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This good practice paper (GPP) is intended to support clinicians in assessing patient fitness for bleomycin and in management of bleomycin pulmonary toxicity (BPT) where it occurs. Bleomycin, originally developed as an antibiotic in the 1960s, has been a cornerstone of therapy for classical Hodgkin lymphoma (CHL) since results of its use in combination with doxorubicin, vincristine and dacarbazine (ABVD) were first published by Bonadonna et al in 1975 1. The same author recognised high rates of respiratory morbidity in these patients 2, and bleomycin-;related pulmonary toxicity (BPT) is now a well-;recognised and feared complication with its use. ABVD and BEACOPP/ BEACOPDac (bleomycin, cyclophosphamide, etoposide, doxorubicin, vincristine and prednisolone, with procarbazine or dacarbazine) are standard first-;line treatments in CHL patients, but considerable variation remains in assessing patient fitness for bleomycin both clinically and with respiratory investigations. A recent survey of British haematologists regularly using bleomycin revealed that 87.5% have no local protocols for assessing patients in an evidence-;based fashion, with wide variations in practice captured in the same survey (personal data). A working group was established and a literature review undertaken with the goal of presenting practical recommendations for clinicians regarding bleomycin use based on available evidence and expert opinion., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Objective: Cervical cancer is the third most common cancer in Brazil. Although rare, its diagnosis during pregnancy represents a great challenge for the medical team and the patient. The objective of this study was to evaluate the maternal and perinatal outcomes of pregnant women who underwent neoadjuvant chemotherapy with carboplatin and paclitaxel for advanced stage cervical cancer., Methods: This was a descriptive, retrospective study that included pregnant women with advanced stage cervical cancer (IB3 a IIIC1) who were treated at our center over 12 years. These patients received neoadjuvant chemotherapy with carboplatin plus paclitaxel during pregnancy to prevent disease progression., Results: Tumor shrinkage of at least 50 % was observed in four patients, while the disease remained stable in three others. There was one case of fetal death without apparent cause at 29 weeks, but all other mothers were discharged from the hospital at the same time as their healthy newborns., Conclusion: Chemotherapy with carboplatin and paclitaxel administered to pregnant women with advanced stage cervical cancer (IB3 - IIIC1) may have prevented disease progression without worsening neonatal outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Pancreatic cancer is predicted to be the second highest cause of cancer deaths by 2030, with a mortality rate of 98 % and a 5-year survival rate of only 4-8 %. FOLFIRINOX which consists of four main ingredients has shown superior efficacy in treating patients with pancreatic cancer compared to other agents and combinations. However, toxicities have prevented full-dose use of FOLFIRINOX. In this study, we present the design of a liposome nanosystem that enables the sequential release of a drug combination that is called FOLFIRINOX using lipid-based nanosystem synergistic chemo/photothermal therapy approaches. The co-eccentric liposome allowed us to locate the drug molecules in different locations giving us the flexibility to release them in a selected order. Core liposome (L2) has a melting temperature of 53.63 °C, it was decorated by gold nanoparticle (L2@AuNP) to bring photothermal responsiveness. The outer liposome structure had a lower melting temperature, which facilitated the sequential release process. The efficacy of photothermal therapy for nanosystem was calculated. The results indicate that coating L2@AuNP nanostructure with L1 liposomes improves efficacy by stabilizing gold nanoparticles. FOLFIRINOX components are encapsulated in a concentric liposome structure according to the order of administration into the body. The concentric liposome structure enables the sequential release of multiple drugs due to the varying phase transition temperatures of the liposomes. The cytotoxic effect of these formulations was evaluated on Panc-1 pancreatic cancer cells; the lowest cell viability was obtained in 4 Liposome(L) under 5 min NIR irradiation. Combination therapy has a higher therapeutic efficacy (70.45 %) when compared to chemotherapy and photothermal therapy used separately. The study's results show the potential of combination therapies to improve therapeutic outcomes, providing a promising path for future research and clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Most patients with small-cell lung cancer (SCLC) present with extensive-stage (ES) disease and have a poor prognosis despite achieving high initial response rates to platinum-based doublet chemotherapy. This study evaluated whether adding hydroxychloroquine (HCQ) to chemotherapy could improve outcomes., Methods: This was a randomised multicentre phase II trial. Eligible patients had untreated ES-SCLC, a performance status 0-2 and measurable disease. Patients were randomly assigned (1:1 ratio) to HCQ (400 mg orally twice daily) plus carboplatin-gemcitabine or carboplatin-etoposide alone. Chemotherapy was administered for up to six cycles, with HCQ given concurrently and then as single agent for up to 30 months. Primary endpoint was PFS, aiming for a hazard ratio (HR) of 0.70., Results: 72 patients were randomised (36 HCQ+chemotherapy and 36 chemotherapy alone). Median HCQ treatment duration was 4.4 months. HCQ did not improve PFS (HR 1·12 95 %CI 0·69-1.84; p = 0·64), with a median of 5.7 months (HCQ+chemotherapy) versus 6.2 months (chemotherapy). The corresponding median OS were 8.9 and 10.2 months (HR 0.83, 95 %CI 0.48-1.45, p = 0.52). Fewer patients in the HCQ arm completed four cycles of chemotherapy due to adverse events (64 % vs. 81 %). Grade ≥ 3 adverse events were higher in the HCQ+chemotherapy arm (83.3 % vs. 27.8 %), primarily anaemia, neutropenia, and thrombocytopenia, partly due to the initially higher gemcitabine dose used CONCLUSIONS: Combining HCQ with platinum doublet chemotherapy did not improve PFS or OS outcomes for ES-SCLC, resulting in more patients stopping chemotherapy due to increased adverse events. When considered alongside other randomised studies of HCQ in cancer, the evidence collectively indicates a limited role for HCQ as a therapeutic option., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In advanced hepatocellular carcinoma (HCC), the triple combination therapy of hepatic arterial infusion chemotherapy (HAIC) with lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has shown promise as a front-line treatment. This study aimed to explore the tumor microenvironment (TME) characteristics of the population benefiting most from this treatment., Methods: The study included 44 patients, with 38 ultimately receiving the HAIC + FOLFOX + lenvatinib + PD-1 inhibitor treatment. Tumor response was evaluated using modified RECIST criteria, classifying patients as responders (complete or partial response) or non-responders (stable or progressive disease). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were assessed. Additionally, genetic sequencing and RNA analysis were conducted on biopsy samples to identify TME differences between the two groups., Results: Among the 38 patients, 22 responded favorably, showing significantly longer median OS (not-reached vs. 8.6 months) and median PFS (15.3 months vs. 2.0 months) compared to non-responders. Common AEs included AST elevation, stomachache, nausea, and hypertension, with limited severe AEs. Genetic analysis revealed no significant differences in DNA features between the groups. However, RNA analysis indicated that responders had a more robust immune status, better drug sensitivity, and increased immune cell infiltration. Notably, higher levels of tumor-infiltrating T lymphocytes were linked to better responses, longer PFS, and OS., Conclusion: The differences in the initial TME of patients, especially in tumor-infiltrating T lymphocytes, may be potential biomarkers for predicting response and prognosis. This finding provides clues to search for biomarkers for this triple combination therapy in advanced HCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria., Materials and Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate. We carried out a survival analysis by a Cox regression model., Results: A total of 524 favorable-risk patients were included in the analysis. After a median follow-up of 37.2 months, the median OS in the overall population was 56.1 months. There was no significant difference in OS between patients receiving sunitinib and those receiving TKI + ICI combinations (p = 0.761). Patients on TKI + ICI had significantly longer PFS compared to patient treated with sunitinib (30.7 vs 22.9 months, p = 0.007). Analysis of OS and PFS based on metastatic site revealed that patients with bone metastases benefited more from ICI plus TKI (56 patients with bone metastases receiving IO + TKI, 38 received pembrolizumab plus axitinib, 15 cabozantinib plus nivolumab and 3 pembrolizumab plus lenvatinib), while sunitinib was more effective for pancreatic and glandular metastases. Additionally, the number of metastatic sites played a role, with TKI plus ICI showing superiority in patients with a single metastatic site. The time from RCC diagnosis to metastatic disease also impacted outcomes, with TKI plus ICI being more effective in patients with a shorter interval (i.e., < 36 months)., Conclusions: The choice between upfront combination or monotherapy for metastatic favorable prognosis RCC remains a current issue. While combination therapy offers prolonged PFS, it does not necessarily translate to improve OS compared to sunitinib. This real-world study supports the superiority in terms of PFS of TKI plus ICI vs TKI monotherapy but not in OS. Probable, other clinical factors should be taking into account to make clinical treatment decisions in this setting., Competing Interests: Declarations. Conflicts of Interest: Javier Molina-Cerrillo declares consultant, advisory or speaker roles for IPSEN, Roche, Pfizer, Sanofi, Janssen and BMS. JMC has received research grants from Pfizer, IPSEN and Roche Francesco Massari has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD and Pfizer outside the submitted work. Linda Cerbone has received honoraria for advisory boards, speaker engagements and scientific consultancy for educational purposes from AstraZeneca, EISAI, MSD, Ipsen, BMS, A.A.A.; past MSD employee in Medical Affairs. Ondrej Fiala received honoraria from Novartis, Janssen, Merck and Pfizer for consultations and lectures unrelated to this project. Fernando Sabino M. Monteiro has received research support from Janssen, Merck Sharp Dome and honoraria from Janssen, Ipsen, Bristol Myers Squibb and Merck Sharp Dome, all unrelated to the present paper. R. Kanesvaran has received fees for speaker bureau and advisory board activities from the following companies; Pfizer, MSD, BMS, Eisai, Ipsen, Johnson and Johnson, Merck, Amgen, Astellas and Bayer. Camillo Porta has received honoraria from Angelini Pharma, AstraZeneca, BMS, Eisai, Ipsen and MSD and acted as a Protocol Steering Committee Member for BMS, Eisai and MSD. Sebastiano Buti has received honoraria for speaking at scientific events and advisory roles from AstraZeneca, Bristol Myers Squibb, Ipsen, Merck, Eisai, MSD, Novartis and Pfizer and research funding from Novartis and Pfizer. Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas, A.A.A. and Bayer, all unrelated to the present paper. The other authors declare no conflicts of interest., (© 2024. The Author(s).)

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.7-NR, median follow-up 50 months). The secondary endpoint, biochemical PFS, was 48.6 months (95% CI: 39.9-NR) and coincided with or preceded SLiM-CRAB in eight patients. For additional secondary objectives, the overall response rate was 93% with 31% achieving complete response (CR) and 45% very good partial response (VGPR) or better. CR correlated strongly with the absence of SLiM-CRAB and biochemical progression. MRD-negativity (10 -5 sensitivity) predicted a 5-year biochemical PFS of 100% versus 40% in MRD-positive patients (p = 0.051), demonstrating that deep responses significantly improve time to progression. Exploratory single-cell RNA sequencing linked tumor MHC class I expression to proteasome inhibitor response, and a lower proportion of GZMB+ T cells within clonally expanded CD8+ T cells associated with suboptimal outcomes., Competing Interests: Competing interests: O.N. reports research support from Takeda and Janssen; advisory board participation for Bristol Myers Squibb, Janssen, Sanofi, Takeda, and GPCR therapeutics; and honorarium from Pfizer. M.B. reports consultancy for Janssen, BMS, Takeda, Epizyme, Karyopharm, Menarini Biosystems, and Adaptive. G.B. reports consultancy for Prothena. E.O. reports advisory board participation and/or honoraria from Janssen, BMS, Sanofi, Pfizer, Exact; consulting for Takeda; and steering committee participation with Natera. K.A. reports consultancy for AstraZeneca, Janssen, and Pfizer; and board participation and stock options for Dynamic Cell Therapies, C4 Therapeutics, Next RNA, Oncopep, Starton, and Window. P.G.R. reports advisory board participation or consulting for Celgene (BMS), GSK, Karyopharm, Oncopeptides, Regeneron, Sanofi, and Takeda; and research grants from Oncopeptides and Karyopharm. R.S.P. is a co-founder, equity holder, and consultant for PreDICTA Bioscience. I.M.G.: Consulting/Advisory role: AbbVie, Adaptive, Amgen, Aptitude Health, Bristol Myers Squibb, GlaxoSmithKline, Huron Consulting, Janssen, Menarini Silicon Biosystems, Oncopeptides, Pfizer, Sanofi, Sognef, Takeda, Binding Site a part of Thermo Fischer Scientific, Window Therapeutics, and 10X Genomics; speaker fees from Vor Biopharma and Veeva Systems, Inc., and is a co-founder of PreDICTA Bioscience. I.M.G.’s spouse is the CMO and an equity holder of Disc Medicine. All other authors declare no conflicts of interest. Inclusion and ethics: One or more of the authors of this paper self-identifies as an underrepresented ethnic and/or gender minority in science. One or more of the authors of this paper self-identifies as a member of the LGBTQIA+ community. We support inclusive, diverse, and equitable conduct of research., (© 2025. The Author(s).)

Aim of the Study: The management of synchronous metastatic rectal cancer (SMRC) is complex and multimodal, involving chemotherapy, surgery and/or radiotherapy. The aim of this study was firstly to confirm the efficacy of the induction FOLFIRINOX, and secondly to evaluate the different therapeutic strategies and outcomes of patients., Patients and Methods: This French study combined data from a prospective FFCD trial and a multicenter cohort. Patients included had SMRC and had undergone induction triplet chemotherapy. Two groups of patients were defined according to the resectability of metastases at baseline: resectable (Res) and unresectable (URes). The primary endpoint was the objective response rate., Results: 146 patients were included in 16 French centers and 65 patients in the FFCD1102 trial. In overall population the median age of patients was 59 years, 86% of tumors were of the lower or middle rectum, 33% were well-differentiated, 53% were RAS mutated and 7% BRAF mutated. Triplet induction was associated with 80% of objective response and 92% of disease control. After the induction phase, 69% and 48% of patients of Res and URes groups underwent rectal surgery, and secondary metastases resection was done in 79% and 39% of patients, respectively. Median overall survival (OS) for Res was 56.3 months (95% CI: 22.54-NA). Median OS for URes who had or not secondary metastases resection were 45.1 months (95% CI: 39.89-NA) and 21.1 months (95% CI 17.31-27.1), respectively. Patients with BRAF mutated tumors were more likely to have unresectable disease, and had worse survivals than the patients with RAS mutated or RAS/BRAF wild-type., Conclusion: Triplet induction chemotherapy is a treatment of choice in selected patients with SMRC, allowing to adapt the therapeutic strategy to the response and invasiveness of the various sites., Structured Abstract: The management of metastatic rectal cancer is essentially based on three main therapeutic approaches: surgery, radiotherapy/chemoradiotherapy and chemotherapy. Induction triplet chemotherapy appears as a good choice for fit and young patients. It allows to adapt the therapeutic strategy to the response and invasiveness of the various sites. In this study dedicated to patients undergoing treatment for rectal cancer with synchronous metastases, FOLFIRINOX-based induction chemotherapy was associated with objective response rate of 77% and disease control rate of 92%. These results are similar with those of the FFCD 1102 trial and confirm the efficacy of induction chemotherapy with FOLFIRINOX with or without targeted therapy in these patients in daily routine practice. Surgery for metastases is a key factor in determining patient's outcome and triplet induction chemotherapy, associated with high response rates, enables a significant percentage of patients to undergo surgery and appears therefore to be a treatment of choice, particularly for patients whose disease is unresectable at baseline., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jean Baptiste Bachet reports a relationship with Amgen Inc that includes: funding grants. Thierry Lecomte reports a relationship with Institut Servier SAS that includes: speaking and lecture fees. Anthony Turpin reports a relationship with Institut Servier SAS that includes: funding grants. David Tougeron reports a relationship with Sanofi that includes: speaking and lecture fees. Come Lepage reports a relationship with Takeda Oncology that includes: funding grants. *J.B. Bachet has received personal fees from Amgen, Bayer, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Sanofi, Servier, and non-financial support from Amgen, Merck Serono, and Roche, outside the submitted work. *T.Lecomte has received honoraria for speaking or consulting role from Servier, Pierre Fabre, Merck Serono, BMS, Astra Zeneca, AAA, Sanofi, IPSEN, Novartis, CHUGAI outside of the submitted work; research funding from Pierre Fabre and Leo Pharma outside of the submitted work; and travel grants from IPSEN, Merck Serono, AMGEN, Astra Zeneca, Pierre Fabre and Servier outside of the submitted work. *A.Turpin has received personal fees from Servier, Viatris, Incyte Bioscience, BMS, Merck and grants and personal fees from AstraZeneca and MSD outside the submitted work. *D.Tougeron has received honoraria as a speaker or in an advisory role from Sanofi, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, BMS, Astra Zeneca, Takeda and MSD. *C.Lepage has received personal fees from Takeda, Pierre Fabre, Amgen, Servier, Novartis. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma, predominantly afflicting older adults. There remains a notable absence of data regarding DLBCL in older adults in Latin America., Materials and Methods: We conducted a retrospective analysis of 608 newly diagnosed Latin American patients with DLBCL aged ≥65 years., Results: The median age at diagnosis was 74 years (range: 65-96 years), 51 % were female, 36 % had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, and 65 % had advanced disease. The most common regimens used were standard-dose R-CHOP (n = 420, 69 %), R-CVP (n = 77, 12 %), R-mini-CHOP (n = 74, 12 %), and CHOP/CVP (n = 30, 5 %). With a median follow-up of 60 months (95 % confidence interval [CI]: 38.7-75.2 months), the five-year overall survival (OS) rate was 50 % (95 % CI, 43-58). An ECOG PS ≥2 (hazard ratio [HR] 1.93; 95 % CI 1.51-2.46; p < 0.01), advanced clinical stage (HR 1.46; 95 % CI 1.12-1.91; p < 0.01), increased serum lactic dehydrogenase level (HR 1.48; 95 % CI 1.16-1.87; p < 0.01), and albumin level < 3.5 mg/dL (HR 1.64; 95 % CI 1.29-2.10; p < 0.01) were associated with an inferior OS. Using anthracyclines (HR 0.50; 95 % CI 0.38-0.66; p < 0.01) and using rituximab (HR 0.51; 95 % CI 0.36-0.73; p < 0.01) were independently associated with a superior OS., Discussion: In a large cohort of Latin American older patients with DLBCL, therapy and outcome patterns are similar to those reported internationally. The lack of standardized geriatric assessments in Latin America represents an essential area for research to better stratify older patients with DLBCL deemed to be at higher risk for toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Hepatic artery infusion (HAI) chemotherapy, particularly with floxuridine (FUDR), has previously shown effectiveness in improving recurrence-free survival (RFS) in colorectal cancer (CRC) patients with colorectal liver metastases (CRLM). Nonetheless, its adjuvant use alongside modern systemic chemotherapy remains unevaluated., Patients and Methods: The HARVEST trial is an open-label, randomized, controlled study conducted from May 2018 to August 2021. CRC patients with resectable primary tumors and CRLM were recruited and randomized to receive standard systemic chemotherapy only (non-HAI group) or in combination with HAI-FUDR (HAI group). However, due to a FUDR manufacturing shortage, the study was terminated early after enrolling 92 patients. The primary endpoint was the 3-year RFS rate, with secondary endpoints including overall survival (OS), liver-specific RFS, and adverse events., Results: Of the 92 randomized patients, 77 were included in the modified intention-to-treat analysis. Three-year RFS rates were comparable between the HAI (N = 38) and non-HAI (N = 39) groups (31.4 % vs. 34.4 %; P = 0.28). However, improved 1-year RFS and a longer expected five-year OS were observed in the HAI group. While exploratory subgroup analysis suggested potential RFS benefits for patients with multiple liver metastases, RAS/BRAF mutations, and positive postoperative ctDNA methylation, multivariable analysis did not identify these as independent factors. Safety analysis showed comparable chemotherapy-related adverse events, except for a higher occurrence of ALT elevation in the HAI group., Conclusions: While our study showed no significant difference in three-year RFS, adjuvant chemotherapy intensification with HAI-FUDR is feasible and may offer early benefits in RFS and long-term OS. Nonetheless, a larger sample size is needed for validation and identifying which patient subgroup might benefit from this regimen., Trial Registration: ClinicalTrials.gov: NCT03500874., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No conflicts of interest to be reported by all authors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) is almost always fatal after the failure of asparaginase. This phase II study aimed to investigate the efficacy and safety of tislelizumab combined with gemcitabine and oxaliplatin (Tisle-GemOx) in patients with ENKTCL failing asparaginase., Methods: Eligible patients received Tisle-GemOx as initial induction for 6-8 cycles at 21-day intervals. Responders continued tislelizumab maintenance every two months for two years. The primary endpoint was the best complete response rate (CRR)., Results: As of September 2023, 32 patients were enrolled in our study. Among the 30 efficacy-evaluable patients, the best CRR was 60 %, meeting the primary efficacy endpoint. With a median follow-up of 22.6 months, the median progression-free survival (PFS) was 7.4 months and the 1-year PFS rate was 46.4 %. Subgroup analyses showed that shorter PFS was associated with previous lines of chemotherapy ≥ 2 (P = 0.034) and concomitant hemophagocytic lymphohistiocytosis (P = 0.040). Pseudo-progression was observed in three patients (10 %). The most common grade ≥ 3 toxicities were lymphopenia (25 %) and anemia (15.6 %)., Conclusions: Tisle-GemOx exhibits promising anti-tumor activity and manageable toxicities as a salvage therapy for ENKTCL failing asparaginase. Further long-term follow-up is necessary to evaluate the durability of the response with tislelizumab maintenance in this patient population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objectives: Gemcitabine plus cisplatin (GP) and docetaxel plus cisplatin plus fluorouracil (TPF) are induction chemotherapy (IC) regimens for locally advanced nasopharyngeal carcinoma (LA-NPC). The oral convenience of capecitabine presents its potential as a fluorouracil substitute in the TPF regimen, which has yet to be thoroughly investigated. This study aims to compare the efficacy and safety of the docetaxel, cisplatin, and capecitabine (TPC) with GP and TPF in LA-NPC., Methods: A retrospective analysis was conducted on newly diagnosed stage III-IVa nasopharyngeal carcinoma patients who received GP, TPC, or TPF induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) between February 2019 and December 2021. A comparison of the prognostic outcomes and associated adverse reactions among patients receiving different IC regimens. Multivariate Cox regression was applied to analyze independent prognostic factors, and subgroup survival analyses were conducted based on these factors., Results: A total of 291 LA-NPC patients were included, with 70 receiving TPC, 119 receiving GP, and 102 receiving TPF. Kaplan-Meier survival analysis indicated no significant differences in OS, PFS, LRFS, and DMFS among the 3 groups. Multivariate Cox regression identified T classification and clinical stage as independent prognostic factors. Subgroup analyses revealed no significant differences in OS and PFS between the 3 groups across T1-2 and T3-4 classifications or III and IVa stages.The TPC group exhibited lower incidence rates of treatment-related acute toxicity reactions, including grade 3-4 toxicities., Conclusion: The TPC induction chemotherapy regimen demonstrates comparable efficacy to GP and TPF, while maintaining a favorable safety profile., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Senescent cells are cells that stop dividing but sustain viability. Cellular senescence is the hallmark of aging, but senescence also appears in cancer, triggered by cells stress, tumor suppression of gene activation, and oncogene activity. In lung cancer, senescent cancer cells secrete VEGF, which initiates a process of angiogenesis, enabling the cancer to grow and proliferate. Chemotherapy kills cancer cells, but some cancer cells become senescent. Hence, a senolytic drug, a drug that eliminates senescent cells, should significantly improve the efficacy of chemotherapy. In this paper, we developed a mathematical spatio-temporal model of combination chemotherapy with senolytic drug in treatment of lung cancer. Model's simulations of tumor volume growth are shown to agree with mouse experiments in the case where cyclophosphamide is combined with the senolytic drug fisetin. It is then shown how the model can be used to assess the benefits of treatments with different combinations and different schedules of the two drugs in order to achieve optimal tumor volume reduction., Competing Interests: Declaration of competing interest none, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Acute myeloid leukemia (AML) is a complex hematological malignancy predominantly affecting the elderly, with a median diagnosis age of 68 years. Despite advances in treatment, elderly AML patients face suboptimal survival outcomes, with an estimated 5-year survival rate below 20 %. Epigenetic dysregulation, notably DNA methylation, is a key factor in the progression of myelodysplastic syndromes (MDS) to AML. This review examines various combination regimens involving azacitidine (AZA), including those with lenalidomide, histone deacetylase inhibitors (HDACi), kinase inhibitors, metabolic enzyme inhibitors, monoclonal antibodies, immune checkpoint inhibitors, and anti-apoptotic protein inhibitors. Notable among these are the combinations with venetoclax, which has demonstrated remarkable efficacy in phase III trials, and the emerging IDH inhibitors ivosidenib and enasidenib, which have shown significant clinical benefits in patients with IDH mutations. While combination therapies with AZA hold great promise, challenges persist, including translating in vitro synergies to in vivo efficacy and identifying optimal regimens for specific patient populations. Cumulative toxicities may also offset clinical benefits, necessitating rigorous clinical trial design. Future research must focus on refining combination strategies, optimizing dosages and sequences, and thoroughly evaluating therapeutic efficacy and safety to advance the treatment of AML and improve patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)