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

Objective: We sought to compare our results of patients treated with Cs-131 prostate brachytherapy (PB) as monotherapy to recently published results of patients treated with stereotactic body radiotherapy.

Methods: We analyzed data from patients treated at our institution with Cs-131 PB as monotherapy who had at least 5 years of follow-up and who prospectively completed expanded prostate cancer index composite questionnaires at baseline, 1 year, 2 years, and 5 years. We compared our data with the recently published data from radiation therapy oncology group (RTOG) 0938 and PACE-B (NCT01584258).

Results: A total of 138 patients were included in our cohort. Using RTOG 0938's definition, the frequency of a decline in urinary function in our PB cohort was 43% compared with 41.3% in RTOG 0938. According to PACE-B's definition, our PB cohort had minimal clinically important differences in the urinary incontinence domain of 26.4% and in the urinary obstructive/irritative domain of 40.7% at 2 years compared with PACE-B's reported rate of 32% and 33%, respectively. The frequency of a >5-point change in the expanded prostate cancer index composite bowel summary score at 5 years was 25% compared with 30.7% in RTOG 0938. Our bowel difference at 2 years was 23% compared with PACE-B's reported 24%. Our 5-year biochemical disease free survival (bDFS) was 97.8%, compared with 91.3% in RTOG 0938 and 95.8% in PACE-B.

Conclusions: Low dose rate (LDR) PB with Cs-131 as monotherapy provides excellent biochemical control of prostate cancer in low and intermediate-risk patients. Our cohort of patients had modest differences in patient-reported urinary and bowel quality of life compared with baseline. These differences were comparable to recently published stereotactic body radiotherapy data. When comparing prostate cancer treatments in terms of patient convenience and available resources, PB certainly should be considered.

Background: Some of the non-small cell lung cancer (NSCLC) cases enhance somatic mutations of the epidermal growth factor receptor (EGFR) gene within the tyrosine kinase inhibitor (TKI) domain. In such cases, first-line treatments are EGFR-TKIs, including osimertinib, erlotinib, or gefitinib. Therefore, this meta-analysis aims to assess the safety and efficacy of first-line targeted therapies for EGFR-mutated advanced NSCLC patients, focusing on osimertinib, erlotinib, and gefitinib.

Methods: A systematic electronic search was conducted on 3 electronic databases-Scopus, PubMed, and Web of Science-from inception to May 2024 to locate relevant trials reporting the safety and efficacy of osimertinib, erlotinib, or gefitinib in treating EGFR-mutated advanced NSCLC. No language or data restriction was applied to the search strategy. The assessed effects were objective response rate (ORR) and disease control rate (DCR). RoB 2 tool was utilized to determine the risk of bias while R programming language performed all the statistical synthesis.

Results: Out of 15,275 search results, only 19 trials were eligible for this meta-analysis. All the 3 EGFR-TKIs depicted effectiveness and safety among NSCLC patients, but osimertinib improved the ORR by 72% (95% CI: 65%, 78%) as compared with erlotinib (69% [95% CI: 58%, 79%]) and gefitinib (64% [95% CI: 64%, 78%]). Overall, the 3 EGFR-TKIs were effective by improving ORR 68% (95% CI: 63%, 73%). Similarly, osimertinib demonstrated highly effective impacts in disease control among NSCLC patients by 94% (95% CI: 91%, 97%) compared with gefitinib (68% [95% CI: 41%, 89%]). Overall, the 2 EGFR-TKIs were effective in disease control among NSCLC patients (82% [95% CI: 67%, 93%]).

Conclusions: The pooled analyses have shown that erlotinib, gefitinib, and osimertinib are safe and effective first-line treatment options for patients with EGFR-mutated advanced NSCLC. The meta-analysis outcomes have demonstrated that osimertinib, erlotinib, or gefitinib positively impact overall response rate and disease control.

Objectives: Traditional breast cancer management involves surgery followed by systemic therapies. However, advancements in neoadjuvant chemotherapy (NACT) raise questions about the necessity of surgery in cases with an excellent response to NACT. This study investigates the outcomes of radiotherapy without surgery in selected patients with nonmetastatic breast cancer after a complete or substantial response to NACT.

Methods: A retrospective study was conducted using the SEER database, reviewing records from 2010 to 2020 for patients with nonmetastatic breast cancer who received NACT, associated with a clinical response, followed by radiotherapy alone. The population included 123 patients, stratified into complete clinical response (cCR) and non-cCR (partial or unspecified clinical response) cohorts. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier and Cox proportional hazards models.

Results: The median follow-up was 41 months. Among the patients, 17 (13.82%) achieved cCR. The 5-year OS and CSS for the entire cohort were 65.8% and 71%, respectively, with the cCR group achieving 100% rates for both. Age above 60 and larger tumor size (T3 to T4) were associated with lower OS. The non-cCR group showed a 5-year OS of 61.5% and CSS of 67.1%.

Conclusions: This study indicates that omitting surgery in patients with a cCR to NACT may be feasible, as evidenced by this subgroup's 100% OS and CSS rates at 5 and 10 years. These promising results support further research into less invasive breast cancer management. However, prospective studies must validate these findings and identify suitable patients for nonsurgical approaches.

Objective: We evaluated survival outcomes by primary tumor site in synovial sarcoma (SS) patients with localized and metastatic disease at diagnosis.

Methods: We conducted a retrospective review of 504 SS patients diagnosed from 1974 to 2020. Kaplan-Meier method, log-rank test, and Cox-proportional hazards regression were used.

Results: Among 504 patients, 401 (79.6%) presented with localized disease, and 103 (20.4%) with metastases. For patients with localized disease, (1) 5-year OS by tumor site was as follows: 80% (95% CI, 67%-89%) for head/neck, 30% (95% CI, 18%-42%) for intrathoracic, 51% (95% CI, 35%-65%) for abdomen/pelvis, 71% (95% CI, 62%-79%) for proximal-extremity, and 83% (71%, 91%) for distal-extremity. (2) On multivariable analysis, tumor site (compared with proximal-extremity: intrathoracic tumors [HR: 1.95; 95% CI, 1.22-3.16]; hand/foot [HR: 0.52; 95% CI, 0.28-0.97]), tumor size (compared with <5 cm, 5-10 cm [HR: 1.80; 95% CI, 1.14-2.85]; ≥10 cm [HR: 4.37; 95% CI, 2.69-7.11]), and use of neo/adjuvant radiation (HR: 0.54; 95% CI, 0.37-0.79) remained significantly associated with OS. For patients with metastatic disease, (1) 5-year OS was 12% (95% CI, 6%-21%) and (2) the only factor that remained significantly associated with OS on multivariable analysis was surgical resection for the primary tumor (HR: 0.14; 95% CI, 0.08-0.26).

Conclusions: The primary tumor location plays a significant role in predicting outcomes for patients with localized SS. Even though patients present with metastatic disease, surgical resection of the primary tumor improves their survival. These findings are critical for patient counseling and designing a personalized treatment plan that reflects the corresponding outcomes.

Objectives: Breast cancer, particularly the hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) subtype, remains a major global health concern. Abemaciclib, a CDK4/6 inhibitor, has shown promising results in treating advanced cases. This study comprehensively assesses the efficacy and safety of abemaciclib in combination with endocrine therapy for HR+/HER2- advanced or metastatic breast cancer.

Methods: Following PRISMA guidelines, a systematic review and meta-analysis was conducted. A thorough literature search was conducted on PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov til December 2023. Inclusion criteria encompassed randomized controlled trials and retrospective cohort studies reporting on abemaciclib in approved doses, either as monotherapy or in combination. Outcome assessments included progression-free survival (PFS), overall response rate (ORR), side effects/adverse effects (SE/AE), and overall survival (OS). Quality assessment utilized Cochrane's revised risk of bias tool and Newcastle-Ottawa scale.

Results: Pooled results of 22 studies involving 14,010 patients revealed that abemaciclib significantly improved PFS (hazard ratio=0.53; 95% CI: 0.48-0.59; P =0.00; I 2 =0%), ORR (risk ratio=2.31; 95% CI: 1.93-2.75; P =0.00; I 2 =0%), and OS (risk ratio=0.76 (95% CI: 0.65-0.87; P =0.001; I 2 =0%). However, abemaciclib increased the risk of adverse events in the fulvestrant and nonsteroidal aromatase inhibitor (NSAI) combinations, respectively.

Conclusions: Abemaciclib, particularly in combination with fulvestrant, emerges as an effective therapeutic option for HR+/HER2- advanced or metastatic breast cancer, improving PFS and OS. The higher toxicity profile warrants cautious use, especially in treatment-naive patients.

Objectives: Surveillance imaging for HPV-associated oropharyngeal carcinomas (OPCs) differs among physicians and institutions. Surveillance imaging can detect disease progression earlier, but can also contribute to anxiety and cost, without proven survival benefits. We sought to determine practice patterns of surveillance imaging and the number of surveillance scans needed to detect one recurrence in patients with HPV-associated OPCs.

Methods: We performed a retrospective cohort study between 2017 and 2019 (median follow-up: 39.9 mo) of consecutive patients with locally advanced HPV-associated OPC who received definitive concurrent chemoradiotherapy (CRT) with 70 Gy at a single institution. Patients were followed post-CRT and their surveillance scans were recorded. Recurrences were classified as detected by first post-treatment scans, surveillance scans, clinical exams, or incidental findings. The number of surveillance scans needed to detect 1 recurrence was determined by dividing the number of surveillance scans by the number of recurrences detected by surveillance scans.

Results: Among 276 patients with a median follow-up of 39.9 months, there were 28 recurrences. Of all recurrences, 11 (39.3%) were detected by the first post-treatment scan, 11 (39.3%) by surveillance scan, 5 (17.9%) by clinical exam, and 1 (3.6%) was incidentally found. A total of 694 surveillance scans were taken. The number of surveillance scans needed to detect 1 recurrence was 64 overall, 45 within 2 years, and 248 beyond 2 years from treatment.

Conclusions: First post-treatment scans and surveillance scans detected more recurrences than clinical exams. A high burden of surveillance scans is needed to detect 1 recurrence, especially beyond 2 years from treatment.

Acute myeloid leukemia (AML) poses significant challenges due to its high relapse rates despite initial successful induction chemotherapy. Maintenance therapy aims to prevent disease recurrence, particularly in high-risk patients. This review explores current maintenance treatments, their impacts on patient outcomes, and ongoing studies shaping the treatment landscape for AML. Hypomethylating agents like azacitidine and decitabine have shown promise in improving relapse-free and overall survival, particularly in older patients with AML ineligible for transplantation. Combination regimens involving azacitidine and venetoclax have demonstrated encouraging outcomes post-hematopoietic stem cell transplantation. Targeted therapies, particularly FLT3 inhibitors like midostaurin and quizartinib, have shown significant benefits in improving survival outcomes, especially in FLT3-mutated AML cases. Gilteritinib and sorafenib also exhibit the potential to reduce relapse rates post-transplant. Isocitrate dehydrogenase inhibitors, including ivosidenib and enasidenib, present novel options for postchemotherapy and posttransplantation maintenance. Immunotherapies, such as Wilms tumor 1 peptide-based vaccines and checkpoint inhibitors, are being explored, although results vary. Despite ongoing research, the role of maintenance chemotherapy remains uncertain, with inconsistent outcomes across trials. The approval of oral azacitidine represents a significant advancement, emphasizing the need for further investigation into personalized maintenance approaches. In conclusion, the evolving landscape of maintenance therapy and integrating targeted therapies in AML offers promising avenues for improving patient outcomes.

Objectives: The gut microbiome is crucial in influencing cancer progression and response to treatment. We evaluate the efficacy and safety of probiotics and synbiotics in cancer treatment, focusing on the incidence of diarrhea, significant complications, surgical site infections, length of hospital stay, progression-free survival (PFS), and overall survival (OS).

Methods: Following PRISMA guidelines, a comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Cochrane CENTRAL up to June 2024. The risk of bias was assessed using the Cochrane Risk-of-Bias tool. Meta-analysis was performed using a random-effects model.

Results: Fifteen studies involving 2197 participants were included. Probiotic use was associated with a significant reduction in the incidence of diarrhea (OR=0.39, 95% CI: 0.15-1.00, P=0.049) with moderate heterogeneity (I2=64%). No significant differences were found in major complications (OR=0.50, 95% CI: 0.05-4.92, P=0.4053, I2=73%), surgical site infections (OR=0.36, 95% CI: 0.12-1.09, P=0.058, I2=0%), length of hospital stay (SMD=-0.30, 95% CI: -1.00 to 0.41, P=0.2726, I2=62%), PFS (HR=0.61, 95% CI: 0.03-10.82, P=0.2715, I2=0%), or OS (HR=0.52, 95% CI: 0.00-58.82, P=0.3298, I2=0%).

Conclusions: Probiotics significantly reduced the incidence of chemotherapy-induced diarrhea, highlighting their potential as supportive care agents in oncology. However, their impact on significant complications, surgical site infections, length of hospital stay, and survival outcomes remains inconclusive.

Objective: To report geographic distribution and characteristics of head and neck cancer (HNC) clinical trials in the United States.

Methods: We conducted a retrospective analysis of U.S. HNC clinical trials searching ClinicalTrials.gov from January 1, 2017 to December 31, 2021 using the terms "head and neck cancer" or "head and neck neoplasms."

Results: A total of 381 clinical trials met inclusion criteria with 2181 trial opportunities, which were correlated with population density. Of the U.S. population, 72% live within a 25-mile radius of trials. California, Pennsylvania, and New York had the greatest number of clinical trial entries. The majority of patients living more than 25 miles from an HNC clinical trial site are located in rural areas. One hundred sixty-five (43.3%) trials were about systemic therapy, of which 138 (83.6%) involved targeted immunotherapy. There were 286 unique principal investigators. One hundred six (37.1%) were females and 180 (62.9%) were males.

Conclusions: We demonstrate disparity in the geographic distribution of HNC trials favoring densely populated urban areas, which may limit patient access due to travel burden. Studies are skewed towards immunotherapy drug trials, with fewer radiation and surgery investigations.

Level of evidence: Level III.

Objective: To evaluate the efficacy of neoadjuvant chemotherapy combination with liposomal irinotecan, 5-fluorouracil, leucovorin, and oxaliplatin in patients with locally advanced rectal cancer.

Methods: This was a phase 2, nonrandomized, multicenter study in adults with stage II or III rectal cancer and an Eastern Cooperative Oncology Group performance status of 0 to 1. Total neoadjuvant therapy (TNT) consisted of neoadjuvant chemotherapy combination with liposomal irinotecan (60 mg/m2), oxaliplatin (60 mg/m2), leucovorin (400 mg/m2), and fluorouracil (2400 mg/m²), followed by chemoradiotherapy [ie, capecitabine (825 mg/m2) and radiotherapy according to the standard of care]. The primary efficacy endpoint was the proportion of patients who achieved clinical complete response (cCR), defined as the normalization of pelvic magnetic resonance imaging, rectoscopy, computed tomography scan, and tumor markers.

Results: The median follow-up was 32.3 months. Of the 30 patients who underwent TNT and were evaluated, 6 (20.0%; 95% CI: 5.2%-34.8%) patients achieved a cCR. There were no deaths. The median disease-free survival (DFS) for patients with cCR was not reached after a follow-up of 32 months; the 1-year DFS rate was 90.0% (95% CI: 71.0%-100%), and the 2-year and 3-year DFS rates were 80.0% (95% CI: 55.0%-100%). No grade ≥4 adverse events (AEs) were observed. Grade 3 AEs occurred in 18 patients (60%), most frequent was diarrhea (n = 9, 30%). Eleven (36.7%) patients experienced serious AEs, with diarrhea being the most frequent (n = 6, 20.0%).

Conclusion: TNT with 5-fluorouracil, leucovorin, and oxaliplatin and chemoradiation is a safe and effective therapeutic alternative for the management of locally advanced rectal cancer.