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Definitive chemoradiotherapy (CRT) with docetaxel (DOC) and 5-fluorouracil (5-FU) is a unique regimen for esophageal cancer. In this prospective phase II study, antitumor effect and safety of CRT using DOC and 5-FU for inoperable locally advanced esophageal cancer were evaluated. DOC 7.5 mg/m2 was infused on days 1, 8, 22, and 29. 5-FU 250 mg/m2/day was infused continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-45. Radiotherapy was given to 66 Gy in 33 fractions. Eleven patients with thoracic and five with cervical esophageal cancer were eligible. All patients had esophageal squamous cell carcinoma (ESCC). The response rate was 94%, with complete response in five patients (31%) and partial response in 10 (63%). Hematologic toxicity was mild; only one patient (6%) had Grade 1 leukopenia. Nonhematologic Grade 3 or higher adverse events were esophagitis (31%), anorexia (6%), and esophago-bronchial fistula (6%). No treatment-related deaths occurred. The median time to progression was 20 months and overall 3-year and 5-year survival were 44% and 31%, respectively. DefinitiveCRT usingDOCand 5-FU could be performed safely, and it demonstrated a favorable antitumor effect for ESCC. This regimen might be indicated in patients in whom it is desirable to avoidmyelosuppression and progression of renal impairment. [ABSTRACT FROM AUTHOR]

Definitive chemoradiotherapy ( CRT) with docetaxel ( DOC) and 5-fluorouracil (5- FU) is a unique regimen for esophageal cancer. In this prospective phase II study, antitumor effect and safety of CRT using DOC and 5- FU for inoperable locally advanced esophageal cancer were evaluated. DOC 7.5 mg/m2 was infused on days 1, 8, 22, and 29. 5- FU 250 mg/m2/day was infused continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-45. Radiotherapy was given to 66 Gy in 33 fractions. Eleven patients with thoracic and five with cervical esophageal cancer were eligible. All patients had esophageal squamous cell carcinoma ( ESCC). The response rate was 94%, with complete response in five patients (31%) and partial response in 10 (63%). Hematologic toxicity was mild; only one patient (6%) had Grade 1 leukopenia. Nonhematologic Grade 3 or higher adverse events were esophagitis (31%), anorexia (6%), and esophago-bronchial fistula (6%). No treatment-related deaths occurred. The median time to progression was 20 months and overall 3-year and 5-year survival were 44% and 31%, respectively. Definitive CRT using DOC and 5- FU could be performed safely, and it demonstrated a favorable antitumor effect for ESCC. This regimen might be indicated in patients in whom it is desirable to avoid myelosuppression and progression of renal impairment. [ABSTRACT FROM AUTHOR]

Abstract Background Leiomyosarcoma (LMS) of the gastrointestinal tract is an extremely rare high-grade neoplasm with poor prognosis. For advanced LMS with distant metastasis, the decision as to the choice of the most appropriate therapeutic strategy, including chemotherapy and surgery, is difficult. Here, we present an unusual case of LMS of the sigmoid colon with liver metastases and gastric cancer. The survival of this patient was prolonged by a combined modality therapy involving chemotherapy and surgery. Case presentation A 66-year-old woman who had been diagnosed with advanced gastric cancer and multiple liver metastases was referred to our hospital. The initial treatment with docetaxel and S-1 considerably reduced both the gastric cancer and liver tumors; consequently we performed surgical resection. Pathological examination revealed that no viable tumor cells remained in the stomach and chemotherapy resulted in complete remission of the gastric cancer. The liver tumors were immunohistochemically diagnosed as LMS. A tumor of the sigmoid colon was subsequently discovered and the liver tumors were found to have recurred. The surgically resected sigmoid colon and liver tumors were all immunohistochemically diagnosed as LMS. These findings indicated that the multiple liver metastases arose from the LMS in the sigmoid colon, and that they were accompanied by advanced gastric cancer. We performed another surgical resection and administered chemotherapy to treat the recurring liver metastases. The patient survived for 4 years and 10 months after initial presentation at our hospital. Conclusion Colonic LMS is rare and its joint occurrence with gastric cancer is extremely unusual. Although LMS is a high-grade neoplasm, a multimodal therapeutic approach can increase patient survival time even when multiple liver metastases are present.

Background: Patients across various cancers who develop immune-related adverse events (irAEs) post-immune checkpoint inhibitor (ICI) treatment tend to experience better tumor response and survival than those who do not. However, studies regarding this association in patients with esophageal squamous cell carcinoma (ESCC) are limited., Methods: We assessed the relationship of irAEs with tumor response and survival in 82 consecutive patients with unresectable advanced or recurrent ESCC treated with second- or later-line nivolumab, an anti-PD-1 antibody, monotherapy., Results: We observed irAEs in 24 (29.3%) patients, with the overall response and disease control rates in the irAE-positive group being significantly better than those in the irAE-negative group (both p < 0.0001). During the entire period and within 8 weeks of nivolumab initiation, progression-free and overall survivals (PFS and OS, respectively) were significantly better in patients with grade1/2 irAEs than in those without. Univariate and multivariate analyses indicated grade1/2 irAEs during the entire period and within 8 weeks as independent covariates for PFS (entire period: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.16-0.49, p < 0.001; within 8 weeks: HR 0.46, 95% CI 0.23-0.93, p = 0.03) and OS (entire period: HR 0.24, 95% CI 0.13-0.44, p < 0.001; within 8 weeks: HR 0.41, 95% CI 0.18-0.92, p = 0.03)., Conclusions: Grade1/2 irAEs during the entire treatment period and within 8 weeks of nivolumab initiation were significantly associated with improved tumor response and survival in patients with advanced ESCC treated with nivolumab monotherapy. Therefore, mild irAEs may be predictive markers for the response and prognosis of ESCC following ICI treatment.

Background: The authors hypothesized that small ribonucleic acid (sRNA) obtained from blood samples after neoadjuvant therapy from patients treated with neoadjuvant chemoradiation therapy (NACRT) could serve as a novel biomarker for predicting pathologic complete response (pCR)., Methods: This study included 99 patients treated with esophagectomy after NACRT between March 2010 and October 2021 whose blood samples were collected between the end of NACRT and surgery. Next-generation sequencing (NGS) was used to analyze sRNAs from the blood samples. A predictive model for pCR comprising micro-RNA isoforms (isomiR), transfer RNA (tRNA)-derived sRNAs (tsRNAs), and clinical factors was constructed using cross-validation., Results: Of the 99 patients, pCR was diagnosed for 30 and non-pCR for 69 of the patients. Among sRNAs, the isomiRs of let-7b and miR-93 and the tsRNA group derived from tRNA-Gly-CCC/GCC were identified as predictive factors. The clinical factors included a decrease in the maximum standardized uptake value (SUVmax) at the primary site, clinical complete response post-NACRT, preoperative biopsy, and post-NACRT carcinoembryonic antigen levels. The combined predictive model for pCR (C-PM) was established using the three sRNAs and four clinical factors. The area under the curve for the C-PM was 0.84, which was a significant factor in the multivariate analysis (odds ratio, 89.41; 95 % confidence interval 8.1-987.5; p < 0.001)., Conclusions: Pathologic complete response after NACRT can be predicted by a predictive model constructed from preoperative clinical factors obtained via minimally invasive procedures and sRNA identified by NGS. Preoperative pCR prediction may influence treatment decision-making after NACRT., (© 2024. The Author(s).)

Background: Patients diagnosed with pathologic T1N0 esophageal squamous cell carcinoma and treated with surgery alone have a good prognosis and are generally followed up without adjuvant therapy. However, recurrence has been observed in this patient group. Therefore, this study aimed to identify recurrence and prognostic factors in patients with pathologic T1N0 esophageal squamous cell carcinoma who were treated with surgery alone., Methods: Of the 532 patients who underwent esophagectomy with R0 resection at Hiroshima University Hospital between August 2003 and November 2018, 124 who underwent only esophagectomy and had pathological T1N0 esophageal squamous cell carcinoma were included in the study. Recurrence and prognostic factors were analyzed and details of recurrence were evaluated., Results: The 5-year recurrence-free survival and 5-year overall survival rates were 84.7% and 87.2%, respectively. Recurrence was observed in 12 (9.7%) patients. Univariate and multivariate analyses showed that the histologic type (poorly differentiated compared with others) and lymphatic and/or vascular invasion (positive compared with negative) were statistically significant for recurrence-free survival. Kaplan-Meier curves for recurrence-free survival and overall survival showed that prognosis was significantly stratified according to these factors. All patients with poorly differentiated and positive lymphatic and/or vascular invasion experienced recurrence and recurrence pattern is all distant metastases., Conclusions: Poorly differentiated and lymphatic and/or vascular invasion are important recurrence and prognostic predictors in pathologic T1N0 esophageal squamous cell carcinoma treated with surgery alone. Patients with these prognostic factors experienced increased recurrence rates, often with distant metastasis. Therefore, adjuvant therapy may be beneficial for such patients and follow-ups should be performed at closer intervals., Competing Interests: Conflict of Interest/Disclosure The authors have no relevant financial disclosures., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Patients with esophageal squamous cell carcinoma (ESCC) with distant metastasis were treated with systemic chemotherapy. Recent advances in multimodal treatments have made conversion therapy a viable option for patients with incurable ESCC., Objective: We aimed to assess the safety and efficacy of conversion therapy for ESCC with distant metastases., Methods: Conversion therapy was defined as surgery or chemoradiotherapy (CRT) used to cure tumors that were previously considered incurable because of distant metastasis. We conducted a retrospective review of patients who underwent ESCC conversion therapy and assessed the treatment outcomes, including adverse events and survival rates., Results: A total of 147 patients from 22 institutions were included. Systemic chemotherapy was initially administered to all patients. The most common M1 factor was the para-aortic lymph node, accounting for 55% of cases. Following the initial treatment, 116 patients underwent surgery, with 31 receiving CRT as conversion therapy. Postoperative complications in surgery patients included pneumonia (16%), anastomotic leakage (7%), and recurrent laryngeal nerve palsy (6%). During CRT, 18% of patients developed grade 3 or higher non-hematological toxicities. The 5-year overall survival (OS) rate was 31.7%. Pathological responders had significantly longer OS than non-responders (hazard ratio 0.493, p = 0.012). The distribution of distant metastasis, regimen type, clinical response, and conversion therapy modality did not have a significant impact on OS., Conclusions: Conversion therapy can be safely performed for ESCC with distant metastasis and has a favorable prognosis., (© 2024. Society of Surgical Oncology.)

Background: Cricothyrotomy is a widely performed potentially life-saving treatment to secure an airway in emergencies. It is also a pneumonia-preventing treatment to secure an expectorant route in patients with difficulty self-expelling sputum; however, its safety and usefulness remain unclear. Thus, we conducted a nationwide survey of cricothyrotomy., Methods: We retrospectively collected and analyzed cricothyrotomy data from the institutions certified by the Japan Broncho-Esophagological Society or the Japanese Esophageal Society. Ultimately, 116 facilities responded to the survey and the present study included 1001 patients from 26 facilities who underwent cricothyrotomies from January 1, 2010 to December 31, 2021., Results: Cricothyrotomy was performed for sputum suctioning after esophagectomy or other surgical procedures in 945 (94.4%) cases and for emergency airway clearance in 48 (4.8%) cases. Complications during puncture were observed in 12 (1.2%) cases. We found significantly fewer complications during puncture for sputum suction (1.0%) compared with emergency airway clearance (4.2%) (p = 0.002), and also at the condition after esophagectomy (0.5%) compared with other surgical procedures (7.8%) (p < 0.001). Complications after puncture were observed in 45 (4.5%) cases, and we found significantly fewer complications after puncture at the condition after esophagectomy (4.2%) compared with other surgical procedures (11.8%) (p = 0.032). There were no significant differences in the type of kit used for complications during and after the puncture., Conclusions: Cricothyrotomy for prophylactic sputum suctioning after esophagectomy was safer compared to emergency airway clearance. However, future studies should verify the efficacy of cricothyrotomy., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Prognosis of patients who achieve pathological complete response (pCR) with neoadjuvant therapy (NAT) is better than that of non-pCR patients. Currently, there is no indication for adjuvant immune checkpoint inhibitor therapy after achieving pCR. However, recurrence risk after pCR is reportedly 10%-20% with a poor prognosis. Therefore, we investigated the preoperative risk factors for recurrence in patients with pCR., Methods: We analyzed 56 patients with esophageal squamous cell carcinoma who underwent esophagectomy after neoadjuvant chemoradiotherapy (NACRT) or neoadjuvant chemotherapy (NAC) and were histologically diagnosed with pCR. Preoperative factors were compared between patients with and without recurrence to identify the risk factors., Results: Forty-eight patients who achieved pCR received NACRT and 8 received NAC. Ten patients who experienced recurrence (17.9%) had undergone NACRT. The cN2 lesions were more frequent, and pre-NAT blood hemoglobin (Hb) was lower in the recurrence group. In addition, the pre-NAT cross-sectional area (CSA) product of the major and minor diameters of the primary tumor before NAT was significantly higher in recurrent cases (p = 0.041). Multivariate analysis, including the cTNM stage, pre-NAT Hb, and pre-NAT CSA, identified high pre-NAT CSA as the only risk factor for recurrence (odds ratio 11.6, 95% confidence interval 1.3-104.1, and p = 0.028). Cox regression analysis of recurrence-free and overall survival identified only high pre-NAT CSA as a prognostic factor., Conclusions: The recurrence risk is relatively high even in patients who achieve pCR after NAT. High pre-NAT CSA of the primary tumor is a risk factor for recurrence necessitating close surveillance., (© 2024 The Author(s). World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background/aim: This study aimed to evaluate the long-term prognosis of definitive chemoradiotherapy and clinical features of postoperative lymph node (LN) recurrence after curative resection of thoracic esophageal squamous cell cancer (ESCC)., Patients and Methods: A total of 586 patients who underwent radical resection of ESCC at the Hiroshima University Hospital from January 2000 to December 2019 were reviewed retrospectively. This study analyzed the clinical characteristics of 54 patients who developed recurrence in a solitary LN by comparing them to 182 patients who experienced total recurrence. Additionally, we analyzed the prognostic factors of 50 patients who received chemo-radiotherapy (CRT)., Results: The results revealed a tendency for a higher incidence of solitary LN recurrence in cases of early esophageal cancer and upper thoracic esophageal cancer among all recurrence cases. The 3-, 5-, and 7-year overall survival (OS) rates were 40.5%, 37.8% and 34.6%, respectively, with a median survival time of 27.9 months. Univariate analysis of OS factors, such as age, depth of the primary tumor at the initial surgery, time to LN recurrence after surgery, site of LN recurrence, and the number of the regional LNs with recurrence showed no significant impact on OS., Conclusion: Approximately 35% of patients with ESCC who experienced LN recurrence after curative resection achieved long-term survival through CRT. Despite the absence of identifiable prognostic factors, CRT proves to be a valuable initial treatment option for LN recurrence., Competing Interests: The Authors declare no conflicts of interest that may have influenced the results of this study., (Copyright 2024, International Institute of Anticancer Research.)

Background: There are few reports on the associations between lymph node (LN) status, determined by preoperative 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET), and prognosis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy post-neoadjuvant chemotherapy (NCT). Additionally, details on the diagnostic performance of LN metastasis determination based on pathological examination versus FDG-PET have not been reported. In this study, we aimed to evaluate the associations among LN status using FDG-PET, LN status based on pathological examination, and prognosis in patients with locally advanced ESCC who underwent esophagectomy post-NCT., Methods: We reviewed the data of 124 consecutive patients with ESCC who underwent esophagectomy with R0 resection post-NCT between December 2008 and August 2022 and were evaluated pre- and post-NCT using FDG-PET. The associations among LN status using FDG-PET, LN status based on pathological examination, and prognosis were assessed., Results: Station-by-station analysis of PET-positive LNs pre- and post-NCT correlated significantly with pathological LN metastases (sensitivity, specificity, and accuracy pre- and post-NCT: 51.6%, 96.0%, and 92.1%; and 28.2%, 99.5%, and 93.1%, respectively; both p < 0.0001). Using univariate and multivariate analyses, LN status determined using PET post-NCT was a significant independent predictor of both recurrence-free survival and overall survival., Conclusion: The LN status assessed using FDG-PET post-NCT was significantly associated with the pathological LN status and prognosis in patients with ESCC who underwent esophagectomy post-NCT. Therefore, FDG-PET is a useful diagnostic tool for preoperatively predicting pathological LN metastasis and survival in these patients and could provide valuable information for selecting individualized treatment strategies., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Pathological lymph node metastasis (LNM) following multimodal therapy is an important indicator of poor prognosis in patients with esophageal cancer. However, a significant number of patients without LNM are still at high risk for recurrence., Methods: We assessed prognostic factors in 143 patients without pathological LNM who were diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) and underwent neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT), followed by surgery., Results: Using univariate and multivariate analyses of recurrence-free survival, carcinoembryonic antigen (CEA) levels (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.12-4.23, and p = 0.02) and neutrophil-to-lymphocyte ratio (NLR) (HR: 1.22, 95% CI: 1.04-1.43, and p = 0.02) were significant independent covariates. Furthermore, pretherapeutic LNM (HR: 1.94, 95% CI: 1.003-3.76, and p = 0.049), NACRT (HR: 3.29, 95% CI: 1.30-8.33, and p = 0.01), poorly differentiated tumors (HR: 2.52, 95% CI: 1.28-4.98, and p = 0.01), and lymphovascular invasion (LVI) (HR: 2.78, 95% CI: 1.27-6.09, and p = 0.01) were also significant independent covariates. The recurrence rates among patients with 0/1, 2, 3, and 4/5 poor prognostic factors were significantly different (5.0%, 25.0%, 35.7%, and 53.8%, respectively; p = 0.001); the survival rates were stratified among these prognostic groups., Conclusions: Pretherapeutic CEA and NLR levels, pretherapeutic LNM, NACRT, poorly differentiated tumors, and LVI were significantly correlated with survivals in patients without pathological LNM after neoadjuvant therapy and surgery. Postoperative therapy should be considered in patients with ESCC with several indicators of recurrence, even in those without pathological LNM who underwent surgery following neoadjuvant therapy., (© 2023 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Purpose: Various treatments are used for early postoperative recurrence of esophageal cancer, which has a poor prognosis. We evaluated the differences in outcomes and prognoses of each treatment modality between patients with early and late recurrence., Methods: Early and late recurrence were defined as recurrence within and after six postoperative months, respectively. Of the 351 patients with esophageal squamous cell carcinoma who underwent R0 resection esophagectomy, 98 experienced postoperative recurrence (early recurrence, n = 41; late recurrence, n = 57). We evaluated the characteristics of patients with early and late recurrence and compared their treatment responses and prognoses., Results: Regarding treatment responses for chemotherapy or immunotherapy, the objective response rate was not significantly different between the early- and late-recurrence groups. For chemoradiotherapy, the objective response rate was significantly lower in the early-recurrence group than in the late-recurrence group. The overall survival was significantly worse in the early-recurrence group than in the late-recurrence group. An analysis by treatment type showed that the early-recurrence group had significantly worse overall survival for chemoradiotherapy, surgery, and radiotherapy than the late-recurrence group., Conclusions: Patients with early recurrence had particularly poor prognoses with worse post recurrence treatment efficacy than those with late recurrence. The differences in the treatment efficacy and prognosis were particularly pronounced for local therapy., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Esophageal fistula (EF) is a serious complication in patients with cT4b esophageal squamous cell carcinoma (ESCC) with adjacent organ involvement. Among EFs, aortoesophageal fistula (AEF), forming a fistula with the aorta, could be fatal. This study aimed to identify the risk factors for AEF in patients with cT4b ESCC with obvious or suspected aortic invasion who underwent definitive radiotherapy (DRT)., Methods: Forty-four patients with cT4b ESCC with obvious or suspected invasion to the aorta who underwent DRT were included. Blood tests and computed tomography (CT) findings before and after DRT were compared between the patients with and without AEF to identify the potential risk factors for AEF., Results: Nine patients (20.5%) developed AEF after DRT. Comparing between patients with and without AEF, pre-DRT white blood cell counts and post-DRT C-reactive protein (CRP) levels were significantly higher in patients with AEF. Furthermore, pre-DRT CT findings were similar between the two groups. However, post-DRT CT findings demonstrated significantly larger picus angle and lower esophageal wall thickness on the aortic side in patients with AEF. Multivariate analysis identified elevated post-DRT CRP levels [<3.3 versus ≥3.3 mg/dL; odds ratio (OR): 30.7; 95% confidence interval (CI): 2.92-323.2; P=0.004] and esophageal wall thinning on post-DRT CT scans (>6 versus ≤6 mm; OR: 13.2; 95% CI: 1.24-140.1; P=0.033) as risk factors for AEF., Conclusions: We found that post-DRT esophageal wall thinning on the aortic side, as observed on CT scans, and elevated CRP levels were predictive factors for AEF in patients with cT4b ESCC with obvious or suspected invasion to the aorta., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-848/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background/aim: Malignant esophageal neuroendocrine carcinoma (ENEC) is rare, and its prognosis is poor. Therefore, a standard strategy for treating ENEC remains controversial, and few reports have described a pathological complete response of ENEC to neoadjuvant chemotherapy (NAC) followed by surgery., Case Report: A 74-year-old woman presented with an esophageal tumor, discovered as a result of dysphagia, that was clinically diagnosed as ENEC (small-cell type). The clinical stage was cT2N1M0 stage II (Union for International Cancer Control, eighth edition). Two cycles of carboplatin and etoposide were administered as NAC, and the overall treatment response to NAC was judged as a partial response according to Response Evaluation Criteria for Solid Tumors v.1.1. The patient then underwent robot-assisted, minimally-invasive esophagectomy with thoracoabdominal lymph node dissection. Postoperative histopathology revealed no residual tumor or lymph node metastasis, and pathological complete response to NAC was achieved. The postoperative course was free of major complications, and the patient has remained recurrence-free for 1 year., Conclusion: We treated ENEC with NAC and robotic surgery. To our knowledge, this is the first report of a pathological complete response for ENEC after NAC with carboplatin and etoposide., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Nivolumab is approved in Japan as a second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC) resistant to fluoropyrimidine and platinum-based drugs. It is also used in adjuvant and primary postoperative therapies. This study aimed to report real-world data on nivolumab use for esophageal cancer treatment., Methods: In total, 171 patients with recurrent or unresectable advanced ESCC who received nivolumab (n = 61) or taxane (n = 110) were included. We collected real-world data of patients treated with nivolumab as a second- or later-line therapy and evaluated treatment outcomes and safety., Results: Median overall survival was longer and progression-free survival (PFS) was significantly longer (p = 0.0172) in patients who received nivolumab than in patients who received taxane as a second- or later-line therapy. Furthermore, subgroup analysis for second-line treatment only showed the superiority of nivolumab in increasing the PFS rate (p = 0.0056). No serious adverse events were observed., Conclusions: In real-world practice, nivolumab was safer and more effective than taxane in patients with ESCC with diverse clinical profiles who did not meet trial eligibility criteria, including those with poor Eastern Cooperative Oncology Group performance status, comorbidities, and receiving multiple treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ohsawa, Hamai, Emi, Ibuki, Kurokawa, Yoshikawa, Hirohata, Kitasaki and Okada.)

Purpose: Various blood cell parameters have been identified as predictive markers of tumor responses and the survival of patients with cancer treated with immune checkpoint inhibitors. The purpose of this study is to assess the ability of various blood cell parameters to predict therapeutic effects and survival in patients with esophageal squamous cell carcinoma (ESCC) treated with nivolumab monotherapy., Patients and Methods: We evaluated neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte (LMR) ratios as predictive markers of patients' survival and effects of nivolumab monotherapy after one or more prior chemotherapies for unresectable advanced or recurrent ESCC., Results: The objective response and disease control rates were 20.3% and 47.5%, respectively. The LMRs before, and 14 and 28 days after nivolumab initiation were significantly higher in patients with complete response (CR)/partial response (PR)/stable disease (SD) than those with progressive disease (PD). The NLRs at 14 and 28 days after nivolumab initiation were significantly lower in patients with CR/PR/SD than with PD. The optimal cutoffs for these parameters significantly discriminated patients with CR/PR/SD and PD. Univariate and multivariate analyses identified pretreatment NLRs as a significant independent factor for progression-free and overall survival (hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.07-1.32, and HR 1.23, 95% CI: 1.11-1.37, respectively; p ≤ 0.001 for both)., Conclusion: The pretreatment LMRs, and NLR and LMR at 14 and 28 days after starting nivolumab monotherapy were significantly associated with the clinical therapeutic effect. The pretreatment NLR was significantly associated with patients' survival. These blood cell parameters before and during the early days of nivolumab monotherapy can help to identify patients with ESCC who would most likely benefit from nivolumab monotherapy., Competing Interests: All authors report no conflicts of interest in this work., (© 2023 Hamai et al.)

Background: Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting., Methods: We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0-1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups., Results: The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22-2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10 -11 ), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10 -3 ). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57-1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02-3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58-2.22; P = 0.717)., Conclusions: NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT., (© 2023. The Author(s).)

Background: We evaluated the long-term results of definitive chemoradiotherapy (CRT) with elective nodal irradiation (ENI) using a three-dimensional (3D) planning system for resectable, locally advanced esophageal squamous cell carcinoma (LA-ESCC)., Methods: This retrospective study included 65 patients with LA-ESCC who started CRT between 2006 and 2017. Patients with Stage I-IV LA-ESCC according to the Union for International Cancer Control TNM classification (eighth edition) were included. In stage IV, only supraclavicular lymph node (LN) metastasis was included. All patients received radiotherapy with ENI and concurrent chemotherapy with platinum and 5-fluorouracil., Results: The median age of the patients was 70 years (range 52-83 years). Stage I, II, III, and IV diseases were observed in 3 (5%), 28 (43%), 22 (34%), and 12 patients (18%), respectively. The median prescription dose was 66 Gy (range 50.4-66 Gy). The median follow-up period for the survivors was 71 months (range 8-175 months). The 5-year overall survival (OS) and progression-free survival rates were 54 and 43%, respectively. The 5-year OS rates for stages I-II and III-IV were 67 and 42%, respectively. Recurrence occurred in 29 patients (45%), and recurrence of regional LNs only occurred in 2 patients (3%). Grade 3 or higher late adverse events were observed in 8 patients (12%). Grade 5 heart failure occurred in two patients (3%); both had cardiovascular disease before treatment., Conclusion: The long-term results of definitive CRT with ENI for resectable LA-ESCC were favorable. ENI with a 3D planning system may reduce regional LN recurrence and late adverse events., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Accurate preoperative evaluation of lymph node (LN) metastasis is important for determining the treatment strategy for superficial esophageal cancer. Blood biomarkers, such as the neutrophil-lymphocyte, platelet-lymphocyte, and lymphocyte-monocyte ratios (NLR, PLR, and LMR, respectively), have clinical applications as predictors of LN metastasis for different cancers. Here, we investigated the use of these ratios as predictors of pathological LN metastasis and prognosis in patients with clinical stage T1N0M0 esophageal squamous cell carcinoma (ESCC). Patients (n = 185) with cT1N0M0 ESCC who underwent esophagectomy with R0 resection between April 2003 and August 2021 were enrolled. We investigated the ability of pretreatment NLR, PLR, and LMR to predict pathological LN metastasis. The optimal cutoff values of NLR, PLR, and LMR to predict pathological LN metastasis were 2.1, 122, and 4.8, respectively. Univariate and multivariate analyses revealed that the primary tumor length, depth of invasion, and NLR were significant predictors of LN metastasis. Furthermore, similar to the 5-year overall survival, the 5-year relapse-free survival was significantly better in the low NLR group than in the high NLR group. The NLR was the most useful predictor of pathological LN metastasis. Patients diagnosed with clinical stage I ESCC and with a high NLR require adequate LN dissection and may be good candidates for preoperative adjuvant therapy., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/aim: To identify the correlations between the 18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) images and the pathological features and recurrence among patients with esophageal squamous cell carcinoma (ESCC) who were administered neoadjuvant chemotherapy (NAC) followed by surgery., Patients and Methods: We assessed the correlations between the maximum standardized uptake value (SUVmax) of primary tumors as reflected on preoperative FDG-PET images, the pathological features, and cancer recurrence in 124 patients with locally advanced ESCC, who were treated with NAC and esophagectomy., Results: The pre-NAC SUVmax significantly differed for the ypT status and venous invasion (VI). The post-NAC SUVmax (post-SUVmax) significantly differed for the ypT and ypN status, VI, lymphatic invasion (LI), pathological tumor response, down-staging, and recurrence. The decrease in SUVmax before and after NAC (ΔSUVmax) significantly differed for ypT status, LI, VI, pathological tumor response, down-staging, and recurrence. The survivals were significantly stratified according to the optimal cutoffs of SUVmax for predicting recurrence (post- and ΔSUVmax cutoffs: 4.2 and 30, respectively; all p<0.0001). Moreover, multivariate analysis showed that the post- and ΔSUVmax were independent predictive factors for recurrence-free survival., Conclusion: The SUVmax on preoperative FDG-PET can predict the degree of aggressiveness of the tumor in locally advanced ESCC treated with NAC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Neoadjuvant chemotherapy (NAC) followed by surgery is a standard treatment for patients with locally advanced esophageal cancer. This study aimed to identify patients who might be eligible for postoperative adjuvant therapy., Patients and Methods: We reviewed the surgical outcomes of 84 patients who received NAC followed by esophagectomy to treat esophageal squamous cell carcinoma (ESCC) and revealed prognostic factors associated with locally advanced ESCC., Results: Univariate and multivariate analyses revealed the pretreatment level of squamous cell carcinoma-related antigen [SCC-A; hazard ratio (HR)=1.50, p=0.01], ypT ≥3 (HR=2.51; p=0.04), ypN ≥1 (HR=5.87; p=0.01), ypM1 (HR=2.38; p=0.049), and lymphovascular invasion (HR=3.12, p=0.049) as significant independent covariates for recurrence-free survival (RFS). The 5-year RFS rates for patients with 0-1, 2-3, or 4-5 of these indicators of poor prognosis were 97.1%, 51.2%, and 6.7% (p≤0.001 for all). Recurrence rates among these groups also significantly differed at 2.9%, 50.0%, and 93.3% (p<0.0001)., Conclusion: Pretreatment SCC-A, ypT, ypN, ypM, and lymphovascular invasion were significantly associated with RFS in patients with ESCC who received NAC followed by surgery. The status of these prognostic factors in ESCC might indicate a need for postoperative adjuvant therapy after NAC followed by surgery., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)