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

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: 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.

Objectives: Beta-blockers, a class of drugs commonly used to manage blood pressure, have been the subject of research regarding their relationship to prostate cancer (PC) risk, prognosis, and treatment. Beta-blockers reduce risk and improve the prognosis of PC. Perioperative use of a nonselective beta-blocker improves outcomes after radical prostatectomy. However, a related class of drugs, beta-2 adrenergic agonists, has received little attention in PC.

Methods: We studied the relationship of the beta-2 adrenergic agonist salbutamol to PC risk and survival. We analyzed Food and Drug Administration MedWatch data to determine whether salbutamol could influence the risk of PC. We used UK Biobank data to assess the effect of salbutamol on PC survival.

Results: Salbutamol significantly reduces PC risk, proportional reporting ratio, and 95% CI (lower bound; upper bound): 0.131 (0.11; 0.155) and improves prognosis. Mean survival was 7.35 years for subjects not taking salbutamol, and 10.5 years for subjects taking salbutamol (P = 0.041, log-rank test. To adjust for the effect of age, we performed proportional hazards regression, survival time-dependent variable, age, and salbutamol use independent variables. Salbutamol use was significantly related to survival time (P = 0.016) and independent of the significant effect of age (P < 0.001).

Conclusions: We found a lower proportion of PCs in salbutamol-treated people, but we have not demonstrated that PC risk is reduced (there is no proof of causality). There is no causality relationship between salbutamol and the survival of patients with PC treated with salbutamol versus those not treated with the drug. Yet, there is a trend in favor of salbutamol-treated patient survival. Therefore, salbutamol and other beta-adrenergic agonists might represent a new class of drugs for the treatment of PC.

Objectives: In the recent MONALEESA-2, MONALEESA-3, and MONALEESA-7 clinical trials, the addition of ribociclib, a CDK4/6 inhibitor, to standard endocrine therapy significantly improved progression-free survival (PFS) compared with hormone therapy alone in the treatment of locally advanced or metastatic estrogen receptor-positive (ER) and HER2-negative breast cancer. However, its toxicity raises concerns when administered concomitantly with radiotherapy, leading most radiotherapists and medical oncologists to prefer to discontinue Ribociclib during radiotherapy (RT). Although there are insufficient published data on this combination, our preliminary experience with the first 2 patients treated at Institut Curie suggests promising results when using Ribociclib with Letrozole or Fulvestrant concurrently with palliative radiotherapy in the treatment of metastatic breast cancer. Our study aimed to evaluate the safety of combining Ribociclib with palliative radiotherapy in patients with metastatic breast cancer, providing crucial insights for clinical decision-making.

Methods: A retrospective analysis was conducted on patients treated for hormone receptor-positive metastatic breast cancer with Ribociclib and concurrent radiotherapy at the Institut Curie (Paris, France) between September 2023 and April 2024. Among 38 patients who received Ribociclib and underwent irradiation, 36 temporarily suspended Ribociclib during radiotherapy, while 2 continued Ribociclib concurrently and were included in the analysis. Palliative radiotherapy was administered using volumetric modulated arc therapy, delivering 20 Gy in 5 fractions to bone metastatic sites. Ribociclib was given at 600 mg/day with hormonotherapy. Follow-up was conducted from the last day of RT until the last medical consultation. Toxicities were graded using CTCAE V5.0.

Results: Two patients received Ribociclib concomitantly with radiotherapy, experiencing pain relief without interruptions in RT. However, Ribociclib treatment was halted in both cases due to grade 3 neutropenia and grade 1 QTc interval prolongation, respectively. One patient had a dose reduction to 400 mg due to neutropenia, with favorable outcomes observed. Both patients continued Ribociclib treatment, with one achieving complete remission and the other partial remission of bone disease. No late toxicities were observed.

Conclusion: Despite the need for further investigation, our results suggest safety consistent with pivotal trials, advocating for a prospective cooperative data collection initiative to explore this combined strategy further, potentially revolutionizing metastatic breast cancer management.

Objectives: With sensitive imaging for breast cancer, the question arises whether present-day oncologists treat dOMBC with palliative systemic therapy (ST), which, a few years earlier, would have been treated with curative intent. We retrospectively analyzed outcomes of dOMBC treated with curative intent using a combination of surgery, metastasis-directed radiotherapy (RT), and adjuvant/neoadjuvant ST and have also explored the possible role of total lesional glycolysis of metastases and p53 immunohistochemistry in predicting outcomes.

Methods: Data were collected from a prospectively maintained database using electronic medical records and Radiation Oncology Information System. In the study, dOMBC was defined as up to 3 metastatic sites, all amenable to treatment with ablative RT and primary and axillary disease amenable to curative surgery. Patients were treated with surgery, ST, and RT.

Results: Patients underwent either breast conservation surgery or modified radical mastectomy. Patients were treated with 6 to 8 cycles of chemotherapy in the neoadjuvant and/or adjuvant setting. Hormone receptor-positive patients received either tamoxifen or aromatase inhibitors. Trastuzumab was offered to Her-2-neu receptor-positive patients. RT included locoregional RT and metastases-directed ablative body RT. The median progression-free survival was 39 months (95% CI: -28.7 to 50.1 mo). Two and 3 year estimated disease-free survival (DFS) was 79% and 60.5%, respectively. The median overall survival was not reached. The estimated 3-year overall survival was 87.3%. Total lesional glycolysis of metastases score and p53 status did not affect DFS.

Conclusion: Combination treatment of surgery, metastases-directed ablative RT, and ST may provide prolonged DFS in dOMBC.

Objective: To analyze the risk factors for grade ≥2 ARE in patients with cervical cancer receiving concurrent chemoradiotherapy.

Methods: A total of 273 patients with cervical cancer receiving concurrent chemoradiotherapy at our hospital were retrospectively enrolled. The patients were divided into training and validation groups. Clinical parameters were analyzed using univariate analysis and multivariate logistic regression analysis. A nomogram model was established based on the independent risk factors selected using multivariate logistic regression. The areas under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. The patients were divided into low-score and high-score groups based on the scores calculated using the nomogram model and compared.

Results: Malnutrition, monocyte-lymphocyte ratio ≥0.82 after radiotherapy, platelet-lymphocyte ratio <307.50 after radiotherapy, and bowelbag volume receiving at least 5 and 40 Gy were independent risk factors for grade ≥2 ARE and were incorporated into the nomogram ( P <0.05). The ROC curve, calibration curve, and DCA suggested that the nomogram had good discrimination, concordance, and net benefit in the clinical. A medium nomogram score of 146.50 points was used as the cutoff point, and the incidence of grade ≥2 ARE in the high-score group was higher than that in the low-score group ( P <0.05).

Conclusion: The nomogram model for grade ≥2 ARE has good predictive ability and clinical utility, and is convenient for clinicians to identify high-risk groups and develop early prevention and treatment strategies.