Dataset Information

The Effect of Timing of Adjuvant Therapy on Survival After Esophagectomy.

ABSTRACT:

Background

Adjuvant chemotherapy (AC) after esophagectomy improves survival in esophageal cancer when induction therapy is not given; however, the optimal timing for initiation of AC is poorly characterized. We aimed to determine the impact of timing of AC on survival after esophagectomy.

Methods

The National Cancer Database was queried for patients with pT1-4aNxM0 esophageal cancer receiving AC with or without radiation from 2004 to 2015. The median and interquartile range of time to AC were determined. Patients were stratified by initiation of AC into 4 cohorts based on quartiles. Kaplan-Meier curves were generated and factors associated with survival were identified by Cox proportional hazards modeling. A separate analysis was performed with time to AC as a continuous variable.

Results

A total of 1634 patients received AC after esophagectomy. Median time to receipt of AC was 59 (interquartile range, 45-78) days. There was no significant difference in overall survival at 5 years (P = .86) between groups. Median survival was 29 months in those receiving AC within 45 days and was 28 months in those receiving AC at other time points. On multivariable analysis, delay in receipt of AC beyond 45 days was not associated with inferior survival. This was preserved when time to AC was analyzed as a continuous variable (hazard ratio, 1.0; 95% confidence interval, 1.0-1.0).

Conclusions

Timing of initiation of AC after esophagectomy does not appear to impact survival. Given the highly variable postoperative course after esophagectomy, the decision to start AC should involve multidisciplinary discussion and be made on a patient-by-patient basis.

SUBMITTER: Rhodin KE

PROVIDER: S-EPMC7483824 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceSurgery followed by adjuvant chemotherapy or chemoradiation is widely used to treat resectable pancreatic cancer. Although studies suggest initiation of adjuvant therapy within 12 weeks of surgery, there is no clear time interval associated with better survival.ObjectiveTo evaluate the ideal timing of adjuvant therapy for patients with stage I to II resected pancreatic cancer.Design, setting, and participantsThis cohort study included 7548 patients with stage I to II resected pancreatic cancer (5453 with adjuvant therapy; 2095 without adjuvant therapy) from the National Cancer Database from 2004 to 2015. Data were collected from January 2014 to December 2015 and analyzed from December 2018 to May 2019.ExposuresAdjuvant chemotherapy or chemoradiation at various time intervals.Main outcomes and measuresOverall survival (OS).ResultsA total of 7548 patients (3770 male [49.9%]; median [interquartile range] age, 67 [59-74] years) were identified from the National Cancer Database. Among 5453 patients with adjuvant therapy, a Cox model with restricted cubic splines identified the lowest mortality risk when adjuvant therapy was started 28 to 59 days after surgery. Patients were divided into early (n = 269, adjuvant therapy initiated within <28 days), reference (n = 3048, adjuvant therapy initiated within 28-59 days), and late (n = 2136, adjuvant therapy initiated after >59 days) interval cohorts. Median (interquartile range) overall follow-up was 38.6 (24.6-62.0) months. Compared with the reference interval cohort on multivariable analysis, both the early cohort (hazard ratio, 1.17; 95% CI, 1.02-1.35; P = .03) and the late cohort (hazard ratio, 1.09; 95% CI, 1.02-1.17; P = .008) were associated with worse mortality. Similarly, the reference interval cohort had improved OS compared with the early cohort in 268 propensity-matched pairs (2-year OS, 52.5% [95% CI, 46.7%-59.0%] vs 45.1% [95% CI, 39.5%-51.6%]; P = .02) and compared with the late cohort in 2042 propensity-matched pairs (2-year OS, 51.3% [95% CI, 49.1%-53.6%] vs 45.4% [95% CI, 43.3%-47.7%]; P = .01). Patients who received adjuvant therapy more than 12 weeks after surgery (n = 683) had improved OS compared with surgery alone in both multivariable analysis (hazard ratio, 0.75; 95% CI, 0.66-0.85; P < .001) and 655 propensity-matched pairs (2-year OS, 47.2% [95% CI, 43.5%-51.3%] vs 38.0% [95% CI, 34.4%-42.0%]; P < .001).Conclusions and relevancePatients with stage I to II pancreatic cancer who commenced adjuvant therapy within 28 to 59 days after primary surgical resection had improved survival outcomes compared with those with adjuvant therapy before 28 days or after 59 days. Patients who recovered slowly from surgery still benefited from delayed adjuvant therapy initiated more than 12 weeks after surgery compared with patients who underwent surgery only.

Project description:The optimal time to initiate adjuvant therapy (AT) in elderly patients with glioblastoma (GBM) remains unclear. We investigated the impact of timing to start AT on overall survival (OS) using two national-scale datasets covering elderly GBM populations in the United States. A total of 3159 and 8161 eligible elderly GBM patients were derived from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked dataset (2004-2013) and the National Cancer Database (NCDB) (2004-2014), respectively. The intervals in days from the diagnosis to the initiation of AT were categorized based on two scenarios: Scenario I (quartiles), ≤ 15, 16-26, 27-37, and ≥ 38 days; Scenario II (median), < 27, and ≥ 27 days. The primary outcome was OS. We performed the Kaplan-Meier and Cox proportional hazards regression methods for survival analysis. A sensitivity analysis was performed using Propensity Score Matching (PSM) method to achieve well-balanced characteristics between early-timing and delayed-timing in Scenario II. Improved OS was observed among patients who underwent resection and initiated AT with either a modest delay (27-37 days) or a longer delay (≥ 38 days) compared to those who received AT immediately (≤ 15 days) from both the SEER-Medicare dataset [adjusted hazard ratio (aHR) 0.74, 95% CI 0.64-0.84, P < 0.001; and aHR 0.81, 95% CI 0.71-0.92, P = 0.002] and the NCDB (aHR 0.83, 95% CI 0.74-0.93, P = 0.001; and aHR 0.87, 95% CI 0.77-0.98, P = 0.017). The survival advantage is observed in delayed-timing group as well in Scenario II. For elderly patients who had biopsy only, improved OS was only detected in a longer delay (Scenario I: ≥ 38 days vs. ≤ 15 days) or the delayed-timing group (Scenario II: ≥ 27 days vs. < 27 days) in the NCDB while no survival difference was seen in SEER-Medicare population. For the best timing to start AT in elderly GBM patients, superior survivals were observed among those who had craniotomy and initiated AT with a modest (27-37 days) or longer delays (≥ 38 days) following diagnosis using both the SEER-Medicare and NCDB datasets (Scenario I). Such survival advantage was confirmed when categorizing delayed-timing vs. early-timing with the cut-off at 27 day in both datasets (Scenario II). The increased likelihood of receiving delayed AT (≥ 27 days) was significantly associated with tumor resection (STR/GTR), years of diagnosis after 2006, African American and Hispanics races, treatments at academic facilities, and being referred. There is no difference in timing of AT on survival among elderly GBM patients who had biopsy in the SEER-Medicare dataset. In conclusion, initiating AT with a modest delay (27-37 days) or a longer delay (≥ 38 days) after craniotomy may be the preferred timing in the elderly GBM population.

Project description:PurposeRadioactive iodine (RAI) is widely used for adjuvant therapy after thyroidectomy, while its value for thyroid cancer has been controversial recently. The primary objectives of this study were to clarify the influence of Radioactive iodine (RAI) on the survival in rare oxyphilic subtype of thyroid cancer (Hürthle cell carcinoma, HCC).MethodsPatients diagnosed with oxyphilic thyroid carcinoma from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results Program database. The Kaplan-Meier method was used to compare overall survival (OS) and cancer-specific survival (CSS) among patients who had adjuvant RAI use or not. Univariate and multivariate Cox proportional hazard models were performed for survival analysis, and subsequently visualized by nomogram.ResultsIn all, 2,799 patients were identified, of which 1529 patients had adjuvant RAI use while 1,270 patients had not. Based on multivariate Cox analysis, the RAI therapy confers an improved OS for HCC patients (HR = 0.57, 95% CI [0.44-0.72], P < 0.001), whereas it has no significant benefit in the survival analysis regarding CSS (HR = 0.79, 95% CI [[0.47-1.34], P = 0.382). In a subgroup analysis, the same survival benefit of RAI treatment on OS, but not CSS was observed among patients stratified by AJCC stage and tumor extension. Nevertheless, patients with regional lymph node metastasis benefited from RAI therapy both in OS and CSS (P < 0.001, respectively). Furthermore, nomograms used for predicting long term survival of HCC patients exhibited a better prediction power for OS compared with traditional tumor, nodal and metastatic (TNM) stage made by American Joint Committee on Cancer (AJCC) (C-index = 0.833 of the nomogram model vs. 0.696 of the AJCC system).ConclusionsThis study suggests that RAI therapy is significantly associated with improved OS in patients with Hürthle cell carcinoma. However, there was no association between treatment with radioiodine and CSS, possibly due to small number of deaths that were related to HCC.

Project description:BackgroundOn the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma.MethodsAfter patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety.ResultsAt a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P=0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P=0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immune-related adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events.ConclusionsAs adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00636168 , and EudraCT number, 2007-001974-10 .).

Project description:The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N+ esophageal cancer, prior to esophagectomy.