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

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.

Objectives: For locally advanced rectal adenocarcinoma (R-ACA), a nonoperative management (NOM) approach has emerged as a guideline-supported treatment option. However, the variables associated with NOM receipt are unknown.

Methods: Utilizing the National Cancer Database, we performed a retrospective cohort study of adults with stage 1 to 3 R-ACA managed with curative intent from 2004 to 2018. The primary outcome was the proportion of patients receiving NOM versus surgery. The secondary outcome was survival among NOM patients.

Results: A total of 128,297 patients were included. In all, 115,888 (90.3%) received surgery and 12,409 (9.7%) received NOM. Receipt of NOM was associated with age above 70, Charlson-Deyo score of 0, race (Black, Asian or Pacific Islander, or other vs. White), insurance status, geographical region, treatment in a community facility, year of diagnosis (2012-2018 vs. 2004-2011), tumor grade 1 versus ≥ 2, clinical T-stage ≥ 2, and clinical N1 or N2 versus N0. In the NOM cohort, poorer overall survival was associated with age 70 and above, male sex, Charlson-Deyo score ≥ 1, insurance status, geographical region, rural urban density versus metro/urban, treatment in a community facility, year of diagnosis (2004-2011 vs. 2012-2018), clinical T4 versus T1, clinical N1 or N2 versus N0, grade 3 versus 1, treatment with a radiotherapy dose <45 Gy versus 45 to 54 Gy, and omission of chemotherapy.

Conclusions: Several demographic factors and social determinants of health were associated with receipt of NOM and overall survival. With the increasing utilization of NOM, it will be important to understand the drivers of treatment decisions and influences on access to the desired treatment approach.

Objectives: To evaluate the association between the KRAS mutational load and the histologic tumor response in patients with resectable pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant treatment (NAC) with pegylated liposomal irinotecan in combination with oxaliplatin, 5-fluorouracil, and leucovorin (NALIRIFOX).

Methods: This was a multicenter, single-arm, interventional, open-label, phase 2 trial in patients 18 years or older who had histologically or cytologically confirmed PDAC and were candidates for surgery and received neoadjuvant NALIRIFOX. The primary outcome was determination of the association between the KRAS mutational load and the histologic tumor response after chemotherapy.

Results: Twenty patients were included in the study. Before initiating NAC, 11 patients were KRAS+, 6 were KRAS-, and 3 were not evaluable for KRAS mutation status. Eight of the 11 (72.7%) patients changed from KRAS+ at baseline to KRAS- after treatment, and none of the 6 (0.0%) patients changed from KRAS- at baseline to KRAS+ after treatment. A good histopathologic response after NAC was observed in 3 (15%) of the 20 patients, with a greater proportion of good responses among patients who were KRAS- (3 out of 16 [18.8%]) than among those who were KRAS+ (0 out of 1 [0.0%]) after NAC, although the differences were not statistically significant (P=0.633).

Conclusions: Our results indicate that patients with potentially resectable PDAC tend to have detectable KRAS in the blood if the disease is locally more advanced and that most patients who are treated with neoadjuvant NALIRIFOX are negative for KRAS at the end of therapy.

Objectives: In this study, we report conditional survival rate for gynecologic malignancies using Surveillance, Epidemiology, and End Results (SEER) database for patients who have received treatment with radiation therapy.

Methods: Utilizing the SEER 22 database and SEER*Stat 8.4.3, regional gynecologic malignancies (cervix uteri, corpus uteri, vagina, vulva) treated with external beam radiation therapy (EBRT), brachytherapy, or both, were identified between 2000 and 2020. 5-year CS was calculated annually for each type of cancer treated with different types of therapies up to 5 years post diagnosis. The timeframes for percentages of survived patients are 12 to 72, 24 to 84, 36 to 96, 48 to 108, and 60 to 120 months, which gives the percentage of patients surviving up to 5 years at 1 to 5 years from when patients received diagnosis.

Results: There were 59,441 patients who received radiation in the initial cohort. This was further subdivided into 24,073 (40%) patients who received EBRT only, 18,528 (31%) who received brachytherapy only, and 16,840 (28%) who received combined EBRT and brachytherapy. 5-year CS was calculated each year after initial diagnosis up to 5 years after. For all types of cancers that were analyzed, the 5-year CS increased as the year after diagnosis increased.

Conclusions: CS is an effective method to prognosticate patients over time. In our cohort of patients with gynecologic malignancies treated with radiation, the overall trends for 5-year CS were similar across any treatment modality. These findings may help elucidate statistics for survivorship care and may help develop evidence-based policies.

Objectives: We report on the biomarker analyses focusing on neutrophil-to-lymphocyte ratios (NLR) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with combined cetuximab and nivolumab.

Methods: Data were obtained from a phase II trial (NCT03370276). Peripheral blood NLR was obtained at baseline (B-NLR) and on-treatment (OT-NLR; 1 mo from treatment initiation). Tumor NLR (T-NLR) was determined by staining of immune cells in primary tumors. Patients were stratified into high (≥median) or low NLR (

Results: While B-NLR did not correlate with survival or responses, low OT-NLR was associated with superior overall survival (OS; P<0.0001), progression-free survival (PFS; P=0.0002), and overall response (P<0.001) compared with high OT-NLR. Multivariable analysis further demonstrated that low OT-NLR was associated with superior OS (HR 0.32, 95% CI, 0.17-0.61) and PFS (HR 0.45, 95% CI, 0.25-0.81). Compared with patients with high OT-NLR, a higher proportion of patients with low OT-NLR had OS≥24 months (P=0.0001). Low OT-NLR was associated with higher baseline PD-L1 combined positive scores (P=0.037). Low pretreatment T-NLR was associated with superior OS and PFS in multivariable analysis and correlated with superior overall response (P=0.011).

Conclusions: Low OT-NLR and pretreatment T-NLR correlated with superior treatment outcomes in patients with R/M HNSCC treated with cetuximab and nivolumab. Further evaluation of T-NLR to improve patient selection and peripheral blood OT-NLR as a dynamic biomarker contributing to clinical benefit assessment given cetuximab and nivolumab is warranted.

Esophageal squamous cell carcinoma (ESCC) is a major global health burden with limited treatment options. Combining immunotherapy with antiangiogenic agents has shown promise. Camrelizumab, a PD-1 inhibitor, and apatinib, a VEGFR-2 inhibitor, offer synergistic effects, improving outcomes in patients with advanced or metastatic ESCC. A literature search was conducted across PubMed, Cochrane, Embase, Scopus, and clinicaltrials.gov from inception till May 2025. Nine studies evaluating the safety and efficacy of camrelizumab plus apatinib were included. Analysis was conducted on R Studio v4.5.0. Pooled estimates were reported as proportions and 95% CI using a random effect model. Statistical heterogeneity was assessed using I². Subgroup analysis was based on treatment exposure. The pooled 1-year overall survival (OS) rate was 71%, with treatment-naive patients exhibiting a statistically higher 1-year OS of 95% compared with 55% in pretreated patients. One-year progression-free survival was 25%. The overall response rate was significantly higher in the treatment-naive group than in the previously treated group (87% vs. 28%). Previously treated patients showed a modest complete response rate (CRR) of 1%, while treatment-naive patients showed a significantly higher CRR of 22%. Partial response rate was significantly higher in the treatment-naive subgroup (64% vs. 26%). Hemangioma was the significant adverse event in the treatment-naive subgroup (47% vs. 12%). Rates of leukopenia, neutropenia, anemia, and thrombocytopenia were comparable between the 2 subgroups. Camrelizumab plus apatinib has shown promising efficacy with improved OS, PFS, and response rates. Large-scale trials are warranted to validate these findings and optimize treatment strategies.