Blood flow restriction Exercise in the perioperative setting to Prevent loss of muscle mass in patients with pancreatic, biliary tract, and liver cancer: study protocol for the PREV-Ex randomized controlled trial.

BACKGROUND: Patients diagnosed with pancreatic, biliary tract, and liver cancer often suffer from a progressive loss of muscle mass. Given the considerable functional impairments in these patients, high musculoskeletal weight loads may not be well tolerated by all individuals. The use of blood-flow restricted resistance training (BFR-T) which only requires low training loads may allow for a faster recovery of muscle due to avoidance of high levels of mechanical muscle stress associated with high-load resistance exercise. This study aims to investigate whether BFR-T can prevent or slow down the loss of skeletal muscle mass and enhance the functional capacity and mental health of patients with pancreatic, biliary tract, and liver cancer. METHODS: The PREV-Ex exercise trial is a multicenter two-armed randomized controlled trial. Patients will be randomized to an exercise program consisting of home-based low-load BFR-T during a combined pre- and postoperative period for a total of 6-10 weeks (prehabilitation and rehabilitation), or to a control group. Protein supplementation will be given to both groups to ensure adequate protein intake. The primary outcomes, skeletal muscle thickness and muscle cross-sectional area, will be assessed by ultrasound. Secondary outcomes include the following: (i) muscle catabolism-related and inflammatory bio-markers (molecular characteristics will be assessed from a vastus lateralis biopsy and blood samples will be obtained from a sub-sample of patients); (ii) patient-reported outcome measures (self-reported fatigue, health-related quality of life, and nutritional status will be assessed through validated questionnaires); (iii) physical fitness/performance/activity (validated tests will be used to evaluate physical function, cardiorespiratory fitness and maximal isometric muscle strength. Physical activity and sedentary behavior (assessed using an activity monitor); (iv) clinical outcomes: hospitalization rates and blood status will be recorded from the patients' medical records; (v) explorative outcomes of patients' experience of the exercise program which will be evaluated using focus group/individual interviews. DISCUSSION: It is worthwhile to investigate new strategies that have the potential to counteract the deterioration of skeletal muscle mass, muscle function, strength, and physical function, all of which have debilitating consequences for patients with pancreatic, biliary tract, and liver cancer. The expected findings could improve prognosis, help patients stay independent for longer, and possibly reduce treatment-related costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05044065. Registered on September 14, 2021.

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.

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.

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.

Role of dietitian support in improving weight loss and nutrition impact symptoms after oesophageal cancer surgery.

BACKGROUND: Oesophageal cancer is frequently accompanied with malnutrition. We aimed to evaluate if early support from dietitians and patient's level of satisfaction with the support from dietitians are associated with better outcomes for weight loss and nutrition impact symptoms (NIS). METHODS: A nationwide and prospective cohort study on patients operated for oesophageal cancer in Sweden from 2013 onwards, included one year after surgery. Study exposures were (1) preoperative dietitian support (yes vs no) and, (2) patient reported satisfaction with dietitian support (high vs low) and outcomes were postoperative (1) percentage weight loss and (2) NIS score (range 0-24); one year after surgery. An ANCOVA model adjusted for predefined confounders was used and presented as mean differences (MD) with 95% confidence intervals (CI). RESULTS: Among 245 patients, as many as 57% had received preoperative dietitian support. Preoperative dietitian support was not associated with statistically significant differences in mean postoperative weight loss (MD 0.2 [95% CI -2.6 to 2.9]) and mean NIS score (MD 0.1 [95% CI: -0.8 to 1.0]). Likewise, satisfaction with the dietitian support was not associated with significant differences in mean postoperative weight loss (MD 1.4 [95% CI: -1.5 to 4.3]) and NIS score (MD -0.1 [95% CI: -1 to 0.8]). CONCLUSIONS: Long-term postoperative weight loss and NIS were not influenced based on whether dietitian support was initiated preoperatively or not and patient's satisfaction level with dietitian support. Similarity in results may reflect effective screening of malnutrition and dietitian support in centres treating oesophageal cancer in Sweden.

Prevalence and intensity of dumping symptoms and their association with health-related quality of life following surgery for oesophageal cancer.

BACKGROUND & AIMS: This study aimed to investigate the prevalence and intensity of symptoms of dumping syndrome (early and late) experienced by oesophageal cancer survivors one year after surgery and their association with health related quality of life (HRQL). METHODS: A prospective cohort study of patients who underwent surgery for oesophageal cancer in Sweden from January 2013 to April 2018, included at one year after surgery with follow-up at 1.5 years. Common symptoms of dumping syndrome were the exposure, classified as early and late onset, further divided into 'moderate' or 'severe' based on symptom intensity, and no dumping symptoms (reference group). The primary outcome was mean summary score of HRQL, and secondary outcomes were global quality of life, physical, role, emotional, cognitive and social function measured using the EORTC QLQ-C30 1.5 years after surgery. An ANCOVA model, adjusted for potential confounders was used to study the association between dumping symptoms and HRQL, presented as mean score differences (MD) with 95% confidence intervals (CI). RESULTS: Among 188 patients, moderate early dumping symptoms was experienced by 45% and severe early dumping by 9%. Moderate late dumping symptoms was reported by 13%, whereas 5% reported severe late dumping symptoms. Severe early dumping symptoms was associated with worse HRQL in 4 out of 7 aspects with worse global quality of life (MD -16, 95% CI: -27 to -4) and social function (MD -17, 95% CI: -32 to -3), which showed clinically large differences compared to having no such symptoms. Patients with moderate late dumping symptoms reported poorer HRQL in 6 out of 7 aspects compared to those with no dumping symptoms. Cognitive function (MD -27, 95% CI: -47 to -7) and emotional function (MD -24, 95% CI: -47 to -2) were significantly declined (clinically large relevance) in those with severe late dumping symptoms. CONCLUSIONS: Patients who have undergone curative treatment for oesophageal cancer experience reduced HRQL from early and late dumping symptoms at one year after surgery that indicate clear implications for clinical routine. Medical support and additional dietary counselling are required as potential ways to alleviate dumping symptoms on clinical repercussions.

Cultural adaptation and psychometric evaluation of the Swedish version of the Reproductive Concerns After Cancer (RCAC) scale.

BACKGROUND: Reproductive concerns are common among young cancer survivors and include worries related to different aspects of fertility and parenthood. The Reproductive Concerns After Cancer (RCAC) scale is an 18-item scale with six dimensions, developed to capture a variety of such concerns. The aim of the present study was to describe the cultural adaptation of the RCAC scale into Swedish and evaluate its psychometric properties among young women who have undergone treatment for cancer. METHODS: The RCAC was forward translated from English into Swedish and assessed for cultural adaptation based on a two-panel approach followed by cognitive interviews with the target group. For the psychometric evaluation, a Swedish cohort of 181 female young adult breast cancer survivors completed a survey including the RCAC scale approximately 1.5 years post-diagnosis. Psychometric properties were examined by analyses of construct validity (confirmatory factor analysis and convergent validity), data quality (score distribution, floor and ceiling effects), reliability and known-groups validity. RESULTS: The confirmatory factor analysis yielded an acceptable fit (RMSEA 0.08, SRMR 0.09, CFI 0.92). Convergent validity was demonstrated by a negative correlation of moderate size (- 0.36) between the RCAC total score and the emotional function scale of the EORTC QLQ-C30. Reliability measured with Revelle Ω total was satisfactory (0.73-0.92) for five of the dimensions, and poor for the dimension Becoming pregnant (Revelle Ω total = 0.60); Cronbach's alpha showed a similar pattern. Known-groups validity was indicated by significant RCAC mean score differences (MD), reflecting more concerns among women with a certain (MD 4.56 [95% CI 3.13 to 5.99]) or uncertain (MD 3.41 [95% CI 1.68 to 5.14]) child wish compared to those with no wish for (additional) children. CONCLUSION: The translation and cultural adaptation of the Swedish RCAC has resulted in a scale demonstrating construct and known-groups validity, and satisfactory reliability for five of six dimensions. The dimension Becoming pregnant showed non-optimal internal consistency and should undergo further evaluation. The Swedish RCAC is recommended to be used in research settings for measurement of concerns related to fertility and parenthood in young women with cancer.

Study protocol for the Fex-Can Childhood project: An observational study and a randomized controlled trial focusing on sexual dysfunction and fertility-related distress in young adult survivors of childhood cancer.

BACKGROUND: This study protocol describes the Fex-Can Childhood project, comprising two studies: The Fex-Can Childhood observational study (OS) and the Fex-Can Childhood randomized controlled trial (RCT). The Fex-Can Childhood OS aims to determine the prevalence and predictors of sexual dysfunction and fertility-related distress in young adult childhood cancer survivors (aged 19-40) compared to an age matched comparison group; the Fex-Can Childhood RCT will evaluate the effect of a web-based psycho-educational intervention (Fex-Can intervention) on sexual dysfunction and fertility-related distress. METHODS: The Fex-Can Childhood OS will have a population-based cross-sectional design. All individuals treated for childhood cancer in Sweden at the age of 0 to 17 years (current age 19-40) will be identified through the National Quality Registry for Childhood Cancer. Established self-reported instruments will be used to measure sexual function, fertility-related distress, body image, anxiety and depression, and health-related quality of life. Self-efficacy related to sexual function and fertility, and fertility-related knowledge, will be assessed by study-specific measures. Clinical variables will be collected from the registry. Results will be compared to an age-matched comparison group from the general population.Participants in the Fex-Can Childhood OS who report a high level of sexual dysfunction and/or fertility-related distress will be invited to participate in the RCT. The Fex-Can intervention comprises two programs: The Fex-Can Sex and the Fex-Can Fertility targeting sexual dysfunction and fertility-related distress, respectively. The control condition will be a wait-list. Sexual function and fertility-related distress will be the primary outcomes. The secondary outcomes include body image, anxiety and depression, health-related quality of life and self-efficacy related to sexual function and fertility. Post- and follow-up assessments will be conducted directly after end of intervention (primary end point), at 3 months and 6 months after end of intervention. Additionally, a process-evaluation including study-specific items and a qualitative interview will be conducted. DISCUSSION: The Fex-Can Childhood project will advance knowledge in the areas of sexual function and fertility-related distress among young adult survivors of childhood cancer. If the Fex-Can intervention proves to be efficacious, steps will be taken to implement it in the follow-up care provided to this population.

Patient-reported outcomes 1 year after oesophageal cancer surgery.

Purpose: To improve survivorship in patients who have undergone curatively intended treatment for oesophageal cancer, we aimed to identify key targets for future patient-reported outcomes research.Methods: This nationwide Swedish prospective cohort study enrolled patients between 2014 and 2019 who had undergone surgical resection for oesophageal cancer 1 year earlier. Eight well-validated patient-reported outcome measures, including health-related quality of life, psychological status and sleep, were presented as proportions and mean scores (MS) with 95% confidence intervals (CIs).Results: Among 281 participants, approximately half of the patients reported problems associated with food intake such as eating restrictions (49%) and food aversion (47%). Other common problems were sleep (51%), fatigue (41%) and anxiety (36%). Fewer patients suffered from financial difficulties (9%), trouble swallowing saliva (4%) and hair loss (7%). However, these problems were perceived as highly burdensome on an individual level.Conclusions: This nationwide, population-based study indicates that symptom burden is high in oesophageal cancer survivors 1 year after surgery. The most common problems are associated with food intake, sleep, fatigue and anxiety. However, less frequent symptoms were sometimes more debilitating for the individual patient.

Predicting the Risk of Weight Loss After Esophageal Cancer Surgery.

BACKGROUND: Malnutrition after esophageal cancer surgery is associated with reduced health-related qualify of life. Therefore, a prediction model identifying patients at risk for severe weight loss after surgery was developed. METHODS: Data from a Swedish population-based cohort study, including 616 patients undergoing esophageal cancer surgery in 2001-2005, was used. Candidate predictors included risk factors available before and immediately after surgery. Severe weight loss was defined as ≥ 15% loss of body weight between the time of surgery and 6 months postoperatively. The prediction model was developed using multivariable models. The accuracy of the model was measured by the area under the receiver operating characteristics curve (AUC) with bootstrap validation. The model was externally validated in a hospital-based cohort of 91 surgically treated esophageal cancer patients in the United Kingdom in 2011-2016. Each predictor in the final model was assigned a corresponding risk score. The sum of risk scores was equivalent to an estimated probability for severe weight loss. RESULTS: Among the 351 patients with 6 months follow-up data, 125 (36%) suffered from severe postoperative weight loss. The final prediction model included body mass index at diagnosis, preoperative weight loss, and neoadjuvant therapy. The AUC for the model was 0.78 (95% CI 0.74-0.83). In the validation cohort, the AUC was 0.76. A clinical risk assessment guide was derived from the prediction model. CONCLUSIONS: This prediction model can preoperatively identify individuals with high risk of severe weight loss after esophageal cancer surgery. Intensive nutritional interventions for these patients are recommended.

Nutrition Impact Symptoms Are Prognostic of Quality of Life and Mortality after Surgery for Oesophageal Cancer.

We aimed to clarify the influence of nutritional problems after surgery for oesophageal cancer on functional health related quality of life (HRQOL) and survival. A prospective nationwide cohort of oesophageal cancer patients operated 2001⁻2005 in Sweden with 6 months postoperative follow up was used. Nutritional problems were categorized as low/moderate/severe/very severe based on weight loss and nutrition impact symptoms. An ANCOVA model calculated mean score differences (MD) with 95% confidence intervals (CI) of global quality of life (QOL), social and physical function scores, stratified by preoperative body mass index (BMI) <25 and ≥25. A Cox proportional hazards model produced hazard ratios (HR) with 95% CI for overall 5-year survival. Of 358 patients, 196 (55%) had preoperative BMI ≥25. Very severe and severe nutritional problems were associated with worse HRQOL in both BMI groups. E.g. MD's for global QOL among 'very severe' group was -29 (95% CI -39⁻-19) and -20 (95% CI -29⁻-11) for <25 and ≥25 BMI, respectively, compared to the 'low' group. Overall 5-year survival among 'very severe' and BMI ≥ 25 was worse; HR 4.6 (95% CI 1.4⁻15.6). Intense nutritional problems negatively impact postoperative HRQOL and combined with preoperative BMI ≥ 25 are associated with poorer 5-year overall survival representing a group needing greater clinical attention.

Profiles of patient and tumour characteristics in relation to health-related quality of life after oesophageal cancer surgery.

Strong deterioration in health-related quality of life (HRQOL) is a major concern in a sub-group of long-term oesophageal cancer survivors. This study aimed to identify potential clustering of patients and tumour variables that predicts such deterioration. Patient and tumour variables were collected in a prospective cohort of patients who underwent surgery for oesophageal cancer in Sweden 2001-2005. Latent cluster analysis identified statistically significant clustering of these variables. Multivariable logistic regression adjusted for age, BMI, tumour stage and marital status was used to determine odds ratios (ORs) with 95% confidence intervals (CIs) between patient profiles and HRQOL at 3 and 5 years from surgery. Among 155 included patients at 3 years, three patient profiles were identified: 1) 'reference profile' (males, younger age, employed, upper secondary education, co-habitating, urban dwellers, adenocarcinoma and advanced tumour stage) (n = 47;30%), 2) 'adenocarcinoma profile' (middle age, unemployed/retired, males, low education, co-habitating, adenocarcinoma, advanced tumour stage, tumour in lower oesophagus/cardia, and co-morbidities (n = 79;51%), and 3) 'squamous-cell carcinoma profile' (unemployed/retired, middle-age, males, low BMI, urban dwellers, squamous-cell carcinoma, tumour in upper/middle oesophagus (n = 29;19%). These profiles did not differ regarding most HRQOL measures. Exceptions were the squamous-cell carcinoma profile, reporting more constipation (OR = 5.69; 95%CI: 1.34-24.28) and trouble swallowing saliva (OR = 4.87; 95%CI: 1.04-22.78) and the adenocarcinoma profile reporting more dyspnoea (OR = 2.60; 95%CI: 1.00-6.77) and constipation (OR = 3.31; 95%CI: 1.00-10.97) compared to the reference profile. Three distinct patient profiles were identified but these could not explain the substantial deterioration in HRQOL observed in the sub-sample of survivors.

Cachexia in patients with oesophageal cancer.

Oesophageal cancer is a debilitating disease with a poor prognosis, and weight loss owing to malnutrition prevails in the majority of patients. Cachexia, a multifactorial syndrome characterized by the loss of fat and skeletal muscle mass and systemic inflammation arising from complex host-tumour interactions is a major contributor to malnutrition, which is a determinant of tolerance to treatment and survival. In patients with oesophageal cancer, cachexia is further compounded by eating difficulties owing to the stage and location of the tumour, and the effects of neoadjuvant therapy. Treatment with curative intent involves exceptionally extensive and invasive surgery, and the subsequent anatomical changes often lead to eating difficulties and severe postoperative malnutrition. Thus, screening for cachexia by means of percentage weight loss and BMI during the cancer trajectory and survivorship periods is imperative. Additionally, markers of inflammation (such as C-reactive protein), dysphagia and appetite loss should be assessed at diagnosis. Routine assessments of body composition are also necessary in patients with oesophageal cancer to enable assessment of skeletal muscle loss, which might be masked by sarcopenic obesity in these patients. A need exists for clinical trials examining the effectiveness of therapeutic and physical-activity-based interventions in mitigating muscle loss and counteracting cachexia in these patients.

Sarcopenic obesity: A probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients.

BACKGROUND & AIMS: Profound weight loss and malnutrition subsequent to severe dysphagia and cancer cachexia are cardinal symptoms in oesophageal cancer (OC). Low muscle mass/sarcopenia has been linked to toxicity during neo-adjuvant therapy in other cancers, with worser effects in sarcopenic obesity. In this study the association between sarcopenia and/or sarcopenic obesity and dose limiting toxicity (DLT) during cycle one chemotherapy in resectable OC patients was evaluated. METHODS: Body composition was assessed from computed tomography scans of 72 consecutively diagnosed OC patients. Lean body mass and body fat mass were estimated. Patients were grouped as sarcopenic or non-sarcopenic based on pre-defined gender-specific cut-offs for sarcopenia, and as underweight/normal (BMI < 25) or overweight/obese (BMI ≥ 25). Sarcopenic obesity was defined as sarcopenia combined with overweight and obesity. DLT was defined as temporary reduction/delay or permanent discontinuation of drugs due to adverse effects. Odds ratios for developing toxicity were ascertained using multiple logistic regression. RESULTS: Of 72 patients, 85% (n = 61) were males. Sarcopenia and sarcopenic obesity were present in 31 (43%) and 10 (14%), respectively, prior to chemotherapy. Sarcopenic patients had significantly lower adipose tissue index (p = 0.02) compared to non-sarcopenic patients. Patients with DLT (n = 24) had lower skeletal muscle mass (p = 0.04) than those without DLT. Sarcopenic patients (OR = 2.47; 95% CI: 0.88-6.93) showed a trend towards increased DLT risk (p < 0.10). Logistic regression with BMI as an interaction term indicated higher DLT risk in sarcopenic patients with normal BMI (OR = 1.60; 95% CI 0.30-8.40), but was non-significant. In the sarcopenic obese, risk of DLT increased significantly (OR = 5.54; 95% CI 1.12-27.44). CONCLUSIONS: Sarcopenic and sarcopenic obese OC patients may be at a higher risk for developing DLT during chemotherapy compared to non-sarcopenic OC patients.