Optimization of radiation target volume for locally advanced esophageal cancer in the immunotherapy era.
Expert opinion on biological therapy
INTRODUCTION:Locally advanced esophageal cancer (EC) has poor prognosis. Preliminary clinical studies have demonstrated the synergistic efficacy of radiotherapy combined with immunotherapy in EC. Adjusting the radiotherapy target volume to protect immune function favors immunotherapy. However, there is no clear consensus on the exact definition of the EC target volume. AREAS COVERED:Preclinical studies have provided a wealth of information on immunotherapy combined with different radiotherapy modalities, and several clinical studies have evaluated the impact of immunotherapy combined with radiotherapy on locally advanced EC. Here, we illustrate the rational target volume delineation for radiotherapy in terms of patient prognosis, pattern of radiotherapy failure, treatment-related toxicities, tumor-draining lymph nodes, and systemic immunity and summarize the clinical trials of radiotherapy combined with immunotherapy in EC. EXPERT OPINION:We recommend applying involved-field irradiation (IFI) instead of elective nodal irradiation (ENI) for irradiated fields when immunotherapy is combined with chemoradiotherapy (CRT) for locally advanced EC. We expect that this target design will be evaluated in clinical trials to further explore more precise diagnostic modalities, long-term toxic responses, and quality of survival, and stratification factors for personalized treatment, and to provide more treatment benefits for patients.
10.1080/14712598.2024.2423009
Survival benefit of combined immunotherapy and chemoradiotherapy in locally advanced unresectable esophageal cancer: an analysis based on the SEER database.
Frontiers in immunology
Background:While simultaneous chemoradiotherapy remains the established therapeutic modality for patients afflicted with locally advanced esophageal cancer, the effectiveness of this radical approach falls short of the desired outcome. Numerous investigations have illuminated the prospect of enhancing therapeutic efficacy through the amalgamation of chemoradiotherapy and immunotherapeutic interventions. Consequently, we embarked on an examination to scrutinize the potential survival advantages conferred by the confluence of chemoradiotherapy and immunotherapy in relation to locally advanced unresectable esophageal carcinoma, drawing upon the extensive SEER database for our analysis. Methods:We extracted clinicopathological attributes and survival statistics of patients afflicted with locally advanced unresectable esophageal carcinoma, diagnosed within the temporal span encompassing the years 2004-2014 and 2019-2020, from the extensive SEER database. To discern disparities in both overall survival (OS) and cancer-specific survival (CSS) between the cohorts subjected to chemoradiotherapy combined with immunotherapy and chemoradiotherapy alone, we employed analytical tools such as Kaplan-Meier analysis, the Log-rank test, the Cox regression proportional risk model, and propensity-matched score (PSM) methodology. Results:A total of 7,758 eligible patients were encompassed in this research, with 6,395 individuals having undergone chemoradiotherapy alone, while 1,363 patients received the combined treatment of chemoradiotherapy and immunotherapy. After 1:4 propensity score matching, 6,447 patients were successfully harmonized, yielding a well-balanced cohort. The Kaplan-Meier curves demonstrated a substantial enhancement in OS (P = 0.0091) and CSS (P < 0.001) for the group subjected to chemoradiotherapy combined with immunotherapy as compared to chemoradiotherapy alone. Further multivariable analysis with PSM confirmed that chemoradiotherapy combined with immunotherapy benefits OS(HR=0.89, 95% CI 0.81-0.98) and CSS (HR=0.68, 95% CI 0.61-0.76). In addition, Univariable and multivariable Cox regression analyses of the matched patient groups unveiled several independent prognostic factors for OS and CSS, including sex, age, marital status, tumor location, tumor size, pathologic grade, SEER historic staging, and treatment modality. Among these factors, being female, married, and receiving chemoradiotherapy combined with immunotherapy emerged as independent protective factors, while age exceeding 75 years, non-superior segment tumor location, tumor size greater than 6 cm, Grade 3-4 pathology, and regional SEER historic staging were all found to be independent risk factors. The survival advantage of the chemoradiotherapy combined with the immunotherapy group over the chemoradiotherapy alone group was substantial. Conclusions:This investigation furnishes compelling evidence that the integration of immunotherapy with chemoradiotherapy confers a noteworthy survival advantage when contrasted with conventional chemoradiotherapy for individuals grappling with locally advanced unresectable esophageal carcinoma.
10.3389/fimmu.2024.1334992
Radiotherapy for patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy combined with chemotherapy.
Scientific reports
With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0 (AJCC 8th), PS 0-1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors plus chemotherapy (albumin paclitaxel, 260 mg/m on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2-4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4 Gy/28F or 50 Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m, d1, carboplatin AUC = 2, d1) or S1 (60 mg bid d1-14, 29-42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, among all the patients, 25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 20.4 months (interquartile range [IQR] 8.7-27 months). The median PFS and OS were 17.9 months (95% confidence interval [CI] 11.0-21.9 months) and 20.5 months (95% CI 11.8-27.9 months), respectively. In the subgroup analysis, the median OS was 26.3 months (95% CI 15.33-NA) for patients exhibiting partial response (PR) to CIT, compared to 17 months (95% CI 8.77-26.4) for those with stable disease (SD) or progressive disease (PD), yielding a hazard ratio (HR) of 0.54 (95% CI 0.27-1.06, P = 0.07). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 0.73 (95% CI 0.72-2.6, P = 0.33). The most common Adverse events (AEs) observed during this study were anemia (98.2%), leukopenia (83.9%), thrombocytopenia (53.6%). AEs of grade ≥ 3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula.
10.1038/s41598-024-67419-6
Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy.
World journal of gastrointestinal oncology
Four major studies (Checkmate577, Keynote-590, Checkmate649 and Attraction-4) of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy, represented by anti-programmed death protein (PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer, from the aspects of proof of concept, long-term survival, overall survival rate and progression-free survival. For unresectable or inoperable nonmetastatic esophageal cancer, concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines. Because its curative effect is still not ideal, it is necessary to explore radical radiotherapy and chemotherapy in the future, and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1. This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.
10.4251/wjgo.v16.i1.1
Radiotherapy for Advanced Esophageal Cancer: from Palliation to Curation.
Current treatment options in oncology
OPINION STATEMENT:Esophageal cancer is a global health problem, which is 7th most common and 6th most deadly cancer. It has been the era of immuno-oncology for esophageal cancer management. Radiation therapy has been one of the key local therapeutic approaches for esophageal cancer treatment, while its role in advanced disease is challenging and debatable. There have been emerging clinical and translational studies of radiation therapy in recurrent or metastatic esophageal cancer. Immunotherapy has been established the standard care of 1st and 2nd line systemic therapies of advanced esophageal cancer, and the development of tumor immunity has opened a new chapter for the esophageal cancer radiation therapy. The current review will summarize the classic radiation therapy research in advanced esophageal cancer, as well as the most recent key findings. The subtitles will cover palliative radiotherapy for dysphagia, re-radiation for recurrent disease, oligo-focal disease management and stereotactic radiation therapy, and radiotherapy with immunotherapy. Radiotherapy plays vital role in multidisciplinary management of advanced EC. External or intratumoral irradiation has been used for palliation of dysphagia and improving QOL in esophageal cancer patients traditionally, while recent clinical and technical advance enables radiotherapy to be considered in recurrent or metastatic disease for curation attention. Novel clinical and translational investigation is opening a new chapter of radiotherapy with immunotherapy for benefiting advanced EC patients.
10.1007/s11864-023-01134-8
Combine radiotherapy and immunotherapy in esophageal squamous cell carcinoma.
Critical reviews in oncology/hematology
Immune checkpoint inhibitors(ICIs) have improved the survival of advanced esophageal squamous cell carcinoma (ESCC) patients. Radiotherapy is one of the common therapies to treat esophageal cancer. However, whether combination radiation therapy can increase the efficacy of immunotherapy is still up for debate. Radiotherapy combined with immunotherapy has proven to be a reliable and effective treatment for tumors, and it can work in combination with immunotherapy to achieve better anti-tumor effects. This review aims to discuss the efficacy and safety of combining radiotherapy and immunotherapy to treat ESCC by stages as well as the optimum radiotherapy dose and target volume, with a summary of clinical trials in ESCC.
10.1016/j.critrevonc.2023.104115