Evaluation and treatment results of trimodality therapy for advanced esophageal squamous cell carcinoma.

OBJECTIVES: The prognosis for highly advanced esophageal squamous cell carcinoma (ESCC) remains poor, and there is currently no standard treatment. The purpose of this study was to examine the benefits of trimodality therapy [chemoradiation plus surgery, (CRT + S)] by evaluating the surgical outcomes of patients with ESCC in Keiyukai Sapporo Hospital, Japan. We assessed the preoperative and postoperative adverse events, treatment effects of preoperative CRT, metastatic diagnosis of the dissected lymph nodes, and survival. PATIENTS AND METHODS: Between 2012 and 2018, 148 patients with highly advanced ESCC who underwent preoperative CRT + S were analyzed for diagnosis and staging, preoperative complications, clinical and histopathological effects of CRT in the resected specimens, survival rates, and recurrences. RESULTS: The grade 3 and higher complications of preoperative CRT were neutropenia in 3 cases and thrombocytopenia in 1 case. Among the postoperative complications, there were 2 cases (1.4%) of direct surgical death, only tracheobronchial bleeding and liver failure. Using the 11th edition of the classification of esophageal cancer by the Japanese Esophageal Society, 60 patients (40.5%) were classified as grade 3 (negative for cancer cells, pathological complete response). However, 20 of them (33.3%) had metastatic tumor cells in the lymph nodes. The overall 5-year survival rate was 58.5%. Including references to the pathological findings and recurrence patterns, there is no effective diagnostic method for selecting the subsequent approach based on the effectiveness of CRT. CONCLUSION: Planned surgery following CRT was the only solution for achieving better treatment results. CRT + S is a promising treatment with low direct surgical mortality.

Endoscopic resection as an independent predictive factor of local control in patients with T1bN0M0 esophageal squamous cell carcinoma treated with chemoradiotherapy: a retrospective study.

BACKGROUND: Although chemoradiotherapy (CRT) is one of the curative treatments for thoracic esophageal squamous cell carcinoma (ESCC) with submucosal invasion, the risk of local recurrence after CRT remains a clinical problem. This retrospective study aimed to analyze the predictive factors for local recurrence after CRT. METHODS: Ninety-one patients with clinical or pathological (c/p) T1bN0M0 thoracic ESCC who underwent CRT from 2004 to 2017 in our institution were analyzed retrospectively. Sixty-three patients were diagnosed with pathological T1b after undergoing initial endoscopic resection (ER) and treated with additional CRT; meanwhile, 28 patients were clinically diagnosed with T1b and underwent definitive CRT. We investigated the predictors of disease-specific survival (DSS) and local recurrence-free survival (LRFS) by performing univariate and multivariate analyses. RESULTS: The median observation period was 59.8 months. The 5-year DSS and LRFS rates were 84.3% (95% confidence interval [CI]: 76.1-92.5) and 87.1% (95% CI: 79.1-95.1), respectively. The multivariate analysis revealed no significant predictors associated with DSS. On the contrary, ER (hazard ratio [HR]: 0.11, 95% CI: 0.02-0.48, p = 0.003) and tumor length (HR: 6.78, 95% CI: 1.28-36.05, p = 0.025) were recognized as independent predictive factors for LRFS. During follow-up, recurrence was observed in 18 patients (19.8%). With regard to the patterns of relapse, local recurrence was the most common in 11 patients, and salvage ER was performed in 9 of 11 patients. CONCLUSIONS: ER and tumor length were independent predictive factors for LRFS. Our study suggested that performance of ER prior to CRT improved the local control in patients with c/p T1bN0M0 ESCC. In addition, most of the patients who experienced local recurrence were treated with salvage ER, which contributed to preserving the organs.

Significance of boost radiotherapy in early invasive ductal breast cancer with ductal carcinoma in situ component under negative surgical margins.

We hypothesize that there is a risk of ipsilateral breast tumor recurrence (IBTR) in surgical margin-free invasive ductal carcinoma (IDC) in the presence of ductal carcinoma in situ (DCIS) component affecting surgical margins in early stage. From 1990 to 2014, 343 patients with IDC in which the DCIS component constitute have received radiotherapy (RT) following breast-conserving surgery (BCS). All patients received whole breast irradiation with a prescribed dose of 50 Gy in 20 fractions (four times a week). This one-arm cohort with boost RT (253 patients) was compared for IBTR with a non-cohort group receiving no boost RT because of freedom from positive margins (90 patients). Median observation months were 98 (boost group) vs 119 (no boost group), respectively. The 15-year local recurrence-free survival (LRFS) rates were 98.5% and 85.6% in the boost and no boost groups, respectively (Cox proportional hazards model univariate analysis; p = 0.013, HR 0.13). Similarly, for other background factors, there was a significant difference in the LRFS between age groups. The 15-year LRFS rate was 91.8% in patients aged 45 years or younger and 94.6% in patients older than 46 years (p = 0.031, HR 0.21), respectively. Only these two factors were independently significant in Cox proportional hazards model multivariate analysis. IBTR risk in margin-free IDC with DCIS component was independently decreased by boost RT in the cohort setting. Tumor size, extensive intraductal component (EIC), boost dose, the presence of lymph node (LN) metastasis and hormonal therapy were not IBTR risk factors in this study.

Esophageal motion characteristics in thoracic esophageal cancer: Impact of clinical stage T4 versus stages T1-T3.

PURPOSE: The main purpose was to investigate the differences of the esophageal motion (EM) and the internal target volume (ITV) margins for the esophagus between clinical T1-T3 (cT1-T3) and cT4 cases, using 4-dimensional computed tomography. A secondary purpose was to assess the metastatic lymph nodal motion (NM) and the ITV margins for lymph nodes (LNs) using the datasets of patients with nodal involvement pathologically defined. METHODS AND MATERIALS: We analyzed patients with thoracic esophageal cancer consecutively treated with definitive chemoradiation, measuring the EM and the ITV margins in the left-right, anteroposterior, and superoinferior directions. All esophageal contours were divided at the carina. The EM and NM were measured from the displacement of the centroid point between 0% images (at the end of inhalation) and 50% images (at the end of exhalation). The ITV margins were defined as the maximum distance in each direction from the clinical target volume at the 4-dimensional computed tomography average images to the intersection of the clinical target volume at the 0% and 50% images of complete coverage in each patient. RESULTS: The EM below the carina in cT4 was significantly smaller than that in cT1-T2 in all directions (P < .01) and than that in cT3 in all directions (left-right: P = .03, anteroposterior and superoinferior: P < .01). The EM in the case of a cT4 tumor located below the carina was smaller than that in the case of cT4 tumor located above the carina. The NM of abdominal-LNs was much larger than that of cervicothoracic-LNs and the EM below the carina. These tendencies were similar in the ITV measurements. CONCLUSIONS: The EM and the ITV margins in cT4 were significantly smaller than those in cT1-T3. The NM and the ITV margins of abdominal LNs were much larger than those of cervicothoracic LNs and the esophagus. In clinical radiation therapy planning for esophageal cancer, we should take cT stage into consideration.

Prognostic factors in clinical T1N0M0 thoracic esophageal squamous cell carcinoma invading the muscularis mucosa or submucosa.

BACKGROUND: Multimodality treatment is widely performed for clinical T1N0M0 (UICC-TNM classification, 7th edition) thoracic esophageal squamous cell carcinoma (ESCC), but available articles regarding treatment results are limited. This study assessed the outcomes of clinical T1N0M0 thoracic ESCC invading the muscularis mucosa (MM) or submucosa (SM) treated with radiotherapy (RT) or chemoradiotherapy (CRT). METHODS: We retrospectively reviewed the medical charts of 90 patients with clinical T1N0M0 thoracic ESCC treated with RT or CRT in our hospital in 2004-2011. Of these 90 patients, we analyzed the cases of 71 patients who met our inclusion criteria. All 71 patients had MM or SM cancer. In the 47 patients treated with CRT, the chemotherapy regimen of 5-fluorouracil (5-FU) plus cisplatin (CDDP) was used for 46 patients and 5-FU and nedaplatin was used for one patient. Forty-five patients underwent endoscopic resection (ER) followed by RT or CRT as an additional treatment. Elective nodal irradiation (ENI) was used in 39 patients. For all analyses, statistical significance was defined as 0.05, and the Bonferroni correction was used for the multivariate analysis. RESULTS: The median age was 70 years (range 47-84). With a median follow-up of 43.6 months (range 1.5-124.2), the 5-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) rates were 64.0, 72.8 and 50.0 %, respectively. The multivariate analysis showed that performance status (PS) was an independent prognostic factors for DSS and DFS (DSS, p < 0.001; DFS, p < 0.001). Chemotherapy in addition to RT showed a trend for better DSS (p = 0.032) but was not significant following Bonferroni correction. ER and ENI were not significant predictive factors for DSS and DFS. CONCLUSIONS: PS was an independent prognostic factor for DSS and DFS. ER and ENI had no significant relationship with DSS or DFS. The present results may be helpful in treatment decisions for clinical T1N0M0 thoracic ESCC.

Dose-volume analysis for respiratory toxicity in intrathoracic esophageal cancer patients treated with definitive chemoradiotherapy using extended fields.

PURPOSE: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. PATIENTS AND METHODS: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0-1 RP (RPG≤1) group and the Grade 2-5 RP (RPG≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. RESULTS: Of these 86 patients, 10 (12%) developed RPG≥2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RPG≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RPG≥2 group. There were two advantages gained from the proposed plan for V5 (<55%) and V10 (< 37%) values and the conformity of the PTV. CONCLUSION: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.

Postoperative external beam radiotherapy for resected pancreatic adenocarcinoma: impact of chemotherapy on local control and survival.

AIM: To analyze retrospectively the results of postoperative external beam radiotherapy (EBRT) for resected pancreatic adenocarcinoma. PATIENTS AND METHODS: The records of 47 patients treated with gross complete resection (R0: 24 patients, R1: 23 patients) and post-operative EBRT were reviewed. The median dose of EBRT was 50 Gy (range, 12-60 Gy), and chemotherapy was used in 37 patients (78.7%). The median follow-up period for all 47 patients was 14.4 months (range, 0.9-67.9 months). RESULTS: At the time of this analysis, 24 patients (51.1%) had disease recurrence. Local failure was observed in 10 patients (21.3%), and the 2-year local control (LC) rate in all patients was 68.7%. Patients treated with EBRT and chemotherapy had a significantly more favorable LC (2-year LC rate: 76.0%) than those treated with EBRT alone (2-year LC rate: 40%, p=0.0472). The median survival time and the 2-year actuarial overall survival (OS) in all 47 patients were 30.0 months and 54.5%, respectively. Patients treated with EBRT and chemotherapy had a significantly more favorable OS (2-year OS rate: 61.6%) than those treated with EBRT alone (2-year OS: 25.0%, p=0.0454). On univariate analysis, chemotherapy use alone had a significant impact on OS, and on multivariate analysis, chemotherapy use also was a significant prognostic factor. There were no late morbidities of NCI-CTC Grade 3 or greater. CONCLUSION: Post-operative EBRT with chemotherapy yields a favorable LC rate for resected pancreatic adenocarcionoma, and EBRT combined with chemotherapy confers a survival benefit compared to EBRT alone.

A multi-institutional survey of the effectiveness of chemotherapy combined with radiotherapy for patients with nasopharyngeal carcinoma.

BACKGROUND: Previous randomized trials have shown a survival advantage of concurrent platinum-based chemoradiotherapy with or without adjuvant chemotherapy for advanced nasopharyngeal cancer. Applicability of these data to a Japanese population is an important issue which remains to be solved. METHODS: A retrospective survey of treatment of patients with nasopharyngeal cancer in 17 institutions in Japan was done with special reference to the relationship between the type of chemotherapy and survival outcome. Chemotherapy used was classified according to: (i) whether > or =2 courses of platinum plus 5-fluorouracil (FP) was given; or (ii) whether platinum was administered concurrently with radiotherapy (RT). This resulted in three groups being produced consisting of (i)/(ii) = YES/YES, other miscellaneous (MISC) and RT alone. RESULTS: Of 333 evaluable replies, 67 patients (20%) corresponded to the YES/YES, 192 (58%) to the MISC and 74 (22%) to the RT alone group. The YES/YES group achieved a better overall survival than RT alone for patients with intermediate stage (T3N0 or T1-3N1, 81.9 versus 60.7% at 5 years, P = 0.042) and advanced stage (T4 or N2/3, 56.6 versus 31.5%, P = 0.017) disease. The MISC group achieved an almost identical survival rate to that in the YES/YES group for patients with intermediate stage disease (81.9% at 5 years, P = 0.968), whereas it was not significantly different from that of the RT alone group for patients with advanced stage disease (44.0%, P = 0.261). CONCLUSION: The results of this survey mirrored the data from previous randomized trials for patients with intermediate and advanced stage nasopharyngeal cancer in Japan. However, confirmatory prospective trials are required to test the efficacy of less toxic approaches for patients with intermediate stage disease.