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

Objectives: For many malignancies, hypofractionated radiotherapy (HFRT) is an accepted standard associated with decreased treatment time and costs. United States provider beliefs regarding HFRT likely impact its adoption but are poorly studied. We surveyed US-based radiation oncologists (ROs) to gauge HFRT utilization rates for prostate (PC), breast (BC), and rectal cancer (RC) and to characterize the beliefs governing these decisions.

Methods: From July to October 2021, an anonymized, online survey was electronically distributed to ROs actively practicing in the United States. Demographic and practice characteristic information was collected. Questions assessing rates of offering HFRT for PC, BC, and RC and perceived limitations towards using HFRT were administered.

Results: A total of 203 eligible respondents (72% male, 72% White, 53% nonacademic practice, 69% with 11+ years in practice) were identified. Approximately 50% offered stereotactic body radiation therapy (SBRT) for early/favorable intermediate risk PC. Although >90% of ROs offered whole-breast HFRT for early-stage BC, only 33% offered accelerated partial-breast irradiation (APBI). Overall, 41% of ROs offered short-course neoadjuvant RT for RC. The primary reported barriers to HFRT utilization were lack of data, inexperience, and referring provider concerns.

Conclusions: HFRT is safe, effective, and beneficial, yet underutilized-particularly prostate SBRT, APBI, and short-course RT for RC. Skills retraining and education of ROs and referring providers may increase utilization rates.

Objectives: Studies investigating preoperative 5-fraction radiation therapy (RT) for soft tissue sarcoma (STS) are limited. We performed a meta-analysis to determine the efficacy and safety of this treatment paradigm.

Methods: This study-level meta-analysis was conducted using Bayesian methods. Statistical estimation for risk of outcome rates was conducted by posterior mean and 95% highest posterior density (HPD) intervals. Studies with 2-year local control (LC) and description of major wound complications (MWC) per the CAN-NCIC-SR2 study were included and served as the primary endpoints. Secondary endpoints included rates of acute and late toxicity. A total of 10 studies were identified and 7 met the inclusion criteria. Subgroup analyses were performed for ≥30 Gy vs <30 Gy.

Results: A total of 209 patients from 7 studies were included. Five studies used ≥30 Gy (n=144), and 2 studies <30 Gy (n=64). Median follow-up was 29 months (range: 21 to 57 mo). Primary tumor location was lower extremity in 68% and upper extremity in 22%. Most tumors were intermediate or high grade (95%, 160/169), and 50% (79/158) were >10 cm. The two-year LC for the entire cohort was 96.9%, and the rate of MWC was 30.6%. There was a trend toward improved LC with ≥ 30 Gy (95% HPD: 0.95 to 0.99 vs 0.84 to 0.99). There was no difference in MWC (95% HPD: 0.18 to 0.42 vs 0.17 to 0.55) or late toxicity between the groups.

Conclusions: Preoperative 5-fraction RT for STS demonstrates excellent 2-year LC with MWC and toxicity similar to standard fractionation preoperative RT. Multi-institutional trials with a universal RT protocol are warranted.

Objectives: Primary cutaneous B-cell lymphoma (PCBCL) is a relatively rare disease, associated with 5-year overall survival of nearly 95% when treated with external beam radiation therapy (EBRT) alone. However, standard EBRT doses yield acute skin toxicity in more than 70% of patients and grade 3 to 4 acute skin toxicity in nearly 10% of patients. Consequently, the PCBCL treatment paradigm is shifting towards lower EBRT doses. This study evaluates our early experience with ultra-low dose EBRT (total dose of 4 Gy in 2 fractions) for PCBCL.

Methods: Four biopsy-confirmed PCBCL lesions (1 anterior thigh and 3 chest) in 2 male patients were treated with 2 Gy×2 fraction EBRT using electrons through a clinical setup. The anterior thigh lesion was treated using a clamshell to protect the scrotum from scatter dose. Treatment was achieved using 9 MeV electrons to the 85% isodose line using no bolus, with follow-up every 4 months and potential retreatment if no visible response at 8 to 9 months.

Results: All lesions demonstrated a response to EBRT by 4 months, visibly manifesting as flattening with changes in pigmentation. At the last follow-up (20, 20, 16.5, and 4 mo, respectively), all lesions had flattened with no evidence of local recurrence and no skin toxicity.

Conclusions: Treatment of PCBCL with ultra-low dose EBRT to 4 Gy total dose in 2 fractions provides durable local control with zero skin toxicity. These results are encouraging for both the success of treatment and the potential to use similarly low doses for retreatment should patients exhibit local recurrence.

Objective: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT).

Methods: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/μL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT.

Results: Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/μL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/μL, P =0.01) and larger target tumor volume (median 125 vs. 62 cm 3 , P =0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death ( P =0.04); 1-year OS rates were 63% vs 77% ( P =0.03). Receipt of photon versus proton-based RT (OR=3.50, P =0.02), higher mean liver dose (OR=1.19, P <0.01), and longer RT duration (OR=1.49, P =0.02) predicted severe lymphopenia.

Conclusions: HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

Objective: This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer over a shorter and longer follow-up period.

Methods: We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% CIs. We assessed the quality of the included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2).

Results: After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had a low risk of bias, while 5 had some concerns. Bevacizumab was associated with a progression free survival benefit for <36 months (HR: 0.59, 95% CI: 0.45-0.76, P <0.0001, I2 =90%) and >36 months (HR: 0.66, 95% CI: 0.55-0.80, P <0.0001, I2 =80%), and an overall survival benefit for <36 months (HR: 0.87, 95% CI: 0.78-0.98, P =0.02, I2 =0%) but not for >36 months (HR: 0.98, 95% CI: 0.89-1.09, P =0.77, I2 =30%). There was no difference in deaths between intervention and control groups <36 months (RR: 0.95, 95% CI: 0.86-1.04, P =0.26, I2 =10%) or >36 months (RR: 1.02, 95% CI: 0.97-1.06, P =0.50, I2 =0%). Bevacizumab reduced disease progression <36 months (RR: 0.82, 95% CI: 0.72-0.92, P =0.0008, I2 =82%) but not at >36 months (RR: 0.83, 95% CI: 0.58-1.19, P =0.30, I2 =94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events.

Conclusion: Bevacizumab may improve progression-free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months.

Objectives: Cancer accounts for 22% of all mortality and is the leading cause of death among Hispanic and/or Latinx patients in the United States. The disparities in access to radiation therapy (RT), mortality rates, and treatment outcomes among Hispanic-American breast cancer patients compared with other populations highlight the urgent need for targeted interventions. The Navigator-Assisted Hypofractionation (NAVAH) program, with its innovative patient navigation approach and culturally sensitive survey, aims to better identify the specific barriers faced by this population. This study is a report of the NAVAH program experience piloting a Spanish-language culturally sensitive survey in Hispanic-American volunteers.

Methods: Hispanic-American volunteers with fluency in Spanish were recruited to participate in survey conduction, identified from local networks. Survey information was assessed by topic category, and survey responses were amalgamated into a representative score for each category. Survey categories include acceptability (comfort and prejudice among interactions with the system), accessibility (transportation, distance to care, and health care literacy), accommodation (access to the internet, navigating transportation), affordability (financial considerations, employment, and level of education), and availability (access to a medical center, coordinating care, and overall quality of care).

Results: A total of 6 volunteers meeting inclusion criteria completed the survey; 4 in person and 2 by telephone. The median survey completion time was 12 minutes 38 seconds. Respondents noted satisfaction and trust in their interactions with medical providers; however, responses in the acceptability category highlighted a high perception of disparities in the medical system, including a high prevalence of racial and ethnic prejudice and a high prevalence of treatment differences between high-income and low-income patients in clinical settings.

Conclusions: In the first Spanish-language survey of its kind, our findings indicate that this survey design is feasible in the Hispanic-American population. Implementation of this survey in breast cancer patients will provide more definitive and comprehensive answers regarding other categories in the survey, including financial challenges during treatment, access to accommodations, and perception of treatment during cancer care. The investigation involving patients actively receiving breast cancer RT is currently underway.

Objectives: Recent DESTINY-Breast trials have demonstrated trastuzumab deruxtecan's effectiveness in HER2-positive and HER2-low metastatic breast cancer. However, safety concerns remain regarding its combination with radiation therapy (RT). The purpose of this work is to assess the toxicity profile of combining trastuzumab deruxtecan and RT in patients with HER2-positive and HER2-low metastatic breast cancer to address these concerns.

Methods: We conducted a retrospective study which included patients treated at Institut Curie Paris between November 2020 and January 2024. Patients with HER2-positive and HER2-low metastatic breast cancer who received concurrent trastuzumab deruxtecan and RT were identified. Data on patient demographics, treatment regimens, radiation doses, toxicity profiles, and treatment discontinuations were collected. Follow-up was conducted from the last day of radiotherapy until death or the last examination and toxicities were graded using the CTCAE V5.0.

Results: The studied population includes all 33 patients with HER2-positive and HER2-low metastatic breast cancer who underwent concurrent treatment with trastuzumab deruxtecan and radiotherapy. The median follow-up was 11 months. The most common acute grade 1 toxicity was nausea. Grade 2 toxicities affected 21.2% of patients, including asthenia, mucositis, cardiac decompensation, and diarrhea. Trastuzumab deruxtecan discontinuation occurred in 5 patients due to systemic treatment-related toxicities, including nausea, thrombocytopenia, neutropenia, and cardiac decompensation. There were 21.2% reported with late toxicities, with nausea being the most prevalent.

Conclusions: Our series of patients who received concurrent treatment of radiotherapy and trastuzumab deruxtecan are showing acceptable toxicity. Larger prospective studies are needed to evaluate the toxicity and efficacy of this combination.

Objectives: Immunotherapy improved the outcome of patients with unresectable hepatocellular carcinoma, but not all studies are in agreement, nor is it clear whether certain subgroups have really benefited. This study aims to perform an updated meta-analysis of trials comparing upfront immunotherapy-based regimens versus tyrosin-kinase inhibitors, and some exploratory analyses.

Methods: After a systematic review, randomized trials of immunotherapy-based regimens versus tyrosin-kinase inhibitors were selected. A meta-analysis assessed the relationship between treatment arm and overall survival. Based on the resulting heterogeneity, a further investigation of 11 variables by meta-regression and an exploration of subgroups were planned.

Results: Eight studies were selected. From the meta-analysis, the overall survival improvement for the immunotherapy-based arms was consistent (HR: 0.77, CI: 0.68-0.88), although heterogeneity between studies was significant ( Q =16.37; P =0.0373; I2 =51.1%). After meta-regression, the effect of the experimental arm was more pronounced in the elderly and lost among patients with HCV-related liver disease. Subgroups suggested a favorable effect of immunotherapy in patients with HBV-related hepatocellular carcinoma, extrahepatic dissemination, and elevated alpha-fetoprotein.

Conclusion: The study results confirm the significant overall survival improvement after immunotherapy-based regimens but suggest different effects on the outcome depending on age, etiology of liver disease, and tumor burden.