Phase II trial of perioperative chemotherapy + avelumab in locally advanced gastroesophageal adenocarcinoma: Preliminary results.

4046 Background: Perioperative chemotherapy improves cure rate in locally advanced gastroesophageal adenocarcinoma (GEA), and immune checkpoint inhibitors are active at the metastatic stage. This trial tests the hypothesis that the addition of avelumab to perioperative chemotherapy will increase the major pathologic response (MPR) rate in comparison with historical controls. Methods: Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: GEA, cT3 and/or cN+, M0, WHO PS 0-1. Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone. Staging studies: CT, PET-CT, endoscopic ultrasound, diagnostic laparoscopy. Surgical resection: D2 lymphadenectomy, en-bloc esophagectomy for type I/II gastroesophageal junction (GEJ) tumors. Aim of the study: MPR as defined as tumor regression grades 0-1 (modified Ryan scheme); as per hypothesis, this experimental regimen will result in a 20% rate of MPR, compared with 7% with chemotherapy alone. Simon 2-stage design: if less than 2 MPR are seen in the first 16 patients, the study will be closed. The study hypothesis cannot be rejected if at least 6 MPR are seen in the first 50 patients. All adverse effects are prospectively recorded per CTCAE guidelines in patients who have received at least one treatment cycle. Survival rates are calculated with Kaplan-Meier method. Preliminary results are presented since the study has met its primary endpoint. Results: Feb 2018-Feb 2020: 28 patients enrolled (25 M/3 F, age 45-78). Location: GEJ (23), stomach (5). Staging: cT3 (25), cT4 (1), cN+ (20). Biomarkers expression: mismatch repair (MMR) protein loss (3/28); PD-L1(clone 73-10) expression in 1% (TPS) or more of tumor cells seen in 12/28 samples, and >10% in 6 patients. Grade 3 toxicity: stomatitis (2/28); nausea (2/28); vomiting (1/28); diarrhea (1/28); hypothyroidism (1/28); arthralgia (3/28); neutropenia (1/28). Grade 4 toxicity: pneumonia (1/28); neutropenia (2/28). Postoperative 30-day mortality: 0%. One patient was excluded from efficacy analyses for M1 staging; 27 patients underwent surgery, 26 with R0 (96%). Six cases (22%) show MPR: 3 grade 0 (11%) and 3 grade 1 (11%) tumor regressions. No correlation was seen between MMR proteins or PD-L1 expression and tumor regression. With a median follow-up of 1.5 years (range 0.4-2.5), the disease-free survival rate is projected to be 0.92 (95% CI 0.83-1.00) at 12 months and 0.77 (95% CI 0.58-1.00) at 24 months. Conclusions: The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile. Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment. Clinical trial information: NCT03288350.

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Phase II study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4050 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4050-4050

Author(s):

Hongli Li ◽

Jingyu Deng ◽

Shaohua Ge ◽

Fenglin Zang ◽

Le Zhang ◽

...

Keyword(s):

Adverse Events ◽

Phase Ii ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Death Receptor ◽

Disease Free Survival ◽

Complete Response ◽

R0 Resection ◽

Combination Regimen

4050 Background: FLOT is the standard perioperative treatment for resectable gastric /gastroesophageal junction (GEJ) adenocarcinoma. However, patient’s outcome is still poor. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. This trial evaluates the addition of Toripalimab to FLOT for resectable patients. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥cT2 or cN+) were enrolled to receive 4 pre-and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w). The primary endpoint was pathological complete response rate (pCR). The secondary endpoints included major pathological (complete and nearly complete) response (MPR), and R0-resection rate, 3-year disease-free survival rate, overall survival, and adverse events. Results: In total, of 36 patients were enrolled from June 2019 through Dec 2020. Male, 66.7%; median age, 60y; cT3 8.3%, T4, 83.3%; cN+ 88.9%; GEJ 47%; MSI-H, 5.6%, Her-2neu-positive, 5.6%, EBER-positive, 5.6%). Two patients refused surgery, six patients have not yet completely neoadjuvant treatment. 100% of patients completed the 4 pre-cycle. Patients who had received gastrectomy after neoadjuvant treatment (n=28) were included in this analysis. 6 (21%) patients had operations involving a thoracic approach (oesophagogastrectomy with two field lymphadenectomy), 21 (75%) gastrectomy with D2 lymphadenectomy. 8 (29%) evaluable patients had Clavien-Dindo grade II post-operative complications and 2 (7%) grade IIIA complications; one patient had an anastomotic leakage that was treated endoscopically. There were no emergency re-operations. All 28 patients achieved R0-resection and were discharged home after a median of 12 days (range:7-63) in hospital. 7 （25%）patients achieved pCR (TRG1a) and 12 (42.9%) patients achieved major pathologic response (MPR, TRG1a/b). Treatment-related adverse events (TRAEs) to any drug were reported in 30 (94%) patients. Mostly TRAEs were grade 1-2, the grade 3 or 4 TRAEs included neutropenia (34%), neutropenia (25%), lymphopenia (3%), Alanine aminotransferase increased (3%), hypokalemia (3%) and anaemia (3%). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate and well tolerated safety profile in patients with resectable gastric/GEJ adenocarcinoma. This combination regimen might present a new option for patients with locally advanced, resectable gastric/GEJ adenocarcinoma. Clinical trial information: NCT04354662.

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HER-2 overexpression in gastroesophageal junction (EGJ) adenocarcinoma as a predictor of prognosis in patients treated with perioperative chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.151 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 151-151

Author(s):

Tiago Felismino ◽

Audrey Oliveira ◽

Ana Caroline Alves ◽

Victor Hugo Fonseca Jesus ◽

Wilson L. Costa ◽

...

Keyword(s):

Cox Model ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Primary Site ◽

Clinical Staging ◽

Prognostic Impact ◽

Perioperative Chemotherapy ◽

Dismal Prognosis ◽

Her 2 ◽

Gastroesophageal Adenocarcinoma

151 Background: Approximately 15% of all gastroesophageal adenocarcinomas overexpress HER-2. This is more common in intestinal subtype and proximal tumors. HER-2 status is associated with poor prognosis in non-metastatic patients, but its prognostic impact on the outcomes of pts treated with perioperative chemotherapy (CT) is unclear. Methods: The aim of this study was to retrospectively analyze the influence of HER-2 status on the overall survival (OS) and Relapse Free Survival (RFS) of pts with locally advanced gastroesophageal adenocarcinoma treated with perioperative CT. HER-2 positive tumors were defined by 3+ immunohistochemical staining or fluorescence in situ hybridization positivity. Independent variables used in the Cox model were: Lauren's subtype, clinical staging, and a combination of primary site and HER-2 status. Results: A total of 97 patients were included: median age was 62y, 62 (63.9%) were male; N = 57 (58.8%) had cT3 tumors and 60 (60.1%) had cN+. Lauren’s subtype was intestinal in N = 35 (36.1%), and diffuse in N = 44 (45.4%). CT regimens were mainly FOLFOX (46.4%), EOX (23.7%) or DCF (13.4%). Regarding primary site and HER-2 status: gastric HER-2 negative N = 61, Gastric HER-2 positive N = 8, GEJ HER-2 negative N = 23, GEJ HER-2 positive N = 5. In a Cox multivariate analyses for OS and RFS, EGJ HER-2 positive pts had higher chance of recurrence (HR = 3.57, 1.08 – 11.77, p = 0.03) and death (HR = 6.14, 1.83 – 20.60, p = 0.003). EGJ HER-2+ 3y RFS was zero and 3y OS was 20%. Conclusions: EGJ HER-2+ tumors carried a dismal prognosis and had little benefit from conventional perioperative CT strategies. Although further studies are needed to confirm our data, we believe that a different approach, possible combining anti-HER-2 drugs, should be tested in this scenario.

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Multicenter, randomized phase II study of neoadjuvant pembrolizumab plus chemotherapy and chemoradiotherapy in esophageal adenocarcinoma (EAC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4005 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4005-4005

Author(s):

Manish A. Shah ◽

Khaldoun Almhanna ◽

Syma Iqbal ◽

Prashant Thakkar ◽

Bryan J. Schneider ◽

...

Keyword(s):

Gastroesophageal Junction ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Free Survival ◽

Complete Response ◽

Type I ◽

Immune Microenvironment ◽

Tumor Immune Microenvironment ◽

Grade 3

4005 Background: Recent transformative studies in the treatment of EAC support adjuvant nivolumab for patients with residual disease following neoadjuvant chemoradiotherapy (CRT) (Checkmate 577) and pembrolizumab (P) with chemotherapy in untreated metastatic disease (Keynote 590). We hypothesized that pre-operative P combined with CRT can further improve outcomes in patients with locally advanced EAC. Methods: Patients with cT3-4Nx or T2N1 M0 EAC or gastroesophageal junction (GEJ) adenocarcinoma eligible for curative surgery were randomized (1:1) to receive either full-dose paclitaxel (T)/ carboplatin (C) or T/C + P induction therapy. All patients then received CRT with weekly T/C, RT 41.4Gy in 23 fractions, and P every 3 weeks. Following resection, patients received P for one year. The primary endpoint is rate of major pathologic response (MPR), defined as pathologic complete response or near complete response ( < 10% residual cancer), with 80% power and 0.1 one-sided significance level to detect the difference between a MPR proportion of 30% (historical control) and an alternative hypothesis of 47% (with preoperative P). Tissue was collected for tumor immune microenvironment (TIME) analysis including bulk and single cell RNA(scRNA) expression analysis, DNA sequencing, and flow cytometry. Results: From 8/4/17 to 10/26/20, 40 patients were enrolled: median age 68 [38-81], male 32, esophagus/GEJ type I (n = 16), GEJ II/III (n = 24). CRT was well tolerated, with no grade 3-4 adverse events attributed to P. Notable toxicity included grade 3-4 pneumonitis (13%), anastomotic leak (13%), infection (35%). In 31 evaluable patients to date, the MPR rate was 50.0% (95% CI, 32.7%-67.3%). 1-yr disease free survival was 100% for patients with MPR vs. 31.8% without MPR, p = 0.002. Esophageal/GEJ type I cancers had a significantly higher MPR rate when compared with GEJ type II/III (76.9% vs 37.5%, p = 0.03). scRNA seq on > 100,000 tumor cells revealed EAC/GEJ type I had higher infiltration of activated dendritic cells (p = 0.12), whereas GEJ tumors have significantly higher infiltration of activated B cells (p = 0.02). Conclusions: The addition of P to preoperative CRT for EAC is safe and associated with a significantly higher MPR rate compared to historical data. We found MPR to be significantly enriched in EAC/GEJ type I tumors compared with GEJ II/III, associated with important differences in the baseline tumor immune microenvironment. Clinical trial information: NCT02998268.

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Phase II trial of preoperative (POP) irinotecan (I) + cisplatin (C) and radiotherapy for esophageal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4056 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4056-4056

Author(s):

A. L. Visbal ◽

G. Darling ◽

R. Wong ◽

M. Guindi ◽

J. Hornby ◽

...

Keyword(s):

Esophageal Cancer ◽

Phase Ii ◽

Phase Ii Trial ◽

Residual Disease ◽

Perioperative Complications ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Disease Free Survival ◽

R0 Resection ◽

Thoracic Esophagus

4056 Background: Esophagectomy (E) for locally advanced esophageal cancer (LAEC) yields limited survival; this phase II trial assess feasibility and efficacy of induction chemo-radiotherapy followed by E. Methods: Patients (pts) with LAEC of the thoracic esophagus (TE) or gastroesophageal junction (GEJ), ECOG PS ≤ 2 and surgical candidates underwent POP I (65mg/m2) + C (30mg/m2) on weeks 1,2,4,5,7,8 + concurrent conformal radiotherapy (40Gy/20 fractions (F) during wk 4–7) and external beam boost (10Gy/5F on wk 8); E was performed on wk 12–16 after restaging. Pts receiving 75% of POP chemotherapy were eligible for pathologic (p) evaluation; planned sample size 36 nonM1A pts. Results: 52 pts enrolled from 11/02 to 12/05, mean age 60 yr (33–79), male:40, GEJ:TE/15:37; 37 adenocarcinoma, 13 SCC, 2 other; 13 pts were stage IIA, 7 IIB, 22 III, and 10 IVA. Toxicity during POP treatment included ANC (G3/4:36%), febrile neutropenia (9%), diarrhea (G3:9%), nausea (G3:6%), esophagitis (G3:2%) and anorexia (G3/4:15%); 3 pts stopped treatment due to toxicity, 2 withdrew, 2 progressed becoming non-operable, 1 died of a stroke and 1 from central line sepsis. Clinical response by RECIST was CR:2%, PR:30%, SD:62% and PD in 6%. Dysphagia improved or resolved in 34/47 pts (72%) during POP treatment. Of 43 evaluable pts, 41 underwent E, achieving R0 resection in 98% (1 refused E, 1 pending). Perioperative complications included anastomotic leak (23%), Afib (21%), pneumonia (21%), delirium (10%) and aspiration (10%); 1 pt died from aspiration. 7 pts (17%) achieved pCR, 2 of whom were pretreatment clinical stage IIA, 1 IIb and 4 III; downstaging occurred in 3/7 pts; 15 pts (36.6%) achieved minimal residual disease, 15 (36.6%) pPR, and 4 (9.8%) pSD. At a median (med) follow-up of 15.2 months (1.3–34.5m), 16/52 patients died (med & 2yr overall survival (OS) of 29 m & 66%). Of 41 resected pts, 17 recurred (med & 2yr disease free survival (DFS) of 20m & 46%) of whom 10 died of progression (med & 2-yr OS of 29m & 68.4%). 2yr DFS & OS was 83% & 86% in pCR vs 41% & 76% in non-pCR. Conclusion: In LAEC, induction I/C and radiotherapy followed by E is associated with 72% dysphagia improvement, a significant but manageable toxicity profile, and encouraging survival compared to historical controls. [Table: see text]

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MONEO: A phase II study of avelumab (Av) plus FLOT in the peri-operative treatment for patients (pts) with resectable gastric or gastroesophageal junction cancer (GC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps4155 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS4155-TPS4155

Author(s):

MARIA ALSINA ◽

Mariano Ponz-Sarvise ◽

Dario Lopez Garcia ◽

Marta Gonzalez ◽

Carlos E De Andrea ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Radical Surgery ◽

Checkpoint Inhibitors ◽

Gastroesophageal Junction ◽

Disease Free Survival ◽

R0 Resection ◽

Type I ◽

Metastatic Setting ◽

Biomarker Analysis

TPS4155 Background: GC represents a worldwide problem; radical surgery remaining the gold standard of curative treatment. In the West, even with peri-operative chemotherapy, 5-year survival rate is approximately 40%. GC is a heterogeneous disease, well characterized by different molecular classifications, all having in common the role of the immune system and a T-cell inflamed phenotype across all subtypes. The anti-PD-L1 Av antibody has demonstrated efficacy in GC with response rates of around 10% in the refractory setting. The addition of other immune checkpoint inhibitors to chemotherapy have demonstrated efficacy in the metastatic setting. The combination of Av to perioperative chemotherapy may increase pathological responses by a synergistic effect, and then improving the survival (OS). Methods: The MONEO is an open-label, non-randomized, multicentric, phase II study that explores the combination of Av plus peri-operative FLOT (docetaxel, oxaliplatin, fluorouracil/leucovorin) in resectable GC pts. EudraCT 2019-000782-21; ClinicalTrials NCT03979131. Main inclusion criteria require pts with histologically proven GC, stage Ib (T1N1 only) - IIIC (7th AJCC Ed), available paraffin block from diagnosis and surgery, evaluable disease (RECIST 1.1) amenable to radical surgery. Significant comorbidities and active autoimmune diseases are excluded. Treatment consists of surgery with 4 peri-operatory cycles of FLOT + Av, followed by Av up to one year. The primary objective is the pathological complete response (pCR) rate, compared to historical data. Secondary objectives include OS, disease-free survival, R0 resection rate, tolerability and biomarker analysis. Key point is the comprehensive biomarker analysis from tissue and blood samples (pathological immune response, TCR clonality, immune contexture characterization, immunodynamic monitoring). Statistics for an estimated 33% pCR (historical 16%), 82% power, 0.1 one-side type I error. 37 pts will be recruited from 10 Spanish centers. The sponsor is Vall d'Hebron Institute of Oncology (VHIO), principal investigators Dr. Melero and Dr. Alsina. In compliance with the Helsinki Declaration. At a data cut-off day of 5th of February 2021, 38 patients have been enrolled, 27 of them have had the surgery. Although the difficulties during the COVID19 pandemia, only two patients had been withdrawn from the study. Clinical trial information: NCT03979131.

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624 A PHASE III STUDY ON NEOADJUVANT TORIPALIMAB PLUS CHEMOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY FOR LOCALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Diseases of the Esophagus ◽

10.1093/dote/doab052.624 ◽

2021 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Yan Zheng ◽

Jiangong Zhang ◽

Wenqun Xing

Keyword(s):

Phase Ii ◽

Checkpoint Inhibitors ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Disease Free Survival ◽

Complete Response ◽

Phase Iii ◽

R0 Resection ◽

Phase Iii Trial ◽

Free Survival

Abstract In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in our Hospital. Methods A two-arm phase III trial was launched in April 2020 in our Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Results Until Dec. 2021, one hundred and twenty ESCC patients recruited in the trial. The trial is ongoing. Conclusion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.

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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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Hypofractionated radiotherapy in ten fractions for postmastectomy patients: a phase II study compared with another hypofractionation schedule with sixteen fractions

BMC Cancer ◽

10.1186/s12885-021-09032-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Huayong Jiang ◽

Lingling Meng ◽

Huijuan Zhang ◽

Xiangkun Dai ◽

Qian Zhang ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Disease Free Survival ◽

Skin Toxicity ◽

Trial Registration ◽

Hypofractionated Radiotherapy ◽

Free Survival ◽

Acute Skin Toxicity

Abstract Background The purpose of this phase II study was to evaluate the feasibility of hypofractionated radiotherapy (HFRT) with a dose of 36.5 Gy in 10 fractions in postmastectomy patients. Methods From March 2014 to December 2015, 85 patients with locally advanced breast cancer were eligible to participate in this study with a schedule of 36.5 Gy in 10 fractions. Intensity-modulated radiation therapy (IMRT) was delivered to the chest wall with or without the supraclavicular region. The primary endpoint was radiation-related toxicities. The secondary endpoints were locoregional failure-free survival (LRFFS), disease-free survival (DFS) and overall survival (OS). And the outcomes were compared with our retrospective study of 72 patients with 42.5 Gy in 16 fractions. Results The median follow-up was 69.0 (range 66.5-71.5) months in the 36.5 Gy group and 93.0 (range 91.9-94.1) months in the 42.5 Gy group, respectively. Radiation-related toxicities were mainly grade 1, although a few patients had grade 2 plexopathy (1.2%) and acute skin toxicity (1.2%) in the 36.5 Gy group, and grade 2 acute skin toxicity (5.6%) and lymphedema (4.2%) in the 42.5 Gy group. There were no significant differences between the groups in acute and late toxicities. For all the patients, the 5-year LRFFS, DFS and OS were 97.7 and 100.0%, 93.1 and 90.3%, 98.8 and 97.2%, respectively, without significant differences between the groups. Conclusion Postmastectomy HFRT with a schedule of 36.5 Gy in 10 fractions was feasible, with mild toxicities and excellent 5-year clinical outcome. Trial registration Trial registration number: ChiCTR-ONRC-14004391. Date of registration: 9/3/2014.

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