American Journal of Clinical Oncology-Cancer Clinical Trials最新文献

{"title":"The Role of Adjuvant Chemotherapy in Endometrial Cancer Following Preoperative Neoadjuvant Chemoradiation Therapy.","authors":"Margaret R Flanigan, Michelle Ertel, John A Vargo, Li Wang, Michelle M Boisen, Sarah Taylor, Shannon K Rush, Paniti Sukumvanich, Jamie L Lesnock","doi":"10.1097/COC.0000000000001205","DOIUrl":"10.1097/COC.0000000000001205","url":null,"abstract":"<p><strong>Objectives: </strong>In patients with surgically unresectable disease who undergo neoadjuvant chemoradiation (CRT) or neoadjuvant radiation therapy (RT) before surgical staging, little is known about whether adjuvant chemotherapy confers a survival benefit. We aim to explore the survival impact of adjuvant chemotherapy in patients with locally advanced endometrial cancer who undergo neoadjuvant CRT or RT.</p><p><strong>Methods: </strong>A retrospective, single-institution review of all patients from April 2008 to October 2021 who underwent neoadjuvant RT or CRT before surgical resection of endometrial cancer was performed. Kaplan-Meier method with log-rank test was used to determine differences in overall survival (OS) and disease-free survival (DFS) between the group that received adjuvant chemotherapy and the group that did not. Subgroup analysis was performed to assess whether specific subgroups benefited from adjuvant chemotherapy.</p><p><strong>Results: </strong>Eighty-nine patients, 48 (54%) of whom received adjuvant chemotherapy, were identified. There was no statistically significant difference in OS ( P =0.062) between those who received adjuvant chemotherapy and those who did not. Adjuvant chemotherapy had a significant association with worse DFS ( P =0.037). On subgroup analysis, there were no statistically significant differences in OS or DFS in any subgroups when examining the impact of adjuvant chemotherapy.</p><p><strong>Conclusions: </strong>After receiving neoadjuvant CRT or RT for advanced and high-grade endometrial cancers, adjuvant chemotherapy was not predictive of improved OS, but was predictive of worse DFS. A larger cohort and longer follow-up are needed to ascertain whether certain high-risk subgroups of patients benefit from adjuvant chemotherapy.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"443-449"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MOSAIC: A Multi-Feature Genomic Instability Score Independently Predicts Sarcoma Survival in 2138 Patients.","authors":"Daniel Schneider, Jacob Gluski, Ethan D L Brown, Akash Mishra, Daniel M Sciubba, Sheng-Fu L Lo","doi":"10.1097/COC.0000000000001207","DOIUrl":"10.1097/COC.0000000000001207","url":null,"abstract":"<p><strong>Objectives: </strong>While genomic profiling has identified prognostic markers in sarcoma, clinical risk stratification remains largely histology-based. The combined impact of multiple genomic instability features on survival remains poorly understood. This study evaluated the prognostic utility of a novel Measure Of Sarcoma Aggregate Instability Complex (MOSAIC) Score.</p><p><strong>Methods: </strong>We conducted a secondary analysis of 2138 sarcoma patients from the Sarcoma (MSK, Nat Commun. 2022) data set in cBioPortal. The MOSAIC score integrated 6 genomic instability markers: mutation burden, whole-genome doubling, copy number alterations, ploidy, microsatellite instability, and a fraction of genome altered. Cox proportional hazards models adjusted for clinical covariates assessed survival associations.</p><p><strong>Results: </strong>Higher MOSAIC scores correlated with worse survival (HR=1.11 per unit, 95% CI: 1.07-1.15, P =4.67 × 10 -8 ). The first principal component explained 47.6% of the total variance. A threshold effect emerged between quartiles, with higher quartiles showing nearly doubled mortality risk (adjusted HRs: Q2=1.89, Q3=1.88, Q4=1.96; all P <0.001). Chromosomal instability markers (copy number alterations: 0.51, whole-genome doubling: 0.49) contributed more than point mutations (mutation burden: 0.15). MOSAIC's prognostic impact varied by anatomic site, with strong effects in thoracic (HR=1.66, P =4.74 × 10 -4 ) and trunk (HR=1.50, P =0.018) sarcomas.</p><p><strong>Conclusions: </strong>MOSAIC provides independent prognostic value across sarcoma subtypes, surpassing conventional clinical factors. Its integration of routine genomic features broadens applicability and may inform immunotherapy response prediction. The observed threshold effect and dominance of chromosomal instability markers offer novel insights into sarcoma biology and therapeutic targeting. Prospective validation is warranted for clinical implementation.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"465-469"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Development of Cachexia Before and After Diagnosis of Non-small Cell Lung Cancer.","authors":"L Anne Gilmore, Jonas Willmann, Santiago Olaechea, Brian W Gilmore, Edward Christopher Dee, Mihir Rao, Bhavani S Gannavarapu, Shivaek Venkateswaran, Christian M Alvarez, Chul Ahn, Dirk K M de Ruysscher, Urvi A Shah, Neil M Iyengar, Daniel R Gomez, Rodney Infante, Puneeth Iyengar","doi":"10.1097/COC.0000000000001211","DOIUrl":"10.1097/COC.0000000000001211","url":null,"abstract":"<p><strong>Objective: </strong>Cachexia is commonly defined based on weight loss at the time of cancer diagnosis. However, regular weight measurements before cancer diagnosis are often lacking and may be subject to recall bias if retrospectively self-reported by patients. To analyze the development and progression of cachexia, we employ body weight trajectories from 1 year before and after diagnosis of non-small cell lung cancer (NSCLC). We hypothesized that cachexia could be detected as early as 1 year before NSCLC diagnosis and that cachexia prevalence would increase in the year following diagnosis.</p><p><strong>Methods: </strong>This retrospective study included consecutive patients with NSCLC treated at UTSW between 2005 and 2019 who had body weight measurements before and after NSCLC diagnosis recorded in their electronic health records. Weights were binned in 3-month intervals. Cachexia was defined per the International Consensus Definition of cachexia, that is, loss of >5% body weight 12 months preceding cancer diagnosis for patients with BMI ≥20 kg/m 2 or weight loss of >2% for patients with a BMI <20 kg/m 2 . The association of disease stage and primary treatment with weight changes was investigated.</p><p><strong>Results: </strong>Among 4294 patients screened, 661 patients were included in the final analysis. Patients had a mean age of 69.3 (SD: 10.6) years, and a majority were current/former smokers (83%), identified as white (76%), and were diagnosed with either stage I (47%) or stage IV (28%) nonsquamous NSCLC (78%). At cancer diagnosis, 28% (n=183) presented with cachexia, having incurred a mean loss of 8.6 (SEM: 0.4%) ( P <0.0001) of body weight within the year before cancer diagnosis. Weight loss after cancer diagnosis was comparable in patients with and without cachexia at cancer diagnosis ( P =0.05). By 12 months postcancer diagnosis, 58% of patients (n=383) met the criteria for cachexia based on weight loss. Weight loss consistent with cachexia occurred over a median period of 220 (IQR: 265) days.</p><p><strong>Conclusion: </strong>Weight loss in patients with cachexia at NSCLC diagnosis may commence as early as 12 months before cancer diagnosis. Within a year after a cancer diagnosis, more than half of patients develop cachexia, particularly those with advanced disease. These findings support the integration of early nutritional and pharmacological interventions in patients with NSCLC.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"470-476"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multicenter Real-Life Evaluation of Safety and Effectiveness of the Antibody-Drug Conjugate Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.","authors":"Federica Martorana, Maria V Sanò, Alessandra Fabi, Ida Paris, Vita Leonardi, Gabriella Bini, Oriana Maiorana, Paolo Vigneri, Vittorio Gebbia, Giuseppina Scandurra, Francesco Giotta, Annabella Curaba, Maria R Valerio","doi":"10.1097/COC.0000000000001201","DOIUrl":"10.1097/COC.0000000000001201","url":null,"abstract":"<p><strong>Objectives: </strong>Randomized trials showed that the third-generation antibody-drug conjugate, sacituzumab govitecan (SG), is active against metastatic triple-negative breast cancer (mTNBC). Real-world data are relatively limited. This retrospective study reports the efficacy and safety of SG in a series of women with mTNBC in clinical practice.</p><p><strong>Methods: </strong>Eighty-four patients with widely pretreated, de novo, or metachronous mTNBC were treated with SG at the recommended dose of 10 mg/kg on days 1 and 8 every 3 weeks over a 3-hour intravenous infusion at 6 medical oncology units.</p><p><strong>Results: </strong>No complete response was observed. Overall, 29 patients (34%; 95% CI: 24.4%-44.7%) achieved a partial response with a median duration of 6 months (range: 5 to 14 mo). Twenty patients 24 (29%; 95% CI: 18.9%-38.2%) had stabilization of disease with a median duration of 7 months (4 to 13 mo), while 31 (37%; 95% CI: 26.6%-47.2%) progressed. The median progression-free survival was 5 months (range: 1 to 14 mo) and the median overall survival as 10 months (range: 1 to 18 mo). Twelve patients (22%) had metastatic deposits in CNS and had received radiotherapy.</p><p><strong>Conclusions: </strong>The real-life data reported in this paper confirm the randomized trial results regarding efficacy and tolerability. The authors stressed the importance of the early identification of severe side effects in managing these patients.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"450-457"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Lasting Cigarette Smoking Alterations in Immune Function Occur in Cannabis Smokers, Possibly Rendering Them Vulnerable to Smoking-Related Tumors in Later Life.","authors":"Steven Lehrer, Peter Rheinstein","doi":"10.1097/COC.0000000000001203","DOIUrl":"10.1097/COC.0000000000001203","url":null,"abstract":"<p><strong>Objectives: </strong>Active cigarette smoking leads to increased CXCL5 production. CXCL5 mediates the immune response by attracting immune cells to areas of inflammation. Elevated CXCL5 levels are associated with various inflammatory diseases and tumorigenesis. In addition, smoking is linked to an increase in the level of the cytokine CEACAM6 in the bloodstream of smokers. CEACAM6 is increased in pancreatic adenocarcinoma, breast cancer, non-small-cell lung cancer, gastric cancer, colon cancer, and other cancers and promotes tumor progression, invasion, and metastasis. Although cytokine secretion in the innate immune response returns to nonsmoker levels after quitting smoking, the effects on the adaptive response appear to persist for years or decades due to epigenetic memory. As a result, epigenetic changes induced by smoking may contribute to long-lasting alterations in immune function, including elevated CXCL5 and CEACAM6. The effects of cannabis smoking might be similar.</p><p><strong>Methods: </strong>In the current study we used UK Biobank (UKB) data to assess the relationship of CXCL5, CEACAM6, and pulmonary function to cigarette and cannabis smoking. Our UK Biobank application was approved as UKB project 57245 (S.L. and P.H.R.). Our analysis included all subjects with smoking and/or marijuana use data in the UK Biobank database. Circulating levels of CXCL5 and CEACAM6 were from UKB Olink data. Individual CXCL5 and CEACAM6 levels are NPX, Normalized Protein expression, Olink arbitrary unit in Log2 scale (Olink Proteomics AB, Uppsala, Sweden; http://www.olink.com ).</p><p><strong>Results: </strong>Current smokers and past smokers had elevated circulating levels of CXCL5 and CECAM6. In multivariate analysis, current, past, or no smoking history was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex. Frequency of cannabis use had a similar effect. In multivariate analysis, frequency of cannabis use was significantly related to CXCL5 level and CECAM6 levels, independent of the effects of age, sex, and years between last cannabis use and enrollment in study.</p><p><strong>Conclusions: </strong>We can confirm a previous report of epigenetic changes induced by cigarette smoking that may contribute to long-lasting alterations in immune function related to CXCL5 and CEACAM6. In addition, we have found that these same long-lasting smoking alterations in immune function related to CXCL5 and CEACAM6 occur in cannabis smokers, possibly rendering them vulnerable to smoking-related tumors in later life.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"460-464"},"PeriodicalIF":1.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Upstaging With MRI for HPV-Associated Oropharynx Cancer: Implications for De-Escalation Trials.","authors":"Steven D Wren, Linda Chen, Yao Yu, Achraf Shamseddine, Amir H Safavi, Sean M McBride, Daphna Gelblum, Nadeem Riaz, Nancy Y Lee, Vaios Hatzoglou, Kaveh Zakeri","doi":"10.1097/COC.0000000000001250","DOIUrl":"https://doi.org/10.1097/COC.0000000000001250","url":null,"abstract":"<p><strong>Objectives: </strong>Human papillomavirus (HPV)-associated oropharynx cancer (OPC) requires accurate staging to guide treatment and de-escalation clinical trial enrollment. MRI provides superior soft tissue contrast and assessment of tumor depth of invasion compared with CT with contrast and FDG-PET/CT. This study aims to evaluate the prevalence of HPV-associated OPC tumor upstaging and newly identified retropharyngeal lymph node (RPLN) metastases with MRI.</p><p><strong>Methods: </strong>Fifty consecutive patients with newly diagnosed, previously untreated HPV-associated OPC planned for treatment with primary radiotherapy at Memorial Sloan Kettering Cancer Center from March 04, 2024, to July 09, 2024, were included. All had histologic confirmation of p16-positive squamous cell carcinoma. Tumor staging and nodal assessment were independently completed by a radiation oncologist and a diagnostic neuroradiologist according to the eighth edition of the American Joint Committee on Cancer. MRI findings were compared with CT with contrast and FDG-PET/CT.</p><p><strong>Results: </strong>The median patient age was 65, 84% were male, and 80% had <10 pack years of smoking history. Primary tumor sites included the base of tongue (50%), tonsil (48%), and glossotonsillar sulcus (2%). The rate of tumor upstaging with MRI was 12% (6/50), all 6 cases upstaged from T2 or T3 to T4. MRI identified RPLN metastases in 10% (5/50) of cases not identified on CT or PET/CT. Overall, 18% (9/50) of patients had either primary tumor upstaging or newly identified RPLN metastases based on MRI.</p><p><strong>Conclusions: </strong>MRI leads to meaningful changes in tumor stage and RPLN detection in HPV-associated OPC. Staging MRI should be incorporated into treatment planning and de-escalation clinical trial enrollment.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACR-ACNM-ARS-SNMMI Practice Parameter for the Performance of Therapy With Radium-223 Dichloride.","authors":"Esma A Akin, Paul E Wallner, Sindu Alexander, Parul Barry, Patrick M Colletti, Curtiland Deville, Phillip H Kuo, Amar Kishan, Zachary Morris, Philipose G Mulugeta, Neeta Pandit-Tasker, Bryan M Rabatic, Babak Saboury, Navesh Sharma, Munir V Ghesani, Rathan M Subramaniam, William Small, Naomi R Schechter","doi":"10.1097/COC.0000000000001245","DOIUrl":"https://doi.org/10.1097/COC.0000000000001245","url":null,"abstract":"<p><strong>Objectives: </strong>This practice parameter was revised collaboratively by the American College of Radiology (ACR), the American College of Nuclear Medicine (ACNM), the American Radium Society (ARS), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The document represents an update of the radium-223 therapy practice parameter developed by the societies in 2019.</p><p><strong>Methods: </strong>This practice parameter was revised according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Nuclear Medicine and Molecular Imaging of the ACR Commissions on Nuclear Medicine and Molecular Imaging and the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology, in collaboration with the ACNM, the ARS, and the SNMMI. Reports available since the publication of the initial document in 2019 were collected and reviewed.</p><p><strong>Results: </strong>Since the publication of the initial radium-223 practice parameter in 2019, there has been significant investigation of the agent in the management of numerous metastatic cancer sites, in addition to additional studies of its use in metastatic hormone-resistant prostate cancer. This updated document considers physical properties of the agent, current and investigative indications, qualifications and responsibilities of personnel, specifications of the evaluation exam and treatment, the therapeutic use of unsealed radiopharmaceutical sources, radiation safety, and quality control.</p><p><strong>Conclusions: </strong>This updated practice parameter is intended to guide appropriately trained and credentialed physicians performing therapy with radium-223 dichloride. All aspects of patient and radioisotope management are considered, as are current indications and ongoing investigations.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes and Safety Profile of Adagrasib in KRAS G12C-Mutated Solid Tumors: A Single-Arm Meta-Analysis.","authors":"Osama Ahmad, Shree Rath, Umm E Shabbar Salma Banatwala, Umama Alam, M Rafiqul Islam, Abdul Wahid, Fatima Sajjad, Wajiha F Khan, Abbas M Gain","doi":"10.1097/COC.0000000000001249","DOIUrl":"https://doi.org/10.1097/COC.0000000000001249","url":null,"abstract":"<p><strong>Objectives: </strong>KRAS G12C mutations are key oncogenic drivers in multiple solid tumors. Adagrasib, a selective KRAS G12C inhibitor, has demonstrated promising efficacy and safety in clinical studies. This single-arm meta-analysis comprehensively evaluates key clinical outcomes of Adagrasib, including survival benefits and adverse events, in patients with KRAS G12C-mutant solid tumors.</p><p><strong>Methods: </strong>Literature search was conducted across 4 databases to identify clinical trials and observational studies evaluating Adagrasib performance in patients with KRAS G12C-mutant solid tumors. A single-arm analysis was performed using the inverse variance method in the \"meta\" package of RStudio. Log Proportion and standardised mean difference (SMD) with a 95% CI were pooled using a random-effects model. Heterogeneity was assessed using I² statistics.</p><p><strong>Results: </strong>Six studies involving 400 patients were included in our analysis. Adagrasib showed a median overall survival (OS) of 14.74 months (95% CI: 12.06-17.42, I²=40.4%) and progression-free survival (PFS) of 6.80 months (95% CI: 6.14-7.46, I²=0%), indicating significant survival benefits. The disease control rate (DCR) was 83%, reflecting robust tumor response and stabilization. Safety analysis revealed that 97% of patients experienced at least one adverse event of varying grades.</p><p><strong>Conclusions: </strong>Adagrasib demonstrated robust efficacy in KRAS G12C-mutant solid tumors, with significant survival benefits and high response rates. However, frequent adverse events and dose modifications, along with variability in response rates, highlight tolerability challenges. Further studies are needed to optimize dosing, improve patient selection, and explore combination strategies to enhance outcomes and minimize unwanted effects.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting and Optimizing Synergistic Drug Combinations for Breast Cancer Treatment Using Machine Learning.","authors":"Dhyanendra Jain, Kamal Upreti, Tan Kuan Tak, Saroj S Date, Pravin R Kshirsagar, Rituraj Jain, Rashmi Agrawal","doi":"10.1097/COC.0000000000001244","DOIUrl":"10.1097/COC.0000000000001244","url":null,"abstract":"<p><strong>Objectives: </strong>The study aims to identify highly synergistic drug combinations for breast cancer treatment using machine learning models. The primary objective is to predict drug synergy scores accurately and rank combinations with the highest potential for therapeutic efficacy.</p><p><strong>Methods: </strong>Machine learning models, including XGBoost, Random Forest (RF), and CatBoost (CB), were employed to analyze breast cancer drug combination data. Four synergy metrics-ZIP, Bliss, Loewe, and HSA-were used to quantify drug interaction effects. The models were trained to predict these synergy scores, and their performance was evaluated using normalized root mean squared error (NRMSE) and Pearson correlation coefficient. Predicted top-ranking drug combinations were further validated by comparing observed versus expected dose-response curves and calculating the area under the curve (AUC) for synergy assessment.</p><p><strong>Results: </strong>XGBoost (XGB_5235) outperformed other models, achieving an NRMSE of 0.074 and a Pearson correlation of 0.90 for the Bliss synergy model. Based on average synergy scores, the top 20 drug combinations were identified, with Ixabepilone+Cladribine, SN 38 Lactone+Pazopanib, and Decitabine+Tretinoin emerging as the most promising. These combinations showed high synergy and were supported by biological insights into their mechanisms of action.</p><p><strong>Conclusions: </strong>The study demonstrates the effectiveness of machine learning in predicting synergistic drug combinations for breast cancer. By accelerating the screening process and reducing experimental burden, the approach offers a promising tool for guiding future in vitro and in vivo validation of combination therapies.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world Safety of Concurrent Pembrolizumab and Radiotherapy in Triple-negative Breast Cancer.","authors":"Assile El Fakih, Pierre Loap, Luc Cabel, Sofiane Allali, Kim Cao, Mariana Mirabel, Jean-Yves Pierga, Youlia Kirova","doi":"10.1097/COC.0000000000001236","DOIUrl":"https://doi.org/10.1097/COC.0000000000001236","url":null,"abstract":"<p><strong>Objectives: </strong>Triple-negative breast cancer (TNBC) accounts for ∼15% of invasive breast cancers and is associated with a poor prognosis. The introduction of pembrolizumab in both neoadjuvant and adjuvant settings, as established by the KEYNOTE-522 trial, has improved event-free survival and is now considered standard of care. Postoperative adjuvant radiotherapy remains essential in reducing recurrence and mortality. However, combining radiotherapy with pembrolizumab may increase the risk of toxicities, particularly cardiac, and its long-term safety profile remains poorly characterized. This study aims to assess the safety of this combination in TNBC patients.</p><p><strong>Methods: </strong>This monocentric retrospective study, conducted at Institut Curie in Paris, included patients with locally advanced TNBC treated according to the KEYNOTE-522 protocol-neoadjuvant chemotherapy and immunotherapy, followed by surgery and adjuvant therapy, including radiotherapy with or without pembrolizumab. Patients were divided into 2 groups: those receiving concurrent radiotherapy and pembrolizumab (RT-P), and those receiving radiotherapy alone (RT). The primary endpoint was treatment tolerance. Secondary endpoints included overall survival and cancer-specific survival. A P-value <0.05 was considered statistically significant.</p><p><strong>Results: </strong>A total of 89 patients were included, with a median follow-up of 16 months. Forty-one patients received radiotherapy alone, and 48 received concurrent radiotherapy and pembrolizumab. No significant differences were observed between groups in baseline characteristics or overall toxicity, except for grade 1 radiodermatitis, which was more frequent in the RT-P group (83.3% vs. 43.9%). No grade ≥3 toxicities were reported. Two cases of grade 1 pulmonary toxicity occurred in the RT-P group. The mean heart dose was 1.8 Gy (range: 0.01-7.9), with no cardiac toxicity attributable to radiotherapy.</p><p><strong>Conclusion: </strong>Adjuvant radiotherapy can be safely administered concurrently with pembrolizumab in TNBC patients without increasing radiation-related adverse events, supporting the continuation of systemic therapy in this high-risk population. Nevertheless, larger prospective studies are needed to assess long-term toxicity.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}