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Background: To analyze prognostic factors associated with long-term outcomes in patients with resected pancreatic cancer treated with chemotherapy (CT) and surgery with or without external beam radiotherapy (EBRT)., Patients and Methods: From January 1995 to December 2012, 95 patients with adenocarcinoma of the pancreas and locoregional disease [clinical stage IB-IIA (n = 45; 47%), IIB-IIIC (n = 50; 53%)] were treated with curative resection [R0 (n = 52; 55%), R1 (n = 43, 45%)] and CT with (n = 60; 63%) or without (n = 35; 37%) EBRT (45-50.4 Gy). Additionally, 29 patients (48%) also received a pre-anastomosis IOERT boost (applicator diameter size, 7-10 cm; dose, 10-15 Gy; beam energy, 9-18 MeV)., Results: With a median follow-up of 17.2 months (range, 1-182), 2-year overall survival (OS), disease-free survival (DFS), and locoregional control were 28, 20, and 53%, respectively. Univariate analyses showed that IIB-IIIC stage (HR, 2.23; p = 0.04), R1 margin resection status (HR, 2.09; p = 0.04), no vascular resection (HR, 0.42; p = 0.02), and not receiving external beam radiotherapy (HR, 2.70; p = 0.004) were associated with locoregional recurrence. In the multivariate analysis, only R1 margin resection status (HR, 2.63; p = 0.009) and not receiving EBRT (HR, 2.91; p = 0.002) retained significance with regard to locoregional recurrence. We observed no difference in toxicity between patients treated with or without EBRT (p = 0.44). Overall treatment mortality was 3%. No long-term treatment-related death occurred., Conclusions: Although adjuvant CT is still the standard of care for resected pancreatic tumors, OS remains modest owing to the high risk of distant metastases. Locoregional treatment needs to be tested in the context of more efficient systemic therapy.

Purpose: To analyze prognostic factors and long-term outcomes in patients with locally recurrent pelvic cancer (LRPC) treated with a multidisciplinary approach., Methods and Materials: From January 1995 to December 2011, 81 patients [rectal (47 %); gynecologic (39 %); retroperitoneal sarcoma (14 %)] underwent extended surgery [multiorgan (58 %), bone (35 %), vascular (9 %), soft tissue (63 %)] and intraoperative electron beam radiation therapy (IOERT) to treat recurrent tumors in the pelvic region. Thirty-five patients (43 %) received external beam radiotherapy (EBRT). Survival was estimated using the Kaplan-Meier method, and risk factors were identified using univariate and multivariate analysis., Results: Median follow-up was 39 months (6-189 months); the 1- 3- and 5-year rates of locoregional control (LRC) were 83, 53, and 41 %, respectively. Univariate Cox proportional hazard analysis revealed worse LRC in patients who did not receive integrated EBRT as rescue treatment of pelvic recurrence (p = 0.003) or underwent non-radical resection (p = 0.01). In the multivariate analysis EBRT, non-radical resection, and tumor fragmentation retained significance (p = 0.002, p = 0.004, and p = 0.05, respectively)., Conclusions: Radical resection, absence of tumor fragmentation and addition of EBRT for rescue are associated with improved LRC in patients with LRPC. Our results suggest that this group can benefit from EBRT combined with extended surgical resection and IOERT.

Background: Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT., Methods: A total of 335 patients with LARC [⩾cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed., Results: Median follow-up was 72.6 months (range, 4-205). In multivariate analysis distal margin distance ⩽10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1-2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC., Conclusions: Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The goal of the present study was to analyze prognostic factors in patients treated with external-beam radiation therapy (EBRT), surgical resection and intraoperative electron-beam radiotherapy (IOERT) for oligorecurrent gynecological cancer (ORGC)., Patients and Methods: From January 1995 to December 2012, 61 patients with ORGC [uterine cervix (52 %), endometrial (30 %), ovarian (15 %), vagina (3 %)] underwent IOERT (12.5 Gy, range 10-15 Gy), and surgical resection to the pelvic (57 %) and paraaortic (43 %) recurrence tumor bed. In addition, 29 patients (48 %) also received EBRT (range 30.6-50.4 Gy). Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses., Results: Median follow-up time for the entire cohort of patients was 42 months (range 2-169 months). The 10-year rates for overall survival (OS) and locoregional control (LRC) were 17 and 65 %, respectively. On multivariate analysis, no tumor fragmentation (HR 0.22; p = 0.03), time interval from primary tumor diagnosis to locoregional recurrence (LRR) < 24 months (HR 4.02; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.95; p = 0.02) retained significance with regard to LRR. Time interval from primary tumor to LRR < 24 months (HR 2.32; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.77; p = 0.04) showed a significant association with OS after adjustment for other covariates., Conclusion: External-beam radiation therapy at the time of pelvic recurrence, time interval for relapse ≥ 24 months and not multi-involved fragmented resection specimens are associated with improved LRC in patients with ORGC. As suggested from the present analysis a significant group of ORGC patients could potentially benefit from multimodality rescue treatment.

Objective: To analyze prognostic factors in patients treated with intraoperative electrons containing resective surgical rescue of locally recurrent gynecological cancer (LRGC)., Methods: From January 1995 to December 2012, 35 patients with LRGC [uterine cervix (57%), endometrial (20%), ovarian (17%), vagina (6%)] underwent extended [multiorgan (54%), bone (9%), soft tissue (54%), vascular (14%)] surgery and intraoperative electron-beam radiation therapy [IOERT (10-15 Gy)] to the pelvic recurrence tumor bed. Sixteen (46%) patients also received external beam radiation therapy [EBRT (30.6-50.4 Gy)]. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses., Results: Median follow-up time for the entire cohort of patients was 46 months (range, 3-169). Ten-year rates for locoregional control (LRC) and overall survival (OS) were 58 and 16%, respectively. On multivariate analysis non-EBRT at the time of pelvic re-recurrence [HR 4.15; p = 0.02], no tumor fragmentation [HR 0.13; p=0.05] and time interval from primary tumor to LRR < 24 months [HR 5.16; p=0.01], retained significance with regard to LRR. Non-EBRT at the time of pelvic re-recurrence [HR 4.18; p=0.02] and time interval from primary tumor to LRR < 24 months [HR 6.67; p=0.02] showed a significant association with OS after adjustment for other covariates., Conclusions: EBRT treatment integrated for rescue, time interval for relapse ≥ 24 months, and not multi-involved fragmented resection specimens are associated with improved LRC in patients with LRGC in the pelvis. Present results suggest that a significant group of patients may benefit from EBRT treatment integrated with extended surgery and IOERT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To analyze prognostic factors associated with survival in patients after intraoperative electrons containing resective surgical rescue of locally recurrent rectal cancer (LRRC)., Methods and Materials: From January 1995 to December 2011, 60 patients with LRRC underwent extended surgery (n=38: multiorgan [43%], bone [28%], soft tissue [38%]) or nonextended (n=22) surgical resection, including a component of intraoperative electron-beam radiation therapy (IOERT) to the pelvic recurrence tumor bed. Twenty-eight (47%) of these patients also received external beam radiation therapy (EBRT) (range, 30.6-50.4 Gy). Survival outcomes were estimated by the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses., Results: The median follow-up time was 36 months (range, 2-189 months), and the 1-year, 3-year, and 5-year rates for locoregional control (LRC) and overall survival (OS) were 86%, 52%, and 44%; and 78%, 53%, 43%, respectively. On multivariate analysis, R1 resection, EBRT at the time of pelvic rerecurrence, no tumor fragmentation, and non-lymph node metastasis retained significance with regard to LRR. R1 resection and no tumor fragmentation showed a significant association with OS after adjustment for other covariates., Conclusions: EBRT treatment integrated for rescue, resection radicality, and not involved fragmented resection specimens are associated with improved LRC in patients with locally recurrent rectal cancer. Additionally, tumor fragmentation could be compensated by EBRT. Present results suggest that a significant group of patients with LRRC may benefit from EBRT treatment integrated with extended surgery and IOERT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: To report feasibility, tolerance, anatomical sites of upper abdominal locoregional recurrence and long-term outcome of gastric cancer patients treated with surgery and a component of intraoperative electron beam radiotherapy (IORT)., Materials and Methods: From January 1995 to December 2010, 32 patients with primary gastric adenocarcinoma treated with curative resection (R0) [total gastrectomy (n = 9; 28 %), subtotal (n = 23; 72 %) and D2 lymphadenectomy in all patients] and apparent disease confined to locoregional area [Stage: II (n = 15; 47 %), III (n = 17; 53 %)] were treated with a component of IORT (IORT applicator size 5-9 cm in diameter, dose 10-15 Gy, beam energy 6-5 MeV) over the celiac axis and peripancreatic nodal areas. Sixteen (50 %) patients also received adjuvant treatment (external beam radiotherapy n = 6, chemoradiation n = 9, chemotherapy alone n = 1)., Results: With a median follow-up time of 40 months (range, 2-60), locoregional recurrence was observed in five (16 %) patients (4 nodal in hepatic hilum and 1 anastomotic). Only pN1 patients developed locoregional relapse. No recurrence was observed in the IORT-treated target volume (celiac trunk and peripancreatic nodes). Overall survival at 5 years was 54.6 % (95 % CI: 48.57-60.58). Postoperative mortality was 6 % (n = 2) and postoperative complications 19 % (n = 6)., Conclusions: It is feasible to integrate IORT as a component of radiotherapy in combined modality therapy of gastric cancer. Local control is high in the radiation boosted area, but marginal regional extension (in particular, involving the hepatic hilum) might be considered as part of the anatomic IORT target volume at risk in pN+ patients.

Background: To report feasibility, tolerance, anatomical topography of locoregional recurrence (LRR), and long-term outcome for esophageal and esophagogastric (EG) cancer patients treated with preoperative chemoradiation (CRT) and surgery with or without a radiation boost of intraoperative electron beam radiotherapy (IOERT)., Methods: From January 1995 to December 2010, 53 patients with primary esophageal (n = 26; 44 %) or EG carcinoma (n = 30; 56 %), and disease confined to locoregional area [clinical stage: IIb (n = 30; 57 %), IIIa (n = 14; 26 %), IIIb (n = 6; 11 %), IIIc (n = 3; 6 %)], were treated with preoperative CRT, curative (R0) resection with an extended (two-field) lymph node dissection in all cases. Thirty-seven patients also received a preanastomotic reconstruction IOERT boost (applicator diameter size 6-9 cm, dose 10-15 Gy, beam energy 6-15 MeV) over the tumor bed in the mediastinum and upper abdominal lymph node area., Results: With a median follow-up time of 27.9 months (range, 0.2-148), LRR rate was 15 % (n = 8). Five-year overall survival (OS) and disease-free survival was 48 and 36 %, respectively. Univariate log-rank analyses showed that receiving IOERT was associated with lower risk of LRR (p = 0.004). On multivariate analysis, only the IOERT group retained significance in relation to LRR (odds ratio, 0.08; 95 % confidence interval, 0.01-0.48; p = 0.01). Postoperative mortality and perioperative complications were 11 % (n = 6) and 30 % (n = 16)., Conclusions: Local control is high in the radiation-boosted area, but OS remains modest, given the high risk of distant metastases. Intensified locoregional treatment needs to be tested in the context of more efficient concurrent, neo-, and adjuvant systemic therapy.

Purpose: To evaluate the feasibility and long-term outcome of surgery combined with intraoperative electron radiotherapy (IOERT) as rescue treatment in patients with recurrent and/or metastatic oligotopic extrapelvic cancer., Methods and Materials: From April 1996 to April 2010, we treated 28 patients using 34 IOERT procedures. The main histopathology findings were adenocarcinoma (39%) and squamous cell carcinoma (29%). The original cancer sites were gynecologic (67%), urologic (14%) and colorectal (14%). The location of recurrence was the para-aortic region in 53.5% of patients., Results: Median follow-up was 39 months (1-84 months), during which time 14% of patients experienced local recurrence and 53.5% developed distant metastasis. Overall survival at 2 and 5 years was 57% and 35% respectively. At the time of the analysis, 13 patients were alive, 6 for more than 55 months of follow-up. Local control was not significantly affected by the following histopathologic characteristics of the resected surgical specimen: number of fragments submitted for pathology study (1 to >6), maximal tumor dimension (≤ 2 to ≥ 6 cm), rate of involved nodes (0-100%) and involved resection margin (local recurrence 23% vs 7%; p = 0.21). Local recurrence was significantly affected by microscopic cancer in more than 50% of specimen fragments (38% vs 9%, p = 0.02)., Conclusions: IOERT for recurrence of oligotopic extrapelvic cancer increased long-term survival in patients with controlled cancer and appears to compensate for some adverse prognostic features in local control. Individualized treatment strategies for this heterogeneous category of patients with recurrent cancer will make it possible to optimize results., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Recurrence of hepatocellular carcinoma is rarely treated by surgical resection and has not been reported in the main series of liver transplantation. In this paper we present the case of a patient transplanted for hepatocellular carcinoma on cirrhosis who developed a tumoral recurrence in the transplanted liver four months later. The new tumor was removed by hepatectomy and the patient is free of tumor 24 months after resection. Surgical resection should be considered a treatment of tumoral recurrence after liver transplantation as is done after hepatectomy.