High versus low dose Stereotactic Body Radiation Therapy for hepatic metastases

Introduction: Stereotactic Body Radiation Therapy (SBRT) is a treatment option for patients with liver metastases. This study evaluated the impact of high versus low dose image-guided SBRT of hepatic metastases. Methods and materials: This is a single-center retrospective study of patients with liver metastases treated with SBRT. For analyses, patients were divided into two groups: ≤100 Gy and >100 Gy near-minimum Biological Effective Doses (BED98%). The main outcomes were local control (LC), toxicity and overall survival (OS). Cox regression analyses were performed to determine prognostic variables on LC and OS. Results: Ninety patients with 97 liver metastases (77% colorectal) were included. Median follow-up was 28.6 months. The two-year LC rates in the ≤100 Gy and >100 Gy BED98% group were 60% (CI: 41–80%) and 90% (CI: 80–100%), respectively (p = 0.004). Grade 3 toxicity occurred in 7% vs 2% in the ≤100 Gy and >100 Gy group (p = 0.23). Two-year OS rates in the ≤100 Gy and >100 Gy group were 48% (CI: 32–65%) and 85% (CI: 73–97%), respectively (p = 0.007). In multivariable Cox regression analyses, group dose and tumor volume were significantly correlated with LC (HR: 3.61; p = 0.017 and HR: 1.01; p = 0.005) and OS (HR: 2.38; p = 0.005 and HR: 1.01; p = <0.0001). Conclusion: High dose SBRT provides significantly better local control and overall survival than low dose SBRT without increasing toxicity. When surgical resection is not feasible, high dose SBRT provides an effective and safe treatment for liver metastases

Risk factors for metachronous isolated peritoneal metastasis after preoperative chemotherapy and potentially curative gastric cancer resection: Results from the CRITICS trial

Gastric cancer (GC) patients at high risk of developing peritoneal metastasis (PM) as a single site of metastasis after curative treatment may be candidates for adjuvant prophylactic strategies. Here we investigated risk factors for metachronous isolated PM in patients who were treated in the CRITICS trial (NCT00407186). Univariable and multivariable analyses on both metachronous isolated PM and ‘other events’, i.e., (concurrent) distant metastasis, locoregional recurrence or death, were performed using a competing risk model and summarized by cumulative incidences. Isolated PM occurred in 64 of the 606 (11%) included patients. Diffuse or mixed histological subtype, ypT4 tumor stage and LNhigh (ypN3 lymph node stage or a lymph node ratio >20%) were independent risk factors for isolated PM in both univariable and multivariable analyses. Likewise, LNhigh was an independent risk factor for ‘other events’. Patients with tumors who were positive for all three independent risk factors had the highest two-year cumulative incidence of 43% for isolated PM development. In conclusion, diffuse or mixed histological subtype, ypT4 and LNhigh were identified as independent risk factors for isolated PM in patients treated with preoperative chemotherapy followed by surgical resection. The combination of these factors may identify a subgroup that may benefit from PM-preventing treatment strategies

White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer

Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer

Quality of Life Is Associated With Survival in Patients With Gastric Cancer:Results From the Randomized CRITICS Trial

Background: The evaluation of health-related quality of life (HRQoL) in clinical trials has become increasingly important because it addresses the impact of treatment from the patient’s perspective. The primary aim of this study was to investigate the effect of postoperative chemotherapy and chemoradiotherapy (CRT) after neoadjuvant chemotherapy and surgery with extended (D2) lymphadenectomy on HRQoL in the CRITICS trial. Second, we investigated the potential prognostic value of pretreatment HRQoL on event-free survival (EFS) and overall survival (OS). Patients and Methods: Patients in the CRITICS trial were asked to complete HRQoL questionnaires (EORTC Quality-of-Life Questionnaire-Core 30 and Quality-of-Life Questionnaire gastric cancer–specific module) at baseline, after preoperative chemotherapy, after surgery, after postoperative chemotherapy or CRT, and at 12 months follow-up. Patients with at least 1 evaluable questionnaire (645 of 788 randomized patients) were included in the HRQoL analyses. The predefined endpoints included dysphagia, pain, physical functioning, fatigue, and Quality-of-Life Questionnaire-Core 30 summary score. Linear mixed modeling was used to assess differences over time and at each time point. Associations of baseline HRQoL with EFS and OS were investigated using multivariate Cox proportional hazards analyses. Results: At completion of postoperative chemo(radio)therapy, the chemotherapy group had significantly better physical functioning (P=.02; Cohen’s effect size = 0.42) and less dysphagia (P=.01; Cohen’s effect size = 0.38) compared with the CRT group. At baseline, worse social functioning (hazard ratio [HR], 2.20; 95% CI, 1.36–3.55; P=.001), nausea (HR, 1.89; 95% CI, 1.39–2.56; P&lt;.001), worse WHO performance status (HR, 1.55; 95% CI, 1.13–2.13; P=.007), and histologic subtype (diffuse vs intestinal: HR, 1.94; 95% CI, 1.42–2.67; P&lt;.001; mixed vs intestinal: HR, 2.35; 95% CI, 1.35–4.12; P=.003) were significantly associated with worse EFS and OS. Conclusions: In the CRITICS trial, the chemotherapy group had significantly better physical functioning and less dysphagia after postoperative treatment. HRQoL scales at baseline were significantly associated with EFS and OS