Therapeutic Advances in Medical Oncology最新文献

{"title":"A real-world study on treatment after TKI progression in HER2-positive MBC.","authors":"Shiyi Li, Lili Zhang, Ting Xu, Jiayuan Huang, Chengjun Zhu, Yuan Yuan","doi":"10.1177/17588359261442687","DOIUrl":"https://doi.org/10.1177/17588359261442687","url":null,"abstract":"<p><strong>Background: </strong>After disease progression on anti-human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors (TKIs), trastuzumab deruxtecan (T-DXd) is recommended as a subsequent therapy. Because T-DXd has only recently been covered by insurance, patients previously opted for alternative regimens.</p><p><strong>Objectives: </strong>This study aimed to report real-world data on HER2-positive metastatic breast cancer (MBC) patients whose disease progressed during TKI therapy and provide a basis for further research.</p><p><strong>Design: </strong>This retrospective study included 216 HER2-positive MBC patients who progressed after TKI therapy between July 2014 and February 2025.</p><p><strong>Methods: </strong>All patients received anti-HER2 TKI therapy (including pyrotinib and lapatinib) in 28-day cycles. Treatment doses and combinations with chemotherapy, HER2-targeted agents, or endocrine therapy were decided by physicians. The primary objectives were to determine the proportion of patients receiving different regimens after TKI failure and evaluate progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events.</p><p><strong>Results: </strong>As of April 1, 2025, treatment distribution was 26.9% in the antibody-drug conjugate (ADC) group, 45.8% in the monoclonal antibody (mAb) group, and 27.3% in the TKI group. The expansion of ADC reimbursement under China's healthcare policy, beginning in 2023, led to increased clinical adoption. Median PFS was 10.2 months (95% confidence interval (CI), 6.7-13.6) in the ADC group, 7.3 months (95% CI, 5.7-9.0) in the mAb group, and 7.2 months (95% CI, 5.8-8.6) in the TKI group, with no significant differences (<i>p</i> = 0.282). T-DXd demonstrated substantial antitumor activity with a 12-month PFS rate of 50.0%. Patients who are acquired-resistant to TKI had better outcomes than primary-resistant ones, particularly among those continuing TKI therapy. No unexpected toxic effects were reported.</p><p><strong>Conclusion: </strong>After progression following TKI therapy, T-DXd exhibited notable antitumor activity, although no significant efficacy differences were observed among ADC, mAb, and TKI groups.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261442687"},"PeriodicalIF":4.2,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating intracranial hypofractionated radiotherapy with immunotherapy for melanoma brain metastases: therapeutic impact and immune modulation.","authors":"Jing Lin, Ting Zhang, Yibin Zeng, Lirui Tang, Jieyuan Cai, Ling Chen, Jiazhen Fang, Yu Chen, Jinluan Li","doi":"10.1177/17588359261444616","DOIUrl":"https://doi.org/10.1177/17588359261444616","url":null,"abstract":"<p><strong>Background: </strong>Combined radiotherapy and immunotherapy can enhance antitumor efficacy, but its effects on melanoma brain metastases (MBM) remain unclear.</p><p><strong>Objectives: </strong>To evaluate the intracranial efficacy, safety, and exploratory immune biomarkers of zimberelimab combined with intracranial hypofractionated radiotherapy in patients with MBM.</p><p><strong>Methods: </strong>Eligible patients were aged 18-75, had an Eastern Cooperative Oncology Group performance status of 0-2 and measurable brain metastases. Patients received 30-50 Gy/5-10 fractions intracranial hypofractionated radiotherapy and two cycles zimberelimab (240 mg every 3 weeks). The primary endpoint was the intracranial objective response rate (ORR). Secondary endpoints included the disease control rate, overall survival, progression-free survival (PFS), quality of life, safety and potential biomarkers. In addition, serum cytokines were profiled and linked to proteomics-based exploratory prognostic model constructed using the UK Biobank dataset.</p><p><strong>Results: </strong>Between November 2022 and February 2025, 10 patients, with median age 60.5 years, completed the treatment, and their data were analyzed. The median intracranial metastatic lesion size was 2.4 cm (range 1.0-5.9 cm). The intracranial ORR was 70%, and intracranial disease control rate was 90%. The median overall survival and intracranial PFS were both 12 months, while the overall PFS was 10.5 months. The patients' quality of life improved, without grade ⩾3 treatment-related adverse events. Furthermore, post-treatment increases in selected immune-related biomarkers, such as CXCL9, were descriptively associated with treatment response, and baseline levels showed exploratory associations with survival outcomes.</p><p><strong>Conclusion: </strong>HFRT plus zimberelimab demonstrated promising intracranial activity, quality of life improvement, and acceptable early safety in patients with MBM and may potentially induce an abscopal antitumor effect. Exploratory immune analyses suggest that baseline immune readiness and therapy-induced immune activation may be associated with treatment benefit.</p><p><strong>Design: </strong>This was a prospective, single-arm, open-label phase II study.</p><p><strong>Trial registration: </strong>ChiCTR, ChiCTR2200057001. Registered 25 February 2022 (https://www.chictr.org.cn/showproj.html?proj=153144).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261444616"},"PeriodicalIF":4.2,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging precision therapeutics for pancreatic ductal adenocarcinoma: KRAS and beyond.","authors":"Ani Misirian, Jonathan Pai, Diana L Hanna","doi":"10.1177/17588359261432058","DOIUrl":"https://doi.org/10.1177/17588359261432058","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related death with a rising incidence in younger individuals and no standard early detection exam. Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated gene of the RAS family, and KRAS mutations are found in approximately 85%-90% of PDAC. Long considered undruggable due to its molecular structure, the advent of sotorasib and adagrasib has ushered in multiple novel therapeutics targeting the RAS pathway, including mutation-selective, pan-KRAS, and pan-RAS inhibitors. Combination strategies using chemotherapy and directed against EGFR, SOS1, SHP2, and immune pathways, among others, aim to overcome resistance to RAS inhibitor monotherapy and enhance the depth and duration of clinical benefit. The minority of PDAC tumors that are KRAS-wildtype are enriched for rare, actionable alterations, including Neuregulin-1, HER2, and BRAF amenable to targeted treatments. For patients with metastatic disease carrying a germline BRCA1/2 or PALB2 pathogenic variant, PARP inhibitors remain an option as maintenance treatment after achieving at least stable disease with platinum-based chemotherapy. Importantly, ongoing and future clinical trials are shifting the use of targeted therapies from the refractory setting to earlier lines and the perioperative setting with promising results. Here, we detail the different areas of investigation targeting KRAS and other precision-based therapies in PDAC, as well as the potential emerging roles of local interventions (radiation, surgery) for select patients with oligometastatic disease. Composite predictive biomarkers using genomic, proteomic, and radiographic factors are needed to refine and individualize treatment selection and ultimately improve patient outcomes.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261432058"},"PeriodicalIF":4.2,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment patterns and clinical outcomes of neoadjuvant chemoimmunotherapy for patients with resected oesophageal squamous cell carcinoma: a Chinese multicentre retrospective study.","authors":"Xiangyang Yu, Jianfei Zhu, Feng Wang, Kai Ma, Xiaotong Guo, Baihua Zhang, Lixu Wang, Xin Yu, Shengcheng Lin, Calvin S H Ng, Ran Yang, Jie He, Zhentao Yu","doi":"10.1177/17588359261443147","DOIUrl":"https://doi.org/10.1177/17588359261443147","url":null,"abstract":"<p><strong>Background: </strong>Several clinical trials of neoadjuvant chemoimmunotherapy (neoCIT) for patients with locally advanced oesophageal carcinoma have been reported recently, with promising anti-tumour efficacy. However, systematic evaluation of the treatment patterns and clinical outcomes in a real-world cohort is lacking.</p><p><strong>Objectives: </strong>This study aimed to describe the real-world treatment patterns and short- and long-term outcomes of neoCIT in patients with resected oesophageal squamous cell carcinoma (ESCC).</p><p><strong>Design: </strong>A multicentre retrospective cohort study.</p><p><strong>Methods: </strong>Data from patients with resected ESCC who received neoCIT in routine clinical practice between January 2020 and December 2022 were retrospectively collected from three tertiary centres in China.</p><p><strong>Results: </strong>A total of 324 consecutive patients were enrolled, and the majority (82.4%) received two cycles of neoCIT. In total, 225 patients achieved a radiographic partial response (PR), resulting in an objective response rate of 69.4%. The rates of minimally invasive oesophagectomy and radical resection were 71.9% and 98.5%, respectively. Fifty-nine patients (18.2%) experienced postoperative complications, and the most common complication was anastomotic leakage (10.2%). The pathological complete response and major pathological response rates were 27.2% and 37.0%, respectively. As of August 31, 2024, the median follow-up was 24.8 months. The estimated 3-year rates of disease-free survival and overall survival were 62.3% and 71.5%, respectively. Multivariate analyses revealed that tumour grade (<i>p</i> = 0.047), number of neoadjuvant therapy cycles (<i>p</i> = 0.042), resection status (<i>p</i> = 0.043), pathological N stage (<i>p</i> < 0.001) and adjuvant treatment (<i>p</i> < 0.001) were independent prognostic factors for disease-free survival. However, advanced pathological N stage was identified as the sole independent factor that correlated with worse overall survival (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>This real-world study validates the clinical efficacy and safety of neoCIT for resected oesophageal squamous cell carcinoma while demonstrating encouraging survival outcomes.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261443147"},"PeriodicalIF":4.2,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microwave ablation for T1N0M0 papillary thyroid carcinoma located in the isthmus: a multicenter prospective cohort study with over 5-year follow-up.","authors":"Lin Zheng, Qiao-Wei Du, Jian-Ping Dou, Fang-Yi Liu, Jie Yu, Zhi-Gang Cheng, Xiao-Ling Yu, Shui-Lian Tan, Hui Wang, Zhi-Bin Cong, Shu-Rong Wang, Ming-An Yu, Zhi-Feng Xu, Ying Che, Nan Bai, Cun Liu, Sheng-Nan Huo, Ying Hao, Xue Wang, Ying Liu, Ying Zhou, Zhi-Yu Han, Ping Liang","doi":"10.1177/17588359261442628","DOIUrl":"https://doi.org/10.1177/17588359261442628","url":null,"abstract":"<p><strong>Background: </strong>Thermal ablation (TA) of papillary thyroid carcinoma (PTC) has been reported to have promising results. However, performing microwave ablation (MWA) on PTCs located in the isthmus remains controversial.</p><p><strong>Objectives: </strong>This study aimed to compare the feasibility, effectiveness, and safety of MWA for treating PTC in the isthmus and lateral lobes.</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Methods: </strong>In this study, between December 2019 and December 2020, patients with clinical T1N0M0 PTC who planned to receive MWA were enrolled from 12 hospitals. All tumors were evaluated by preoperative ultrasound and divided into isthmus-located tumors and lobe-located tumors. The patients were followed until 1 February 2025. The primary endpoints included technical success and disease-free survival. The secondary endpoints included treatment parameters, complications, and tumor shrinkage. Variables were compared between the two groups, and subgroup analysis was performed.</p><p><strong>Results: </strong>After exclusion, 652 patients (mean age, 43 years ± 11 (SD), 481 females) were included: 109 with PTC in the isthmus and 543 with PTC in the lateral lobes. One isthmic tumor terminated MWA, 108 versus 543 (mean tumor volume of 0.1 ml ± 0.1 vs 0.2 ml ± 0.2, <i>p</i> = 0.14), was analyzed, with a mean follow-up period of 61 months ± 5 (range, 54-67 months). Comparable technical success rates were achieved (99% (108/109) versus 100% (543/543), <i>p</i> = 0.17) for isthmic tumors and lobe tumors, with 1 versus 24 complications (0.9% (1/108) vs 4.4% (24/543), <i>p</i> = 0.08). Although fewer isthmic tumors achieved the targeted safety margin (2 mm) than did lobe tumors (50.0% (54/108) vs 61.0% (331/543), <i>p</i> = 0.03), no differences in disease-free survival (97.2% (105/108) vs 97.4% (529/543), <i>p</i> = 0.91) or tumor shrinkage (96 ± 16% (SD) vs 95 ± 17% (SD), <i>p</i> = 0.70) were detected. In the tumor stage, capsular invasion, safety margin, sex, age, and thyroid disease subgroups, the outcomes remained comparable.</p><p><strong>Conclusion: </strong>MWA was feasible for T1N0M0 PTC in the isthmus and showed comparable efficacy in comparison with tumors in the lobes.</p><p><strong>Trial registration: </strong>NCT04197960.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261442628"},"PeriodicalIF":4.2,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effectiveness of first-line taxane-platinum versus fluorouracil-platinum chemotherapy in advanced esophageal squamous cell carcinoma: a propensity score-matched real-world study.","authors":"Sisi Ye, Chao Li, Rongrui Liu, Chuanhua Zhao, Juan Li, Jianming Xu","doi":"10.1177/17588359261436621","DOIUrl":"https://doi.org/10.1177/17588359261436621","url":null,"abstract":"<p><strong>Background: </strong>While immune-chemotherapy represents the first-line standard for advanced esophageal squamous cell carcinoma (ESCC), fluorouracil-platinum (FP) and taxane-platinum (TP) regimens remain the fundamental cytotoxic backbones. Despite their widespread clinical application, robust comparative data on their relative efficacy and safety in real-world populations are lacking, creating an evidence gap that hampers optimal backbone selection.</p><p><strong>Objectives: </strong>This study aimed to compare the effectiveness and safety of first-line FP versus TP chemotherapy in patients with advanced ESCC using large-scale, multicenter real-world data.</p><p><strong>Design: </strong>This was a large-scale, multicenter, retrospective cohort study employing a propensity score-matched design to compare two treatment cohorts: patients receiving FP chemotherapy versus those receiving TP chemotherapy for unresectable advanced ESCC. Data spanned from January 2013 to December 2023, ensuring a contemporary and representative treatment population.</p><p><strong>Methods: </strong>Data were extracted from a national cancer database. Patients with unresectable ESCC receiving first-line FP or TP chemotherapy were included. Propensity score matching (PSM) in a 1:1 ratio was used to balance the baseline characteristics. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety.</p><p><strong>Results: </strong>After PSM, 3440 matched pairs were generated (<i>N</i> = 6880 total). The median follow-up was 6.3 years. The TP regimen demonstrated superior short-term efficacy compared to FP: median PFS was 5.2 versus 4.4 months (hazard ratio (HR), 0.91; 95% confidence interval (CI), 0.86-0.96; <i>p</i> = 0.0004); ORR was 22.2% versus 19.5% (<i>p</i> = 0.026); and among responders, median DOR was 10.8 versus 4.4 months (HR, 0.77; 95% CI, 0.64-0.94; <i>p</i> = 0.009). However, no significant difference was observed in OS (median OS: 15.9 vs 16.1 months; HR, 1.00; 95% CI, 0.94-1.06; <i>p</i> = 0.901). Toxicity profiles were distinctly regimen-specific, with FP associated with higher rates of hand-foot syndrome and gastrointestinal events, whereas TP was linked to higher incidences of neuropathy and alopecia.</p><p><strong>Conclusion: </strong>In this large-scale real-world analysis, first-line TP chemotherapy provided significantly better disease control and response durability compared to FP in advanced ESCC, albeit without an OS benefit. The distinct toxicity profiles of each regimen offer additional considerations for individualized treatment selection. These findings offer critical evidence to guide backbone selection in contemporary treatment algorithms.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261436621"},"PeriodicalIF":4.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-PD-1 matches interferon as adjuvant therapy for acral melanoma: a retrospective study.","authors":"Yu Du, Yu Chen, Jiaxiang Wang, Jing Lin, Xiaoting Wei, Junjie Gu, Jun Guo, Lu Si, Lili Mao","doi":"10.1177/17588359261436189","DOIUrl":"https://doi.org/10.1177/17588359261436189","url":null,"abstract":"<p><strong>Background: </strong>Programmed cell death protein (PD-1) inhibitors constitute the standard adjuvant therapy for cutaneous melanoma (CM), but well-established strategies for acral melanoma (AM) remain limited.</p><p><strong>Objective: </strong>To compare the efficacy of adjuvant anti-PD-1 immunotherapy versus high-dose interferon α-2b (HDI) in patients with stage IIB-IV AM and CM.</p><p><strong>Design: </strong>This multicenter, retrospective study enrolled 511 patients with resected stage IIB-IV AM and CM between January 2017 and December 2023.</p><p><strong>Methods: </strong>Patients were divided into four groups by subtype and treatment: patients with CM and treated with anti-PD-1 (CM-PD-1), patients with CM and treated with HDI (CM-HDI), patients with AM and treated with anti-PD-1 (AM-PD-1), and patients with AM and treated with HDI (AM-HDI). Recurrence-free survival (RFS), overall survival (OS), and patient safety were evaluated.</p><p><strong>Results: </strong>This study comprised 362 AM and 149 CM cases. AM cases presented with thicker primary lesions, higher ulceration rates, and fewer <i>BRAF</i> mutations. Median follow-up was 49 months. Among patients with stage IIB/C, median RFS was not reached in any groups. Among stage III/IV patients, median RFS was 14.6 (CM-PD-1), 13.7 (CM-HDI), 13.3 (AM-PD-1), and 11.7 months (AM-HDI), and median OS was 61.6, 40.7, 42.4, and 53.4 months, respectively, without significant intergroup differences. Anti-PD-1 significantly improved RFS in patients with stage III/IV AM with <i>KIT</i> mutations (9.1 vs 5.0 months, <i>p</i> = 0.048) and ⩾4 lymph node metastases (10.5 vs 6.6 months, <i>p</i> = 0.036). Anti-PD-1 had significantly fewer adverse effects than HDI (60.4% vs 88.6%, <i>p</i> < 0.001), including fewer grades 3-4 events (4.6% vs 30.7%, <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Adjuvant anti-PD-1 therapy provides RFS comparable to that of HDI in AM and CM, with a superior safety profile. Patients with AM harboring <i>KIT</i> mutations derive greater benefits from adjuvant anti-PD-1 therapy.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261436189"},"PeriodicalIF":4.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of prolonged progression-free survival in patients with unresectable or recurrent pancreatic cancer treated with nanoliposomal irinotecan with fluorouracil and folinic acid (NAPOLEON-2 study).","authors":"Yasunori Kawaguchi, Kohei Hayashi, Mototsugu Shimokawa, Taiga Otsuka, Junichi Nakazawa, Hozumi Shimokawa, Yudai Shinohara, Futa Koga, Noriko Oza, Hisanobu Oda, Shigeyuki Takeshita, Shiho Arima, Shuji Arita, Kazuo Nishikawa, Satoshi Otsu, Hiroki Taguchi, Kenichi Jikuya, Tatsunori Sakai, Yujiro Ueda, Takahiro Sakae, Norimasa Araki, Hironori Sawase, Yasushi Ide, Machiko Kawahira, Kenta Nio, Tsuyoshi Shirakawa, Toshihiko Mizuta, Kenji Mitsugi","doi":"10.1177/17588359261442386","DOIUrl":"https://doi.org/10.1177/17588359261442386","url":null,"abstract":"<p><strong>Background: </strong>Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard second- or later-line regimen for unresectable or recurrent pancreatic cancer (urPC). However, validated prognostic biomarkers are lacking.</p><p><strong>Objectives: </strong>In this study, we aimed to identify clinical predictors of progression-free survival (PFS) in patients receiving NFF and to develop a nomogram for early prediction of therapeutic efficacy.</p><p><strong>Design: </strong>This was a pre-planned analysis of a prospective, multicenter observational study conducted across 17 hospitals in Japan.</p><p><strong>Methods: </strong>We enrolled 150 patients with urPC who received NFF between 2021 and 2023. Prognostic factors independently associated with PFS were identified using multivariable Cox proportional hazards regression analysis. Based on these factors, we constructed a nomogram to estimate the probabilities of 2-, 4-, and 6-month PFS. Finally, we performed risk stratification according to total nomogram scores and validated this model using an independent retrospective cohort.</p><p><strong>Results: </strong>The median overall survival was 7.8 months, and the median PFS was 3.7 months. Multivariable analysis identified a longer duration of previous chemotherapy (hazard ratio (HR), 0.52; 95% confidence interval (CI), 0.38-0.71; <i>p</i> < 0.01) as a favorable prognostic factor; third-line treatment (vs second-line; HR, 1.67; 95% CI, 1.04-2.67, <i>p</i> = 0.03) and higher C-reactive protein/albumin ratio (CAR; HR, 1.14; 95% CI, 1.01-1.29, <i>p</i> = 0.04) were associated with unfavorable PFS. In risk stratification, median PFS in the low-, moderate-, and high-risk groups was 5.9 months (reference), 3.9 months (HR, 1.78; 95% CI, 1.16-2.71; <i>p</i> < 0.01), and 2.2 months (HR, 2.30; 95% CI, 1.51-3.50; <i>p</i> < 0.01), respectively. Significant risk stratification was also confirmed in an independent retrospective cohort.</p><p><strong>Conclusion: </strong>The duration of previous chemotherapy, treatment line, and the CAR are useful predictors of PFS in patients with urPC receiving NFF. The proposed nomogram and risk stratification system may facilitate individualized treatment planning and support clinical decision-making.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261442386"},"PeriodicalIF":4.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A real-world study on the comparative effectiveness of first-line treatment regimens in advanced NSCLC patients with <i>PACC</i> mutations.","authors":"Dujiang Liu, Xinyue Li, Kailai Yin, Yi Lu, Na Han, Yanjun Xu","doi":"10.1177/17588359261442625","DOIUrl":"https://doi.org/10.1177/17588359261442625","url":null,"abstract":"<p><strong>Background: </strong>P-loop and αC-helix compressing (<i>PACC</i>) mutations are a distinct structural subset of atypical epidermal growth factor receptor (<i>EGFR</i>) alterations in non-small-cell lung cancer (NSCLC), yet no standard first-line strategy has been established.</p><p><strong>Objectives: </strong>This study aimed to evaluate first-line treatment outcomes in patients with <i>PACC</i>-mutant NSCLC.</p><p><strong>Design: </strong>A real-world retrospective study.</p><p><strong>Methods: </strong>This retrospective cohort study enrolled 100 patients with <i>PACC</i>-mutant NSCLC who were diagnosed between February 2015 and April 2025. The efficacy of different first-line treatment strategies in this population was evaluated.</p><p><strong>Results: </strong>Among the 100 patients, compared with chemotherapy, treatment with tyrosine kinase inhibitors (TKIs) significantly prolonged progression-free survival (PFS; 14.2 vs 5.2 months, hazard ratio (HR) = 0.348, <i>p</i> = 0.005). The inverse probability of treatment weighting (IPTW)-weighted Cox analysis produced results consistent with the primary analysis (IPTW-adjusted HR = 0.487, <i>p</i> = 0.039). Among patients treated with TKIs, both second-generation (13.9 vs 13.1 months, HR = 0.338, <i>p</i> = 0.015) and third-generation TKIs (16.8 vs 13.9 months, HR = 0.239, <i>p</i> = 0.011) appeared to be associated with longer PFS compared with first-generation TKIs; however, given the relatively small subgroup sizes, these comparisons should be interpreted with caution. In patients with brain metastases, third-generation TKIs were associated with numerically longer PFS (28.0 vs 11.2 months, HR = 0.324, <i>p</i> = 0.132) and significantly longer overall survival (not reached vs 29.0 months, HR = 0.097, <i>p</i> = 0.030) compared with second-generation TKIs. In patients with a single <i>PACC</i> mutation, second-generation TKIs significantly prolonged PFS compared with non-second-generation TKIs (18.0 vs 11.0 months, HR = 0.347, <i>p</i> = 0.032). In addition, subgroup analyses indicated that, relative to the <i>E709X</i> subset, patients with <i>S768I</i> mutations had significantly prolonged PFS under TKI treatment (24.6 vs 10.6 months, HR = 0.263, <i>p</i> = 0.027).</p><p><strong>Conclusion: </strong>TKIs may represent a promising first-line option for advanced NSCLC with <i>PACC</i> mutations. The choice of specific TKIs may depend on genomic characteristics and brain metastasis status.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261442625"},"PeriodicalIF":4.2,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of radiotherapy in the treatment of <i>EGFR</i>-mutant non-small-cell lung cancer: a narrative review.","authors":"Qian Wang, Fengxin Sun, Meng Wu, Zhaoyun Liu, Shuangqing Lu, Rong Xiao, Xueqi Xie, Minxin Chen, Xiaozheng Sun, Xiaoke Xing, Baochao Wei, Jinming Yu, Dawei Chen","doi":"10.1177/17588359261432059","DOIUrl":"https://doi.org/10.1177/17588359261432059","url":null,"abstract":"<p><p>The emergence of targeted therapies, such as epidermal growth factor receptor (<i>EGFR</i>) and anaplastic lymphoma kinase inhibitors, has marked a new chapter in the management of non-small-cell lung cancer (NSCLC). However, monotherapy with targeted agents often falls short in achieving optimal outcomes. The addition of radiotherapy (RT) has been shown to enhance therapeutic efficacy in various clinical settings. The LAURA trial (consolidation osimertinib) and POLESTAR trial (consolidation aumolertinib) suggest that targeted consolidation therapy following chemoradiotherapy is a promising approach for Stage III unresectable <i>EGFR</i>-mutant NSCLC. The integration of radiation with targeted therapies, while promising, is complex and requires ongoing research and multidisciplinary efforts to optimize patient outcomes. This review examines the role of radiotherapy in treating <i>EGFR</i>-mutant NSCLC across various stages, highlighting the significance of minimal residual disease and circulating tumor DNA, and identifies key challenges for advancing the field.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261432059"},"PeriodicalIF":4.2,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}