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

Objectives: Breast cancer is the most diagnosed cancer in women, with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) being the predominant subtype. Sacituzumab govitecan (SG), a novel antibody-drug conjugate, has emerged as a promising treatment for metastatic HR+/HER2- breast cancer. This systematic review and meta-analysis aimed to evaluate its efficacy and safety.

Methods: Adhering to "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines, a comprehensive search was conducted in PubMed, Scopus, and Cochrane databases up to December 2023. We included clinical trials and observational studies evaluating SG in patients with HR+/HER2- advanced breast cancer. The primary outcome was progression-free survival (PFS). In contrast, the secondary outcomes included overall survival, objective response rate, clinical benefit rate, duration of response (DOR), and adverse event profiles. Review Manager (Version 5.4) was used for the statistical analysis.

Results: Nine studies met the inclusion criteria for systematic review; 2 were suitable for meta-analysis. The pooled analysis showed a hazard ratio of 0.53 (95% CI: 0.34-0.83; P= 0.005; I2 = 86%) for PFSl and a hazard ratio of 0.63 (95% CI: 0.36-1.11; P= 0.11; I2 = 92%) for overall survival. The pooled analysis of the duration of response showed significant results with a standard mean difference = 0.22 (95% CI: 0.03-0.42; P = 0.02; I2 = 61%).

Conclusion: SG demonstrates significant benefit in PFS and duration of response in patients of HR+/HER2- advanced breast cancer.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for various hematological malignancies. Still, its remarkable efficacy is accompanied by unique adverse events that must be carefully managed. This comprehensive literature review evaluates the safety profile of CAR T-cell therapy, focusing on cytopenia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), and other potential complications. Cytopenia, characterized by reduced blood cell counts, affects a significant proportion of patients, with rates of anemia, neutropenia, and thrombocytopenia reaching up to 60%, 70%, and 80%, respectively. Risk factors include high tumor burden, prior chemotherapy, and bone marrow involvement. Cytokine release syndrome (CRS) occurs in 13% to 77% of patients and is linked to the cytokine storm induced by CAR T cells, target antigen expression, and preexisting immune dysregulation. Other notable adverse events discussed are cytokine release syndrome, neurotoxicity, and infections. Understanding the mechanisms, risk factors, and management strategies for these adverse events is crucial for optimizing patient outcomes and unlocking the full potential of this revolutionary therapy. The review highlights the need for continued research, interdisciplinary collaboration, and evidence-based approaches to enhance the safety and efficacy of CAR T-cell therapy.

Objectives: The adoption of transoral robotic surgery and shifting epidemiology in oropharyngeal squamous cell cancer have stimulated debate over upfront and adjuvant treatment. Institutional variation in practice patterns can be obscured in patient-level analyses. We aimed to characterize institutional patterns of care as well as identify potential associations between patterns of care and survival.

Methods: This was a retrospective cohort study of patients identified from 2004-2015 in the National Cancer Database. We analyzed 42,803 cases of oropharyngeal squamous cell cancer Stage cT1-2N0-2bM0 (AJCC 7th edition) treated with curative intent surgery and/or radiotherapy. We defined facility-4-year periods to account for changing institutional practice patterns. The 42,803 patients were treated within 2578 facility-4-year periods. We assessed institutional practice patterns, including the ratio of upfront surgery to definitive radiotherapy, case volumes, use of adjuvant therapies (radiotherapy or chemoradiotherapy), and margin positivity rates. Survival associations with institutional practice patterns were estimated with Cox regression.

Results: The ratio of upfront surgery to definitive radiotherapy ranged from 80-to-1 to 1-to-23. The institution-level median rate of adjuvant radiotherapy was 69% (IQR 50%-100%), adjuvant chemoradiotherapy was 44% (IQR 0%-67%), and margin-positive resection was 33% (IQR 0%-50%). On patient-level MVA, worse overall survival was not significantly associated with institutional case volume, adjuvant radiotherapy, or adjuvant chemoradiotherapy utilization.

Conclusions: High rates of multimodal therapy and positive margins underscore the importance of multidisciplinary care and highlight variable patterns of care across institutions. Further work is warranted to explore indicators of high-quality care and to optimize adjuvant therapy in the HPV era.

Breast cancer is the second leading cause of women's cancer deaths after lung cancer. Risk factors such as environment, lifestyle, and genetics contribute to its development, including mutation in the breast cancer (BRCA) gene. Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) target these mutations, benefiting patients with advanced cancers. This review summarizes PARPi' safety and efficacy in the treatment of BRCA-mutated breast cancer. PubMed, The Cochrane Library for Clinical Trials, and Science Direct, were searched for articles from inception to April 2024. Eligible articles were analyzed, and data were extracted for meta-analysis using RevMan 5.4 software with a random-effect model. Out of 430 articles identified from online databases, only 6 randomized control trials including 3610 patients were included in the analysis. PARPi therapy improved progression-free survival (hazard ratio: 0.64; 95% CI: 0.56, 0.73; P< 0.00001) and overall survival (hazard ratio: 0.84; 95% CI: 0.73, 0.98 P = 0.02), according to the analysis. In our safety analysis, the risk of adverse events was not statistically different between PARPi versus chemotherapy (relative risk [RR]: 1.08; 95% CI: 0.44, 2.68; P = 0.86), and combined PARPi and standard chemotherapy (RR: 1.00; 95% CI: 0.93, 1.07; P = 0.80). The only statistically significant difference was observed in anemia, where PARPi increased the risk of developing anemia compared with standard chemotherapy (RR: 6.17; 95% CI: 2.44, 15.58; P = 0.0001). In BRCA-mutated breast cancer, PARPi treatment shows better overall survival and progression-free survival compared with standard chemotherapy or placebo. Furthermore, PARPi, either alone or in combination therapy, does not increase the risk of adverse events in these patients, as per the meta-analysis.

Objectives: Left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) have shown distinct clinical and prognostic features. We investigated the effect of adjuvant chemotherapy (ACT) on cause-specific survival (CSS) in patients with stage II LSCC and RSCC.

Methods: Using the Surveillance, Epidemiology and End Results (SEER) database, a cohort of patients with stage II colon cancer, aged between 20 and 49 years was identified. Both Cox proportional hazards regression and Kaplan-Meier survival analysis as well as propensity score matching were used.

Results: Overall, 5633 patients were eligible. Patients with RSCC were more likely to be male, black, and younger, with a poor grade and histologic type, and were more likely to have more regional nodes examined and larger tumor size. After propensity score matching, CSS was significantly superior in patients with RSCC compared to those with LSCC (Hazard Ratio (HR): 0.80, 95% CI: 0.68-0.95, P =0.01). However, no survival benefit was observed for patients with LSCC after ACT (HR: 1.10, 95% CI: 0.90-1.35, P =0.35), and surprisingly, ACT was found to do more harm than good in patients with RSCC (HR: 1.31, 95% CI: 1.05-1.63, P =0.02). Even among patients with high-risk features such as T4 stage and regional nodes examined<12 in both groups, ACT still did not improve CSS except for T4 stage LSCC (HR: 0.65, 95% CI: 0.44-0.97, P =0.02).

Conclusions: The results of this analysis indicate that the prognosis of RSCC is better than that of LSCC in stage II colon cancer, and ACT did not improve CSS in patients with either LSCC or RSCC. Even in patients with parts of high-risk features, ACT still did not improve CSS, except for T4 stage LSCC.

Objectives: This study aims to examine the treatment outcomes and related factors in locally advanced sinonasal cancer across Turkiye.

Methods: Twelve centers participants of the Turkish Society for Radiation Oncology Head and Neck Study Group attended the study. One hundred and ninety-four patients treated with intensity-modulated radiation therapy between 2001 and 2021 were analyzed retrospectively. The survival analysis was performed using the Kaplan-Meier method. Acute and late toxicity were recorded per Common Toxicity Criteria for Adverse Events V4.0.

Results: The median age was 58 years and 70% were male. The majority of tumors were located in maxillary sinus (59%). Most of the patients (%83) had T3 and T4A disease. Fifty-three percent of patients were in stage 4A. Radiotherapy was administered to 80% of the patients in the adjuvant settings. Median 66 Gy dose was administered in median 31 fractions. Chemotherapy was administered concomitantly with radiotherapy in 45% of the patients mostly with weekly cisplatin. No grade ≥4 acute and late toxicity was observed. The median follow-up was 43 months. The 5-year and 10-year overall survival (OS); locoregional recurrence-free survival (LRFS); distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 61% and 47%; 69% and 61%; 72%, and 69%, and 56% and 49%, respectively. In the multivariate analysis, several factors demonstrated significant influence on OS, such as performance status, surgery, and lymph node involvement. Moreover, surgery was the key prognostic factor for LRFS. For DMFS, lymph node involvement and surgical margin were found to be influential factors. In addition, performance status and lymph node involvement were identified as significantly affecting PFS.

Conclusions: In our study, the authors obtained promising results with IMRT. Performance status, lymph node involvement, and surgery emerged as the primary factors significantly influencing OS.

Objectives: Androgen receptor-targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including treatment-related toxicity. We aim to describe reasons for ART treatment discontinuation and identify predictors associated with increased risk of treatment discontinuation due to toxicity.

Methods: We performed a single-institution retrospective review of patients with mCRPC receiving ART between 2010 and 2021. Our primary aim was to identify risk factors for treatment discontinuation due to toxicity. Our secondary aim was to describe ART discontinuation patterns among patients with mCRPC.

Results: One hundred thirty-three patients with mCRPC started and discontinued ARTs. Fourteen patients (10.5%) discontinued treatment due to toxicity. Common reasons for treatment discontinuation include Prostate Specific Antigen test progression, radiographic progression, toxicity, and death. Significant predictors of treatment discontinuation due to toxicity on bivariate analysis and multivariate analysis included patient-reported falls (odds ratio [OR]: 7.67, CI: [1.31-40.42]; P =0.016), rash (OR: 13.4, CI: [1.35-134.81]; P =0.026), and weakness (OR: 4.16, CI: [1.15-15.0]; P =0.019).

Conclusions: Our work presents the first description of ART treatment discontinuation and its causes in the real-world setting, as well as patient-reported side effects. Most patients with mCRPC discontinued treatment due to the progression of disease and a minority of patients discontinued secondary to treatment toxicity. Initial multivariable analysis suggests that patient-reported weakness, falls, and rash were associated with a higher likelihood of treatment discontinuation due to toxicity. Early monitoring of this population can prolong the duration of treatment and prevent unnecessary treatment burden.

With the global incidence of non-small cell lung cancer (NSCLC) on the rise, the development of innovative treatment strategies is increasingly vital. This review underscores the pivotal role of precision medicine in transforming NSCLC management, particularly through the integration of genomic and epigenomic insights to enhance treatment outcomes for patients. We focus on the identification of key gene mutations and examine the evolution and impact of targeted therapies. These therapies have shown encouraging results in improving survival rates and quality of life. Despite numerous gene mutations being identified in association with NSCLC, targeted treatments are available for only a select few. This paper offers an exhaustive analysis of the pathogenesis of NSCLC and reviews the latest advancements in targeted therapeutic approaches. It emphasizes the ongoing necessity for research and development in this domain. In addition, we discuss the current challenges faced in the clinical application of these therapies and the potential directions for future research, including the identification of novel targets and the development of new treatment modalities.

Objectives: Spinal metastases are common in metastatic cancer, affecting around 40% of patients. The primary treatment involves radiation therapy, transitioning from conventional external beam radiation therapy (EBRT) to stereotactic body radiation therapy (SBRT) for its superior, durable response. While spine SBRT has gained popularity in the United States, Level I evidence supporting it over EBRT is limited to a Canadian trial using a 2-fraction SBRT regimen. We present our findings from one of the earliest US experiences of 2-fraction spine SBRT for spinal metastases.

Methods: A retrospective analysis of patients with metastatic spine cancer receiving 2-fraction spine SBRT at a single center was conducted. Patients received treatment based on Level 1 evidence (24 Gy in 2 fractions). Follow-up records were assessed for local control outcomes and toxicity.

Results: Twenty patients since August 2022 have been treated with 2-fraction spine SBRT. Most patients were treated at 1 (45%) or 2 (40%) spinal levels, with the thoracic (55%) and lumbar (50%) spine being the most common locations. Common primary sites included the lung (30%), breast (20%), esophagus (15%), and prostate (10%). The rate of local control was 100%, while the rate of vertebral compression fracture was 15%. No esophageal or bowel toxicity occurred, and no fractures required intervention.

Conclusions: These findings suggest that 2-fraction spine SBRT is safe and effective, consistent with existing Level I evidence. Our local control rate exceeding 95% aligns with the literature, indicating the feasibility and achievability of implementing this approach in the United States over a short period of time.

Objectives: Glioblastoma (GBM) is a fatal adult central nervous system tumor. Due to its high heterogeneity, the survival rate and prognosis of patients are poor. Thousands of people die of this disease every year all over the world. At present, the treatment of GBM is mainly through surgical resection and the combination of later drugs, radiotherapy, and chemotherapy. An abnormal redox system is involved in the malignant progression and treatment tolerance of glioma, which is the main reason for poor survival and prognosis. The construction of a GBM redox-related prognostic model may be helpful in improving the redox immunotherapy and prognosis of GBM.

Methods: Based on glioma transcriptome data and clinical data from The Cancer Genome Atlas, databases, a risk model of redox genes was constructed by univariate and multivariate Cox analysis. The good prediction performance of the model was verified by the internal validation set of The Cancer Genome Atlas, and the external data of Chinese Glioma Genome Atlas.

Results: The results confirmed that the higher the risk score, the worse the survival of patients. Age and isocitrate dehydrogenase status were significantly correlated with risk scores. The analysis of immune infiltration and immunotherapy found that there were significant differences in the immune score, matrix score, and ESTIMATE score between high and low-risk groups. reverse transcription polymerase chain reaction and immunohistochemical staining of glioma samples confirmed the expression of the hub gene.

Conclusion: Our study suggests that the 5 oxidative-related genes nitricoxidesynthase3 , NCF2 , VASN , FKBP1B , and TXNDC2 are hub genes, which may provide a reliable prognostic tool for glioma clinical treatment.