Hepatopancreaticobiliary Resection Arginine Immunomodulation (PRIMe) trial: protocol for a randomised phase II trial of the impact of perioperative immunomodulation on immune function following resection for hepatopancreaticobiliary malignancy.

INTRODUCTION: Surgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery. METHODS AND ANALYSIS: This is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04549662.

Minimally Invasive Compared to Open Colorectal Cancer Resection for Older Adults: A Population-based Analysis of Long-term Functional Outcomes.

OBJECTIVE: We sought to compare long-term healthcare dependency and time-at-home between older adults undergoing minimally invasive surgery (MIS) for colorectal cancer (CRC) and those undergoing open resection. BACKGROUND: Although the benefits of MIS for CRC resection are established, data specific to older adults are lacking. Long-term functional outcomes, central to decision-making in the care for older adults, are unknown. METHODS: We performed a population-based analysis of patients ≥70years old undergoing CRC resection between 2007 to 2017 using administrative datasets. Outcomes were receipt of homecare and "high" time-at-home, which we defined as years with ≤14 institution-days, in the 5years after surgery. Homecare was analyzed using time-to-event analyses as a recurrent dichotomous outcome with Andersen-Gill multivariable models. High timeat-home was assessed using Cox multivariable models. RESULTS: Of 16,479 included patients with median follow-up of 4.3 (interquartile range 2.1-7.1) years, 7822 had MIS (47.5%). The MIS group had lower homecare use than the open group with 22.3% versus 31.6% at 6 months and 14.8% versus 19.4% at 1 year [hazard ratio 0.87,95% confidence interval (CI) 0.83-0.92]. The MIS group had higher probability ofhigh time-at-home than open surgery with 54.9% (95% CI 53.6%-56.1%) versus 41.2% (95% CI 40.1%-42.3%) at 5years (hazard ratio 0.71, 95% CI 0.68-0.75). CONCLUSIONS: Compared to open surgery, MIS for CRC resection was associated with lower homecare needs and higher probability of high time-at-home in the 5 years after surgery, indicating reduced long-term functional dependence. These are important patient-centered endpoints reflecting the overall long-term treatment burden to be taken into consideration in decision-making.

PATCH-DP: a single-arm phase II trial of intra-operative application of HEMOPATCH™ to the pancreatic stump to prevent post-operative pancreatic fistula following distal pancreatectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the most significant cause of morbidity following distal pancreatectomy. Hemopatch™ is a thin, bovine collagen-based hemostatic sealant. We hypothesized that application of Hemopatch™ to the pancreatic stump following distal pancreatectomy would decrease the incidence of clinically-significant POPF. METHODS: We conducted a prospective, single-arm, multicentre phase II study of application of Hemopatch™ to the pancreatic stump following distal pancreatectomy. The primary outcome was clinically-significant POPF within 90 days of surgery. A sample size of 52 patients was required to demonstrate a 50% relative reduction in Grade B/C POPF from a baseline incidence of 20%, with a type I error of 0.2 and power of 0.75. Secondary outcomes included incidence of POPF (all grades), 90-day mortality, 90-day morbidity, re-interventions, and length of stay. RESULTS: Adequate fixation Hemopatch™ to the pancreatic stump was successful in all cases. The rate of grade B/C POPF was 25% (95%CI: 14.0-39.0%). There was no significant difference in the incidence of grade B/C POPF compared to the historical baseline (p = 0.46). The 90-day incidence of Clavien-Dindo grade ≥3 complications was 26.9% (95%CI: 15.6-41.0%). CONCLUSION: The use of Hemopatch™ was not associated with a decreased incidence of clinically-significant POPF compared to historical rates. (NCT03410914).

Patient-reported symptoms in metastatic gastric cancer patients in the last 6 months of life.

BACKGROUND: Patients with metastatic gastric cancer have poor survival outcomes and may experience high symptom burden. We evaluated symptom trajectory and risk factors for increased symptom severity among metastatic gastric cancer patients during the last 6 months of life. METHODS: We conducted a retrospective cohort study among patients ≥ 18 years diagnosed with metastatic gastric cancer from January 2007 to December 2014 in the province of Ontario, Canada. We included patients who died during the study period and who reported at least one Edmonton Symptom Assessment System (ESAS) score during the last 6 months of life. We described the proportion of patients who reported moderate-to-severe symptom scores (≥ 4) by month. Multivariable logistic regression models were created to identify risk factors for moderate-to-severe symptom scores. RESULTS: Seven hundred eighty-eight eligible patients with 3286 unique symptom scores completed during their last 6 months of life were identified. The highest prevalence of moderate-to-severe scores was observed for tiredness and lack of appetite, while nausea and depression had the lowest prevalence of elevated scores. The prevalence of moderate-to-severe was consistently high for all symptoms, particularly approaching end-of-life. Timing of ESAS scores, receipt of cancer-directed therapy, urban residence, and female sex were associated with increased odds of reporting moderate-to-severe symptom scores. CONCLUSION: Patients with metastatic gastric cancer experience significant symptom burden at the end-of-life. Routine screening with patient-reported outcome tools may assist in shared decision-making and effective palliative care by ensuring patients' health status and supportive care needs are identified promptly at the time of clinical encounters.

Association Between Preoperative Patient-Reported Symptoms and Postoperative Outcomes in Rectal Cancer Patients: A Retrospective Cohort Study.

BACKGROUND: Rectal cancer patients undergoing preoperative radiotherapy experience a significant symptom burden. However, it is unknown whether symptoms during radiotherapy may portend adverse postoperative outcomes and healthcare utilization. METHODS: A retrospective cohort study was performed of rectal cancer patients undergoing neoadjuvant radiotherapy and proctectomy in Ontario from 2007 to 2014. The primary outcome was a complicated postoperative course-a dichotomous variable created as a composite of postoperative mortality, major morbidity, or hospital readmission. Patient-reported Edmonton Symptom Assessment System (ESAS) scores, collected routinely at outpatient provincial cancer center visits, were linked to administrative healthcare databases. The receiver-operating characteristic analysis was used to compare ESAS scoring approaches and to stratify patients into low versus high symptom score groups. Multivariable regression models were constructed to evaluate associations between preoperative symptom scores and postoperative outcomes. RESULTS: 1455 rectal cancer patients underwent sequential radiotherapy and proctectomy during the study period and recorded symptom assessments. Patients with high preoperative symptom scores were significantly more likely to experience a complicated postoperative course (OR 1.55, 95% CI 1.23-1.95). High preoperative ESAS scores were also associated with the secondary outcomes of emergency department visits (OR 1.34, 95% CI 1.08-1.66) and longer length of stay (IRR 1.23, 95% CI 1.04-1.45). CONCLUSIONS: Rectal cancer patients reporting elevated symptom scores during neoadjuvant radiotherapy have increased odds of experiencing a complicated postoperative course. Preoperative patient-reported outcome screening may be a useful tool to identify at-risk patients and to efficiently direct perioperative supportive care.

Symptom Burden of Nonresected Pancreatic Adenocarcinoma: An Analysis of 10,753 Patient-Reported Outcome Assessments.

OBJECTIVES: Pancreatic adenocarcinoma (PAC) is a debilitating disease. We sought to analyze symptom burden and trajectories after diagnosis of PAC and identify predictors of severe symptoms for nonresected patients. METHODS: This was a retrospective review of linked administrative health care databases examining patients with PAC not undergoing resection. Primary outcome was severe patient-reported symptoms (Edmonton Symptom Assessment System ≥7). Multivariable modified Poisson regression models were used to identify factors associated with reporting severe symptoms. RESULTS: A total of 10,753 symptom assessments from 2168 patients were analyzed. The median age was 67 years, and 47% were female; median survival was 7 months. Most common severe symptoms were tiredness (54.7%), anorexia (53.6%), overall impaired well-being (45.3%), and drowsiness (37.1%). Severity of symptoms decreased 1 month after diagnosis and plateaued 4 months after diagnosis. Female sex, comorbidities, and older age were associated with reporting severe symptoms; recent radiation treatment and residence in a rural community were associated with reporting less severe symptoms. CONCLUSIONS: The prevalence of severe symptoms in patients with nonresected PAC was high, but potentially modifiable. We identified vulnerable groups of patients that may benefit from focused interventions. This information is important for patient counseling and design of supportive care strategies.

Patient-Reported Symptom Severity Among 22,650 Cancer Outpatients in the Last Six Months of Life.

CONTEXT: Understanding the magnitude and risk factors for symptom burden of patients with cancer at the end of life is critical to guiding effective patient- and system-level interventions. OBJECTIVES: We aimed to estimate the prevalence of severe patient-reported symptoms among cancer outpatients during the six months before death and to identify patient groups at a higher risk for reporting severe symptoms. METHODS: This was a retrospective cohort study of cancer decedents at regional cancer centers from 2010 to 2016. Patient-reported Edmonton Symptom Assessment System (ESAS) scores from the last six months of life were linked to administrative databases. The proportion of patients reporting severe symptom scores (≥7) for anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and overall well-being during the six months before death was described. Multivariable modified Poisson regression analyses were used to identify risk factors for reporting severe symptom scores. RESULTS: Of 39,084 cancer decedents, 22,650 had one or more symptom assessments recorded in the last six months of life, resulting in 92,757 ESAS assessments. Severe scores were highest for tiredness (56%), lack of appetite (46%), and impaired well-being (45%). The proportion of patients reporting severe symptom scores was stable before progressively increasing at three months before death. Elderly, women, patients with high comorbidity, immigrants, and living in urban areas or with high material deprivation were at increased risk of reporting severe scores. CONCLUSIONS: Despite an integrated symptom screening program, rates of severe patient-reported symptom scores before death were high for outpatients with cancer. Patient subgroups at increased risk of severe symptom burden may benefit from targeted interventions. Ongoing review of routinely collected symptom data may be used to assess the supportive care needs and guide targeted interventions at the health-system level.

Symptom burden among head and neck cancer patients in the first year after diagnosis: Association with primary treatment modality.

PURPOSE: Head and neck cancer (HNC) and its treatment affects quality of life, with significant symptom burden. The main objectives of this study were to examine symptom trajectories of HNC patients by treatment and to identify factors associated with high ESAS scores. METHODS AND MATERIALS: We conducted a retrospective cohort study in patients diagnosed with HNC in Ontario, Canada from 2007 to 2015 using linked health administrative databases. The primary outcome was a monthly patient self-reported moderate-to-severe (≥4) symptom score in the year following diagnosis. Multivariable Modified Poisson regression analyses with robust variance were used to investigate factors associated with moderate-to-severe scores. RESULTS: Of 13,827 HNC patients identified, 4793 had ≥1 ESAS assessment within 12 months of cancer diagnosis. Overall, 60% (n = 2708) and 65% (n = 2903) of patients reported moderate-to-severe pain and poor appetite, respectively. The proportion of patients reporting a score ≥4 increased significantly during treatment and was most pronounced for those who received chemoradiation (CRT). On multivariable analysis, patients who were female (Relative Risk (RR) 1.15, 95% CI 1.08-1.23, received CRT, had a higher comorbidity burden (RR 1.31, 1.23-1.39), and had a diagnosis of oropharyngeal (1.10, 1.02-1.19), or oral cavity cancer (1.31, 1.19-1.45), were at an increased risk of reporting severe pain scores (p < 0.01 for all). CONCLUSION: The majority of HNC patients report high pain scores, with symptom burden highest during the treatment phase, and especially for patients who received radiation or chemoradiation. This large study highlights the need for proactive symptom management during the HNC patients' cancer journey.

Comparison of Patient-Reported Outcomes in Laparoscopic and Open Right Hemicolectomy: A Retrospective Cohort Study.

BACKGROUND: Open and laparoscopic resections for colon cancer have equivalent perioperative morbidity and mortality. However, there are little data concerning patient-reported outcomes in the early postdischarge period. OBJECTIVE: We examined patient-reported outcomes in the early postdischarge period for open and laparoscopic right hemicolectomy for colon cancer. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted using linked administrative healthcare databases in the province of Ontario, Canada. PATIENTS: Patients undergoing laparoscopic or open right hemicolectomy for colon cancer between January 2010 and December 2014 were identified using the Ontario Cancer Registry and physician billing data. MAIN OUTCOME MEASURES: The primary outcome was the presence of moderate-to-severe symptom scores on the Edmonton Symptom Assessment System (≥4 of 10) within 6 weeks of hospital discharge after right hemicolectomy. RESULTS: A total of 1022 patients completed ≥1 Edmonton Symptom Assessment System survey within 6 weeks of surgery and were included in the study. Patients undergoing laparoscopic resection were more likely to have an urban residence, to have undergone planned resections, and to have had proportionally more stage 1 disease compared with patients undergoing open resection. On multivariable analyses, adjusting for patient demographics, cancer stage, and planned versus unplanned admission status, there were no differences in the adjusted odds of moderate-to-severe symptom scores between the laparoscopic and open approaches. LIMITATIONS: Edmonton Symptom Assessment System scores are not collected for inpatients and thus only represent outpatient postoperative visits. Scores were reported by 19% of all resections in the population, with a bias to patients treated at cancer centers, and therefore they are not fully representative of the general population of right hemicolectomy. The Edmonton Symptom Assessment System is not a disease-specific tool and may not measure all relevant outcomes for patients undergoing right hemicolectomy. CONCLUSIONS: Receipt of the open or laparoscopic surgical technique was not associated with increased risk of elevated symptom burden in the early postdischarge period. See Video Abstract at http://links.lww.com/DCR/B27. REPORTE COMPARATIVO DE RESULTADOS INFORMADOS DE PACIENTES CON HEMICOLECTOMÍA DERECHA LAPAROSCÓPICA Y ABIERTA: UN ESTUDIO DE COHORTE RETROSPECTIVO: Las resecciones abiertas y laparoscópicas para el cáncer de colon, presentan semejante morbilidad y mortalidad perioperatoria. Sin embargo, en el período inicial posterior al alta, hay pocos datos sobre los resultados informados por los pacientes.Examinamos los resultados informados por los pacientes, en el período temprano posterior al alta, para hemicolectomía derecha abierta y laparoscópica en cáncer de colon.Estudio de cohorte retrospectivo.El estudio se realizó utilizando bases de datos administrativas de atención médica en la provincia de Ontario, Canadá.Pacientes sometidos a hemicolectomía derecha abierta o laparoscópica para cáncer de colon, de enero 2010 a diciembre 2014, se identificaron mediante el Registro de cáncer de Ontario y de los datos médicos de facturación.El resultado primario, después de la hemicolectomía derecha, fue la presencia de síntomas de moderados a graves en el Sistema de evaluación de síntomas de Edmonton (≥4 de cada 10) dentro de las seis semanas posteriores al alta hospitalaria.Un total de 1022 pacientes completaron al menos una encuesta del Sistema de evaluación de síntomas de Edmonton, dentro de las seis semanas de la cirugía y se incluyeron en el estudio. Los pacientes sometidos a resección laparoscópica fueron más propensos a residir en zona urbana, a resecciones planificadas y proporcionalmente más enfermedad en estadio 1; en comparación con los pacientes sometidos a resecciones abiertas. En los análisis multivariables, que se ajustaron a la demografía del paciente, al estadio del cáncer y del estado de ingreso planificado versus no planificado, no hubo diferencias en las probabilidades ajustadas de las puntuaciones de los síntomas moderados a severos entre el abordaje abierto o laparoscópico.Las puntuaciones del Sistema de evaluación de síntomas de Edmonton no se recopilan para pacientes hospitalizados y por lo tanto, solo representan las visitas postoperatorias de pacientes ambulatorios. Las puntuaciones informadas fueron del 19% de todas las resecciones en la población, con un sesgo en los pacientes tratados en los Centros de Cáncer y por lo tanto, no son totalmente representativos de la población general de hemicolectomía derecha. El Sistema de evaluación de síntomas de Edmonton no es una herramienta específica de la enfermedad y puede no medir todos los resultados relevantes para los pacientes que se someten a una hemicolectomía derecha.La recepción entre una técnica quirúrgica abierta o laparoscópica, no se asoció con un aumento del riesgo de síntomas en el período temprano posterior al alta. Vea el Resumen del Video en http://links.lww.com/DCR/B27.

Population-Level Symptom Assessment Following Pancreaticoduodenectomy for Adenocarcinoma.

Importance: Postoperative morbidity associated with pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA) remains as high as 70%. However, to our knowledge, few studies have examined quality of life in this patient population. Objective: To identify symptom burden and trajectories and factors associated with high symptom burden following PD for PA. Design, Setting, and Participants: This population-based cohort study of patients undergoing PD for PA diagnosed between 2009 and 2015 linked population-level administrative health care data to routinely prospectively collected Edmonton Symptom Assessment System (ESAS) scores from 2009 to 2015, with a data analysis undertaken in 2018. Exposures: Baseline characteristics, including age, sex, income quintile, rurality, immigration status, and comorbidity burden, as well as treatment characteristics, including year of surgery and receipt of chemotherapy. Main Outcome and Measures: The outcome of interest was moderate to severe symptoms (defined as ESAS ≥4) for anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and impaired well-being. The monthly prevalence of moderate to severe symptoms was presented graphically for each symptom. Multivariable regression models identified factors associated with the reporting of moderate to severe symptoms. Results: We analyzed 6058 individual symptom assessments among 615 patients with PA who underwent resection (285 women [46.3%]) with ESAS data. Tiredness (443 [72%]), impaired well-being (418 [68%]), and lack of appetite (400 [65%]) were most commonly reported as moderate to severe. The proportion of patients with moderate to severe symptoms was highest immediately after surgery (range, 14%-66% per symptom) and decreased over time, stabilizing around 3 months (range, 8%-42% per symptom). Female sex, higher comorbidity, and lower income were associated with a higher risk of reporting moderate to severe symptoms. Receipt of adjuvant chemotherapy was not associated with the risk of moderate to severe symptoms. Conclusions and Relevance: There is a high prevalence of symptoms following PD for PA, with improvement over the first 3 months following surgery. In what to our knowledge is the largest cohort reporting on symptom burden for this population, we have identified factors associated with symptom severity. These findings will aid in managing patients' perioperative expectations and designing strategies to improve targeted symptom management.

Economic Analysis of Adjuvant Chemoradiotherapy Compared with Chemotherapy in Resected Pancreas Cancer.

BACKGROUND: Population-based survival and costs of pancreas adenocarcinoma patients receiving adjuvant chemoradiation and chemotherapy following pancreaticoduodenectomy are poorly understood. METHODS: This retrospective cohort study used linked administrative and pathological datasets to identify all patients diagnosed with pancreas adenocarcinoma and undergoing pancreaticoduodenectomy in Ontario between April 2004 and March 2014, who received postoperative chemoradiation or chemotherapy. Stage and margin status were defined by using pathology reports. Kaplan-Meier and Cox proportional hazards regression survival analyses were used to determine associations between adjuvant treatment approach and survival, while stratifying by margin status. Median overall health system costs were calculated at 1 and 3 years for chemoradiation and chemotherapy, and differences were tested using the Kruskal-Wallis test. RESULTS: Among 709 patients undergoing pancreaticoduodenectomy for pancreas cancer during the study period, the median survival was 21 months. Median survival was 19 months for chemoradiation and 22 months for chemotherapy. Patients receiving chemoradiation were more likely to have positive margins: 47.7% compared with 19.2% in chemotherapy. After stratifying by margin status and controlling for confounders, adjusted hazard ratio of death were not statistically different between chemotherapy and chemoradiation [margin positive, hazard ratio (HR) = 0.99, 95% confidence interval (CI) = 0.88-1.27; margin negative, HR 0.95, 95% CI 0.91-1.18]. Overall 1-year health system costs were significantly higher for chemoradiation (USD $70,047) than chemotherapy (USD $54,005) (p ≤ 0.001). CONCLUSIONS: Chemotherapy and chemoradiation yielded similar survival, but chemoradiation resulted in higher costs. To create more sustainable healthcare systems, both the efficacy and costs of therapies should be considered.

Symptom trajectories and predictors of severe symptoms in pancreatic adenocarcinoma at the end-of-life: a population based analysis of 2,538 patients.

BACKGROUND: We evaluated symptom trajectories and predictors of reporting severe symptoms in the last 6 months of life among non-resected pancreatic adenocarcinoma (PAC) decedents. METHODS: A retrospective cohort study of non-resected PAC decedents receiving care at regional cancer centres between January 2007 and December 2015. Symptoms were measured using the Edmonton Symptom Assessment System (ESAS). We described the proportion of patients reporting severe (score ≥7) symptoms by 2-week intervals during the six months prior to death. Multivariable modified Poisson regression models identified predictors of reporting severe symptom scores in the last 6 months of life. RESULTS: 2538 non-resected PAC decedents treated at regional cancer centres had ≥1 symptom ESAS record in the last six months of life, totaling 10,893 unique symptom assessments. Tiredness was the most commonly reported symptom (59% reporting ≥1 severe score), followed by lack of appetite (57%), impaired-wellbeing (49%) and drowsiness (42%). All symptoms increased closer to death. Older age, female sex, higher comorbidity status, survival less than 6 months, and urban residence were associated with a significantly higher risk of reporting severe symptoms. CONCLUSION: Non-resected PAC patients experience significant symptom burden nearing death. Patient subsets may benefit from personalized supportive care interventions.

Patterns of Symptoms Burden in Neuroendocrine Tumors: A Population-Based Analysis of Prospective Patient-Reported Outcomes.

BACKGROUND: How to best support patients with neuroendocrine tumors (NETs) remains unclear. Improving quality of care requires an understanding of symptom trajectories. Objective validated assessments of symptoms burden over the course of disease are lacking. This study examined patterns and risk factors of symptom burden in NETs, using patient-reported outcomes. SUBJECTS, MATERIALS, AND METHODS: A retrospective, population-based, observational cohort study of patients with NETs diagnosed from 2004 to 2015, who survived at least 1 year, was conducted. Prospectively collected patient-reported Edmonton Symptom Assessment System scores were linked to provincial administrative health data sets. Moderate-to-severe symptom scores were presented graphically for both the 1st year and 5 years following diagnosis. Multivariable Poisson regression identified factors associated with record of moderate-to-severe symptom scores during the 1st year after diagnosis. RESULTS: Among 2,721 included patients, 7,719 symptom assessments were recorded over 5 years following diagnosis. Moderate-to-severe scores were most frequent for tiredness (40%-51%), well-being (37%-49%), and anxiety (30%-40%). The proportion of moderate-to-severe symptoms was stable over time. Proportion of moderate-to-severe anxiety decreased by 10% within 6 months of diagnosis, followed by stability thereafter. Changes were below 5% for other symptoms. Similar patterns were observed for the 1st year after diagnosis. Primary tumor site, metastatic disease, younger age, higher comorbidity burden, lower socioeconomic status, and receipt of therapy within 30 days of assessment were independently associated with higher risk of elevated symptom burden. CONCLUSION: Patients with NETs have a high prevalence of moderate-to-severe patient-reported symptoms, with little change over time. Patients remain at risk of prolonged symptom burden following diagnosis, highlighting potential unmet needs. Combined with identified patient and disease factors associated with moderate-to-severe symptom scores, this information is important to support symptom management strategies to improve patient-centered care. IMPLICATIONS FOR PRACTICE: This study used population-level, prospectively collected, validated, patient-reported outcome measures to appraise the symptoms burden and trajectory of patients with neuroendocrine tumors (NETs) after diagnosis. It is the largest and most detailed analysis of patient-reported symptoms for NETs. Patients with NETs present a high burden of symptoms at diagnosis that persists up to 5 years later, highlighting unmet needs. Early and comprehensive symptom screening and management programs are needed. This information should serve to devise pathways and policies to better support patients, evaluate supportive interventions, and assess the effectiveness of symptom management at the provider, institutional, and system levels.

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

OBJECTIVE: Readmission following esophagectomy affects the patient experience, has important economic implications, and can be tied to hospital reimbursement. Ontario has regionalized thoracic centers; regionalized surgery may lower the readmission rate. We investigated whether surgery at regionalized thoracic centers is associated with reduced readmission following esophageal cancer resection. METHODS: A retrospective, population-based cohort study (2002-2014) was conducted in Ontario, Canada (population 13.6 million). Adults with resected esophageal cancer were identified through the Ontario Cancer Registry. Multivariable regression was used to estimate the effect of surgery at a regionalized thoracic surgery center on readmission to any Ontario hospital within 90 days following discharge. RESULTS: Of 3670 patients, 27.9% were readmitted within 90 days of discharge (n = 1022). Median hospital length of stay was 12 days (interquartile range 9-20). The readmission rate at thoracic centers was similar to other hospitals (28.1% vs 27.1%, P = .57). The readmission rate did not change during the 13-year study period. Case-mix adjusted readmission rates varied from 17.6% to 35.2% even across thoracic centers and were not related to hospital volume or perioperative mortality. After adjusting for confounders, we found that surgery at a thoracic center was not significantly associated with readmission (odds ratio, 1.10; 95% confidence interval, 0.95-1.27, P = .22). CONCLUSIONS: Surgery at a designated thoracic surgery center did not reduce the risk of 90-day readmission following esophageal cancer resection, and readmission rates varied significantly even across thoracic centers. Our results suggest that despite universal, regionalized esophageal cancer care, there appears to be a minimum readmission threshold following esophagectomy that may be clinically necessary.

Symptom Burden at the End of Life for Neuroendocrine Tumors: An Analysis of 2579 Prospectively Collected Patient-Reported Outcomes.

BACKGROUND: Given a slow course of disease, end-of-life issues are understudied in neuroendocrine tumors (NETs). To date, there are no data regarding symptoms at the end of life. This study examined symptom trajectories and factors associated with high symptom burden in NETs at the end of life. METHODS: We conducted a retrospective cohort study of NET patients diagnosed from 2004 to 2015 and who died between 2007 and 2016, in Ontario, Canada. Prospectively collected patient-reported Edmonton Symptom Assessment System scores were linked to administrative healthcare datasets. Moderate-to-severe symptom scores (≥ 4 out of 10) in the 6 months before death were analyzed, with multivariable modified Poisson regression identifying factors associated with moderate-to-severe symptoms scores. RESULTS: Among 677 NET decedents, 2579 symptom assessments were recorded. Overall, moderate-to-severe scores were most common for tiredness (86%), wellbeing (81%), lack of appetite (75%), and drowsiness (68%), with these proportions increasing as death approached. For symptoms of lack of appetite, drowsiness, and shortness of breath, the increase was steepest in the 8 weeks before death. On multivariable analyses, the risk of moderate-to-severe symptoms was significantly higher in the last 2 months before death and for patients with shorter survival (< 6 months). Women had higher risks of anxiety, nausea, and pain. CONCLUSION: A high prevalence of moderate-to-severe symptoms was observed for NETs at the end of life, not previously described. The proportion of moderate-to-severe symptoms increases steeply as death nears, highlighting an opportunity for improved management. Combined with identified factors associated with moderate-to-severe symptoms, this information is important to improve patient-centred and personalized supportive care for NETs at the end of life.

Patient-reported symptoms following mastectomy alone or lumpectomy plus radiation for early stage breast cancer: a cohort study.

PURPOSE: Studies examining symptom differences between surgeries for breast cancer patients rarely incorporate the effects of adjuvant treatment choice. We sought to understand differences in patient-reported symptoms between lumpectomy plus radiation and mastectomy in the year following surgery. METHODS: This cohort study used linked administrative datasets. The exposure was defined as lumpectomy plus radiation or mastectomy. The outcomes of moderate-to-severe (score ≥ 4) patient-reported symptoms were obtained using the Edmonton symptom assessment system (ESAS). Line plots were created to determine symptom trajectories in the 12 months following surgery, and the relationships between surgery and each of the nine symptoms were assessed using multivariable analyses. Clinical significance was determined as a difference of 10%. RESULTS: Of 13,865 Stage I-II breast cancer patients diagnosed 2007-2015, 11,497 underwent lumpectomy plus radiation and 2368 underwent mastectomy. Symptom trajectories were similar for all nine symptoms until approximately 5 months postoperatively when they diverged and mastectomy symptoms started becoming more severe. On multivariable analyses, patients undergoing mastectomy were at an increased risk of reporting moderate-to-severe depression (RR 1.19, 95% CI 1.09-1.30), lack of appetite (RR 1.11, 95% CI 1.03-1.20), and shortness of breath (RR 1.16, 95% CI 1.04-1.15) compared to those undergoing lumpectomy plus radiation. CONCLUSIONS: Even with the addition of adjuvant radiation, patients who are treated with lumpectomy fare better in three of nine patient-reported symptoms. Further examination of these differences will assist in better shared decision-making regarding surgical treatments.

Patient-reported symptoms after breast cancer diagnosis and treatment: A retrospective cohort study.

AIM: Breast cancer and its treatment are associated with varying symptoms. The province of Ontario (13.6 million) has implemented a provincial programme to screen for symptoms among cancer patients using the Edmonton Symptom Assessment System (ESAS). The purpose of this study was to describe symptom burden in the year after diagnosis among women with breast cancer. METHODS: This observational study linked cancer incidence, stage, treatment and demographic data with ESAS scores collected at cancer clinic visits. The cohort consisted of all adult women diagnosed with stage I-III breast cancer between 2007 and 2013 who received surgery as their primary treatment and had at least one symptom screening record. The prevalence and trajectory of moderate-to-severe and severe symptom scores in the year after diagnosis were described. Multivariable logistic regression models identified factors associated with moderate-to-severe and severe symptom scores. RESULTS: The cohort included 23,840 breast cancer patients and with 90,556 unique symptom assessments, within the first year from diagnosis. Tiredness had the highest incidence of moderate-to-severe scores; 60% reported at least one moderate-to-severe score in the 12 months after diagnosis, followed by impaired well-being (53%) and anxiety (44%). Elevated symptom scores were most commonly reported in 6 months after diagnosis. Higher comorbidity score (Aggregated Diagnosis Group ≥10), more advanced stage at diagnosis, younger age, urban residence, lower income and treatment course were associated with moderate-to-severe and severe symptom scores. CONCLUSION: These findings identify time points and patient subgroups at risk for elevated symptom scores and may benefit from personalised or targeted supportive care interventions.

Symptom Burden in the First Year After Cancer Diagnosis: An Analysis of Patient-Reported Outcomes.

Purpose Improvement in the quality of life of patients with cancer requires attention to symptom burden across the continuum of care, with the use of patient-reported outcomes key to achieving optimal care. Yet there have been few studies that have examined symptoms in the early postdiagnosis period during which suboptimal symptom control may be common. A comprehensive analysis of temporal trends and risk factors for symptom burden in newly diagnosed patients with cancer is essential to guide supportive care strategies. Methods A retrospective observational study was performed of patients who were diagnosed with cancer between January 2007 and December 2014 and who survived at least 1 year. Patient-reported Edmonton Symptom Assessment System scores, which are prospectively collected at outpatient visits, were linked to provincial administrative health care data. We described the proportion of patients who reported moderate-to-severe symptom scores by month during the first year after diagnosis according to disease site. Multivariable logistic regression models were constructed to identify risk factors for moderate-to-severe symptom scores. Results Of 120,745 patients, 729,861 symptom assessments were recorded within 12 months of diagnosis. For most symptoms, odds of elevated scores were highest in the first month, whereas nausea had increased odds of elevated scores up to 6 months after diagnosis. On multivariable analysis, cancer site, younger age, higher comorbidity, female sex, lower income, and urban residence were associated with significantly higher odds of elevated symptom burden. Conclusion A high prevalence of moderate-to-severe symptom scores was observed in cancers of all sites. Patients are at risk of experiencing multiple symptoms in the immediate postdiagnosis period, which underscores the need to address supportive care requirements early in the cancer journey. Patient subgroups who are at higher risk of experiencing moderate-to-severe symptoms should be targeted for tailored supportive care interventions.

Differences in single gland and multigland disease are seen in low biochemical profile primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism is characterized by increased levels of serum calcium and parathyroid hormone. Recently, 2 additional mild biochemical profiles have emerged, normocalcemic and normohormonal primary hyperparathyroidism. We reviewed our surgical experience of mild biochemical profile patients and compared them with classic primary hyperparathyroidism patients. METHODS: This is a single institution, retrospective cohort review of all patients who underwent parathyroidectomy for primary hyperparathyroidism from 2006-2012. Preoperative and intraoperative variables were analyzed. Univariable analysis was performed with analysis of variance and the χ2 test. A logistic regression was performed to identify significantly independent predictor variables for multigland disease. RESULTS: A total of 573 patients underwent parathyroidectomy for primary hyperparathyroidism (classic, n = 405; normohormonal, n = 96; normocalcemic, n = 72). Normocalcemic primary hyperparathyroidism was associated with multigland disease in 43 (45%, P < .001) patients as compared with the normohormonal (7, 10%) and classic (36, 9%) groups. On logistic regression, significant predictors for multigland disease were the normocalcemic subtype and positive family history. Twelve month biochemical normalization rates after operative treatment were >98% in all 3 groups. CONCLUSION: Our series shows that normocalcemic primary hyperparathyroidism is associated with a high incidence of multigland disease. Normohormonal disease is similar to classic disease patients with >90% presenting with single adenomas. Excellent rates of biochemical normalization can be obtained by operative treatment in all 3 groups.