Long-term outcomes of esophageal squamous cell carcinoma with invasion depth of pathological T1a-muscularis mucosae and T1b-submucosa by endoscopic resection followed by appropriate additional treatment.

OBJECTIVES: Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited. METHODS: Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months). RESULTS: In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively. CONCLUSIONS: Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated.

Additional Treatment Following Noncurative Endoscopic Resection for Esophageal Squamous Cell Carcinoma: A Comparison of Outcomes between Esophagectomy and Chemoradiotherapy.

BACKGROUND: Endoscopic resection (ER) has been widely implemented for cT1N0 esophageal squamous cell carcinoma (ESCC). Additional therapy, including esophagectomy and chemoradiotherapy (CRT), is sometimes required after noncurative ER. METHODS: We retrospectively reviewed 108 patients who received any additional treatment following noncurative ER (positive vertical margins, lymphovascular invasion, or invasion depth of submucosa or more), and compared the short- and long-term outcomes between the two treatment modalities. RESULTS: Of 108 patients, 56 underwent esophagectomy (E group), and 52 received CRT (CRT group). A positive vertical margin was observed in 17 (14.8%) patients and high risks of occult lymph node metastasis were observed in 91 (85.2%) patients, as well as lymphovascular invasion in 35 (32.4%) patients, invasion depth of the submucosa or more in 27 (25.0%) patients, and both in 29 (26.9%) patients. The E group patients were significantly younger (p = 0.046) and tended to present with larger tumors than those in the CRT group (p = 0.057). Lymphatic invasion was more frequent in the E group (p = 0.019), and, furthermore, one treatment-related death was observed in the E group. There were no significant differences between the groups in overall and disease-specific survival (p = 0.406 and 0.151, respectively), however, recurrence was only observed in the CRT group. CONCLUSION: Both esophagectomy and CRT are safe and effective as additional treatments after noncurative ER in patients with ESCC. Esophagectomy is oncologically safe, whereas a risk of postoperative morbidity and mortality remains. Although the adverse events are acceptable, CRT has a certain degree of risk of disease recurrence.

Efficacy of postoperative radiotherapy in esophageal squamous cell carcinoma patients with positive circumferential resection margin.

BACKGROUND: The significance of postoperative radiotherapy for residual disease after esophageal cancer surgery remains controversial. The purpose of this study was to elucidate the efficacy of postoperative radiotherapy in esophageal squamous cell carcinoma (ESCC) patients with positive circumferential resection margin (CRM). METHODS: We retrospectively analyzed data from 1190 patients who underwent esophagectomy for ESCC at our hospital from 2005 to 2018, of whom 61 (5.1%) patients were diagnosed with positive CRM of ESCC. Overall survival (OS), progression-specific survival (PSS), local progression-specific survival (LPSS), and clinicopathological factors were compared between patients with and without postoperative radiotherapy. The efficacy of additional radiotherapy on patient outcomes was evaluated. RESULTS: Among the 61 patients analyzed, 29 (47.5%) underwent radiotherapy (RT group) and 32 (52.5%) did not (NRT group). In the RT group, 22 patients (75.9%) received radiotherapy and 7 patients (24.1%) received chemoradiotherapy. The RT group included younger patients, a greater number of upper-esophageal tumors, and a greater rate of R2 resections than the NRT group. The LPSS and PSS of the RT group were significantly better than those of the NRT group (P = 0.007, P < 0.001, respectively). In multivariate analysis, postoperative radiotherapy was an independent factor for LPSS [P < 0.001; hazard ratio (HR) 0.17; 95% confidence interval (CI) 0.06-0.46] and PSS (P < 0.001; HR 0.31; 95% CI 0.16-0.60). CONCLUSIONS: Postoperative radiotherapy contributed to the control of residual tumor and was significantly associated with better LPSS and PSS among patients with positive CRM after esophagectomy for ESCC.

Neoadjuvant Chemoradiotherapy with Cisplatin Plus Fluorouracil for Borderline Resectable Esophageal Squamous Cell Carcinoma.

BACKGROUND: The optimal treatment strategy for patients with borderline resectable (BR) esophageal squamous cell carcinoma (ESCC), in which tumors grow very close to the adjacent vital organs, remains unclear. This study evaluated the efficacy of neoadjuvant chemoradiotherapy (NACRT) with cisplatin plus fluorouracil (CF) and irradiation (40 Gy) for these patients. METHODS: The study cohort included 50 patients with BR-ESCC who received NACRT as the initial treatment and were allocated to one of two groups: patients who achieved curative resection (R0 group) or those who did not (Non-R0 group). The overall survival (OS), relapse-free survival (RFS), and pre-therapeutic predictive factors for Non-R0 were evaluated. RESULTS: Among the 50 patients, 22 (44%) achieved curative resection clinically. The median OS was significantly better in the R0 group than in the Non-R0 group (2.4 vs 0.8 years; hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.12-0.67; p < 0.01). The independent predictive factors before NACRT for Non-R0 were higher serum SCC antigen level (p < 0.01) and clinical nodal involvement (p = 0.02). In addition, OS was significantly worse for the patients with higher levels of serum SCC antigen than for those with lower levels (p < 0.01). CONCLUSIONS: Curative resection was achieved for about 40% of the patients who received NACRT for BR-ESCC. Therefore, NACRT could be a useful neoadjuvant treatment option for BR-ESCC. However, a higher serum SCC antigen level before NACRT is predictive of treatment failure and poor survival.

Treatment Strategy for Esophageal Squamous Cell Carcinoma With Endoscopic Intramural Metastasis.

PURPOSE: Intramural metastasis (IM) in esophageal squamous cell carcinoma (ESCC) is sometimes found, and the prognosis of ESCC patients with pathologically diagnosed IM is known to be dismal. However, there are few reports on ESCC patients with clinically diagnosed IM. METHODS: This study assessed 2,772 ESCC patients who underwent endoscopy for initial evaluation. Among them, 85 patients (3.1%) were diagnosed with endoscopic IM. In this study, we investigated these patients' characteristics, survival among the groups stratified by the treatment modalities, and survival predictors. RESULTS: Of 85 patients, 76 (89.4%) had T3 or T4 tumors, 73 (85.9%) had nodal metastases, and 36 (42.4%) had M1 diseases. Curative-intent treatment could be given to 63 patients (74.1%) with a median survival time (MST) of 15.6 months (95% CI: 10.7-20.4). As initial treatment, upfront surgery (US), neoadjuvant chemotherapy (NAC) using cisplatin and 5-fluorouracil (CF), neoadjuvant chemoradiotherapy, and definitive chemoradiotherapy (dCRT) were given to 17 (27.0%), 27 (42.9%), 2 (3.2%), and 17 patients (27.0%), respectively. dCRT was preferred for T4 tumors compared with US or NAC (P = 0.02). The MST of US and NAC patients was 19.3 (95% CI: 12.9-25.6) and 23.4 months (95% CI: 9.4-37.4), respectively. No significant difference was noted between US and NAC patients (P= 0.89). CONCLUSION: The prognosis of ESCC patients with endoscopic IM is poor even if curative-intent treatment is done. Moreover, no significant survival benefit of NAC with CF for these patients was observed when compared with US.

Radiotherapy for 41 patients with stages I and II MALT lymphoma: a retrospective study.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following radiation therapy (RT) alone. PATIENTS AND METHODS: Forty-one patients with Stages I (37) and II (4) disease were treated between 2000 and 2006. Patients with transformed MALT were excluded. The median age was 60 years (range, 25-86 years), male: female ratio 1:1. Presenting sites included stomach, 11; orbital adnexa, 21; thyroid, 1; other head and neck, 3; small bowel, 3; skin, 1; and rectum, 1. Thirty-five patients (85%) received RT-alone and 6 (15%) received antibiotics followed by RT. RT dose was 30Gy in 20 fractions (fr) in all 41 patients. Mean follow-up time was 32.0 months (range, 2.1-162 months). RESULTS: A first complete response was achieved in all 41 patients. Only one patient died from bile duct carcinoma at 22 months from the start of irradiation for conjunctiva MALT lymphoma without recurrence of lymphoma. The other 40 patients were alive. Thirty-eight patients out of them were alive without recurrence. One patient with a duodenal lymphoma had a recurrence in non-irradiated distant sites at 1 month. Another patient with a bilateral eye lid lymphoma had a recurrence within radiation field at 41 months. The absolute local control rate with radiation was 98% (40/41 patients). CONCLUSION: Localized MALT lymphomas have excellent prognosis following moderate-dose RT (30Gy/20fr).

Long-term outcomes of combined endoscopic resection and chemoradiotherapy for esophageal squamous cell carcinoma with submucosal invasion.

BACKGROUND: For esophageal squamous cell carcinoma (ESCC) with submucosal (SM) invasion, surgery is the standard treatment. Definitive chemoradiotherapy (D-CRT) is a less invasive alternative option, but sometimes results in locoregional failure. AIM: To examine whether endoscopic resection for primary lesion removal combined with chemoradiotherapy (ER-CRT) reduces locoregional failure rates in cases of ESCC with SM invasion. METHODS: We retrospectively compared clinical outcomes between ER-CRT and D-CRT in patients diagnosed with ESCC with SM invasion between 2003 and 2014. Twenty-one patients underwent ER-CRT based on a pathological diagnosis, and 43 patients underwent D-CRT based on a clinical diagnosis. RESULTS: Locoregional failure developed in 26% of patients in the D-CRT group, and in no patients in the ER-CRT group (p < 0.01). Thus, the 5-year relapse-free survival in the ER-CRT group was significantly more favorable than that in the D-CRT group (85.1% vs 59.2%; p < 0.05), although there was no difference in overall survival (85.1% vs 79.1%) nor in cause-specific survival (90.5% vs 87.2%) between the groups. There were no instances of perforation or hemorrhage associated with ER. CONCLUSION: ER-CRT is a safe and effective treatment strategy and can be considered as a new minimally invasive treatment option for patients with ESCC with SM invasion.

Correlation among six biologic factors (p53, p21(WAF1), MIB-1, EGFR, HER2, and Bcl-2) and clinical outcomes after curative chemoradiation therapy in squamous cell cervical cancer.

PURPOSE: The expressions of six cell-cycle-associated proteins were analyzed in cervical squamous cell carcinomas in correlation in a search for prognostic correlations in tumors treated with concurrent chemoradiation therapy (cCRT). METHODS AND MATERIALS: The expressions of p53, p21/waf1/cip1, molecular immunology borstel-1 (MIB-1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2), and Bcl-2 were studied using an immunohistochemical method in 57 cases of cervical squamous cell carcinoma treated with cCRT. Patients received cCRT between 1998 and 2005. The mean patient age was 61 years (range, 27-82 years). The number of patients with Stage II, III, and IVA disease was 18, 29, and 10, respectively. RESULTS: The number of patients with tumors positive for p53, p21/waf1/cip1, MIB-1, EGFR, HER2, and Bcl-2 was 26, 24, 49, 26, 13, and 11, respectively; no significant correlation was noted. The 5-year overall survival rates of HER2-positive and -negative patients was 76% vs. 44%, which was of borderline significance (p = 0.0675). No significant correlation was noted between overall survival and expressions of p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2. No correlation was observed between local control and expression of any of the proteins. CONCLUSION: Expression of HER2 protein had a weak impact of borderline significance on overall survival in squamous cell carcinoma of the uterine cervix treated with cCRT. However, no clinical associations could be established for p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2 protein expressions.