4016 Background: 70% of esophageal carcinoma are unresectable at diagnosis. Despite active clinical research on the treatment of esophageal squamous cell carcinoma (ESCC), the long-term survival rate of advanced patients is still very low, with a 5-year survival rate of 30%-40%. A prospective, randomized-controlled, double-blinded, multicenter, and phase III study (NXCEL1311) was designed to investigate the efficacy and safety of nimotuzumab (anti-EGFR humanized monoclonal antibody;abbreviate,Nimo) plus concurrent chemo-radiotherapy compared with placebo plus chemo-radiotherapy in unresectable locally advanced ESCC. Methods: Unresectable locally advanced ESCC patients were randomized (1:1) to receive Nimo (400 mg, qw) or placebo in combination with concurrent chemo-radiotherapy (paclitaxel+ cisplatin+3DCRT/IMRT) for seven weeks. Patients were followed for five years.The primary endpoints were OS, and the secondary endpoints included ORR, DCR, PFS. Results: 200 patients were assigned to the Nimo group (n = 99) or placebo group (n = 101). An interim analysis was conducted for short term efficacy, i.e secondary endpoints (ORR, DCR) and safety, after completing the 6 months follow-up. The OS events are not enough for analysis. The two groups were comparable on baseline characteristics. Eighty patients in the Nimo group and eighty-two patients in the placebo group were evaluable. The ORR of the Nimo group (75/80, 93.8%) was significantly higher than the placebo group (59/82, 72.0%;Chi-square test, p < 0.001). Twenty-six patients in the Nimo group reached the complete response (CR), and ten placebo group patients were CR. The CR rate in the Nimo group was significantly higher than placebo group (32.5% vs.12.2%, p = 0.002). The DCR of the Nimo group and placebo group were 98.8% (79/80) and 91.5% (75/82), respectively (p = 0.064). Single factor logistic aggression analysis showed that age, sex, target lesion number, and BMI did not affect ORR, CR, and DCR (p > 0.05). Multiple factor correction analysis showed the difference of CR, ORR and DCR between two groups is 20% (95%CI 6.0%̃40.2%), 30% (95%CI 10.6%̃52.1%) and 10% (95%CI -5.2%̃31.1%). The incidence of grade 3-5 drug-related AEs was 11.1%vs.10.9% (p > 0.05). Common drug-related AEs in patients with Nimo plus chemo-radiotherapy treatment were leucopenia, neutrophilic granulocytopenia, thrombocytopenia, hemoglobin, bone marrow inhibition, nutritional anemia, and radioactive inflammation. Conclusions: This interim analysis showed that nimotuzumab in combination with chemo-radiotherapy is safe and can increase the CRR and ORR of the treated patients. The OS needs to be followed and finally analyzed. Clinical trial information: 02409186.

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Background To study lymphatic recurrence distribution after radical surgery in the real world and guide clinical tumor volume delineation for regional lymph nodes during postoperative radiotherapy for lower thoracic squamous cell esophageal carcinomas. Methods We enrolled patients who underwent radical esophagectomy, without radiation before or after surgery, at 3 cancer hospitals. Patients were classified into groups according to tumor locations. We included patients with tumors in the lower thoracic segment and analyzed the postoperative lymph node recurrence mode. A cutoff value of 10% was used to differentiate high-risk lymph node drainage areas from others. Results We enrolled 1905 patients in the whole study series, including 652 thoracic esophageal carcinomas that met our inclusion criteria; there were 241 cases of lower thoracic esophageal carcinomas. 1st, 2nd, 4th, 7th, 8th groups of lymph nodes, according to the 8th edition of the AJCC classification, displayed as high-risk recurrence areas, representing 17.8%, 23.9%, 11.7%, 10.9% and 12.2% of lymph node recurrence. Stage III-IV tumors located in the lower segment of the thoracic esophagus showed a tendency to recur in the left gastric nodes (7.9%) and celiac nodes (10.6%). Conclusions According to our results, we recommended including the 4th, 7th and 8th groups of lymph nodes in the radiation field, and for patients with stage III-IV disease, the 17th and 20th groups of nodes should be irradiated during postoperative treatment. Whether including 1st/2nd groups in preventive irradiation needed more proofs.

INTRODUCTION: Adjuvant radiotherapy is recommended for pT1b esophageal squamous cell cancer (ESCC) after endoscopic submucosal dissection (ESD). However, it is unclear whether additional radiotherapy can improve patient survival. This study aimed to evaluate the efficacy of adjuvant radiotherapy after ESD for pT1b ESCC. METHODS:This was a multicenter, cross-sectional study involving 11 hospitals in China. Between January 2010 and December 2019, patients with T1bN0M0 ESCC treated with or without adjuvant radiotherapy after ESD were included. Survival between groups was compared. RESULTS:Overall, 774 patients were screened, and 161 patients were included. Forty-seven patients (29.2%) received adjuvant radiotherapy after ESD (RT group) and 114 (70.8%) underwent ESD alone (non-RT group). There were no significant differences in overall survival (OS) and disease-free survival (DFS) between the RT and non-RT groups. Lymphovascular invasion (LVI) was the only prognostic factor. In the LVI1 group, adjuvant radiotherapy significantly improved survival (5-year OS: 91.7% vs 59.5%, P 5 0.050; 5-year DFS: 92.9% vs 42.6%, P 5 0.010). In the LVI2 group, adjuvant radiotherapy did not improve survival (5-year OS: 83.5% vs 93.9%, P 5 0.148; 5-year DFS: 84.2% vs 84.7%, P 5 0.907).The standardized mortality ratios were 1.52 (95% confidence interval 0.04-8.45) in the LVI1 group with radiotherapy and 0.55 (95% confidence interval 0.15-1.42) in the LVI2 group without radiotherapy. DISCUSSION:Adjuvant radiotherapy could improve survival in pT1b ESCC with LVI1 other than LVI2 after ESD. Selective adjuvant radiotherapy based on LVI status achieved survival rates similar to those of the general population.

TPS8607 Background: Stereotactic body radiation therapy (SBRT) is a standard treatment for patients with unresectable (UR) stage I/II, lymph-node negative NSCLC, with excellent safety and high rates of primary tumor control. Despite predominant regional and distant failure that increases with tumor size, no adjuvant therapy is approved for these patients. Durvalumab is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1/CD80. In the placebo-controlled, phase 3 PACIFIC trial of patients with stage III UR-NSCLC without disease progression on/after concurrent chemoradiotherapy, durvalumab improved progression-free survival (PFS) and overall survival (OS) with manageable safety (Antonia, et al. 2017; 2018), leading to its approval in stage III UR-NSCLC. Osimertinib is a 3rd-generation, irreversible CNS-active EGFR tyrosine kinase inhibitor that selectively inhibits NSCLC tumors with EGFR-sensitizing mutations (EGFRm). In the recent placebo-controlled, phase 3 ADAURA trial, osimertinib demonstrated statistically significant and clinically meaningful improvement in disease-free survival (DFS) (HR, 0.20 [99.12% CI, 0.14–0.30], P < 0.001) in patients with resected stage IB-IIIA EGFRm NSCLC (Wu, et al. 2020), leading to its approval in an adjuvant setting. Based on data for durvalumab and osimertinib in the early-stage setting, PACIFIC-4 is designed to assess the efficacy and safety of durvalumab combined with SBRT in patients with stage I/II UR-NSCLC and osimertinib after SBRT in patients with stage I/II EGFRm UR-NSCLC. Methods: PACIFIC-4 (NCT03833154) is an international, phase 3 study with two independent cohorts. Eligible patients are ≥18 years of age with stage T1-T3, N0, M0 unresected NSCLC and ECOG PS 0–2. The main cohort of approximately 630 patients will be randomized (1:1) in a double-blind manner, stratified by tumor size and location, to receive durvalumab (1500 mg IV) or placebo every 4 weeks for up to 26 cycles with concurrent standard of care (SoC) SBRT. The primary endpoint in this cohort is PFS (RECIST v1.1) by blinded independent central review; other endpoints include OS, health-related quality of life, and safety. The protocol was amended (v4) to exclude patients with an identified EGFRm from the main cohort and add a separate cohort of approximately 60 patients with EGFRm (L858R or Ex19del) who will receive osimertinib 80 mg PO QD, following SoC SBRT, for up to 36 months. The primary endpoint in this cohort is 4-year PFS (RECIST v1.1) by independent central review; secondary endpoints include PFS, OS, and safety. Trial recruitment is ongoing. Previously presented at the European Lung Cancer Congress (ELCC) 2022, FPN (Final Publication Number): 122TiP, Clifford Robinson et al. – Reused with permission. Clinical trial information: NCT03833154 .