Patterns of failure following trimodality therapy for locally advanced esophageal cancer (EC).

88 Background: Patterns of local-regional failure (LRF) after neoadjuvant chemoradiotherapy (CRT) and surgery for locally-advanced EC are poorly defined. Methods: This study reviewed pts treated with CRT followed by surgery for M0 esophageal cancer from 1995-2009. Staging and regional nodes (supraclavicular (SCV) through celiac) were defined based on AJCC 7th edition. Patterns of first failure were analyzed. LRF included: 1) initially involved nodal failure (INF), 2) initially uninvolved (subclinical) nodal failure (SNF), and/or 3) anastomotic. Abdominal para-aortic failure (PAF) at or below the superior mesenteric artery was scored separately. Isolated SNF or PAF was defined as no other local or distant failure. Actuarial local-regional control (LRC), event-free survival (EFS), and overall survival (OS) were estimated by the Kaplan-Meier method. Results: 156 patients were identified with a median age of 60 years. Primary location was upper in 1%, middle 17%, lower 32% and gastroesophageal junction (GEJ) 50% (Adeno: 79%; SCC: 21%). Staging included EUS (73%), CT (46%), and/or PET/CT (54%). 40% had stage II and 60% stage III disease. Concurrent CRT was primarily cisplatin/taxane and/or 5-FU-based. Primary RT fields (median dose: 45Gy) encompassed the tumor with an approximate 5 cm proximal and distal margin and included standard regional nodes. Boost fields (median total dose: 50.4Gy) encompassed gross disease with a 2 cm margin. Surgical technique was transhiatial (28%), Ivor-Lewis (47%), or tri-incisional (25%) with a median of 8 nodes dissected. Median f/u was 1.3 years. 2-yr LRC, EFS, and OS were 83%, 36%, and 49%. 2-yr SNF was 15% (n=14); anastomotic failure was 7% (n=7). SNFs were SCV (n=5), mediastinal (n=12), and/or celiac (n=3). 95% of SNFs were outside or near the margin of the primary RT fields. 2-yr isolated SNF was 3% (n=3), PAF was 11% (n=9), and isolated PAF 6% (n=5). Conclusions: SNF is the most common type of LRF after tri-modality therapy for locally-advanced EC. A limited subset of patients experience isolated SNF or PAF as first disease recurrence. The potential benefit of targeting additional SN or PA regions with RT is small and likely eclipsed by high rates of distant failure.

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The recurrence patterns and post-recurrence survivals in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with preoperative paclitaxel/cisplatin-based chemoradiotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.80 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 80-80

Author(s):

Hung-Yang Kuo ◽

Jhe-Cyuan Guo ◽

Ta-Chen Huang ◽

Chia-Chi Lin ◽

Min-Shu Hsieh ◽

...

Keyword(s):

Distant Metastasis ◽

Locally Advanced ◽

Disease Recurrence ◽

Regional Recurrence ◽

Recurrence Pattern ◽

Term Survival ◽

Distant Failure ◽

Phase Ii Clinical Trials ◽

Kaplan Meier ◽

Recurrence Patterns

80 Background: More than half of patients (pts) with locally advanced ESCC would have disease recurrence after curative preoperative chemoradiation (CRT) followed by surgery. Whether recurrence pattern correlates with the post-recurrence survival remains uncertain. Methods: We included 131 pts with locally advanced ESCC (clinical T3N0-1M0 or T1-3N1M0 or M1a according to AJCC 6thedition) who were enrolled in 3 phase II clinical trials of preoperative CRT followed by surgery and had successfully completed CRT and surgery. These pts received preoperative twice weekly paclitaxel/cisplatin-based CRT with radiotherapy 40Gy given in 20 fractions followed by esophagectomy. When pts had first disease recurrence, we divided them into three groups according to their recurrence patterns: loco-regional recurrence (LRR), distant metastasis only (DM), and both LRR and DM (LRR+DM). Survival outcomes were compared using the Kaplan-Meier curves. Results: With a median follow-up of 34.8 months, 75 pts (57.3%) had disease recurrence (Table 1) and the median post-recurrence survival of these pts is 6.7 months (m). Among them, 24 pts (32.0%) had LRR, 19 (25.3%) pts had DM, and 32 pts (42.7%) had LRR+DM. There is no statistical difference of the post-recurrence survivals (Fig. 1) among 3 groups (5.4, 7.5, 4.9m, p = 0.43 in LRR, DM, and LRR+DM group respectively). It is noteworthy that 4 pts in the DM group with limited distant metastasis (1 had brain metastasis, 3 had lung metastasis) had long post-recurrence survival (56.2+, 51.6+, 13.8+, 13.1+m) after receiving metastasectomy with or without chemotherapy. Conclusions: The post-recurrencesurvival of locally advanced ESCC pts who received preoperative CRT followed by surgerywere similar regardless of recurrence pattern (loco-regional recurrence or both loco-regional and distant failure). However, in pts with limited metastasis, curative metastasectomy might provide the opportunity of achieving long-term survival. (The work was supported by the Grant of MOST 103-2314-B-002-092, MOST 104-2314-B-002-111- and HCH104-024)

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Clinical characteristics of recurrent esophageal cancer after definitive chemoradiotherapy for stage II//III (non T4) esophageal squamous cell cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.137 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 137-137

Author(s):

Akiko Nishikawa ◽

Ken Kato ◽

Yoshitaka Honma ◽

Satoru Iwasa ◽

Atsuo Takashima ◽

...

Keyword(s):

Esophageal Cancer ◽

Clinical Stage ◽

Locally Advanced ◽

Disease Recurrence ◽

Advanced Esophageal Cancer ◽

Definitive Chemoradiotherapy ◽

Locoregional Failure ◽

Distant Failure ◽

Time To Recurrence ◽

Locally Advanced Esophageal Cancer

137 Background: Recurrence after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer is associated with poor outcome. No standard treatment strategy exist for recurrence after complete response (CR) to dCRT. We examined patterns of recurrence and clinical outcomes in patients with disease recurrence after dCRT. Methods: We retrospectively investigated 197 patients who had achieved initial CR after dCRT for locally advanced esophageal cancer between January 2000 and December 2008. We analyzed data from the 69 patients who had developed disease recurrence after CR, excluding 11 who died of other causes. Time to event was calculated by the Kaplan-Meier method, and the Cox proportional hazard model was used in univariate and multivariate analyses. Results: Characteristics of the 69 patients were as follows: male: female = 61:8; median age = 65 years (range 47 to 82); clinical stage at diagnosis (UICC 6th edition) IIA/IIB/III = 15/22/32; and performance status at recurrence (0/1/2) = (35/32/2). Primary CRT consisted of 5-FU+cisplatin (n = 66), 5-FU+nedaplatin (n = 2), or S-1+cisplatin (n = 1). The pattern of recurrence was locoregional failure (n = 35), or any distant failure (n = 34). Median time to recurrence from the start of dCRT was 13.6 months, and median survival time after recurrence was 17.4 months. Median survival time according to pattern of failure was 27.5 months (locoregional failure), and 17.4 months (any distant failure). In the univariate analysis, locoregional failure (HR 0.51), time to recurrence >13 months (HR0.38), clinical stage II (HR0.48), and any treatment for recurrence (HR: 0.15) were associated with better prognosis after recurrence. In the multivariate analysis, only time to recurrence (>13 months) was associated with better prognosis with HR 0.31(95%CI:0.14-0.66) Conclusions: Our study suggested that patients with early recurrence have a poor prognosis. More intensive treatment is needed to improve survival.

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Impact of comorbidity in the choice of curative treatment for esophageal cancer: A population-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.131 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 131-131 ◽

Cited By ~ 1

Author(s):

Zohra Faiz ◽

Margreet Van Putten ◽

Rob H.A. Verhoeven ◽

Johanna W. van Sandick ◽

Grard A. P. Nieuwenhuijzen ◽

...

Keyword(s):

Esophageal Cancer ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Treatment Decision ◽

Population Based ◽

Curative Intent ◽

Kaplan Meier ◽

Co Morbidity ◽

Study Support ◽

The Impact

131 Background: Surgery after neoadjuvant chemoradiotherapy (nCRT) is the most common treatment with curative intent for esophageal cancer (EC) patients. Definitive chemoradiotherapy (dCRT) is an alternative for patients who are not eligible for resection because of comorbidity. The purpose of this retrospective study was to evaluate patient and tumor characteristics which are associated with the type of treatment. Methods: We selected all consecutive patients with a locally advanced EC (cT1 N + / T2-3N0-3M0-1a) who were treated with curative intent (nCRT, dCRT or surgery only) in the South East Netherlands between 1995 and 2013. For a proper assessment of the impact of co-morbidity, T4 tumors were excluded. The effect of co-morbidity on treatment decision and on survival was analyzed using a multivariable logistic regression and Kaplan-Meier method. Survival time was defined as time from 6 months after diagnosis until death or until January 1st 2015 for patients who were still alive. Results: Of the 1098 patients, surgery only was performed in 46%, nCRT in 28% and dCRT in 26%. Patients with ≥ 2 co-morbidities underwent more frequently dCRT (OR = 2.35; 95% CI: 1.45-3.86), or resection only (OR = 2.29; 95% CI: 1.41-3.69). Patients > 75 years (OR = 6.66; 95% CI: 3.48-12.77), patients with hypertension and diabetes (OR: 4.05;95% CI: 1.96-8.37-3.90) and patients with cardiovascular (mostly myocardial infarction) and pulmonary comorbidity (OR = 3:33; 95% CI: 1:51 to 7:34) underwent frequently more dCRT than nCRT. Patients with esophageal squamous cell carcinoma (ESCC) also had more frequently dCRT (OR = 2.27; 95% Cl: 1.38-3.73). Patients with an adenocarcinoma and ≥ 2 co-morbidities had favorable 3-year overall survival (OS) after nCRT compared with dCRT and surgery alone (p < 0.01). However, the 3-year OS after nCRT was similar after dCRT in ESCC patients with ≥ 2 co-morbidities (p = 0.75). Conclusions: The results of this study support the treatment with dCRT in patients with SCC of the esophagus, and with at least two co-morbidities, in particular, the combination of cardiovascular / pulmonary disorders and hypertension plus diabetes.

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Surveillance for locally advanced esophageal and gastroesophageal junction (GEJ) cancers: Patterns of recurrence and methods of detection.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.32 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 32-32

Author(s):

Jubin Eghbali Matloubieh ◽

Alexandra Pilar Licona-Freudensten ◽

Andrea M Baran ◽

Michal J Lada ◽

Carolyn E Jones ◽

...

Keyword(s):

Surgical Resection ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Neoadjuvant Chemoradiation ◽

Trimodality Therapy ◽

Entire Cohort ◽

Post Surgery ◽

Kaplan Meier ◽

Trimodality Treatment ◽

Routine Imaging

32 Background: Trimodality treatment with neoadjuvant chemoradiation (CRT) followed by surgery is a standard treatment for esophageal/GEJ (E/GJ) cancers. Following esophagectomy, there is no strong consensus about optimal surveillance and routine imaging. At our institution, patients have surveillance CT scans every 4-6 months for the first 2 years post-surgery and every 6-12 months for the next 3 years. Methods: An IRB-approved chart review was performed identifying patients who underwent surgical resection for locally advanced E/GJ cancer between January 2011 and December 2015 at the University of Rochester. Study objectives were to describe timing of and methods used to detect recurrence as well as their impact on patient outcomes. Recurrence-free (RFS) and overall survival (OS) were graphed via the Kaplan-Meier method. Results: 138 patients underwent surgical resection for E/GJ cancer during the study period: 107 (77.5%) were male, median age was 64, and 116 patients (84.1%) had adenocarcinoma. 111 patients (80.4%) received neoadjuvant CRT. Median OS for entire cohort was 43.4 months. 65 patients (47.1%) relapsed with a median RFS of 19.8 months. Recurrence was detected by routine imaging in 34 patients (52.3%), imaging triggered by symptoms in 25 patients (38.5%), and symptoms alone in 6 patients (9.2%). Median OS post-relapse was 1.5 months when detected based on symptoms alone, 5.0 months when detected by imaging triggered by symptoms, and 13.5 months when detected by routine scans (Log-rank p = 0.046). There were no significant associations between baseline patient /tumor characteristics and subsequent method of recurrence detection. Conclusions: 47.1% of patients suffered relapse after trimodality therapy for E/GJ cancer, consistent with published literature. Almost half of these were detected based on symptoms despite routine imaging. Increased OS for patients with relapse detected by routine scans is likely related to lead time bias, but may be related to increased treatment intensity, or due to less aggressive tumors. Prospective randomized trials are needed to determine the true benefit of regular surveillance scans among esophageal cancer survivors.

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Chemoradiotherapy Using Carboplatin plus Paclitaxel versus Cisplatin plus Fluorouracil for Esophageal or Gastroesophageal Junction Cancer

Oncology ◽

10.1159/000510446 ◽

2020 ◽

Vol 99 (1) ◽

pp. 49-56

Author(s):

Di Maria Jiang ◽

Hao-Wen Sim ◽

Osvaldo Espin-Garcia ◽

Bryan A. Chan ◽

Akina Natori ◽

...

Keyword(s):

Cox Regression ◽

Gastroesophageal Junction ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Free Survival ◽

Standard Of Care ◽

Sensitivity Analyses ◽

Trimodality Therapy ◽

Gastroesophageal Junction Cancer ◽

Kaplan Meier

Background: Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT. Methods: A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis. Results: Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (n = 67; 72%) or dCRT (n = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; p = 0.001; HR 3.1; 95% CI: 1.2–7.7) and DFS (0 vs. 41%; p = 0.004; HR 3.6; 95% CI: 1.4–8.9) on multivariable and IPTW sensitivity analyses. Conclusions: TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.

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A Phase II Trial of Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study

Frontiers in Oncology ◽

10.3389/fonc.2021.736620 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hirva Mamdani ◽

Bryan Schneider ◽

Susan M. Perkins ◽

Heather N. Burney ◽

Pashtoon Murtaza Kasi ◽

...

Keyword(s):

T Cells ◽

Adverse Events ◽

Phase Ii ◽

Residual Disease ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

M2 Macrophages ◽

Activated T Cells ◽

Trimodality Therapy ◽

Surgical Specimen

BackgroundMost patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients.MethodsWe conducted a phase II study (ClinicalTrials.gov Identifier: NCT02639065) evaluating the efficacy and safety of PD-L1 inhibitor durvalumab in patients with locally advanced esophageal and GEJ AC who have undergone neoadjuvant CRT followed by R0 resection with evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every 4 weeks for up to 1 year. The primary endpoint was 1-year relapse free survival (RFS). Secondary endpoint was safety and tolerability of durvalumab following trimodality therapy. Exploratory endpoints included correlation of RFS with PD-L1 expression, HER-2 expression, and tumor immune cell population.ResultsThirty-seven patients were enrolled. The majority (64.9%) had pathologically positive lymph nodes. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events. One-year RFS was 73% (95% CI, 56–84%) with median RFS of 21 months (95% CI, 14–40.4 months). Patients with GEJ AC had a trend toward superior 1-year RFS compared to those with esophageal AC (83% vs. 63%, p = 0.1534). There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10 (100% vs. 66.7%, p = 0.1551) and ≥1 (84.2% vs. 61.1%, p = 0.1510) cutoffs. A higher relative proportion of M2 macrophages and CD4 memory activated T cells was associated with improved RFS (HR = 0.16; 95% CI, 0.05–0.59; p = 0.0053; and HR = 0.37; 95% CI, 0.15–0.93, p = 0.0351, respectively).ConclusionsAdjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ AC led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting. Higher proportion of M2 macrophages and CD4 memory activated T cells was associated with superior RFS.

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