mucosal Melanoma of the Head and Neck.

Laryngoscope 2021 Oct 15;131(10):2269-2276. Epub 2021 Apr 15.

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

Objectives/hypothesis: The ideal strategy in the treatment of mucosal melanoma of the head and neck (MMHN) remains unclear. Our objective was to evaluate the importance of surgical margins, radiotherapy, and systemic therapy in MMHN.

Study Design: Retrospective Single Institutional Review.

Methods: Retrospective review of patients with MMHN treated at a tertiary care oncology center between 1999 and 2016.

Results: Seventy-six patients were included, 60 of whom were treated with curative intent. Negative or close margins compared with positive margins were associated with higher 3-year overall survival (OS) (62% vs. 29% vs. 13% P = .012), disease-free survival (33% vs. 29% vs. 4% P = .003), and distant control (48% vs. 29% vs. 22% P = .039). Cases with pre-/postoperative radiotherapy had a marginally higher locoregional control versus without (69% vs. 59%, P = .117). Immunotherapy for recurrent and/or metastatic disease was associated with an increase in 3-year OS (15% vs. 3% P = .01).

Conclusion: Achieving negative surgical margins is relevant in disease control. Despite small sample size, our data suggest that radiotherapy may enhance surgical outcomes. Immunotherapy has therapeutic benefit.

Level Of Evidence: 3 Laryngoscope, 131:2269-2276, 2021.
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http://dx.doi.org/10.1002/lary.29555DOI Listing
October 2021

Implementation of Cardiac Stereotactic Radiotherapy: From Literature to the Linac.

Cureus 2021 Feb 28;13(2):e13606. Epub 2021 Feb 28.

Radiation Medicine Program/Radiation Oncology, Princess Margaret Cancer Centre/University of Toronto, Toronto, CAN.

Stereotactic radiotherapy (SBRT) has been applied to treat cardiac arrhythmias, but our institution had not yet implemented this technique. Here, we explain how we used implementation science and knowledge translation to provide cardiac SBRT to a critically ill patient with malignancy-associated refractory ventricular tachycardia. We reviewed the critical factors that enabled the implementation of this urgent treatment, such as the context of the implementation, the characteristics of the intervention, and the stakeholders. These principles can be used by other radiation programs to implement novel treatments in urgent settings, where the gold standard process of planning and developing policies and protocols is not possible.
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http://dx.doi.org/10.7759/cureus.13606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011471PMC
February 2021

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

Br J Cancer 2021 04 10;124(9):1543-1551. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076306PMC
April 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

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 03 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

Practical Considerations for the Implementation of a Stereotactic Body Radiation Therapy Program for Oligo-Metastases.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100499. Epub 2020 Jun 18.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Purpose: With multiple phase 2 trials supporting the use of stereotactic body radiation therapy (SBRT) in oligo-metastatic disease, we evaluated practices that could inform effective implementation of an oligo-metastasis SBRT program.

Methods And Materials: Using a context-focused realist methodology, an advisory committee of interprofessional clinicians met over a series of semistructured teleconference meetings to identify challenges in implementing an oligo-metastasis SBRT program. Consideration was given to 2 models of care: a subspecialist anatomic expertise model versus a single-practitioner "quarterback" model.

Results: The advisory committee structured recommendations within a context-mechanism-outcome framework. In summary, the committee recommends that during patient workup, a single practitioner arranges the minimum number of necessary tests, with case presentation at an appropriate multidisciplinary tumor board, including careful review of all previous treatments, and enrollment on clinical trials when possible. At simulation, common patient positions and immobilization on a single simulation scan for multiple sites is recommended. During radiation planning, dose-fractionation regimens should safely facilitate cumulative dose calculations, a single isocenter should be considered for multiple close targets to reduce treatment time, and adherence to strict quality assurance protocols is strongly recommended. Treatment duration should be minimized by treating multiple sites on the same day or choosing shorter dose fractionations. Team communication, thorough documentation, and standardized nomenclature can reduce system errors. Follow-up should aim to minimize redundant clinical appointments and imaging scans. Expert radiology review may be required to interpret post-SBRT imaging.

Conclusions: These guidelines inform best clinical practices for implementing an oligo-metastasis SBRT program. Iterations using a realist approach may further expand on local contexts.
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http://dx.doi.org/10.1016/j.adro.2020.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811116PMC
June 2020

Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial.

Lancet Oncol 2021 02 12;22(2):190-197. Epub 2021 Jan 12.

Princess Margaret Cancer Centre, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, ON, Canada.

Background: A novel approach for managing malignant pleural mesothelioma, surgery for mesothelioma after radiotherapy (SMART), consisting of a short accelerated course of high-dose, hemithoracic, intensity modulated radiotherapy (IMRT) followed by extrapleural pneumonectomy was developed. The aim of this study was to evaluate the clinical feasibility of the SMART protocol.

Methods: In this single-centre, phase 2 trial, patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, with histologically proven, resectable, cT1-3N0M0 disease who had previously untreated malignant pleural mesothelioma were eligible for inclusion. Patients received 25 Gy in five daily fractions over 1 week to the entire ipsilateral hemithorax with a concomitant 5 Gy boost to high risk areas followed by extrapleural pneumonectomy within 1 week. Adjuvant chemotherapy was offered to patients with ypN+ disease on final pathology. The primary endpoint was feasibility, which was defined as the number of patients with 30-day perioperative treatment-related death (grade 5 events) or morbidity (grade 3 or 4 events). A key secondary endpoint was cumulative incidence of distant recurrence. The final analysis was done on an intention-to-treat basis (including all eligible patients). This trial is registered with ClinicalTrials.gov, NCT00797719.

Findings: Between Nov 1, 2008, and Oct 31, 2019, 102 patients were enrolled onto the trial and 96 eligible patients were treated with SMART on protocol and included in the analysis. Extrapleural pneumonectomy was done at a median of 5 days (range 2-12) after completing IMRT. 47 (49%) patients had 30-day perioperative grade 3-4 events and one (1%) patient died within 30 days perioperatively (grade 5 event; pneumonia). After a median follow-up of 46·8 months (IQR 13·4-61·2), the 5-year cumulative incidence of distant recurrence was 62 (63·3% [95% CI 52·3-74·4]). The most common first sites of recurrence were the contralateral chest (33 [46%] of 72 patients) and the peritoneal cavity (32 [44%]).

Interpretation: Results from this study suggest that extrapleural pneumonectomy after radiotherapy can be done with good early and long-term results. However, minimising grade 4 events on the protocol is technically demanding and might affect survival beyond the post-operative period.

Funding: Princess Margaret Hospital Foundation Mesothelioma Research Fund.
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http://dx.doi.org/10.1016/S1470-2045(20)30606-9DOI Listing
February 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

Validating impact of pretreatment tumor growth rate on outcome of early-stage lung cancer treated with stereotactic body radiation therapy.

Thorac Cancer 2021 01 30;12(2):201-209. Epub 2020 Nov 30.

Radiation Medicine Program, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada.

Background: To assess correlation of pretreatment specific growth rate (SGR) value of 0.43 × 10 with overall and failure-free survival of patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT).

Methods: A retrospective chart review of 160 patients with pathologically confirmed stage I NSCLC treated with SBRT between June 2010 and December 2012 in a large, tertiary cancer institute was undertaken. Both diagnostic and archived planning CT were uploaded to the treatment planning system to determine tumor volume at diagnosis (GTV1) and planning time (GTV2). The time (t) between both CTs was recorded. SGR was calculated using GTV1, GTV2, and t. The median SGR (0.43 × 10 ) from our previous data was used to group patients into low and high SGR cohorts. Log-rank test was used to compare overall (OS) and failure-free survivals (FFS) of SGR groups.

Results: The median time interval between diagnostic and planning CT scans was 87 days. The median OS was 38 and 66 months for high and low SGR cohorts, respectively (P = 0.03). The median FFS was 27 and 55 months for high and low SGR cohorts, respectively (P = 0.005). High SGR (P < 0.05), male gender (P = <0.01), and GTV2 (P = <0.05) were associated with poorer FFS.

Conclusions: High SGR was associated with poorer outcome in patients with early-stage NSCLC treated with SBRT. SGR can be used in conjunction with other well-known predictive factors to formulate a practical predictive model to identify subgroups of the patient at higher risk of recurrence after SBRT.
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http://dx.doi.org/10.1111/1759-7714.13744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812066PMC
January 2021

From multisource data to clinical decision aids in radiation oncology: The need for a clinical data science community.

Radiother Oncol 2020 12 13;153:43-54. Epub 2020 Oct 13.

Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Centre+, The Netherlands. Electronic address:

Big data are no longer an obstacle; now, by using artificial intelligence (AI), previously undiscovered knowledge can be found in massive data collections. The radiation oncology clinic daily produces a large amount of multisource data and metadata during its routine clinical and research activities. These data involve multiple stakeholders and users. Because of a lack of interoperability, most of these data remain unused, and powerful insights that could improve patient care are lost. Changing the paradigm by introducing powerful AI analytics and a common vision for empowering big data in radiation oncology is imperative. However, this can only be achieved by creating a clinical data science community in radiation oncology. In this work, we present why such a community is needed to translate multisource data into clinical decision aids.
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http://dx.doi.org/10.1016/j.radonc.2020.09.054DOI Listing
December 2020

Impact of tiny targets on Glossina fuscipes quanzensis, the primary vector of human African trypanosomiasis in the Democratic Republic of the Congo.

PLoS Negl Trop Dis 2020 10 16;14(10):e0008270. Epub 2020 Oct 16.

Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Over the past 20 years there has been a >95% reduction in the number of Gambian Human African trypanosomiasis (g-HAT) cases reported globally, largely as a result of large-scale active screening and treatment programmes. There are however still foci where the disease persists, particularly in parts of the Democratic Republic of the Congo (DRC). Additional control efforts such as tsetse control using Tiny Targets may therefore be required to achieve g-HAT elimination goals. The purpose of this study was to evaluate the impact of Tiny Targets within DRC. In 2015-2017, pre- and post-intervention tsetse abundance data were collected from 1,234 locations across three neighbouring Health Zones (Yasa Bonga, Mosango, Masi Manimba). Remotely sensed dry season data were combined with pre-intervention tsetse presence/absence data from 332 locations within a species distribution modelling framework to produce a habitat suitability map. The impact of Tiny Targets on the tsetse population was then evaluated by fitting a generalised linear mixed model to the relative fly abundance data collected from 889 post-intervention monitoring sites within Yasa Bonga, with habitat suitability, proximity to the intervention and intervention duration as covariates. Immediately following the introduction of the intervention, we observe a dramatic reduction in fly catches by > 85% (pre-intervention: 0.78 flies/trap/day, 95% CI 0.676-0.900; 3 month post-intervention: 0.11 flies/trap/day, 95% CI 0.070-0.153) which is sustained throughout the study period. Declines in catches were negatively associated with proximity to Tiny Targets, and while habitat suitability is positively associated with abundance its influence is reduced in the presence of the intervention. This study adds to the body of evidence demonstrating the impact of Tiny Targets on tsetse across a range of ecological settings, and further characterises the factors which modify its impact. The habitat suitability maps have the potential to guide the expansion of tsetse control activities in this area.
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http://dx.doi.org/10.1371/journal.pntd.0008270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608941PMC
October 2020

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

Head Neck 2021 02 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

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

Mechanisms of Impaired Swallowing on Thin Liquids Following Radiation Treatment for Oropharyngeal Cancer.

J Speech Lang Hear Res 2020 09 5;63(9):2870-2879. Epub 2020 Aug 5.

Swallowing Rehabilitation Research Laboratory, KITE, Toronto Rehabilitation Institute, University Health Network, Ontario, Canada.

Purpose Dysphagia is one of the most debilitating chronic symptoms experienced by patients who undergo radiation treatment for head and neck cancer. Despite the high prevalence of dysphagia in patients with head and neck cancer, we lack understanding of the specific changes in swallowing physiology that arise in the short-term following radiation therapy and how these changes impact the key functions of swallowing safety and efficiency. This study sought to identify pathophysiological mechanisms underlying impairments in swallowing safety and efficiency on thin liquids following (chemo)radiation for oropharyngeal cancer. Method Videofluoroscopic swallowing studies were completed in 12 male patients within 6 months following completion of (chemo)radiation and in 12 healthy male controls. To compare swallowing function and physiology between groups, we analyzed three discrete sips of 20% w/v thin liquid barium per participant. The videofluoroscopic swallowing study recordings were rated for swallowing safety, efficiency, timing parameters, and pixel-based measures of structural area or movement. Results The oropharyngeal cancer cohort displayed significantly higher frequencies of penetration-aspiration, incomplete laryngeal vestibule closure, prolonged time-to-laryngeal vestibule closure, and poor pharyngeal constriction. Incomplete or delayed laryngeal vestibule closure was associated with airway invasion, while poor pharyngeal constriction was associated with pharyngeal residue. Conclusions This study highlights the primary mechanisms behind impaired safety and efficiency of the swallow in patients following (chemo)radiation for oropharyngeal cancer.
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http://dx.doi.org/10.1044/2020_JSLHR-19-00220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890220PMC
September 2020

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

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

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

Cancer 2020 09 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

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

Correlating Dose Variables with Local Tumor Control in Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Modeling Study on 1500 Individual Treatments.

Int J Radiat Oncol Biol Phys 2020 07 15;107(3):579-586. Epub 2020 Mar 15.

Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland.

Background: Large variation regarding prescription and dose inhomogeneity exists in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. The aim of this modeling study was to identify which dose metric correlates best with local tumor control probability to make recommendations regarding SBRT prescription.

Methods And Materials: We combined 2 retrospective databases of patients with non-small cell lung cancer, yielding 1500 SBRT treatments for analysis. Three dose parameters were converted to biologically effective doses (BEDs): (1) the (near-minimum) dose prescribed to the planning target volume (PTV) periphery (yielding BED); (2) the (near-maximum) dose absorbed by 1% of the PTV (yielding BED); and (3) the average between near-minimum and near-maximum doses (yielding BED). These BED parameters were then correlated to the risk of local recurrence through Cox regression. Furthermore, BED-based prediction of local recurrence was attempted by logistic regression and fast and frugal trees. Models were compared using the Akaike information criterion.

Results: There were 1500 treatments in 1434 patients; 117 tumors recurred locally. Actuarial local control rates at 12 and 36 months were 96.8% (95% confidence interval, 95.8%-97.8%) and 89.0% (87.0%-91.1%), respectively. In univariable Cox regression, BED was the best predictor of risk of local recurrence, and a model based on BED had substantially less evidential support. In univariable logistic regression, the model based on BED also performed best. Multivariable classification using fast and frugal trees revealed BED to be the most important predictor, followed by BED.

Conclusions: BED was generally better correlated with tumor control probability than either BED or BED. Because the average between near-minimum and near-maximum doses was highly correlated to the mean gross tumor volume dose, the latter may be used as a prescription target. More emphasis could be placed on achieving sufficiently high mean doses within the gross tumor volume rather than the PTV covering dose, a concept needing further validation.
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http://dx.doi.org/10.1016/j.ijrobp.2020.03.005DOI Listing
July 2020

Alpha Test of Intelligent Machine Learning in Staging Head and Neck Cancer.

J Clin Oncol 2020 04 2;38(12):1255-1257. Epub 2020 Mar 2.

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

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http://dx.doi.org/10.1200/JCO.19.03309DOI Listing
April 2020
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