Progression-Free Survival Early Assessment Is a Robust Surrogate Endpoint of Overall Survival in Immunotherapy Trials of Hepatocellular Carcinoma

Background: Radiology-based outcomes, such as progression-free survival (PFS) and objective response rate (ORR), are used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of PFS with overall survival (OS) in clinical trials of systemic therapies targeting advanced hepatocellular carcinoma (HCC) by novel meta-regression methods. Methods: A search of databases (PubMed, American Society of Clinical Oncology (ASCO), and European Society for Medical Oncology (ESMO) Meeting Libraries, Clinicaltrials.gov) for trials of systemic therapies for advanced HCC reporting both OS and PFS was performed. Individual patient data were extracted from PFS and OS Kaplan–Meier curves. Summary median PFS and OS data were obtained from random-effect model. The surrogate relationships of median PFS, first quartile (Q1), third quartile (Q3), and restricted mean survival time (RMST) for OS were evaluated by the coefficient of determination R2. Heterogeneity was explored by meta-regression. Results: We identified 49 trials, 11 assessing immune-checkpoint inhibitors (ICIs) and 38 multikinase inhibitors (MKIs). Overall, the correlation between median PFS and median OS was weak (R2 = 0.20. 95% Confidence Intervals [CI]-0.02;0.42). Surrogacy robustness varied between treatment classes and PFS endpoints. In ICI trials only, the correlations between Q1-PFS and Q1-OS and between 12-month PFS-RMST and 12-month OS-RMST were high (R2 = 0.89, 95%CI 0.78–0.98, and 0.80, 95% CI 0.63–0.96, respectively). Interaction p-values obtained by meta-regression confirmed the robustness of results. Conclusions: In trials of systemic therapies for advanced HCC, the surrogate relationship of PFS with OS is highly variable depending on treatment class (ICI or MKI) and evaluation time-point. In ICI trials, Q1-PFS and 12-month PFS-RMST are robust surrogate endpoints for OS

Perception of the Role of Food and Dietary Modifications in Patients with Inflammatory Bowel Disease: Impact on Lifestyle

Background: Diet has a relevant role in triggering symptoms in inflammatory bowel disease (IBD) from the patients’ perspective, but there is gap the between patients’ and doctors’ perceptions. Few studies have addressed this topic. The aim of this study was to evaluate food habits and nutrition knowledge in a homogeneous cohort of patients with IBD from southern Italy. Methods: 167 consecutive patients with IBD were recruited. The survey was based on the administration of a semi-structured questionnaire assessing demographics, disease features, dietary behavior, and food intolerance. Results: The majority of patients did not consider food a cause of their disease. However more than 80% changed their diet after the diagnosis and most report an improvement in symptoms. Spiced and seasoned foods, dairy products, vegetables, and fruit were often avoided. A dairy-free diet was adopted by 33.7%. Food choices were based on self-experience and not on medical counselling. Dietary modifications deeply impact on lifestyle. Conclusions: Most of the patients with IBD set diet and lifestyle on self-experience and give up many foods. This has an impact on psychosocial functioning and can lead to nutritional deficiencies. High quality studies are warranted to assess evidence-based dietary strategies and develop patient-targeted dietary recommendations

BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms

This dataset includes the text, figures and supplementary material associated with the Oncogene submission MS#ONC-2022-0172

Surveillance for hepatocellular carcinoma with a 3-months interval in “extremely high-risk” patients does not further improve survival

Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. Conclusions A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics

Monofocal hepatocellular carcinoma: how much does size matter?

none88mixedPelizzaro, Filippo; Penzo, Barbara; Peserico, Giulia; Imondi, Angela; Sartori, Anna; Vitale, Alessandro; Cillo, Umberto; Giannini, Edoardo G.; Forgione, Antonella; Rapaccini, Gian Ludovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Sacco, Rodolfo; Cabibbo, Giuseppe; Marra, Fabio; Mega, Andrea; Morisco, Filomena; Gasbarrini, Antonio; Svegliati‐Baroni, Gianluca; Foschi, Francesco Giuseppe; Olivani, Andrea; Masotto, Alberto; Nardone, Gerardo; Raimondo, Giovanni; Azzaroli, Francesco; Vidili, Gianpaolo; Oliveri, Filippo; Trevisani, Franco; Farinati, Fabio; Biselli, Maurizio; Caraceni, Paolo; Garuti, Francesca; Gramenzi, Annagiulia; Neri, Andrea; Santi, Valentina; Granito, Alessandro; Muratori, Luca; Piscaglia, Fabio; Sansone, Vito; Tovoli, Francesco; Dajti, Elton; Marasco, Giovanni; Ravaioli, Federico; Cappelli, Alberta; Golfieri, Rita; Mosconi, Cristina; Renzulli, Matteo; Marina Cela, Ester; Facciorusso, Antonio; Cacciato, Valentina; Casagrande, Edoardo; Moscatelli, Alessandro; Pellegatta, Gaia; de Matthaeis, Nicoletta; Allegrini, Gloria; Lauria, Valentina; Ghittoni, Giorgia; Pelecca, Giorgio; Chegai, Fabrizio; Coratella, Fabio; Ortenzi, Mariano; Missale, Gabriele; Inno, Alessandro; Marchetti, Fabiana; Busacca, Anita; Cabibbo, Giuseppe; Cammà, Calogero; Di Martino, Vincenzo; Emanuele Maria Rizzo, Giacomo; Stella Franzè, Maria; Saitta, Carlo; Sauchella, Assunta; Bevilacqua, Vittoria; Borghi, Alberto; Casadei Gardini, Andrea; Conti, Fabio; Chiara Dall’Aglio, Anna; Ercolani, Giorgio; Mirici, Federica; Campani, Claudia; Di Bonaventura, Chiara; Gitto, Stefano; Coccoli, Pietro; Malerba, Antonio; Guarino, Maria; Brunetto, Maurizia; Romagnoli, VeronicaPelizzaro, Filippo; Penzo, Barbara; Peserico, Giulia; Imondi, Angela; Sartori, Anna; Vitale, Alessandro; Cillo, Umberto; Giannini, Edoardo G.; Forgione, Antonella; Rapaccini, Gian Ludovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Sacco, Rodolfo; Cabibbo, Giuseppe; Marra, Fabio; Mega, Andrea; Morisco, Filomena; Gasbarrini, Antonio; Svegliati‐baroni, Gianluca; Foschi, Francesco Giuseppe; Olivani, Andrea; Masotto, Alberto; Nardone, Gerardo; Raimondo, Giovanni; Azzaroli, Francesco; Vidili, Gianpaolo; Oliveri, Filippo; Trevisani, Franco; Farinati, Fabio; Biselli, Maurizio; Caraceni, Paolo; Garuti, Francesca; Gramenzi, Annagiulia; Neri, Andrea; Santi, Valentina; Granito, Alessandro; Muratori, Luca; Piscaglia, Fabio; Sansone, Vito; Tovoli, Francesco; Dajti, Elton; Marasco, Giovanni; Ravaioli, Federico; Cappelli, Alberta; Golfieri, Rita; Mosconi, Cristina; Renzulli, Matteo; Marina Cela, Ester; Facciorusso, Antonio; Cacciato, Valentina; Casagrande, Edoardo; Moscatelli, Alessandro; Pellegatta, Gaia; de Matthaeis, Nicoletta; Allegrini, Gloria; Lauria, Valentina; Ghittoni, Giorgia; Pelecca, Giorgio; Chegai, Fabrizio; Coratella, Fabio; Ortenzi, Mariano; Missale, Gabriele; Inno, Alessandro; Marchetti, Fabiana; Busacca, Anita; Cabibbo, Giuseppe; Cammà, Calogero; Di Martino, Vincenzo; Emanuele Maria Rizzo, Giacomo; Stella Franzè, Maria; Saitta, Carlo; Sauchella, Assunta; Bevilacqua, Vittoria; Borghi, Alberto; Casadei Gardini, Andrea; Conti, Fabio; Chiara Dall’Aglio, Anna; Ercolani, Giorgio; Mirici, Federica; Campani, Claudia; Di Bonaventura, Chiara; Gitto, Stefano; Coccoli, Pietro; Malerba, Antonio; Guarino, Maria; Brunetto, Maurizia; Romagnoli, Veronic

Recalibrating survival prediction among patients receiving trans\u2010arterial chemoembolization for hepatocellular carcinoma

Background & Aims The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role. Methods We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model. Results The four risk-categories identified by the Pre-TACE-Predict model had gradient monotonicity, with median survivals of 52.0, 36.2, 29.9, and 14.1 months respectively. However, predicted survivals systematically underestimated observed survivals (R2: 0.667). A recalibration was adopted maintaining fixed the prognostic index and modifying the baseline survival function. This resulted in an almost perfect calibration (R2: 0.995) in all the four risk categories. Cox regressions showed that aetiology and macrovascular invasion, included in the Pre-TACE-Predict model, had no prognostic impact in the present study population, and that coefficients for tumour size and multiplicity were overestimated. The c-index was similar to that of the m-HAP-III, but higher than those of HAP, m-HAP-II and the six-and-twelve models. Conclusions The recalibration of Pre-TACE-Predict model improved the estimation of survival probabilities of HCC patients treated with TACE. The highest discriminatory ability of the Pre-TACE-model in comparison to other available models, together with risk stratification and recalibration, makes it the best prognostic tool currently available for these patients

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment

Aim: This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. Methods: 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material depriva- tion (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. Results: In more deprived regions, HCC was more frequently diagnosed during surveillance, while the incidental diagnosis was prevalent in the least deprived. Tumour characteristics did not differ among regions. The proportion of patients undergoing potentially curative treat- ments progressively decreased as the SMD worsened. Consequently, overall survival was bet- ter in less deprived regions. Patients who moved from most deprived to less deprived regions increased their probability of receiving potentially curative treatments by 1.11 times (95% CI 1.03 to 1.19), decreasing their mortality likelihood (hazard ratio 0.78 95% CI 0.67 to 0.90). Conclusions: Socioeconomic status measured through SMD does not seem to influence HCC features at diagnosis but brings a negative effect on the chance of receiving potentially curative treatments. Patient mobility from the most deprived to the less deprived regions increased the access to curative therapies, with the ultimate result of improving survival

Material deprivation affects the management and clinical outcome of hepatocellular carcinoma in a high-resource environment

Aim: This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. Methods: 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material depriva- tion (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. Results: In more deprived regions, HCC was more frequently diagnosed during surveillance, while the incidental diagnosis was prevalent in the least deprived. Tumour characteristics did not differ among regions. The proportion of patients undergoing potentially curative treat- ments progressively decreased as the SMD worsened. Consequently, overall survival was bet- ter in less deprived regions. Patients who moved from most deprived to less deprived regions increased their probability of receiving potentially curative treatments by 1.11 times (95% CI 1.03 to 1.19), decreasing their mortality likelihood (hazard ratio 0.78 95% CI 0.67 to 0.90). Conclusions: Socioeconomic status measured through SMD does not seem to influence HCC features at diagnosis but brings a negative effect on the chance of receiving potentially curative treatments. Patient mobility from the most deprived to the less deprived regions increased the access to curative therapies, with the ultimate result of improving survival