Sarcopenia is associated with chemoradiotherapy discontinuation and reduced progression-free survival in glioblastoma patients.

PURPOSE: Sarcopenia may complicate treatment in cancer patients. Herein, we assessed whether sarcopenia measurements derived from radiation planning computed tomography (CT) were associated with complications and tumor progression during radiochemotherapy for glioblastoma. METHODS: Consecutive patients undergoing radiotherapy planning for glioblastoma between 2010 and 2021 were analyzed. Retrocervical muscle cross-sectional area (CSA) was measured via threshold-based semi-automated radiation planning CT analysis. Patients in the lowest sex-specific quartile of muscle measurements were defined as sarcopenic. We abstracted treatment characteristics and tumor progression from the medical records and performed uni- and multivariable time-to-event analyses. RESULTS: We included 363 patients in our cohort (41.6% female, median age 63 years, median time to progression 7.7 months). Sarcopenic patients were less likely to receive chemotherapy (p < 0.001) and more likely to be treated with hypofractionated radiotherapy (p = 0.005). Despite abbreviated treatment, they more often discontinued radiotherapy (p = 0.023) and were more frequently prescribed corticosteroids (p = 0.014). After treatment, they were more often transferred to inpatient palliative care treatment (p = 0.035). Finally, progression-free survival was substantially shorter in sarcopenic patients in univariable (median 5.1 vs. 8.4 months, p < 0.001) and multivariable modeling (hazard ratio 0.61 [confidence interval 0.46-0.81], p = 0.001). CONCLUSION: Sarcopenia is a strong risk factor for treatment discontinuation and reduced progression-free survival in glioblastoma patients. We propose that sarcopenic patients should receive intensified supportive care during radiotherapy and during follow-up as well as expedited access to palliative care.

Cervical body composition on radiotherapy planning computed tomography scans predicts overall survival in glioblastoma patients.

Background and purpose: Glioblastoma (GBM) patients face a strongly unfavorable prognosis despite multimodal therapy regimens. However, individualized mortality prediction remains imprecise. Harnessing routine radiation planning cranial computed tomography (CT) scans, we assessed cervical body composition measures as novel biomarkers for overall survival (OS) in GBM patients. Materials and methods: We performed threshold-based semi-automated quantification of muscle and subcutaneous fat cross-sectional area (CSA) at the levels of the first and second cervical vertebral body. First, we tested this method's validity by correlating cervical measures to established abdominal body composition in an open-source whole-body CT cohort. We then identified consecutive patients undergoing radiation planning for recent GBM diagnosis at our institution from 2010 to 2020 and quantified cervical body composition on radiation planning CT scans. Finally, we performed univariable and multivariable time-to-event analyses, adjusting for age, sex, body mass index, comorbidities, performance status, extent of surgical resection, extent of tumor at diagnosis, and MGMT methylation. Results: Cervical body composition measurements were well-correlated with established abdominal markers (Spearman's rho greater than 0.68 in all cases). Subsequently, we included 324 GBM patients in our study cohort (median age 63 years, 60.8% male). 293 (90.4%) patients died during follow-up. Median survival time was 13 months. Patients with below-average muscle CSA or above-average fat CSA demonstrated shorter survival. In multivariable analyses, continuous cervical muscle measurements remained independently associated with OS. Conclusion: This exploratory study establishes novel cervical body composition measures routinely available on cranial radiation planning CT scans and confirms their association with OS in patients diagnosed with GBM.

Sarcopenia on preoperative chest computed tomography predicts cancer-specific and all-cause mortality following pneumonectomy for lung cancer: A multicenter analysis.

BACKGROUND: Mortality risk prediction in patients undergoing pneumonectomy for non-small cell lung cancer (NSCLC) remains imperfect. Here, we aimed to assess whether sarcopenia on routine chest computed tomography (CT) independently predicts worse cancer-specific (CSS) and overall survival (OS) following pneumonectomy for NSCLC. METHODS: We included consecutive adults undergoing standard or carinal pneumonectomy for NSCLC at Massachusetts General Hospital and Heidelberg University from 2010 to 2018. We measured muscle cross-sectional area (CSA) on CT at thoracic vertebral levels T8, T10, and T12 within 90 days prior to surgery. Sarcopenia was defined as T10 muscle CSA less than two standard deviations below the mean in healthy controls. We adjusted time-to-event analyses for age, body mass index, Charlson Comorbidity Index, forced expiratory volume in 1 second in % predicted, induction therapy, sex, smoking status, tumor stage, side of pneumonectomy, and institution. RESULTS: Three hundred and sixty-seven patients (67.4% male, median age 62 years, 16.9% early-stage) underwent predominantly standard pneumonectomy (89.6%) for stage IIIA NSCLC (45.5%) and squamous cell histology (58%). Sarcopenia was present in 104 of 367 patients (28.3%). Ninety-day all-cause mortality was 7.1% (26/367). After a median follow-up of 20.5 months (IQR, 9.2-46.9), 183 of 367 patients (49.9%) had died. One hundred and thirty-three (72.7%) of these deaths were due to lung cancer. Sarcopenia was associated with shorter CSS (HR 1.7, p = 0.008) and OS (HR 1.7, p = 0.003). CONCLUSIONS: This transatlantic multicenter study confirms that sarcopenia on preoperative chest CT is an independent risk factor for CSS and OS following pneumonectomy for NSCLC.

Muscle Loss Is Associated with Overall Survival in Patients with Metastatic Colorectal Cancer Independent of Tumor Mutational Status and Weight Loss.

BACKGROUND: Survival in patients with metastatic colorectal cancer (mCRC) has been associated with tumor mutational status, muscle loss, and weight loss. We sought to explore the combined effects of these variables on overall survival. MATERIALS AND METHODS: We performed an observational cohort study, prospectively enrolling patients receiving chemotherapy for mCRC. We retrospectively assessed changes in muscle (using computed tomography) and weight, each dichotomized as >5% or ≤5% loss, at 3, 6, and 12 months after diagnosis of mCRC. We used regression models to assess relationships between tumor mutational status, muscle loss, weight loss, and overall survival. Additionally, we evaluated associations between muscle loss, weight loss, and tumor mutational status. RESULTS: We included 226 patients (mean age 59 ± 13 years, 53% male). Tumor mutational status included 44% wild type, 42% RAS-mutant, and 14% BRAF-mutant. Patients with >5% muscle loss at 3 and 12 months experienced worse survival controlling for mutational status and weight (3 months hazard ratio, 2.66; p < .001; 12 months hazard ratio, 2.10; p = .031). We found an association of >5% muscle loss with BRAF-mutational status at 6 and 12 months. Weight loss was not associated with survival nor mutational status. CONCLUSION: Increased muscle loss at 3 and 12 months may identify patients with mCRC at risk for decreased overall survival, independent of tumor mutational status. Specifically, >5% muscle loss identifies patients within each category of tumor mutational status with decreased overall survival in our sample. Our findings suggest that quantifying muscle loss on serial computed tomography scans may refine survival estimates in patients with mCRC. IMPLICATIONS FOR PRACTICE: In this study of 226 patients with metastatic colorectal cancer, it was found that losing >5% skeletal muscle at 3 and 12 months after the diagnosis of metastatic disease was associated with worse overall survival, independent of tumor mutational status and weight loss. Interestingly, results did not show a significant association between weight loss and overall survival. These findings suggest that muscle quantification on serial computed tomography may refine survival estimates in patients with metastatic colorectal cancer beyond mutational status.

Associations of Skeletal Muscle With Symptom Burden and Clinical Outcomes in Hospitalized Patients With Advanced Cancer.

BACKGROUND: Low muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle radiodensity (quality). We sought to describe the associations of muscle mass and radiodensity with symptom burden, healthcare use, and survival in hospitalized patients with advanced cancer. METHODS: We prospectively enrolled hospitalized patients with advanced cancer from September 2014 through May 2016. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used CT scans performed per routine care within 45 days before enrollment to evaluate muscle mass and radiodensity. We used regression models to examine associations of muscle mass and radiodensity with patients' symptom burden, healthcare use (hospital length of stay and readmissions), and survival. RESULTS: Of 1,121 patients enrolled, 677 had evaluable muscle data on CT (mean age, 62.86 ± 12.95 years; 51.1% female). Older age and female sex were associated with lower muscle mass (age: B, -0.16; P<.001; female: B, -6.89; P<.001) and radiodensity (age: B, -0.33; P<.001; female: B, -1.66; P=.014), and higher BMI was associated with higher muscle mass (B, 0.58; P<.001) and lower radiodensity (B, -0.61; P<.001). Higher muscle mass was significantly associated with improved survival (hazard ratio, 0.97; P<.001). Notably, higher muscle radiodensity was significantly associated with lower ESAS-Physical (B, -0.17; P=.016), ESAS-Total (B, -0.29; P=.002), PHQ-4-Depression (B, -0.03; P=.006), and PHQ-4-Anxiety (B, -0.03; P=.008) symptoms, as well as decreased hospital length of stay (B, -0.07; P=.005), risk of readmission or death in 90 days (odds ratio, 0.97; P<.001), and improved survival (hazard ratio, 0.97; P<.001). CONCLUSIONS: Although muscle mass (quantity) only correlated with survival, we found that muscle radiodensity (quality) was associated with patients' symptoms, healthcare use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address adverse muscle changes in oncology.

Feasibility, Safety and Effects of a One-Week, Ski-Based Exercise Intervention in Brain Tumor Patients and Their Relatives: A Pilot Study.

A brain tumor diagnosis poses a significant psychological burden and it severely impacts quality of life (QOL), both in patients and relatives. However, comprehensive strategies addressing QOL in this setting remain rare. Here, we aim to share our findings of a one-week ski exercise intervention, with emphasis on feasibility, safety, QOL, and physical exercise. The intervention consisted of week-long daily ski sessions with professional ski guides as well as dedicated physicians present. The participants were handed questionnaires, including distress and QOL items before, during, and after the intervention. Using fitness watches, exercise intensity was also tracked at these timepoints. During the intervention, patients were checked for adverse events daily. Fifteen participants, nine patients after multidisciplinary treatment, and six relatives were included in the study. Additionally, 13 children participated in the exercise, but not in the study. All of the participants completed the entire program. No severe adverse events were documented during daily checks. There was a strong increase in quantified activity and QOL with a corresponding decrease in distress during the intervention, and, partly, afterwards. This prospective brain tumor rehabilitation study demonstrates the feasibility and safety of challenging ski exercise in brain tumor patients. The findings also underline the exercise-mediated QOL benefits, emphasizing the need for more comprehensive brain tumor rehabilitation programs.

Computed Tomography-based Body Composition Analysis and Its Role in Lung Cancer Care.

Body composition analysis, also referred to as analytic morphomics, morphomics, or morphometry, describes the measurement of imaging biomarkers of body composition such as muscle and adipose tissue, most commonly on computed tomography (CT) images. A growing body of literature supports the use of such metrics derived from routinely acquired CT images for risk prediction in various patient populations, including those with lung cancer. Metrics include cross-sectional area and attenuation of skeletal muscle and subcutaneous, visceral, and intermuscular adipose tissue. The purpose of this review is to provide an overview of the concepts, definitions, assessment tools, segmentation techniques and associated pitfalls, interpretation of those measurements on chest and abdomen CT, and a discussion of reported outcomes associated with body composition metrics in patients with early-stage and advanced lung cancer.

Safety and Success of Repeat Lung Needle Biopsies in Patients with Epidermal Growth Factor Receptor-Mutant Lung Cancer.

BACKGROUND: Postprogression repeat biopsies are critical in caring for patients with lung cancer with epidermal growth factor receptor (EGFR) mutations. However, hesitation about invasive procedures persists. We assessed safety and tissue adequacy for molecular profiling among repeat postprogression percutaneous transthoracic needle aspirations and biopsies (rebiopsies). MATERIALS AND METHODS: All lung biopsies performed at our hospital from 2009 to 2017 were reviewed. Complications were classified by Society of Interventional Radiology criteria. Complication rates between rebiopsies in EGFR-mutants and all other lung biopsies (controls) were compared using Fisher's exact test. Success of molecular profiling was recorded. RESULTS: During the study period, nine thoracic radiologists performed 107 rebiopsies in 75 EGFR-mutant patients and 2,635 lung biopsies in 2,347 patients for other indications. All biopsies were performed with computed tomography guidance, coaxial technique, and rapid on-site pathologic evaluation (ROSE). The default procedure was to take 22-gauge fine-needle aspirates (FNA) followed by 20-gauge tissue cores. Minor complications occurred in 9 (8.4%) rebiopsies and 503 (19.1%; p = .004) controls, including pneumothoraces not requiring chest tube placement (4 [3.7%] vs. 426 [16.2%] in rebiopsies and controls, respectively; p < .001). The only major complication was pneumothorax requiring chest tube placement, occurring in zero rebiopsies and 38 (1.4%; p = .4) controls. Molecular profiling was requested in 96 (90%) rebiopsies and successful in 92/96 (96%). CONCLUSION: At our center, repeat lung biopsies for postprogression molecular profiling of EGFR-mutant lung cancers result in fewer complications than typical lung biopsies. Coaxial technique, FNA, ROSE, and multiple 20-gauge tissue cores result in excellent specimen adequacy. IMPLICATIONS FOR PRACTICE: Repeat percutaneous transthoracic needle aspirations and biopsies for postprogression molecular profiling of epidermal growth factor receptor (EGFR)-mutant lung cancer are safe in everday clinical practice. Coaxial technique, fine-needle aspirates, rapid on-site pathologic evaluation, and multiple 20-gauge tissue cores result in excellent specimen adequacy. Although liquid biopsies are increasingly used, their sensitivity for analysis of resistant EGFR-mutant lung cancers remains limited. Tissue biopsies remain important in this context, especially because osimertinib is now in the frontline setting and T790M is no longer the major finding of interest on molecular profiling.

Chronic liver disease promotes lesions of the colorectal adenoma-carcinoma sequence, independent of liver cirrhosis.

Background: Research increasingly focuses on identifying individuals at greater risk of colorectal cancer (CRC) to enhance colonoscopy screening efficacy. Objective: The objective of this article is to determine associations between chronic liver disease and lesions along the colorectal adenoma-carcinoma sequence. Methods: This retrospective study encompasses consecutive liver disease patients (LDPs) of all etiologies evaluated for liver transplantation at a single institution and a control group of liver-healthy patients (LHPs) undergoing colonoscopy as part of the German CRC screening program.Rates of polyps, adenomas, high-risk situations (HRS) and CRC were analyzed in univariable and multivariable settings adjusting for age, gender, body mass index and number of colonoscopies. Differences between LHPs and LDPs and between cirrhotic and noncirrhotic hepatopathy were assessed. Results: In total, 1046 patients (52.6% male, median age 59.6 years) were included, of whom 38.9% had liver disease. A total of 41.0% of all patients showed polyps, 23.2% adenomas, 10.0% HRS, and 0.5% CRC. LDPs were more likely to develop polyps, adenomas and HRS than LHPs, both in univariable and multivariable analysis. There were no significant differences between cirrhotic and noncirrhotic patients. Conclusion: Chronic liver disease of any etiology is associated with colonic lesions of the colorectal adenoma-carcinoma sequence, independent of cirrhosis. LDPs should receive intensified, and earlier, colonoscopy screening.