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BACKGROUND: Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC. METHODS: In this randomised, open-label, phase 3 trial, patients aged 20-75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1-5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1-5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1-4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete. FINDINGS: A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8-70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4-77·8] vs 62·6% [55·5-68·9]; hazard ratio [HR] 0·68, 95% CI 0·50-0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3-74·3]; HR 0·84, 0·63-1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group. INTERPRETATION: Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy. FUNDING: Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Docetaxel , Neoplasias Esofágicas , Fluorouracilo , Terapia Neoadyuvante , Humanos , Persona de Mediana Edad , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Masculino , Femenino , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Anciano , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Adulto , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Quimioradioterapia/métodos , EsofagectomíaRESUMEN
BACKGROUND: Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). METHODS: Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. RESULTS: The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. CONCLUSION: There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/cirugía , Cisplatino/uso terapéutico , Terapia Neoadyuvante , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica , Resultado del Tratamiento , Biomarcadores , Fluorouracilo/uso terapéuticoRESUMEN
BACKGROUND: Drug-induced interstitial lung disease (DIILD) is a serious adverse event potentially induced by any antineoplastic agent. Whether cancer patients are predisposed to a higher risk of DIILD after receiving immune checkpoint inhibitors (ICIs) is unknown. METHODS: This study retrospectively assessed the cumulative incidence of DIILD in consecutive cancer patients who received post-ICI antineoplastic treatment within 6 months from the final dose of ICIs. There was also a separate control cohort of 55 ICI-naïve patients with non-small cell lung cancer (NSCLC) who received docetaxel. RESULTS: Of 552 patients who received ICIs, 186 met the inclusion criteria. The cohort predominantly comprised patients with cancer of the lung, kidney/urinary tract, or gastrointestinal tract. The cumulative incidence of DIILD in the entire cohort at 3 and 6 months was 4.9% (95% confidence interval [CI] 2.4%-8.7%) and 7.2% (95% CI 4.0%-11.5%), respectively. There were significant differences according to cancer type (Gray's test, P = .04), with the highest cumulative incidence of DIILD in patients with lung cancer being 9.8% (95% CI 4.3%-18.0%) at 3 months and 14.2% (95% CI 7.3%-23.3%) at 6 months. DIILD was caused by docetaxel in six of these 11 lung cancer patients (54.5%). After matching, the cumulative incidence of docetaxel-induced ILD in patients with NSCLC in the post-ICI setting was higher than that in the ICI-naïve setting: 13.0% (95% CI 3.3%-29.7%) vs 4.3% (95% CI 0.3%-18.2%) at 3 months; and 21.7% (95% CI 7.9%-39.9%) vs 4.3% (95% CI 0.3%-18.2%) at 6 months. However, these were not significant differences (hazard ratio, 5.37; 95% CI 0.64-45.33; Fine-Gray P = .12). CONCLUSIONS: Patients with lung cancer were at high risk of developing DIILD in subsequent regimens after ICI treatment. Whether NSCLC patients are predisposed to additional risk of docetaxel-induced ILD by prior ICIs warrants further study.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Docetaxel/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/epidemiologíaRESUMEN
PURPOSE: The long-term prognosis of stapled and hand-sewn ileal pouch-anal anastomoses in familial adenomatous polyposis patients in Japan remains unknown. This study aimed to compare the overall survival in familial adenomatous polyposis patients who underwent stapled or hand-sewn ileal pouch-anal anastomosis. METHODS: This multicenter retrospective study was conducted at 12 institutions in Shizuoka Prefecture, Japan. The clinical outcomes of 53 eligible familial adenomatous polyposis patients who underwent stapled (n = 24) and hand-sewn (n = 29) ileal pouch-anal anastomosis were compared. RESULTS: The median follow-up duration was 171.5 months. The incidence of adenoma in the remnant rectum or anal transitional zone and metachronous rectal cancer was significantly more common in stapled ileal pouch-anal anastomosis (adenoma: stapled, 45.8%, vs. hand-sewn, 10.3%, p = 0.005; metachronous rectal cancer: 29.2%, vs. none, p = 0.002). The number of deaths was remarkably higher in stapled ileal pouch-anal anastomosis (p = 0.002). Metachronous rectal cancer was the most common cause of death. Overall survival was worse in stapled ileal pouch-anal anastomosis than in hand-sewn ileal pouch-anal anastomosis (120 months, 90.7% vs. 96.6%; 240 months, 63.7% vs. 96.6%; p = 0.044). Cox regression analysis revealed the independent effects of preoperative advanced colorectal cancer and stapled ileal pouch-anal anastomosis on overall survival. CONCLUSION: Stapled ileal pouch-anal anastomosis negatively affected the overall survival of familial adenomatous polyposis patients. Therefore, hand-sewn ileal pouch-anal anastomosis is recommended for better prognosis in these patients.
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Adenoma , Poliposis Adenomatosa del Colon , Reservorios Cólicos , Proctocolectomía Restauradora , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Anastomosis Quirúrgica/efectos adversos , Proctocolectomía Restauradora/efectos adversos , Poliposis Adenomatosa del Colon/cirugía , Pronóstico , Neoplasias del Recto/cirugía , Reservorios Cólicos/efectos adversos , Resultado del TratamientoRESUMEN
Chemoradiotherapy has been considered as one of the standard treatment options for clinical T1bN0M0 esophageal squamous cell carcinoma with organ preservation. However, 20% of patients develop locoregional recurrence after chemoradiotherapy, which requires salvage treatment including salvage surgery and endoscopic resection. Salvage surgery can cause complications and treatment-related death. Interestingly, chemoradiotherapy with elective nodal irradiation has been reported to reduce the locoregional recurrence of advanced esophageal squamous cell carcinoma. Hence, we are conducting a clinical trial to confirm whether modified chemoradiotherapy with elective nodal irradiation was superiority to that without elective nodal irradiation for the patients with cT1bN0M0 esophageal squamous cell carcinoma. The primary endpoint is major progression-free survival, defined as the time from randomization to the date of death or disease progression, excluding successful curative resection through salvage endoscopic resection. We plan to enroll 280 patients from 54 institutions over 4 years. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031200067).
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Recurrencia Local de Neoplasia/patología , Quimioradioterapia , Japón , Resultado del Tratamiento , Terapia Recuperativa , Estudios RetrospectivosRESUMEN
Treatment strategies for oesophagogastric junction adenocarcinoma have not been standardized despite its poor prognosis due to differences in the incidence rates between Western countries and Asia. This randomized Phase II/III trial was initiated in June 2023 to determine which neoadjuvant chemotherapy regimen, docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel, is a more promising treatment in Phase II and confirm the superiority of neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel followed by surgery and postoperative chemotherapy over upfront surgery and postoperative chemotherapy in terms of overall survival in patients with Clinical Stage III or IVA oesophagogastric junction adenocarcinoma in Phase III. A total of 460 patients, including 150 patients in Phase II and 310 patients in Phase III, are planned to be enrolled from 85 hospitals in Japan over 5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230182 (https://jrct.niph.go.jp/latest-detail/jRCTs031230182).
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Docetaxel/uso terapéutico , Oxaliplatino/uso terapéutico , Neoplasias Gástricas/patología , Japón , Terapia Neoadyuvante/métodos , Resultado del Tratamiento , Unión Esofagogástrica/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/patología , Fluorouracilo/uso terapéutico , Adenocarcinoma/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
BACKGROUND: Enteral feeding (EF) is recommended to enhance nutritional status after esophagectomy; however, diarrhea is a common complication of EF. We investigated the clinical and prognostic impact of diarrhea during EF after esophagectomy. METHODS: One hundred and fifty-two patients who underwent transthoracic esophagectomy were enrolled. The King's stool chart was used for stool characterization. The short- and long-term outcomes were compared between a non-diarrhea (Group N) and diarrhea group (Group D). RESULTS: A higher dysphagia score (≥ 1) was observed more frequently in Group D than in Group N (45.7% vs. 19.8%, p = 0.002). Deterioration of serum total protein, serum albumin, serum cholinesterase, and the prognostic nutritional index after esophagectomy was greater in Group D than in Group N (p = 0.003, 0.004, 0.014, and 0.001, respectively). Patients in Group D had significantly worse overall survival (OS) and recurrence-free survival (RFS) than those in Group N (median survival time (MST): OS, 21.9 vs. 30.6 months, p = 0.001; RFS, 12.4 vs. 27.7 months, p < 0.001). In stratified analysis due to age, although there was no difference in OS with or without diarrhea in young patients (MST: 24.1 months in a diarrhea group vs. 33.6 months in a non-diarrhea group, p = 0.218), patients in a diarrhea group had significantly worse OS than those in a non-diarrhea group in elderly patients (MST: 17.8 months vs. 27.9 months, p < 0.001). CONCLUSIONS: Diarrhea during EF can put elderly patients at risk of postoperative malnutrition and a poor prognosis after esophagectomy.
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Nutrición Enteral , Neoplasias Esofágicas , Humanos , Anciano , Preescolar , Nutrición Enteral/efectos adversos , Esofagectomía/efectos adversos , Estado Nutricional , Diarrea/etiología , Estudios Retrospectivos , Complicaciones Posoperatorias/etiologíaRESUMEN
PURPOSE: To compare changes in liver enzyme levels on postoperative day 1 between patients with and without silicone disc (SD) use during liver retraction in laparoscopic gastrectomy for gastric cancer and laparoscopic gastric mobilization for esophageal cancer. METHODS: This prospective randomized controlled phase II trial was conducted between June 30, 2020, and November 30, 2022, to investigate the benefits of using an SD with a Nathanson liver retractor (NLR) compared with those using an NLR in laparoscopic gastrectomy and gastric mobilization. The primary endpoint was the change in transaminase level on postoperative day 1. RESULTS: A total of 86 patients received randomized assignments and were included in the analysis, with 44 assigned to the SD (-) group and 42 to the SD (+) group. On postoperative day 1, the SD (+) group showed a significantly lower increase in the aspartate aminotransferase levels than the SD (-) group (SD [+], 94.4% vs. SD [-], 179.8%; p = 0.012). Similarly, the SD (+) group showed a significantly lower increase in alanine aminotransferase levels than the SD (-) group (SD [+], 71.6% vs. SD [-], 201.5%; p = 0.014). CONCLUSION: In laparoscopic gastrectomy, the use of an SD combined with an NLR appears to mitigate postoperative liver dysfunction.
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BACKGROUND: Minimal data was reported regarding the characteristics, risks of lymph node metastasis, and prognostic factors in esophageal cancer patients who achieved remarkable response in the primary lesion to neoadjuvant treatment (NAT). METHODS: This study evaluated the nationwide data of esophageal squamous cell carcinoma (ESCC) patients who underwent surgery following NAT in Japan. Of 4484 patients, 300 (6.7%) had ypT0 following NAT and curative esophagectomy. Factors associated with lymph node metastasis and prognosis were analyzed. RESULTS: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) were administered in 260 (86.2%) and 40 (13.8%) patients, respectively. Pathologically, 72 (24.0%) had lymph node metastasis (residual nodal disease; RND), and pretherapeutic lymph node metastasis was the independent risk factor for RND (odd ratio [OR]: 3.21; 95% confidence interval [CI]: 1.44-8.20; P = 0.008). The 5-year overall and relapse-free survivals were significantly longer in patients with pathological complete response (pCR) than in those with RND (both P < 0.001). Pretherapeutic cT3 or T4a tumors (hazard ratio [HR]: 1.71; 95% CI: 1.02-2.88; P = 0.043), RND (HR: 3.30; 95% CI: 1.98-5.50; P < 0.001), and operative blood loss (Liter, HR: 1.53; 95% CI: 1.07-2.19; P = 0.021) were independent risk factors affecting relapse-free survival in multivariable analysis. CONCLUSIONS: Of patients with ypT0 after NAT, 24.0% had RND, and pretherapeutic lymph node metastasis was the risk factor. In addition, pretherapeutic cT3, or T4a tumors, RND, and operative blood loss were the poor prognosticators in patients with ypT0 after NAT.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/patología , Japón , Estudios de Cohortes , Carcinoma de Células Escamosas/patología , Terapia Neoadyuvante , Metástasis Linfática , Pérdida de Sangre Quirúrgica , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Respuesta Patológica CompletaRESUMEN
Esophagectomy for esophageal cancer is a highly invasive gastrointestinal surgical procedure. The National Clinical Database (NCD) of Japan, initiated in 2011, has compiled real-world data on esophagectomy, one of nine major gastroenterological surgeries. This review examines outcomes after esophagectomy analyzed using the Japanese big databases. Certification systems by the Japanese Society of Gastroenterological Surgery (JSGS) and the Japan Esophageal Society (JES) have shown that institutional certification has a greater impact on short-term surgical outcomes than surgeon certification. Minimally invasive esophagectomy has emerged as a viable alternative to open esophagectomy, although careful patient selection is crucial, especially for elderly patients with advanced tumors. The NCD has significantly contributed to the assessment and enhancement of surgical quality and short-term outcomes, while studies based on Comprehensive Registry of Esophageal Cancer in Japan (CRECJ) have provided data on patient characteristics, treatments, and long-term outcomes. The JES has conducted various questionnaire-based retrospective clinical reviews in collaboration with authorized institutions certified by JES. The Diagnosis Procedure Combination (DPC) database provides administrative claims data including itemized prices for surgical, pharmaceutical, laboratory, and other inpatient services. Analyzing these nationwide databases can offer precise insights into surgical quality for esophageal cancer, potentially leading to improved treatment outcomes.
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In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/tratamiento farmacológico , Endoscopía , Quimioradioterapia , Carcinoma de Células Escamosas/patologíaRESUMEN
BACKGROUND: Second primary esophageal cancer often develops in patients with head and neck cancer, and esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. However, the clinical outcomes of these patients have yet to be examined in a multicenter setting. METHODS: We evaluated the surgical outcomes of a nationwide cohort of 62 patients who underwent esophagectomy for esophageal cancer with a history of TPL. RESULTS: Ivor-Lewis and McKeown esophagectomies were performed in 32 (51.6%) and 30 (48.4%) patients, respectively. Postoperatively, 23 patients (37.1%) developed severe complications, and 7 patients (11.3%) required reoperation within 30 days. Pneumonia and anastomotic leakage occurred in 13 (21.0%) and 16 (25.8%) patients, respectively. Anastomotic leakage occurred more frequently in the McKeown group than in the Ivor-Lewis group (46.7% vs. 6.2%, P < 0.001). The adjusted odds ratio for anastomotic leakage in the McKeown group was 9.64 (95% confidence intervals (CI), 2.11-70.82, P = 0.008). Meanwhile, the 5-year overall survival rates were comparable between the groups (41.8% for Ivor-Lewis and 42.7% for McKeown), and the adjusted hazard ratio of overall survival was 1.44 (95% CI, 0.64-3.29; P = 0.381; Ivor-Lewis as the reference). CONCLUSIONS: In our cohort, anastomotic leakage occurred more frequently after McKeown than Ivor-Lewis esophagectomy, and almost half of patients in the McKeown group experienced leakage. Ivor-Lewis esophagectomy is preferred for decreasing anastomotic leakage when oncologically and technically feasible.
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OBJECTIVE: This study aimed to validate the prognostic significance of stratification using pathological stage and response to neoadjuvant chemotherapy with a nationwide database from an authorized institute by the Japan Esophageal Society. BACKGROUND: We proposed the combined criteria using pStage and pathological response. Conducting a validation study using an expanded cohort in the clinical setting would be valuable since it was developed using retrospective data collection. METHODS: Patients with esophageal squamous cell carcinoma who underwent subtotal esophagectomy at 85 authorized institutes were retrospectively reviewed for esophageal cancer between 2010 and 2015. The prognostic value of the pathological response was evaluated within the same pStage. Moreover, risk stratification was developed to predict cancer-specific survival (CSS). RESULTS: The pathological response showed significant stratification of CSS in 3761 patients included in this analysis. We classified the patients into 7 groups as survival was significantly different between responders and nonresponders under the stratification with pStage, excluding pStage I comprising pStage 0-I/II responder/II nonresponder/III responder/III nonresponder/IV responder/IV nonresponder with the 5-year CSS of 83.7%/75.8%/68.9%/59.8%/44.4%/40.7%/23.1%, respectively. Furthermore, the area under the curve was significantly higher under the new classification than in the pStage alone ( P <0.001). CONCLUSIONS: The prognostic value of classification using pStage and the pathological response was successfully validated using real-world data in Japan. This result would guide appropriate treatment for patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy followed by esophagectomy.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/cirugía , Pronóstico , Neoplasias Esofágicas/tratamiento farmacológico , Estudios Retrospectivos , Carcinoma de Células Escamosas/tratamiento farmacológico , Terapia Neoadyuvante , Resultado del Tratamiento , Estadificación de Neoplasias , Esofagectomía/efectos adversosRESUMEN
OBJECTIVE: We aimed to evaluate the efficacy of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy over cisplatin and 5-fluorouracil (CF) in patients with surgically resectable advanced esophageal squamous cell carcinoma (ESCC), using real-world data from 85 esophageal centers. BACKGROUND: JCOG1109 trial, which assessed the superiority of DCF over CF, and the superiority of chemoradiotherapy with CF over CF alone demonstrated the significant survival advantage of neoadjuvant DCF in overall survival (OS) over CF for ESCC. METHODS: The ESCC patients who received neoadjuvant CF or DCF at 85 Japanese esophageal centers certified by the Japan Esophageal Society were retrospectively reviewed. After propensity score (PS) matching, the OS and recurrence-free survival were compared between CF and DCF. RESULTS: We initially enrolled 4781 patients. After data cleaning and PS matching using pretreatment variables, 1074 patients for each group were selected for subsequent analysis. There was no significant difference in the incidence of postoperative pneumonia and anastomotic leakage. In the survival analysis, OS was significantly longer in DCF group than CF group (hazard ratio, 0.868; 95% confidence interval, 0.770-0.978; P =0.02), as well as recurrence-free survival (hazard ratio, 0.850; 95% confidence interval, 0.761-0.949; P =0.004). The survival advantage of DCF was not observed in patients with 76 years old or older. CONCLUSIONS: Neoadjuvant DCF therapy showed a remarkable survival advantage in surgically resectable ESCC patients, especially in patients who were 75 years old or younger. The current real-world evidence will encourage recommendations for DCF as a standard regimen in neoadjuvant chemotherapy-based treatment strategy for ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Anciano , Carcinoma de Células Escamosas de Esófago/cirugía , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/tratamiento farmacológico , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Terapia Neoadyuvante , Fluorouracilo/efectos adversos , Puntaje de Propensión , Japón/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Taxoides , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Neoadjuvant treatment has become the standard of care for patients with advanced esophageal cancer. However, few studies have elucidated the clinical factors that predict response to neoadjuvant therapy in a large multicenter cohort. We aimed to develop a predictive model of therapeutic effect in patients with esophageal squamous cell carcinoma (SCC) who received neoadjuvant treatment. METHODS: This nationwide study included 4078 patients from 85 institutions. Patients who received neoadjuvant treatment followed by surgery for esophageal SCC were eligible. We developed a logistic regression model to predict good pathological therapeutic effects, and a predictive nomogram was generated by applying the logistic regression formula. RESULTS: Among neoadjuvant regimens, cisplatin plus 5-fluorouracil (CF) was the most frequently used (60.2%), followed by docetaxel plus CF (DCF, 27.4%), CF with radiotherapy (CF-RT, 4.5%), adriamycin plus CF (3.6%), nedaplatin plus 5-fluorouracil (0.9%), and DCF-RT (0.5%). Multivariable analysis revealed that male sex, advanced cT category, and increased pretherapeutic SCC antigen level were independently associated with not achieving a good therapeutic effect. Moreover, intensified neoadjuvant regimens were independently associated with favorable therapeutic effects; DCF-RT elicited the best therapeutic effect, followed by CF-RT and DCF. A predictive model including nine commonly measured preoperative variables was generated, and the area under the curve was 0.679 (95% confidence interval: 0.658-0.700). This nomogram was also adequately validated internally. CONCLUSIONS: The model developed in this study was validated and predicts the therapeutic effect in patients with esophageal SCC who received neoadjuvant treatment. This model might contribute to individualized treatment strategies.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Masculino , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Neoplasias Esofágicas/patología , Terapia Neoadyuvante , Estudios Retrospectivos , Japón , Taxoides , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino , Docetaxel , FluorouraciloRESUMEN
BACKGROUND: We previously reported that endoscopic response evaluation can preoperatively predict the prognosis and distribution of residual tumors after neoadjuvant chemotherapy (NAC). In this study, we developed artificial intelligence (AI)-guided endoscopic response evaluation using a deep neural network to discriminate endoscopic responders (ERs) in patients with esophageal squamous cell carcinoma (ESCC) after NAC. METHOD: Surgically resectable ESCC patients who underwent esophagectomy following NAC were retrospectively analyzed in this study. Endoscopic images of the tumors were analyzed using a deep neural network. The model was validated with a test data set using 10 newly collected ERs and 10 newly collected non-ER images. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the endoscopic response evaluation by AI and endoscopists were calculated and compared. RESULTS: Of 193 patients, 40 (21%) were diagnosed as ERs. The median sensitivity, specificity, PPV, and NPV values for ER detection in 10 models were 60%, 100%, 100%, and 71%, respectively. Similarly, the median values by the endoscopist were 80%, 80%, 81%, and 81%, respectively. CONCLUSION: This proof-of-concept study using a deep learning algorithm demonstrated that the constructed AI-guided endoscopic response evaluation after NAC could identify ER with high specificity and PPV. It would appropriately guide an individualized treatment strategy that includes an organ preservation approach in ESCC patients.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/cirugía , Terapia Neoadyuvante/métodos , Inteligencia Artificial , Estudios Retrospectivos , Redes Neurales de la Computación , EsofagoscopíaRESUMEN
BACKGROUND: Detecting pathological complete response (pCR) before surgery would facilitate nonsurgical approach after neoadjuvant chemotherapy (NAC). We developed an artificial intelligence (AI)-guided pCR evaluation using a deep neural network to identify pCR before surgery. METHODS: This study examined resectable esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy after NAC. The same number of histological responders without pCR and non-responders were randomly selected based on the number of pCR patients. Endoscopic images were analyzed using a deep neural network. A test dataset consisting of 20 photos was used for validation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AI and four experienced endoscopists' pCR evaluations were calculated. For pathological response evaluation, Japanese Classification of Esophageal Cancer was used. RESULTS: The study enrolled 123 patients, including 41 patients with pCR, the same number of histological responders without pCR, and non-responders [grade 0, 5 (4%); grade 1a, 36 (30%); grade 1b, 21 (17%); grade 2, 20 (16%); grade 3, 41 (33%)]. In 20 models, the median values of sensitivity, specificity, PPV, NPV, and accuracy for endoscopic response (ER) detection were 60%, 81%, 77%, 67%, and 70%, respectively. Similarly, the endoscopists' median of these was 43%, 90%, 85%, 65%, and 66%, respectively. CONCLUSIONS: This proof-of-concept study demonstrated that the AI-guided endoscopic response evaluation after NAC could identify pCR with moderate accuracy. The current AI algorithm might guide an individualized treatment strategy including nonsurgical approach in ESCC patients through prospective studies with careful external validation to demonstrate the clinical value of this diagnostic approach including primary tumor and lymph node.
RESUMEN
BACKGROUND: Although neoadjuvant treatment has become the standard of care for patients with locally advanced esophageal cancer, previous studies comparing neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) have demonstrated inconclusive results. METHODS: Our study cohort included 3978 patients from 85 institutions. Those who underwent NAC or NACRT followed by surgery for esophageal squamous cell carcinoma (ESCC) were eligible for inclusion. We used the inverse probability of treatment weighting (IPTW) method to compare the outcomes between NAC and NACRT. RESULTS: Among the 3978 patients, 3777 (94.9%) received NAC and 201 (5.1%) received NACRT. After IPTW adjustment, the NACRT group had more patients with pathologically downstaged diseases and significantly better pathological response compared with the NAC group (p < 0.001); however, 5-year overall survival (OS), recurrence-free survival (RFS), and regional recurrence-specific survival (RRSS) were comparable between the groups. Subgroup analysis stratifying patients according to cT category showed that among cT1-2 patients, those in the NACRT group had significantly longer 5-year OS, RFS, and RRSS than those in the NAC group (P = 0.024, < 0.001, and 0.020, respectively). In contrast, no significant differences were observed among cT3-4a patients. The competing risks regression model showed comparable subdistribution hazard ratios for 10-year cancerous and noncancerous deaths between the NAC and NACRT groups. CONCLUSIONS: Compared with NAC, NACRT for ESCC did not promote better survival despite better therapeutic effects and did not increase noncancerous deaths.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Terapia Neoadyuvante , Neoplasias Esofágicas/patología , Pueblos del Este de Asia , Quimioradioterapia , Estudios RetrospectivosRESUMEN
OBJECTIVE: To predict sac enlargement with type II endoleak (ELII) before endovascular aneurysm repair (EVAR) using four dimensional flow sensitive magnetic resonance imaging (4D flow MRI). METHODS: A single centre retrospective analysis of prospectively collected data was conducted. Patients with an abdominal aortic aneurysm (AAA) who underwent EVAR between 2013 and 2019 were included. Aortic branches occluded pre-EVAR, and patients with endoleaks other than ELII were excluded. The aortic branch diameter, peak flow velocity (PFVe), and amplitude of the dynamics of flow volume (AFV) were measured in each aortic branch pre-EVAR. Total flow volume per minute (TFV/min), defined as the sum of AFV/min, was calculated in each case. According to computed tomography findings one year post-EVAR, the aortic branches and patients were divided into patent vessel and occluded vessel groups and sac expanding and non-expanding groups. PFVe, AFV/min, and TFV/min were analysed via receiver operating characteristic curve analysis. RESULTS: The patent aortic branches pre-EVAR (69 inferior mesenteric arteries [IMAs]; 249 lumbar arteries [LAs]) of 100 patients were included. Patent IMAs (n = 14) and occluded IMAs (n = 55), patent LAs (n = 23) and occluded LAs (n = 226), and expanding (n = 9) and non-expanding (n = 91) groups were compared, respectively. No statistically significant difference was observed in branch diameters (IMA; patent, 2.5 ± 0.8 mm, occluded, 2.5 ± 0.8 mm, p < .78 and LA; patent, 1.5 ± 0.3 mm, occluded, 1.5 ± 0.4 mm, p < .35). PFVe (IMA; patent, 262.6 mm2/sec, occluded, 183.4 mm2/sec and LA; patent, 142.6 mm2/sec, occluded, 47.7 mm2/sec) and AFV/min (IMA; patent, 8.4 mL, occluded, 5.2 mL and LA; patent, 4.2 mL, occluded, 1.4 mL) were higher in the patent vessel group (p < .050). TFV/min was statistically significantly higher in the expanding group (24.1 mL/min) than in the non-expanding group (7.0 mL/min) (p < .010). CONCLUSION: Pre-EVAR haemodynamic analyses using 4D flow MRI were useful to detect aortic branches responsible for ELII and to predict AAA cases with sac enlargement. This analysis suggests a new strategy for pre-EVAR aortic branch embolisation.
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Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Endofuga/diagnóstico por imagen , Endofuga/etiología , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/patología , Estudios Retrospectivos , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/cirugía , Aorta Abdominal/patología , Factores de Riesgo , Imagen por Resonancia Magnética , Resultado del TratamientoRESUMEN
Despite advances in multidisciplinary treatment, esophagectomy remains the main curative treatment for esophageal cancer. The advantages and disadvantages of thoracic duct (TD) resection have been controversial for decades. We have herein reviewed relevant published literature regarding 'thoracic duct,' 'esophageal cancer,' and 'esophagectomy' describing the anatomy and function of the TD, and incidence of thoracic duct lymph nodes (TDLN) and TDLN metastases, as well as the oncological and physiological effects of TD resection. The presence of lymph nodes around the TD, referred to as TDLN, has been reported previously. The delineation of TDLNs is clearly defined by a thin fascial structure covering the TD and the surrounding adipose tissue. Previous studies have examined the number of TDLNs and the percentage of patients with TDLN metastasis and revealed that each patient had approximately two TDLNs. The percentage of patients with TDLN metastasis was reported to be 6-15%. Several studies have been conducted to compare the survival after TD resection with that after TD preservation. However, no consensus has been reached because all studies were retrospective, precluding firm conclusions. Although the issue of whether the risk of postoperative complications is affected by TD resection is still unclear, resecting the TD has been shown to have a long-term impact on nutritional status after surgery. In summary, TDLNs are quite common and present in most patients, while metastasis in the TDLNs occurs in a minority. However, the oncological value of TD resection in esophageal cancer surgery remains controversial due to varying findings and methodological limitations of previous comparative studies. Considering the potential but unproven oncological benefits and possible physiological drawbacks of TD resection, including postoperative fluid retention and disadvantages in the long-term nutritional outcome, clinical stage, and nutritional status should be considered before deciding whether to perform TD resection or not.