Claudio V. Sole

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.

ISIORT pooled analysis 2013 update: clinical and technical characteristics of intraoperative radiotherapy

Purpose: Data from centers active in intraoperative radiotherapy (IORT) were collected within the International Society of Intraoperative Radiation Therapy (ISIORT)-Europe program. The purpose of the present study was to analyze and report the main clinical and technical variables of IORT performed by the participating centers. Materials and methods: Since 2007, ISIORT-Europe centers were invited to record data of IORT procedures in a common database. Other centers worldwide joined this initiative over time. Collected data included demographic, clinical and technical information. Results: Thirty-one centers participated in the survey and data of 7,196 IORT procedures have been recorded to 2013. Median age of patients was 60.6 years (range 5 months-94 years). Gender was female in 80.2% of cases and male in 19.8%. Treatment intent was curative in 7,054 cases (98%) and 1,587 patients (22.1%) were included in study protocols. The most frequent tumor was breast cancer with 5,654 cases (78.6%) followed by rectal cancer with 641 cases (8.9%), soft-tissue and bone sarcoma with 257 cases (3.6%), prostate cancer with 128 cases (1.8%), pancreatic cancer with 87 cases (1.2%), gastric cancer with 65 cases (0.9%), and esophageal cancer with 53 cases (0.7%). Treatment chronology shows how IORT number of recorded cases increased according with the interest in the ISIORT project. C onclusions: This report gives an overview of patient selection and treatment modalities for the main tumor types effectively treated in a large group of active and experienced international centers using IORT. This data can be a basis for further surveys and for prospective studies devoted to analyze in depth IORT containing multimodal cancer treatment approaches.

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 radiotherapy with electrons: fundamentals, results, and innovation.

Rationale and objectives To analyse the programme activity and clinical innovation and/or technology developed over a period of 17 years with regard to the introduction and the use of intraoperative radiotherapy (IORT) as a therapeutic component in a medical–surgical multidisciplinary cancer hospital. Material and methods To standardise and record this procedure, the Radiation Oncology service has an institutional programme and protocols that must be completed by the different specialists involved. For 17 years, IORT procedures were recorded on a specific database that includes 23 variables with information recorded on institutional protocols. As part of the development and innovation activity, two technological tools were implemented (RADIANCE and MEDTING) in line with the standardisation of this modality in clinical practice. Results During the 17 years studied, 1,004 patients were treated through 1,036 IORT procedures. The state of the disease at the time of IORT was 77% primary and 23% recurrent. The origin and distribution of cancers were 62% gastrointestinal, 18% sarcomas, 5% pancreatic, 2% paediatric, 3% breast, 7% less common locations, and 2% others. The research and development projects have generated a patent on virtual planning (RADIANCE) and proof of concept to explore as a professional social network (MEDTING). During 2012, there were 69 IORT procedures. There was defined treatment volume (target or target region) in all of them, and 43 were conducted by the virtual planning RADIANCE system. Eighteen have been registered on the platform MEDTING as clinical cases. Conclusion The IORT programme, developed in a university hospital with an academic tradition, and interdisciplinary surgical oncology, is a feasible care initiative, able to generate the necessary intense clinical activity for tending to the cancer patient. Moreover, it is a competitive source for research, development, and scientific innovation.

Anticipated Intraoperative Electron Beam Boost, External Beam Radiation Therapy, and Limb-Sparing Surgical Resection for Patients with Pediatric Soft-Tissue Sarcomas of the Extremity: A Multicentric Pooled Analysis of Long-Term Outcomes

PURPOSE To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas. METHODS AND MATERIALS From June 1993 to May 2013, 62 patients (aged <21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis. RESULTS After a median follow-up of 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size >5 cm (P=.04) and R1 margin status (P=.04) remained significantly associated with local relapse. In regard to overall survival only margin status (P=.04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3). CONCLUSIONS An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results.

In Regard to Habr-Gama et al

I would like to underline the fact that 8 of 10 patients are still alive and well. Of the 2 deceased patients mentioned by the commentators, 1 patient died because of a sudden blockage of the stent inserted a few weeks earlier, and the other patient died of cardiac failure 40 years after the combined modality treatment. I do not believe that a Framingham score could be multiplied by a factor derived from radiation planning, as there are large radiation dose gradients along the coronary artery network partly because of the variety of shapes, sizes, and geographical locations of Hodgkin lymphoma mediastinal masses (A. Moignier, work in preparation). I do not believe that a score-based approach would help detect patients with coronary artery abnormalities with certainty. It will remain, at best, a more or less strong assumption of possible disease, unless a CCTA is performed. Such patients might be deprived of more aggressive medical and/or surgical procedures that could prolong their lives as well as their quality of life. On the other hand, a score-based approach (possibly including telomere length measurements, a genetic approach suggested in the article) could help determine which patients really require a CCTA or any other radiological investigations. As for the controversy about the value of revascularization (3), it was not the scope of the article.

Integrando la irradiación parcial acelerada de la mama en la práctica clínica

El uso de la irradiacion parcial acelerada de la mama (IPAM) en lugar de la irradiacion total de la mama (ITM) para la terapia conservadora de la mama (TCM) es un area de intensiva investigacion clinica . El debate se ha mantenido generalmente en ambientes especializados, pero la divulgacion de esta modalidad terapeutica a la comunidad medica no especialista y al publico general requiere que esta discusion se extienda a publicaciones de amplia divulgacion entre la comunidad medica general.

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.

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.