Barriers and Unequal Access to Timely Molecular Testing Results: Addressing the Inequities in Cancer Care Delays across Canada.

Genomic medicine is a powerful tool to improve diagnosis and outcomes for cancer patients by facilitating the delivery of the right drug at the right dose at the right time for the right patient. In 2023, a Canadian conference brought together leaders with expertise in different tumor types. The objective was to identify challenges and opportunities for change in terms of equitable and timely access to biomarker testing and reporting at the education, delivery, laboratory, patient, and health-system levels in Canada. Challenges identified included: limited patient and clinician awareness of genomic medicine options with need for formal education strategies; failure by clinicians to discuss genomic medicine with patients; delays in or no access to hereditary testing; lack of timely reporting of results; intra- and inter-provincial disparities in access; lack of funding for patients to access testing and for laboratories to provide testing; lack of standardized testing; and impact of social determinants of health. Canada must standardize its approach to biomarker testing across the country, with a view to addressing current inequities, and prioritize access to advanced molecular testing to ensure systems are in place to quickly bring innovation and evidence-based treatments to Canadian cancer patients, regardless of their place of residence or socioeconomic status.

Breaking Down Barriers to Detection and Care in Early-Age-Onset Colorectal Cancer in Canada.

The second Early-Age-Onset Colorectal Cancer Symposium, convened in October 2022, sought solutions to the barriers to early detection and care for colorectal cancer in Canada. This meeting built on a previous symposium, held in 2021 and reported in this journal. Early-age-onset colorectal cancer (EAOCRC) affects increasing numbers of people under the age of 50 in Canada and throughout the developed world. Two main themes emerged from the meeting: the importance of timely detection, and the need for a tailored approach to the care of EAOCRC. Early detection is crucial, especially in light of the later stage at diagnosis and unique tumour characteristics. Symposium participants were strongly in favour of reducing the age of eligibility for screening from 50 to 45, and promoting the development of non-invasive screening techniques such as testing for circulating tumour DNA and biomarkers. Leading approaches to care were described and discussed, which meet the unique treatment needs of younger CRC patients. Multidisciplinary practices within and outside Canada address such factors as fertility, family roles, education, careers and financial responsibilities. These models can be applied in treatment centres across the country.

Mortality among patients with diffuse large B-cell lymphoma and mental disorders: a population-based study.

BACKGROUND: Mental disorders have been reported in patients with diffuse large B-cell lymphoma (DLBCL), but studies examining their association with mortality are lacking. METHODS: We conducted a population-based study using linked administrative health-care databases from Ontario, Canada. All patients with DLBCL 18 years of age or older treated with rituximab-based therapy between January 1, 2005, and December 31, 2017, were identified and followed until March 1, 2020. Mental disorders were defined as either preexisting or postdiagnosis (after lymphoma treatment initiation). Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) between mental disorders and 1-year and all-cause mortality while controlling for covariates. RESULTS: We identified 10 299 patients with DLBCL. The median age of the cohort was 67 years; 46% of patients were female, and 28% had a preexisting mental disorder. At 1-year follow-up, 892 (9%) had a postdiagnosis mental disorder, and a total of 2008 (20%) patients died. Preexisting mental disorders were not associated with 1-year mortality (adjusted HR = 1.06, 95% confidence interval [CI] = 0.96 to 1.17, P = .25), but postdiagnosis disorders were (adjusted HR = 1.51, 95% CI = 1.26 to 1.82, P = .0001). During a median follow-up of 5.2 years, 2111 (22%) patients had a postdiagnosis mental disorder, and 4084 (40%) patients died. Both preexisting and postdiagnosis mental disorders were associated with worse all-cause mortality (preexisting adjusted HR = 1.12, 95% CI = 1.04 to 1.20, P = .0024; postdiagnosis adjusted HR = 1.63, 95% CI = 1.49 to 1.79, P < .0001). CONCLUSIONS: Patients with DLBCL and mental disorders had worse short-term and long-term mortality, particularly those with postdiagnosis mental disorders. Further studies are needed to examine mental health service utilization and factors mediating the relationship between mental disorders and inferior mortality.

Erythroblastic oncogene B-2 status and intracranial metastatic disease in patients with gastrointestinal cancer: a systematic review.

PURPOSE: The incidence of intracranial metastatic disease (IMD) in patients with gastrointestinal (GI) cancers is rising. Expression of the erythroblastic oncogene B-2 (ERBB2) is associated with an in increased risk of IMD in patients with breast cancer. The implications of ERBB2 expression for IMD risk in patients with GI cancers is less clear. The objective of this systematic review was to determine the incidence of IMD and OS in patients with ERBB2+ gastrointestinal cancers. METHODS: A literature search of MEDLINE, EMBASE, CENTRAL, and grey literature sources was conducted from date of database inception to July 2021. Included studies reported outcomes on patients with IMD secondary to ERBB2 GI cancers. RESULTS: Fourteen cohort studies met inclusion criteria, of which thirteen were retrospective. Eleven studies reported on gastric, esophageal, or gastroesophageal junction cancers. Three studies directly compared incidence of IMD based on ERBB2 status and among these, ERBB2+ patients had a higher incidence of IMD. One study indicated that ERBB2+ patients had significantly longer OS from the times of primary cancer (P = .015) and IMD diagnosis (P = .01), compared with patients with ERBB2- disease. CONCLUSIONS: In this systematic review, patients with ERBB2+ GI cancer were more likely to develop IMD. Future study is required on the prognostic and predictive value of ERBB2 status in patients with GI cancers.

Comparison of Use of Neoadjuvant Systemic Treatment for Breast Cancer and Short-term Outcomes Before vs During the COVID-19 Era in Ontario, Canada.

Importance: In response to an increase in COVID-19 infection rates in Ontario, several systemic treatment (ST) regimens delivered in the adjuvant setting for breast cancer were temporarily permitted for neoadjuvant-intent to defer nonurgent breast cancer surgical procedures. Objective: To examine the use and compare short-term outcomes of neoadjuvant-intent vs adjuvant ST in the COVID-19 era compared with the pre-COVID-19 era. Design, Setting, and Participants: This was a retrospective population-based cohort study in Ontario, Canada. Patients with cancer starting selected ST regimens in the COVID-19 era (March 11, 2020, to September 30, 2020) were compared to those in the pre-COVID-19 era (March 11, 2019, to March 10, 2020). Patients were diagnosed with breast cancer within 6 months of starting systemic therapy. Main Outcomes and Measures: Estimates were calculated for the use of neoadjuvant vs adjuvant ST, the likelihood of receiving a surgical procedure, the rate of emergency department visits, hospital admissions, COVID-19 infections, and all-cause mortality between treatment groups over time. Results: Among a total of 10 920 patients included, 7990 (73.2%) started treatment in the pre-COVID-19 era and 7344 (67.3%) received adjuvant ST; the mean (SD) age was 61.6 (13.1) years. Neoadjuvant-intent ST was more common in the COVID-19 era (1404 of 2930 patients [47.9%]) than the pre-COVID-19 era (2172 of 7990 patients [27.2%]), with an odds ratio of 2.46 (95% CI, 2.26-2.69; P < .001). This trend was consistent across a range of ST regimens, but differed according to patient age and geography. The likelihood of receiving surgery following neoadjuvant-intent chemotherapy was similar in the COVID-19 era compared with the pre-COVID-19 era (log-rank P = .06). However, patients with breast cancer receiving neoadjuvant-intent hormonal therapy were significantly more likely to receive surgery in the COVID-19 era (log-rank P < .001). After adjustment, there were no significant changes in the rate of emergency department visits over time between patients receiving neoadjuvant ST, adjuvant ST, or ST only during the ST treatment period or postoperative period. Hospital admissions decreased in the COVID-19 era for patients who received neoadjuvant ST compared with adjuvant ST or ST alone (P for interaction = .01 for both) in either setting. Conclusions and Relevance: In this cohort study, patients were more likely to start neoadjuvant ST in the COVID-19 era, which varied across the province and by indication. There was limited evidence to suggest any substantial impact on short-term outcomes.

Regional Therapy for Colorectal Cancer Liver Metastases: Which Modality and When?

For patients with unresectable colorectal liver metastases (uCRLM), regional therapies leverage the unique, dual blood supply to the liver; the hepatic artery is the main blood supply for liver tumors, whereas the portal vein supplies most normal hepatic parenchyma. Infusion of cancer therapies via the hepatic artery allows selective delivery to the tumors with relative sparing of normal liver tissue and little extrahepatic exposure, thus limiting systemic side effects. There is a paucity of randomized controlled trial evidence to inform the optimal integration of regional therapies into the management of CRLM. Hepatic arterial infusion pump (HAIP) chemotherapy has a potential survival benefit when used in the adjuvant setting after resection of CRLM. HAIP chemotherapy can be safely given with contemporary systemic therapies and is associated with a high objective response and rate of conversion to resectability in patients with uCRLM. Drug-eluting beads coated with irinotecan transarterial chemoembolization is associated with high objective response rates within the liver and has a well-established safety profile in patients with uCRLM. Transarterial radioembolization achieves high rates of response within the liver but is not associated with improvements in overall survival or quality of life in the first- or second-line setting for uCRLM. The best treatment approach is the one that most aligns with a given patients' values, preferences, and philosophy of care. In the first-line setting, HAIP could be offered to motivated patients who hope to achieve conversion to resectability. After progression on chemotherapy, HAIP, transarterial chemoembolization, and transarterial radioembolization are valuable treatment options to consider for patients with liver-limited or liver-predominant CRLM who seek to optimize response rates and regional control.

Real-World Cost-Effectiveness of First-Line Gemcitabine Plus Nab-Paclitaxel vs FOLFIRINOX in Patients With Advanced Pancreatic Cancer.

BACKGROUND: There are no randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and fluorouracil, folinic acid, irinotecan, oxaliplatin (FOLFIRINOX) for advanced pancreatic cancer (APC). Although it is well known that RCT-based efficacy often does not translate to real-world effectiveness, there is limited literature investigating comparative cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC. We aimed to examine the real-world cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC in Ontario, Canada. METHODS: This study compared patients treated with first-line Gem-Nab or FOLFIRINOX for APC in Ontario from April 2015 to March 2019. Patients were linked to administrative databases. Using propensity scores and a stabilizing weights method, an inverse probability of treatment weighted cohort was developed. Mean survival and total costs were calculated over a 5-year time horizon, adjusted for censoring, and discounted at 1.5%. Incremental cost-effectiveness ratio and net monetary benefit were computed to estimate cost-effectiveness from the public health-care payer's perspective. Sensitivity analysis was conducted using the propensity score matching method. RESULTS: A total of 1988 patients were identified (Gem-Nab: n = 928; FOLFIRINOX: n = 1060). Mean survival was lower for patients in the Gem-Nab than the FOLFIRINOX group (0.98 vs 1.26 life-years; incremental effectiveness = -0.28 life-years [95% confidence interval = -0.47 to -0.13]). Patients in the Gem-Nab group incurred greater mean 5-year total costs (Gem-Nab: $103 884; FOLFIRINOX: $101 518). Key cost contributors include ambulatory cancer care, acute inpatient hospitalization, and systemic therapy drug acquisition. Gem-Nab was dominated by FOLFIRINOX, as it was less effective and more costly. Results from the sensitivity analysis were similar. CONCLUSIONS: Gem-Nab is likely more costly and less effective than FOLFIRINOX and therefore not considered cost-effective at commonly accepted willingness-to-pay thresholds.

An Evaluation of Sex- and Gender-Based Analyses in Oncology Clinical Trials.

BACKGROUND: The objective of this study was to evaluate whether sex- and gender-based analyses and proper sex and gender terminology were used in oncology trials leading to regulatory drug approval. METHODS: The Food and Drug Administration (FDA) Hematology/Oncology Approvals and Safety Notifications page was used to identify all anticancer therapies that received FDA approval between 2012 and 2019. The trials used to support FDA drug approval were collected along with all available supplemental tables and study protocols. Documents were reviewed to determine if there was a plan to analyze results according to sex and gender and to determine if consistent sex and gender terminology were used. RESULTS: We identified 128 randomized, controlled trials corresponding to a cancer medicine, which received FDA approval. No study specified how sex and gender were collected or analyzed. No study reported any information on the gender of participants. Sex and gender terminology were used inconsistently at least once in 76% (97 of 128) of studies. Among the 102 trials for nonsex-specific cancer sites, 89% (91 of 102) presented disaggregated survival outcome data by sex. No study presented disaggregated toxicity data by sex or gender. CONCLUSION: The majority of pivotal clinical trials in oncology fail to account for the important distinction between sex and gender and conflate sex and gender terminology. More rigor in designing clinical trials to include sex- and gender-based analyses and more care in using sex and gender terms in the cancer literature are needed. These efforts are essential to improve the reproducibility, generalizability, and inclusiveness of cancer research.

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer.

Importance: Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with single-agent gemcitabine in clinical trials. Objective: To describe changes in the survival of patients with advanced pancreatic cancer associated with sequential drug-funding approvals and to determine if there exist distinct patient populations for whom GEMNAB and FOLFIRINOX are associated with survival benefit. Design, Setting, and Participants: This population-based, retrospective cohort study examined all incident cases of advanced pancreatic cancer treated with first-line chemotherapy in Ontario, Canada (2008-2018) that were identified from the Cancer Care Ontario (Ontario Health) New Drug Funding Program database. Statistical analysis was performed from October 2020 to January 2021. Exposures: First-line chemotherapy for advanced pancreatic cancer. Main Outcomes and Measures: The main outcomes were the proportion of patients treated with each chemotherapy regimen over time and overall survival for each regimen. Cox proportional hazards regression models were used to compare overall survival between treatment regimens after adjustment for confounding variables, inverse probability of treatment weighting, and matching. Results: From 2008 to 2018, 5465 patients with advanced pancreatic cancer were treated with first-line chemotherapy in Ontario, Canada. The median (range) age of patients was 66.9 (27.8-93.4) years; 2447 (45%) were female; 878 (16%) had prior pancreatic resection, and 328 (6%) had prior adjuvant gemcitabine. During the time period when only gemcitabine and FOLFIRINOX were funded (2011-2015), 49% (929 of 1887) received FOLFIRINOX. When GEMNAB was subsequently funded (2015-2018), 9% (206 of 2347) received gemcitabine, 44% (1034 of 2347) received FOLFIRINOX, and 47% (1107 of 2347) received GEMNAB. The median overall survival increased from 5.6 months (95% CI, 5.1-6.0 months) in 2008 to 2011 to 6.9 months (95% CI, 6.5-7.4 months) in 2011 to 2015 to 7.6 months (95% CI, 7.1-8.0 months) in 2015 to 2018. Patients receiving FOLFIRINOX were younger and healthier than patients receiving GEMNAB. After adjustment and weighting, FOLFIRINOX was associated with better overall survival than GEMNAB (hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]). In analyses comparing patients treated with GEMNAB and gemcitabine, GEMNAB was associated with better overall survival (HR, 0.86 [95% CI, 0.78-0.94]). Conclusions and Relevance: This cohort study of patients with advanced pancreatic cancer receiving first-line palliative chemotherapy within a universal health care system found that drug funding decisions were associated with increased uptake of new treatment options over time and improved survival. Both FOLFIRINOX and GEMNAB were associated with survival benefits in distinct patient populations.

Mental Health Resource Use Among Patients Undergoing Curative Intent Treatment for Bladder Cancer.

BACKGROUND: Patients with bladder cancer may experience mental health distress. Mental health-care service (MHS) use can quantify the magnitude of the problem. METHODS: The Ontario Cancer Registry was used to identify all patients with bladder cancer treated with curative-intent cystectomy or radiotherapy in Ontario, Canada (2004-2013). Population-level databases were used to identify MHS use (visits to general practitioner, psychiatrist, emergency department, or hospitalization). Generalized estimating equations were used to compare rates of MHS use. Baseline, peritreatment, and posttreatment MHS use were defined as visits from 2 years to 3 months before, 3 months before to 3 months after, and from 3 months after to 2 years after start of treatment, respectively. RESULTS: From 2004 to 2013, 4296 patients underwent cystectomy (n = 3332) or curative-intent radiotherapy (n = 964). Compared with baseline, the rate of MHS use was higher in the peritreatment (adjusted rate ratio [aRR] = 1.64, 95% confidence interval [CI] = 1.48 to 1.82) and posttreatment periods (aRR = 1.45, 95% CI =1.30 to 1.63). By 2 years posttreatment, 24.6% (95% CI = 23.4% to 25.9%) of all patients had MHS use. Patients with baseline MHS use had substantially higher MHS use in the peritreatment (aRR = 5.77, 95% CI = 4.86 to 6.86) and posttreatment periods (aRR = 4.58, 95% CI = 3.78 to 5.55). Female patients had higher use MHS use overall, but males had a higher incremental increase in the posttreatment period compared with baseline (2-sided Pinteraction = .02). Male patients had a statistically significant increase in MHS use following surgery or radiotherapy, whereas female patients only had an increase following surgery. CONCLUSIONS: MHS use is common among patients undergoing treatment for bladder cancer, particularly in the peritreatment period. Screening for mental health concerns in this population is warranted.

Long-Term Mental Health Service Utilization Among Survivors of Testicular Cancer: A Population-Based Cohort Study.

PURPOSE: Testicular cancer survivors may experience mental illness as a consequence of their cancer diagnosis and treatment. METHODS: All incident cases of testicular cancer treated with orchiectomy in Ontario, Canada (2000-2010), were identified using the Ontario Cancer Registry. Cases were matched to controls in a 1:5 ratio on age and geography. Population-level databases were used to identify mental health service use episodes; outpatient use included visits to a general practitioner for a mental health concern or any visit to a psychiatrist. Negative binomial regression modeling was used to estimate the rate of mental health service use in the pretreatment (2 years prior until 1 month before orchiectomy), peritreatment (1 month before until 1 month after orchiectomy), and post-treatment periods (1 month after orchiectomy until end of follow-up). Rate ratios (RR) comparing cases with controls in the peri- and post-treatment periods were adjusted for baseline mental health service use. RESULTS: Two thousand six hundred nineteen cases of testicular cancer were matched to 13,095 controls. There was no baseline difference in the rate of mental health service use. Cases were significantly more likely than controls to have an outpatient visit for a mental health concern in the peritreatment (adjusted RR [aRR], 2.45; 95% CI, 2.06 to 2.92) and post-treatment periods (aRR, 1.30; 95% CI, 1.12 to 1.52). The difference in mental health service use persisted over a median follow-up of 12 years. In the postorchiectomy period, cases with baseline mental health service use were those most likely to use mental health services (aRR, 5.64; 95% CI, 4.64 to 6.85). CONCLUSION: Testicular cancer survivors use mental health services more often than healthy controls. Survivorship care plans that address the long-term mental healthcare needs of this population are needed.

Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma: Use, Risk Factors, and Outcomes in a Canadian Population.

BACKGROUND: Previous studies have reported that 30% to 40% of patients with squamous cell carcinoma of the anus will require salvage abdominoperineal resection after chemoradiotherapy. OBJECTIVE: The purpose of this study was to identify the use, risk factors, and impact on survival of salvage abdominal perineal resection for squamous cell carcinoma of the anus. DESIGN: This was a retrospective, population-based cohort study. SETTINGS: Patients treated in Ontario, Canada through a single-payer universal healthcare system, were included. PATIENTS: Patients included all incident cases of squamous cell anal cancer who underwent curative intent radiotherapy from 2007 to 2015. MAIN OUTCOME MEASURES: Risk of salvage abdominoperineal resection, factors associated with salvage abdominoperineal resection, and survival were measured. RESULTS: A total of 1125 patients were treated with curative intent radiotherapy for squamous cell cancer of the anus. Within this cohort, salvage surgery was performed in 8% (93/1125), whereas 14% (156/1125) required a permanent colostomy. In log-binomial regression, younger age was associated with salvage surgery, whereas sex, cancer stage, socioeconomic status, and HIV were not. There was a suggested lower risk of salvage surgery in those who completed chemoradiation (relative risk = 0.67 (95% CI, 0.43-1.03)). Crude 5-year overall survival rate was 73% (95% CI, 70%-76%) in those not requiring salvage surgery and 48% (95% CI, 37%-58%) in those who did. In Cox models, mortality was higher in patients requiring salvage surgery compared with those who did not (adjusted HR = 2.20 (95% CI, 1.65-2.94), whereas improved survival was seen in those who completed chemoradiation (HR = 0.65 (95% CI, 0.42-0.82)) LIMITATIONS:: The study was limited by its potential residual confounding by indication for salvage surgery. CONCLUSIONS: In this large, contemporary cohort of patients with squamous cell carcinoma of the anus, the proportion of patients undergoing salvage surgery was considerably lower than previous reports. Younger age was associated with salvage surgery, and there was a suggestion of lower risk of salvage surgery with completion of chemoradiation. Patients requiring salvage surgery had poor 5-year overall survival. See Video Abstract at http://links.lww.com/DCR/B205. RAP DE RESCATE PARA EL CARCINOMA ANAL DE CéLULAS ESCAMOSAS: USO, FACTORES DE RIESGO Y RESULTADOS EN UNA POBLACIóN CANADIENSE: Estudios anteriores han reportado que 30-40% de los pacientes con carcinoma de células escamosas del ano requerirán una resección abdominoperineal de rescate después de la quimiorradioterapia.Identificar la utilización, los factores de riesgo y el impacto en la supervivencia de la resección abdominoperineal de rescate para el carcinoma de células escamosas del ano.Estudio de cohorte retrospectivo, basado en la población.Todos los casos incidentes de cáncer anal de células escamosas que se sometieron a radioterapia con fines curativos de 2007 a 2015.Pacientes tratados en Ontario, Canadá, un sistema de salud universal de un solo pagador.Riesgo de resección abdominoperineal de rescate, factores asociados con la resección abdominoperineal de rescate y la supervivencia.1125 pacientes fueron tratados con radioterapia de intención curativa para el cáncer de células escamosas del ano. Dentro de esta cohorte, la cirugía de rescate se realizó en el 8% (93/1125), mientras que el 14% (156/1125) requirió una colostomía permanente. En la regresión log-binomial, la edad más joven se asoció con la cirugía de rescate, mientras que el sexo, la etapa del cáncer, el estado socioeconómico y el VIH no. Se sugirió un menor riesgo de cirugía de rescate en aquellos que completaron la quimiorradiación (RR 0,67; IC del 95%: 0,43 a 1,03). La tasa de supervivencia global bruta a 5 años fue del 73% (IC del 95%: 70-76%) en aquellos que no requirieron cirugía de rescate y del 48% (IC del 95%: 37-58%) en los que sí lo requirieron. En los modelos de Cox, la mortalidad fue mayor en los pacientes que requirieron cirugía de rescate en comparación con aquellos que no lo requirieron (HR ajustado 2.20, IC 95%: 1.65 - 2.94), mientras que se observó una mejor supervivencia en aquellos que completaron la quimiorradiación (HR 0.65, IC 95% 0.42 - 0,82).Posible confusión residual por indicación de cirugía de rescate.En esta gran cohorte contemporánea de pacientes con carcinoma de células escamosas del ano, la proporción de pacientes sometidos a cirugía de rescate fue considerablemente menor que los informes anteriores. La edad más temprana se asoció con la cirugía de rescate, y se sugirió un menor riesgo de cirugía de rescate con la finalización de la quimiorradiación. Los pacientes que requirieron cirugía de rescate tuvieron una deficiente supervivencia general de 5 años. Consulte Video Resumen en http://links.lww.com/DCR/B205. (Traducción-Dr Gonzalo Hagerman).

Factors Associated With Chemoradiation Therapy Interruption and Noncompletion Among Patients With Squamous Cell Anal Carcinoma.

Importance: Definitive chemoradiation for anal cancer is effective but may be associated with toxic effects, and some patients may not be able to complete the planned treatment. Identifying factors associated with treatment interruption and noncompletion is important to target quality improvement efforts. Objective: To identify rates of chemoradiation treatment interruption or noncompletion and factors associated with this among patients with anal cancer treated in routine clinical practice. Design, Setting, and Participants: In this population-based, retrospective cohort study, the Ontario Cancer Registry was used to identify all incident cases of squamous cell anal cancer treated with curative-intent radiation from 2007 to 2015 in Ontario, Canada. Final analysis of data was performed on August 9, 2019. Exposures: Curative-intent radiation therapy. Main Outcomes and Measures: Treatment interruption was defined as more than 7 days between fractions of radiation. Radiation completion was defined as receipt of 45 Gy or more and 25 fractions of radiation. Chemoradiation completion was defined as radiation completion and 2 doses of combination chemotherapy. Associations between patient factors and treatment interruption and noncompletion were estimated with log-binomial models. Cox proportional hazard models were used to estimate the association of treatment interruption or noncompletion with all-cause death, cancer-specific death, and the combined outcome of colostomy or death. Results: Overall, 1125 patients with stage I-III anal cancer were treated with curative-intent radiation. Treatment interruptions occurred in 262 (23%). Radiation and chemoradiation noncompletion occurred in 199 (18%) and 280 (25%), respectively. No associations were found to correlate with an increased risk of treatment interruption. Patients older than 70 years were less likely to complete chemoradiation (risk ratio [RR], 0.60; 95% CI, 0.52-0.70), compared with those younger than 50 years. Patients with a higher number of comorbidities were also less likely to complete chemoradiation (RR, 0.70; 95% CI, 0.51-0.95). Patients who did not complete chemoradiation had a higher risk of requiring salvage abdominoperineal resection (RR, 1.54; 95% CI, 1.03, 2.31), overall death (hazard ratio [HR], 1.54; 95% CI, 1.23-1.92), cancer-specific death (HR, 1.59; 95% CI, 1.14-2.22), and colostomy or death (HR, 1.80; 95% CI: 1.10-2.93). Treatment interruptions longer than 7 days were not associated with death. Conclusions and Relevance: Many patients undergoing curative-intent chemoradiation for anal cancer experienced treatment interruption or noncompletion. Quality improvement initiatives to optimize treatment continuity and completion are needed.

Anxiety, Depression and Quality of Life Improve After One Month and Three Months of Home Parenteral Nutrition: A Pilot Study in a Canadian Population.

BACKGROUND: Patients receiving home parenteral nutrition (HPN) have a reduced quality of life (QoL), but it is unknown if this is associated with psychiatric comorbidities such as anxiety or depression. AIM: The aim of this study was to assess anxiety, depression and QoL in patients transitioning from hospital to HPN. METHODS: We conducted a prospective study in adult patients receiving parenteral nutrition (PN) during transition from hospital to home. We assessed anxiety and depression (Hospital Anxiety and Depression Scale; HADS), health-related quality of life (HRQoL; SF-36) and health status (EQ-5D) before discharge and again later at one and three months after HPN was started. RESULTS: Of the 29 patients, 15 had an underlying malignancy. At baseline, 93% of patients with malignancy had anxiety or depression (HADS A and/or HADS D >7) or both, while of the patients without malignancy, 60% had anxiety, and 40% had depression. Questionnaires were completed by 21 patients at one month and by 15 at three months. Anxiety and depression scores decreased significantly after one month of HPN (mean difference [MD] anxiety: 4.3; 95% CI, 1.2-7.5, P = 0.004; MD depression: 4.0; 95% CI, 1.5-6.5, P = 0.001), and the decrease persisted at three months (MD anxiety: 35; 95% CI, 0.35-6.6, P = 0.02; MD depression: 2.5; 95% CI, 0.06-5.0, P = 0.04). Overall, patients reported an improvement in HRQoL (SF-36) after one month of HPN, and this improvement was maintained at three months in those patients who survived. CONCLUSION: Home parenteral nutrition is associated with improvements in anxiety, depression and HRQoL at one month and three months after discharge from hospital. The improvements in Qol, anxiety and depression seem greater in patients with underlying malignancy.

The Value of Progression-Free Survival as a Treatment End Point Among Patients With Advanced Cancer: A Systematic Review and Qualitative Assessment of the Literature.

Importance: It is unclear whether patients with advanced cancer value surrogate end points, particularly progression-free survival (PFS). Despite this uncertainty, surrogate end points form the basis of regulatory approval for the majority of new cancer treatments. Objective: To summarize and qualitatively assess studies evaluating whether patients with advanced cancer understand and value PFS. Evidence Review: MEDLINE, Embase, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature databases were searched from database inception to November 12, 2018. Articles eligible for inclusion investigated patient understanding, preference, or perceived value of disease progression or PFS in the setting of advanced cancer. Three authors independently reviewed and extracted data from all studies eligible for inclusion. Findings: In total, 17 studies representing 3646 patients were included. Of these studies, 15 specifically aimed to assess patients' values toward, and their willingness to trade off toxic effects for gains or losses in the end point of PFS. All studies examined used widely disparate definitions when attempting to describe the meaning of PFS to patients. Ten studies specifically presented patients with the term progression-free survival as an attribute choice. In the words used to define the attribute of PFS, 6 studies used the term survival. Five studies clarified that PFS may not translate into better overall survival, and 5 studies explained that improvements in PFS may not reflect how well the patient may feel. No study clarified that a PFS event could represent either progression or death, and no study defined for the patient what constituted progression. The studies assessed herein underrepresented ethnic and racial minorities (mean percentage of white patients, 88%; range, 77%-96%). Values and preferences may vary across cultural backgrounds given that different relative preferences were assigned to cost and efficacy outcomes in North American vs Asian studies, although only a few studies were evaluated. Conclusions and Relevance: The existing literature evaluating patients' understanding, preferences, and values toward the end point of PFS was severely limited by the heterogeneity of methods, attribute selection, and descriptions used to define PFS to patients. High-quality studies are needed that clearly define PFS for patients and that systematically document their understanding of the term. Only then can it be assessed whether PFS is an end point of value to patients with advanced cancer.

Medical oncology job satisfaction: Results of a global survey.

BACKGROUND: While physician burnout is increasingly recognized, little is known about medical oncologist job satisfaction, and the factors associated with low satisfaction. Here, we report the results of an international survey of medical oncologists. METHODS: An online survey was distributed using a modified snowball methodology via national oncology societies to chemotherapy-prescribing physicians in 65 countries. Oncologist job satisfaction was assessed by asking, "On a scale of 1-10, how would you rate your satisfaction as an oncologist? 1 = unsatisfying, 10 = satisfying." Low, moderate and high job satisfaction was defined as scores of 1-6, 7-8, and 9-10, respectively. RESULTS: 1,115 physicians from 42 countries completed the survey. Overall job satisfaction rates were 20% (222/1,115), 51% (573/1,115), and 29% (320/1,115) for low-, moderate-, and high-satisfaction, respectively. Respondents with low job satisfaction were younger (P = 0.001) and had fewer years in clinical practice (P = 0.013) compared to those with high satisfaction. Increasing hours worked by per week (p = 0.042), decreasing annual weeks of paid vacation (P = 0.007), being on-call every night (P = 0.016), higher clinic volumes (P = 0.004) and lack of access to on-site radiotherapy (P = 0.049), palliative care (P = 0.005), and chemotherapy pharmacists (P = 0.033) were associated with low-job satisfaction. Respondents with low-job satisfaction were less likely to discuss prognosis with their patients compared to those with moderate or high job satisfaction (median 45% of patients v 65% v 75%, P < 0.001). CONCLUSIONS: Globally, 1 in 5 medical oncologists report low job satisfaction. The main correlates of job satisfaction are related to system-level pressures resulting in less time for quality patient care and personal resilience. Improving oncologist job satisfaction will require new approaches to models of care delivery.

Neurotoxicity Outcomes in a Population-based Cohort of Elderly Patients Treated With Adjuvant Oxaliplatin for Colorectal Cancer.

BACKGROUND: The addition of oxaliplatin to adjuvant treatment regimens for colorectal cancer has been shown to improve overall survival at the expense of increased toxicity. The incidence and severity of toxicity might be greater among older patients who might also derive less benefit from oxaliplatin. We evaluated the association between adjuvant oxaliplatin-based chemotherapy and neurotoxicity outcomes in an elderly cohort of patients. PATIENTS AND METHODS: A population-based cohort of patients aged > 65 years with stage II and III colorectal cancer treated with adjuvant therapy in Ontario, Canada was identified using the Ontario Cancer Registry. Cause-specific hazard models were used to estimate the effect of oxaliplatin exposure on the cause-specific hazard ratio (CHR) of peripheral neuropathy after accounting for the competing risk of death. RESULTS: We identified 3607 patients aged > 65 years with stage II and III colorectal cancer. Of these patients, 1541 (43%) had been treated with an oxaliplatin-based regimen. Compared with subjects receiving non-oxaliplatin-based regimens, patients aged ≥ 70 years at the time of cancer diagnosis who are subsequently treated with oxaliplatin were more likely to develop peripheral neuropathy (CHR, 2.3; 95% confidence interval [CI], 1.53-3.35; P < .0001). This association was not significant in patients aged 66 to 69 years (CHR, 0.93; 95% CI, 0.50-1.72; P = .812). Formal interaction testing confirmed that the effect of oxaliplatin on neuropathy was more pronounced in patients aged ≥ 70 years compared with patients aged 66 to 69 years (P = .03). CONCLUSION: Colorectal cancer patients aged ≥ 70 years at the time of cancer diagnosis who are subsequently treated with oxaliplatin have a significant risk of developing peripheral neuropathy. This should be considered in clinical decision making, especially because of the limited data supporting an oxaliplatin benefit in this age group.