Prediction of local and metastatic recurrence in solitary fibrous tumor: construction of a risk calculator in a multicenter cohort from the French Sarcoma Group (FSG) database.

BACKGROUND: Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. PATIENTS AND METHODS: A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. RESULTS: We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. CONCLUSION: LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation.

Intraoperative electron-beam radiation therapy with or without external-beam radiotherapy in the management of paraaortic lymph-node oligometastases from gynecological malignancies.

PURPOSE: To analyze long-term outcomes and prognostic factors in patients with paraaortic lymph-node oligometastases (LNO) from gynecological malignancies treated in a multimodal protocol. METHODS: Patients with a histological diagnosis of LNO gynecological cancer [uterine cervix (n = 14, 40 %), endometrial (n = 18, 51 %), ovarian (n = 3, 9 %)] who underwent surgery with radical intent and intraoperative radiotherapy (IORT), median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 51 % received external-beam radiotherapy (EBRT). RESULTS: From 1997 to 2012, a total of 35 patients from a single institution were analyzed. With a median follow-up time of 55 months (range 2-148), 5-year loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS) were 79, 44 and 49 %, respectively. On multivariate analysis, no EBRT treatment to the LNO (p = 0.03), and time interval from primary tumor diagnosis to LNO <24 months (p = 0.04) remained significantly associated with locoregional recurrence (LRR). We found on multivariate analysis that only R1 margin status (p = 0.01) was significantly associated with OS. CONCLUSION: From the current series of patients with gynecological LNO, it emerges the fact that EBRT promotes local control. Future prospective studies might be designed according to the predicted risk of LRR focusing on different subgroups.

The use of radiotherapy for early breast cancer in woman at different ages.

Age is an important feature at the time of early breast cancer diagnosis. Radiotherapy is a mandatory component of treatment for breast-conserving strategies in early disease stages. Breast radiotherapy has rapidly evolved in the last 20 years. A tendency to less treatment volume (partial-breast irradiation) and less treatment time (hypofractionation) is consolidated in modern radiation oncology practice. Age and risk for local recurrence guide the decision-making process to electro-optimal treatment. Radiotherapy technological versatility offers multiple options for individualized (risk-age adapted) recommendations.

Intraoperative radiotherapy-containing multidisciplinary management of trunk-wall soft-tissue sarcomas.

PURPOSE: A joint analysis of data from centers within the intraoperative radiotherapy (IORT)-Spanish cooperative initiative was performed to investigate the main contributions of IORT to the multidisciplinary treatment of trunk-wall soft-tissue sarcoma (TW-STS). MATERIALS AND METHODS: Patients with a histologic diagnosis of TW-STS (primary tumor 53 %; locally recurrent 47 %) with absence of distant metastases, undergoing surgery with radical intent and IORT (median dose 12.5 Gy) were considered eligible for participation in this study. In addition, all primary tumors received external-beam radiotherapy (median dose 50 Gy). RESULTS: From 1986 to 2012, a total of 68 patients were analyzed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4-316), 5-year local control (LC) was 58 %. Five-year IORT in-field control, disease-free survival (DFS) and overall survival were 70, 45 and 51 %, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 3.97, p < 0.001). In regard to IORT in field control, incomplete resection (HR 3.23, p = 0.008) and recurrent disease status (HR 2.52, p = 0.04) retained a significant association in multivariate analysis. CONCLUSION: From this joint analysis emerges the fact that margin and disease status influences local and central control, but DFS remains modest, given the high risk of distant metastases. Intensified local treatment needs to be tested in the context of more efficient concurrent, neo-, and adjuvant systemic therapy.

Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Long-term outcome analysis.

BACKGROUND AND PURPOSE: It has been previously reported that a short FOLFOX-4 induction significantly improves pathologic complete response in locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of sphincter preservation and long-term outcomes. PATIENTS AND METHODS: From January 1995 to December 2010, 335 LARC patients were treated with preoperative chemoradiation (4500-5040 cGy). Starting in May 2001, 207 consecutive patients additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3-12 weeks) after chemoradiation. RESULTS: Incidence of total tumor (63 vs. 54 %, p = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up time for the entire cohort of patients was 72.6 months (range 4-205 months). FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p = 0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15). CONCLUSION: Short-intense induction FOLFOX-4 significantly improves downstaging and sphincter preservation in low rectal tumors. Long-term outcomes were not improved in the FOLFOX-4 group of patients.

External-beam radiation therapy after surgical resection and intraoperative electron-beam radiation therapy for oligorecurrent gynecological cancer. Long-term outcome.

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.

Post-chemoradiation anastomotic recurrence in locally advanced rectal cancer: no increased risk associated with distal margin.

BACKGROUND AND PURPOSE: Anastomotic recurrence after radical sphincter-preserving surgery preceded by neoadjuvant therapy in locally advanced rectal cancer is an uncommon event that merits further assessment. The aim of this study is to analyze the effect of preoperative chemoradiation on the risk of anastomotic recurrence. Based on the initial extension of the tumor, we analyzed whether the distal surgical section was calculated through the virtual initial extension of the rectal tumor. PATIENTS AND METHODS: Eligible patients with locally advanced rectal cancer were offered preoperative chemoradiation, sphincter sparing surgery and intraoperative radiation therapy boost. RESULTS: 180 patients were treated with anterior resection (40 %), low anterior resection (45.6 %) and ultra-low anterior resection (14.4 %). With a median follow-up of 41.1 months (0.36-143 months), anastomotic recurrence was diagnosed in 9 patients (5 %). There was no statistical correlation with downstaging (T or N), downsizing effects, or with distance from the lower limit of the residual lesion to the distal margin. Virtual intratumoral surgical section was speculated in 44 patients (3 developed anastomotic recurrence; 6.8 vs 4.8 %, p = 0.482). CONCLUSION: Anastomotic recurrence in patients with rectal cancer treated with neoadjuvant chemoradiation is an infrequent event. Virtual intratumoral surgical sections followed by anastomosis do not contribute to an excessive risk of recurrence. Our findings encourage the development of policies for preservation of the ano-rectal complex in rectal cancer patients.

Research opportunities in intraoperative radiation therapy: the next decade 2013-2023

The reality of intraoperative radiation therapy (IORT) practice is consistent with an efficient and highly precise radiation therapy technique to safely boost areas at risk for local recurrence. Long-term clinical experience has shown that IORT-containing multi-modality regimens appear to improve local disease control, if not survival in many diseases. Research with IORT is a multidisciplinary scenario that covers knowledge from radiation beam adapted development to advance molecular biology for bio-predictability of outcome. The technical parameters employed in IORT procedures are important information to be recorded for quality assurance and clinical results analysis. In addition, specific treatment planning systems for IORT procedures are available, to help in the treatment decision-making process. A systematic revision of opportunities for research and innovation in IORT is reported including radiation beam modulation, delivery, dosimetry and planning; infrastructure and treatment factors; experimental and clinical radiobiology; clinical trials, innovation and translational research development (AU)

Clinical and technical characteristics of intraoperative radiotherapy. Analysis of the ISIORT-Europe database.

BACKGROUND: A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. MATERIALS AND METHODS: In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. RESULTS: The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. CONCLUSION: This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.

Intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma: topography of locoregional recurrences and long-term outcomes

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 (AU)

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.

Research opportunities in intraoperative radiation therapy: the next decade 2013-2023.

The reality of intraoperative radiation therapy (IORT) practice is consistent with an efficient and highly precise radiation therapy technique to safely boost areas at risk for local recurrence. Long-term clinical experience has shown that IORT-containing multi-modality regimens appear to improve local disease control, if not survival in many diseases. Research with IORT is a multidisciplinary scenario that covers knowledge from radiation beam adapted development to advance molecular biology for bio-predictability of outcome. The technical parameters employed in IORT procedures are important information to be recorded for quality assurance and clinical results analysis. In addition, specific treatment planning systems for IORT procedures are available, to help in the treatment decision-making process. A systematic revision of opportunities for research and innovation in IORT is reported including radiation beam modulation, delivery, dosimetry and planning; infrastructure and treatment factors; experimental and clinical radiobiology; clinical trials, innovation and translational research development.

Intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma: topography of locoregional recurrences and long-term outcomes.

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.

Stereotactic ablative radiotherapy delivered by image-guided helical tomotherapy for extracranial oligometastases.

PURPOSE: To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases. METHODS: From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis. RESULTS: A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses. CONCLUSIONS: SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS.

Intraoperative EBRT and resection for renal cell carcinoma : twenty-year outcomes.

PURPOSE: We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. PATIENTS AND METHODS: From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. RESULTS: Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. CONCLUSION: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation.