Objectives: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis, integrating data from the latest clinical trials, aimed to evaluate the safety and efficacy of T-DXd in this patient population.
Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd's efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data.
Results: Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR=0.37, 95% CI: 0.27-0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR=2.10, 95% CI: 1.36-3.25), fatigue (OR=1.56, 95% CI: 1.21-2.02), nausea (OR=6.42, 95% CI: 4.37-9.42), vomiting (OR=6.21, 95% CI: 3.14-12.25), constipation (OR=2.26, 95% CI: 1.53-3.34), and notably, drug-related interstitial lung disease (OR=10.89, 95% CI: 3.81-31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis.
Conclusions: T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles.
{"title":"Safety and Efficacy of Trastuzumab Deruxtecan for Metastatic HER2+ and HER2-low Breast Cancer: An Updated Systematic Review and Meta-Analysis of Clinical Trials.","authors":"Zaheer Qureshi, Faryal Altaf, Abdur Jamil, Rimsha Siddique, Eeshal Fatima","doi":"10.1097/COC.0000000000001126","DOIUrl":"https://doi.org/10.1097/COC.0000000000001126","url":null,"abstract":"<p><strong>Objectives: </strong>Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis, integrating data from the latest clinical trials, aimed to evaluate the safety and efficacy of T-DXd in this patient population.</p><p><strong>Methods: </strong>We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd's efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data.</p><p><strong>Results: </strong>Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR=0.37, 95% CI: 0.27-0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR=2.10, 95% CI: 1.36-3.25), fatigue (OR=1.56, 95% CI: 1.21-2.02), nausea (OR=6.42, 95% CI: 4.37-9.42), vomiting (OR=6.21, 95% CI: 3.14-12.25), constipation (OR=2.26, 95% CI: 1.53-3.34), and notably, drug-related interstitial lung disease (OR=10.89, 95% CI: 3.81-31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis.</p><p><strong>Conclusions: </strong>T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477926","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}
Pub Date : 2024-07-01Epub Date: 2024-03-15DOI: 10.1097/COC.0000000000001096
Fei Chen, Xiaoqin Gong, Kaijun Zhang, Yunpeng Yu, Tao You, Ye Hua, Chunhua Dai, Jing Hu
Objective: To analyze the risk factors for grade ≥2 ARE in patients with cervical cancer receiving concurrent chemoradiotherapy.
Methods: A total of 273 patients with cervical cancer receiving concurrent chemoradiotherapy at our hospital were retrospectively enrolled. The patients were divided into training and validation groups. Clinical parameters were analyzed using univariate analysis and multivariate logistic regression analysis. A nomogram model was established based on the independent risk factors selected using multivariate logistic regression. The areas under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. The patients were divided into low-score and high-score groups based on the scores calculated using the nomogram model and compared.
Results: Malnutrition, monocyte-lymphocyte ratio ≥0.82 after radiotherapy, platelet-lymphocyte ratio <307.50 after radiotherapy, and bowelbag volume receiving at least 5 and 40 Gy were independent risk factors for grade ≥2 ARE and were incorporated into the nomogram ( P <0.05). The ROC curve, calibration curve, and DCA suggested that the nomogram had good discrimination, concordance, and net benefit in the clinical. A medium nomogram score of 146.50 points was used as the cutoff point, and the incidence of grade ≥2 ARE in the high-score group was higher than that in the low-score group ( P <0.05).
Conclusion: The nomogram model for grade ≥2 ARE has good predictive ability and clinical utility, and is convenient for clinicians to identify high-risk groups and develop early prevention and treatment strategies.
{"title":"Nomogram Predicting Grade ≥2 Acute Radiation Enteritis in Patients With Cervical Cancer Receiving Concurrent Chemoradiotherapy.","authors":"Fei Chen, Xiaoqin Gong, Kaijun Zhang, Yunpeng Yu, Tao You, Ye Hua, Chunhua Dai, Jing Hu","doi":"10.1097/COC.0000000000001096","DOIUrl":"10.1097/COC.0000000000001096","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the risk factors for grade ≥2 ARE in patients with cervical cancer receiving concurrent chemoradiotherapy.</p><p><strong>Methods: </strong>A total of 273 patients with cervical cancer receiving concurrent chemoradiotherapy at our hospital were retrospectively enrolled. The patients were divided into training and validation groups. Clinical parameters were analyzed using univariate analysis and multivariate logistic regression analysis. A nomogram model was established based on the independent risk factors selected using multivariate logistic regression. The areas under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. The patients were divided into low-score and high-score groups based on the scores calculated using the nomogram model and compared.</p><p><strong>Results: </strong>Malnutrition, monocyte-lymphocyte ratio ≥0.82 after radiotherapy, platelet-lymphocyte ratio <307.50 after radiotherapy, and bowelbag volume receiving at least 5 and 40 Gy were independent risk factors for grade ≥2 ARE and were incorporated into the nomogram ( P <0.05). The ROC curve, calibration curve, and DCA suggested that the nomogram had good discrimination, concordance, and net benefit in the clinical. A medium nomogram score of 146.50 points was used as the cutoff point, and the incidence of grade ≥2 ARE in the high-score group was higher than that in the low-score group ( P <0.05).</p><p><strong>Conclusion: </strong>The nomogram model for grade ≥2 ARE has good predictive ability and clinical utility, and is convenient for clinicians to identify high-risk groups and develop early prevention and treatment strategies.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-04-10DOI: 10.1097/COC.0000000000001093
James R Janopaul-Naylor, Jimmy S Patel, Manali Rupji, David C Qian, Kimberly B Hoang, Neal S McCall, Ashley J Schlafstein, Madison L Shoaf, Shawn Kothari, Jeffrey J Olson, Hui-Kuo Shu, Jim Zhong, Stewart G Neill, Bree Eaton
Objectives: Progression of PCNSL remains a challenge with salvage therapies, including the risk of substantial morbidity and mortality. We report patterns of first tumor progression to inform opportunities for improvement.
Methods: This is an institutional retrospective review from 2002 to 2021 of 95 consecutive patients with pathologically confirmed PCNSL, of whom 29 experienced progressive disease. Kaplan-Meier method, log-rank test, and Cox proportional hazard models are used to characterize associations of patient, tumor, and treatment variables with LC, PFS, and patterns of first failure.
Results: Most patients were below 65 years old (62%) with KPS >70 (64%) and negative CSF cytology (70%). In 70 patients with MRIs, the median tumor volume was 12.6 mL (range: 0.5 to 67.8 mL). After a median follow-up of 11 months, 1-year PFS was 48% and 1-year LC was 80%. Of the 29 patients with progression, 24% were distant only, 17% were distant and local, and 59% were local only. On MVA, LC was associated with age (HR: 1.08/y, P =0.02), KPS (HR: 0.10, P =0.02), completion of >6 cycles of HD-MTX (HR: 0.10, P <0.01), and use of intrathecal chemotherapy (HR: 0.03, P <0.01). On UVA, local only first failure trended to be increased with >14 mL tumors (OR: 5.06, P =0.08) with 1-year LC 83% (<14 mL) versus 64% (>14mL). There were no significant associations with LC and WBRT ( P =0.37), Rituximab ( P =0.12), or attempted gross total resection ( P =0.72).
Conclusions: Our findings reaffirm the importance of systemic and intrathecal therapies for local control in PCNSL. However, bulky tumors trend to fail locally, warranting further investigation about the role of local therapies or systemic therapy intensification.
{"title":"Patterns of Treatment Failure in Primary Central Nervous System Lymphoma.","authors":"James R Janopaul-Naylor, Jimmy S Patel, Manali Rupji, David C Qian, Kimberly B Hoang, Neal S McCall, Ashley J Schlafstein, Madison L Shoaf, Shawn Kothari, Jeffrey J Olson, Hui-Kuo Shu, Jim Zhong, Stewart G Neill, Bree Eaton","doi":"10.1097/COC.0000000000001093","DOIUrl":"10.1097/COC.0000000000001093","url":null,"abstract":"<p><strong>Objectives: </strong>Progression of PCNSL remains a challenge with salvage therapies, including the risk of substantial morbidity and mortality. We report patterns of first tumor progression to inform opportunities for improvement.</p><p><strong>Methods: </strong>This is an institutional retrospective review from 2002 to 2021 of 95 consecutive patients with pathologically confirmed PCNSL, of whom 29 experienced progressive disease. Kaplan-Meier method, log-rank test, and Cox proportional hazard models are used to characterize associations of patient, tumor, and treatment variables with LC, PFS, and patterns of first failure.</p><p><strong>Results: </strong>Most patients were below 65 years old (62%) with KPS >70 (64%) and negative CSF cytology (70%). In 70 patients with MRIs, the median tumor volume was 12.6 mL (range: 0.5 to 67.8 mL). After a median follow-up of 11 months, 1-year PFS was 48% and 1-year LC was 80%. Of the 29 patients with progression, 24% were distant only, 17% were distant and local, and 59% were local only. On MVA, LC was associated with age (HR: 1.08/y, P =0.02), KPS (HR: 0.10, P =0.02), completion of >6 cycles of HD-MTX (HR: 0.10, P <0.01), and use of intrathecal chemotherapy (HR: 0.03, P <0.01). On UVA, local only first failure trended to be increased with >14 mL tumors (OR: 5.06, P =0.08) with 1-year LC 83% (<14 mL) versus 64% (>14mL). There were no significant associations with LC and WBRT ( P =0.37), Rituximab ( P =0.12), or attempted gross total resection ( P =0.72).</p><p><strong>Conclusions: </strong>Our findings reaffirm the importance of systemic and intrathecal therapies for local control in PCNSL. However, bulky tumors trend to fail locally, warranting further investigation about the role of local therapies or systemic therapy intensification.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-02-29DOI: 10.1097/COC.0000000000001090
Nicolette R Drescher, Tayna Latortue, Ryan J Brisson, Vincent D Cassidy, Robert J Amdur, William M Mendenhall, Kathryn E Hitchcock
Objective: There is an inverse relationship between cancer cure and overall treatment time (OTT) in patients treated with surgical resection and radiotherapy (RT).
Methods: OTT was evaluated based on the reconstruction procedure in 420 patients with oral cavity and larynx cancers treated with surgery and RT between 1991 and 2020.
Results: With OTT >85 days, the difference between no versus yes flap reconstruction was ~20 percentage points and significant for all comparisons: primary closure (+/- skin graft), 49%, vs. rotation or free flap, 71% ( P <0.0001); primary closure (+/- skin graft), 49%, versus free flap without bone, 66% ( P =0.0358); and primary closure (+/- skin graft), 49%, versus free flap with bone, 82% ( P <0.0001).
Conclusions: The use of flap reconstructions results in substantial increases in OTT. Findings suggest a need to reevaluate current policies regarding the choice of reconstruction and starting RT sooner after surgery.
摘要在接受手术切除和放射治疗(RT)的患者中,癌症治愈率与总体治疗时间(OTT)之间存在反比关系:方法:根据1991年至2020年期间接受手术和放疗治疗的420例口腔癌和喉癌患者的重建程序对OTT进行评估:结果:在OTT大于85天的情况下,无皮瓣重建与有皮瓣重建之间的差异约为20个百分点,且在所有比较中均有显著性差异:初次闭合(+/-植皮)49%,旋转或游离皮瓣71%(PConclusions:使用皮瓣重建会导致 OTT 大幅增加。研究结果表明,有必要重新评估有关重建选择和术后尽早开始 RT 的现行政策。
{"title":"Flap Reconstruction Results in Longer Overall Treatment Time in Patients Treated With Surgery and Adjuvant Radiotherapy for Carcinoma of the Oral Cavity and Larynx.","authors":"Nicolette R Drescher, Tayna Latortue, Ryan J Brisson, Vincent D Cassidy, Robert J Amdur, William M Mendenhall, Kathryn E Hitchcock","doi":"10.1097/COC.0000000000001090","DOIUrl":"10.1097/COC.0000000000001090","url":null,"abstract":"<p><strong>Objective: </strong>There is an inverse relationship between cancer cure and overall treatment time (OTT) in patients treated with surgical resection and radiotherapy (RT).</p><p><strong>Methods: </strong>OTT was evaluated based on the reconstruction procedure in 420 patients with oral cavity and larynx cancers treated with surgery and RT between 1991 and 2020.</p><p><strong>Results: </strong>With OTT >85 days, the difference between no versus yes flap reconstruction was ~20 percentage points and significant for all comparisons: primary closure (+/- skin graft), 49%, vs. rotation or free flap, 71% ( P <0.0001); primary closure (+/- skin graft), 49%, versus free flap without bone, 66% ( P =0.0358); and primary closure (+/- skin graft), 49%, versus free flap with bone, 82% ( P <0.0001).</p><p><strong>Conclusions: </strong>The use of flap reconstructions results in substantial increases in OTT. Findings suggest a need to reevaluate current policies regarding the choice of reconstruction and starting RT sooner after surgery.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991775","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}
Objectives: Radiation proctitis is a misunderstanding complication of chemoradiation in locally advanced cervical cancer. The objective of our study is to provide a detailed description and analysis of predictive factors associated with radiation proctitis in a retrospective cohort of patients treated by chemoradiation for locally advanced cervical cancer.
Methods: All patients treated by exclusive chemoradiation or chemoradiation followed by brachytherapy for locally advanced cervical cancer from 2011 to 2017 were included in the study. A bivariate analysis was conducted to establish correlations between the occurrence of radiation proctitis and various clinical and technical variables.
Results: A total of 128 patients were included in the study. The mean dose (SD) to the planning target volume was 47.1 Gy (6.2). Fifty-nine (46.1%) patients underwent brachytherapy. Sixteen patients (12.5%) developed radiation proctitis, grade 2 or higher in 12 patients (9.3%). In univariate analysis, anticoagulant or antiplatelet treatments ( P =0.039), older age ( P =0.049), rectal volume irradiated at 40 Gy ( P =0.01) and 30 Gy ( P =0.037) were significantly associated with the occurrence of a grade ≥2 radiation proctitis. The delivered dose to 2 cm 3 of rectum (D2cm 3 ) showed a potential association with the occurrence of radiation proctitis of all grades ( P =0.064).
Conclusions: This study highlights clinical and technical factors that should be considered in assessing the risk of radiation proctitis. These results contribute to a better understanding of this complication.
{"title":"Radiation Proctitis in Patients With Locally Advanced Cervical Cancer Treated by Chemoradiation: Analysis and Predictive Factors From a Retrospective Cohort.","authors":"Louis-Marie Sauvage, Rita Bentahila, Yohan Tran, Armelle Guénégou-Arnoux, Emmanuelle Fabiano, Anne-Sophie Bats, Bruno Borghese, Catherine Durdux","doi":"10.1097/COC.0000000000001092","DOIUrl":"10.1097/COC.0000000000001092","url":null,"abstract":"<p><strong>Objectives: </strong>Radiation proctitis is a misunderstanding complication of chemoradiation in locally advanced cervical cancer. The objective of our study is to provide a detailed description and analysis of predictive factors associated with radiation proctitis in a retrospective cohort of patients treated by chemoradiation for locally advanced cervical cancer.</p><p><strong>Methods: </strong>All patients treated by exclusive chemoradiation or chemoradiation followed by brachytherapy for locally advanced cervical cancer from 2011 to 2017 were included in the study. A bivariate analysis was conducted to establish correlations between the occurrence of radiation proctitis and various clinical and technical variables.</p><p><strong>Results: </strong>A total of 128 patients were included in the study. The mean dose (SD) to the planning target volume was 47.1 Gy (6.2). Fifty-nine (46.1%) patients underwent brachytherapy. Sixteen patients (12.5%) developed radiation proctitis, grade 2 or higher in 12 patients (9.3%). In univariate analysis, anticoagulant or antiplatelet treatments ( P =0.039), older age ( P =0.049), rectal volume irradiated at 40 Gy ( P =0.01) and 30 Gy ( P =0.037) were significantly associated with the occurrence of a grade ≥2 radiation proctitis. The delivered dose to 2 cm 3 of rectum (D2cm 3 ) showed a potential association with the occurrence of radiation proctitis of all grades ( P =0.064).</p><p><strong>Conclusions: </strong>This study highlights clinical and technical factors that should be considered in assessing the risk of radiation proctitis. These results contribute to a better understanding of this complication.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337562","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}
Retroperitoneal tumors (RPTs) encompass both benign and malignant entities, constituting ~0.1% to 0.2% of all malignant tumors, of which 70% to 80% manifest malignancy. Predominantly, retroperitoneal sarcomas (RPS) represent the most prevalent subtype among RPT. With over 70 histologic forms identified, liposarcomas and leiomyosarcomas emerge as the primary constituents of RPS. Accurate diagnosis of RPTs necessitates preoperative core-needle biopsy and comprehensive imaging assessment. The current staging protocol for RPS relies on the eighth edition of the American Joint Committee on Cancer/TNM classification. Surgical excision remains the established gold standard for treating RPS. Therapeutic approaches vary according to the underlying pathophysiology. Although chemotherapy and radiotherapy exhibit efficacy in managing metastatic and recurrent unresectable RPS, their role in primary RPS remains unresolved, necessitating further clinical trials for validation. Concurrently, ongoing research explores the potential of targeted therapies and immunotherapy. This literature review aims to provide a comprehensive overview of existing research, delineating diagnostic pathways and optimal therapeutic strategies for RPT.
{"title":"Advancements in Diagnosis and Multimodal Treatment Strategies for Retroperitoneal Tumors: A Comprehensive Review.","authors":"Shuai Zhao, Longhe Sun, Jiajie Zhou, Ruiqi Li, Qiannan Sun, Wei Wang, Daorong Wang","doi":"10.1097/COC.0000000000001094","DOIUrl":"10.1097/COC.0000000000001094","url":null,"abstract":"<p><p>Retroperitoneal tumors (RPTs) encompass both benign and malignant entities, constituting ~0.1% to 0.2% of all malignant tumors, of which 70% to 80% manifest malignancy. Predominantly, retroperitoneal sarcomas (RPS) represent the most prevalent subtype among RPT. With over 70 histologic forms identified, liposarcomas and leiomyosarcomas emerge as the primary constituents of RPS. Accurate diagnosis of RPTs necessitates preoperative core-needle biopsy and comprehensive imaging assessment. The current staging protocol for RPS relies on the eighth edition of the American Joint Committee on Cancer/TNM classification. Surgical excision remains the established gold standard for treating RPS. Therapeutic approaches vary according to the underlying pathophysiology. Although chemotherapy and radiotherapy exhibit efficacy in managing metastatic and recurrent unresectable RPS, their role in primary RPS remains unresolved, necessitating further clinical trials for validation. Concurrently, ongoing research explores the potential of targeted therapies and immunotherapy. This literature review aims to provide a comprehensive overview of existing research, delineating diagnostic pathways and optimal therapeutic strategies for RPT.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112115","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}
Pub Date : 2024-07-01Epub Date: 2024-03-14DOI: 10.1097/COC.0000000000001095
Colton Ladbury, James Sanchez, Arnab Chowdhury, Joycelynne Palmer, An Liu, Anthony Stein, Myo Htut, Leonardo Farol, Ji-Lian Cai, George Somlo, Michael Rosenzweig, Jeffrey C Wong, Firoozeh Sahebi
Objective: We conducted a phase 1 study of a conditioning regimen with or without total marrow irradiation (TMI) before allogeneic hematopoietic stem cell transplantation for patients with high-risk or refractory multiple myeloma.
Methods: Eighteen patients were enrolled on one of 2 strata. Patients with no prior radiation received TMI (900 cGy), fludarabine (FLU), and melphalan (MEL) conditioning, with bortezomib added in the second cohort (stratum I). Patients with prior radiation received FLU, MEL, and bortezomib, without TMI (stratum II).
Results: Eight patients were enrolled in the TMI arm (stratum I). One of 3 patients in cohort 1 experienced dose-limiting toxicity (DLT), which led to the expansion to 3 more patients with no DLT. Cohort 2 enrolled only 2 patients due to low accrual, with bortezomib, added at 0.5 mg/m 2 ; neither experienced DLT. Nine patients were enrolled in the non-TMI arm (stratum II). Three patients were enrolled in cohort 1 (bortezomib 0.5 mg/m 2 ) and none experienced DLT. Three were enrolled in cohort 2 (bortezomib 0.7 mg/m 2 ), and 1 experienced DLT; therefore, the cohort expanded to 3 more patients. One more patient experienced DLT. Median overall survival on strata I and II was 44.5 months (95% CI: 1.73-not reached) and 21.6 months (95% CI: 4.1-72.7), respectively. Median progression-free survival on strata I and II was 18.1 months (95% CI: 1.73-not reached) and 8.9 months (95% CI: 2.7-24.4), respectively.
Conclusion: TMI 900 cGy, FLU, and MEL are considered feasible as conditioning for allogeneic stem cell transplantation and may warrant further investigation due to favorable response rates and survival.
{"title":"Phase 1 Study of Bortezomib, Fludarabine, and Melphalan, With or Without Total Marrow Irradiation, as Allogeneic Hematopoietic Stem Cell Transplant Conditioning for High-risk or Relapsed/Refractory Multiple Myeloma.","authors":"Colton Ladbury, James Sanchez, Arnab Chowdhury, Joycelynne Palmer, An Liu, Anthony Stein, Myo Htut, Leonardo Farol, Ji-Lian Cai, George Somlo, Michael Rosenzweig, Jeffrey C Wong, Firoozeh Sahebi","doi":"10.1097/COC.0000000000001095","DOIUrl":"10.1097/COC.0000000000001095","url":null,"abstract":"<p><strong>Objective: </strong>We conducted a phase 1 study of a conditioning regimen with or without total marrow irradiation (TMI) before allogeneic hematopoietic stem cell transplantation for patients with high-risk or refractory multiple myeloma.</p><p><strong>Methods: </strong>Eighteen patients were enrolled on one of 2 strata. Patients with no prior radiation received TMI (900 cGy), fludarabine (FLU), and melphalan (MEL) conditioning, with bortezomib added in the second cohort (stratum I). Patients with prior radiation received FLU, MEL, and bortezomib, without TMI (stratum II).</p><p><strong>Results: </strong>Eight patients were enrolled in the TMI arm (stratum I). One of 3 patients in cohort 1 experienced dose-limiting toxicity (DLT), which led to the expansion to 3 more patients with no DLT. Cohort 2 enrolled only 2 patients due to low accrual, with bortezomib, added at 0.5 mg/m 2 ; neither experienced DLT. Nine patients were enrolled in the non-TMI arm (stratum II). Three patients were enrolled in cohort 1 (bortezomib 0.5 mg/m 2 ) and none experienced DLT. Three were enrolled in cohort 2 (bortezomib 0.7 mg/m 2 ), and 1 experienced DLT; therefore, the cohort expanded to 3 more patients. One more patient experienced DLT. Median overall survival on strata I and II was 44.5 months (95% CI: 1.73-not reached) and 21.6 months (95% CI: 4.1-72.7), respectively. Median progression-free survival on strata I and II was 18.1 months (95% CI: 1.73-not reached) and 8.9 months (95% CI: 2.7-24.4), respectively.</p><p><strong>Conclusion: </strong>TMI 900 cGy, FLU, and MEL are considered feasible as conditioning for allogeneic stem cell transplantation and may warrant further investigation due to favorable response rates and survival.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121323","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}
Pub Date : 2024-07-01DOI: 10.1097/COC.0000000000001130
Paul E Wallner, Michael L Steinberg, Jay Burmeister, Walter J Curran, Prajnan Das, Brian J Davis, Bruce G Haffty, Brian Marples, Anthony L Zietman
{"title":"Why Basic Science Education Matters in Radiation Oncology.","authors":"Paul E Wallner, Michael L Steinberg, Jay Burmeister, Walter J Curran, Prajnan Das, Brian J Davis, Bruce G Haffty, Brian Marples, Anthony L Zietman","doi":"10.1097/COC.0000000000001130","DOIUrl":"https://doi.org/10.1097/COC.0000000000001130","url":null,"abstract":"","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472229","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}
Pub Date : 2024-06-28DOI: 10.1097/COC.0000000000001128
Olajumoke A Olateju, Osaro Mgbere, J Douglas Thornton, Zhen Zeng, Ekere J Essien
Objectives: Disparities exist in the length and quality of survival from melanoma. This study evaluated, in a Texas cohort, patient factors associated with melanoma survival and examined if newer immune-oncologic agents extend survival compared with conventional therapies.
Methods: A retrospective analysis of patients diagnosed with metastatic melanoma from 2011 to 2018 in the Texas Cancer Registry database. Multivariable Cox proportional hazard regression was used to evaluate patient characteristics associated with cancer-specific survival (CSS) and overall survival (OS). The patient cohort was then grouped based on receipt of first-line immunotherapy or other therapies. The association between receipt of immunotherapy and survival was assessed with Kaplan-Meier analysis and inverse probability treatment weighted Cox regression.
Results: There were 1372 patients with metastatic melanoma. Factors associated with increased melanoma mortality risk (CSS) included being male (HR: 1.13, 95% CI: 1.02-1.26), non-Hispanic black (HR: 1.28, 95% CI: 1.13-1.45), living in poorer counties (HR: 1.40, 95%CI: 1.20-1.64), and having multimorbidity (HR: 1.35, 95% CI: 1.05-1.74). All minority races and Hispanics had poorer OS compared with non-Hispanic Whites. Patients who received first-line immunotherapy had significantly longer median (interquartile range) survival (CSS: 27.00 [21.00 to 42.00] mo vs. 16.00 [14.00 to 19.00] mo; OS: 22.00 [17.00 to 27.00] mo vs. 12.00 [11.00 to 14.00] mo). They also had reduced mortality risk (HR for CSS: 0.80; 95% CI: 0.73-0.88; P<0.0001; HR for OS: 0.76; 95% CI: 0.69-0.83; P<0.0001) compared with the nonimmunotherapy cohort.
Conclusions: This study showed differences in risks from melanoma survival based on patient demographic and clinical characteristics. Low socioeconomic status increased mortality risk, and first-line immunotherapy use favored survival. Health policies and tailored interventions that will promote equity in patient survival and survivorship are essential for managing metastatic melanoma.
{"title":"Disparities in Survival Outcomes Among Patients With Metastatic Melanoma in Texas: Implications for Policy and Interventions in the Era of Immune Checkpoint Inhibitors.","authors":"Olajumoke A Olateju, Osaro Mgbere, J Douglas Thornton, Zhen Zeng, Ekere J Essien","doi":"10.1097/COC.0000000000001128","DOIUrl":"https://doi.org/10.1097/COC.0000000000001128","url":null,"abstract":"<p><strong>Objectives: </strong>Disparities exist in the length and quality of survival from melanoma. This study evaluated, in a Texas cohort, patient factors associated with melanoma survival and examined if newer immune-oncologic agents extend survival compared with conventional therapies.</p><p><strong>Methods: </strong>A retrospective analysis of patients diagnosed with metastatic melanoma from 2011 to 2018 in the Texas Cancer Registry database. Multivariable Cox proportional hazard regression was used to evaluate patient characteristics associated with cancer-specific survival (CSS) and overall survival (OS). The patient cohort was then grouped based on receipt of first-line immunotherapy or other therapies. The association between receipt of immunotherapy and survival was assessed with Kaplan-Meier analysis and inverse probability treatment weighted Cox regression.</p><p><strong>Results: </strong>There were 1372 patients with metastatic melanoma. Factors associated with increased melanoma mortality risk (CSS) included being male (HR: 1.13, 95% CI: 1.02-1.26), non-Hispanic black (HR: 1.28, 95% CI: 1.13-1.45), living in poorer counties (HR: 1.40, 95%CI: 1.20-1.64), and having multimorbidity (HR: 1.35, 95% CI: 1.05-1.74). All minority races and Hispanics had poorer OS compared with non-Hispanic Whites. Patients who received first-line immunotherapy had significantly longer median (interquartile range) survival (CSS: 27.00 [21.00 to 42.00] mo vs. 16.00 [14.00 to 19.00] mo; OS: 22.00 [17.00 to 27.00] mo vs. 12.00 [11.00 to 14.00] mo). They also had reduced mortality risk (HR for CSS: 0.80; 95% CI: 0.73-0.88; P<0.0001; HR for OS: 0.76; 95% CI: 0.69-0.83; P<0.0001) compared with the nonimmunotherapy cohort.</p><p><strong>Conclusions: </strong>This study showed differences in risks from melanoma survival based on patient demographic and clinical characteristics. Low socioeconomic status increased mortality risk, and first-line immunotherapy use favored survival. Health policies and tailored interventions that will promote equity in patient survival and survivorship are essential for managing metastatic melanoma.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472228","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}
Pub Date : 2024-06-28DOI: 10.1097/COC.0000000000001117
Kathleen M Mulligan, Hanna Kakish, Omkar Pawar, Fasih Ali Ahmed, Mohamedraed Elshami, Luke D Rothermel, Jeremy S Bordeaux, Iris Y Sheng, Ankit Mangla, Richard S Hoehn
Objectives: Melanoma survival has greatly improved with the advent of immunotherapy, but unequal access to these medications may exist due to nonmedical patient factors such as insurance status, educational background, and geographic proximity to treatment.
Methods: We used the National Cancer Database to assess patients with nonmetastatic cutaneous melanoma who underwent surgical resection and sentinel lymph node biopsy (SLNB) with tumor involvement from 2015 to 2020. We evaluated rates of adjuvant immunotherapy among this patient population based on patient, tumor, and facility variables, including insurance status, socioeconomic status, pathologic stage (IIIA-IIID), and treatment facility type and volume.
Results: Adjuvant immunotherapy was associated with improved survival for stage III melanoma, with a slight increase in 5-year OS for stage IIIA (87.9% vs. 85.9%, P=0.044) and a higher increase in stages IIIB-D disease (70.3% vs. 59.6%, P<0.001). Receipt of adjuvant immunotherapy was less likely for patients who were older, low socioeconomic status, or uninsured. Low-volume and community cancer centers had higher rates of adjuvant immunotherapy overall for all stage III patients, whereas high-volume and academic centers used adjuvant immunotherapy much less often for stage IIIA patients compared with those in stages IIIB-D.
Conclusions: Our results demonstrate inconsistent use of adjuvant immunotherapy among patients with stage III melanoma despite a significant association with improved survival. Notably, there was a lower use of adjuvant immunotherapy in patients of lower SES and those treated at high-volume centers. Equity in access to novel standards of care represents an opportunity to improve outcomes for patients with melanoma.
{"title":"Disparities in Receipt of Adjuvant Immunotherapy among Stage III Melanoma Patients.","authors":"Kathleen M Mulligan, Hanna Kakish, Omkar Pawar, Fasih Ali Ahmed, Mohamedraed Elshami, Luke D Rothermel, Jeremy S Bordeaux, Iris Y Sheng, Ankit Mangla, Richard S Hoehn","doi":"10.1097/COC.0000000000001117","DOIUrl":"https://doi.org/10.1097/COC.0000000000001117","url":null,"abstract":"<p><strong>Objectives: </strong>Melanoma survival has greatly improved with the advent of immunotherapy, but unequal access to these medications may exist due to nonmedical patient factors such as insurance status, educational background, and geographic proximity to treatment.</p><p><strong>Methods: </strong>We used the National Cancer Database to assess patients with nonmetastatic cutaneous melanoma who underwent surgical resection and sentinel lymph node biopsy (SLNB) with tumor involvement from 2015 to 2020. We evaluated rates of adjuvant immunotherapy among this patient population based on patient, tumor, and facility variables, including insurance status, socioeconomic status, pathologic stage (IIIA-IIID), and treatment facility type and volume.</p><p><strong>Results: </strong>Adjuvant immunotherapy was associated with improved survival for stage III melanoma, with a slight increase in 5-year OS for stage IIIA (87.9% vs. 85.9%, P=0.044) and a higher increase in stages IIIB-D disease (70.3% vs. 59.6%, P<0.001). Receipt of adjuvant immunotherapy was less likely for patients who were older, low socioeconomic status, or uninsured. Low-volume and community cancer centers had higher rates of adjuvant immunotherapy overall for all stage III patients, whereas high-volume and academic centers used adjuvant immunotherapy much less often for stage IIIA patients compared with those in stages IIIB-D.</p><p><strong>Conclusions: </strong>Our results demonstrate inconsistent use of adjuvant immunotherapy among patients with stage III melanoma despite a significant association with improved survival. Notably, there was a lower use of adjuvant immunotherapy in patients of lower SES and those treated at high-volume centers. Equity in access to novel standards of care represents an opportunity to improve outcomes for patients with melanoma.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472227","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}