scholarly journals Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer: a national cohort study

2019 ◽  
Vol 33 (5) ◽  
Author(s):  
F Klevebro ◽  
K Nilsson ◽  
M Lindblad ◽  
S Ekman ◽  
J Johansson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cohort Study ◽  
Gastroesophageal Junction ◽  
Neoadjuvant Chemoradiotherapy ◽  
Population Based ◽  
R0 Resection ◽  
Time Interval ◽  
Histological Response ◽  
Time To Surgery ◽  
Prolonged Time

SUMMARY The optimal time interval from neoadjuvant therapy to surgery in the treatment of esophageal cancer is not known. The aim of this study was to investigate if a prolonged interval between completed neoadjuvant chemoradiotherapy and surgery was associated with improved histological response rates and survival in a population-based national register cohort. The population-based cohort study included patients treated with neoadjuvant chemoradiotherapy and esophagectomy due to cancer in the esophagus or gastroesophageal junction. Patients were divided into two groups based on the median time from completed neoadjuvant treatment to surgery. The primary outcome was complete histological response. Secondary outcomes were lymph node tumor response, postoperative complications, R0 resection rate, 90-day mortality, and overall survival. In total, 643 patients were included, 344 (54%) patients underwent surgery within 49 days, and 299 (47%) after 50 days or longer. The groups were similar concerning baseline characteristics except for a higher clinical tumor stage (P = 0.009) in the prolonged time to surgery group. There were no significant differences in complete histological response, R0 resection rate, postoperative complications, 90-day mortality, or overall survival. Adjusted odds ratio for ypT0 in the prolonged time to surgery group was 0.99 (95% confidence interval: 0.64–1.53). Complete histological response in the primary tumor (ypT0) was associated with significantly higher overall survival: adjusted hazard ratio: 0.55 (95% CI 0.41–0.76). If lymph node metastases were present in these patients, the survival was, however, significantly lower: adjusted hazard ratio for ypT0N1: 2.30 (95% CI 1.21–4.35). In this prospectively collected, nationwide cohort study of esophageal and junctional type 1 and 2 cancer patients, there were no associations between time to surgery and histological complete response, postoperative outcomes, or overall survival. The results suggest that it is safe for patients to postpone surgery at least 7 to 10 weeks after completed chemoradiotherapy, but no evidence was seen in favor of recommending a prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. A definitive answer to this question requires a randomized controlled trial of standard vs. prolonged time to surgery.

O122 INTERVAL DISTANT METASTASES DURING OR AFTER NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL OR GASTROESOPHAGEAL JUNCTION CANCER: A NATION-WIDE POPULATION-BASED COHORT STUDY

2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
Tiuri E Kroese ◽  
Willemieke P Dijksterhuis ◽  
Peter S N van Rossum ◽  
Rob H A Verhoeven ◽  
Stella Mook ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Supportive Care ◽  
Gastroesophageal Junction ◽  
Neoadjuvant Chemoradiotherapy ◽  
Distant Metastases ◽  
Best Supportive Care ◽  
Population Based ◽  
Signet Ring Cell ◽  
Time Interval

Abstract Aim A certain proportion of esophageal or gastro-esophageal junction cancer patients develop interval distant metastases during neoadjuvant chemoradiotherapy (nCRT) or in the time interval after nCRT to planned surgery. The aims of this study were to assess the post-detection survival rates and prognostic factors affecting post-detection survival in patients with interval distant metastases. Background & Methods Esophageal and gastro-esophageal junction cancer patients who underwent nCRT and in whom distant metastases were detected during nCRT, after nCRT in the time interval to surgery or at the time of planned surgery, between 2010 and 2016, were included in this nation-wide population-based cohort study. The primary outcome measure was post-detection overall survival. Prognostic factors (including management) affecting the post-detection overall survival were studied using multivariable Cox proportional hazard models. Results A total of 150 patients were included in this study. The median post-detection overall survival was 6.1 months (95% confidence interval [CI] 5.1–7.7). Multivariable analysis identified signet ring cell carcinoma morphology (hazard ratio [HR] 2.88, 95%CI 1.35-6.13; p=0.021), poor tumor differentiation (HR 2.70, 95%CI 1.60-4.57; p<0.001), and palliative anti-tumor treatment as opposed to best supportive care (HR 0.38, 95%CI 0.23-0.61; p<0.001) as independent prognostic factors associated with post-detection survival. An observed survival advantage in a small selected group of 11 patients who received localized treatment with curative intent (metastasectomy and/or stereotactic body radiotherapy) did not reach statistical significance as compared to best supportive care (HR 0.62, 95% CI 0.26-1.43; p=0.263). Patient characteristics including WHO performance score, age, number of comorbidities, and characteristics of interval distant metastases including the location or number of affected locations were not significantly related to overall survival. Conclusion In this study the largest series of patients with esophageal or gastroesophageal junction cancer with interval distant metastases are reported. These patients have a poor prognosis with a median post-detection overall survival of 6.1 months. Prognostic factors independently associated with detrimental survival include poor tumor differentiation and signet ring cell carcinoma morphology. Anti-tumor treatment with palliative intent is associated with improved survival as compared to best supportive care.

511b: Natural History of Intestinal Metaplasia of the Gastroesophageal Junction in Olmsted County, MN: A Population Based Cohort Study

2010 ◽  
Vol 71 (5) ◽  
pp. AB121 ◽  
Author(s):  
Kee Wook Jung ◽  
Kelly T. Dunagan ◽  
Mary Fredericksen ◽  
Debra M. Geno ◽  
Yvonne Romero ◽  
...  
Keyword(s):  
Cohort Study ◽  
Natural History ◽  
Intestinal Metaplasia ◽  
Gastroesophageal Junction ◽  
Population Based ◽  
Olmsted County ◽  
History Of

Association of total neoadjuvant therapy with favorable clinical outcomes in patients with locally advanced esophageal and gastroesophageal junction adenocarcinomas (LA-GEJ CA).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 231-231
Author(s):  
Lauren Jurkowski ◽  
Aditya Varnam Shreenivas ◽  
Sakti Chakrabarti ◽  
Mandana Kamgar ◽  
James P. Thomas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Clinical Outcomes ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Metabolic Imaging ◽  
R0 Resection ◽  
Curative Intent

231 Background: Both peri-operative chemotherapy and neoadjuvant chemoradiation have been shown to improve outcomes in patients (pts) with LA-GEJ CA compared to surgery alone. Rates of post-operative chemotherapy delivery remain suboptimal. Total neo-adjuvant therapy (TNT) in LA-GEJ CA - induction chemotherapy (IC) followed by concurrent chemoradiation (CRT) - may improve systematic delivery of neoadjuvant therapy and result in favorable clinical outcomes. Methods: We retrospectively reviewed medical records of 135 pts with LA-GEJ CA at our institution between 2/2007 and 11/2019; pertinent clinical data were abstracted with Institutional Review Board approval. Patients treated with IC and curative-intent CRT with ≥40 Gy dose of radiation for adenocarcinoma were included in this analysis (N = 59). Doublet or triplet IC regimens utilizing 5-Flurouracil(5-FU), Cisplatin/Oxaliplatin and Docetaxel were commonly administered while combinations of Carboplatin +Paclitaxel or 5-FU + Oxaliplatin were used in CRT. Clinical complete response (CCR) was defined as metabolic imaging and endoscopic biopsies negative for residual malignancy after completion of TNT. Patients were followed from diagnosis to recurrence and overall survival. Survival probabilities were estimated using the Kaplan-Meier method and compared between groups using a log-rank test. Results: Out of 59 evaluable pts, 69% were clinical stage T3, 71% were node positive. 37 pts (63%) underwent surgery, R0 resection rate was 89% (33/37), pathologic complete response (pCR) rate was 19% (7/37). Among the pts who did not undergo surgery, 41% (9/22) opted to forego surgery since they attained a CCR. For the entire cohort, median Disease-Free Survival (mDFS), median Overall Survival (mOS), and 3-yr OS were 2.4 yrs, 4.7 yrs, and 67% respectively. Pts who did not undergo surgery had a mDFS, mOS, and 3-yr OS of 1.5 yrs, 4.2 yrs, and 59% respectively. Median DFS, mOS, and 3-yr OS of patients who underwent surgery were 3.5 yrs, 5.8 yrs and 72% respectively. Patients who achieved a CCR and opted to forego surgery (N = 9) had a 3 -yr DFS of 42% vs 83% for pts (N = 7) who demonstrated a pCR after curative intent tri-modality therapy. (P = 0.0099) Interestingly, the same group that achieved CCR and opted out of surgery had 3yr OS of 89% vs 83% of those who demonstrated a pCR (p = 0.0042). Conclusions: TNT for pts with LA-GEJ CA is associated with high rates of R0 resection as well as excellent DFS and OS compared to historical controls, warranting prospective evaluation. The remarkable DFS and OS in patients who opted to forego surgery due to achieving CCR is reflective of the local and systemic control rendered by this approach. Careful characterization and close longitudinal follow-up of patients who achieve CCR may help identify a subgroup of LA-GEJ CA pts who may benefit from surgery sparing approaches.

scholarly journals Preadmission antidepressant use and bladder cancer: a population-based cohort study of stage at diagnosis, time to surgery, and surgical outcomes

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Ellen Hollands Steffensen ◽  
Clint Cary ◽  
Jørgen Bjerggaard Jensen ◽  
Heidi Larsson ◽  
Michael Weiner ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cohort Study ◽  
Surgical Outcomes ◽  
Population Based ◽  
Stage At Diagnosis ◽  
Time To Surgery ◽  
Antidepressant Use

Autoimmune Cytopenia in Chronic Lymphocytic Leukemia: Effect on Outcome and Survival, a Population Based Analysis in British Columbia, Canada

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1945-1945 ◽  
Author(s):  
Alaa A Alzaki ◽  
Alina S Gerrie ◽  
Tanya L. Gillan ◽  
Steven Huang ◽  
Miriam Ahmed ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Population Based ◽  
Lymphocytic Leukemia ◽  
Time Interval ◽  
Poor Prognostic Factor ◽  
Significant Difference ◽  
Positive Direct ◽  
Time To First Treatment

Abstract Background: Among Chronic Lymphocytic Leukemia (CLL) patients (pts), 4-10% are diagnosed with autoimmune cytopenias (AC) at some point during the course of their disease. This is less common than cytopenias related to bone marrow infiltration (10-20%). Infiltrative cytopenias (IC) are clearly a poor prognostic factor. However, the effect of AC on survival and prognosis of CLL pts remains understudied. Objectives: To determine the prevalence of AC and IC among CLL pts and their effect on overall survival (OS) and time to first treatment (TTFT) compared to patients without cytopenia. Furthermore, the effect of different treatment modalities including chemotherapy and chemo-immunotherapy on the disease course was evaluated in patients with AC. Methods: A population-based retrospective analysis through an electronic search of pts within the Providence Health Care CLL database between 1978 and 2013 was carried out. The diagnostic criteria for autoimmune hemolytic anemia (AIHA) were positive direct antiglobulin test and laboratory evidence of hemolysis, for immune thrombocytopenia (ITP) the exclusion of other etiologies of thrombocytopenia and for pure red cell aplasia (PRCA) anemia with low reticulocyte count and bone marrow evidence of decreased erythropoiesis. Infiltrative cytopenia diagnosis was confirmed by bone marrow biopsy based on lymphocyte percentage and cellularity. Anemia was defined as hemoglobin <100 g/L. Thrombocytopenia was defined as platelets <100 x 109/L. Baseline features of pts with AC and IC were compared using Chi-squared analysis for categorical and the Kruskal-Wallis test for continuous variables. Overall survival was calculated from the date of initial treatment to the date of death from any cause. Time to first treatment (TTFT) was defined as the time interval between the date of diagnosis and date of first CLL treatment. Survival analysis was performed by the Kaplan–Meier method using IBM SPSS statistics for windows. Results: Among 754 pts with CLL, 80 (10.6%) developed cytopenias (anemia and thrombocytopenia). Of those, 50 (6.6%) had IC and 30 (4%) had AC. There was no significant difference between the 2 groups in terms of age, gender, hemoglobin, platelets, LDH, WBC and lymphocyte count at diagnosis. The time to development of cytopenias for the IC and AC groups was similar with median of 3 and 4 years (yrs) from diagnosis, respectively. Within the AC group 16 pts had AIHA, 8 had ITP, 5 had both (Evan's Syndrome) and 1 had PRCA. The median OS was 12.2 yrs (5.9–18.3) and 13 yrs (1.6-24.3) for IC and AC, respectively (p=0.260). However, when compared to CLL pts without cytopenias (median not reached), the AC group had worse OS (p< 0.005) (Fig 1). For the IC and AC groups, the median TTFT was 6.5 yrs (4.5-8.5) and 8.2 yrs (4.1–12.3), respectively (p=0.191). For the CLL pts without cytopenias TTFT was 8.1 yrs (2-12.2), similar to the AC group (p=0.88) (Fig 2). For AC pts, the OS was not significantly different based on treatment received: alkylator based therapy vs. chemo-immunotherapy (p= 0.885). The effect of concomitant hypo-gammaglobulinemia on OS and treatment outcome was studied.Of the 30 pts with AC, 26 had a serum protein electrophoresis done. Of those, 10 (38.5%) had normal results and 16 (61.5%) had low gammaglobulin levels (IgG< 6 g/L); the mean OS was 18.1 yrs and 15.7 yrs respectively (median not reached), (P=0.433). Conclusion: The prognosis of pts with autoimmune and infiltrative cytopenias was similar.However, CLL pts with AC had worse OS compared to those without cytopenias. There was no significant difference in TTFT between AC and IC or when compared to CLL pts without cytopenias. For the AC group, neither treatment with chemotherapy vs. chemo-immunotherapy nor having concomitant hypo-gammaglobulinemia had an effect on outcome. To our knowledge, there are limited population based studies addressing the importance of determining the etiology of cytopenias in CLL pts and the effect of AC on survival. CLL immune complications need to be studied further especially in the context of novel agents and their effects on immune reconstitution. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals BJS.03Markov Decision Analysis of Treatment Pathways for Resectable Malignancy of the Oesophagus or Gastrooesophageal Junction

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Alison Bradley ◽  
Leo Brown
Keyword(s):  
Sensitivity Analysis ◽  
Overall Survival ◽  
Monte Carlo ◽  
Decision Analysis ◽  
Randomised Controlled Trials ◽  
Gastroesophageal Junction ◽  
Neoadjuvant Chemoradiotherapy ◽  
Controlled Trials ◽  
Treatment Pathways ◽  
Randomised Controlled

Abstract Aims To perform decision-analysis of treatment options for resectable malignancy of the oesophagus or gastroesophageal junction including: surgery alone, neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy and surgery followed by adjuvant therapy based on current highest-level evidence. Methods A Markov decision analysis model in an advanced decision-tree format was constructedand populated with data from existing randomised controlled trials. Markov model transition probabilities were based on weighted pooled estimates of proportions from included studies, calculated using Freeman-Tukey arcsine square root transformation under random effects model to account for heterogeneity.Each Markov cycle equated with one month and Markov states within the model included: alive without disease, alive with disease and dead. Extensive deterministic and Monte Carlo probabilistic sensitivity analysis was performed to test all parameters contained within the model. Results 23 randomised controlled trials were included. Intention-to-treat analysis of the treatment pathways showed that neoadjuvant chemoradiotherapy was the superior pathway with an overall survival time of 50.52 months (42.26 QALMs). Monte Carlo sensitivity analysis run over 10000 iterations showed that neoadjuvant chemoradiotherapy was selected as the superior treatment pathway at a frequency of 93.21% followed by surgery followed by adjuvant therapy with a frequency of 6.79%. Subgroup analysis of only squamous cell carcinomas demonstrated that neoadjuvant chemoradiotherapy was the superior pathway with an overall survival time of 62.67 months (55.22 QALMs). Conclusions Based on current best available evidence this decision analysis supports neoadjuvant chemoradiotherapy as the treatment strategy of choice for resectable malignancy of the oesophagus or gastroesophageal junction.

scholarly journals Factors Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer: The Experience of a Single Institution with 269 Patients (STONE-01)

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6074
Author(s):  
Michele Fiore ◽  
Pasquale Trecca ◽  
Luca E. Trodella ◽  
Roberto Coppola ◽  
Marco Caricato ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Female Gender ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Time Interval ◽  
Interval Time ◽  
Time To Surgery

Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. Results: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27–0.93 and p = 0.003; OR: 0.42, CI: 0.24–0.75, respectively). Conclusions: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time.

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