Multimodal prehabilitation in elective oncological colorectal surgery enhances preoperative physical fitness: a single center prospective real-world data analysis.

BACKGROUND: Surgery can lead to curation in colorectal cancer (CRC) but is associated with significant morbidity. Prehabilitation plays an important role in increasing preoperative physical fitness to reduce morbidity risk; however, data from real-world practice is scarce. This study aimed to evaluate the change in preoperative physical fitness and to evaluate which patients benefit most from prehabilitation. MATERIALS AND METHODS: In this single-arm prospective cohort study, consecutive patients undergoing elective colorectal oncological surgery were offered a 3- to 4-week multimodal prehabilitation program (supervised physical exercise training, dietary consultation, protein and vitamin supplementation, smoking cessation, and psychological support). The primary outcome was the change in preoperative aerobic fitness (steep ramp test (SRT)). Secondary outcomes were the change in functional walking capacity (6-minute walk test (6MWT)), and muscle strength (one-repetition maximum (1RM) for various muscle groups). To evaluate who benefit most from prehabilitation, participants were divided in quartiles (Q1, Q2, Q3, and Q4) based on baseline performance. RESULTS: In total, 101 patients participated (51.4% male, aged 69.7 ± 12.7 years). The preoperative change in SRT was +28.3 W, +0.36 W/kg, +16.7% (P<0.001). Patients in all quartiles improved at the group level; however, the relative improvement decreased from Q1-Q2, Q2-Q3, and Q3-Q4 (P=0.049). Change in 6MWT was +37.5 m, +7.7% (P<0.001) and 1RM improved with 5.6-33.2 kg, 16.1-32.5% for the various muscle groups (P<0.001). CONCLUSION: Prehabilitation in elective oncological colorectal surgery is associated with enhanced preoperative physical fitness regardless of baseline performance. Improvements were relatively larger in less fit patients.

Improved survival prediction and comparison of prognostic models for patients with hepatocellular carcinoma treated with sorafenib.

BACKGROUND: The 'Prediction Of Survival in Advanced Sorafenib-treated HCC' (PROSASH) model addressed the heterogeneous survival of patients with hepatocellular carcinoma (HCC) treated with sorafenib in clinical trials but requires validation in daily clinical practice. This study aimed to validate, compare and optimize this model for survival prediction. METHODS: Patients treated with sorafenib for HCC at five tertiary European centres were retrospectively staged according to the PROSASH model. In addition, the optimized PROSASH-II model was developed using the data of four centres (training set) and tested in an independent dataset. These models for overall survival (OS) were then compared with existing prognostic models. RESULTS: The PROSASH model was validated in 445 patients, showing clear differences between the four risk groups (OS 16.9-4.6 months). A total of 920 patients (n = 615 in training set, n = 305 in validation set) were available to develop PROSASH-II. This optimized model incorporated fewer and less subjective parameters: the serum albumin, bilirubin and alpha-foetoprotein, and macrovascular invasion, extrahepatic spread and largest tumour size on imaging. Both PROSASH and PROSASH-II showed improved discrimination (C-index 0.62 and 0.63, respectively) compared with existing prognostic scores (C-index ≤0.59). CONCLUSIONS: In HCC patients treated with sorafenib, individualized prediction of survival and risk group stratification using baseline prognostic and predictive parameters with the PROSASH model was validated. The refined PROSASH-II model performed at least as good with fewer and more objective parameters. PROSASH-II can be used as a tool for tailored treatment of HCC in daily practice and to define pre-planned subgroups for future studies.

Are we SHARP enough? The importance of adequate patient selection in sorafenib treatment for hepatocellular carcinoma.

BACKGROUND: Upon FDA/EMEA registration for hepatocellular carcinoma (HCC), sorafenib received a broader therapeutic indication than the eligibility criteria of the landmark SHARP trial. This allowed treatment of SHARP non-eligible patients in daily clinical practice. AIM: To assess sorafenib efficacy and safety in SHARP eligible and non-eligible patients, and determine the validity of the current therapeutic indication as described by the FDA/EMEA. PATIENTS AND METHODS: Consecutive patients treated with sorafenib for advanced HCC at two Dutch tertiary referral centers between 2007 and 2016 were analyzed retrospectively. Primary outcome was overall survival (OS). Secondary outcomes were time to progression (TTP), response rate, adverse events and reasons for discontinuation. Outcomes were compared between SHARP eligible and non-eligible patients. RESULTS: One hundred and ninety-three of 257 (75%) patients were SHARP eligible. SHARP eligible patients (9.5 months, 95% CI 7.7-11.3) had a longer median OS than non-eligible patients (5.4 months, 95% CI 3.6-7.1) (log-rank p < .001). SHARP non-eligible patients were more often Child-Pugh B, had higher AST and ALT levels and developed more grade 3-4 liver dysfunction (44 versus 23%, p < .001) during treatment. SHARP ineligibility remained the strongest predictor of OS (HR 1.78, 95% CI 1.32-2.41) and an independent predictor of TTP (HR 1.45, 95% CI 1.05-2.00) in multivariable analysis. CONCLUSIONS: Landmark trial outcomes of sorafenib for HCC are reproducible in daily practice, provided that the SHARP eligibility criteria are respected. Based on the findings of this and previous studies, sorafenib usage should be restricted to Child-Pugh A patients.