Intraoperative radiation therapy for rectal cancer and recurrent intra-abdominal sarcomas.

PURPOSE: The aim of this study was to evaluate the effect of high-dose-rate intraoperative radiation therapy (HDR-IORT) in a multimodality treatment on the local control (LC) and the overall survival (OS) rate in locally advanced rectal cancer (LARC), locally recurrent rectal cancer (LRRC) and recurrent intra-abdominal sarcomas (RS). MATERIALS AND METHODS: A retrospective analysis was performed on 27 patients who were treated with radical resection and HDR-IORT between April 2007 and January 2017. Patient, tumor and surgical characteristics were analyzed and the perioperative (<30 days) and long-term complications (>30 days) were assessed and graded. RESULTS: None of the patients with LARC (n = 4) developed a local recurrence and all patients were still alive at the end of the follow-up. The LC rates of LRRC (n = 17) after one and three years were respectively 48% and 40% and the one, three and five years OS were respectively 93%, 62% and 44%. For RS (n = 6), the LC rates after one and three years were both 33% and the one and three years OS rate were respectively 83% and 46%. CONCLUSIONS: The results of our study show that HDR-IORT could be a valuable asset in the multimodality management of LARC, LRRC and RS.

Contribution of intraoperative radiotherapy (IORT) for therapeutic de-escalation in early breast cancer: Report of a single institution's experience.

The spread of systematic screening and the emergence of oncoplastic techniques allow more breast conservative treatment associating lumpectomy and external beam radiation therapy. In order to furthermore facilitate the patient's treatment, intraoperative radiation therapy (IORT) has been developed. The oncological safety of this technique has been studied, and is considered acceptable. Many questions remain unsolved in regard of the toxicity of this procedure as well as the patient's selection criteria. In this study, we present the first results and complications rate of patients treated by IORT in a single French institution. Between 2012 and 2015, all patients with breast cancer treated in a one-step procedure associating lumpectomy and IORT were retrospectively included in a monocentric cohort. Acute and long-term toxicities were evaluated using CTCAE v4.0 classification. 280 breast cancers were treated using IORT procedure. Additional external beam radiation therapy was requested for 45.7% patients. The acute complications rate was 14.6%, with 5 surgical revisions needed (1.78%). With a median follow up of 911 days, the long-term grade-3 toxicity rate was 1.1%. The only risk factor for local fibrosis was external beam radiation therapy (EBRT) (OR = 1.99; IC95 [1.05-3.81], P = 0.036). Three patients (1.07%) were diagnosed with local recurrence. The results from this cohort confirm the low complication and recurrence rate of IORT procedure. A good selection of patients is necessary in order to lower the EBRT rate and allow therapeutic de-escalation. The classification of tumors into IHC subsets seems a good selection gate. Intraoperative radiation therapy appears to have a low toxicity rate with an acceptable local recurrence risk, and should therefore be considered as an option in the treatment of early breast cancer.

Safety, effectiveness and economic evaluation of intra-operative radiation therapy: a systematic review.

BACKGROUND: Intra-operative radiation therapy (IORT) is the transfer of a single large radiation dose to the tumor bed during surgery with the final goal of improving regional tumor control. This study aimed to investigate the safety, effectiveness and economic evaluation of intra-operative radiation therapy. METHODS: The scientific literature was searched in the main biomedical databases (Centre for Reviews and Dissemination, Cochrane Library and PubMed) up to March 2014. Two independent reviewers selected the papers based on pre-established inclusion criteria, with any disagreements being resolved by consensus. Data were then extracted and summarized in a structured form. RESULTS from studies were analyzed and discussed within a descriptive synthesis. RESULTS: Sixteen studies met the inclusion criteria. It seems that outcomes from using intraoperative radiation therapy can be considered in various kinds of cancers like breast, pancreatic and colorectal cancers. The application of this method may provide significant survival increase only for colorectal cancer, but this increase was not significant for other types of cancer. This technology had low complications; and it is relatively safe. Using intra-operative radiation therapy could potentially be accounted as a cost-effective strategy for controlling and managing breast cancer. CONCLUSION: According to the existing evidences, that are the highest medical evidences for using intra-operative radiation therapy, one can generally conclude that intra-operative radiation therapy is considered as a relatively safe and cost-effective method for managing early-stage breast cancer and it can significantly increase the survival of patients with colorectal cancer. Also, the results of this study have policy implications with respect to the reimbursement of this technology.

Does intra-operative radiation at the time of pelvic exenteration improve survival for patients with recurrent, previously irradiated cervical, vaginal, or vulvar cancer?

OBJECTIVE: To determine whether intra-operative radiation therapy (IORT) at the time of pelvic exenteration (PE) or laterally extended endopelvic resection (LEER) improves progression-free survival (PFS) in patients with recurrent, previously irradiated gynecologic cancers. METHODS: We conducted a single institution retrospective review of patients who had undergone a complete PE for locally recurrent gynecologic cancer. Demographic and clinicopathologic data were collected. RESULTS: 32 patients were identified (2000-2012); 21 (66%) cervical cancer, 8 (25%) vaginal, and 3 (9%) vulvar cancer. All patients were previously irradiated. Twenty-one (66%) received IORT. Mean age was 51. Eight patients had a LEER, all with IORT. Median PFS and OS, respectively, for those with PE alone was 33 and 41 vs. 10 and 10 months for PE+IORT compared to 9 and 17 months for LEER+IORT (P=.04). Increasing tumor size negatively impacted PFS (hazard ratio 1.3; 95%CI 1.12-1.52). Margin status was not associated with survival. No patients undergoing LEER+IORT recurred only locally whereas 62% recurred with a distant component (+/- local). Patients with PE alone had mainly local (36%) and few (9%) distant recurrences compared to 31% local and 38% distant (+/- local) recurrences for those with PE+IORT. CONCLUSIONS: We failed to demonstrate that IORT changes survival and recurrence outcomes. However, patients with clinical indications for IORT at the time of PE have worse prognosis compared to those who do not require IORT. If the need for IORT is anticipated, the surgeon may consider performing a LEER to decrease local recurrence if cure is the goal or consider palliative treatment options.

What we know about intra-operative radiation exposure and hazards to operating theatre staff: A systematic review.

BACKGROUND: The widespread adoption of minimally invasive surgery and increased use of intra-operative fluoroscopy places surgeons and trainees at risk of cumulative occupational radiation exposure. Unfortunately, there is limited published data specific to surgeons on the potential health implications. This study aims to review current literature regarding the hazards of cumulative radiation exposure among operating theatre staff. METHODS: A systematic review was conducted of four databases for studies reporting on cumulative intra-operative radiation exposure for operating theatre staff and the hazards associated with prolonged and frequent use. References from relevant studies were screened for additional texts. English language studies, controlled trials and cross-sectional studies were included. Abstracts and full-text studies were assessed for relevance and eligibility independently by two authors using Covidence. RESULTS: Six studies were included, with cancer being the most commonly reported long-term health hazard possibly associated with cumulative radiation exposure. A 1.85 fold greater prevalence of all cancers and 2.9 fold greater prevalence of breast cancer was reported amongst female orthopaedic surgeons compared to a sex- and age-adjusted population, but the results were not replicated amongst other surgical specialties. Multiple limitations of quantifying health risks of intra-operative radiation exposure were identified, including identifying a dose-effect relationship and confounders such as nulliparity and maternal age. CONCLUSION: This article highlights the lack of robust evidence regarding the potential hazards of cumulative occupational intra-operative radiation exposure. This study demonstrates the importance of developing standardised national radiation safety protocols for surgical colleges and subspecialties to minimise risks to operating theatre staff.

Validation of Monte Carlo-based calculations for megavolt electron beams for IORT and FLASH-IORT.

In Intra-Operative Radiation Therapy (IORT) the tumour site is surgically exposed and normal tissue located around the tumour may be avoided. Electron applicators would require large surgical incisions; therefore, the preferred mechanism for beam collimation is the IORT cone system. FLASH radiotherapy (FLASH-RT) involves the treatment of tumours at ultra-high dose rates and the IORT cone system can also be used. This study validates the Monte Carlo-based calculations for these small electron beams to accurately determine the dose characteristics of each possible cone-energy combination as well as custom-built alloy cutouts attached to the end of the IORT cone. This will contribute to accurate dose distribution and output factor calculations that are essential to all radiation therapy treatments. A Monte Carlo (MC) model was modelled for electron beams produced by a Siemens Primus LINAC and the IORT cones. The accelerator was built with the component modules available in the BEAMnrc code. The phase-space file generated by the BEAM simulation was used as the source input for the subsequent DOSXYZnrc simulations. Percentage Depth Dose (PDD) data and profiles were extracted from the dose distributions obtained with the DOSXYZnrc simulations. These beam characteristics were compared with measured data for 6, 12, and 18 MeV electron beams for the IORT open cones of diameters 19, 45, and 64 mm and irregularly shaped cutouts. The MC simulations could replicate electron beams within a criterion of 3%/3 mm. Applicator factors were within 0.7%, and cone factors showed good agreement, except for the 9 mm cone size. Based on the successful comparisons between measurement and MC-calculated dose distributions, output factors for the open cones and for small irregularly shaped IORT beams, it may be concluded that the Monte Carlo based dose calculation could replicate electron beams used for IORT and FLASH-IORT.

Impact of "critical lesions" on outcomes following cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy.

BACKGROUND: Peritoneal Cancer Index (PCI) and complete cytoreduction are the best outcome predictors following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Lesions in critical areas, regardless of PCI, complicate surgery and impact oncological outcomes. We prospectively defined "Critical lesions" (CL) as penetrating the hepatic hilum, diaphragm at hepatic outflow, major blood vessels, pancreas, or urinary tract. METHODS: Retrospective analysis of a prospective database of 352 CRS + HIPEC patients from 2015 to 2019. Excluded patients with aborted/redo operation (n = 112), or incomplete data (n = 19). Patients categorized by CL status and compared: operative time, estimated blood loss (EBL), PCI, transfusions, hospital stay, post-operative complications and mortality, overall survival (OS) and disease-free survival (DFS). RESULTS: Included 221 patients (78 CL; 143 no-CL). No difference in patients' characteristics: age, BMI, gender or co-morbidities noted. Operative time longer (5.3 h vs 4.3 h, p < 0.01), EBL higher (769 ml vs 405 ml, p < 0.01), transfusions higher (1.9 vs 0.7 Units, p < 0.001) and PCI higher (15.5 vs 9.5, p < 0.01) in CL. No difference in major complications. Postoperative complications, CL, OR-time and transfusions were predictive of OS in univariate analysis, while only complications remained on multivariate analysis. Median follow up of 21.4 months, 3-year DFS/OS was 22% vs 30% (p < 0.037) and 73% vs 87% (p < 0.014) in CL and non-CL, respectively. Despite CL complete resection, 17/38 patients (44.7%) that recurred had recurrence at previous CL site. CONCLUSIONS: Critical lesions complicate surgery and may be associated with poor oncological outcomes with high local recurrence rate, despite no significant difference in complications. Utilizing adjuvant or intra-operative radiation may be beneficial.

Monte Carlo evaluation of the effect of inhomogeneities on dose calculation for low energy photons intra-operative radiation therapy in pelvic area.

The aim of this study was to evaluate the effect of inhomogeneities on dose calculation for low energy photons intra-operative radiation therapy (IORT) in pelvic area. A GATE Monte Carlo model of the INTRABEAM® was adapted for the study. Simulations were performed in the CT scan of a cadaver considering a homogeneous segmentation (water) and an inhomogeneous segmentation (5 tissues from ICRU44). Measurements were performed in the cadaver using EBT3 Gafchromic® films. Impact of inhomogeneities on dose calculation in cadaver was 6% for soft tissues and greater than 300% for bone tissues. EBT3 measurements showed a better agreement with calculation for inhomogeneous media. However, dose discrepancy in soft tissues led to a sub-millimeter (0.65 mm) shift in the effective point dose in depth. Except for bone tissues, the effect of inhomogeneities on dose calculation for low energy photons intra-operative radiation therapy in pelvic area was not significant for the studied anatomy.

Characterization of a microDiamond detector in high-dose-per-pulse electron beams for intra operative radiation therapy.

PURPOSE: To characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator. METHODS: The dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.). The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors. RESULTS: A good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under (60)Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R50 values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes. CONCLUSIONS: The microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions.