4057 Background: The postoperative recurrence and metastasis rate of esophageal squamous cell carcinoma (ESCC) remains high and prognosis is poor. PD-1 immune checkpoint inhibitors have shown efficacy in targeting advanced esophageal cancer. This phase II study aims to explore the efficacy and safety of concurrent chemoradiotherapy and immunotherapy for ESCC patients with oligometastatic recurrence after radical surgery. Methods: This phase II study enrolled ESCC patients from 3 hospitals in China, diagnosed oligometastatic recurrence after radical surgery. The 1st stage, with 10 patients enrolled, was designed to explore the safety level and the 2nd stage was to explore efficacy. The oligorecurrence is defined as progression occurring three months after the operation with no more than three metastatic regions. The local recurrence was defined as tumor bed or anastomotic recurrence. The regional lymph node recurrences were regarded as mediastinal region and celiac lymph, respectively. The distal recurrences were considered as supraclavicular, retroperitoneal region and other distal organs. All of the positive regional lymph nodes were collectively counted as one lesion if regional lymph node recurrences existed. Tisleizumab was delivered on D1,22. Nab-paclitaxel 150mg/m2 (starting on D2,23) and cisplatin, 75mg/m2(starting on D2-4,22-24) were administered for two cycles. The radiotherapy was delivered with 50.4-60Gy, 1.8-2Gy per fraction. After CRT, patients received Tisleizumab every 3 weeks for 3-6 months and 2-4 cycle consolidation chemotherapy. The primary endpoint was 1-year OS, the second endpoints were 1-year PFS, ORR and toxicities. Results: Between Jan 2021 and May 2023,50 patients were screened for enrolment and 44 patients met the eligibility criteria. The metastatic regions were made up by the local (15.9%),regional (47.7%), distal (13.6%) and mixed recurrence (22.7%). In the 1st stage, one patient had a grade-3 Immune-related erythra out of ten patients. All patients were delivered chemoradiotherapy, 36(81.8%) patients had completed two cycles of immunotherapy. The ORR rate was 84.1%. During concurrent chemoradiotherapy, the incidence of grade≥3 treatment-related adverse events was nausea (9.1%), vomit (4.5%), anorexia (4.5%), leukopenia (13.6%), hepatitis (2.3%), radiation esophagitis (1.4%), erythra (4.5%). There were 5 cases of Immune-related adverse, including 2 cases of erythra, 1 case of hypothyroidism, hepatitis, gastroenteritis, respectively. With the median follow-up time of 19 months (range:4-30 months), 1-year OS and PFS was 83.2% and 79.2%. The median OS and the median PFS were not reached. Conclusions: Concurrent chemoradiotherapy and immunotherapy yielded satisfactory 1-year OS rate and manageable toxicities in oligometastatic recurrence patients with ESCC after radical surgery. Clinical trial information: NCT04821765 .

PSCCE is characterized by a high degree of malignancy with high risks of lymphatic and distant metastasis, N and M stages are the most important prognostic factor. In terms of treatment, comprehensive treatment is most likely to benefit patients without distant metastasis.

Purpose/Objective(s) There has been a steady increase in the incidence of esophageal squamous cell carcinoma (ESCC) among elderly patients. The optimal treatment approach of elderly ESCC patients was still vague. Materials/Methods Between March 2017 and April 2020, 339 patients were screened in 10 centers in China; 184 and 146 patients were randomized into the S-1 based chemoradiotherapy followed by S-1 monotherapy (CRT-CT arm) or radiotherapy alone (RT arm). CRT-CT arm consisted simultaneous integrated boost radiotherapy (SIB-RT) (dose, 59.92 Gy/50.4 Gy) in 28 daily fractions administered using intensity-modulated radiotherapy or volumetric modulated arc therapy. S-1 was orally administered (40–60 mg/m2) concurrently with radiotherapy and 4–8 weeks later, for up to four 3-week cycles at the same dose. RT arm performed SIB-RT alone with the same radiotherapy dose. The primary endpoint was overall survival (OS) of the intention-to-treat (ITT) population. Results In the ITT population, 63.9% and 24.8% had T3 and T4 stage disease, and 68.8% had nodal metastases. The median OS was 27.8 months in the CRT-CT arm and 20.8 months in the RT arm and the OS rates were 72.5% vs 62.8% at 1 year; 55.2% vs 43.7% at 2 years; 45.5% vs 33.7% at 3 years ((hazard ratio, 0.75; 95% CI, 0.56–0.99; P = 0.041). The median PFS was 19.5 months in the CRT-CT arm and 11.5 months in the RT arm. Time dependent cox regression model revealed Charlson comorbidity index, BMI and cumulative chemotherapy cycles were independent prognostic factors associated with OS. OS and PFS of patients treated with 5–6 cycles of chemotherapy were superior to those of the patients treated with 0 (treated with radiotherapy alone), 1–2 and 3–4 cycles. There was no significant increase in the incidence of toxicities higher than grade 3 in the CRT-CT arm. Grades 4 and 5 toxicities were reported in 2.8% and 2.8%, respectively, of the CRT-CT arm compared with 0% and 4.2%, respectively, of the RT arm Conclusion Oral S-1 chemotherapy administered with SIB-RT is highly recommended for elderly patients with inoperable ESCC as an alternative treatment modality that improves survival outcomes with a more favorable side-effects profile.

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

This study aimed to assess the toxicity profile and efficiency of S1 based simultaneous integrated boost radiotherapy (SIB-RT) followed by consolidated chemotherapy with S1 in elderly pts with esophageal cancer (EC) and to evaluate the feasibility and usefulness of comprehensive geriatric assessment (CGA). We enrolled pts if they met the following criteria with stratifications of medical center and clinical TNM stage: (1) ≥ 70 years, (2) histopathologically proved squamous cell carcinoma of EC, (3) clinical stage II-III, or IV consisting of metastatic lymph nodes in the supraclavicular/abdominal para-aortic area according to AJCC 6th, (4) Charlson score ≤ 3. SIB-RT consisted two dose levels (59.92 and 50.4 Gy in 28 fractions) with concurrent S-1 80, 100, 120 mg/d based on body surface area, 5 days/week. S-1 was repeated up to four cycles (the same daily dosage as chemoradiotherapy (CRT), days 1-14, every 3 weeks) 4-8 weeks after CRT. The primary endpoint was overall responding rate (ORR) determined within three months after CRT. All pts completed CGA before CRT including functional status, comorbidity, cognitive function, psychological state, social support, and nutritional status. Among these questionnaires, QOL and dysphagia were evaluated before and after CRT. This trial was registered with ClinicalTrials.gov, number NCT 02979691. Between September 2016 and March 2017, 46 pts (median age, 75 years; stage II vs III vs IV, 21 vs 19 vs 6, 46% vs 41% vs 13%) were enrolled from eight medical centers. The ORR was seen in 36 (78.3%) pts. Grade 3 toxicities were: esophagitis (5, 11%), nausea (4, 9%) and anorexia (3, 7%). No Grade 4-5 toxicity occurred. Consolidation monotherapy with S-1 was continued for 2 cycles in 37 pts (80%), 3 cycles in 32 pts (70%), and 4 cycles in 30 pts (65%). The reasons for withdrawal of S-1 monotherapy included refusal of the patient (5 pts) and poor recovery from CRT (1 pts). With a median follow-up time of 22.4 months, the median overall survival was 22.1 months. The 1- and 2- year overall survival, progression-free survival, locoregional-recurrence free survival and distant-metastasis free survival were 80.4% and 48.9%, 71.3% and 52.4%, 79.8% and 67.0%, 86.1% and 80.7%, respectively. The scores of QOL (P=0.119) and dysphagia (P=0.106) showed no significant difference after CRT compared to baseline. However, 70% of the pts were found to be with malnutrition, 40% with poor activities of daily living, 36% with cognitive impairment, and 27% with moderate to severe depression at diagnosis before CRT. S-1 with concurrent SIB-RT followed by four cycles of S-1 monotherapy was feasible and tolerable for selected elderly pts with EC. It was worth noticing that CGA could uncover numerous health problems in the elderly before treatment and may allow appropriate support of care provided for these pts. A multicenter randomized phase III study comparing S-1 based SIB-RT followed by S-1 monotherapy with SIB-RT alone for EC in the elderly is ongoing.

Large-scale reports on survival outcomes of Chinese patients with esophageal cancer are scarce. The aim of this study is to investigate the impact of definitive (chemo)radiotherapy using three dimensional conformal radiation (3DCRT) or intensity-modulated radiotherapy (IMRT) on survival outcomes in non-operated localized esophageal squamous cell carcinoma (LESCC). A total of 2,762 patients with LESCC extracted from 3,325 patients primarily treated in ten Chinese institutions between 2001 and 2015 were retrospectively analyzed. The enrolled criteria included: age >18, histologically confirmed squamous cell carcinoma, staged as cT1-4N0-1M0-M1b (according to AJCC 6th edition) without visceral metastasis and no metastatic lymph nodes other than supraclavicular or celiac trunk area, treated with 3DCRT or IMRT, prescription dose ≥40 Gy, no prior thoracic radiation or chemotherapy and follow-up time ≥6 months for patients alive. The overall survival (OS) was calculated with the Kaplan-Meier method and possible prognostic factors were analyzed based on COX regression. Median age was 65 years (range, 30-90), and most patients were male (68.9%). Primary tumor location in cervical, upper, middle and lower of esophagus were determined in 4.8%, 28.4%, 45.4%, and 20.5%. The median length of tumor was 5cm (range, 1-19). The median target volume of primary tumor and metastatic lymph node (GTVv) was 43.9cm3 (range, 1-293). The patients were clinically staged as stage I (0.8%), IIa/b (24.7%), III (52.5%), and IVa/b (22%). Treatment including chemoradiotherapy (CRT), CRT plus adjuvant chemotherapy (CRT+CT), radiotherapy (RT), RT plus adjuvant chemotherapy (RT+CT) were 32.2%, 10.6%, 50.7%, and 6.5% of the patients. With a median follow-up of 60.8 months, the 5-year OS and median survival time (MST) were 30.9% and 23.0 months for the whole group. OS and MST based on clinical stage were stage I, 67.6% and 66 months, stage IIa, 46.3% and 51.3 months, stage IIb, 35.9% and 25.8 months, stage III, 27.7% and 21.8 months, stage IVa, 24.3% and 17.1 months, stage IVb, 23.5% and 16.8 months. In the multivariate analysis, age>68 (HR: 1.14, 95% CI: 1.03-1.26, P = 0.014), female (HR: 0.90, 95% CI: 0.81-0.99, P = 0.051), length > 5cm (HR: 1.10, 95% CI: 1.0-1.22, P = 0.055), clinical stage IVa/b (HR: 2.54, 95% CI: 1.34-4.8, P = 0.004), CRT+CT (HR: 0.79, 95% CI: 0.66-0.95, P = 0.012), RT dose ≥60Gy (HR: 0.59, 95% CI:0.38-0.91, P =0.017) and GTVv > 50cm3 (HR: 1.38, 95% CI:1.25-1.53, P < 0.001) were independent prognostic factors. While, radiotherapy technique (3D-CRT vs IMRT) and tumor location did not significantly impacted on prognosis. Compared with contemporary outcomes, this cohort had better prognosis even nearly two thirds of patients with locally advanced stage III or IV esophageal cancer. These results may be due to the superior radiotherapy techniques and chemotherapy applied. We will conduct further analysis to provide more scientific evidence for individualized treatment in LESCC.

The role of definitive intensity-modulated radiotherapy with a simultaneous integrated boost (SIB-IMRT) in treating non-operated localized esophageal squamous cell carcinoma (LESCC) remains unclear. We investigated the effect of SIB-IMRT on the survival outcome of patients with LESCC who receiving definitive radio/chemoradiotherapy. A total of 1606 patients with LESCC from nine institutions were retrospectively reviewed. Among them, 556 patients (34.6%) received SIB-IMRT which consisted a prognostic dose delivered to the planning target volume (PTV) with a median of 54 Gy/1.8-2.0Gy fraction. The boost dose was given to the primary tumor and metastatic regional lymph nodes to a median total dose of 61.5Gy/2.0-2.3Gy fraction. For patients with conventional fractionated radiotherapy (CFR), PTV was prescribed to 60Gy/1.8-2.0Gy fraction. A propensity score matching (PSM) method (1:1 for SIB-IMRT vs CFR) was used to identify 932 well-balanced patients for validation studies. Actuarial survival was calculated with the Kaplan-Meier method, and univariate comparison between groups was performed by using the log-rank test. Cox regression served as a multivariate technique using a backward elimination model for all covariates. Median age was 64 years, and most patients were male (72.7 %). Primary tumor location in cervical, upper, middle and lower of esophagus were determined in 6%, 35%, 48% and 12%. The patients were clinically staged as stage IIa/b (22%), III (56%), and IVa/b (without visceral metastasis or positive lymph node out of regional site) (22%), according to AJCC 6th TNM classification. After PSM, the 2-year overall survival (OS) and median survival were 51.5% and 28 months in SIB-IMRT group, which is significantly higher than that in CFR group (46.5% and 24 months, P<0.001). In the multivariate survival analysis, clinical stage (Hazard Ratio [HR]: 1.53, 95% CI: 1.38-1.97, P < 0.001), tumor length (HR: 1.05, 95% CI: 1.02-1.08, P = 0.001), female (HR: 0.81, 95% CI: 0.69-0.95, P = 0.011), concurrent chemoradiotherapy (HR: 0.76, 95% CI: 0.67-0.88, P < 0.001) and SIB-IMRT (HR: 0.89, 95% CI: 0.77-0.97, P = 0.034) were independent prognostic factors. Subgroup analysis suggested patients with age ≤70, upper 1/3 esophageal cancer, tumor length ≤5cm, and cN0 stage tumors were more likely to demonstrate survival benefit from SIB-IMRT. Compared with CFR, SIB-IMRT may provide a survival benefit to LESCC patients. A prospective study is needed to verify our findings and to provide scientific evidence for this subject.