Primary Bladder Sarcoma: A multi-institutional experience from the Rare Cancer Network.

PURPOSE OR OBJECTIVE: Primary sarcoma of the urinary bladder (SUB) is a rare but aggressive form of bladder cancer (BCa). Available evidence on SUB is limited to case reports and small series. The aim of the present multi-institutional study was to assess the clinical features, treatments, and outcomes of patients with SUB. MATERIALS AND METHODS: Using a standardized database, 7 institutions retrospectively collected the demographics, risk factors, clinical presentation, treatment modalities and follow-up data on patients with SUB between January 1994 and September 2021. The main inclusion criteria included BCa with soft tissue tumor histology and sarcomatoid differentiation. RESULTS: Fifty-three patients (38 men and 15 women) were identified. Median follow-up was 18 months (range 1-263 months). Median age at presentation was 69 years (range 16-89 years). Twenty-six percent of patients had a prior history of pelvic radiotherapy (RT), and 37% were previous smokers. The main presenting symptoms at diagnosis were hematuria (52%), pelvic pain (27%), and both hematuria and pelvic pain (10%). American Joint Committee on Cancer (AJCC) 8 th edition stage II, III and IV at diagnosis were 21%, 63% and 16%, respectively. Treatment modalities included surgery alone (45%), surgery plus neo- or adjuvant-chemotherapy (17%), surgery plus neo- or adjuvant-RT (11%), RT with concurrent chemotherapy (4%), neo-adjuvant chemotherapy plus surgery plus adjuvant RT (2%) and palliative treatment (21%). Rates of local and distant recurrences were 49% and 37%, respectively. Five-year overall survival and progression-free survival (PFS) were 66.5% and 37.6%, respectively. No statistically significant differences in PFS between the treatment modalities were observed. CONCLUSIONS: Primary SUB is a heterogeneous disease group, commonly presenting at advanced stages and exhibiting aggressive disease evolution. In contrast to urothelial carcinoma, the primary pattern of recurrence of SUB is local, suggesting the need for multimodal approaches. Continuous international collaborative efforts seem warranted to provide guidance on how to best tailor treatments based on SUB-specific indices.

Clinical feasibility of combining intraoperative electron radiation therapy with minimally invasive surgery: a potential for electron-FLASH clinical development

Background Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. Methods Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. Results In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. Conclusions Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams (AU)

Clinical feasibility of combining intraoperative electron radiation therapy with minimally invasive surgery: a potential for electron-FLASH clinical development.

BACKGROUND: Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. METHODS: Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. RESULTS: In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. CONCLUSIONS: Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams.

ESTRO/ACROP IORT recommendations for intraoperative radiation therapy in primary locally advanced rectal cancer.

Carcinoma of the rectum is a heterogeneous disease. The clinical spectrum identifies a subset of patients with locally advanced tumours that are close to or involve adjoining structures, such as the sacrum, pelvic sidewalls, prostate or bladder. Within this group of patients categorized as "locally advanced", there is also variability in the extent of disease with no uniform definition of resectability. A practice-oriented definition of a locally advanced tumour is a tumour that cannot be resected without leaving microscopic or gross residual disease at the resection site. Since these patients do poorly with surgery alone, irradiation and chemotherapy have been added to improve the outcome. Intraoperative irradiation (IORT) is a component of local treatment intensification with favourable results in this subgroup of patients. International guidelines (National Comprehensive Cancer Network (NCCN) guidelines) currently recommend the use of IORT for rectal cancer resectable with very close or positive margins, especially for T4 and recurrent cancers. We report the ESTRO-ACROP (European Society for Radiotherapy and Oncology - Advisory Committee on Radiation Oncology Practice) recommendations for performing IORT in primary locally advanced rectal cancer.

ESTRO/ACROP IORT recommendations for intraoperative radiation therapy in locally recurrent rectal cancer.

Multimodal strategies have been implemented for locally recurrent rectal cancer scheduled for complete surgical resection. Irradiation and systemic therapy have been added to improve the oncological outcome, as surgery alone was associated with a poor prognosis. Intraoperative irradiation (IORT) is a component of irradiation intensification. Long-term cancer control and a higher survival rate were consistently reported in patients who had IORT as a component of their multidisciplinary treatment. The experience reported by expert IORT groups is reviewed and recommendations to guide clinical practice are explained in detail.

Postoperative Radiation Therapy in Patients with Extracranial Chondrosarcoma: A Joint Study of the French Sarcoma Group and Rare Cancer Network.

PURPOSE: Postoperative radiation therapy (poRT) of intracranial/skull base chondrosarcomas (CHSs) is standard treatment. However, consensus is lacking for poRT in extracranial CHS (eCHS) owing to their easier resectability and intrinsic radioresistance. We assessed the practice and efficacy of poRT in eCHS. METHODS AND MATERIALS: This multicentric retrospective study of the French Sarcoma Group/Rare Cancer Network included patients with eCHS who were operated on between 1985 and 2015. Inverse propensity score weighting (IPTW) was used to minimize poRT allocation biases. RESULTS: Of 182 patients, 60.4% had bone and 39.6% had soft-tissue eCHS. eCHS were of conventional (31.9%), myxoid (28.6%; 41 extraskeletal, 11 skeletal), mesenchymal (9.9%), or other subtypes. En-bloc surgery with complete resection was performed in 52.6% and poRT in 36.8% of patients (median dose, 54 Gy). Irradiated patients had unfavorable initial characteristics, with higher grade and incomplete resection. Median follow-up time was 61 months. Five-year incidence of local relapse was 10% with poRT versus 21.6% without (P = .050). Using the IPTW method, poRT reduced the local relapse risk (hazard ratio, 0.27; 95% confidence interval, 0.14-0.52; P < .001). Five-year disease-free survival (DFS) was 71.8% with poRT and 64.2% without (P = .680). Using the IPTW method, poRT improved DFS (hazard ratio, 0.51; 95% confidence interval, 0.30-0.85; P = .010). The benefit of poRT on local relapse and DFS was confirmed after exclusion of the extraskeletal subtype. There was no difference in overall survival. Prognostic factors of poorer DFS in multivariate analysis were deeper location, higher grade, incomplete resection, and no poRT. CONCLUSIONS: poRT should be offered in patients with eCHS and high-grade or incomplete resection, regardless of the histologic subtype.

Intraoperative computed tomography imaging for dose calculation in intraoperative electron radiation therapy: Initial clinical observations.

In intraoperative electron radiation therapy (IOERT) the energy of the electron beam is selected under the conventional assumption of water-equivalent tissues at the applicator end. However, the treatment field can deviate from the theoretic flat irradiation surface, thus altering dose profiles. This patient-based study explored the feasibility of acquiring intraoperative computed tomography (CT) studies for calculating three-dimensional dose distributions with two factors not included in the conventional assumption, namely the air gap from the applicator end to the irradiation surface and tissue heterogeneity. In addition, dose distributions under the conventional assumption and from preoperative CT studies (both also updated with intraoperative data) were calculated to explore whether there are other alternatives to intraoperative CT studies that can provide similar dose distributions. The IOERT protocol was modified to incorporate the acquisition of intraoperative CT studies before radiation delivery in six patients. Three studies were not valid to calculate dose distributions due to the presence of metal artefacts. For the remaining three cases, the average gamma pass rates between the doses calculated from intraoperative CT studies and those obtained assuming water-equivalent tissues or from preoperative CT studies were 73.4% and 74.0% respectively. The agreement increased when the air gap was included in the conventional assumption (98.1%) or in the preoperative CT images (98.4%). Therefore, this factor was the one mostly influencing the dose distributions of this study. Our experience has shown that intraoperative CT studies are not recommended when the procedure includes the use of shielding discs or surgical retractors unless metal artefacts are removed. IOERT dose distributions calculated under the conventional assumption or from preoperative CT studies may be inaccurate unless the air gap (which depends on the surface irregularities of the irradiated volume and on the applicator pose) is included in the calculations.

Radiotherapy in the treatment of extracranial hemangiopericytoma/solitary fibrous tumor: Study from the Rare Cancer Network.

BACKGROUND AND PURPOSE: The role of radiotherapy (RT) in the treatment of hemangiopericytoma/solitary fibrous tumor (HPC/SFT) is still under debate. We aimed at investigating whether radiotherapy can improve the results in patients operated for extracranial HPC/SFT. MATERIALS AND METHODS: Data from patients with HPC/SFT, treated from 1982 to 2012, were retrospectively reviewed within the Rare Cancer Network framework. Actuarial local control (LC), disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) were calculated with Kaplan-Meyer method. Patient and tumor parameters were analyzed by univariate and multivariate analysis. RESULTS: Of 114 HPC/SFT, 58 (50.9%) occurred in the extremities/superficial trunk and 56 (49.1%) in intra-thoracic/retroperitoneum. Seventy-eight patients (68.4%) underwent surgery only (Sx), and 36 (31.6%) Sx and RT (Sx + RT). Median RT dose was 60 Gy (range 45-68.4 Gy) in 1.6-2.2 Gy fractions. In the extremities/superficial trunk group of patients, actuarial 5-year LC rates were 50.4% after Sx and 91.6% after Sx + RT (p < 0.0001) for LC, and 50.4% after Sx and 83.1% after Sx + RT (p = 0.008) for DFS. In the intra-thoracic/retroperitoneum group of patients, actuarial 5-year rates were 89.3% after Sx and 77.8% after Sx + RT (p = 0.99) for LC, and 73.8% after Sx and 77.8% after Sx + RT (p = 0.93) for DFS. At multivariate analysis, the addition of RT resulted in better LC and DFS in the whole series. The advantage was confirmed for LC in the group of patients affected by extremity/superficial trunk tumors. CONCLUSION: Addition of RT to Sx could improve the prognosis, in terms of LC and DFS, essentially in patients with extremities/superficial trunk tumor locations.

Radiation Therapy in Resectable Intrathoracic Sarcomas. A Rare Cancer Network Study.

PURPOSE: Intrathoracic sarcomas (ITS) are considered rare tumors and have a dismal prognosis. We investigated outcomes and risk factors for local control (LC), disease-free survival (DFS), and overall survival (OS) in patients with resected nonmetastatic ITS treated with or without adjuvant radiation therapy (RT) and/or chemotherapy. METHODS AND MATERIALS: Patients from the Rare Cancer Network database were studied. A Kaplan-Meier estimate was used to assess survival curves, and Cox proportional hazards regression was used to assess risk factors for LC, DFS, and OS. RESULTS: Between 2000 and 2017, 121 patients met inclusion criteria. The primary site was lung in 30%, mediastinum in 34%, and pleura in 36%. Thirty-nine percent and 32% received RT and chemotherapy. Median follow-up was 34 months (range, 2-141). LC, DFS, and OS at 10 years were 52%, 18.7%, and 7.2%, respectively. In multivariate analysis, RT (P = .003) and R1 margin status (P = .041) retained a significant association with LC. Only R1 resection (P = .002) remained associated with an increased risk of death in multivariate analysis. Overall, 7 patients (6%) developed grade 3 treatment-related chronic toxicity events. CONCLUSIONS: This joint analysis revealed that OS remains modest in this group of patients, mainly given by the high risk of local and distant failure. Our results suggest that resected ITS can benefit from adjuvant RT.

Cosmesis after early stage breast cancer treatment with surgery and radiation therapy: experience of patients treated in a Chilean radiotherapy centre.

AIM: To analyse the overall cosmetic outcome according to patient self-assessment in relation to the fractionation received. MATERIALS AND METHODS: A questionnaire, drawn up on the basis of subjective rating scales of cosmesis and of acute and late toxicity RTOG/EORTC, EORTC QLQ-C30 (v3) and LENT SOMA, was applied to patients with early-stage breast cancer who received radiotherapy with tangential fields between June 2014 and July 2015. Self-perception of cosmesis, changes in the treated breast, pain and fractionation used (hypofractionation (HF) 42.56 Gy in 16 fractions or conventional fractionation (CF) 50 Gy in 25 fractions) were evaluated. RESULTS: Three hundred and fifty-two questionnaires were obtained. The median age was 58 years. 45% of patients reported 'excellent' cosmesis, 53% 'good', and 2% 'poor' cosmesis. Cosmesis was considered 'excellent/good' by 98% of patients. No statistically significant difference was found in overall cosmesis according to fractionation received (p = 0.6).The most frequent alteration was 'difference between both breasts' (77%), and 48% reported change in normal breast colour.Fifteen percent of patients who are younger than 58 years reported a change of normal breast colour affecting cosmesis compared to 9% of patients older than 58 years (p = 0.04).Complications affecting breast cosmesis were reported by 9% of patients with stages I-II compared with 2% with cancer in situ (DCIS) (p = 0.04); 14% in stages I-II referred colour change affecting cosmesis compared to 6% of those with DCIS (p = 0.03).Ninety-four percent of patients stated that they would accept treatment again. CONCLUSIONS: No difference in cosmetic results was found between HF and CF in our patients. Great satisfaction regarding cosmetic outcome of cancer treatment was reported, given by 98% of excellent/good cosmesis, and 94% of patients who would receive treatment again.

The impact of active breathing control on internal mammary lymph node coverage and normal tissue exposure in breast cancer patients planned for left-sided postmastectomy radiation therapy.

PURPOSE: The purpose of this study was to evaluate the impact of the active breathing control (ABC) technique on IMN coverage and organs at risk in patients planned for postmastectomy radiation therapy (PMRT), with the inclusion of the internal mammary lymph nodes (IMNs). The effect of body mass index (BMI) on recorded dosimetric parameters was examined in the same patient cohort. METHODS AND MATERIALS: Fifty left-sided postmastectomy patients with breast cancer who underwent free-breathing (FB) and ABC-Elekta CT simulation scans were selected at random from an institutional breast cancer database between 2008 and 2014. The ABC plans were directly compared with FB plans from the same patient. RESULTS: The IMN planning target volume coverage met dosimetric criteria for coverage of receiving more than 90% of the prescribed dose (V90) >90%, although it decreased with ABC compared with FB (94.5% vs 98%, P < .001). Overall, ABC significantly reduced doses to all measured heart and left anterior descending coronary artery parameters, ipsilateral lung V20, and mean lung dose compared with FB (P < .001). There was no difference seen between the ABC and FB plans with respect to the dose to contralateral lung or contralateral breast. There was no correlation identified between BMI and any of the dosimetric parameters recorded from the ABC and FB plans. CONCLUSIONS: Our results suggest that ABC reduces IMN coverage in left-sided breast cancer patients planned for PMRT; however, dosimetric criteria for IMN coverage were still met, suggesting that this is not likely to be clinically significant. ABC led to significant sparing of organs at risk compared with FB conditions and was not affected by BMI. Collectively, the results support the use of ABC for breast cancer patients undergoing left-sided PMRT requiring regional nodal irradiation that includes the IMNs. Further prospective clinical studies are required to determine the impact of these results on late normal tissue effects.

Assessment of intraoperative 3D imaging alternatives for IOERT dose estimation.

Intraoperative electron radiation therapy (IOERT) involves irradiation of an unresected tumour or a post-resection tumour bed. The dose distribution is calculated from a preoperative computed tomography (CT) study acquired using a CT simulator. However, differences between the actual IOERT field and that calculated from the preoperative study arise as a result of patient position, surgical access, tumour resection and the IOERT set-up. Intraoperative CT imaging may then enable a more accurate estimation of dose distribution. In this study, we evaluated three kilovoltage (kV) CT scanners with the ability to acquire intraoperative images. Our findings indicate that current IOERT plans may be improved using data based on actual anatomical conditions during radiation. The systems studied were two portable systems ("O-arm", a cone-beam CT [CBCT] system, and "BodyTom", a multislice CT [MSCT] system) and one CBCT integrated in a conventional linear accelerator (LINAC) ("TrueBeam"). TrueBeam and BodyTom showed good results, as the gamma pass rates of their dose distributions compared to the gold standard (dose distributions calculated from images acquired with a CT simulator) were above 97% in most cases. The O-arm yielded a lower percentage of voxels fulfilling gamma criteria owing to its reduced field of view (which left it prone to truncation artefacts). Our results show that the images acquired using a portable CT or even a LINAC with on-board kV CBCT could be used to estimate the dose of IOERT and improve the possibility to evaluate and register the treatment administered to the patient.

Postoperative radiotherapy in the management of keloids.

BACKGROUND: The high recurrence rate following keloid resection has generated interest in adjuvant treatments for this disease. OBJECTIVE: This study assesses keloid recurrence when treated with surgery and adjuvant radiotherapy. METHODS: Retrospective analysis of resected keloids in patients referred to a Chilean radiation oncology centre between 2006 and 2013. Local recurrence was defined as new tissue growth on the surgical scar margin. RESULTS: Around103 keloids were analysed in 63 patients treated with 15 Gy in three fraction radiotherapy which was initiated on the same day as the surgery (75% of cases). The median keloid diameter was 6 cm; the most common site was thoracic (22%); the most common cause was prior surgery (35%); 37% caused symptoms, and several (47%) had received prior treatment with corticosteroids (32%), or surgery (30%). The median follow-up was three years, and 94% of recurrences occurred during the first year following treatment. Uni and multivariate analyses showed that an absence of symptoms was a protective factor for recurrence (OR: 0.24), while the time interval from onset to treatment with surgery plus radiotherapy >4.2 years was a risk factor (OR: 2.23). The first year recurrence rate was 32% and stabilised at 32% by the second year with no recurrences after 15 months. CONCLUSIONS: The combination of surgery and radiotherapy proved to be a good therapeutic alternative in the management of keloids. Our results are similar to those described in the literature for a dose of 15 Gy. Given these results, our centre will implement a new dose escalation protocol to improve future outcomes.

Adjuvant radiation therapy in resected high-grade localized skeletal osteosarcomas treated with neoadjuvant chemotherapy: Long-term outcomes.

PURPOSE: To assess long-term outcomes and toxicity of adjuvant radiotherapy in the post-surgical management of patients with resected high-grade skeletal osteosarcomas. METHODS AND MATERIALS: Seventy-two patients with primary resected osteosarcomas underwent adjuvant radiotherapy after neoadjuvant chemotherapy from December 1984 to December 2008. Local control (LC), overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier methods. For survival outcomes potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: After a median follow-up of 174months (range, 33-363months), 10-year LC, DFS, and OS rates were 82%, 58%, and 73%, respectively. In the multivariate analysis only R1 margin status (p=0.02) remained significantly associated with LC. Patients with tumor necrosis <90% (p=0.04) and R1 resection margin (p=0.05) remained at a significantly higher risk of mortality on multivariate analysis. Six patients (8%) developed grade ⩾3 treatment-related chronic toxicity events. No grade 5 toxicities were reported. CONCLUSIONS: A multimodal radiotherapy-containing approach is a well-tolerated component of treatment for patients with osteosarcomas undergoing programed resection, allowing low toxicity rates while maintaining high local control rates.

Metabolic and molecular relative percentage coreduction in patients with locally advanced rectal cancer treated with neoadjuvant therapy.

PURPOSE: Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR) and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumour progression and are important targets for cancer therapeutics. (18)F-FDG maximum standardized uptake value (SUVmax) on PET/CT is a marker of tumour metabolic activity. The purpose of this study was to measure percentage reductions in SUVmax (∆SUVmax%), VEGFR-2 (∆VEGFR-2%), EGFR (∆EGFR%) and COX-2 (∆COX-2%) in patients with locally advanced rectal cancer (LARC) after preoperative treatment, and to correlate the changes in these markers of response with pathological response in terms of tumour regression grade (TRG) using Rödel's scale and long-term clinical outcome. METHODS: VEGFR-2, EGFR and COX-2 were measured using a quantitative and qualitative compound immunohistochemistry analysis (immunoreactive score) of the pretreatment endoscopic biopsy and definitive surgical specimens. Composite indexes using ∆SUVmax% and the three molecules were developed to differentiate patients with metabolic and molecular responses from nonresponders. Cox proportional hazards model was used to explore associations between the tumour markers, disease-free survival (DFS) and overall survival (OS). RESULTS: The analysis included 38 patients with a median follow-up of 86 months (range 5 - 113 months). The ∆VEGFR-2%/∆SUVmax% index correctly identified 13 of 19 pathological responders (TRG 3 and 4) and 17 of 19 nonresponders (TRG 0 - 2) (sensitivity 68 %, specificity 89 %, accuracy 79 %, positive predictive value 87 %, negative predictive value 74 %). In multivariate analysis, only the ∆VEGFR-2%/∆SUVmax% index was associated with DFS (HR 0.11, p = 0.001) and OS (HR 0.15, p = 0.02). CONCLUSION: In patients with LARC the ∆VEGFR-2%/∆SUVmax% response index is associated with outcome. Determination of the optimal diagnostic cut-off level for this novel biomarker association should be explored. Evaluation in a clinical trial is required to determine whether selected patients could benefit from treatment with a VEGFR-targeted therapeutic agent.

Why a D2 gastrectomy plus adjuvant chemotherapy is insufficient in locally advanced gastric cancer.

This review discusses all the important published evidence regarding adjuvant treatments in locally advanced gastric cancer. In this process it revealed facts that demonstrate the superiority of radiotherapy and concomitant chemotherapy to chemotherapy alone. Some outstanding work that has not yet been published is also discussed.

Intraoperative Electron-Beam Radiation Therapy for Pediatric Ewing Sarcomas and Rhabdomyosarcomas: Long-Term Outcomes.

PURPOSE: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). METHODS AND MATERIALS: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). CONCLUSIONS: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.

Single-Institution Multidisciplinary Management of Locoregional Oligo-Recurrent Pelvic Malignancies: Long-Term Outcome Analysis.

PURPOSE: The aim of this study was to analyze long-term outcomes and prognostic factors associated with survival in patients with locoregional oligo-recurrent (LROR) pelvic malignancies treated in a multimodal protocol. METHODS: Patients with an histologic diagnosis of LROR pelvic cancer (rectal 50 %, gynecological 50 %) with absence of distant metastases, undergoing surgery with radical intent and intraoperative radiotherapy (median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 48 % received external beam radiotherapy (EBRT) (median dose 50 Gy). RESULTS: From 1995 to 2012, a total of 143 patients from a single institution were analyzed. With a median follow-up time of 48 months (range 2-189), 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were 53, 44, and 46 %, respectively. On multivariate analysis, no EBRT treatment to the locoregional (p ≤ 0.001), R1 margin status (p = 0.03), time interval from primary tumor diagnosis to LROR <24 months (p = 0.05), and fragmentation in the resected specimen (p = 0.004) retained significance in relation to LRC. On multivariate analysis we found that only R1 margin status (p = 0.003), primary tumor diagnosis to LROR <24 months (p = 0.02), and high histological grade (p = 0.02) were significantly associated with OS. CONCLUSIONS: From this analysis emerges the fact that EBRT influences local control but, given the high risk of distant metastases, DFS remains modest. Margin status, tumor fragmentation, no EBRT to the LR, and time interval from primary tumor diagnosis to LROR are the dominant factors for subsequent locoregional recurrence (LRR). Accordingly, future prospective studies might be designed which adapt treatment according to the predicted risk of subsequent LRR.

Intraoperative radiotherapy for gastrointestinal malignancies: contemporary outcomes with multimodality therapy.

The integration of intraoperative radiotherapy (IORT) into the multimodal treatment of gastrointestinal cancer is feasible and leads to high rates of local control. In-field tumoral control using IORT-containing strategies can be achieved in over 90 % of most cases, regardless of the site or status of the tumor (primary or recurrent). Electron beam IORT, or intraoperative electron radiation therapy, is the dominant technology used in institutions reporting data in publications the 21st century. Neither surgery nor systemic therapy is compromised by the integration of IORT-containing radiotherapy.

Human cytomegalovirus and Epstein-Barr virus infection impact on (18)F-FDG PET/CT SUVmax, CT volumetric and KRAS-based parameters of patients with locally advanced rectal cancer treated with neoadjuvant therapy.

PURPOSE: It has long been debated whether human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are associated with rectal cancer. The gene products of HCMV and EBV contribute to cell-cycle progression, mutagenesis, angiogenesis and immune evasion. The aim of this prospective study was to analyse the association between infection of a tumour by HCMV and EBV and clinical, histological, metabolic ((18)F-FDG uptake), volumetric (from CT) and molecular (KRAS status) features and long-term outcomes in a homogeneously treated group of patients with locally advanced rectal cancer. METHODS: HCMV and EBV were detected in pretreatment biopsies using polymerase chain reaction (PCR). The Cox proportional hazards regression model was used to explore associations between viral infection and disease-free survival (DFS) and overall survival (OS). RESULTS: We analysed 37 patients with a median follow-up of 74 months (range 5-173 months). Locoregional control, OS and DFS at 5 years were 93%, 74% and 71%, respectively. Patients with HCMV/EBV coinfection had a significantly higher maximum standardized uptake value than patients without viral coinfection (p = 0.02). Significant differences were also observed in staging and percentage relative reduction in tumour volume between patients with and without HCMV infection (p < 0.01) and EBV infection (p < 0.01). KRAS wildtype status was significantly more frequently observed in patients with EBV infection (p <0.01) and HCMV/EBV co-infection (p = 0.04). No significant differences were observed in OS or DFS between patients with and without EBV infection (p = 0.88 and 0.73), HCMV infection (p = 0.84 and 0.79), and EBV/CMV coinfection (p = 0.24 and 0.39). CONCLUSION: This pilot study showed that viral infections were associated with metabolic staging differences, and differences in the evolution of metabolic and volumetric parameters and KRAS mutations. Further findings of specific features will help determine the best candidates for metabolic and volumetric staging and restaging. Further toxicity profile findings will help to determine the best candidates for specific supportive treatment during pelvic chemoradiotherapy in patients with locally advanced rectal cancer.