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Background: Biomarkers to predict the recurrence risk are required to optimize perioperative treatment. Adjuvant chemotherapy for patients with human epidermal growth factor 2-positive (HER2-positive) early breast cancer is decided by pathological responses of neoadjuvant chemotherapy (NAC). However, whether pathological responses are appropriate biomarkers is unclear. Currently, there are several studies using minimal residual disease (MRD) as a predictor of prognosis in solid tumors. However, there is no standard method for detecting MRD. Objectives: This study aimed at prospectively evaluating the relationship between MRD detection and recurrence in Asian patients with HER2-positive early breast cancer. Design: Prospective, observational, single-group, and exploratory. This study will include 60 patients from 2 institutions in Japan and the Philippines. The invasive disease-free survival (IDFS) rates of the MRD-positive and MRD-negative groups are compared in patients with HER2-positive early breast cancer who undergo surgery after receiving NAC. Methods and analysis: Circulating tumor DNA (ctDNA) levels of patients will be evaluated 6 times: before NAC, after NAC, after surgery, and annually after surgery for 3 years. We will analyze the genetic profile of blood and tissue samples using the Todai OncoPanel (TOP) and the methylation level of DNA. The primary endpoint is IDFS. Secondary endpoints include overall survival (OS) and disease-free survival (DFS). Patient enrollment began in June 2022, and new participants are still being recruited. Ethics: This study has been approved by the National Cancer Center Hospital Certified Review Board in March 2022 and has been approved by the Research Ethics Board of the participating center. Discussion: Our findings will contribute to determining whether MRD detection using TOP is useful for predicting the recurrence of HER2-positive early breast cancer. If this is proven, MRD detected by TOP could be used in the future as a biomarker to assist in the de-/escalation of treatment strategies in the next interventional trial, thereby avoiding overtreatment in patients at low risk, and in the addition of intensive treatment modalities for those in patients at high risk. [ABSTRACT FROM AUTHOR]

Little is known about the toxicity of various therapeutics for cancer over time because randomized controlled clinical trials that compare several treatments are limited. In this study, we focused on the toxicities most frequently discussed, which are investigations (lab abnormalities), gastrointestinal disorders, skin and subcutaneous tissue disorders, and cardiac disorders, and compared their longitudinal toxicity data among four types of cancer therapeutics. In total, 28,235 patients who were enrolled into 772 early‐phase trials to evaluate the monotherapies of cytotoxic drugs, molecularly targeted agents, immunomodulatory drugs, or cancer vaccines were evaluated. For each toxicity, we compared their grade prevalence, mean grade at each cycle, and time to toxicity occurrence and identified the potential underlying similarities and differences of longitudinal toxicities among the four cancer treatment types. Our results will further help in understanding the profile of cancer therapeutic toxicities and their impact on oncology treatment in practice. [ABSTRACT FROM AUTHOR]

Objective: The goal of surveillance after therapy of localized esophageal cancer (LEC) is to identify actionable relapses amenable to salvage; however, the current surveillance algorithms are not optimized. We report on a large cohort of LEC patients with actionable locoregional relapses (LRRs). Methods: Between 2000 and 2013, 127 (denominator = 752) patients with actionable LRR were identified. Histologic/cytologic confirmation was the gold standard. All surveillance tools (imaging, endoscopy, fine needle aspiration) were assessed. Results: Most patients were men (89%), had adenocarcinoma (79%), and had no new symptoms (72%) when diagnosed with LRR. In trimodality patients, endoscopic confirmation of positron emission tomography-computed tomography-suspected LRR occurred in only 44%, and 56% required additional tools (e.g., fine needle aspiration). Alternatively, in bimodality patients, endoscopy confirmed LRRs in 81%. Trimodality patients had a higher risk of subsequent LRR/distant metastases after the first LRR than the bimodality patients (p = 0.03). In all patients, 78% of the subsequent relapses were distant. For patients who were salvaged, survival was significantly prolonged (50.6 vs. 25.1 months, p < 0.01). Conclusions: Patients live longer after successful salvage of the LRR than if salvage is not possible. After LRR, patients have a high risk of subsequent distant metastasis and whether the second relapse is local or distant, survival is uniformly poor. [ABSTRACT FROM AUTHOR]

Background: Nearly 50% of gastric cancer patients are diagnosed with advanced gastric cancer (AGC). Therapy is palliative but results in ill effects. The median overall survival (OS) of AGC patients is often <12 months. It is unclear if the early initiation of therapy in all AGC patients is beneficial. Methods: A retrospective analysis of AGC patients in our database was carried out. The patients were divided into two groups: asymptomatic or symptomatic. We sought to assess whether the delay of systemic therapy was harmful in asymptomatic patients. Results: A total of 135 patients were analyzed. Most patients were symptomatic (68%), males (67%), and had low ECOG scores (0-1; 85%). In univariate analyses, ECOG performance status 0 (p = 0.005), delayed initiation of therapy (p = 0.03), and lack of symptoms (p = 0.03) were associated with a longer OS. The multivariate model for OS identified only ECOG performance status as an independent prognosticator of longer OS (p = 0.02). Asymptomatic patients who had delayed (≥4 weeks) systemic therapy had an OS rate of 77% at 1 year compared to 58% for patients treated within 4 weeks (p = 0.47). Conclusion: Symptomatic AGC patients had a poor outcome compared to asymptomatic AGC patients. Treatment delay in asymptomatic patients had no detrimental effect on OS, suggesting that the timing of therapy can be based on patient selection. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: We have limited knowledge of the geographic distribution of resistant esophageal adenocarcinoma (EAC) in resected specimens, but its clinical importance can be enormous. Method: We selected patients with baseline stage III EAC who had had chemoradiation followed by surgery and had residual EAC (resistant cases only). Outcomes were correlated with various endpoints (percentage of resistant EAC and anatomic distribution). Results: A total of 100 clinical stage III patients were studied; 90% had an R0 resection, and 99% had either moderate or poorly differentiated EAC. Twelve percent had >50% residual cancer, 31% had 11-50% residual cancer, 53% had 1-10% residual cancer, and 3% had positive nodes only. Each compartment was frequently involved: mucosa/submucosa (66%), muscularis propria (76%), and serosa (62%); all compartments were involved in 35% of the cases. Lack of EAC (meaning response) was observed in the mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%). Although the endoscopic biopsies prior to surgery showed no EAC in 79% of the patients, in the surgical specimens, resistant EAC was frequently occurring in the mucosa/submucosa (66%). Conclusion: Contrary to our hypothesis that resistant EAC would be frequent in the nodes, our data show that its distribution is heterogeneous and unpredictable. Most importantly, the postchemoradiation biopsies are misleading, and a decision to delay/avoid surgery based on negative biopsies can be detrimental for the patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aim: Malignant nodes in patients with localized esophageal adenocarcinoma (L-EAC) portend a poor prognosis. We assessed the correlation of the distribution of nodes with the outcome of patients undergoing chemoradiation/surgery (trimodality therapy). Methods: We studied 209 L-EAC patients who had confirmed or suspicious nodes at baseline staging. All patients received trimodality therapy and were grouped according to the nodal geography: above the diaphragm (AD), below the diaphragm (BD), or above and below the diaphragm (ABD). Survival estimates were calculated using the Kaplan-Meier method, and the outcomes of the groups were assessed by the log-rank test. Results: Patients were primarily Caucasian (91%) and male (93%), with a baseline stage III L-EAC (89%). The median follow-up was 2.8 years (range, 0.4-11.7). Of the 209 patients, 35% (n = 73) had AD nodes, 20% (n = 41) had BD nodes, and 45% (n = 95) had ABD nodes. ABD patients had a 5-year overall survival rate of 33%, whereas this rate was 55% in AD patients and 60% in BD patients (p = 0.02). Patients with a higher histology grade were also at a higher risk of relapse and had a poor survival (p < 0.01 for both). Conclusions: L-EAC patients in the ABD group had the worst outcome after trimodality treatment compared to those in the AD or BD group. Novel strategies are needed for ABD patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Patients with localized esophageal and esophagogastric junction cancer (EAC) receive chemoradiation and then surgery (trimodality, TMT) or definitive chemoradiation (bimodality, BMT). Distant metastases (DMs) are common but the details of their distribution and timing in a large cohort have not been described. Methods: 629 patients with localized EAC who had TMT or BMT were analyzed. Standard statistical methods were used to define the end points. Results: The median follow-up time was 37.2 months (interquartile range 17.8-65.0). Of 356 TMT patients, 33% (119) developed DM as their first relapse and of 273 BMT patients, 40% (109) developed DM; 91% (TMT) and 96% (BMT) of the DMs were diagnosed within 2 years of local therapy. The most common sites of DM were: lung, distant nodes, liver, peritoneal cavity, bone, brain and pleura in order of frequency. The median overall survival of TMT patients with DM was 10.2 months (95% CI 7.8-12.7) and that for BMT patients with DM was 7.8 months (95% CI 5.7-9.9). Conclusions: Following TMT or BMT, ≥33% of patients developed DMs and most of these occurred within 2 years (>90%) of local therapy. A clinical model is desirable that associates clinical parameters with a high risk for DM in TMT-eligible patients prior to surgery. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: It is unclear whether patients undergoing trimodality therapy (TMT) should be screened or surveyed for brain metastases. Methods: We retrospectively analyzed esophageal cancer (EC) patients who underwent TMT between the years 2000 and 2010. All were systematically staged and surveyed but none had screening or surveillance brain imaging. Results: The median follow-up time for 518 patients was 29.3 months (range 1-149.2); all patients had adenocarcinoma of the esophagus. Of 188 (36.3%) patients who developed distant metastases, 20 (10.6% of 188 patients or 3.9% of 518 patients) had brain metastases. A higher baseline clinical stage (stage III or IVa) was associated with brain metastases. Most (90%) patients with brain metastases were diagnosed within 24 months of surgery. Sixteen patients had central nervous system symptoms at diagnosis. Twelve (60%) patients had solitary metastasis and 8 (40%) patients had multiple metastases. Although 17 patients received therapy for brain metastases, the median overall survival time of 20 patients was only 10.5 months (95% CI 6.6-14.0). Conclusion: After TMT, 3.9% of EC patients developed brain metastases and their prognosis was poor. Our data suggest that screening and/or surveillance for brain metastases in the EC population undergoing TMT is not warranted. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Trimodality therapy (TMT; chemoradiation plus surgery) has level-1 evidence for survival advantage for TMT-eligible esophagogastric cancer patients. Some patients, however, decline surgery after preoperative chemoradiation. The question of which patient should have esophagectomy and which one should not is unlikely to be answered by a prospective comparison; therefore, we matched the clinical covariates of several patients who had surgery with those who declined surgery (DS). Methods: Between 2002 and 2011, we identified 623 patients in our databases. Of 623 patients, 244 patients had TMT and 61 TMT-eligible patients were in the DS group. Using the propensity-score method, we matched 16 covariates between 36 DS patients and 36 TMT patients. Results: Baseline characteristics between the two groups were balanced (p = NS). The median overall survival times were: 57.9 months (95% CI: 27.7 to not applicable, NA) for the DS group and 50.8 months (95% CI: 30.7 to NA) for the TMT group (p = 0.28). The median relapse-free survival times were: 18.5 (95% CI: 11.5-30.4) for the DS group and 26.5 months (95% CI: 15.5-NA) for the TMT group (p = 0.45). Eleven (31%) of 36 patients in the DS group had salvage surgery. Conclusions: Our results are intriguing but skewed by the patients who had salvage surgery in the DS group. Until highly reliable predictive models are developed for esophageal preservation, TMT must be encouraged for all TMT-eligible gastroesophageal cancer patients. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]