Oesophageal cancer surgery : nutritional determinants of survivorship

Oesophagectomy, the surgery offered as a curative treatment for cancer of the oesophagus is highly invasive with a radical change in anatomy and carries a risk for significant morbidity and mortality. The recovery is lengthy, burdened by deterioration in health-related quality of life (HRQOL). Eating difficulties and symptoms affecting patients’ nutritional status, termed nutrition impact symptoms (NIS) are commonly reported in the survivorship even up to 10 years after surgery. Clinically noticeable weight loss is a problem right from diagnosis but also persists after surgery as a troublesome trait of the survivorship. Hence, this thesis aimed to clarify how nutritional problems after surgery for oesophageal cancer influence HRQOL and survival, and to assess the role of dietitian support in improving nutritional status and thereby contribute to the clinical decision-making process. Studies I-IV included in this thesis are prospective cohort studies in design based on two large cohorts comprising of patients who underwent surgery for oesophageal cancer in Sweden. Studies I and II were based on a prospective cohort including patients operated between 2001 and 2005 and followed up for HRQOL and nutritional outcomes until 2015. Studies III and IV were based on a cohort of patients who underwent surgery from 2013 and 2016 and followed up for one and half years after surgery. Clinical variables obtained from medical charts of patients included in both the cohorts provided the possibility to adjust for potential confounders. In Study I, the interactive influence of eating difficulties and weight loss on HRQOL up to 10 years after oesophagectomy were assessed. Severe eating difficulties irrespective of the degree of weight loss were associated with clinically and significantly worse HRQOL in almost all aspects up to 10 years after surgery. Study II examined the combined effect of NIS and weight loss on specific HRQOL aspects at six months after surgery and five-year overall survival, stratified by preoperative body mass index (BMI). Patients with severe NIS, regardless of preoperative BMI status and extent of postoperative weight loss, exhibited worse HRQOL. Patients with a higher preoperative BMI and postoperative weight loss, showed worse survival when they experienced severe NIS after surgery. Study III investigated the impact of symptoms of early and late dumping syndrome at one year after surgery for oesophageal cancer on specific HRQOL aspects. Clinically and statistically relevant differences in several HRQOL aspects were seen in both early and late dumping when compared with no dumping, with late dumping showing worse effects. Study IV evaluated if preoperative dietitian support in addition to postoperative support and a high level of patient reported satisfaction of the support are associated with an improved nutritional status. No differences in nutritional status existed with respect to whether dietitian support was initiated preoperatively or postoperatively and with regards to the level of satisfaction of the support as reported by patients. In conclusion, symptoms that affect eating and in turn nutrition, experienced after surgery for oesophageal cancer are important determinants of HRQOL. In those who are overweight or obese before surgery the presence of severe nutritional problems after surgery adversely impacted survival. Patients with symptoms of dumping syndrome, especially late dumping have poorer HRQOL and need attention. Preoperative dietitian support and high level of patient satisfaction of the support did not determine the nutritional status but are integral components of nutritional status

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.Peer reviewe

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

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

Characteristics at diagnosis of patients who responded to HRQOL questionnaires at 3 years and 5 years following surgery for oesophageal cancer.

<p>Characteristics at diagnosis of patients who responded to HRQOL questionnaires at 3 years and 5 years following surgery for oesophageal cancer.</p

Graph illustrating association between the three patient profiles created from latent class cluster analysis and risk of deterioration in healthelated quality of life (HRQOL) aspects assessed by multivariable logistic regression analysis adjusted for age, BMI, tumour stage and marital status in patients who survived at least 3 years after surgery for oesophageal cancer.

<p>The blue squares represents odds ratio obtained from adenocarcinoma profile versus the reference profile and grey lines represent the confidence intervals. Red dots represent odds ratio obtained from the squamous-cell carcinoma profile versus the reference profile and dotted red lines represent confidence intervals. HRQOL was assessed at 6 months and 3 years from surgery using the European Organisation for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-OES18. Scores obtained were converted into linear scale scores of 0 to 100 and mean score differences of ≥10 between scores at 6 months and 3 years were considered clinically moderately relevant and ≥20 as clinically strongly relevant. HRQOL of patients were also categorised as improved and stable/deteriorated for each aspect of HRQOL. Latent class cluster analysis of patient’s socio-demographic, anthropometric and clinical characteristics at diagnosis yielded three patient profiles: Reference profile: Younger age, male gender, upper secondary education, employed, cohabitating, urban dwellers. Adenocarcinoma profile: Unemployed/retired, male gender, low education, cohabitating, adenocarcinoma, higher tumour stage, lower oesophagus and cardia, co-morbidities present. Squamous-cell carcinoma profile: Unemployed/retired, male gender, low BMI, unemployed, urban dwellers, squamous cell carcinoma, upper and middle oesophagus. AC—Adenocarcinoma; SCC—Squamous–cell carcinoma; EORTC—European Organisation for Research and Treatment of Cancer; QLQ—Quality of life questionnaire; HRQOL—Health Related Quality of Life; BMI—Body mass index.</p

Proportion of socio-demographic, anthropometric and clinical characteristics at diagnosis among the reference, adenocarcinoma and squamous-cell carcinoma profiles created from latent class cluster analysis of 3-year survivors of oesophageal cancer following surgery.

<p>Proportion of socio-demographic, anthropometric and clinical characteristics at diagnosis among the reference, adenocarcinoma and squamous-cell carcinoma profiles created from latent class cluster analysis of 3-year survivors of oesophageal cancer following surgery.</p

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

BACKGROUND &amp; 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