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.

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.

Randomized controlled trial of nasogastric tube use after esophagectomy: study protocol for the kinetic trial.

Esophagectomy is a complex and complication laden procedure. Despite centralization, variations in perioparative strategies reflect a paucity of evidence regarding optimal routines. The use of nasogastric (NG) tubes post esophagectomy is typically associated with significant discomfort for the patients. We hypothesize that immediate postoperative removal of the NG tube is non-inferior to current routines. All Nordic Upper Gastrointestinal Cancer centers were invited to participate in this open-label pragmatic randomized controlled trial (RCT). Inclusion criteria include resection for locally advanced esophageal cancer with gastric tube reconstruction. A pretrial survey was undertaken and was the foundation for a consensus process resulting in the Kinetic trial, an RCT allocating patients to either no use of a NG tube (intervention) or 5 days of postoperative NG tube use (control) with anastomotic leakage as primary endpoint. Secondary endpoints include pulmonary complications, overall complications, length of stay, health related quality of life. A sample size of 450 patients is planned (Kinetic trial: https://www.isrctn.com/ISRCTN39935085). Thirteen Nordic centers with a combined catchment area of 17 million inhabitants have entered the trial and ethical approval was granted in Sweden, Norway, Finland, and Denmark. All centers routinely use NG tube and all but one center use total or hybrid minimally invasive-surgical approach. Inclusion began in January 2022 and the first annual safety board assessment has deemed the trial safe and recommended continuation. We have launched the first adequately powered multi-center pragmatic controlled randomized clinical trial regarding NG tube use after esophagectomy with gastric conduit reconstruction.

Extent of Lymphadenectomy and Long-term Survival in Esophageal Cancer.

OBJECTIVE: To examine the hypothesis that survival in esophageal cancer increases with more removed lymph nodes during esophagectomy up to a plateau, after which it levels out or even decreases with further lymphadenec-tomy. SUMMARY OF BACKGROUND DATA: There is uncertainty regarding the ideal extent of lymphadenectomy during esophagectomy to optimize long-term survival in esophageal cancer. METHODS: This population-based cohort study included almost every patient who underwent esophagectomy for esophageal cancer in Sweden or Finland in 2000-2016 with follow-up through 2019. Degree of lymphadenectomy, divided into deciles, was analyzed in relation to all-cause 5-year mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for all established prognostic factors. RESULTS: Among 2306 patients, the second (4-8 nodes), seventh (21-24 nodes) and eighth decile (25-30 nodes) of lymphadenectomy showed the lowest all-cause 5-year mortality compared to the first decile [hazard ratio (HR) = 0.77, 95% CI 0.61-0.97, HR = 0.76, 95% CI 0.59-0.99, and HR = 0.73, 95% CI 0.57-0.93, respectively]. In stratified analyses, the survival benefit was greatest in decile 7 for patients with pathological T-stage T3/T4 (HR = 0.56, 95% CI0.40-0.78), although it was statistically improved in all deciles except decile 10. For patients without neoadjuvant chemotherapy, survival was greatest in decile 7 (HR = 0.60, 95% CI 0.41-0.86), although survival was also statistically significantly improved in deciles 2, 6, and 8. CONCLUSION: Survival in esophageal cancer was not improved by extensive lymphadenectomy, but resection of a moderate number (20-30) of nodes was prognostically beneficial for patients with advanced T-stages (T3/T4) and those not receiving neoadjuvant therapy.

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.

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.

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.

Comparison between Swedish EORTC QLQ-C30 general population norm data published in 2000 and 2019.

BACKGROUND: Normative health-related quality of life (HRQoL) data from the general population are regularly used to facilitate the interpretation of HRQoL as reported by cancer patients participating in cancer clinical trials, especially when conducting long-term follow-up studies after treatment. The aim of the present study is to compare two Swedish normative data sets, published in 2000 and 2019 respectively, and explore whether HRQoL as reported by the Swedish general population has changed over time. MATERIAL AND METHODS: 'Sample 2000' was comprised of normative data from the Swedish general population who responded to the EORTC QLQ-C30 in a Swedish mail survey in 1999 (n = 3069). 'Sample 2019' consisted of data from the Swedish general population collected as part of a European norm data study using online panels, published in 2019 (n = 1027). Data were analyzed stratified by sex and age (40-49; 50-59; 60-69; 70-79 years). RESULTS: For most of the subscales and single items, no age group differences between the two samples were found, with the exception of the oldest age group (70-79 years), where Sample 2019 generally showed better HRQoL as compared to Sample 2000. Lower (worse) levels of Global quality of life and higher (worse) levels of Dyspnoea were found in Sample 2019 for most age groups. CONCLUSION: There were no differences found between the samples for most EORTC QLQ-C30 subscales and single items, with the exception of the oldest age group of both sexes in Sample 2019 who reported better HRQoL on many variables. When deciding which normative dataset to use, the mode of data collection and age group have to be considered.

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.

The long-term experience of being a family caregiver of patients surgically treated for oesophageal cancer.

AIM: This qualitative study aimed to explore the experience of being family caregivers of patients treated for oesophageal cancer 2 years after treatment. To better understand the family caregiver's situation, a conceptual model was used in the analysis. The results of the study can guide future interventions to support family caregivers of patients treated for oesophageal cancer. DESIGN: A qualitative descriptive study using semi-structured telephone interviews. An abductive approach was used in the analysis to reach deeper knowledge about the family caregivers' experiences and to better understand deeper patterns. METHODS: A qualitative study was conducted and included 13 family caregivers of patients surgically treated for oesophageal cancer in Sweden in 2018 who participated in a population-based nationwide cohort study. Individual telephone interviews were held in 2020, 2 years after the patients' surgery. The analysis of the interviews started with an inductive approach using thematic analysis. Thereafter, a deductive approach was used to interpret the findings in relation to the conceptual model, The Cancer Family Caregiving Experience. RESULTS: The most essential/evident stress factors for the family caregivers were distress regarding the patients' nutrition, fear of tumour recurrence and worry about the future. In addition, a transition was experienced, going from a family member to a caregiver, and the many psychosocial aspects of this transition were highlighted during the disease trajectory. CONCLUSION: Despite, the long-term survival of the patient, family caregivers were still struggling with psychosocial consequences because of the patient's cancer diagnosis and treatment. Furthermore, there is a need to improve supportive interventions for family caregivers during the whole disease trajectory. IMPACT: The current study includes comprehensive information about the family caregivers' experiences when caring for a patient treated for oesophageal cancer. Family caregivers struggle with the psychosocial consequences of the patient's cancer and worry about tumour recurrence even 2 years after surgery. These findings can be useful in the development of supportive interventions, which may facilitate life for family caregivers. PATIENT OR PUBLIC CONTRIBUTION: The study was discussed and planned together with our research partnership group including patients and family caregivers. In addition, the manuscript was reviewed by some of the members to cross-check the results and discussed them to avoid misinterpretation.

Long-term Survival in Esophageal Cancer After Minimally Invasive Esophagectomy Compared to Open Esophagectomy.

OBJECTIVE: To examine 5-year survival in esophageal cancer after MIE compared to OE. SUMMARY BACKGROUND DATA: MIE is becoming an increasingly common approach in the surgical treatment of esophageal cancer. A recent meta-analysis suggested 18% lower 5-year all-cause mortality after MIE compared to OE, but the quality of the included studies was limited. METHODS: Population-based cohort study including almost all patients who underwent elective esophagectomy for esophageal cancer in Sweden or Finland in 2010 to 2016, with follow-up until end of 2019. Cox regression was used to provide hazard ratios (HRs) with 95% confidence intervals (CIs) of all-cause 5-year mortality (main outcome) after MIE (hybrid or total) versus OE. Adjustments were made for age, sex, comorbidity, pathological tumor stage, histological tumor type, neoadjuvant chemo(radio)therapy, country, and annual hospital volume of esophagectomy. RESULTS: Among all 1264 patients, 470 (37.2%) underwent MIE and 794 (62.8%) underwent OE. MIE was associated with an 18% decreased risk of all-cause 5-year mortality, compared to OE [adjusted HR 0.82, 95% CI 0.67- 1.00 ( P = 0.048)]. The HR of all-cause 5-year mortality was seemingly lower after total MIE compared to OE (adjusted HR 0.77, 95% CI 0.60-0.98) than after hybrid MIE compared to OE (adjusted HR 0.87, 95% CI 0.68-1.11). CONCLUSIONS: This bi-national study indicates that MIE is associated with a higher 5-year survival than OE in patients with esophageal cancer, and that the survival benefit is greater after total MIE than hybrid MIE.

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.

Life Expectancy in Survivors of Esophageal Cancer Compared with the Background Population.

It is unknown whether the survival of patients cured of esophageal cancer differs from that of the corresponding background population. This nationwide and population-based cohort study included all patients who survived for at least 5 years after surgery for esophageal cancer in Sweden between 1987 and 2015, with follow-up throughout 2020. Relative survival rates with 95% confidence intervals (95% CI) were calculated by dividing the observed with the expected survival. The expected survival was assessed from the entire Swedish population of the corresponding age, sex, and calendar year. Yearly relative survival rates were calculated between 6 and 10 years postoperatively. Among all 762 participants, the relative survival was initially similar to the background population (96.1%, 95% CI 94.3-97.9%), but decreased each following postoperative year to 83.5% (95% CI 79.5-87.6%) by year 10. The drop in relative survival between 6 and 10 years was more pronounced in participants with a history of squamous cell carcinoma [from 94.5% (95% CI 91.2-97.8%) to 70.8% (95% CI 64.0-77.6%)] than in those with adenocarcinoma [from 96.9% (95% CI 94.8-99.0%) to 91.5% (95% CI 86.6-96.3%)], and in men [from 96.0% (95% CI 93.8-98.1%) to 81.8% (95% CI 76.8-86.8%)] than in women [from 96.4% (95% CI 93.4-99.5%) to 88.1% (95% CI 81.5-94.8%)]. No major differences were found between age groups. In conclusion, esophageal cancer survivors had a decline in survival between 6 and 10 years after surgery compared with the corresponding general population, particularly those with a history of squamous cell carcinoma of the esophagus and male sex.

Cancer-Related Fatigue After Esophageal Cancer Surgery: Impact of Postoperative Complications.

BACKGROUND: The impact of postoperative complications on cancer-related fatigue is unknown. This nationwide prospective cohort study aimed to assess the trajectory of cancer-related fatigue and the influence of predefined postoperative complications on cancer-related fatigue up to 2 years after esophageal cancer surgery. METHODS: The patients in this study underwent esophagectomy between 2013 and 2019 in Sweden. The exposure was predefined postoperative complications. The outcome was cancer-related fatigue measured by 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. Linear mixed-effects models provided adjusted fatigue scores and mean score differences (MDs) with 95% confidence intervals (CIs) between patients with and without predefined complications. RESULTS: The study enrolled 331 patients. The QLQ-C30 fatigue score increased with clinical relevance among patients with any complications (MD, 5.8; 95% CI, 2.6-9.0) who had a higher Clavien-Dindo classification (grades 2 to 3a: MD, 7.3; 95% CI, 3.1-11.5), a medical complication (MD, 6.9; 95% CI, 3.0-10.7), or a pulmonary complication (MD, 6.9; 95% CI, 2.1-11.6) for 1-1.5 years and remained stable until 2 years after esophagectomy. Similar patterns were found in the QLQ-FA12 fatigue and QLQ-FA12 physical and emotional subscales, but not in the cognitive subscales. CONCLUSIONS: Complications in general and medical and pulmonary complications in particular might be associated with increased cancer-related fatigue after esophagectomy.

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.

Patient and public involvement in oesophageal cancer survivorship research.

BACKGROUND: Good clinical research is often conducted in close collaboration between patients, the public, and researchers. Few studies have reported the development of patient and public involvement (PPI) in research outside the United States and the United Kingdom, and for patients with more aggressive cancers. The study aimed to describe and evaluate the development of PPI in oesophageal cancer survivorship research in Sweden by the use of a framework to support the process. METHODS: Oesophageal cancer survivors were recruited to a PPI research collaboration at Karolinska Institutet, Sweden. The development process was supported by the use of a framework for PPI, 'Patient and service user engagement in research'. Insights, benefits, and challenges of the process were described and discussed among the collaborators. RESULTS: The collaboration resulted in joint publications with a more patient- and family-focussed perspective. It also contributed to the development of information folders about survivorship after oesophageal cancer surgery and national conference arrangements for patients, their families, healthcare workers, and researchers. Since the PPI contributors were represented in patient organisations and care programmes, the dissemination of research results increased. Their contributions were highly valued by the researchers, but also revealed some challenges. The use of a structured framework contributed to support and facilitated the process of establishing PPI in research collaboration. CONCLUSIONS: A genuine interest in establishing PPI in research and an understanding and respect for the patients' expertise in providing a unique inside perspective was imperative for a successful collaboration. Research focus should not only be on mortality and reductions in daily life, but also on positive outcomes. Using a framework supports development and avoids pitfalls of PPI collaboration. PATIENT AND PUBLIC CONTRIBUTION: Patient partners were equal collaborators in all aspects of the study.

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.

Experiences of being a family caregiver to a patient treated for oesophageal cancer-1 year after surgery.

PURPOSE: There is a need to put family caregivers on the cancer survivorship research agenda. Therefore, the aim of this is study is to explore the experiences of being a family caregiver to a patient treated for oesophageal cancer. METHOD: This qualitative study was based on the ongoing nationwide and prospective Oesophageal Surgery on Cancer patients - Adaptation and Recovery study (OSCAR) including patients surgically treated for oesophageal cancer in Sweden and their closest family caregiver. One year after the patient's surgery, each family caregiver received a self-report questionnaire kit to fill in. For the purpose of this study, the responses to the open-ended question "Is there anything else you would like to share?" were used and analysed by conducting thematic analysis. RESULTS: In total, 112 responses to the open-ended question were transcribed and analysed. The text rendered three themes: Discontinued support from healthcare-mostly a positive experience before surgery and in the acute survivorship phase. However, after discharge from the hospital, the family caregiver felt as though they were left alone, fully responsible for the patient's care. A changed life-unprepared for life-changing situation after the patient received the cancer diagnosis. A feeling that nothing will ever be the same and like your sense of self is lost. Psychological distress-was described as a feeling of being alone. Family caregivers felt invisible and no longer important to family and friends. The patient was the one that mattered. CONCLUSION: This study indicates that patients and family caregivers would benefit from a more family-centred healthcare, where the patients' as well as the caregivers' perspectives would be acknowledged.

Psychological distress after esophageal cancer surgery and the predictive effect of dispositional optimism: a nationwide population-based longitudinal study.

PURPOSE: To examine the trajectory of psychological distress from 1 to 2 years after esophageal cancer surgery, and whether dispositional optimism could predict the risk of postoperative psychological distress. METHODS: This Swedish nationwide longitudinal study included 192 patients who had survived for 1 year after esophageal cancer surgery. We measured dispositional optimism with the Life Orientation Test-Revised (LOT-R) 1 year post-surgery and psychological distress with the Hospital Anxiety and Depression Scale 1, 1.5, and 2 years post-surgery. Latent growth curve models were used to assess the trajectory of postoperative psychological distress and to examine the predictive validity of dispositional optimism. RESULTS: One year after surgery, 11.5% (22 of 192) patients reported clinically significant psychological distress, and the proportion increased to 18.8% at 1.5 years and to 25.0% at 2 years post-surgery. Higher dispositional optimism predicted a lower probability of self-reported psychological distress at 1, 1.5, and 2 years after esophageal cancer surgery. For each point increase in the LOT-R sum score, the odds of psychological distress decreased by 44% (OR, 0.56; 95% CI, 0.40 to 0.79). CONCLUSION: The high prevalence and longitudinal increase of self-reported psychological distress after esophageal cancer surgery indicate the unmet demands for timely psychological screening and interventions. Measuring dispositional optimism may help identify patients at higher risk of developing psychological distress, thereby contributing to the prevention of postoperative psychological distress.