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Background The aim of this study was to quantify changes in body composition during ovarian cancer treatment and relate these changes to rates of complete gross resection (CGR). Methods One hundred two patients with stage III or IV ovarian cancer who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery were a part of a prospectively collected database that included computed tomography scans at three time points-diagnosis, following NACT, and following debulking surgery. Skeletal muscle, visceral adipose, and subcutaneous adipose tissue volumes were obtained from a 30-mm volumetric slab beginning at the third lumbar vertebrae. Results Following NACT, skeletal muscle volume was significantly reduced (352.5 to 335.0 cm3, P < 0.001), whereas adiposity was unchanged. Body mass index (BMI) and skeletal muscle volume were significantly lower in patients who achieved CGR (P < 0.05). When these patients were stratified by BMI, the significant association of skeletal muscle to CGR was limited to patients with a BMI < 25 kg/m2 (P = 0.007). Conclusion Skeletal muscle volume was significantly reduced in patients undergoing NACT for ovarian cancer. Non-overweight patients were more likely to achieve CGR if they had lower skeletal muscle volume. Use of volumetric-based measurement for ascertaining body composition should be explored further.

A 71 year-old man with heart failure, porcelain aorta, and mitral regurgitation presented for heart transplant evaluation. He was in cardiogenic shock requiring inotropic support. An echocardiogram showed a dilated left ventricle, severely reduced systolic function, restricted mitral valve leaflet motion, an elevated mean transmitral gradient, and severe mitral regurgitation. The differential of mixed stenotic and regurgitant mitral valve pathology included rheumatic heart disease and congenital mitral valve anomaly. Hemodynamic management of cardiogenic shock in the setting of mixed mitral valve disease presented unique challenges due to a narrow therapeutic window of optimal preload, afterload reduction, inotropic support, and chronotropic control. He was not a candidate for percutaneous mitral valve interventions or surgery. A porcelain aorta made him high risk for vascular complications with mechanical circulatory support. His course was complicated by worsening shock requiring escalation of inotropes, rapid atrial fibrillation, and recurrent episodes of acute pulmonary edema. Ultimately, he underwent an orthotropic heart transplant. A transesophageal echocardiogram at the time of transplant suggested a parachute mitral valve, where all chordae appeared be originating from one papillary muscle. However, additional views revealed the presence of two papillary muscles with asymmetric, shortened anterior chordae and a hypertrophied anterior papillary muscle. Findings were consistent with a rare parachute-like asymmetric mitral valve complicated by mild mitral stenosis and severe mitral regurgitation. Examination of the explanted native heart confirmed these findings.This case highlights: 1) complex management of mixed valvular disease in the setting of cardiogenic shock, 2) echocardiographic evaluation of mixed valvular heart disease, and 3) a rare congenital malformation of a parachute-like mitral valve presenting in adulthood.

Purpose To evaluate the effects of exercise therapy on cardiorespiratory fitness (CRF) in randomized controlled trials (RCTs) among patients with adult-onset cancer. Secondary objectives were to evaluate treatment effect modifiers, safety, and fidelity. Methods A systematic search of PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library was conducted to identify RCTs that compared exercise therapy to a nonexercise control group. The primary end point was change in CRF as evaluated by peak oxygen consumption (VO2peak; in mL O2 × kg−1 × min−1) from baseline to postintervention. Subgroup analyses evaluated whether treatment effects differed as a function of exercise prescription (ie, modality, schedule, length, supervision), study characteristics (ie, intervention timing, primary cancer site), and publication year. Safety was defined as report of any adverse event (AE); fidelity was evaluated by rates of attendance, adherence, and loss to follow-up. Results Forty-eight unique RCTs that represented 3,632 patients (mean standard deviation age, 55 ± 7.5 years; 68% women); 1,990 (55%) and 1,642 (45%) allocated to exercise therapy and control/usual care groups, respectively, were evaluated. Exercise therapy was associated with a significant increase in CRF (+2.80 mL O2 × kg−1 × min−1) compared with no change (+0.02 mL O2 × kg−1 × min−1) in the control group (weighted mean differences, +2.13 mL O2 × kg−1 × min−1; 95% CI, 1.58 to 2.67; I2, 20.6; P < .001). No statistical significant differences were observed on the basis of any treatment effect modifiers. Thirty trials (63%) monitored AEs; a total of 44 AEs were reported. The mean standard deviation loss to follow-up, attendance, and adherence rates were 11% ± 13%, 84% ± 12%, and 88% ± 32%, respectively. Conclusion Exercise therapy is an effective adjunctive therapy to improve CRF in patients with cancer. Our findings support the recommendation of exercise therapy for patients with adult-onset cancer.

AIM: To assess whether changes in body composition could be assessed serially using conventional thoracic computed tomography (CT) and positron-emission tomography (PET)/CT imaging in patients receiving induction chemotherapy for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: CT-based skeletal muscle volume and density were measured retrospectively from thoracic and lumbar segment CT images from 88 patients with newly diagnosed and untreated NSCLC before and after induction chemotherapy. Skeletal muscle 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) uptake was measured from PET/CT images from a subset of patients (n=42). Comparisons of each metric before and after induction chemotherapy were conducted using the non-parametric Wilcoxon signed-rank test for paired data. The association between clinical factors and percentage change in muscle volume was examined using univariate linear regression models, with adjustment for baseline muscle volume. RESULTS: Following induction chemotherapy, thoracic (−3.3%, p=0.0005) and lumbar (−2.6%, p=0.0101) skeletal muscle volume were reduced (adiposity remained unchanged). The proportion of skeletal muscle with a density

O1 Combinatorial CD8+ and PD-L1+ cell densities correlate with response and improved survival in non-small cell lung cancer (NSCLC) patients treated with durvalumab #### Sonja Althammer1, Keith Steele2, Marlon Rebelatto2, Tze Heng Tan1, Tobias Wiestler1, Guenter Schmidt1, Brandon Higgs2, Xia

Background Concurrent chemotherapy and radiation (CTRT) improves disease-free survival in locally advanced head and neck cancer but is associated with numerous acute and chronic toxicities resulting in substantial alterations in body mass and composition. We aim to summarize the current evidence on body composition changes experienced by patients undergoing CTRT, examine the impact of these changes on clinical outcomes and address potential interventions aimed at mitigating the loss. Main Body Loss of 20 % of pre-CTRT weight predicts poorer treatment tolerance and 30-day mortality. While clinical practice focuses on body weight, emerging data indicates that CTRT causes profound adverse changes in lean body mass (sarcopenia). Higher prevalence of sarcopenia predicts poorer disease-free survival as well as overall survival, lower quality of life and functional performance. The magnitude of CTRT-induced sarcopenia is the equivalent to that observed in a decade of aging in a healthy adult. Alterations in body composition are only explained, in part, by decreased caloric intake; other significant predictors include body mass index, stage, and dysphagia. Lifestyle interventions aimed at preventing loss of whole-body and especially lean mass include nutritional counseling, nutritional supplements, dietary supplements and exercise training. Personalized nutritional counseling has been associated with improvement in quality of life, while the benefits of feeding tube placement are inconsistent. There are inconsistently reported benefits of resistance training in this population. Conclusion Patients with head and neck cancer undergoing CTRT therapy experience dramatic shifts in body composition, including sarcopenia, which can negatively impact clinical outcomes. Efforts to understand the magnitude, clinical importance and mechanisms of sarcopenia are needed to inform a more personalized approach to mitigating the body composition changes associated with CTRT.

OBJECTIVE: Evaluate the accuracy of CT-derived regional skeletal muscle volume (SMV) measurements to predict whole body SMV in patients with melanoma. METHODS: 148 patients with advanced melanoma who underwent whole body positron emission tomography/CT were studied. Whole body SMV was measured on CT and used as the reference standard. CT-derived regional measures of SMV were obtained in the thorax, abdomen, pelvis, and lower limbs. Models were developed on a discovery cohort (n-98), using linear regression to model whole body SMV as a function of each regional measure, and clinical factors. Predictive performance of the derived models was evaluated in a validation cohort (n = 50) by estimating the explained variation (R(2)) of each model. RESULTS: In the discovery cohort, all regional SMV measurements were significantly associated with whole body SMV [β1 range: 0.673–1.153, all p < 0.001)]. The magnitude of association was greatest for pelvic regional measurements {β = 1.153, [95% confidence interval (0.989, 1.317)]}. Prediction algorithms incorporating clinical variables and regional SMVs were developed to estimate whole body SMV from regional assessments. Using the validation cohort to predict whole body SMV, the R(2) values for the pelvic, abdominal and thoracic regional measurements were 0.89, 0.86, 0.78. CONCLUSION: Regional measures of SMV are strong predictors of whole body SMV in patients with advanced melanoma. ADVANCES IN KNOWLEDGE: The first study utilizing whole body imaging as a reference standard validating the use of regional SMVs in cancer patients, including validating the use of regional SMVs outside of traditionally assessed areas.