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Background: To present findings from a retrospective study conducted by the Ultra-Rare Sarcoma Working Group on metastatic low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid (H)-LGFMS/SEF across 28 global centres., Methods: Patients treated at participating institutions from January 2000 to September 2022 were retrospectively selected. Diagnosis was confirmed by expert pathologists. Primary endpoint was progression-free survival (PFS-1) from metastasis detection to first progression or death. PFS-2 was calculated from therapy initiation., Results: A total of 101 patients were identified (32 LGFMS, 50 SEF, 19 H-LGFMS/SEF). Median (m) follow-up was 62.1 months. mPFS-1 was 28.7, 11.8, and 20.3 months for LGFMS, SEF, and H-LGFMS/SEF, respectively. mOS was 145.8, 41.9, and 113.5 months, respectively. Treatments included anthracycline-based chemotherapy, gemcitabine-based chemotherapy (G), pazopanib, trabectedin, others. mPFS-2 was: 20.1, 5.5, and 3.5 months in H-LGFMS/SEF, SEF, and LGFMS, respectively, with anthracyclines; 19.5, 7.7, and 6.9 months in LGFMS, SEF, and H-LGFMS/SEF, respectively, with pazopanib; 12.0, 9.7, and 3.1 months in H-LGFMS/SEF, LGFMS, and SEF, respectively. Occasional responses occurred with ifosfamide/oral cyclophosphamide, and prolonged stable disease with immune checkpoint inhibitors., Conclusions: In this series, the largest available, metastatic LGFMS, SEF, and H-LGFMS/SEF showed different courses. Systemic agents have modest efficacy, informing future trials of novel agents for these tumours., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers., Methods: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration., Results: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC., Conclusion: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The number of randomized trials of agents targeting oncogene-addicted tumors has surged in the past 10 years. Using a meta-analysis, we explored whether improvements in objective response rate (ORR) in comparative trials using targeted agents could serve as a potential surrogate endpoint for improvements in progression-free survival (PFS) or overall survival (OS) in populations with oncogene-addicted cancer., Patients and Methods: Using commercial text mining software I2E, we searched ClinicalTrials.gov and MEDLINE databases for randomized, phase III trials based on prospectively defined criteria, including (i) use of agents targeting EGFR activating mutations, ALK rearrangements, BRAF V600E or V600K mutations, and BCR-ABL fusion protein; (ii) molecularly enriched trial population or subpopulation; (iii) control arm only randomized to chemo/cytotoxic therapy. Correlative analyses were performed using ORR, OS, and PFS data from trials that met these criteria., Results: A total of 62 trials were identified; 15 met all of the prespecified criteria. The ORR effect size (both the difference in ORR between arms and the log odds ratio) and log PFS hazard ratio were strongly correlated: -0.78 (P = 0.0007) for the ORR difference model; -0.74 (P = 0.0017) for the log odds ratio model. ORR effect size was positively correlated with the log OS hazard ratio, but more weakly: -0.67 (P = 0.013) for the ORR difference model and -0.58 (P = 0.036) for the log odds ratio model. Analysis of the treatment effects between OS and PFS found no correlation., Conclusions: These analyses identified a strong correlation between treatment effects on ORR and PFS in randomized clinical trials investigating agents targeting oncogene-driven cancers. A weaker correlation was observed between ORR and OS. These meta-analysis results support the use of a high ORR forming the basis of an initial regulatory approval in biomarker-driven studies., Competing Interests: Disclosure BJS reports personal fees from Loxo Oncology, during the conduct of the study; personal fees from AstraZeneca, Novartis, Roche/Genentech, Bristol Myers Squibb, Merck, Gritstone Oncology, Amgen, Sanofi/Regeneron, and grants and personal fees from Pfizer, all outside the submitted work. HHL reports personal fees for Advisory Board participation from Bayer, Boehringer Ingelheim, Celgene, and Eli Lilly; personal fees for Advisory Board and Speaker’s Bureau participation and research funding from Novartis; personal fees for Speaker’s Bureau participation from Guardant Health and Eisai; travel support and research funding from Merck; research funding from Mundipharma, and travel support from Pfizer. YS reports personal fees from Eli Lilly, Roche, AstraZeneca, Takeda, Pfizer, and Merck. ZMT, PF, BKL, and AS report employment and stock ownership with Eli Lilly. JW reports Advisory Board and lecture fees from AbbVie, Amgen, AstraZeneca, Blueprint, Bristol Myers Squibb, Boehringer Ingelheim, Chugai, Ignyta, Janssen, Eli Lilly, Loxo Oncology, Merck, Novartis, Pfizer, Roche, and Takeda; and research support to the institution from Bristol Myers Squibb, Johnson and Johnson, Novartis, and Pfizer. JC-HY reports honoraria for speeches and Advisory Boards from Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai, Merck, Pfizer, Novartis, Bristol Myers Squibb, and Ono Pharmaceutical; and honoraria for Advisory Boards from AstraZeneca, Astellas, Merck Serono, Celgene, Merrimack, Yuhan Pharmaceuticals, Daiichi Sankyo, Hansoh, Takeda, and Blueprint Medicines. AD reports honoraria from Advisory Board participation from Ignyta/Genentech/Roche, Loxo Oncology/Bayer/Eli Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BerGenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, AbbVie, 14ner/Elevation Oncology, Remedica Ltd., ArcherDX, Monopteros, Novartis, EMD Serono, Melendi, Liberum, Repare therapeutics; associated research support paid to the institution by Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, PharmaMar; CME honoraria from Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, Axis, PeerView Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences; royalties from Wolters Kluwer; and other support from Merck, Puma, Merus, and Boehringer Ingelheim., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The prognostic impact of comorbidities in patients with sarcomas is not well defined. The aims of this study were to examine the implications of comorbidities and abnormal peripheral blood indices in patients with sarcomas., Methods: A population-based database was assembled to extract patients with sarcoma in Hong Kong between January 2004 and March 2018. Charlson's Comorbidity Index (CCI) score and prevalence of comorbidities, neutrophil, lymphocyte and platelet counts at diagnosis were assessed. The prognostic values of CCI, neutrophil-lymphocyte (NLR) and platelet-lymphocyte ratios (PLR) were estimated using Cox proportional hazard models. Restricted cubic spline plots were used to explore the association of baseline NLR and PLR with all-cause and cancer-specific mortality., Results: Among 3358 eligible patients with sarcomas, 52.2% died after a median 26 months of follow-up. The most common comorbidities were diabetes mellitus (9.8%) and cerebrovascular disease (4.8%). Patients with higher CCI had higher mortality (CCI=3 vs CCI=2; HR 1.49; 95% CI 1.19 to 1.87; p<0.01; CCI ≥7 vs CCI =2; HR 3.20; 95% CI 2.62 to 3.92; p<0.001). Abnormal NLR and PLR levels were associated with higher all-cause mortality (NLR: HR 1.698, p<0.001, 95% CI 1.424 to 2.025; PLR: HR 1.346, p<0.001, 95% CI 1.164 to 1.555) and cancer-related mortality (NLR: HR 1.648, p<0.001, 95% CI 1.341 to 2.024; PLR: HR 1.430, p<0.001, 95% CI 1.205 to 1.697)., Conclusions: This is the largest population-based soft-tissue or bone sarcoma cohort worldwide. Comorbidities have significant negative prognostic impact on the survival of patients with sarcomas. Moreover, NLR and PLR are robust prognostic factors, and abnormal NLR and PLR have negative effects yet non-linear effects on survival., Competing Interests: Competing interests: HH-fL reports receipt of research funding of from MSD and Mundipharma for projects outside of this submitted work. HH-fL has also received personal fees from Novartis, Pfizer, Eisai and Boehringer-Ingelheim for advisory activities outside the scope of this submitted work. CK-HW reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund. No other disclosures were reported., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Together with surgery and radiotherapy, systemic treatment with cytotoxic chemotherapy and molecular targeted agents is one of the main therapeutic pillars in the treatment of soft-tissue sarcomas and is the mainstay of treatment in patients with advanced or metastatic disease. Unlike other more common malignancies such as breast and colorectal cancer, the role of chemotherapy when used in the adjuvant setting in soft-tissue sarcomas is less well defined. Results from prior studies have been conflicting, in part due to the heterogeneity and rarity of the disease, and large-scale meta-analysis has been performed to address this issue. Neoadjuvant chemotherapy, defined as the use of chemotherapy before definitive treatment with surgery or radiotherapy, has distinct theoretical and practical advantages, which can potentially be beneficial to the patient. However, the currently available evidence to support its use is even more scarce. In this review article, we describe the current established data behind the use of adjuvant chemotherapy in selected patients with localised soft-tissue sarcomas and, through extrapolation of available data, discuss the potential role of it when used in the upfront setting., Competing Interests: Competing interests: None declared.