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

Objectives: Black breast cancer patients have substantially decreased access to optimal breast-conserving cancer care than white patients. Patient navigation has never been formally implemented into the receipt of radiation therapy (RT) for black patients. We present initial results from an ongoing phase I trial assessing the impact of patient navigation on RT completion in this patient population.

Methods: The Navigator-Assisted Hypofractionation (NAVAH) program is a phase I trial (clinicaltrials.gov, NCT05978232) involving black breast cancer patients consented for postlumpectomy RT. Participants were assigned a patient navigator throughout the course of RT and post-RT care, and provided travel vouchers to offset RT transportation cost. Patients refusing trial participation were assessed to determine RT completion rate. The primary trial endpoint is RT completion rate following initiation of patient navigation.

Results: Of 54 trial-eligible patients, 36 accepted and 18 declined; no patient had received navigation before being offered trial enrollment. Of those declining enrollment 12/18 (66.7%) completed RT; of these 12, 9 (75%) completed RT without delay. 34/36 patients (94.4%) who enrolled completed RT, of whom 19 (55.9%) completed RT without delay. The differences in RT completion between patients having accepted versus declined trial enrollment were statistically significant ( P = 0.0124).

Conclusions: Early results of an ongoing phase I trial reveal that incorporation of patient navigation following initial radiation oncology consultation significantly improves adjuvant RT completion rates in early-stage black breast cancer patients. Further work examining patient navigation is ongoing.

Objectives: Antibody-drug conjugates (ADCs) have improved outcomes for metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative or low breast cancer; however, direct efficacy comparisons are limited. We compared trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd) in chemotherapy-pretreated HR+/HER2-negative or low metastatic breast cancers.

Methods: This meta-analysis conducted a comprehensive search of the Embase and Ovid Medline databases up to July 2025. Efficacy endpoints were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Hazard and odds ratios were calculated for the relevant outcomes. Safety was assessed using grade ≥3 treatment-related adverse events (TRAEs).

Results: Four randomized controlled trials were included. All 3 ADCs significantly improved PFS (P<0.00001) and ORR (P=0.008) compared with chemotherapy. Both T-DXd and SG demonstrated significant OS benefits (P=0.002), whereas Dato-DXd did not (P=0.94). For SG, OS benefit was observed primarily in later (≥3) lines (P=0.03). Among them, T-DXd demonstrated the most favorable outcomes across PFS, OS, and ORR, particularly in earlier lines. Grade ≥3 treatment-related adverse events (TRAEs) were most frequent with SG (60.2%), followed by T-DXd (52.6%) and Dato-DXd (20.8%). Neutropenia was the most common grade ≥3 TRAE with SG and T-DXd, while stomatitis was most common with Dato-DXd.

Conclusions: T-DXd demonstrated better efficacy in pretreated HR+/HER2-low metastatic breast cancer (MBC), especially in earlier lines. SG showed significant OS benefit primarily in later lines. Dato-DXd showed no OS benefit but had the most favorable safety profile.

Objectives: We evaluated the cost-effectiveness of adjuvant alectinib versus adjuvant platinum-based chemotherapy for patients with resectable (stage IB to IIIA) ALK+ non-small cell lung cancer using a US societal perspective.

Methods: We developed a cohort-level Markov model to compare adjuvant alectinib versus platinum-based chemotherapy using a lifetime time horizon (40 y) with a monthly cycle length and 3% discounting of health state utilities and costs. Patients started in a disease-free health state; downstream health states included treated (first- or second-line) or untreated metastatic or nonmetastatic recurrence, or death. Patient characteristics, adjuvant treatment patterns, and health utilities were based on the ALINA trial.

Results: When measured across a lifetime time horizon, adjuvant alectinib was estimated to lead to 3.1 additional quality-adjusted life-years (QALYs) with $429,925 lower total costs per patient, demonstrating a dominant cost-effectiveness ratio compared with adjuvant platinum-based chemotherapy (more effective and less costly). The net monetary benefit in favor of adjuvant alectinib was $895,766 at a willingness-to-pay (WTP) threshold of $150,000/QALY gained. In probabilistic sensitivity analysis, adjuvant alectinib has a 99.6% probability of being more effective and less costly than adjuvant chemotherapy. The incremental cost-effectiveness ratio for adjuvant alectinib remained dominant when all model inputs were varied in the one-way sensitivity analysis.

Conclusions: In comparison with platinum-based chemotherapy, adjuvant alectinib offers substantial additional clinical and economic value to society.

Objectives: Breast cancer remains the most prevalent cancer among women in the United States, with hormone receptor-positive (HR+) and HER2-negative subtypes comprising a significant proportion of cases. Despite advancements in treatment, resistance to endocrine therapies remains a substantial clinical challenge, especially in patients with mutations in the PIK3CA gene.

Methods: A literature review was conducted to evaluate the safety and efficacy of inavolisib in breast cancer. Studies published through November 2024 were identified using PubMed, Google Scholar, and ClinicalTrials.gov. Phases I to III clinical trials in English were included. The review focused on safety outcomes (eg, serious adverse events) and efficacy outcomes (eg, progression-free survival), which were summarized narratively.

Results: Inavolisib, a selective PI3Kα inhibitor, presents a promising option for patients with PIK3CA-mutated HR+HER2-negative advanced or metastatic breast cancer. In the INAVO120 trial, inavolisib combined with palbociclib and fulvestrant significantly extended progression-free survival (PFS) in patients with PIK3CA mutations. The median PFS was 15.0 months for the treatment arm compared with 7.3 months in the placebo group (hazard ratio: 0.43, P <0.001). The objective response rate (ORR) was 58.4% in the treatment arm, underscoring the drug's antitumor efficacy. Safety profiles revealed manageable adverse events, primarily hyperglycemia, neutropenia, and stomatitis. The incidence of these side effects was notable but manageable with appropriate supportive care. Inavolisib offers a new treatment for HR+HER2-negative advanced breast cancer, showing promising efficacy and safety. However, implementation challenges include high costs, insurance coverage issues, and limited access to required genetic testing through FoundationOne Liquid CDx assay, potentially creating barriers to equitable patient access.

Conclusions: Inavolisib represents a significant advancement in the treatment of advanced HR+HER2-negative breast cancer, offering an effective option for patients with PIK3CA mutations. However, to fully realize its potential, health care systems must address challenges related to patient access, insurance coverage, and the availability of companion diagnostics. Further long-term studies will be essential to assess the enduring impact of this treatment on patient outcomes.

The incidence of head and neck cancer ranks sixth among malignant tumors in the world. According to the GLOBOCAN 2020 database, there are about 930,000 new cases and 467,000 deaths per year. Among malignant head and neck tumors, head and neck squamous cell carcinoma (HNSCC) comprises approximately 90% of cases. Between 70% and 80% of HNSCC patients are diagnosed at an advanced stage (III or IV). Following comprehensive treatment, the recurrence rate within 2 years ranges from 40% to 60%. In cases of recurrent or metastatic HNSCC, the median survival period after traditional chemotherapy or targeted therapy is about 1 year, with a 5-year survival rate below 10%. However, several current trials are examining new tactics, such as better prediction biomarkers and combination strategies with chemotherapy, targeted therapy, additional immunotherapy, or radiotherapy, given the relatively poor response rate of immune checkpoint inhibitor monotherapy. Consequently, the research on stereotactic body radiation therapy (SBRT) in conjunction with immunotherapy for locally advanced head and neck tumors is reviewed in this article.

The microbiome is a significant multimicrobial community that coexists with the human body in a symbiotic relationship. These microbial communities participate in mechanisms, such as defense against infections, absorption of nutrients, and maintenance of internal homeostasis. Although the microbiome is involved in physiological processes that are beneficial to host health, it can also lead to serious problems. Despite being far apart, the oral cavity and colon are both highly colonized by different microbial communities. Studies have shown that oral bacteria can migrate to and colonize the colon, which is most evident in diseases such as periodontitis. These oral pathogenic bacteria, which contain a large number of carcinogenic factors such as Fusobacterium nucleatum and Porphyromonas gingivalis , can penetrate the large intestine and cause intestinal microbial imbalance and dysfunction, thereby stimulating carcinogenesis. Increasing evidence suggests that oral microbiota, especially certain periodontal pathogens, may be used as biomarkers for colorectal cancer (CRC). Understanding the exact mechanisms of microbiome interactions and their impact on CRC will provide future opportunities for the prevention and treatment of colorectal cancer, and is an important prerequisite for its use as a precise noninvasive biomarker, which is crucial for the early detection of CRC. This review aims to summarize the current research status of oral microbiota, gut microbiota, and their association with CRC, and to evaluate the effectiveness of oral microbiome-derived biomarkers.

Objectives: Radiation therapy (RT) may potentiate an antitumor immune response when combined with immunotherapy in advanced hepatocellular carcinoma (HCC) but carries the potential risk of bowel toxicity and impaired liver function. We describe our single-center experience of adding liver-directed RT to atezolizumab and bevacizumab (A/B) in patients with advanced HCC.

Methods: This was a single-center retrospective cohort study of patients with HCC naive to systemic therapy who received A/B with or without liver-directed RT from January 1, 2020 until May 1, 2023. We assessed safety outcomes, the real-world response rate (rwRR), overall survival (OS), and time-to-progression (TTP) from initiation of A/B. Time-to-event outcomes were analyzed by Kaplan-Meier methodology. Given anticipated baseline imbalances between cohorts, no formal comparisons were performed.

Results: We identified 49 patients (n=34 control, n=15 RT) who met the inclusion criteria. The cohorts differed in the presence of ascites, baseline liver dysfunction, infection with hepatitis B, and alcoholic liver disease. Two patients in the control group (5.8%) and 1 patient in the RT group (6.7%) experienced clinically significant bleeding. One patient (6.7%) developed possible RT-induced liver disease. The rwRR in the RT group was 73.3% (11/15) compared with 17.6% (6/34) in the control group. The median OS in the RT group was 14.4 months, and 10.8 months in the control group. Median TTP was 6.4 months with RT compared with 5.8 months in the control group.

Conclusions: The addition of liver RT to A/B resulted in limited additional toxicity with increased response rates, although significant differences in baseline characteristics limit a full interpretation of this data. Ongoing trials and trials under development will provide informative data regarding the addition of RT to A/B, particularly to assess the impact on OS and TTP.

Objectives: With the rising cost of chemotherapy, the financial toxicity (FT) of systemic therapy can substantially impair patient quality of life. FT is also associated with various socioeconomic factors, one being race. Patients of African American race often bear the worst burden of cancer treatment-related FT, with a 40% increased mortality from breast cancer. The degree to which chemotherapy before radiation therapy (RT) impacts FT has yet to be formally quantified. We report early FT findings among African American breast cancer patients before receipt of adjuvant RT on the ongoing Navigator-Assisted Hypofractionation (NAVAH) phase I clinical trial to assess the impact of chemotherapy on FT.

Methods: African American breast cancer patients undergoing RT were eligible if age 18+ with pathologically confirmed breast cancer following resection. FT was measured using the validated 12-item COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) survey instrument. Values from 26 to 44 represent grade 0 FT (none), 14 to 25 grade 1 FT (mild), 1 to 13 grade 2 FT (moderate), and 0 represents grade 3 FT (severe). The χ 2 test assessed statistically significant differences ( P < 0.05) between patients who received chemotherapy versus no chemotherapy before RT receipt.

Results: Mean COST-FACIT score was 25 (±10.4); 61% experienced mild to severe FT. Of the 38 patients, 53% underwent chemotherapy before RT. Patients with prior chemotherapy treatment reported 16% grade 0 FT, 53% grade 1 FT, 26% grade 2 FT, and 5% grade 3 FT. The relationship between adjuvant chemotherapy and FT was statistically significant ( P = 0.0028).

Conclusions: Over 60% of participants in this study experienced some degree of meaningful FT. These results from an ongoing phase I clinical trial indicate a subsection of patients may benefit from proactive financial assistance to reduce the detrimental effect of FT on their breast cancer treatment, highlighting patients requiring chemotherapy before RT being more likely to experience FT.

Objective: To reveal the global trends in the burden and quality of care for childhood ALL from 1990 to 2021, along with inequalities in quality of care across regions, thus identifying regions requiring targeted interventions for optimizing health care resource allocation.

Methods: Utilizing Global Burden of Disease Study 2021 data, this research analyzed the temporal trends in the global burden of childhood ALL from 1990 to 2021. The quality of care index (QCI) was used to quantify care quality, and the gender disparity ratio (GDR) was used to assess gender disparities. Trend analyses were conducted using the estimated annual percentage change (EAPC), and the associations between QCI, GDR, and the sociodemographic index (SDI) were explored. Inequalities in QCI and GDR across regions were evaluated using the slope index of inequality (SII) and health inequality concentration index.

Results: From 1990 to 2021, the incidence and death rates, as well as disability-adjusted life years (DALYs) and years of life lost (YLLs) due to childhood ALL, significantly decreased. However, the number of prevalence and prevalence crude rate increased by 66.818% and 37.923%, respectively. Global care quality continued to improve, with an EAPC of 2.566 (95% CI: 2.488-2.645). In 2021, regions with high QCI were concentrated in high-income areas like Western Europe, while low QCI regions were primarily in low-income areas like sub-Saharan Africa and Oceania. Although the health inequality concentration index of global quality of care decreased from 0.550 in 1990 to 0.395 in 2021, the SII increased from 35.396 to 87.141. Care quality was consistently higher in females than in males, particularly in low and low-middle SDI regions, while the disparities in high and middle SDI regions were gradually narrowing.

Conclusion: Despite the gradual decrease in the burden of childhood ALL globally and the steady improvement in quality of care, absolute inequalities remain a significant challenge. Future efforts should focus on increasing health care resource allocation in low SDI regions, enhancing international cooperation, improving the quality and accessibility of care in priority regions, and promoting global health equity.

Objectives: For decades, pelvic lymph node dissection (PLND) has been a critical component of radical cystectomy in patients with bladder cancer. Although its role in curative surgery for high-risk non-muscle-invasive and muscle-invasive cases is well-established, the therapeutic advantages of extended PLND remain a topic of ongoing debate.

Methods: A comprehensive literature search of major bibliographic databases was performed from inception to November 2024. Studies comparing extended PLND (extended or super extended) with standard PLND were identified. Data for clinical outcomes was extracted and pooled estimates were calculated using a random effects model with RevMan 5.4.

Results: A total of 11 studies (2 RCTs and 9 observational) were included reporting data for 4001 patients. The pooled analysis demonstrated that extended PLND was associated with significantly better recurrence-free survival (HR=0.67, 95% CI: 0.60-0.74). Standard PLND led to significantly higher 5-year recurrence rates (RR=1.44, 95% CI: 1.28-1.62) compared with the extended approach. The pooled estimates for disease-specific survival (HR=0.86, 95% CI: 0.62-1.19), overall survival (HR=0.99, 95% CI: 0.86-1.16), and complications remained comparable.

Conclusions: Extended PLND can lead to favorable recurrence-free survival and 5-year recurrence rates. However, retrospective observational studies mainly drive the evidence, and additional RCTs are required to reach a definitive conclusion.