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Background: The aim was to evaluate the efficacy of gemcitabine combined with a platinum agent compared to single-agent gemcitabine in a pooled analysis of two randomized trials. Methods: The French Multidisciplinary Clinical Research Group (GERCOR)/Italian Group for the Study of Gastrointestinal Tract Cancer (GISCAD) intergroup study comparing gemcitabine plus oxaliplatin to gemcitabine and a German multicenter trial comparing gemcitabine plus cisplatin versus gemcitabine were included in a pooled analysis based on individual patient data. Results: Among 503 evaluable patients, 252 received gemcitabine plus a platinum analog (GP), while 251 patients were treated with gemcitabine alone. For progression-free survival (PFS), the pooled univariate analysis indicated a hazard ratio (HR) of 0.75 (P = 0.0030) in favour of the GP combination. The benefit from the GP combination was greatest in the subgroup of patients with performance status (PS) = 0 (HR = 0.64; P = 0.013). Also overall survival was significantly superior in patients receiving the GP combination (HR = 0.81; P = 0.031). Again, patients with PS = 0 appeared to have a greater benefit from treatment intensification (HR = 0.72; P = 0.063). Conclusion: The pooled analysis of the GERCOR/GISCAD intergroup study and the German multicenter study indicates that the combination of gemcitabine with a platinum analog such as oxaliplatin or cisplatin significantly improves progression-free survival and overall survival as compared to single-agent gemcitabine in advanced pancreatic cancer. The benefit seems to prevail in patients with a good performance status. [ABSTRACT FROM AUTHOR]

This article summarizes the expert discussion on the management of hepatocellular carcinoma (HCC), which took place during the 10th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, June 2008. A multidisciplinary approach to a patient with HCC is essential, to guarantee optimal diagnosis and staging, planning of surgical options and selection of embolisation strategies or systemic therapies. In many patients, the underlying cirrhosis represents a challenge and determines therapeutic options. There is now robust evidence in favour of systemic therapy with sorafenib in patients with advanced HCC with preserved liver function. Those involved in the care for patients with HCC should be encouraged to participate in well-designed clinical trials, to increase evidence-based knowledge and to make further progress. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node biopsy (SLNB) was developed to axillary lymph node dissection (ALND) in the treatment of breast cancer. SLNB is predictive of axillary node status. Major concern is the occurrence of a false-negative SLN. Purpose of this study is to determine the rate of axillary recurrence in our series of unselected patients. Patients and methods: All patients with a negative SLNB from November 1999 to December 2006 have been treated and followed at our unit. Information on patients characteristics, treatment and follow-up has been collected. Results: Eight-hundred and four patients with negative SLNB did not receive ALND. After a median follow-up of 38.8 months, 21 patients had distant metastases, four had axillary relapse, nine had an in-breast recurrence and two had both. All patients with axillary recurrence received axillary dissection and systemic adjuvant therapy. They are all presently alive and free from disease. Conclusion: Data from this series, the largest from a general hospital, showed that isolated axillary node recurrence after negative SLNB is rare (<1%) and comparable with those reported from referral cancer institutions. We confirm that SLNB for the treatment of early breast cancer patients of a community-based hospital is safe and reliable. [ABSTRACT FROM AUTHOR]

Background: The aim was to investigate the outcomes associated with venous thromboembolism (VTE) among irresectable pancreatic cancer patients. Methods: This is a follow-up study of consecutive irresectable cancer patients, treated and followed up in clinical trials between December 2001 and December 2004 in order to evaluate the prognostic impact of symptomatic VTE on clinical outcomes, such as response to treatment, progression-free survival (PFS) and overall survival (OS). Results: Among 227 irresectable pancreatic cancer patients, with Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤ 2, 59 (26.0%) patients developed a VTE. A synchronous VTE occurred in 28 (12.3%) patients, while a VTE during chemotherapy was observed in 15 (6.6%) patients, and 16 (7.0%) patients experienced both events. Presence of synchronous VTE was associated with a higher probability of not responding to treatment (odds ratio 2.98, 95% CI 1.42–6.27, P = 0.004), but showed no effect on both PFS and OS at least at multivariate analysis. Occurrence of a VTE during chemotherapy showed a statistically significant effect on PFS (hazard ratio [HR] 2.59, 95% CI 1.69–3.97, P < 0.0001) and OS (HR 1.64, 95%CI 1.04–2.58, P = 0.032). Conclusions: Our data suggest that the occurrence of VTE may be associated with a reduced response rate and a shorter PFS and OS among patients with irresectable pancreatic cancer. In these patients the development of VTE may reflect the presence of a biologically more aggressive cancer that in turn leads to a worse prognosis. [ABSTRACT FROM AUTHOR]

This article summarizes the expert discussion on the management of pancreatic cancer, which took place during the 8th World Congress on Gastrointestinal Cancer in June 2006 in Barcelona. A multidisciplinary approach to a patient with pancreatic cancer is essential, in order to guarantee an optimal staging, surgery, selection of the appropriate (neo-)adjuvant strategy and chemotherapeutic choice management. Moreover, optimal symptomatic management requires a dedicated team of health care professionals. Quality control of surgery and pathology is especially important in this disease with a high locoregional failure rate. There is now solid evidence in favour of chemotherapy in both the adjuvant and palliative setting, and gemcitabine combined with erlotinib, capecitabine or platinum compounds seems to be slightly more active than gemcitabine alone in advanced pancreatic cancer. There is a place for chemoradiotherapy in selected patients with locally advanced disease, while the role in the adjuvant setting remains controversial. Those involved in the care for patients with pancreatic cancer should be encouraged to participate in well-designed clinical trials, in order to increase the evidence-based knowledge and to make further progress. [ABSTRACT FROM AUTHOR]

Background: RIGHT (Research for the Identification of the most effective and hIGhly accepted clinical guidelines for the cancer Treatment) is a project promoted by the Italian Association of Medical Oncology (AIOM) to measure the concordance between oncology guidelines and clinical practice. The goal of this pilot phase was to develop and test a reliable process to measure this concordance nationwide. Materials and methods: Twenty Italian centers participated to the survey. Breast cancer (BC) and colorectal cancer (CRC): guidelines issued by AIOM in 2003 were selected. A total of 29 indicators linked to the process of care were abstracted. Patients who had their first visit at the oncology center between February 2004 and June 2005, with a diagnosis of invasive BC (stage 1 or 2), colon cancer (stage 3), rectal cancer (stage T3–4 or N1–2) or advanced CRC were enclosed. Results and conclusion: One hundred and sixty-one patients (80%) were analyzed. On average, 93% of BC and 80.3% of colorectal patients received recommended care. These first results indicate that the RIGHT system provides a valid measurement of oncology care to assess agreement with guidelines. A second larger phase of this nationwide monitoring program will enable results to be generalized. [ABSTRACT FROM AUTHOR]

Pancreatic and periampullary cancers pose significant challenges in oncological care due to their complexity and diagnostic difficulties. Global experiences underscore the crucial role of multidisciplinary collaboration and centralized care in improving patient outcomes in this context. Recognizing these challenges, Lombardy, Italy's most populous region, embarked on establishing pancreas units across its territory to enhance clinical outcomes and organizational efficiency. This initiative, driven by a multistakeholder approach involving the Lombardy Welfare Directorate, clinicians, and a patient association, emphasizes the centralization of complex care in high-volume hospitals, adopting a hub-and-spoke model and a multidisciplinary approach. This article outlines the process and criteria set forth for pancreas unit implementation, aiming to provide a structured framework for enhancing pancreatic cancer care. Central to this initiative is the establishment of structured criteria and minimal requirements, not only for surgery but also for other essential components of care, ensuring a comprehensive approach to pancreatic cancer management. The Lombardy model offers a structured framework for enhancing pancreatic cancer care, with potential applicability to other regions and countries seeking to improve their cancer care infrastructure., Competing Interests: Declaration of competing interest The following authors declare conflict of interest: Other authors declare no conflicts of interest, (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Despite contributions provided by the recent clinical trials, several issues and challenges still remain unsolved in adjuvant colon cancer (CC). Hence, further studies should be planned to better refine risk assessment as well as to establish the optimal treatment strategy in the adjuvant setting. However, it is necessary to request adequate, contemporary and relevant variables and report them homogeneously in order to bring maximal information when analyzing their prognostic value., Material and Methods: The project was devised to gain a consensus from experts engaged in the planning, accrual and analyses of stage II and III CC clinical trials, to identify mandatory and recommended baseline variables in order to i) harmonize future data collection worldwide in clinical trials dedicated to adjuvant treatment of CC; ii) propose guidance for Case Report Forms to be used for clinical trials in this setting. A total of 72 questions related to variables that should be reported and how to report them in adjuvant clinical trials were approved and then voted to reach a final consensus from panelists., Results: Data items on patient-related factors, histopathological features, molecular profile, circulating biomarkers and blood analyses were analyzed and discussed by the whole expert panel. For each item, we report data supporting the acquired consensus and the relevant issues that were discussed. Nineteen items were deemed to be mandatory for resected stage III patients and 24 for resected stage II disease. In addition, 9 and 4 items were judged as recommended for stage III and II, respectively., Conclusion: In our opinion, these 28 variables should be used and uniformly reported in more comprehensive CRFs as research groups design future clinical trials in the field of adjuvant colon cancer., Competing Interests: Declaration of Competing Interest All authors declare no competing interest regarding this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: A number of studies suggest that older patients may have reduced or no benefit from the addition of oxaliplatin to fluoropyrimidines as adjuvant chemotherapy for stage III colon cancer (CC)., Materials and Methods: We studied the prognostic impact of age, as well as treatment adherence/toxicity patterns according to age, in patients with stage III CC who received 3 or 6 months of infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin (CAPOX) on the basis of data collected from trials from the ACCENT and IDEA databases. Associations between age and time to recurrence (TTR), disease-free survival (DFS), overall survival (OS), survival after recurrence (SAR), and cancer-specific survival (CSS) were assessed by a Cox model or a competing risk model, stratified by studies and adjusted for sex, performance status, T and N stage, and year of enrollment., Results: A total of 17,909 patients were included; 24% of patients were age older than 70 years (n = 4,340). Patients age ≥70 years had higher rates of early treatment discontinuation. Rates of grade ≥3 adverse events were similar between those older and younger than 70 years, except for diarrhea and neutropenia that were more frequent in older patients treated with CAPOX (14.2% v 11.2%; P = .01 and 12.1% v 9.6%; P = .04, respectively). In multivariable analysis, TTR was not significantly different between patients <70 years and those ≥70 years, but DFS, OS, SAR, and CSS were significantly shorter in those patients ≥70 years., Conclusion: In patients ≥70 years with stage III CC fit enough to be enrolled in clinical trials, oxaliplatin-based adjuvant chemotherapy was well tolerated and led to similar TTR compared with younger patients, suggesting similar efficacy. TTR may be a more appropriate end point for efficacy in this patient population.

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers. The Khorana risk score (KRS), new-Vienna CATS, PROTECHT, and CONKO risk assessment models (RAMs) were applied. (3) Results: Within 6 months, the cumulative incidences of VTE and mortality were 12% and 29%, respectively. Patients with VTE showed significantly increased levels of D-dimer, FVIII, prothrombin fragment 1 + 2, and TG. D-dimer and ECOG performance status were identified as independent risk factors for VTE and mortality by multivariable analysis and utilized to generate a risk score that provided a cumulative incidence of VTE of 6% vs. 25%, death of 19% vs. 55%, and in the low- vs. high-risk group, respectively ( p < 0.001). While all published RAMs significantly stratified patients for risk of death, only the CATS and CONKO were able to stratify patients for VTE. (4) Conclusions: A new prediction model was generated to stratify lung cancer patients for VTE and mortality risk, where other published RAMs failed.

Background: Risk assessment models (RAMs) are relevant approaches to identify cancer outpatients at high risk of venous thromboembolism (VTE). Among the proposed RAMs, the Khorana (KRS) and the new-Vienna CATS risk scores have been externally validated in ambulatory patients with cancer., Objectives: To test KRS and new-Vienna CATS scores in 6-month VTE prediction and mortality in a large prospective cohort of metastatic cancer outpatients during chemotherapy., Patients/methods: Newly diagnosed patients with metastatic non-small cell lung, colorectal, gastric, or breast cancers were analyzed (n = 1286). The cumulative incidence of objectively confirmed VTE was estimated with death as a competing risk and multivariate Fine and Gray regression., Results: Within 6 months, 120 VTE events (9.7%) occurred. The KRS and the new-Vienna CATS scores showed comparable c-stat. Stratification by KRS provided VTE cumulative incidences of 6.2%, 11.4%, and 11.5% in the low-, intermediate-, and high-risk categories, respectively (p = ns), and of 8.5% vs. 11.8% (p = ns) in the low- vs. high-risk group by the single 2-point cut-off value stratification. Using a pre-defined 60-point cut-off by the new-Vienna CATS score, 6.6% and 12.2% cumulative incidences were obtained in the low- and high-risk groups, respectively (p < 0.001). Furthermore, having a KRS ≥2 = or a new-Vienna CATS score >60 points was also an independent risk factor for mortality., Conclusion: In our cohort, the 2 RAMs showed a comparable discriminating potential; however, after the application of cut-off values, the new-Vienna CATS score provided statistically significant stratification for VTE. Both RAMs proved to be effective in identifying patients at increased risk of mortality., Competing Interests: Declaration of competing interests All authors declare that they have no potential conflicts of interest related to this research., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration., Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR)., Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007)., Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity., Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus., Competing Interests: The Federation of Italian Cooperative Oncology Groups (FICOG) received funding for the present study from Roche S.p.A. and Seqirus, and outside the present research from Astra Zeneca, Bristol-Myers Squibb (BMS), and Sanofi. MB received funding for the present study from Roche S.p.A. and Seqirus (through FICOG as Institution, no personal fees). She also received, outside the current work: research funding from Pfizer and Novartis (through Institutions); honoraria as a speaker at scientific events (personal fees) by BMS, MSD, IPSEN, Novartis, Astra Zeneca, Pierre Fabre, and Pfizer; as a consultant for advisory role (personal fees) by IPSEN, Novartis, Sanofi, Pierre-Fabre, and Merck; personal fees for copyright transfer by Sciclone Pharmaceuticals, Pierre-Fabre, MSD, IPSEN, Pfizer, and Sanofi. AC received speakers fees/grant consultancies from Astrazeneca, BMS, MSD, EISAI, IQVIA, and OncoC4. UDG has served as a consultant for Astellas, Bayer, BMS, Ipsen, Janssen, Novartis, Pfizer, Sanofi, and Pharmamar; he received research funding from AstraZeneca, Roche, and Sanofi; and received travel funds from BMS, Ipsen, Janssen, Pfizer, and Roche during the conduct of the study. MDM reports personal fees from Bristol Myers Squibb, personal fees from Merck Sharp & Dohme, personal fees from AstraZeneca, personal fees from Janssen, personal fees from Astellas, personal fees from Pfizer, personal fees from Eisai, personal fees from Takeda, grants from Tesaro GSK, outside the submitted work. SB received honoraria as a speaker at scientific events and in advisory role by BMS, Pfizer; MSD, Ipsen, Roche S.p.A., Eli-Lilly, AstraZeneca, and Novartis; he also received research funding from Novartis. VS participated, with personal fees, to advisory boards and speaker's bureaus for Roche S.p.A. SC declared his role in an international board for Eli Lilly international. AR declares Advisory Board activity for Bristol, Pfizer, Bayer, and Kyowa Kirin, and speaker honorarium from Roche Diagnostics. PAZ reports outside the submitted work personal fees for advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme (MSD), Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer. MS received honoraria for advisory role from Janssen, and travel and accommodation expenses from Janssen, IPSEN, BMS, Astellas, and Pfizer. ER had a role as consultant for MSD, Novartis, Pierre Fabre, Immunocore and Pfizer. FG received personal fees from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, MSD, BMS, Pierre Fabre, Novartis, Merck, Takeda, Bayer, Novartis, and AMGEN for consulting activity; from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, BMS, AMGEN, MSD, Celgene, and Pierre Fabre for speakers bureaus. GG declares speaker and advisory fees from MSD; Travels and Accommodations from AstraZeneca. DaS declares honoraria for advisory board from Astellas, Janssen, Bayer, Novartis, Astra-Zeneca, MSD, BMS, Roche. FM received personal fees for advisory role by Roche, MSD, Takeda, Novartis, Sanofi. RRS received travel grants from AIOM and CIPOMO, and declares memberships in AIOM, CIPOMO, ESMO, ASCO and Rotary Club. SP received honoraria as a speaker from Roche, Astra Zeneca, MSD, and GSK. DG received honoraria as a speaker from Amgen. MR received honoraria as speaker/consultant by MSD, Astra Zeneca, Bristol-MyersSquibb (BMS), Novartis, and Pfizer. All the cited competing interests were outside the current work and not related to the content of our manuscript if not differently specified. All remaining authors have declared no conflicts of interest., (© 2023 The Authors.)

Purpose: Oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) for 6 months remains a standard in high-risk stage III patients. Data are lacking as to whether early discontinuation of all treatment (ETD) or early discontinuation of oxaliplatin (EOD) could worsen the prognosis., Materials and Methods: We studied the prognostic impact of ETD and EOD in patients with stage III CC from the ACCENT/IDEA databases, where patients were planned to receive 6 months of infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin. ETD was defined as discontinuation of treatment and EOD as discontinuation of oxaliplatin only before patients had received a maximum of 75% of planned cycles. Association between ETD/EOD and overall survival and disease-free survival (DFS) were assessed by Cox models adjusted for established prognostic factors., Results: Analysis of ETD and EOD included 10,447 (20.9% with ETD) and 7,243 (18.8% with EOD) patients, respectively. Compared with patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, with Eastern Cooperative Oncology Group performance status ≥ 1, and for ETD, older with a lower body mass index. In multivariable analyses, ETD was associated with a decrease in disease-free survival and overall survival (hazard ratio [HR], 1.61, P < .001 and HR, 1.73, P < .001), which was not the case for EOD (HR, 1.07, P = .3 and HR, 1.13, P = .1). However, patients who received < 50% of the planned cycles of oxaliplatin had poorer outcomes., Conclusion: In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III CC, ETD was associated with poorer oncologic outcomes. However, this was not the case for EOD. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.

Background: the tight and reciprocal interaction between cancer and hemostasis has stimulated investigations on the possible role of hemostatic biomarkers in predicting specific cancer outcomes, such as disease progression (DP) and overall survival (OS). In a prospective cohort of newly diagnosed metastatic gastrointestinal (GI) cancer patients from the HYPERCAN study, we aimed to assess whether the hemostatic biomarker levels measured before starting any anticancer therapy may specifically predict for 6-months DP (6m-DP) and for 1-year OS (1y OS). Methods: plasma samples were collected and tested for thrombin generation (TG) as global hemostatic assay, and for D-dimer, fibrinogen, and prothrombin fragment 1 + 2 as hypercoagulation biomarkers. DP and mortality were monitored during follow-up. Results: A prospective cohort of 462 colorectal and 164 gastric cancer patients was available for analysis. After 6 months, DP occurred in 148 patients, providing a cumulative incidence of 24.8% (21.4−28.4). D-dimer and TG endogenous thrombin potential (ETP) were identified as independent risk factors for 6m-DP by multivariate Fine−Gray proportional hazard regression model corrected for age, cancer site, and >1 metastatic site. After 1 year, we observed an OS of 75.7% (71.9−79.0). Multivariate Cox regression analysis corrected for age, site of cancer, and performance status identified D-dimer and ETP as independent risk factors for 1y OS. Patients with one or both hemostatic parameters above the dichotomizing threshold were at higher risk for both 6m-DP and 1-year mortality. Conclusion.: in newly diagnosed metastatic GI cancer patients, pretreatment ETP and D-dimer appear promising candidate biomarkers for predicting 6m-DP and 1y OS. In this setting, for the first time, the role of TG as a prognostic biomarker emerges in a large prospective cohort.

During the coronavirus disease 2019 (COVID-19) pandemic, to protect patients with cancer, reduction in hospital access, reduction in myelosuppression risk, and postponing/withholding unnecessary treatments were important in order to reduce risk of infection. Little is known about the risk burden for patients with resected colorectal cancer (CRC). Use of an oral chemotherapy regimen represents a convenient, safe, and manageable therapy for both fit and elderly patients. In the metastatic setting, treatment of solitary metastases may be performed, omitting postresection chemotherapy due to lack of literature data. In case of unresectable CRC, short induction chemotherapy, followed by a maintenance phase, may improve compliance and reduce toxicity. In the adjuvant setting, a shorter duration (3 months) may be discussed with patients except in very high-risk cases. Clinical judgment may reduce the risk of COVID-19 exposure in patients with CRC. Oral regimens, treatment delay, and chemotherapy holiday are ways to minimize the global risk for patients during the COVID-19 era.

Background: EOX (epirubicin, oxaliplatin, and capecitabine) is one of the standard regimens for metastatic or locally advanced gastric cancer (GC). A new combination based on fractional docetaxel (low-TOX) has been developed in an attempt to increase the efficacy of EOX and reduce the heavy toxicity of classical docetaxel regimens., Methods: Overall, 169 previously untreated GC patients were randomized between EOX (arm A) and low-TOX (arm B). The primary endpoint was progression-free survival (PFS), while secondary ones were overall survival (OS), overall response rate (ORR), disease control rate (DCR), and tolerability. The study was designed to detect a 35% (80% power at a two-sided 5% significance level) PFS increase with low-TOX and an interim analysis for futility was planned after the first 127 events., Results: At the cut-off date of interim analysis, median PFS was 6.3 months [95% confidence interval (CI) 5.0-8.1] in arm A vs 6.3 months (95% CI 5.0-7.8) in arm B, without statistical difference. OS was comparable in the two arms: 12.4 in arm A (95% CI 9.1-19.2) vs 11.5 months in arm B (95% CI 8.6-15.0). ORR was 33% and 24%, while DCR was 68% and 67%, respectively. Treatment modification (91% vs 78%, P = 0.017) and number of patients with CTC grade ≥ 3 adverse events (42 vs 35) were higher in arm B., Conclusions: A triplet regimen based on the fractional dose of docetaxel achieves no improvement over EOX which remains a potential standard treatment in many patients with inoperable, locally advanced or metastatic GC., (© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: Diabetes mellitus (DM) has been associated with increased colorectal cancer (CRC) risk and worse prognosis in metastatic CRC patients. In this large, pooled analysis of non-metastatic colon cancer (CC) patients, we investigated the impact of DM and metformin treatment on recurrence and survival., Patients and Methods: A patient-level pooled analysis from three randomised adjuvant trials was performed. All patients had resection with curative intent of stage II or III CC and were treated with standard adjuvant fluoropyrimidine and oxaliplatin (±cetuximab). We investigated the impact of DM and metformin treatment on time to recurrence (TTR) and overall survival (OS)., Results: Of 5922 CC patients who had a median follow-up of 6.8 years, 621 patients (10.5%) had DM at CC diagnosis. Of those with DM, 327 patients (52.7%) were defined as metformin users and 294 patients (47.3%) as non-metformin users. CC patients with DM had a significantly shorter TTR (adjHR: 1.21; 95% CI, 1.03-1.42; p = 0.017) and OS (adjHR: 1.29; 95% CI, 1.09-1.52; p = 0.003) compared to non-diabetic CC patients. Diabetic CC patients not receiving metformin had a significantly worse TTR (adjHR: 1.28; 95% CI, 1.02-1.60; p = 0.032) and OS (adjHR: 1.41; 95% CI, 1.13-1.77; p = 0.003) as compared to non-diabetic patients. These worse outcomes were not significant in metformin users (TTR: adjHR: 1.16; 95% CI, 0.94-1.43; p = 0.168; OS: adjHR: 1.19; 95% CI, 0.95-1.48, p = 0.127)., Conclusions: CC patients with DM had not only a significantly worse survival but also TTR. Furthermore, our data suggest that metformin may attenuate the detrimental effect of DM on CC patient outcomes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years)., Materials and Methods: Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non-cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered., Results: Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85)., Conclusion: Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology., Competing Interests: Elisa FontanaEmployment: HCA/Sarah CannonConsulting or Advisory Role: Astellas Pharma (I), Celgene (I), Servier (I), Bristol Myers Squibb (I)Patents, Royalties, Other Intellectual Property: Patent No: 1716712.3 pending (I)Travel, Accommodations, Expenses: Bristol Myers Squibb (I), Servier (I) Alberto SobreroStock and Other Ownership Interests: BayerConsulting or Advisory Role: Merck Serono, Servier, Sanofi, Celgene, Amgen, Bayer, MenariniSpeakers' Bureau: Sanofi, Merck Serono, Takeda, Roche, Bayer, Amgen, Celgene, Lilly, AstraZeneca, Bristol Myers SquibbTravel, Accommodations, Expenses: Bayer, Merck Serono, Roche, Takeda Timothy IvesonHonoraria: ServierConsulting or Advisory Role: Servier, Bristol Myers Squibb, Pierre Fabre, MSD Oncology Anthony F. ShieldsConsulting or Advisory Role: ImaginAb, Caris Life SciencesSpeakers' Bureau: Caris Life SciencesResearch Funding: Taiho Pharmaceutical, Bayer, Boehringer Ingelheim, Plexxikon, Eisai, Inovio Pharmaceuticals, H3 Biomedicine, Caris Life Sciences, ImaginAb, Exelixis, Xencor, Lexicon, Daiichi Sankyo, Halozyme, Incyte, LSK BioPharma, Esperas Pharma, Nouscom, Boston Biomedical, Astellas Pharma, AstraZeneca, Five Prime Therapeutics, MSK Pharma, Esperas Pharma, Alkermes, Repertoire Immune Medicines, Telix Pharmaceuticals, Hutchison China Meditech, Seattle Genetics, Jiangsu Alphamab Biopharmaceuticals, Shanghai HaiHe Pharmaceutical, TopAlliance BioSciences Inc (Inst)Travel, Accommodations, Expenses: GE Healthcare, Caris Life Sciences, TransTarget, ImaginAb, Inovio Pharmaceuticals Julien TaiebConsulting or Advisory Role: Roche, Merck KGaA, Amgen, Servier, MSD, Pierre Fabre, NovartisSpeakers' Bureau: Servier, Amgen, Roche/Genentech, Sanofi, Merck, Lilly, MSD, Pierre Fabre Takayuki YoshinoHonoraria: Chugai Pharma, Merck, Bayer Yakuhin, Ono Pharmaceutical, Lilly, Taiho PharmaceuticalResearch Funding: Chugai Pharma (Inst), MSD (Inst), Daiichi Sankyo Company, Limited (Inst), PAREXEL International Inc (Inst), Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), Amgen (Inst), Sanofi (Inst) Ioannis SouglakosConsulting or Advisory Role: Roche (Inst), Servier (Inst), Ipsen (Inst), Pierre Fabre, MSD, Bristol Myers Squibb-Ono PharmaceuticalSpeakers' Bureau: Sanofi, Merck KGaA (Inst), Roche (Inst), MSDResearch Funding: Amgen (Inst), Sanofi (Inst)Travel, Accommodations, Expenses: Merck Serono, Amgen, Sanofi, Roche, Servier Elizabeth C. SmythEmployment: HCA International (I)Honoraria: Servier, Novartis, Bristol Meyer Squibb, PfizerConsulting or Advisory Role: Servier, Amal Therapeutics, BeiGene, Zymeworks, Novartis, Bristol Myers Squibb, Merck Serono, Roche, AstraZeneca, AmgenResearch Funding: Bristol Myers Squibb (Inst) Florian LordickHonoraria: Lilly, Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Elsevier, BioNTech AG, Servier, Merck KGaA, Roche, Medscape, Incyte, Art Tempi, Medupdate, Streamedup!Consulting or Advisory Role: Lilly, Merck Sharp & Dohme, Bristol Myers Squibb, Astellas Pharma, Servier, Zymeworks, AmgenResearch Funding: Bristol Myers Squibb (Inst), MSD (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Lilly Markus MoehlerHonoraria: Amgen, Roche/Genentech, Merck Serono, MSD Oncology, Bristol Myers Squibb, AstraZeneca/MedImmune, Servier, Pierre Fabre, SanofiConsulting or Advisory Role: Bayer, MSD, Merck Serono, Amgen, Taiho Pharmaceutical, Pfizer, Roche, Lilly, Servier, BeiGene, BMSResearch Funding: Amgen (Inst), Leap Therapeutics (Inst), Merck Serono (Inst), AstraZeneca (Inst), MSD (Inst)Travel, Accommodations, Expenses: Amgen, Merck Serono, Roche, Bayer, ASCO, German Cancer Society, MSD, ESMO Roberto LabiancaConsulting or Advisory Role: Roche, Lilly, Sanofi, Merck SeronoTravel, Accommodations, Expenses: Roche, Merck Serono, Servier Jeffrey MeyerhardtHonoraria: Cota Healthcare, Taiho PharmaceuticalResearch Funding: Boston Biomedical (Inst) Thierry AndréHonoraria: Roche/Genentech, Bristol Myers Squibb, Servier, Bayer, Sanofi, Amgen, Pierre Fabre, Ventana Medical Systems, GlaxoSmithKlineConsulting or Advisory Role: Amgen, Bristol Myers Squibb, HalioDX, MSD Oncology, Servier, Bayer, AstraZeneca/MedImmune, Tesaro, Clovis Oncology, Gastrointestinal Cancers Advice, Pierre Fabre, GamaMabs Pharma, Astellas Pharma, Kaleido Biosciences, Gritstone Oncology, GlaxoSmithKline, Seagen, TransgeneTravel, Accommodations, Expenses: Roche/Genentech, Amgen, Bristol Myers Squibb, MSD Oncology, Roche, Ventana Medical Systems Ioannis BoukovinasEmployment: Pierre Fabre (I)Honoraria: Roche, MSD, Bristol Myers Squibb, Pfizer, Novartis, Merck, AstraZeneca, LEO Pharma, ServierConsulting or Advisory Role: Roche, Sanofi, AstraZeneca, Bristol Myers Squibb, LEO Pharma, MSD, Novartis, Ipsen, Genesis PharmaResearch Funding: Roche, Novartis, Bristol Myers Squibb, MSD, Regeneron, Boehringer Ingelheim, Lilly, PfizerTravel, Accommodations, Expenses: MSD, Roche, Pfizer, Bristol Myers Squibb, Servier, Ipsen Sara LonardiConsulting or Advisory Role: Amgen, Merck Serono, Lilly, Servier, AstraZeneca, Incyte, Daiichi Sankyo, Bristol Myers Squibb, MSDSpeakers' Bureau: Roche, Lilly, Bristol Myers Squibb, Servier, Merck Serono, Pierre Fabre, GlaxoSmithKline, AmgenResearch Funding: Amgen, Merck Serono, Bayer (Inst), Roche (Inst), Lilly (Inst), AstraZeneca (Inst), Bristol Myers Squibb (Inst) Mark SaundersHonoraria: Servier, Merck SeronoTravel, Accommodations, Expenses: Servier Dewi VernereyConsulting or Advisory Role: OSE Immunotherapeutics, Janssen-Cilag, HalioDx, Pfizer, CellProthera, GERCOR, Incyte, Fondazione Smith Kline, Invectys, AC BiotechTravel, Accommodations, Expenses: MSD Eiji OkiSpeakers' Bureau: Chugai Pharma, Lilly Japan, Takeda, Ono Pharmaceutical, Bayer Yakuhin, Bristol Myers Squibb Japan Vassilis GeorgouliasConsulting or Advisory Role: Novartis, Pfizer, AstraZeneca Qian ShiStock and Other Ownership Interests: Amgen, Johnson & Johnson, MerckHonoraria: Chugai PharmaConsulting or Advisory Role: Yiviva, Boehringer Ingelheim, Regeneron, Hoosier Cancer Research NetworkResearch Funding: Celgene (Inst), Roche/Genentech (Inst), Janssen (Inst), BMS (Inst), Novartis (Inst)No other potential conflicts of interest were reported.

Background: Regorafenib is a key agent in metastatic colorectal cancer (mCRC), but no validated factors predicting longer survival are available., Patients and Methods: REALITY was a retrospective multicenter trial in regorafenib-treated mCRC patients with overall survival (OS) ≥ 6 months. We aimed to assess the association between clinical parameters and outcome to define a panel identifying long term survivors among regorafenib candidates. Primary and secondary endpoints were OS and progression free survival (PFS), respectively. Statistical analysis was performed with MedCalc (survival distribution: Kaplan-Meier; survival comparison: log-rank test; independent role of significant variables at univariate analysis: logistic regression)., Results: Hundred regorafenib-treated mCRC patients with OS ≥ 6 months were enrolled. Median OS was 11.5 m (95%CI:9.60-12.96); median PFS was 4.2 months (95% CI:3.43-43.03). The absence of liver progression and of dose and/or schedule changes during the first 4 cycles (mainly for good tolerability) were independently correlated at multivariate analysis with OS (Exp(b)1.8869, P= .0277and Exp(b)2.2000, P = .0313) and PFS (Exp(b)2.1583, P = .0065 and Exp(b)2.3036, P= .0169). Patients with neither of these variables had a significantly improved OS (n = 14, 20.8 months; 95% CI:12.967-55.267) versus others (n = 86, 10 months; 95% CI:8.367-12.167; HR = 0.4902, P = .0045) and PFS (11.3 months, 95%CI:4.267-35.8 vs. 3.9 months, 95% CI:3.167-43.033; HR = 0.4648, P = .0086)., Conclusion: These 2 factors might allow clinicians to better identify patients more likely to benefit from regorafenib. Toxicity management remains crucial., (Copyright © 2021. Published by Elsevier Inc.)