American Journal of Clinical Oncology最新文献

Trophoblast cell-surface antigen-2 (Trop-2) is a transmembrane calcium signal transducer and its overexpression is common in many types of malignant epithelial tumors, including breast cancer (BC). Sacituzumab govitecan-hziy (SG), the anti-Trop-2 antibody-drug conjugate, resulted in a significant survival benefit over chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). The greatest efficacy was observed in those who had a medium or high Trop-2 score. However, the importance of Trop-2 as a potential predictive factor requires further research. Elderly patients also appear to benefit from treating with SG. While the early results are encouraging, the ultimate benefit of SG in patients with brain metastases has yet to be determined. Early phase studies have shown that SG is also active in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic BC. The most common side effects of SG are nausea, neutropenia and diarrhea. Currently, several clinical trials are in progress with SG in monotherapy and in combination treatment for various types of BC. Taken together, SG should be considered as a new standard of care in patients with pretreated mTNBC. This review summarizes the development and highlights recent advances of the SG in BC.

Introduction: Homologous recombination mutations (HRM) have led to increased responses to platinum chemotherapy in pancreatic cancer. However, HRMs' role in nonpancreatic gastrointestinal (GI) cancers remains to be determined. Our objective was to evaluate the prognostic and predictive role of core (BRCA1, BRCA2, PALB2) and noncore HRM in nonpancreatic GI cancers receiving platinum therapy.

Materials and methods: This study performed at Moffitt Cancer Center included metastatic nonpancreatic GI cancer patients treated with platinum therapy. All patients had either a core or noncore HRM, determined by next generation sequencing. Response rates, median progression-free survival (PFS), and median overall survival (OS) were determined and compared between core versus noncore HRM patients.

Results: In the study, 69 patients with one or more HRM were included: 63.8% were male, 87.0% were Caucasian, and 47.9% had colorectal cancer. Twenty-one (30.4%) patients had a core HRM and 48 (69.6%) had a noncore HRM. Among evaluable patients (n=64), there was no significant difference in objective response: 20.0% with core HRM versus 22.7% with noncore HRM responded to platinum therapy (P=0.53). Median PFS was 10.4 months versus 7.1 months for core HRM versus noncore HRM, respectively (P=0.039). Median OS was 68.9 months versus 24.3 months (P=0.026) for core HRM versus noncore HRM, respectively.

Conclusions: Our study demonstrated response of core and noncore HRM to platinum therapy in metastatic nonpancreatic GI malignancies, suggesting benefit in both groups. Core HRM patients had significantly increased median OS and median PFS compared with those with noncore HRM, suggesting potential prognostic and predictive significance. Larger prospective studies are needed to confirm our findings.

The present work aims to review the clinical evidence of survival outcome after treatment of colorectal cancer liver metastases using yttrium-90 radioembolization, existence, and relevance of clinical, imaging, and genomic predictors of treatment efficacy and the amount of administered activity. Publications listed in PubMed between July 2016 and May 2021 were screened. Predictors of overall survival were reported and distinguished in clinical, imaging, and genomic variables. Administered activity is reported as median and mean value; overall survival is presented as a median value from the treatment. Fourteen papers resulted to be eligible for this systematic review, 11 retrospective, and 3 prospective studies. Ten studies reported administered activity data, with an average mean administered activity of 1.63 GBq and an average median administered activity of 1.53 GBq. Many clinical, imaging and genomic variables have been identified or defined as predictors of efficacy, leading to the possibility of improvements in patient selection criteria. The overall survival resulted to be about 9 months. The clinical evidence on the application of radioembolization with yittrium-90 resumed in this work underlines the importance to analyze several clinical, imaging, and genomic variables to predict the outcome of the therapy. The overall survival has not improved significantly with respect to older studies. Further developments on treatment planning and patient selection could lead to better clinical outcomes.

Purpose: This is a single arm phase 2 study (Clinical trials.gov NCT02568033) to examine the role of stereotactic body radiotherapy (SBRT) along with full dose systemic chemotherapy in the treatment of unresectable stage 2 and stage 3 nonsmall cell lung cancer. Primary endpoints are disease free survival and toxicity.

Materials: Patients were treated with SBRT to all sites of gross disease. Dosing consisted of 60 Gy in 3 fractions for peripheral lung tumors, 50 Gy in 5 fractions for central lung tumors, and 40 to 50 Gy in 5 fractions for hilar and mediastinal lymph nodes. Chemotherapy consisted of 4 cycles of pemetrexed and cisplatin or carboplatin and paclitaxel for nonsquamous histology and cisplatin and docetaxel or cisplatin and paclitaxel for squamous histology. SBRT was given in between the chemotherapy cycles. There was a 7 days break between chemotherapy and SBRT. Quality of life was measured using functional assessment of cancer therapy-lung.

Results: Twenty two patients were enrolled and analyzed. Seventeen (77%) were stage III and 19 (86%) had lymph node involvement. Median follow-up for all patients was 23.1 months. Median overall survival is 27.2 months. Overall survival at 1 year was 82% and overall survival at 2 years was 53%. Median disease free survival is 16.0 months with a 2-year regional failure rate of 19% and 2-year distant failure rate of 47.2%. There were 6 grade 3 acute toxicities and 2 late grade 3 or higher toxicities including 1 grade 5 hemoptysis. Quality of life scores were unchanged compared with baseline.

Conclusion: A combination of SBRT and full dose chemotherapy appears to be a safe and effective treatment for locally advanced NSCLC and warrants further investigation.