Early-Onset Esophageal Adenocarcinoma Presents With Advanced-Stage Disease But Has Improved Survival Compared With Older Individuals.
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ABSTRACT:
SUBMITTER: Kolb JM
PROVIDER: S-EPMC9440641 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Early-Onset Esophageal Adenocarcinoma Presents With Advanced-Stage Disease But Has Improved Survival Compared With Older Individuals.
Kolb Jennifer M JM Han Samuel S Scott Frank I FI Murphy Caitlin C CC Hosokawa Patrick P Wani Sachin S
Gastroenterology 20200808 6
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Project description:ObjectiveTo compare the efficacy and safety of induction FOLFOX followed by PET-directed nCRT, induction CP followed by PET-directed nCRT, and nCRT with CP alone in patients with EAC.Summary of background datanCRT with CP is a standard treatment for locally advanced EAC. The results of cancer and leukemia group B 80803 support the use of induction chemotherapy followed by PET-directed chemo-radiation therapy.MethodsWe retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and evaluated using the log-rank test and extended Cox regression.ResultsIn total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n = 70; CP, n = 239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs. 16%, P = 0.004), near-pCR (57% vs. 33%, P < 0.001), and 2-year DFS (68% vs. 50%, P = 0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs. 42%, P = 0.04) and 2-year DFS (68% vs. 44%, P < 0.001) were significantly higher in the FOLFOX group than in the no-induction group.ConclusionsInduction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone.
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Project description:Apatinib plus chemotherapy demonstrates good efficacy in multiple advanced carcinomas; however, its use in patients with advanced lung adenocarcinoma (LUAD) has not yet been assessed. The present study evaluated the potential benefits of apatinib plus chemotherapy in patients with advanced LUAD. A total of 145 patients with advanced LUAD and negative driver genes who received apatinib plus chemotherapy (n=65) or chemotherapy alone (n=80) were analyzed. The overall response rate was significantly improved by apatinib plus chemotherapy vs. chemotherapy alone (53.8 vs. 36.3%; P=0.034). Moreover, progression-free survival (PFS) was significantly longer in patients who received apatinib plus chemotherapy, compared with those who received chemotherapy alone [median (95% CI), 13.4 months (11.5-15.3) vs. 8.2 months (6.9-9.5); P<0.001], as was overall survival (OS) [median (95% CI), 23.1 months (not reached) vs. 17.0 months (14.6-19.4; P=0.001). Following adjustment by multivariate Cox regression analysis, apatinib plus chemotherapy was associated with a significantly longer PFS [hazard ratio (HR), 0.444; P<0.001] and OS (HR, 0.347; P<0.001), compared with chemotherapy alone. Subgroup analyses revealed that PFS and OS were significantly improved following apatinib plus chemotherapy vs. chemotherapy alone (all P<0.05) in patients receiving first- or second-line treatment. Notably, the incidence of hypertension was significantly increased following apatinib plus chemotherapy vs. chemotherapy alone (43.1 vs. 25.0%; P=0.021), whereas the incidence of other adverse events was not significantly different between the two treatment groups (all P>0.05). In conclusion, apatinib plus chemotherapy is associated with an improved treatment response and survival compared with chemotherapy alone, with a tolerable safety profile in patients with advanced LUAD.
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Project description:BackgroundThere are limited data on the safe interval from diagnosis to surgery in patients with stage I esophageal adenocarcinoma. We hypothesized that increased time to surgery would be associated with worse survival and increased nodal upstaging.MethodsThe National Cancer Database was used to identify patients with cT1N0M0 esophageal adenocarcinoma (2004-2015) who underwent esophagectomy without induction therapy. The primary outcome was survival, and the secondary outcomes were the rate of margin-positive resection and pathologic nodal upstaging. Time to surgery was modeled as a categoric variable, dividing patients into quartiles (Q1-4), and as a continuous variable using piecewise linear splines centered on 50 and 100 days.ResultsA total of 2495 patients met study criteria. When examined in quartiles, there was no difference in survival between groups based on time to surgery in both unadjusted and multivariable analyses. As a continuous variable, increasing time to surgery less than 50 days was associated with improved survival (hazard ratio, 0.99; 95% confidence interval, 0.98-1.00), and time to surgery greater than 100 days was associated with worse survival (hazard ratio, 1.00; 95% confidence interval, 1.00-1.01) and increased margin-positive resection (odds ratio, 1.01; 95% confidence interval, 1.00-1.02). Treatment at a high-volume center, government insurance, and diagnosis and treatment at different centers were associated with surgery beyond 100 days.ConclusionsIncreasing time to surgery greater than 100 days is associated with worse outcomes in patients with stage I esophageal adenocarcinoma. In this patient population, esophagectomy should be offered as soon as safely possible.
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Project description:There is an increasing incidence of esophageal adenocarcinoma (EA) among younger people in the western populations. However, the association between genetic polymorphisms and the age of EA onset is unclear. In this study, 1330 functional/tagging single-nucleotide polymorphisms (SNPs) from 354 cancer-related genes were genotyped in 335 white EA patients. Twenty important SNPs that have the highest importance scores and lowest classification error rate were identified by the random forest algorithm to be associated with early onset of EA (age ? 55 years). Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (?55 vs >55 years, all P < .05 after adjusting for co-variates and false discovery rate). Among them, five SNPs in the NOS3, BCL2, TNFRSF10A, and CASP8 genes were known to be involved in apoptosis processes. In Kaplan-Meier analyses, rs2070744 of NOS3, rs720321 of BCL2, and rs1035142 of CASP8 were also significantly associated with early onset of EA. Moreover, there was a higher risk of developing EA at a younger age when one had more risk genotypes. In conclusion, polymorphisms in cancer-related genes, especially those in the apoptotic pathway, play an important role in the development of younger-aged EA in a dose-response manner.
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Project description:Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by triggering the PD1 pathway. Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic growth signals. This study aimed to evaluate the potential clinical relevance of PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the AEG.Patients with AEG who underwent esophagectomy from 1992 to 2011 were included in the study. Expression of PD1was evaluated by immunohistochemistry and correlated with long-term overall survival (OS), disease-free survival (DFS), and various clinicopathologic parameters.Tumor biospecimens from 168 patients were analyzed. In the analysis, 81% of the patients showed high tumoral frequencies (>5%) of PD1-expressing TILs (TIL-PD1+), and 77% of patient tumors harbored high levels (>5%) of PD1+ cancer cells (cancer-PD1+). Expression of PD1 by TILs and cancer cells correlated significantly (p < 0.05) with patients' tumor stage and lymph node involvement. Compared with the patients who had low tumoral frequencies of PD1+ TILs or cancer cells, the TIL-PD1+ and cancer-PD1+ patients demonstrated significantly reduced DFS in the univariate analysis (5-year DFS: 73.3 vs. 41.9%, log-rank 0.008 and 71.3 vs. 41.6%, p = 0.008, respectively). Additionally, the cancer-PD1+ patients showed significantly decreased OS in the univariate analysis compared with the cancer-PD1- patients (5-year OS: 68.8 vs. 43.5%; p = 0.047). However, these correlations did not reach significance in the multivariate analysis.The PD1 receptor is expressed by both TILs and cancer cells in AEG. High expression of PD1 is associated with advanced tumor stage and lymph node involvement, but not with survival.
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Project description:ObjectivesAnaplastic thyroid cancer (ATC) is the most aggressive and fatal thyroid malignancy. Currently, there still exists a paucity of literature studying the relationship between available ATC-targeted therapy, immunotherapy, and survival. We aim to investigate how systemic therapies affect survival outcomes in ATC.MethodsA single-tertiary-institution chart review of patients diagnosed with advanced-stage ATC, and who underwent surgery as part of their treatment, was performed between 2000 and 2023, with 41 patients included. Demographics, clinical characteristics, and survival data were collected and analyzed via Kaplan-Meier and Cox proportional hazards analyses.Results54% of patients were female, and average age was 67.4 years old. The most common mutations identified were BRAF (15 patients), p53 (9 patients), and p63 (2 patients). A total of 18 patients utilized targeted or immunotherapy, with Trametinib and Dabrafenib (9 patients) as the most common agents used. Two-year overall survival was 24%, and 5-year overall survival was 23%, with median survival time of 7.6 months. Kaplan-Meier analysis demonstrated improved survival in patients who received chemotherapy (p = 0.048). Cox proportional hazards analysis demonstrated that patients treated with immunotherapy or targeted therapy had a statistically significant increase in survival compared with patients who did not receive these therapies (p = 0.016). Additionally, females and those with a p63 mutation demonstrated improved survival outcomes (p = 0.010, p = 0.001).ConclusionsTargeted therapy and immunotherapy use should be strongly considered when treating patients with ATC. Further studies into novel drugs targeting immune checkpoints and combination therapy are needed to better optimize treatment of patients with ATC.Level of evidence3 Laryngoscope, 135:478-484, 2025.
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Project description:BackgroundEfforts to reduce mortality from esophageal adenocarcinoma (EA) have focused on screening and surveillance of Barrett's esophagus (BE).AimsWe sought to determine the frequency of prior diagnosis of BE in patients with EA and to evaluate the impact of a prior BE diagnosis on mortality in EA patients.MethodsThis was a retrospective cohort study of patients diagnosed with EA in the VA during 2002-2016. We compared the distributions of EA stage and receipt of treatment between EA patients with and without a prior BE diagnosis and used Cox proportional hazards models to compare mortality risk (all-cause and cancer specific) unadjusted and adjusted for stage and treatment to assess their impact on any survival differences.ResultsAmong 8564 EA patients, only 4.9% had a prior BE diagnosis. The proportion with prior BE diagnosis increased from 3.2% in EA patients diagnosed during 2005-2007 to 7.0% in those diagnosed during 2014-2016. EA patients with a prior BE diagnosis were more likely to have stage 1 disease and receive any treatment. A prior BE diagnosis was associated with lower all-cause mortality risk (hazard ratio [HR] unadjusted for stage, 0.69; 95% CI, 0.61-0.80), which was largely explained by the earlier stage of EA at the time of diagnosis (HR adjusted for stage, 0.87; 95% CI, 0.75-0.99). There was no evidence of lead time bias or length time bias.ConclusionsPrior diagnosis of BE was associated with better survival, largely due to earlier EA stage at diagnosis.
| S-EPMC6185782 | biostudies-literature
Project description:IntroductionFor patients with T2aN0 stage IB lung adenocarcinoma, benefits of adjuvant chemotherapy remain controversial. Here, we aimed to evaluate such benefits.MethodsThis retrospective cohort study was conducted on the database of the National Taiwan Cancer Registry. We analyzed patients with T2aN0 stage IB lung adenocarcinoma (re-classified by AJCC 8th edition) diagnosed during the period from January 2011 to December 2017. They were divided into two groups: (1) group 1: tumor <=3 cm with visceral pleural invasion (VPI); (2) group 2: tumor >3 cm, but <=4 cm. Overall survival (OS) and cancer specific survival (CSS) were evaluated. Risk factors for survival were determined.ResultsA total of 2,100 patients with T2aN0 stage IB lung adenocarcinoma (1,265 in group 1 and 835 in group 2) were enrolled for study. The proportions of patients receiving adjuvant chemotherapy in group 1 and 2 were 39.1% and 68.6%, respectively. Amongst group 1 patients, adjuvant chemotherapy was not an independent risk factor for OS and CSS. Amongst group 2 patients, high-grade histologic findings and receiving sublobar resection were two risk factors for poorer survival. Adjuvant chemotherapy was also associated with an OS (adjusted hazard ratio (aHR), 0.52; 95% confidence interval (CI), 0.38-0.72; P<0.001) and CSS (aHR, 0.54; 95% CI, 0.37-0.78; p=0.001) benefit regardless of the presence or absence of risk factors.ConclusionFor patients with T2aN0 stage IB lung adenocarcinoma, adjuvant chemotherapy improved OS and CSS in those with tumors >3 cm, but <=4 cm.For patients with tumors <=3 cm with VPI, adjuvant chemotherapy had no survival benefit.
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