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Background This study aimed to analyze the effect of preoperative chemoradiation on the adequacy of lymph node dissection. Methods Patients with esophageal cancer treated with esophagectomy by the same surgeon between 2004 and 2011 were reviewed. Specimens were examined by the same pathologist. Patients were grouped into two depending on the type of treatment received. Results Forty-seven patients with curative esophagectomy were included in the study. Twenty patients had preoperative chemoradiation followed by surgery and 27 had surgery alone. Open and hybrid esophagectomy approaches were used. The average number of lymph nodes dissected was 16 ± 10 (1–39). There was a significant decrease in the number of lymph nodes examined in patients with preoperative chemoradiotherapy in comparison to surgery alone ( p  = 0.001). Median length of stay was 12 days. R0 resection rate was 96 %. The median survival was 36.3 months, with a 42 % 5-year survival. Seven patients (25 %) had complete pathologic response following chemoradiation. No significant difference was recorded in terms of disease recurrence ( p  = 0.3). While morbidity was higher in the preoperative therapy group with 30 day mortality of 10 %, type of surgical approach does not seem to influence the number of lymph nodes dissected ( p  = 0.7). Conclusions Preoperative chemoradiation decreases the number of harvested lymph nodes following esophagectomy regardless of the surgical technique used. The optimum number of lymph nodes currently recommended to be dissected for accurate nodal staging and survival needs revision in this group of patients.

Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands. Here, we provide an overview of the outcomes and consensus statements that originated from this meeting. Consensus (≥80% agreement) was reached on a total of seven statements: (1) TRS is important because it provides information about the effect of neoadjuvant treatment that is not provided by other histopathology-based descriptors. (2) TRS for resected PDAC following neoadjuvant therapy should assess residual (viable) tumor burden instead of tumor regression. (3) The CAP scoring system is considered the most adequate scoring system to date because it is based on the presence and amount of residual cancer cells instead of tumor regression. (4) The defining criteria of the categories in the CAP scoring system should be improved by replacing subjective terms including “minimal” or “extensive” with objective criteria to evaluate the extent of viable tumor. (5) The improved, consensus-based system should be validated retrospectively and prospectively. (6) Prospective studies should determine the extent of tissue sampling that is required to ensure adequate assessment of the residual cancer burden, taking into account the heterogeneity of tumor response. (7) In future scientific publications, the extent of tissue sampling should be described in detail in the “Materials and methods” section.

Abstract Whether preoperative chemoradiotherapy (CRT) or perioperative chemotherapy is superior for localized esophageal or gastro-esophageal junction (GEJ) cancers has been a topic of long-standing debate. For years, standard of care in the United States for localized esophageal or GEJ adenocarcinoma (EAC) has been physician’s choice between the 2 strategies. More recently, adjuvant immunotherapy has also been introduced into the treatment approach for those who received neoadjuvant CRT. While preoperative radiation remains an important option for patients with esophageal squamous cell carcinomas, the ESOPEC trial presented in 2024 suggested that perioperative chemotherapy is superior to preoperative CRT in EAC. In addition, the results of the TOPGEAR trial presented in 2024 showed that adding CRT to perioperative chemotherapy did not lead to improved outcomes. This has led to a shift in practice among oncologists. However, there are various complexities and factors to consider when interpreting these studies. In this review, we outline both trials and what their findings may mean for the future of preoperative CRT in EAC. Ultimately, until more data are available that incorporate novel agents such as immunotherapy, these studies indicate that we should defer the routine inclusion of radiation in preoperative treatment for EAC.

Background The survival benefit of neoadjuvant therapy in resectable carcinoma esophagus has been elucidated. We performed a meta-analysis in light of new studies and long-term results of past trials. The search strategy was refined to include only “neoadjuvant” so that any bias by adjuvant treatment is eliminated. Methods A detailed search of MEDLINE, Embase, and Cochrane Library was done. Only published randomized English language trials were included. Data were categorized as neoadjuvant concurrent chemoradiation (NACRT), neoadjuvant chemotherapy (NACT), neoadjuvant radiotherapy (NART), and neoadjuvant sequential chemoradiotherapy (SCRT). Meta-analysis was done using odds ratio (OR) and 95% CI using fixed/random effects model. Heterogeneity was tested by chi-square and I 2 test. Z probability calculated significant difference across subgroups. Outcomes assessed were overall survival (OS) and disease-free survival (DFS) at 3 and 5 years, respectively, mortality (30/90 day) and failures (local/systemic). Results Twenty-five randomized trials involving 5272 patients were included for quantitative analysis. NACRT was evaluated in 12 studies (2676 patients). Superior 3-year OS (OR = 0.68 CI 0.52–0.90, p = 0.007), 3-year DFS (OR = 0.55 CI 0.45–0.68, p = 0.00001), and 5-year DFS (OR = 0.59 CI 0.47–0.74, p = 0.00001), with lower failures (OR = 0.52 CI 0.37–0.73, p = 0.0001), were seen in favor of NACRT at the cost of increased perioperative mortality (OR = 1.79 CI 1.15–2.80, p = .01). However, 5-year OS (OR = 0.78 CI 0.60–0.1.01, p = 0.06) was not found to be significantly superior. NACT, NART, and SCRT were not found to have any benefit over surgery alone. Conclusion This meta-analysis presents strong evidence favoring NACRT over upfront surgery. It also shows no survival advantage of neoadjuvant chemotherapy.

Background Duke pancreatic mono-clonal antigen type 2 (DUPAN-II) is a famous tumour maker for pancreatic cancer (PC) as well as carbohydrate antigen 19–9 (CA19-9). We evaluated the clinical implications of DUPAN-II levels as a biological indicator for PC during preoperative chemoradiation therapy (CRT). Methods This retrospective analysis included data from 221 consecutive patients with resectable and borderline resectable PC at diagnosis who underwent preoperative CRT between 2008 and 2017. We focused on 73 patients with elevated pre-CRT DUPAN-II levels (> 230 U/mL; more than 1.5 times the cut-off value for the normal range). Pre- and post-CRT DUPAN-II levels and the changes in DUPAN-II ratio were measured. Results Univariate analysis identified normalisation of DUPAN-II levels after CRT as a significant prognostic factor (hazard ratio [HR] = 2.06, confidence interval [CI] = 1.03–4.24, p  = 0.042). Total normalisation ratio was 49% ( n  = 36). Overall survival (OS) in patients with normalised DUPAN-II levels was significantly longer than that in 73 patients with elevated levels (5-year survival, 55% vs. 21%, p  = 0.032) and in 60 patients who underwent tumour resection (5-year survival, 59% vs. 26%, p  = 0.039). Conclusion Normalisation of DUPAN-II levels during preoperative CRT was a significant prognostic factor and could be an indicator to monitor treatment efficacy and predict patient prognosis.

Several therapeutic regimens, including neoadjuvant chemoradiation therapy (NACRT), have been reported to serve as anticancer immune effectors. However, there remain insufficient data regarding the immune response after NACRT in pancreatic ductal adenocarcinoma (PDAC) patients. Data from 40 PDAC patients that underwent surgical resection after NACRT (NACRT group) and 30 PDAC patients that underwent upfront surgery (US group) were analyzed to examine alterations in immune cell counts/distribution using a multiplexed fluorescent immunohistochemistry system. All immune cells were more abundant in the cancer stroma than in the cancer cell nest regardless of preoperative therapy. Although the stromal counts of CD4+ T cells, CD20+ B cells, and Foxp3+ T cells in the NACRT group were drastically decreased in comparison with those of the US group, counts of these cell types in the cancer cell nest were not significantly different between the two groups. In contrast, CD204+ macrophage counts in the cancer stroma were similar between the NACRT and US groups, while those in the cancer cell nests were significantly reduced in the NACRT group. Following multivariate analysis, only a high CD204+ macrophage count in the cancer cell nest remained an independent predictor of shorter relapse‐free survival (odds ratio = 2.37; P = .033). NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT. This study sought to investigate any potential alterations in the distribution and clinical impact of immune cells in patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemoradiation therapy (NACRT). The present analysis revealed that NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT.

Background: The purpose of this study was to evaluate the long-term outcomes of patients with locally advanced gastric adenocarcinoma (LAGC) intended to receive induction chemotherapy, chemoradiation and surgery and to develop an algorithm to estimate the individual risk of relapse in a population-based setting. Methods: Patients with LAGC (cT3-4 and/or N+) were retrospectively evaluated. A pathological response was graded according to the Becker criteria. The nodal regression grade was assessed by a 4-point scale (A–D). A comprehensive analysis of 155 individual patient variables was performed, and logistic regression (LR) was utilized to develop a predictive model for relapse risk. Results: From 2010 to 2024, 48 patients were analyzed. After a median follow-up of 49 months (range, 12–212), the 5-year actuarial PFS and OS rates were 44% and 48%, respectively. Four variables were identified as the most relevant features for training the LR model. Scores for the model accuracy, sensitivity and specificity (mean +/− sd) were 0.79 +/− 0.12, 0.74 +/− 0.221 and 0.88 +/− 0.14, respectively. For a validation dataset, the figures were 0.78, 0.88 and 0.73, respectively. Conclusions: This neoadjuvant strategy seems to correlate with a favorable long-term outcome in a subset of intestinal-type LAGA patients who achieve ypN0 features.

Background We assessed whether the time interval between neoadjuvant therapy and surgery affects the operative and postoperative morbidity and mortality, the pathologic complete response (pCR) rate, and disease recurrence in locally advanced rectal cancer. Methods One–hundred and thirty-two patients with locally advanced low– and mid–rectal cancer underwent neoadjuvant chemoradiation followed by radical resection (October 2000 to December 2006). Data on the neoadjuvant regime, neoadjuvant–surgery interval, final pathology, type of operation, operative time, intraoperative blood transfusions, postoperative complications, length of hospital stay, disease recurrence, and mortality were reviewed. The patients were divided into two groups according to the neoadjuvant–surgery interval: ≤7 weeks (group A, n = 48), and >7 weeks (group B, n = 84). Results The groups were demographically comparable except for the group A patients being younger at operation. The median interval between chemoradiation and surgery was 56 days (range 13–173 days). Thirty-seven patients (28%) had a pCR and near pCR. Fifty three patients (40%) had complications. There was no in-hospital mortality. Surgery type, operative time, number of intraoperative blood transfusions, postoperative complications, and length of hospitalization were not influenced by the interval length. The pCR and near pCR rates were higher with longer interval: 17% in group A, 35% in group B ( P = 0.03). Patients operated at an interval >7 weeks had significantly better disease–free survival ( P = 0.05). Conclusions A neoadjuvant–surgery interval >7 weeks was associated with higher rates of pCR and near pCR, decreased recurrence and improved disease–free survival.

Purpose Distant metastasis (DM) and neoadjuvant treatment response prediction remain critical challenges in the management of locally advanced rectal cancer (LARC). The aim of this study was to investigate the clinical relevance of viable circulating tumor cells (CTCs) for DM or response in patients with LARC in a neoadjuvant setting. Methods The detection of viable CTCs at different stages of treatment was planned for consecutive patients from a prospective trial. The Kaplan–Meier method, Cox proportional hazards model, and logistic regression model were utilized to analyze factors associated with DM or pathological complete response (pCR) and clinical complete response (cCR). Results Between December 2016 and July 2018, peripheral blood samples from 83 patients were collected before any treatment (median follow‐up time, 49.3 months). CTCs were present in 76 of 83 patients (91.6%) at baseline, and more than three CTCs detected in the blood sample was considered high risk. Only the CTC risk group was significantly associated with 3‐year metastasis‐free survival (MFS) (high risk vs. low risk, 57.1% (95% CI, 41.6–72.6) vs. 78.3% (95% CI, 65.8–90.8), p = 0.018, log‐rank test). When all the important variables were entered into the Cox model, the CTC risk group remained the only significant independent factor for DM (hazard ratio (HR), 2.74; 95% CI, 1.17–6.45, p = 0.021). The pCR and continuous cCR rates were higher in patients with a decreased number of CTCs of more than one after radiotherapy (HR, 4.00; 95% CI, 1.09–14.71, P = 0.037). Conclusions The dynamic detection of viable CTCs may strengthen pretreatment risk assessment and postradiotherapy decision making for LARC. This observation requires further validation in a prospective study.

BackgroundThe benefit of preoperative chemoradiation (CXRT) over preoperative chemotherapy alone (“chemotherapy” hereafter) is unknown. By analyzing the National Cancer Database (NCDB), we investigated whether preoperative CXRT improves the incidence of primary tumor pathologic complete response (ypT0) and overall survival (OS) compared with preoperative chemotherapy in patients with gastric cancer.MethodsPatients with non-metastatic gastric adenocarcinoma who underwent CXRT or chemotherapy followed by gastrectomy were included. Propensity score matching with a ratio of 1:1 was implemented to reduce selection bias. A conditional logistic regression model was used to compare incidences of ypT0 between groups, and Cox proportional hazards model was used to compare OS.ResultsWe identified 8464 patients. Median patient age was 63 years; 76% were male and 79% were white. ypT0 was observed in 16.1% of patients in the CXRT group and 6.6% in the chemotherapy group (p < 0.001). After propensity score matching, a total of 2408 patients were matched. CXRT was associated with a higher incidence of ypT0 (OR 2.28, 95% CI 1.76–2.95; p < 0.0001) and higher frequency of R0 resection (92 vs. 86%; p < 0.001). However, CXRT was not associated with longer OS (HR 1.03, 95% CI 0.92–1.15; p = 0.63). Safety profiles (30-day mortality, 30-day readmission, and length of hospital stay) were equivalent between groups.ConclusionsIn this study of gastric cancer patients from the NCDB, CXRT was associated with a higher incidence of ypT0 and R0 resection compared with chemotherapy, although it was not associated with a longer OS.