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

Objectives: Most patients receiving curative-intent surgery for pancreatic cancer will experience cancer recurrence. However, evidence that postoperative surveillance testing improves survival or quality of life is lacking. We evaluated the use and characteristics of surveillance with serial imaging and CA 19-9 tumor marker testing at an NCI-designated comprehensive cancer center.

Methods: We conducted a retrospective cohort study of patients who entered surveillance after curative-intent resection of pancreatic adenocarcinoma. We abstracted information from the electronic medical record about oncology office visits, surveillance testing (cross-sectional imaging and CA 19-9 tumor marker testing), and pancreatic cancer recurrence, with follow-up through 2 years after pancreatectomy. We conducted analyses to describe the use of surveillance testing and to characterize the sensitivity and specificity of CA 19-9 tumor marker testing for the identification of cancer recurrence.

Results: We identified 90 patients entering surveillance after pancreatectomy. CA 19-9 was the most frequently used surveillance test, followed by CT imaging. Forty-seven patients (52.2%) experienced recurrence within two years of pancreatectomy. Recurrence risk was 58.8% versus 31.8% in patients with elevated versus normal CA 19-9 at diagnosis ( P =0.03). Elevated CA 19-9 at any point during surveillance was significantly associated with 2-year recurrence risk ( P <0.001). Elevated CA 19-9 had a sensitivity of 83% (95% CI 0.72-0.95) and specificity of 87% (0.76-0.98) for identification of recurrence within 2 years of pancreatectomy.

Conclusions: CA 19-9 demonstrates clinical validity for identifying recurrence of pancreatic cancer during surveillance. Surveillance approaches with reduced reliance on imaging should be prospectively evaluated.

Objective: Low-grade serous ovarian cancer (LGSC) represents 5% of all epithelial ovarian cancers. They are characterized by indolent growth and KRAS and BRAF mutations, differing from high-grade serous ovarian cancer both clinically and molecularly. LGSC has low response rates to traditional systemic therapies, including chemotherapy and hormonal therapy. The objective of this systematic review was to appraise the literature describing the efficacy of MEK inhibitors in the treatment of LGSC.

Methods: A comprehensive search was conducted of the following databases: Medline ALL, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Sciences, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICFRP), and International Standard Randomized Controlled Trials Number (ISRCTN) Registry. All studies investigating MEKi in the treatment of LGSC in the adjuvant or recurrent setting for patients 18 years of age or older were included. All titles/abstracts were then screened by 2 independent reviewers (A.K. and C.C.). The full-text articles were then screened. All disagreements were resolved by a third independent reviewer (T.Z.). Two independent reviewers (A.K. and C.C.) extracted data from the studies deemed eligible for final review.

Results: A total of 2108 studies were identified in the initial search. Of these, a total of 4 studies met the eligibility criteria for systematic review. In these studies, 416 patients were treated with an MEKi alone. All patients included in the studies were being treated for LGSC in the recurrent setting. Varied results and efficacy of the MEKi were reported in each study.

Conclusions: The results highlighted in this systematic review demonstrate varied responses to MEKi for recurrent LGSC. Further research is needed in this field comparing the efficacy to current therapies, as well as to further evaluate the safety and toxicity profile with long-term use of MEKi.

Objectives: Artificial intelligence (AI) chatbots are a new, publicly available tool for patients to access health care-related information with unknown reliability related to cancer-related questions. This study assesses the quality of responses to common questions for patients with cancer.

Methods: From February to March 2023, we queried chat generative pretrained transformer (ChatGPT) from OpenAI and Bing AI from Microsoft questions from the American Cancer Society's recommended "Questions to Ask About Your Cancer" customized for all stages of breast, colon, lung, and prostate cancer. Questions were, in addition, grouped by type (prognosis, treatment, or miscellaneous). The quality of AI chatbot responses was assessed by an expert panel using the validated DISCERN criteria.

Results: Of the 117 questions presented to ChatGPT and Bing, the average score for all questions were 3.9 and 3.2, respectively ( P < 0.001) and the overall DISCERN scores were 4.1 and 4.4, respectively. By disease site, the average score for ChatGPT and Bing, respectively, were 3.9 and 3.6 for prostate cancer ( P = 0.02), 3.7 and 3.3 for lung cancer ( P < 0.001), 4.1 and 2.9 for breast cancer ( P < 0.001), and 3.8 and 3.0 for colorectal cancer ( P < 0.001). By type of question, the average score for ChatGPT and Bing, respectively, were 3.6 and 3.4 for prognostic questions ( P = 0.12), 3.9 and 3.1 for treatment questions ( P < 0.001), and 4.2 and 3.3 for miscellaneous questions ( P = 0.001). For 3 responses (3%) by ChatGPT and 18 responses (15%) by Bing, at least one panelist rated them as having serious or extensive shortcomings.

Conclusions: AI chatbots provide multiple opportunities for innovating health care. This analysis suggests a critical need, particularly around cancer prognostication, for continual refinement to limit misleading counseling, confusion, and emotional distress to patients and families.

Objective: The aim of this study was to estimate the recurrence risk based on the number of prognostic factors for patients with stage I uterine endometrioid carcinoma (EC) who underwent surgical lymph node evaluation (SLNE) and were managed with observation.

Methods: We queried our database for women with FIGO-2009 stage I EC who underwent surgical staging including SLNE. Multivariate analysis with stepwise model selection was used to determine independent risk factors for 5-year recurrence-free survival (RFS). Study groups based on risk factors were compared for RFS, disease-specific survival, and overall survival.

Results: A total of 706 patients were identified: median age was 60 years (range, 30 to 93 y) and median follow-up was 120 months. Median number of examined lymph nodes was 8 (range, 1 to 66). 91% were stage IA, 75% had grade 1 and lymphovascular space invasion was detected in 6%. Independent predictors of 5-year RFS included age 60 years and above ( P =0.038), grade 2 ( P =0.003), and grade 3 ( P <0.001) versus grade 1. Five-year RFS for group 0 (age less than 60 y and grade 1) was 98% versus 92% for group 1 (either: age 60 y and older or grade 2/3) versus 84% for group 2 (both: age 60 y and above and grade 2/3), respectively ( P <0.001). Five-year disease-specific survival was 100% versus 98% versus 95%, ( P =0.012) and 5-year overall survival was 98% versus 90% versus 81%, for groups 0, 1, and 2, respectively ( P <0.001).

Conclusions: In patients with stage I EC who received SLNE and no adjuvant therapy, only age 60 years and above and high tumor grade were independent predictors of recurrence and can be used to quantify individualized recurrence risk, whereas lymphovascular space invasion was not an independent prognostic factor in this cohort.

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors are standard therapy for patients with non-small cell lung cancer (NSCLC) with EGFR mutation; however, resistance is common. Combinatorial strategies have been explored to improve survival. This meta-analysis assesses the efficacy and safety of combination therapy versus monotherapy in patients with advanced NSCLC who failed first-line EGFR-tyrosine kinase inhibitor treatment.

Methods: We searched randomized controlled trials from PubMed, Web of Science, Google Scholar, Cochrane Library, and ClinicalTrial.gov. The efficacy and toxicity of combination treatment groups were assessed in terms of progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs).

Results: This meta-analysis included 6 randomized controlled trials covering 785 participants. The results showed that the combined regimen arm had no significant improvement of PFS (log hazard ratio = -0.228, 95% CI: -0.543 to 0.087, P = 0.157), ORR (odds ratio = 1.147 [95% CI: 0.577, 2.281], P = 0.695), DCR (odds ratio = 1.578 [95% CI: 0.428, 5.821], P = 0.493), and AEs, including fatigue and diarrhea (odds ratio = 0.833 [95% CI: 0.297, 2.333], P = 0.728 for fatigue and odds ratio = 2.268 [95% CI: 0.544, 9.448], P = 0.261 for diarrhea).

Conclusions: Combination therapy may not provide a significant improvement in PFS, ORR, DCR, and incidence of AEs compared with monotherapy in patients with advanced NSCLC with EGFR mutations. Further research is needed to investigate the optimal sequencing of combination therapy in patients with NSCLC with different molecular targets to determine the most effective treatment strategy that can improve outcomes and quality of life for these patients.

Objectives: Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC.

Methods: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. χ 2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD).

Results: Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2 cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC.

Conclusions: All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.

Background: Liver tumors are commonly encountered in oncology. The study aimed to assess the impact of magnetic resonance imaging (MRI)-guided stereotactic body radiation therapy (SBRT) (MRgSBRT) on disease-related outcomes and the toxicity profile.

Methods: Patients who received MRgSBRT from 2019 to 2021 for primary and metastatic liver tumors were included in this analysis. The protocol for treatment simulation included Gadoxetate disodium injection followed by a single-dimensional post-exhale MRI (0.35-T MRI linear accelerator) and computed tomography simulation. The patient demographics and treatment-related outcomes were assessed. The time-to-event curves were analyzed for freedom from local progression (FFLP) and overall survival (OS).

Results: A total of 35 patients were eligible for analysis with a median age of 70 years (range 25 to 95). The median follow-up was 19.4 months (range 1 to 37 mo). The one-year OS was 77.7%, with an estimated 3 years of 47.9%. Patients with the locally controlled disease had a better median OS of 27.8 months (95% CI [23.8-31.6]) compared with 13.5 months (95% CI [5.6-21.3], P =0.007) in patients with local disease progression. The 1-year FFLP was 95.6%, and 3-year estimated FFLP was 87.1%. Patients who received a radiation dose of biologically equivalent dose≥100 Gy had FFLP of 30.9 months (95% CI [28.7-33.1]) compared with 13.3 months (95% CI [5.3-21.3], P =0.004) in patients who received <100 Gy biologically equivalent dose.

Conclusion: MRI-guided SBRT provides optimal local control, associated with improved OS in a heavily morbid, pretreated older cohort of patients with reasonable safety profiles.

Objectives: Angiosarcoma is a rare complication of breast-conserving therapy. This study evaluated the change in incidence between 1992 and 2016 of secondary breast angiosarcoma (SBA) in patients with a history of breast cancer and the impact of management strategies for the original breast carcinoma on angiosarcoma treatment.

Methods: Breast cancer and angiosarcoma cases were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database. SBAs were defined as angiosarcomas located in the breast occurring after a prior breast cancer diagnosis. Primary breast angiosarcomas (PBAs) were defined as an angiosarcoma diagnosis listed as "one primary only." Incidence rates were estimated using a proportion of the US total population. Survival was analyzed by the Kaplan-Meier method, and Cox proportional hazard models were used to assess the association of clinicopathologic characteristics on overall survival.

Results: Between 1992 and 2016, 193 cases of SBA were reported in the SEER dataset in patients with a prior history of breast cancer. The incidence of breast angiosarcoma in patients with a prior diagnosis of breast cancer increased 3-fold from about 10 cases per 100,000 person-years to about 30 cases per 100,000 person-years over this same period ( P =0.0037). For treatment of SBA (n=193), almost all (95%) had surgery. Nine percent received radiation (compared with 35% of patients with PBA, P <0.001) and 23% received chemotherapy (vs. 45% for PBA, P =0.11).

Conclusions: We demonstrate an increasing incidence of SBA over the study period. These data can help inform shared decision-making for optimal management of locoregional breast cancer and raise awareness of secondary angiosarcoma.

Ovarian carcinosarcoma (OCS) is a rare malignancy with a poor prognosis. It is a biphasic tumor with malignant epithelial and mesenchymal components. A few mutations commonly seen in cancer have been identified in OCS, including TP53, PIK3CA, c-myc, ZNF217, ARID1A, and CTNNB1. Some OCS tumors have shown vascular endothelial growth factor positivity and limited HER2 expression. There is evidence of homologous recombination deficiency in OCS. This malignancy can be categorized as copy number high but has not been shown to have a high tumor mutational burden. There are mixed findings regarding the presence of biomarkers targeted by immune checkpoint inhibitors in OCS. For treatments other than systemic chemotherapy, the data available are largely based on in vitro and in vivo studies. In addition, there are case reports citing the use of poly-ADP ribose polymerase inhibitors, vascular endothelial growth factor inhibitors, and immunotherapy with varying degrees of success. This review paper will discuss the molecular and genomic characteristics of OCS, which can guide future treatment strategies.