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Patterns and predictors of failure following tri-modality therapy for locally advanced esophageal cancer.

ABSTRACT: BACKGROUND:Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy. MATERIALS AND METHODS:We retrospectively reviewed patients who underwent chemoradiation followed by esophagectomy between 2006 and 2011 at two NCI-designated cancer centers. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher's exact test, non-parametric Wilcoxon rank-sum test, and multiple logistic regression. Kaplan-Meier curves were generated for relapse-free survival (RFS) and overall survival. RESULTS:A total of 132 patients met the inclusion criteria with a median age of 62 (range 36-80) and median follow-up of 28 months (range 4-128). There were a total of six (4.5%) local, 13 (10%) regional nodal, and 32 (23.5%) distant failures. Local failure was correlated with fewer lymph nodes (LN) assessed (p?=?0.01) and close/positive margins (p?13 LN evaluated (p?=?0.003). Distant recurrence was correlated with higher pathologic nodal stage (p?

SUBMITTER: Shaikh T

PROVIDER: S-EPMC6854665 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Patterns and predictors of failure following tri-modality therapy for locally advanced esophageal cancer.

Shaikh Talha T Zaki Mark A MA Dominello Michael M MM Handorf Elizabeth E Konski Andre A AA Cohen Steven J SJ Shields Anthony A Philip Philip P Meyer Joshua E JE

Acta oncologica (Stockholm, Sweden) 20151119 3

<h4>Background</h4>Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy.<h4>Materials and methods</h4>We retrospectively reviewed patients who underwent chemoradiation followed by esophagectomy between 2006 and 2011 at two NCI-designated cancer centers. First failure sites were categor ...[more]

PMID: 26581671

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Project description:LESSONS LEARNED:There is no presenting parameter that predicts the success of neoadjuvant therapy for pancreatic cancer.Despite the images on scans following neoadjuvant therapy, all patients should be evaluated, because inflammation following radiation therapy (RT) may overstate the extent of tumor and vascular involvement. BACKGROUND:In patients presenting with locally advanced pancreatic adenocarcinoma deemed unresectable by two pancreatic cancer surgeons, we analyzed presenting tumor size, extent of vascular involvement, tumor markers, response to neoadjuvant gemcitabine (G), docetaxel (T), and capecitabine (X) with or without additional chemoradiotherapy with GX on R0 resection rates (?2 mm margins), and survival. METHODS:All patients had baseline magnetic resonance imaging (MRI) and/or computed tomography (CT) scans and endoscopic ultrasound. A baseline positron emission tomography-computed tomography (PET-CT) was performed in 39 patients. The scans were reviewed by two radiologists.GTX (gemcitabine 750 mg/m2 and docetaxel 30 mg/m2 on days 4 and 11 with capecitabine 1,500 mg/m2 days 1-14) was administered on a 3-week schedule for 6 cycles to patients with both arterial and venous-only involvement. Patients in the arterial arm received GX/RT before surgery, and those in the venous arm received GX/RT after R1 resection. Standard-dose RT was delivered by intensity-modulated radiation therapy (IMRT) or conformal fields to 5040 cGy along with capecitabine for 5 days and gemcitabine on day 5 of weeks 1, 2, 4, and 5 of RT, starting with the first full week of RT.A cancer antigen test 19-9 (CA 19-9) was obtained at baseline and days 4 and 11 of each cycle. The rate of change in CA 19-9 was calculated using the formula: (Log10 CA 19-9 time 0)?-?(Log10 CA 19-9 at 9 weeks)/9 weeks. This was derived based on the observation that the fall in CA 19-9 following effective chemotherapy is a second-order function. RESULTS:Of the 34 patients with arterial involvement and 11 with extensive venous involvement who met the eligibility criteria and began GTX, only 5 patients in the arterial arm did not undergo subsequent resection. The remaining 40 patients were included in this analysis of presenting parameters with respect to R0 resection, disease-free survival (DFS), and overall survival (OS). R0 resection was achieved in 28 of 40 patients (70%), and R1 resection in the remaining 12 (30%). The OS after R0 resection was a median 37 months (95% confidence interval [CI]: 29.3-44.7) compared with 29 months (95% CI: 28.5-41.5) for those with R1 resection.Excluding four postoperative deaths, median DFS for the 25 (71%) with R0 resection was 31 months (95% CI: 11.3-51.1), and the median DFS for R1 resection was only 14 months (95% CI: 11.1-17). Eleven of the twenty-eight (39%) patients achieving R0 resection have not relapsed (median?=?45 months, range?=?25-71 months). CONCLUSION:R0 resection, the goal of neoadjuvant treatment, can be achieved in 70% of patients presenting with locally advanced pancreatic cancer. The median DFS was 31 months (95% CI: 11. 3-51.1). No relationship was found with tumor size, degree of vascular involvement, carcinoembryonic antigen test (CEA), CA 19-9, degree of tumor regression on scan, fall in CA 19-9, or SUV on PET scan and subsequent survival.

Project description:Background:There is recent interest in treating locally advanced rectal cancer (LARC) patients with total neoadjuvant therapy (TNT). However, whether TNT is associated with improved overall survival (OS) remains unknown. This study compares outcomes following TNT and following neoadjuvant chemoradiation therapy (nCRT) in patients with LARC, clinically defined cT3/4 or node positive disease, using the National Cancer Database. Methods:LARC patients diagnosed between 2004-2015 were included. TNT was defined as multi-agent chemotherapy given at least 2 months before RT followed by pre-operative chemoradiation therapy and definitive surgery without adjuvant chemotherapy. nCRT was defined as pre-operative RT and chemotherapy started within 2 weeks from each other followed by definitive surgery with or without adjuvant chemotherapy. Kaplan-Meier curve with logrank test and multivariable Cox proportional hazards regression modelling were used to analyse the primary endpoint of overall survival (OS). Multivariable logistic regression modelling was used for secondary outcomes to determine if TNT is associated with pathological complete response (pCR), defined as ypT0N0, and negative circumferential resection margin (CRM). Findings:Data from 372 TNT patients and 707 nCRT patients were analysed after a 2:1 propensity matching with replacement. Kaplan-Meier curve showed that OS with TNT was comparable to that with nCRT (p = 0•16). The 5-year OS rates for TNT and nCRT were 73•6% vs. 78•5% (p = 0•20). Multivariable Cox proportional hazards regression modelling confirmed no difference in OS between TNT and nCRT (HR = 1•21, p = 0•25). With TNT, 16•9% patients achieved pCR, whereas 13•1% patients achieved pCR with nCRT (p = 0•12). TNT was not found to be significantly associated with pCR (OR = 1•36, p = 0•13) or negative CRM (OR = 1•77, p = 0•19) in multivariable logistic regression modelling. Interpretation:With results from current clinical trials pending, our data suggested that TNT and nCRT resulted in similar survival, while TNT led to higher pCR and CRM negative rate, albeit not statistically significant.

Project description:PurposeWhether dosimetric advantages of proton beam therapy (PBT) translate to improved clinical outcomes compared with intensity-modulated radiation therapy (IMRT) remains unclear. This randomized trial compared total toxicity burden (TTB) and progression-free survival (PFS) between these modalities for esophageal cancer.MethodsThis phase IIB trial randomly assigned patients to PBT or IMRT (50.4 Gy), stratified for histology, resectability, induction chemotherapy, and stage. The prespecified coprimary end points were TTB and PFS. TTB, a composite score of 11 distinct adverse events (AEs), including common toxicities as well as postoperative complications (POCs) in operated patients, quantified the extent of AE severity experienced over the duration of 1 year following treatment. The trial was conducted using Bayesian group sequential design with three planned interim analyses at 33%, 50%, and 67% of expected accrual (adjusted for follow-up).ResultsThis trial (commenced April 2012) was approved for closure and analysis upon activation of NRG-GI006 in March 2019, which occurred immediately prior to the planned 67% interim analysis. Altogether, 145 patients were randomly assigned (72 IMRT, 73 PBT), and 107 patients (61 IMRT, 46 PBT) were evaluable. Median follow-up was 44.1 months. Fifty-one patients (30 IMRT, 21 PBT) underwent esophagectomy; 80% of PBT was passive scattering. The posterior mean TTB was 2.3 times higher for IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) than PBT (17.4; 10.5-25.0). The mean POC score was 7.6 times higher for IMRT (19.1; 7.3-32.3) versus PBT (2.5; 0.3-5.2). The posterior probability that mean TTB was lower for PBT compared with IMRT was 0.9989, which exceeded the trial's stopping boundary of 0.9942 at the 67% interim analysis. The 3-year PFS rate (50.8% v 51.2%) and 3-year overall survival rates (44.5% v 44.5%) were similar.ConclusionFor locally advanced esophageal cancer, PBT reduced the risk and severity of AEs compared with IMRT while maintaining similar PFS.

Project description:BackgroundThe level of evidence for palliative second-line therapy in advanced esophageal squamous cell carcinoma (aESCC) is limited. This is the first study that reports efficacy data comparing second-line therapy + active symptom control (ASC) versus ASC alone in aESCC.MethodsWe conducted a tri-center retrospective cohort study (n = 166) including patients with aESCC who had experienced disease progression on palliative first-line therapy. A propensity score model using inverse probability of treatment weighting (IPTW) was implemented for comparative efficacy analysis of overall survival (OS) in patients with second-line + ASC (n = 92, 55%) versus ASC alone (n = 74, 45%).ResultsThe most frequent second-line regimens used were docetaxel (36%) and paclitaxel (18%). In unadjusted primary endpoint analysis, second-line + ASC was associated with significantly longer OS compared with ASC alone [hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.35-0.69, p < 0.0001]. However, patients in the second-line + ASC group were characterized by more favorable baseline features including a better Eastern Cooperative Oncology Group (ECOG) performance status, a longer first-line treatment duration and lower C-reactive protein levels. After rigorous adjusting for baseline confounders by re-weighting the data with the IPTW the favorable association between second-line and longer OS weakened but prevailed. The median OS was 6.1 months in the second-line + ASC group and 3.2 months in the ASC group, respectively (IPTW-adjusted HR = 0.40, 95% CI: 0.24-0.69, p = 0.001). Importantly, the benefit of second-line was consistent across several clinical subgroups, including patients with ECOG performance status ⩾1 and age ⩾65 years. The most common grade 3 or 4 adverse events associated with palliative second-line therapy were hematological toxicities.ConclusionThis real-world study supports the concept that systemic second-line therapy prolongs survival in patients with aESCC.

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Patterns and predictors of failure following tri-modality therapy for locally advanced esophageal cancer.

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Patterns and predictors of failure following tri-modality therapy for locally advanced esophageal cancer.

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