Jose Luis García-Sabrido

Prognostic Value of External Beam Radiation Therapy in Patients Treated With Surgical Resection and Intraoperative Electron Beam Radiation Therapy for Locally Recurrent Soft Tissue Sarcoma: A Multicentric Long-Term Outcome Analysis

BACKGROUND A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. METHODS AND MATERIALS Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). RESULTS From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). CONCLUSION This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy.

Prognostic Impact of External Beam Radiation Therapy in Patients Treated With and Without Extended Surgery and Intraoperative Electrons for Locally Recurrent Rectal Cancer: 16-Year Experience in a Single Institution

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.

Intraoperative electron beam radiotherapy and extended surgical resection for gynecological pelvic recurrent malignancies with and without external beam radiation therapy: Long-term outcomes

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.

Surgery and intraoperative electron radiotherapy in recurrent or metastatic oligotopic extrapelvic cancer: Long-term outcome

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.

Tumores sacropélvicos primarios y secundarios. Tratamiento con cirugía radical y radioterapia intraoperatoria

Resumen Introduccion La reseccion sacropelvica es el tratamiento de eleccion de los tumores primitivos o secundarios de los huesos pelvicos. Sin embargo, es una tecnica compleja asociada a una elevada tasa de recidiva local. Para optimizar el control local y la supervivencia proponemos la asociacion de radioterapia intraoperatoria (RIO) a la cirugia radical. Pacientes y metodo Desde 1997-2002 hemos evaluado a 17 pacientes, de los que 15 fueron operados. En 13 casos se realizo sacrectomia (siete por invasion de cancer de recto, tres por cordomas sacros, uno por histiocitoma maligno, uno por neurofibrosarcoma y uno por condrosarcoma). En 2 pacientes se llevo a cabo una escision subtotal del ilion izquierdo y del pubis por sarcomas de la region. En 7 casos se practicaron procedimientos asociados (3 exenteraciones pelvicas completas, 2 posteriores y 2 resecciones intestinales). En todos los casos se aplico un componente de RIO sobre el area de reseccion, con dosis entre 10-12,5 Gy. Resultados Un paciente murio (6,5%) en el postoperatorio inmediato por infarto agudo de miocardio. Las complicaciones mayores incluyeron dos reoperaciones y 7 infecciones o retraso en la curacion de la herida pelviperineal. El seguimiento medio ha sido de 26 meses (rango, 6-60 meses). Dos pacientes presentaron una recaida sistemica con metastasis a distancia, sin recidiva local, a los 41-48 meses de la cirugia. Los otros 13 pacientes siguen vivos, sin evidencia de enfermedad, a los 6-60 meses de la intervencion quirurgica. Conclusiones La invasion tumoral sacropelvica no debe ser considerada como signo de inoperabilidad. La prolongada supervivencia con control de los sintomas locales en el 86% de nuestros pacientes sometidos a cirugia radical y RIO avalan esta terapia multimodal. El presente articulo contribuye a la descripcion de las indicaciones de reseccion sacropelvica, los tiempos tecnicos y los resultados a medio plazo. Consideramos que la RIO durante la cirugia radical ha sido de gran importancia para el control local de la enfermedad. Segun nuestro conocimiento, esta es la primera descripcion en Espana de una serie clinica de reseccion sacropelvica asociada a radioterapia intraoperatoria.

Recurrent Colorectal Cancer

Aggressive, curative intent treatment approaches in patients with local or regional relapse after resection of primary rectal or colon cancers are often not considered. A growing body of evidence supports an aggressive approach combining external beam irradiation (EBRT) ± chemotherapy, resection, and intraoperative irradiation (IORT) in conjunction with systemic chemotherapy. Data will be presented in this chapter summarizing disease control and survival results with IORT-containing regimens from US and European institutions including the impact of prognostic factors on results and the results in previously irradiated patients. IORT tolerance and future potential as a component of treatment will be discussed.

Post-chemoradiation intraoperative electron-beam radiation therapy boost in resected locally advanced rectal cancer: long-term results focused on topographic pattern of locoregional relapse.

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.

Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy

Background: Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper‐perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation. Methods: An extended (90%) hepatectomy was performed in swine undergoing (portal vein embolization) or not undergoing (control) a portal vein embolization 24 hours earlier (n = 10/group). Blood tests, hepatic and systemic hemodynamics, hepatic function (plasma disappearance rate of indocyanine green), liver histology, and volumetry (computed tomographic scanning) were assessed before and after the hepatectomy. Hepatocyte proliferating cell nuclear antigen expression and hepatic gene expression also were evaluated. Results: Swine in the control and portal vein embolization groups maintained stable systemic hemodynamics and developed similar increases of portal blood flow (302 ± 72% vs 486 ± 92%, P = .13). Portal pressure drastically increased in Controls (from 9.4 ± 1.3 mm Hg to 20.9 ± 1.4 mm Hg, P < .001), while being markedly attenuated in the portal vein embolization group (from 11.4 ± 1.5 mm Hg to 16.1 ± 1.3 mm Hg, P = .061). The procedure also improved the preservation of the hepatic artery blood flow, liver function, and periportal edema. These effects occurred in the absence of hepatocyte proliferation or hepatic growth and were associated with the induction of the vasoprotective gene Klf2. Conclusion: Portal vein embolization preconditioning represents a potential hepato‐protective strategy for extended hepatic resections. Further preclinical studies should assess its medium‐term effects, including survival. Our study also supports the relevance of hepatic hemodynamics as the main pathogenetic factor of post‐hepatectomy liver failure.