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The feasibility and safety of radical esophagectomy in patients receiving neoadjuvant chemoradiotherapy with pembrolizumab for esophageal squamous cell carcinoma.

ABSTRACT: Background: Immune checkpoint inhibitors have been tried for several thoracic malignancies; however, their application as a neoadjuvant therapy in esophageal squamous cell carcinoma (ESCC) has not been studied. We evaluated the feasibility and safety of esophagectomy and total lymphadenectomy after neoadjuvant chemoradiation therapy with pembrolizumab.

Methods: Between 2017 and 2018, 38 patients who received the neoadjuvant therapy followed by radical esophagectomy and total lymphadenectomy for ESCC were analyzed. Twenty-two patients received conventional neoadjuvant chemoradiation therapy (Group 1), and sixteen patients received neoadjuvant chemoradiation therapy with pembrolizumab in clinical trial (Group 2). Two groups were compared retrospectively.

Results: The basic characteristics of age, clinical stage, location and methods of operation were not different between the two groups. The pathologic stages were higher in Group 2, but the difference was not statistically significant. The operative outcomes, i.e., operation time, blood loss, and numbers of dissected lymph nodes in the thorax, neck, and abdomen were comparable. Complications, including pulmonary complications and anastomotic leakage, were also comparable. The rate of recurrent laryngeal nerve palsy was also comparable between the two groups (31.8% vs. 18.8%, P=0.469). Operative mortalities developed in 2 patients [0 vs. 2 (12.5%), P=0.171] due to acute respiratory distress syndrome (ARDS).

Conclusions: Radical esophagectomy for esophageal squamous cell carcinoma after neoadjuvant chemoradiation therapy with pembrolizumab may not increase the operative risk or reduce the quality of radical dissection including lymphadenectomy. The risk of ARDS after neoadjuvant neoadjuvant chemoradiation therapy with pembrolizumab has to be studied in the further analysis.

SUBMITTER: Park SY

PROVIDER: S-EPMC7711420 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The feasibility and safety of radical esophagectomy in patients receiving neoadjuvant chemoradiotherapy with pembrolizumab for esophageal squamous cell carcinoma.

Park Seong Yong SY Hong Min Hee MH Kim Hye Ryun HR Lee Chang Geol CG Cho Jae Ho JH Cho Byoung Chul BC Kim Dae Joon DJ

Journal of thoracic disease 20201101 11

<h4>Background</h4>Immune checkpoint inhibitors have been tried for several thoracic malignancies; however, their application as a neoadjuvant therapy in esophageal squamous cell carcinoma (ESCC) has not been studied. We evaluated the feasibility and safety of esophagectomy and total lymphadenectomy after neoadjuvant chemoradiation therapy with pembrolizumab.<h4>Methods</h4>Between 2017 and 2018, 38 patients who received the neoadjuvant therapy followed by radical esophagectomy and total lymphad ...[more]

PMID: 33282345

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Project description:BackgroundTumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT.MethodsA total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT.ResultsThe 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2-3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2-3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant.ConclusionsNACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).

Project description:ObjectiveThe safety and feasibility of preoperative pembrolizumab combined with chemoradiotherapy (PPCT) for resectable esophageal squamous cell carcinoma have been confirmed by the prior Preoperative Anti-PD-1 Antibody combined with Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus (PALACE)-1 trial. Potential therapeutic benefit was also observed with a pathologic complete response rate of 55.6% after PPCT. We will conduct the multicenter single-arm PALACE-2 study to investigate the efficacy and to further confirm the safety of PPCT (ClinicalTrials.gov ID: NCT04435197).MethodsA total of 143 patients with previously untreated, locally advanced, and surgically resectable esophageal squamous cell carcinoma (T2 through T4a, N0 through N+, M0) will be enrolled in PALACE-2. Main exclusion criteria are autoimmune disease, interstitial lung disease, ongoing immunosuppressive therapy, and having received chemotherapy, radiotherapy, target therapy, or immune therapy for this or any other malignancies. Positive programmed cell death ligand 1 expression is not mandatory for enrollment. Patients will receive PPCT, which includes concurrent pembrolizumab (200 mg on day 1 and day 22), carboplatin (area under the curve = 2, once a week for 5 weeks), nab-paclitaxel (50 mg/m2, once a week for 5 weeks), and radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week). Esophagectomy will be performed within 4 to 6 weeks after the completion of PPCT.ResultsThe primary end point is the rate of pathologic complete response. Secondary outcome measures are 3-year disease-free survival rate, 3-year overall survival rate, R0 resection rate, and adverse events during neoadjuvant and perioperative periods.ConclusionsPPCT was preliminarily demonstrated to be safe, feasible, and to provide potential therapeutic benefits by the PALACE-1 trial. The subsequent multicenter PALACE-2 study will investigate the efficacy and further confirm the safety of PPCT for locally advanced, resectable esophageal squamous cell carcinoma.

Project description:ImportanceSafety and efficacy of neoadjuvant chemoradiotherapy (nCRT) vs neoadjuvant chemotherapy (nCT) for treatment of locally advanced esophageal squamous cell carcinoma (ESCC) remain uncertain given lack of high-level clinical evidence.ObjectiveTo compare safety and long-term survival of nCRT followed by minimally invasive esophagectomy (MIE) with that of nCT followed by MIE for patients with locally advanced ESCC.Design, setting, and participantsA prospective, multicenter, open-label, randomized clinical trial that compared safety and efficacy of nCRT vs nCT followed by MIE for patients with locally advanced ESCC. From January 1, 2017, to December 31, 2018, 264 patients with ESCC of clinical stages from cT3 to T4aN0 to 1M0 were enrolled. Analysis was performed on an intention-to-treat basis from January 1, 2017, to August 30, 2020.InterventionsEligible patients were randomized to the nCRT group (n = 132) or the nCT group (n = 132) by a computer-generated random system. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while 40 Gy of concurrent radiotherapy was added for the nCRT group. At about 6 weeks after neoadjuvant therapy, MIE via thoracoscopy and laparoscopy was performed for the patients in both groups.Main outcomes and measuresThe primary outcome was 3-year overall survival. Secondary outcomes included postoperative complications, mortality, postoperative pathologic outcome, recurrence-free survival time, and quality of life.ResultsAmong 264 patients (226 men [85.6%]; mean [SD] age, 61.4 [6.8] years), postoperative morbidity was 47.4% in the nCRT group (54 of 114) and 42.6% in the nCT group (46 of 108), with no significant difference between groups (difference, 4.8%; 95% CI, -8.2% to 17.5%; P = .48). Distribution of the severity of complications was similar between the 2 groups based on Clavien-Dindo classification. The 90-day perioperative mortality rate was 3.5% for the nCRT group (4 of 114) and 2.8% for the nCT group (3 of 108) (P = .94). The R0 resection rates were similar between groups (109 of 112 [97.3%] vs 100 of 104 [96.2%]; P = .92). However, patients in the nCRT group had a higher pathologic complete response (residual tumor, 0%) rate (40 of 112 [35.7%] vs 4 of 104 [3.8%]; P < .001) and a higher rate of negative lymph nodes (ypN0, 74 of 112 [66.1%] vs 48 of 104 [46.2%]; P = .03) than those in the nCT group. One-year overall survival using intention-to-treat analysis was 87.1% in the nCRT group (115 of 132) and 82.6% in the nCT group (109 of 132) (P = .30). Furthermore, deaths caused by tumor progression or recurrence were significantly less in the nCRT group than in the nCT group (9 of 132 [6.8%] vs 19 of 132 [14.4%]; P = .046); however, deaths from nontumor causes were similar (8 of 132 [6.1%] vs 4 of 132 [3.0%]; P = .24).Conclusions and relevanceInitial results of the trial showed that nCRT followed by MIE has similar safety to and better histopathologic outcome than nCT followed by MIE for treatment of locally advanced ESCC.Trial registrationClinicalTrials.gov Identifier: NCT03001596.

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The feasibility and safety of radical esophagectomy in patients receiving neoadjuvant chemoradiotherapy with pembrolizumab for esophageal squamous cell carcinoma.

Publications

The feasibility and safety of radical esophagectomy in patients receiving neoadjuvant chemoradiotherapy with pembrolizumab for esophageal squamous cell carcinoma.

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