A population-based analysis of the management of symptoms of depression among patients with stage IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

PURPOSE: Patients with lung cancer can experience significant psychological morbidities including depression. We characterize patterns and factors associated with interventions for symptoms of depression in stage IV non-small cell lung cancer (NSCLC). METHODS: We conducted a population-based cohort study using health services administrative data in Ontario, Canada of stage IV NSCLC diagnosed from January 2007 to September 2018. A positive symptom of depression score was defined by reporting at least one ESAS (Edmonton Symptom Assessment System) depression score ≥ 2 following diagnosis until the end of follow-up (September 2019). Patient factors included age, sex, comorbidity burden, rurality of residence, and neighbourhood income quintile. Interventions included psychiatry assessment, psychology referral, social work referral and anti-depressant medical therapy (for patients ≥ 65 years with universal drug coverage). Multivariable modified Poisson regression models were used to examine the association between patient factors and intervention use for patients who reported symptoms of depression. RESULTS: In the cohort of 13,159 patients with stage IV NSCLC lung cancer, symptoms of depression were prevalent (71.4%, n = 9,397). Patients who reported symptoms of depression were more likely to receive psychiatry assessment/psychology referral (7.8% vs 3.5%; SD [standardized difference] 0.19), social work referral (17.4% vs 11.9%; SD 0.16) and anti-depressant prescriptions (23.8% vs 13.8%; SD 0.26) when compared to patients who did not report symptoms of depression respectively. In multivariable analyses, older patients were less likely to receive any intervention. Females were more likely to obtain a psychiatry assessment/psychology referral or social work referral. In addition, patients from non-major urban or rural residences were less likely to receive psychiatry assessment/psychology referral or social work referral, however patients from rural residences were more likely to be prescribed anti-depressants. CONCLUSIONS: There is high prevalence of symptoms of depression in stage IV NSCLC. We identify patient populations, including older patients and rural patients, who are less likely to receive interventions that will help identifying and screening for symptoms of depression.

A trans-Canadian positive deviance seminar for paraesophageal hernia surgery: Reporting national postoperative outcomes and consensus recommendations.

BACKGROUND: The incidence of adverse events (AEs) and length of stay (LOS) varies significantly following paraesophageal hernia surgery. We performed a Canadian multicenter positive deviance (PD) seminar to review individual center and national level data and establish holistic perioperative practice recommendations. METHODS: A national virtual PD seminar was performed in October 2021. Recent best evidence focusing on AEs and LOS was presented. Subsequently, anonymized center-level AE and LOS data collected between 01/2017 and 01/2021 from a prospective, web-based database that tracks postoperative outcomes was presented. The top two performing centers with regards to these metrics were chosen and surgeons from these hospitals discussed elements of their treatment pathways that contributed to these outcomes. Consensus recommendations were then identified with participants independently rating their level of agreement. RESULTS: Twenty-eight surgeons form 8 centers took part in the seminar across 5 Canadian provinces. Of the 680 included patients included, Clavien-Dindo grade I and II/III/IV/V complications occurred in 121/39/12/2 patients (17.8%/5.7%/1.8%/0.3%). Respiratory complications were the most common (effusion 12/680, 1.7% and pneumonia 9/680, 1.3%). Esophageal and gastric perforation occurred in 7 and 4/680, (1.0% and 0.6% respectively). Median LOS varied significantly between institutions (1 day, range 1-3 vs. 7 days, 3-8, p < 0.001). A strong level of agreement was achieved for 10/12 of the consensus statements generated. CONCLUSION: PD seminars provide a supportive forum for centers to review best evidence and experience and generate recommendations based on expert opinion. Further research is ongoing to determine if this approach effectively accomplishes this objective.

Long-term Functional Outcomes Among Older Adults Undergoing Video-assisted Versus Open Surgery for Lung Cancer: A Population-based Cohort Study.

OBJECTIVE: To examine the long-term healthcare dependency outcomes of older adults undergoing VATS compared to open lung cancer resection. SUMMARY OF BACKGROUND DATA: Although the benefits of VATS for lung cancer resection have been reported, there is a knowledge gap related to long-term functional outcomes central to decision-making for older adults. METHODS: We conducted a population-based retrospective comparative cohort study of patients ≥70 years old undergoing lung cancer resection between 2010 and 2017 using linked administrative health databases. VATS was compared to open surgery for lung cancer resection. Outcomes were receipt of homecare and high time-at-home, defined as <14 institution-days within 1 year, in 5 years after surgery. We used time-to-event analyses. Homecare was analyzed as recurrent dichotomous outcome with Andersen-Gill multivariable models, and high time-at-home with Cox multivariable models. RESULTS: Of 4974 patients, 2951 had VATS (59.3%). In the first three months postoperatively, homecare use ranged from 17.5% to 34.4% for VATS and 23.0% to 36.6% for open surgery. VATS was independently associated with lower need for postoperative homecare over 5 years (hazard ratio 0.82, 95% confidence interval 0.74-0.92). 1- and 5-year probability of high "time-at-home" were superior for VATS (74.4% vs 66.7% and 55.6% vs 45.4%, p < 0.001). VATS was independently associated with higher probability of high "time-at-home" (hazard ratio 0.81, 95% confidence interval 0.74-0.89) compared to open surgery. CONCLUSIONS: Compared to open surgery, VATS was associated with lower homecare needs and higher probability of high "time-at-home," indicating reduced long-term functional dependence. Those important patient-centered endpoints reflect the overall long-term treatment burden on mortality and morbidity that can inform surgical decision-making.

Long-term Dependency in Older Adults After Surgery or Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer.

OBJECTIVE: To examine long-term healthcare dependency outcomes of stereotactic body radiation therapy (SBRT) to surgery for older adults with stage I non-small cell lung cancer (NSCLC). BACKGROUND: SBRT is an emerging alternative to surgery in patients with early-stage lung cancer. There remains a paucity of prospective studies comparing these modalities, especially with respect to long-term dependency outcomes in older adults with lung cancer. METHODS: Adults 70 years old and above with stage I NSCLC treated with surgery or SBRT from January 2010 to December 2017 were analyzed using 1:1 propensity score matching. Homecare use, days at home, and time spent alive and at home were compared. E-value methods assessed residual confounding. RESULTS: A total of 1129 and 2570 patients underwent SBRT and surgery, respectively. In all, 1016 per group were matched. SBRT was associated with a higher overall risk of homecare utilization [hazard ratio (HR)=1.75, 95% confidence interval (CI): 1.37-2.23] than surgery up to 5 years following treatment. While the hazards of death or nursing home admission were lower in the first 3 months after SBRT (HR=0.55, 95% CI: 0.36-0.85), they became consistently higher beyond this period and remained high up to 5 years compared with surgery (HR=2.13; 95% CI: 1.85-2.45). The above findings persisted in stratified analyses for frail patients and those with no pretreatment homecare. E-values indicated it was unlikely that the observed estimates could be explained by unmeasured confounders. CONCLUSIONS: Surgery offers robust long-term dependency outcomes compared with SBRT. These are important patient-centered endpoints which may be used for counseling and shared decision-making in older adults with stage I NSCLC.

Symptom Assessment Following Surgery for Lung Cancer: A Canadian Population-based Retrospective Cohort Study.

OBJECTIVE: To conduct a population-level analysis of temporal trends and risk factors for high symptom burden in patients receiving surgery for non-small cell lung cancer (NSCLC). BACKGROUND: A population-level overview of symptoms after curative intent surgery is necessary to inform decision making and supportive care for patients with lung cancer. METHODS: Retrospective cohort study of patients receiving surgery for stages I to III NSCLC between January 2007 and September 2018. Prospectively collection Edmonton Symptom Assessment System (ESAS) scores, linked to provincial administrative data, were used to describe the prevalence, trajectory, and predictors of moderate-to-severe symptoms in the year following surgery. RESULTS: A total of 5350 patients, with 28,490 unique ESAS assessments, were included in the analysis. Moderate-to-severe tiredness (68%), poor wellbeing (63%), and shortness of breath (60%) were the most common symptoms reported. The rise and fall in the proportion of patients experiencing moderate-to-severe symptoms after surgery coincided with the median time to first (58 days, interquartile range: 47-72) and last cycle of chemotherapy (140 days, interquartile range: 118-168), respectively. There was eventual stabilization, albeit above the preoperative baseline, within 6 to 7 months after surgery. Female sex (relative risk [RR] 1.09- 1.26), lower income (RR 1.08-1.23), stage III disease (RR 1.15-1.43), adjuvant therapy (RR 1.09-1.42), chemotherapy within 2 weeks of an ESAS assessment (RR 1.14-1.73), and pneumonectomy (RR 1.05-1.15) were associated with moderate-to-severe symptoms following surgery. CONCLUSIONS: Knowledge of population-level prevalence, trajectory, and predictors of moderate-to-severe symptoms after surgery for NSCLC can be used to facilitate shared decision making and improve symptom management throughout the course of illness.

Variation in Anesthesiology Provider-Volume for Complex Gastrointestinal Cancer Surgery: A Population-Based Study.

OBJECTIVE: Examine between-hospital and between-anesthesiologist variation in anesthesiology provider-volume (PV) and delivery of high-volume anesthesiology care. BACKGROUND: Better outcomes for anesthesiologists with higher PV of complex gastrointestinal cancer surgery have been reported. The factors linking anesthesiology practice and organization to volume are unknown. METHODS: We identified patients undergoing elective esophagectomy, hepatectomy, and pancreatectomy using linked administrative health data sets (2007-2018). Anesthesiology PV was the annual number of procedures done by the primary anesthesiologist in the 2 years before the index surgery. High-volume anesthesiology was PV>6 procedures/year. Funnel plots to described variation in anesthesiology PV and delivery of high-volume care. Hierarchical regression models examined between-anesthesiologist and between-hospital variation in delivery of high-volume care use with variance partition coefficients (VPCs) and median odds ratios (MORs). RESULTS: Among 7893 patients cared for at 17 hospitals, funnel plots showed variation in anesthesiology PV (median ranging from 1.5, interquartile range: 1-2 to 11.5, interquartile range: 8-16) and delivery of HV care (ranging from 0% to 87%) across hospitals. After adjustment, 32% (VPC 0.32) and 16% (VPC: 0.16) of the variation were attributable to between-anesthesiologist and between-hospital differences, respectively. This translated to an anesthesiologist MOR of 4.81 (95% CI, 3.27-10.3) and hospital MOR of 3.04 (95% CI, 2.14-7.77). CONCLUSIONS: Substantial variation in anesthesiology PV and delivery of high-volume anesthesiology care existed across hospitals. The anesthesiologist and the hospital were key determinants of the variation in high-volume anesthesiology care delivery. This suggests that targeting anesthesiology structures of care could reduce variation and improve delivery of high-volume anesthesiology care.

The Association Between Hospital High-volume Anesthesiology Care and Patient Outcomes for Complex Gastrointestinal Cancer Surgery: A Population-based Study.

OBJECTIVE: To examine the association of between hospital rates of high-volume anesthesiology care and of postoperative major morbidity. BACKGROUND: Individual anesthesiology volume has been associated with individual patient outcomes for complex gastrointestinal cancer surgery. However, whether hospital-level anesthesiology care, where changes can be made, influences the outcomes of patients cared at this hospital is unknown. METHODS: We conducted a population-based retrospective cohort study of adults undergoing esophagectomy, pancreatectomy, or hepatectomy for cancer from 2007 to 2018. The exposure was hospital-level adjusted rate of high-volume anesthesiology care. The outcome was hospital-level adjusted rate of 90-day major morbidity (Clavien-Dindo grade 3-5). Scatterplots visualized the relationship between each hospital's adjusted rates of high-volume anesthesiology and major morbidity. Analyses at the hospital-year level examined the association with multivariable Poisson regression. RESULTS: For 7893 patients at 17 hospitals, the rates of high-volume anesthesiology varied from 0% to 87.6%, and of major morbidity from 38.2% to 45.4%. The scatter plot revealed a weak inverse relationship between hospital rates of high-volume anesthesiology and of major morbidity (Pearson: -0.23). The adjusted hospital rate of high-volume anesthesiology was independently associated with the adjusted hospital rate of major morbidity (rate ratio: 0.96; 95% CI, 0.95-0.98; P <0.001 for each 10% increase in the high-volume rate). CONCLUSIONS: Hospitals that provided high-volume anesthesiology care to a higher proportion of patients were associated with lower rates of 90-day major morbidity. For each additional 10% patients receiving care by a high-volume anesthesiologist at a given hospital, there was an associated reduction of 4% in that hospital's rate of major morbidity.

Comparison of Four Clinical Prognostic Scores in Patients with Advanced Gastric and Esophageal Cancer.

BACKGROUND: Prognostic scores that can identify patients at risk for early death are needed to aid treatment decision-making and patient selection for clinical trials. We compared the accuracy of four scores to predict early death (within 90 days) and overall survival (OS) in patients with metastatic gastric and esophageal (GE) cancer. METHODS: Advanced GE cancer patients receiving first-line systemic therapy were included. Prognostic risks were calculated using: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune (GRIm-Score), and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) scores. Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to analyze associations between prognostic scores and OS. The predictive discrimination was estimated using Harrell's c-index. Predictive ability for early death was measured using time-dependent AUCs. RESULTS: In total, 451 patients with metastatic GE cancer were included. High risk patients had shorter OS for all scores (RMH high- vs. low-risk median OS 7.9 vs. 12.2 months, P < .001; MDACC 6.8 vs. 11.9 months P < .001; GRIm-Score 5.3 vs. 13 months, P < .001; MDA-ICI 8.2 vs. 12.2 months, P < .001). On multivariable analysis, each prognostic score was significantly associated with OS. The GRIm-Score had the highest predictive discrimination and predictive ability for early death. CONCLUSIONS: The GRIm-Score had the highest accuracy in predicting early death and OS. Clinicians may use this score to identify patients at higher risk of early death to guide treatment decisions including clinical trial enrolment. This score could also be used as a stratification factor in future clinical trial designs.

Omission of intraoperative pyloric procedures in minimally invasive esophagectomy: assessing the impact on patients.

Pyloroplasty or pyloromyotomy is often undertaken during esophagectomy to aid gastric emptying postoperatively. Minimally invasive esophagectomy (MIE) frequently omits a pyloric procedure. The impact on perioperative outcomes and the need for subsequent interventions is unclear. This study assesses the requirements for endoscopic balloon dilation of the pylorus (EPD) following MIE. Patients undergoing MIE from 2016 to 2020 were reviewed. Patients undergoing open resection, or an intraoperative pyloric procedure were excluded. Demographic, clinical and pathological data were reviewed. Univariable and multivariable analysis were performed as appropriate. In total, 171 patients underwent MIE. There were no differences in age (median 65 vs. 65 years, P = 0.6), pathological stage (P = 0.10) or ASA status (P = 0.52) between those requiring and not requiring endoscopic pyloric dilation (EPD). Forty-three patients (25%) required EPD, with a total of 71 procedures. Twenty-seven patients (16%) had EPD on their index admission. Seventy-five patients (43%) had a postoperative complication. Higher ASA status was associated with increased requirement for EPD (odds ratio 10.8, P = 0.03). On multivariable analysis, there was no association between the need for a pyloric procedure and overall survival (P = 0.14). Eight patients (5%) required insertion of a feeding jejunostomy in the postoperative period, with no difference between those with or without EPD (P = 0.11). Two patients required subsequent surgical pyloromyotomy for delayed gastric emptying. Although pyloroplasty or pyloromyotomy can safely be excluded during MIE, a quarter of patients will require postoperative EPD procedures. The impact of excluding pyloric procedures on gastric emptying requires further study.

Impact of Sites of Metastatic Dissemination on Survival in Advanced Gastroesophageal Adenocarcinoma.

INTRODUCTION: Metastatic gastroesophageal adenocarcinoma (GEA) is a heterogeneous disease with an overall poor prognosis. The impact of sites of metastatic dissemination on survival is not well characterized. This study aimed to evaluate whether certain sites of metastatic disease impacts survival. METHODS: A retrospective analysis of 375 patients with metastatic GEA treated at the Princess Margaret Cancer Centre from 2006 to 2016 was performed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association between sites of metastases and OS adjusting for baseline patient characteristics. RESULTS: Median duration of follow-up was 47.8 months. Median OS in this cohort was 11.8 months (95% CI: 10.2-12.9 months). Patients with lymph node only disease, compared to those with other sites of metastases, had the longest median OS (20.4 vs. 10.6 months; p < 0.001) and PFS (11.4 vs. 6.3 months; p < 0.001). On multivariable analysis adjusting for relevant clinical factors including age, sex, and Eastern Cooperative Oncology Group performance status, the presence of lung (HR 1.67, 95% CI: 1.23-2.26; p < 0.001) or bone metastases (HR 1.84, 95% CI: 1.31-2.59; p < 0.001) were independently associated with shorter OS. The majority of patients (68%) were treated with palliative intent first-line platinum-based chemotherapy. DISCUSSION/CONCLUSION: Patients with metastatic GEA have an overall poor prognosis. The presence of lung or bone metastases is an independent risk factor for decreased survival. Prognostic models incorporating sites of metastasis should be considered in the clinical evaluation of metastatic GEA.

Influence of sarcopenia, clinical data, and 2-[18F] FDG PET/CT in outcome prediction of patients with early-stage adenocarcinoma esophageal cancer.

PURPOSE: To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. METHODS: Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI < 34.4cm2/m2 in women and < 45.4cm2/m2 in men. RESULTS: Of the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, lymphovascular invasion (LVI) positive lymph nodes, and sarcopenia were significant prognostic factors concerning RFS and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging-derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS. CONCLUSION: Combining the patients' imaging-derived sarcopenic status with standard clinical data, but not metabolic parameters, offered an overall improved prognostic value concerning OS and RFS.

Preoperative and Postoperative Approaches to Gastroesophageal Cancer: What is All the Fuss About.

Gastroesophageal cancers carry poor prognoses, and are a leading cause of cancer-related morbidity and mortality worldwide. Even in those with resectable disease, more than half of patients treated with surgery alone experience disease recurrence. Multimodality approaches using preoperative and postoperative chemotherapy and/or radiotherapy have been established, resulting in incremental improvements in outcomes. Globally, there is no standardized approach, and treatment varies with geographic location. The question remains of how to select the optimal perioperative treatment that will maximize benefit for patients while avoiding toxicities from unnecessary therapies. This article reviews currently available evidence supporting preoperative and postoperative therapy in gastroesophageal cancers, with an emphasis on recent practice-changing trials and ongoing areas of investigation, including the role of immune checkpoint inhibition and biomarker-guided treatment.

Province-Wide Analysis of Patient-Reported Outcomes for Stage IV Non-Small Cell Lung Cancer.

BACKGROUND: In Ontario, Canada, patient-reported outcome (PRO) evaluation through the Edmonton Symptom Assessment System (ESAS) has been integrated into clinical workflow since 2007. As stage IV non-small cell lung cancer (NSCLC) is associated with substantial disease and treatment-related morbidity, this province-wide study investigated moderate to severe symptom burden in this population. MATERIALS AND METHODS: ESAS collected from patients with stage IV NSCLC diagnosed between 2007 and 2018 linked to the Ontario provincial health care system database were studied. ESAS acquired within 12 months following diagnosis were analyzed and the proportion reporting moderate to severe scores (ESAS ≥4) in each domain was calculated. Predictors of moderate to severe scores were identified using multivariable Poisson regression models with robust error variance. RESULTS: Of 22,799 patients, 13,289 (58.3%) completed ESAS (84,373 assessments) in the year following diagnosis. Patients with older age, with high comorbidity, and not receiving active cancer therapy had lower ESAS completion. The majority (94.4%) reported at least one moderate to severe symptom. The most prevalent were tiredness (84.1%), low well-being (80.7%), low appetite (71.7%), and shortness of breath (67.8%). Most symptoms peaked at diagnosis and, while declining, remained high in the following year. On multivariable analyses, comorbidity, low income, nonimmigrants, and urban residency were associated with moderate to severe symptoms. Moderate to severe scores in all ESAS domains aside from anxiety were associated with radiotherapy within 2 weeks prior, whereas drowsiness, low appetite and well-being, nausea, and tiredness were associated with systemic therapy within 2 weeks prior. CONCLUSION: This province-wide PRO analysis showed moderate to severe symptoms were prevalent and persistent among patients with metastatic NSCLC, underscoring the need to address supportive measures in this population especially around treatments. IMPLICATIONS FOR PRACTICE: In this largest study of lung cancer patient-reported outcomes (PROs), stage IV non-small cell lung cancer patients had worse moderate-to-severe symptoms than other metastatic malignancies such as breast or gastrointestinal cancers when assessed with similar methodology. Prevalence of moderate-to-severe symptoms peaked early and remained high during the first year of follow-up. Symptom burden was associated with recent radiation and systemic treatments. Early and sustained PRO collection is important to detect actionable symptom progression, especially around treatments. Vulnerable patients (e.g., older, high comorbidity) who face barriers in attending in-person clinic visits had lower PRO completion. Virtual PRO collection may improve completion.

Prognostic Impact of CXCR7 and CXCL12 Expression in Patients with Esophageal Adenocarcinoma.

BACKGROUND: Chemokines are major regulators of cell trafficking and adhesion. The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, have been reported as biomarkers in various cancers, including esophageal cancer; however, there are few studies in esophageal adenocarcinoma (EAC). In this study, we investigated the relationship between expression of CXCL12, CXCR4, and CXCR7, and prognosis in patients with EAC. METHODS: This study examined 55 patients with EAC who were treated in Toronto General Hospital from 2001 to 2010. Tissue microarray immunohistochemistry was used to evaluate the expression of CXCL12, CXCR4, and CXCR7. Evaluation of immunohistochemistry was performed by a pathologist without knowledge of patients' information and results were compared with the patients' clinicopathological features and survival. RESULTS: High CXCR7 expression was significantly associated with lymphatic invasion (present vs absent, P = 0.005) and higher number of lymph node metastases (pN0-1 vs pN2-3, P = 0.0014). Patients with high CXCR7 expression (n = 23) were associated with worse overall (OS) and disease-free survival (DFS) (P = 0.0221, P = 0.0090, respectively), and patients with high CXCL12 (n = 24) tended to have worse OS and DFS (P = 0.1091, P = 0.1477, respectively). High expression of both CXCR7 and CXCL12 was an independent prognostic factor for OS and DFS on multivariate analysis (HR = 0.3, 95% CI: 0.1-0.9, P = 0.0246, HR = 0.3, 95% CI: 0.1-0.8, P = 0.0134, respectively). CONCLUSIONS: High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 with its ligand CXCL12 had a stronger association with prognosis. Further study of this potential biomarker using whole tissue samples and a larger sample size is warranted.

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

BACKGROUND: Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT. METHODS: A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis. RESULTS: Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (n = 67; 72%) or dCRT (n = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; p = 0.001; HR 3.1; 95% CI: 1.2-7.7) and DFS (0 vs. 41%; p = 0.004; HR 3.6; 95% CI: 1.4-8.9) on multivariable and IPTW sensitivity analyses. CONCLUSIONS: TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.

Geographic impact on access to care and survival for non-curative esophagogastric cancer: a population-based study.

BACKGROUND: Among patients not undergoing curative-intent therapy for esophagogastric cancer, access to care may vary. We examined the geographic distribution of care delivery and survival and their relationship with distance to cancer centres for non-curative esophagogastric cancer, hypothesising that patients living further from cancer centres have worse outcomes. METHODS: We conducted a population-based analysis of adults with non-curative esophagogastric cancer from 2005 to 2017 using linked administrative healthcare datasets in Ontario, Canada. Outcomes were medical oncology consultation, receipt of chemotherapy, and overall survival. Using geographic information system analysis, we mapped locations of cancer centres and outcomes across census divisions. Bivariate choropleth maps identified regional outcome discordances. Multivariable regression models assessed the relationship between distance from patient residence to the nearest cancer centre and outcomes, adjusting for demographic, clinical, and socioeconomic factors. RESULTS: Of 10,228 patients surviving a median 5.1 months (IQR: 2.0-12.0), 68.5% had medical oncology consultation and 32.2% received chemotherapy. Certain distances (reference ≤ 10 km) were associated with lower consultation [relative risk 0.79 (95% CI 0.63-0.97) for ≥ 101 km], chemotherapy receipt [relative risk 0.67 (95% CI 0.53-0.85) for ≥ 101 km], and overall survival [hazard ratio 1.07 (95% CI 1.02-1.13) for 11-50 km, hazard ratio 1.13 (95% CI 1.04-1.23) for 51-100 km]. CONCLUSION: A third of patients did not see medical oncology and most did not receive chemotherapy. Outcomes exhibited high geographic variability. Location of residence influenced outcomes, with inferior outcomes at certain distances > 10 km from cancer centres. These findings are important for designing interventions to reduce access disparities for non-curative esophagogastric cancer care.

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

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

Impact of rarity on Canadian oncology health technology assessment and funding.

OBJECTIVES: The pan-Canadian Oncology Drug Review (pCODR) evaluates new cancer drugs for public funding recommendations. While pCODR's deliberative framework evaluates overall clinical benefit and includes considerations for exceptional circumstances, rarity of indication is not explicitly addressed. Given the high unmet need that typically accompanies these indications, we explored the impact of rarity on oncology HTA recommendations and funding decisions. METHODS: We examined pCODR submissions with final recommendations from 2012 to 2017. Incidence rates were calculated using pCODR recommendation reports and statistics from the Canadian Cancer Society. Indications were classified as rare if the incidence rate was lower than 1/100,000 diagnoses, a definition referenced by the Canadian Agency for Drugs and Technologies in Health. Each pCODR final report was examined for the funding recommendation/justification, level of supporting evidence (presence of a randomized control trial [RCT]), and time to funding (if applicable). RESULTS: Of the ninety-six pCODR reviews examined, 16.6 percent were classified as rare indications per above criteria. While the frequency of positive funding recommendations were similar between rare and nonrare indication (78.6 vs. 75 percent), rare indications were less likely to be presented with evidence from RCT (50 vs. 90 percent). The average time to funding did not differ significantly across provinces. CONCLUSION: Rare indications appear to be associated with weaker clinical evidence. There appears to be no association between rarity, positive funding recommendations, and time to funding. Further work will evaluate factors associated with positive recommendations and the real-world utilization of funded treatments for rare indications.

Benchmarking Complications Associated with Esophagectomy.

OBJECTIVE: Utilizing a standardized dataset with specific definitions to prospectively collect international data to provide a benchmark for complications and outcomes associated with esophagectomy. SUMMARY OF BACKGROUND DATA: Outcome reporting in oncologic surgery has suffered from the lack of a standardized system for reporting operative results particularly complications. This is particularly the case for esophagectomy affecting the accuracy and relevance of international outcome assessments, clinical trial results, and quality improvement projects. METHODS: The Esophageal Complications Consensus Group (ECCG) involving 24 high-volume esophageal surgical centers in 14 countries developed a standardized platform for recording complications and quality measures associated with esophagectomy. Using a secure online database (ESODATA.org), ECCG centers prospectively recorded data on all resections according to the ECCG platform from these centers over a 2-year period. RESULTS: Between January 2015 and December 2016, 2704 resections were entered into the database. All demographic and follow-up data fields were 100% complete. The majority of operations were for cancer (95.6%) and typically located in the distal esophagus (56.2%). Some 1192 patients received neoadjuvant chemoradiation (46.1%) and 763 neoadjuvant chemotherapy (29.5%). Surgical approach involved open procedures in 52.1% and minimally invasive operations in 47.9%. Chest anastomoses were done most commonly (60.7%) and R0 resections were accomplished in 93.4% of patients. The overall incidence of complications was 59% with the most common individual complications being pneumonia (14.6%) and atrial dysrhythmia (14.5%). Anastomotic leak, conduit necrosis, chyle leaks, recurrent nerve injury occurred in 11.4%, 1.3%, 4.7%, and 4.2% of cases, respectively. Clavien-Dindo complications ≥ IIIb occurred in 17.2% of patients. Readmissions occurred in 11.2% of cases and 30- and 90-day mortality was 2.4% and 4.5%, respectively. CONCLUSION: Standardized methods provide contemporary international benchmarks for reporting outcomes after esophagectomy.