Effect of Extending the Original Eligibility Criteria for the CROSS Neoadjuvant Chemoradiotherapy on Toxicity and Survival in Esophageal Cancer

Patients with curable esophageal cancer (EC) who proceed beyond the original Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect that extending the CROSS eligibility criteria for nCRT has on treatment-related toxicity and overall survival (OS) in EC. The study enrolled 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0) treated with the CROSS schedule followed by esophagectomy. Group 1 consisted of 89 patients who met the CROSS criteria, and group 2 consisted of 72 patients who met the extended eligibility criteria, i.e. a tumor length greater than 8 cm (n = 24), more than 10% weight loss (n = 35), more than 2-4 cm extension in the stomach (n = 21), celiac lymph node metastasis (n = 13), and/or age over 75 years (n = 2). The study assessed the differences in nCRT-associated toxicity [National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) grade3] and 90-day postoperative mortality. Moreover, the prognostic value for OS was assessed with multivariate Cox regression analysis. No difference was found in nCRT-associated toxicity (P = 0.117), postoperative complications (P = 0.783), and 90-day mortality (P = 0.492). The OS differed significantly (P = 0.004), with a median of 37.3 months [95% confidence interval (CI), 10.4-64.2 months] for group 1 and 17.2 months (95% CI 13.8-20.7 months) for group 2. Pathologic N stage (P = 0.023), pathologic T stage (P = 0.043), and group 2 (P = 0.008) were independent prognostic factors for OS. Extension of the CROSS study eligibility criteria for nCRT did not affect nCRT-associated toxicity, postoperative complications, and postoperative mortality, but was prognostic for OS

Prognostic Value of the Circumferential Resection Margin in Esophageal Cancer Patients After Neoadjuvant Chemoradiotherapy

Background. Circumferential resection margins (CRM) for esophageal cancer (EC), defined by the College of American Pathologists (CAP; >0 mm) or the Royal College of Pathologists (RCP; >1 mm) as tumor-free (R0), are based on a surgery-alone approach. We evaluated the usefulness of both definitions in current practice with neoadjuvant chemoradiotherapy (nCRT). Methods. CRMs were measured in 209 patients (104 with nCRT) with locally advanced EC after transthoracic esophagectomy. Local recurrence and cancer related death were scored as events. Patients were followed for at least 2 years or until death. Prognostic factors (P <0.1 in univariate analyses) for 2-year disease-free survival (DFS) and local recurrence-free survival (LRFS) were incorporated in multivariate Cox regression analyses. Both CRM measurements were analyzed separately and prognostic cutoff values (0-1.0 mm) were assessed in both groups. Results. Independent prognostic factors (P <0.05) for 2-year DFS were tumor length, lymph node ratio, angioinvasion, and CAP R0 in the surgery-alone group and pN stage (P <0.01) in the nCRT group. Prognostic factors (P <0.05) for 2-year LRFS were CAP, lymph node ratio, and tumor length in the surgery-alone group, and CAP and grade in the nCRT group. Optimal CRM cutoff values between 0.0 and 0.2 mm were prognostic for 2-year DFS in the surgery-alone and at 0.3 mm for the nCRT group. Conclusions. nCRT affected the CRM cutoff values. After nCRT, the CRM R0 according to the CAP was only prognostic for 2-year LRFS. However, in the surgery-alone group, it was prognostic for both the 2-year DFS and LRFS

Impact of Endoscopic Ultrasonography on (18)F-FDG-PET/CT Upfront Towards Patient Specific Esophageal Cancer Treatment

INTRODUCTION: In patients with potentially resectable esophageal cancer (EC), the value of endoscopic ultrasonography (EUS) after fluorine-18 labeled fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) is questionable. Retrospectively, we assessed the impact of EUS after PET/CT on the given treatment in EC patients. METHODS: During the period 2009-2015, 318 EC patients were staged as T1-4aN0-3M0 with hybrid (18)F-FDG-PET/CT or (18)F-FDG-PET with CT and EUS if applicable in a nonspecific order. We determined the impact of EUS on the given treatment in 279 patients who also were staged with EUS. EUS had clinical consequences if it changed curability, extent of radiation fields or lymph node resection (AJCC stations 2-5), and when the performed fine-needle aspiration (FNA) provided conclusive information of suspicious lymph node. RESULTS: EUS had an impact in 80 (28.7%) patients; it changed the radiation field in 63 (22.6%), curability in 5 (1.8%), lymphadenectomy in 48 (17.2%), and FNA was additional in 21 (7.5%). In patients treated with nCRT (n = 194), EUS influenced treatment in 53 (27.3%) patients; in 38 (19.6%) the radiation field changed, in 3 (1.5%) the curability, in 35 (18.0%) the lymphadenectomy, and in 17 (8.8%) FNA was additional. EUS influenced both the extent of radiation field and nodal resection in 31 (16.0%) nCRT patients. CONCLUSIONS: EUS had an impact on the given treatment in approximately 29%. In most patients, the magnitude of EUS found expression in the extent of radiotherapy target volume delineation to upper/high mediastinal lymph nodes

Outcomes of surgery and postoperative radiation therapy in managing medullary thyroid carcinoma

Background and Objectives We evaluated the outcomes of surgery with or without postoperative radiation therapy (PORT) in the management of medullary thyroid carcinoma (MTC). Methods From two tertiary cancer centers, 297 consecutive patients with MTC treated with PORT (n = 46) between 1990 and 2016 or surgery alone (n = 251) between 2000 and 2016 were reviewed. Results Ten-year cumulative incidences of locoregional and distant failure were 30.2% and 24.9% in the surgery cohort, and 16.9% and 55.2% in the PORT cohort. In the surgery alone cohort, T4 disease, extrathyroidal extension, N1 disease, extranodal extension (ENE), and residual disease after surgery were associated with local failure. The PORT cohort had significantly higher proportions of patients with T4 disease, N1 disease, ENE, and residual disease. Conclusions High-risk clinical features can help identify patients with MTC at high-risk for local failure after surgery alone. Patients with high-risk clinical features had effective locoregional control after PORT

Timing of Parathyroidectomy Does Not Influence Renal Function After Kidney Transplantation

BACKGROUND: Parathyroidectomy (PTx) is the treatment of choice for end-stage renal disease (ESRD) patients with therapy-resistant hyperparathyroidism (HPT). The optimal timing of PTx for ESRD-related HPT-before or after kidney transplantation (KTx)-is subject of debate.METHODS: Patients with ESRD-related HPT who underwent both PTx and KTx between 1994 and 2015 were included in a multicenter retrospective study in four university hospitals. Two groups were formed according to treatment sequence: PTx before KTx (PTxKTx) and PTx after KTx (KTxPTx). Primary endpoint was renal function (eGFR, CKD-EPI) between both groups at several time points post-transplantation. Correlation between the timing of PTx and KTx and the course of eGFR was assessed using generalized estimating equations (GEE).RESULTS: The PTxKTx group consisted of 102 (55.1%) and the KTxPTx group of 83 (44.9%) patients. Recipient age, donor type, PTx type, and pre-KTx PTH levels were significantly different between groups. At 5 years after transplantation, eGFR was similar in the PTxKTx group (eGFR 44.5 ± 4.0 ml/min/1.73 m2) and KTxPTx group (40.0 ± 6.4 ml/min/1.73 m2, p = 0.43). The unadjusted GEE model showed that timing of PTx was not correlated with graft function over time (mean difference -1.0 ml/min/1.73 m2, 95% confidence interval -8.4 to 6.4, p = 0.79). Adjustment for potential confounders including recipient age and sex, various donor characteristics, PTx type, and PTH levels did not materially influence the results.CONCLUSIONS: In this multicenter cohort study, timing of PTx before or after KTx does not independently impact graft function over time.</p

Value of EUS in Determining Curative Resectability in Reference to CT and FDG-PET: The Optimal Sequence in Preoperative Staging of Esophageal Cancer?

Background: The separate value of endoscopic ultrasonography (EUS), multidetector computed tomography (CT), and18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the optimal sequence in staging esophageal cancer has not been investigated adequately. Methods: The staging records of 216 consecutive operable patients with esophageal cancer were reviewed blindly. Different staging strategies were analyzed, and the likelihood ratio (LR) of each module was calculated conditionally on individual patient characteristics. A logistic regression approach was used to determine the most favorable staging strategy. Results: Initial EUS results were not significantly related to the LRs of initial CT and FDG-PET results. The positive LR (LR+) of EUS-fine-needle aspiration (FNA) was 4, irrespective of CT and FDG-PET outcomes. The LR+ of FDG-PET varied from 13 (negative CT) to 6 (positive CT). The LR+ of CT ranged from 3-4 (negative FDG-PET) to 2-3 (positive FDG-PET). Age, histology, and tumor length had no significant impact on the LRs of the three diagnostic tests. Conclusions: This study argues in favor of PET/CT rather than EUS as a predictor of curative resectability in esophageal cancer. EUS does not correspond with either CT or FDG-PET. LRs of FDG-PET were substantially different between subgroups of negative and positive CT results and vice versa

Adequate debridement and drainage of the mediastinum using open thoracotomy or video-assisted thoracoscopic surgery for Boerhaave’s syndrome

Background Boerhaave's syndrome has a high mortality rate (14-40%). Surgical treatment varies from a minimal approach consisting of adequate debridement with drainage of the mediastinum and pleural cavity to esophageal resection. This study compared the results between a previously preferred open minimal approach and a video-assisted thoracoscopic surgery (VATS) procedure currently considered the method of choice. Methods In this study, 12 consecutive patients treated with a historical nonresectional drainage approach (1985-2001) were compared with 12 consecutive patients treated prospectively after the introduction of VATS during the period 2002-2009. Baseline characteristics were equally distributed between the two groups. Results In the prospective group, 2 of the 12 patients had the VATS procedure converted to an open thoracotomy, and 2 additional patients were treated by open surgery. In the prospective group, 8 patients experienced postoperative complications compared with all 12 patients in the historical control group. Four patients (17%), two in each group, underwent reoperation. Six patients, three in each group, were readmitted to the hospital. The overall in-hospital mortality was 8% (1 patient in each group), which compares favorably with other reports (7-27%) based on drainage alone. Conclusions Adequate surgical debridement with drainage of the mediastinum and pleural cavity resulted in a low mortality rate. The results for VATS in this relatively small series were comparable with those for an open thoracotomy

Extended Esophagectomy in Elderly Patients with Esophageal Cancer: Minor Effect of Age Alone in Determining the Postoperative Course and Survival

Elderly patients who undergo esophagectomy for cancer often have a high prevalence of coexisting diseases, which may adversely affect their postoperative course. We determined the relationship of advanced age (i.e., a parts per thousand yen70 years) with outcome and evaluated age as a selection criterion for surgery. Between January 1991 and January 2007, we performed a curative-intent extended transthoracic esophagectomy in 234 patients with cancer of the esophagus. Patients were divided into two age groups: <70 years (group I; 170 patients) and a parts per thousand yen70 years (group II; 64 patients). Both groups were comparable regarding comorbidity (American Society of Anesthesiologists classification), and tumor and surgical characteristics. The overall in-hospital mortality rate was 6.2% (group I, 5%, vs. group II, 11%, P = 0.09). Advanced age was not a prognostic factor for developing postoperative complications (odds ratio, 1.578; 95% confidence interval, 0.857-2.904; P = 0.143). The overall number of complications was equal with 58% in group I vs. 69% in group II (P = 0.142). Moreover, the occurrence of complications in elderly patients did not influence survival (P = 0.174). Recurrences developed more in patients <70 years (58% vs. 42%, P = 0.028). The overall 5-year survival was 35%, and, when included, postoperative mortality was 33% in both groups (P = 0.676).The presence of comorbidity was an independent prognostic factor for survival (P = 0.002). Advanced age (a parts per thousand yen70 years) has minor influence on postoperative course, recurrent disease, and survival in patients who underwent an extended esophagectomy. Age alone is not a prognostic indicator for survival. We propose that a radical resection should not be withheld in elderly patients with limited frailty and comorbidity

Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer:The Randomized Controlled CROSS Trial

PURPOSE: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS: From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS: The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION: The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years