Sex-related differences in oncologic outcomes, operative complications and health-related quality of life after curative-intent oesophageal cancer treatment: multicentre retrospective analysis.

BACKGROUND: Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. METHODS: All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed. RESULTS: Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P < 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms. CONCLUSION: This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women.

Recurrence and Survival after Minimally Invasive and Open Esophagectomy for Esophageal Cancer - A Post Hoc Analysis of the Ensure Study.

OBJECTIVE: The aim of this study was to determine the impact of operative approach (open [OE], hybrid [HMIE] and total minimally invasive esophagectomy [TMIE]) on operative and oncologic outcomes for patients treated with curative intent for esophageal and junctional cancer. SUMMARY BACKGROUND DATA: The optimum oncologic surgical approach to esophageal and junctional cancer is unclear. METHODS: This secondary analysis of the European multicenter ENSURE study includes patients undergoing curative-intent esophagectomy for cancer between 2009-2015 across 20 high-volume centers. Primary endpoints were disease-free survival (DFS) and the incidence and location of disease recurrence. Secondary endpoints included among others R0 resection rate, lymph node yield and overall survival (OS). RESULTS: In total, 3,199 patients were included. Of these, 55% underwent OE, 17% HMIE and 29% TMIE. DFS was independently increased post TMIE (HR 0.86 [95% CI 0.76-0.98], P=0.022) compared with OE. Multivariable regression demonstrated no difference in absolute locoregional recurrence risk according to operative approach (HMIE vs. OE OR 0.79, P=0.257, TMIE vs. OE OR 0.84, P=0.243). The probability of systemic recurrence was independently increased post HMIE (OR 2.07, P=0.031), but not TMIE (OR 0.86, P=0.508). R0 resection rates (P=0.005) and nodal yield (P<0.001) were independently increased after TMIE, but not HMIE (P=0.424; P=0.512) compared with OE. OS was independently improved following both HMIE (HR 0.79, P=0.009) and TMIE (HR 0.82, P=0.003) as compared with OE. CONCLUSION: In this European multicenter study, TMIE was associated with improved surgical quality and DFS, while both TMIE and HMIE were associated with improved OS as compared with OE for esophageal cancer.

Validity assessment of the POLARS score tool in the prediction of post rectal cancer surgery LARS score in a population-based Swedish cohort.

OBJECTIVE: Low anterior resection syndrome (LARS) is one of the most common functional impairments after rectal cancer surgery with a high impact on quality of life. The Pre-Operative LARS score (POLARS) nomogram and its online tool has been developed to predict the degree of postoperative LARS. The aim of this study was to analyse how accurately the POLARS score could predict LARS scores when compared with actual patient-reported LARS (PR-LARS) scores in a population-based Swedish cohort. DESIGN: This retrospective cohort study included patients who underwent curative rectal cancer surgery between 2007 and 2013 in Stockholm County and were identified using the Swedish Colorectal Cancer Registry (SCRCR). Information regarding preoperative risk factors, patient and treatment characteristics, and presence of LARS postoperatively were collected from patient charts, SCRCR and patient questionnaires. The POLARS model formula was used to predict LARS scores, which then were compared with the actual PR-LARS scores. Individual LARS score differences between the two estimates were shown with a modified Bland-Altman plot of difference. RESULTS: The cohort included 477 patients, of whom 359 (75%) of patients were categorised as having no/minor LARS based on the POLARS score. The correctly identified patients by the POLARS score were 80/255 (31%) in the major LARS group and 184/222 (83%) no/minor LARS group. The sensitivity was 31% for major LARS and the positive predictive value was 68%. CONCLUSION: The POLARS score has a low sensitivity for major LARS in this Swedish cohort. Other methods to predict the risk of LARS need to be developed.

Cancer-related fatigue trajectories up to 5 years after curative treatment for oesophageal cancer.

BACKGROUND: Whether cancer-related fatigue develops differently after curative-intended oesophageal cancer treatment and the related modifiable factors are unclear. METHODS: This population-based and longitudinal cohort included 409 oesophageal cancer patients who underwent curative oesophagectomy in 2013-2020 in Sweden. The main outcome was cancer-related fatigue trajectories with measurements at 1, 1.5, 2, 2.5, 3, 4 and 5 years postoperatively by validated EORTC QLQ-FA12 questionnaire, and analysed using growth mixture models. Weighted logistic regressions provided odds ratios (OR) with 95% confidence intervals (95% CI) for underlying sociodemographic, clinical, and patient-reported outcome factors in relation to the identified trajectories. RESULTS: Two distinct overall cancer-related fatigue trajectories were identified: low level of persistent fatigue and high level of increasing fatigue, with 64% and 36% of patients, respectively. The odds of having high level of fatigue trajectory were increased by Charlson comorbidity index (≥ 2 versus 0: OR = 2.52, 95% CI 1.07-5.94), pathological tumour Stage (III-IV versus 0-I: OR = 2.52, 95% CI 1.33-4.77), anxiety (OR = 7.58, 95% CI 2.20-26.17), depression (OR = 15.90, 95% CI 4.44-56.93) and pain (continuous score: OR = 1.02, 95% CI 1.01-1.04). CONCLUSIONS: Long-term trajectories with high level of increasing cancer-related fatigue and the associated modifiable factors were identified after oesophageal cancer treatment. The results may facilitate early identification and targeted intervention for such high-risk patients.

Health-related quality of life trajectories up to 15 years after curative treatment for esophageal cancer: a prospective cohort study.

BACKGROUND: The differentiation of specific, long-term health-related quality of life (HRQL) trajectories among esophageal cancer survivors remains unclear. The authors aimed to identify potentially distinctly different HRQL-trajectories and uncover the underlying factors of such trajectories in patients having undergone surgery (esophagectomy) for esophageal cancer. MATERIALS AND METHODS: This nationwide, prospective, and longitudinal cohort study included 420 patients who underwent curative treatment for esophageal cancer, including esophageal cancer surgery, in Sweden from 2001to 2005. The main outcome was HRQL summary score trajectories, measured by the well-validated EORTC QLQ-C30 questionnaire at 6 months, 3, 5, 10, and 15 years after esophagectomy, and analyzed using growth mixture models. Potentially underlying factors for these trajectories (age, sex, education, proxy baseline HRQL, comorbidity, tumor histology, chemo(radio)therapy, pathological tumor stage, and postoperative complications) were analyzed using weighted logistic regression providing odds ratios (OR) with 95% CI. RESULTS: Four distinct HRQL summary score trajectories were identified: Persistently good, improving, deteriorating, and persistently poor. The odds of belonging to a persistently poor trajectory were decreased by longer education (>12 years versus <9 years: OR 0.18, 95% CI: 0.05-0.66) and adenocarcinoma histology (adenocarcinoma versus squamous cell carcinoma: OR 0.37, 95% CI: 0.16-0.85), and increased by more advanced pathological tumor stage (III-IV versus 0-I: OR 2.82, 95% CI: 1.08-7.41) and postoperative complications (OR 2.94, 95% CI: 1.36-6.36). CONCLUSION: Distinct trajectories with persistently poor or deteriorating HRQL were identified after curative treatment for esophageal cancer. Education, tumor histology, pathological tumor stage, and postoperative complications might influence HRQL trajectories. The results may contribute to a more tailored follow-up with timely and targeted interventions. Future research remains to confirm these findings.

Neoadjuvant Chemoradiotherapy Versus Chemotherapy for the Treatment of Locally Advanced Esophageal Adenocarcinoma in the European Multicenter ENSURE Study.

OBJECTIVE: This study aimed to compare clinicopathologic, oncologic, and health-related quality of life (HRQL) outcomes following neoadjuvant chemoradiation (nCRT) and chemotherapy (nCT) in the ENSURE international multicenter study. BACKGROUND: nCT and nCRT are the standards of care for locally advanced esophageal cancer (LAEC) treated with curative intent. However, no published randomized controlled trial to date has demonstrated the superiority of either approach. METHODS: ENSURE is an international multicenter study of consecutive patients undergoing surgery for LAEC (2009-2015) across 20 high-volume centers (NCT03461341). The primary outcome measure was overall survival (OS), secondary outcomes included histopathologic response, recurrence pattern, oncologic outcome, and HRQL in survivorship. RESULTS: A total of 2211 patients were studied (48% nCT, 52% nCRT). pCR was observed in 4.9% and 14.7% ( P <0.001), with R0 in 78.2% and 94.2% ( P <0.001) post nCT and nCRT, respectively. Postoperative morbidity was equivalent, but in-hospital mortality was independently increased [hazard ratio (HR)=2.73, 95% CI: 1.43-5.21, P= 0.002] following nCRT versus nCT. Probability of local recurrence was reduced (odds ratio=0.71, 95% CI: 0.54-0.93, P =0.012), and distant recurrence-free survival time reduced (HR=1.18, 95% CI: 1.02-1.37, P =0.023) after nCRT versus nCT, with no difference in OS among all patients (HR=1.10, 95% CI: 0.98-1.25, P =0.113). On subgroup analysis, patients who underwent R0 resection following nCT as compared with nCRT had improved OS (median: 60.7 months, 95% CI: 49.5-71.8 vs 40.8 months, 95% CI: 42.8-53.4, P <0.001). CONCLUSIONS: In this European multicenter study, nCRT compared with nCT was associated with reduced probability of local recurrence but reduced distant recurrence-free survival for patients with LAEC, without differences in OS. These data support tailored patient-specific decision-making in the overall approach to achieving optimum outcomes in LAEC.

Home-based physical activity after treatment for esophageal cancer-A randomized controlled trial.

BACKGROUND: The treatment of most esophageal cancer patients includes chemo(radio)therapy and extensive surgery, causing physical decline with loss of muscles. This trial aimed to test the hypothesis that a tailored home-based physical activity (PA) intervention improves muscle strength and mass in patients having undergone curative treatment for esophageal cancer. METHODS: Patients operated for esophageal cancer 1 year earlier were included in a nationwide randomized controlled trial in Sweden in 2016-2020. The intervention group was randomized to a 12-week home-based exercise program, while the control group was encouraged to maintain routine daily PA. The primary outcomes were changes in maximal/average hand grip strength measured with hand grip dynamometer and lower extremity strength measured using 30-second chair stand test and muscle mass measured using a portable bio-impedance analysis monitor. Intention-to-treat analysis was used, and results were presented as mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Among 161 randomized patients, 134 completed the study, 64 in the intervention group and 70 in the control group. Compared with the control group (MD 2.73; 95% CI 1.75-3.71), patients in the intervention group (MD 4.48; 95% CI 3.18-5.80) had statistically significantly (p = 0.03) improved lower extremity strength. No differences were seen for hand grip strength or muscle mass. CONCLUSION: A home-based PA intervention 1 year after surgery for esophageal cancer improves lower extremity muscle strength.

Associations in health-related quality of life between patients and family caregivers 1 year after oesophageal cancer surgery.

PURPOSE: Whether patients' health-related quality of life (HRQL) influences the HRQL of their family caregivers remains to be clarified. Therefore, the aim of this study was to investigate the association in HRQL between patients and family caregivers one year after oesophageal cancer surgery. METHODS: The study was based on a prospective, nationwide, and population-based cohort including patients treated by surgery for oesophageal cancer in Sweden from 2013 to 2021 and their family caregivers. Data were collected one year after surgery, using the summary score of the EORTC QLQ-C30 and the RAND-36 questionnaire. Univariate and multivariate linear regression models providing regression coefficients with confidence intervals (CI) were used to estimate the association between the HRQL among patients and family caregivers. The analyses were adjusted for potential covariates. RESULTS: In total, 275 patients and paired family caregivers were included in the study. Patients reported a mean HRQL summary score of 81.4, indicating reductions in functions as well as many burdensome symptoms. Among family caregivers, lowest HRQL scores were reported for pain (69.2 ± 26.0) and energy/fatigue (65.1 ± 20.4). A 10-point change in the patients' summary score corresponded to a 7-point change for family caregivers' emotional role function (ß = 7.0; 95% CI: 3.6-10.3). For other HRQL dimensions among the family caregivers, no clinically relevant associations with patients HRQL were found. CONCLUSION: The current study indicates that family caregivers' emotional role function is influenced by patients' overall HRQL one year after surgery. The finding suggests that follow-up interventions should include not only patients but also their family caregivers.

Health-related quality of life 15 years after oesophageal cancer surgery: a prospective nationwide cohort study.

PURPOSE: We aimed to study oesophageal cancer survivors' health-related quality of life (HRQL) 15 years after surgery and to identify factors related to reduced HRQL. METHODS: A nationwide, prospective cohort study enrolling 616 patients who underwent open oesophageal cancer surgery in Sweden between April 2, 2001, and December 21, 2005. HRQL was evaluated by questionnaires 15 years after surgery. HRQL data for the 15-year survivors were individually matched for age, sex and comorbidity by using values from a Swedish background population. Multivariable linear regression models provided mean score differences (MSD) with 95% confidence intervals (CI) for each HRQL scale and item. RESULTS: Among the 616 individuals in the original study group, 70 (11%) survived for 15 years and 52 (74%) responded to the questionnaires. Compared with a matched background population, the survivors reported problems in 10 of 25 HRQL aspects. Most of these were related to symptoms of the digestive tract, such as reflux (MSD 26.4, 95%CI: 18.3 to 34.4), dysphagia (MSD 17.7, 95%CI: 10.0 to 25.4) and eating difficulties (MSD 16.4, 95%CI: 11.3 to 21.4). Major postoperative complications after surgery were related to worse HRQL in 11 of 25 aspects. CONCLUSIONS: This study suggests that surgery for oesophageal cancer entails long-term, possibly life-long, symptoms related to the digestive tract. IMPLICATION FOR CANCER SURVIVORS: Comprehensive support from healthcare may be imperative for oesophageal cancer survivors to adapt to and cope with consequences of oesophageal cancer surgery. Prevention, early identification and adequate treatment of postoperative complications may improve patient outcome.

A Randomized Controlled Clinical Trial of Transanal Irrigation Versus Conservative Treatment in Patients With Low Anterior Resection Syndrome After Rectal Cancer Surgery.

OBJECTIVE: The aim of the study was to evaluate transanal irrigation (TAI) as a treatment for low anterior resection syndrome (LARS). BACKGROUND: LARS is a bowel disorder that is common after sphincter preserving rectal cancer surgery. Despite symptomatic medical treatment of LARS many patients still experience bowel symptoms that may have a negative impact on quality of life (QoL). TAI is a treatment strategy, of which the clinical experience is promising but scientific evidence is limited. MATERIALS AND METHODS: A multicenter randomized trial comparing TAI (intervention) with conservative treatment (control) was performed. Inclusion criteria were major LARS, age above 18 years, low anterior resection with anastomosis and a defunctioning stoma as primary surgery, >6 months since stoma reversal, anastomosis without signs of leakage or stricture, and no signs of recurrence at 1-year follow-up. The primary endpoint was differences in bowel function at 12-month follow-up measured by LARS score, Cleveland Clinic Florida Fecal Incontinence Score, and 4 study-specific questions. The secondary outcome was QoL. RESULTS: A total of 45 patients were included, 22 in the TAI group and 23 in the control group. Follow-up was available for 16 and 22 patients, respectively. At 12 months, patients in the TAI group reported significantly lower LARS scores (22.9 vs 32.4; P =0.002) and Cleveland Clinic Florida Fecal Incontinence Score (6.4 vs 9.2; P =0.050). In addition, patients in the TAI group also scored significantly higher QoL [8 of 16 European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) QoL aspects] compared with the control group. CONCLUSIONS: The results confirm our clinical experience that TAI reduces symptoms included in LARS and improves QoL.

An International Multicenter Study Exploring Whether Surveillance After Esophageal Cancer Surgery Impacts Oncological and Quality of Life Outcomes (ENSURE).

OBJECTIVE: To determine the impact of surveillance on recurrence pattern, treatment, survival and health-related quality-of-life (HRQL) following curative-intent resection for esophageal cancer. SUMMARY BACKGROUND DATA: Although therapies for recurrent esophageal cancer may impact survival and HRQL, surveillance protocols after primary curative treatment are varied and inconsistent, reflecting a lack of evidence. METHODS: European iNvestigation of SUrveillance after Resection for Esophageal cancer was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers (2009-2015) across 20 centers (NCT03461341). Intensive surveillance (IS) was defined as annual computed tomography for 3 years postoperatively. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival, recurrence pattern, and HRQL. Multivariable linear, logistic, and Cox proportional hazards regression analyses were performed. RESULTS: Four thousand six hundred eighty-two patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median followup 60 months, 47.5% developed recurrence, oligometastatic in 39%. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12-0.25]) and increased tumor-directed therapy (OR 2.09 [1.58-2.77]). After adjusting for confounders, no OS benefit was observed among all patients (HR 1.01 [0.89-1.13]), but OS was improved following IS for those who underwent surgery alone (HR 0.60 [0.47-0.78]) and those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58-0.89]). IS was associated with greater anxiety ( P =0.016), but similar overall HRQL. CONCLUSIONS: IS was associated with improved oncologic outcome in select cohorts, specifically patients with early-stage disease at presentation or favorable pathological stage post neoadjuvant therapy. This may inform guideline development, and enhance shared decision-making, at a time when therapeutic options for recurrence are expanding.

Quality of life and patient reported symptoms after colorectal cancer in a Swedish population.

AIM: A proportion of patients treated for colorectal cancer have impaired quality of life (QoL) but it is uncertain if the level of QoL differs from the corresponding background population. This population-based cohort study aimed to evaluate health-related QoL in colorectal cancer patients and compare their QoL with that of a Swedish reference population. METHODS: Patients who underwent surgery for colorectal cancer Stages I-III in the Stockholm-Gotland region in 2013-2015 received the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the QLQ-CR29 questionnaires and the low anterior resection syndrome score, 1 year after surgery. Patient and tumour data were collected from the Swedish Colorectal Cancer Registry. The patient cohort was matched to a Swedish reference population regarding EORTC QLQ-C30. Global QoL was compared to the reference population and a patient group with impaired QoL was defined. Detailed patient-reported outcomes were analysed in relation to global QoL in the patient cohort. RESULTS: A total of 925 patients returned the questionnaires and 358 patients (38.70%) reported a clinically relevant impaired global QoL compared to the reference population. Patients with impaired QoL reported clinically relevant and statistically significantly more complaints regarding bowel habits, pain and anxiety. After adjustment for sex, age and stoma, anxiety was the strongest predictor for impaired QoL, with OR 6.797 (95% CI 4.677-9.879). CONCLUSION: A substantial proportion of patients treated for colorectal cancer have impaired global QoL. This impairment is strongly associated with several physical symptoms and anxiety.

Minimally invasive surgical techniques for oesophageal cancer and nutritional recovery: a prospective population-based cohort study.

OBJECTIVES: To explore whether the minimally invasive oesophagectomy (MIE) or hybrid minimally invasive oesophagectomy (HMIE) are associated with better nutritional status and less weight loss 1 year after surgery, compared with open oesophagectomy (OE). DESIGN: Prospective cohort study. SETTING: All patients undergoing oesophagectomy for cancer in Sweden during 2013-2018. PARTICIPANTS: A total of 424 patients alive at 1 year after surgery were eligible, and 281 completed the 1-year assessment. Of these, 239 had complete clinical data and were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was nutritional status at 1 year after surgery, assessed using the abbreviated Patient-Generated Subjective Global Assessment questionnaire. The secondary outcomes included postoperative weight loss at 6 months and 1 year after surgery. RESULTS: Of the included patients, 78 underwent MIE, 74 HMIE while 87 patients underwent OE. The MIE group had the highest prevalence of malnutrition (42% vs 22% after HMIE vs 25% after OE), reduced food intake (63% vs 45% after HMIE vs 39% after OE), symptoms reducing food intake (60% vs 45% after HMIE vs 60% after OE) and abnormal activities/function (45% vs 32% after HMIE vs 43% after OE). After adjustment for confounders, MIE was associated with a statistically significant increased risk of reduced food intake 1 year after surgery (OR 2.87, 95% CI 1.47 to 5.61), compared with OE. Other outcomes were not statistically significantly different between the groups. No statistically significant associations were observed between surgical techniques and weight loss up to 1 year after surgery. CONCLUSIONS: MIE was statistically significantly associated with reduced food intake 1 year after surgery. However, no differences were observed in weight loss between the surgical techniques. Further studies on nutritional impact of surgical techniques in oesophageal cancer are needed.

Caregiver burden and health-related quality of life among family caregivers of oesophageal cancer patients: a prospective nationwide cohort study.

BACKGROUND: Oesophageal cancer surgery is extensive with high risk of long-term health-related quality of life (HRQL) reductions. After hospital discharge, the family members often carry great responsibility for the rehabilitation of the patient, which may negatively influence their wellbeing. The purpose was to clarify whether a higher caregiver burden was associated with psychological problems and reduced HRQL for family caregivers of oesophageal cancer survivors. MATERIAL AND METHODS: This was a nationwide prospective cohort study enrolling family members of all patients who underwent surgical resection for oesophageal cancer in Sweden between 2013 and 2020. The family caregivers reported caregiver burden, symptoms of anxiety, depression, post-traumatic stress, and HRQL 1 year after the patient's surgery. Associations were analysed with multivariable logistic regression and presented as odds ratios (OR) with 95% confidence intervals (CI). Differences between groups were presented as mean score differences (MSD). RESULTS: Among 319 family caregivers, 101 (32%) reported a high to moderate caregiver burden. Younger family caregivers were more likely to experience a higher caregiver burden. High-moderate caregiver burden was associated with an increased risk of symptoms of anxiety (OR 5.53, 95%CI: 3.18-9.62), depression (OR 8.56, 95%CI: 3.80-19.29), and/or posttraumatic stress (OR 5.39, 95%CI: 3.17-9.17). A high-moderate caregiver burden was also associated with reduced HRQL, especially for social function (MSD 23.0, 95% CI: 18.5 to 27.6) and role emotional (MSD 27.8, 95%CI: 19.9 to 35.7). CONCLUSIONS: The study indicates that a high caregiver burden is associated with worse health effects for the family caregiver of oesophageal cancer survivors.

Dispositional optimism and all-cause mortality after esophageal cancer surgery: a nationwide population-based cohort study.

PURPOSE: To examine the association between dispositional optimism and all-cause mortality after esophageal cancer surgery and whether pathological tumor stage and the COVID-19 pandemic modified this association. METHODS: This nationwide, population-based prospective cohort study included 335 patients undergoing esophageal cancer surgery in Sweden between January 1, 2013, and December 31, 2019. Dispositional optimism was measured 1 year post-surgery using Life Orientation Test-Revised (LOT-R). A higher LOT-R sum score represents higher dispositional optimism. Mortality information was obtained from the Swedish Register of the Total Population. All patients were followed up until death or until December 31, 2020, whichever occurred first. Cox regression with adjustments for confounders was used. RESULTS: The median follow-up was 20.8 months, during which 125 (37.3%) patients died. Among the included 335 patients, 219 (65.4%) patients had tumor pathologically staged Tis-II, and 300 (89.6%) patients entered the cohort before the COVID-19 pandemic. Both tumor stage and the COVID-19 pandemic were effect modifiers. For each unit increase in LOT-R sum score, the risk of all-cause mortality decreased by 11% (HR 0.89, 95% CI 0.81 to 0.98) among patients with tumor staged Tis-II before the COVID-19 pandemic. This association was non-significant in patients with tumor staged III-IV (HR 0.99, 95% CI 0.92 to 1.07) and during the COVID-19 pandemic (HR 1.08, 95% CI 0.94 to 1.25). CONCLUSION: Assessing dispositional optimism may help predict postoperative survival, especially for patients with early and intermediate esophageal cancer. Increasing dispositional optimism might be a potential intervention target to improve survival after esophageal cancer surgery.

The weight loss grading system as a predictor of cancer cachexia in oesophageal cancer survivors.

BACKGROUND: Oesophageal cancer survivorship is afflicted by cancer cachexia related weight loss and nutrition impact symptoms. Identifying the factors which predict cancer cachexia specifically is warranted in order to identify those at risk and render the right kind of support. We aimed to assess if preoperative and postoperative body mass index (BMI) adjusted weight loss grading system (WLGS) is predictive of cancer cachexia at one year after surgery for oesophageal cancer. METHODS: Data were used from a prospective nationwide cohort study on patients operated on for oesophageal cancer in Sweden between 2013 and 2018 included at one year after surgery. The study exposure is BMI adjusted weight loss graded into one of five distinct weight loss grades (grades 0-4), defined in accordance with the WLGS by combining BMI and percentage weight loss, assessed at two clinical time points: preoperative and at 6 months post-surgery for oesophageal cancer. The study outcome is subjective measures of cancer cachexia one year after surgery, assessed using the cancer-cachexia specific questionnaire EORTC QLQ-CAX24. Multivariable linear regression models calculated mean score differences (MD) with 95% confidence intervals (CI) adjusted for predefined confounders. Statistical significance at p < 0.05 together with a clinically relevant difference of 10-points in mean scores was considered as a significant difference. RESULTS: Among a total of 232 patients, the highest grade of preoperative WLGS 4 was associated with significantly worse physical decline than lower grades of WLGS 1 (MD -10, 95% CI: -20 to -1) and WLGS 2 (MD -11, 95% CI: -20 to -2). Those with preoperative WLGS 2, 3 and 4 reported lower scores on the adequacy of information on weight loss provided to them than those with preoperative WLGS 0. Those with the highest postoperative WLGS 4 had greater eating and weight loss worry than WLGS 2 (MD -17, 95% CI: -32 to -3) and WLGS 3 (MD -11, 95% CI: -21 to -2) and worse physical decline than WLGS 0 (MD -14, 95% CI: -25 to -2). CONCLUSIONS: Higher grades of both preoperative and postoperative WLGS are predictive of cancer cachexia related physical decline one year after surgery for oesophageal cancer. Additionally, preoperative and postoperative WLGS were also predictive of inadequate information concerning weight loss and more worry regarding eating and weight loss, respectively. The WLGS may be an effective risk prediction tool for postoperative cachexia related physical decline in patients undergoing treatment for oesophageal cancer emphasizing its usability in the clinical setting.

Body Mass Index-Adjusted Weight Loss Grading System and Cancer-Related Fatigue in Survivors 1 Year After Esophageal Cancer Surgery.

BACKGROUND: The association between pre- and postoperative weight loss and cancer-related fatigue after esophageal cancer surgery is unclear. This nationwide, prospective, longitudinal cohort study aimed to assess the influence of weight loss on cancer-related fatigue among esophageal cancer survivors. METHODS: Patients who underwent esophagectomy for cancer between 2013 and 2019 in Sweden were enrolled in this study. Exposure was measured by the body mass index-adjusted weight loss grading system (WLGS). Cancer-related fatigue was assessed using the fatigue scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the EORTC QLQ-Fatigue 12 (QLQ-FA12) questionnaire measuring overall fatigue and physical, emotional, and cognitive fatigue. Growth mixture models were used to identify unobserved trajectories of cancer-related fatigue. Multivariable linear and logistic regression models were fitted to assess the associations between WLGS and cancer-related fatigue, adjusting for potential confounders. RESULTS: Three trajectories were identified-low, moderate, and severe persistent fatigue. Cancer-related fatigue remained stable in each trajectory between 1 and 3 years after esophagectomy. Among the 356 enrolled patients, 4.5-22.6% were categorized into the severe persistent fatigue trajectory in terms of QLQ-C30 (19.9%), FA12 overall (10.5%), physical (22.6%), emotional (15.9%), and cognitive fatigue (4.5%). No association between pre- or postoperative WLGS and cancer-related fatigue was found between 1 and 3 years after esophageal cancer surgery. CONCLUSIONS: Weight loss did not seem to influence cancer-related fatigue after esophageal cancer surgery.

Health-related quality of life among family caregivers of oesophageal cancer survivors one year after curative intended treatment - a nationwide population-based study.

BACKGROUND: To investigate factors that might influence the quality of life of the family caregivers of oesophageal cancer patients. MATERIAL AND METHODS: A cross-sectional study within a prospective, population-based nationwide cohort study including family caregivers to oesophageal cancer patients was conducted. The exposures were family caregivers' age, sex, education level and patients' tumour stage, postoperative complications, weight loss and comorbidities. The outcome was health-related quality of life (HRQL) one year after the patient's cancer surgery measured by the RAND-36. Multivariable linear regression analysis provided mean score differences (MSD) with 95% confidence intervals (CI). RESULTS: In total 257 family caregivers were included. Family caregivers ≥65 years displayed lower physical function (MSD=-8.5; p = 0.001) but a higher level of energy (MSD = 9.2; p = 0.002). Those with a higher education level had less pain (MSD = 11.2; p = 0.01) and better physical function (MSD = 9.1; p = 0.006).Among the patient related exposures, postoperative complications were associated with family caregivers' physical function (MSD= -6.0; p = 0.01) and pain (MSD= -7.9; p = 0.01). Tumour stage and comorbidities were not associated with the HRQL of the family caregiver. CONCLUSION: The study suggests that patients' complications and age and education level of the family caregivers are associated with family caregivers HRQL. This information provides guidance in the process of creating support for family caregivers of oesophageal cancer patients.

Lasting Symptoms After Esophageal Resection (LASER): European Multicenter Cross-sectional Study.

OBJECTIVE: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. BACKGROUND: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. PATIENTS AND METHODS: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. RESULTS: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ±â€Š0.02 and 0.82 ±â€Š0.09 respectively. CONCLUSION: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.

Severe Reflux and Symptoms of Anxiety and Depression After Esophageal Cancer Surgery.

BACKGROUND: Approximately 30% of patients suffer from severe reflux after surgery for esophageal cancer, which may serve as a continuous reminder of the cancer and catalyze fear of recurrence. OBJECTIVE: The aim of this study was to investigate the association between severe reflux and symptoms of anxiety and depression after esophageal cancer surgery. METHODS: This was a nationwide prospective cohort study including all Swedish patients who underwent esophageal cancer surgery between 2013 and 2018. Patients reported reflux on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module for gastroesophageal symptoms and psychological distress on the Hospital Anxiety and Depression Scale at 1 and 2 years after surgery. Repeated-measures logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for age, sex, comorbidity, body mass index, TNM classification, neoadjuvant therapy, surgery type, postoperative complications, antireflux medication, and elevated headrest at night. RESULTS: Among 154 included patients, 43 (28%) and 37 (24%) reported severe reflux 1 and 2 years after surgery, respectively. No association between severe reflux and anxiety (OR, 2.1; 95% CI, 0.7-6.3) or depression (OR, 1.2; 95% CI, 0.3-4.6) was found 1 year after surgery. After 2 years, there was still no association between severe reflux and anxiety (OR, 0.9; 95% CI, 0.3-2.8) or depression (OR, 1.2; 95% CI, 0.5-3.3). CONCLUSIONS: Findings suggest that severe reflux is not associated with anxiety or depression after esophageal cancer surgery. IMPLICATIONS FOR PRACTICE: For esophageal cancer survivors, other factors than severe reflux may be more important for the psychological recovery.