Comparison of the Oncological Efficacy Between Intraoperative Radiotherapy With Whole-Breast Irradiation for Early Breast Cancer: A Meta-Analysis

BackgroundIntraoperative radiotherapy (IORT) and whole-breast irradiation (WBI) are both effective radiotherapeutic interventions for early breast cancer patients undergoing breast-conserving surgery; however, an issue on whether which one can entail the better prognosis is still controversial. Our study aimed to investigate the 5-year oncological efficacy of the IORT cohort and the WBI cohort, respectively, and compare the oncological efficacy between the cohorts.Materials and MethodsWe conducted a computerized retrieval to identify English published articles between 2000 and 2021 in the PubMed, the Web of Science, the Cochrane Library, and APA PsycInfo databases. Screening, data extraction, and quality assessment were performed in duplicate.ResultsA total of 38 studies were eligible, with 30,225 analyzed participants. A non-comparative binary meta-analysis was performed to calculate the weighted average 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in the two cohorts, respectively. The LRFS, DMFS, and OS (without restriction on the 5-year outcomes) between the two cohorts were further investigated by a comparative binary meta-analysis. The weighted average 5-year LRFS, DMFS, and OS in the IORT cohort were 96.3, 96.6, and 94.1%, respectively, and in the WBI cohort were 98.0, 94.9, and 94.9%, respectively. Our pooled results indicated that the LRFS in the IORT cohort was significantly lower than that in the WBI cohort (pooled odds ratio [OR] = 2.36; 95% confidential interval [CI], 1.66–3.36). Nevertheless, the comparisons of DMFS (pooled OR = 1.00; 95% CI, 0.76–1.31), and OS (pooled OR = 0.95; 95% CI, 0.79–1.14) between the IORT cohort with the WBI cohort were both not statistically significant.ConclusionsDespite the drastically high 5-year oncological efficacy in both cohorts, the LRFS in the IORT cohort is significantly poorer than that in the WBI cohort, and DMFS and OS do not differ between cohorts.

The POLO (Partially Omitted Lobe) approach to safely treat in-breast recurrence after intraoperative radiotherapy with electrons

Objectives: The aim of this study is to evaluate feasibility of salvage 4-week hypofractionated whole breast radiotherapy (WBRT) in patients with in-breast recurrence after receiving intraoperative radiotherapy with electrons (IOERT) for primary breast cancer (BC). Methods: BC patients who had repeated quadrantectomy underwent modified WBRT with intensity-modulated radiotherapy using Helical Tomotherapy to underdose the IOERT region. This approach, called POLO (Partially Omitted Lobe), excluded the IOERT volume from receiving the full prescription dose. Results: Nine patients were treated with this approach, receiving 45 Gy in 20 fractions. A simultaneous integrated boost of 2.5 Gy in 20 fractions was delivered in 6/9 patients. Dose constraints and planning objectives were reported. No severe toxicity was reported while local control and overall survival were 100%. Conclusion: The POLO approach is technically feasible and capable to achieve a significant reduction of radiation dose delivered to the previous treated IOERT area. Advances in knowledge: The study demonstrates the technical and dosimetric feasibility of conservative salvage whole breast radiotherapy, while sparing the area already treated with IORT, in patients with in-breast recurrence.

Intraoperative Radiotherapy Is Not a Better Alternative to Whole Breast Radiotherapy as a Therapeutic Option for Early-Stage Breast Cancer

ObjectiveIntraoperative radiotherapy (IORT) in early-stage breast cancer has been studied over the years. However, it has not been demonstrated whether IORT is more suitable as a therapeutic option for early-stage breast cancer than whole breast radiotherapy (WBRT). Therefore, we performed a meta-analysis to compare the efficacy and safety of IORT to those of WBRT as therapeutic options for early-stage breast cancer patients receiving breast-conserving surgery (INPLASY2020120008).MethodsPubMed, Embase, and Cochrane Library databases were searched from inception to October 2021. Computerized and manual searches were adopted to identify eligible randomized control trials from online databases. Risk ratio (RR) and 95% confidence intervals (CI) were calculated by random-effect models to assess the relative risk. Potential publication bias was quantified by Begg’s and Egger’s tests.ResultsBased on our inclusion criteria, 10 randomized control trials involving 5,698 patients were included in this meta-analysis. This meta-analysis showed that the IORT group was associated with a higher local recurrence risk (RR = 2.111, 95% CI, 1.130–3.943, p = 0.0191), especially in the long-term follow-up subgroup or published after 2020 subgroup or Caucasian subgroup (RR = 2.404, 95% CI, 1.183–4.885, p = 0.0154). Subgroup analysis showed that the IORT group had a higher recurrence risk than the WBRT group in the polycentric randomized controlled trial subgroup (RR = 1.213, 95% CI, 1.030–1.428, p = 0.0204). Pooled analysis showed that there was no statistically significant difference in overall survival, recurrence-free survival, distant metastasis-free survival, and cancer-specific survival between IORT and WBRT groups. Additionally, the risk of skin toxicity was reduced, but the incidences of fat toxicity, edema, and scar calcification were significantly increased in the patients who underwent IORT in comparison to those who underwent WBRT.ConclusionThis meta-analysis revealed that IORT was not a better alternative to WBRT. More large-scale and well-designed clinical trials with longer follow-up periods are encouraged to further investigate the value of IORT.Systematic Review Registrationhttps://inplasy.com/inplasy-2020-12-0008/.

Dosimetric Comparison of Intraoperative Radiotherapy and SRS for Liver Metastases

Purpose/ObjectivesTo perform a dosimetric comparison between kilovoltage intraoperative radiotherapy (IORT) and stereotactic radiosurgery (SRS) simulating both deep-inspiration breath-hold (DIBH) and free-breathing (FB) modalities for patients with liver metastases.Methods/MaterialsDiagnostic computed tomographies (CT) of patients carrying one or two lesions <4 cm and who underwent surgery were retrospectively screened and randomly selected for the study. For DIBH-SRS, a gross target volume (GTV) plus planning target volume (PTV) were delineated. For FB-SRS, a GTV plus an internal target volume (ITV) and PTV were defined. Accounting for the maximal GTV diameters, a modified GTV (GTV-IORT) was expanded circumferentially to simulate a resection cavity. The best suitable round-applicator size was thereafter selected. All treatment plans were calculated homogeneously to deliver 40 Gy. Doses delivered to organs at risk (OAR) and target volumes were compared for IORT vs. both SRS modalities.ResultsEight patients encompassing 10 lesions were included in the study. The mean liver volume was 2,050.97 cm3 (SD, 650.82), and the mean GTV volume was 12.23 cm3 (SD, 12.62). As for target structures, GTV-IORT [19.44 cm3 (SD, 17.26)] were significantly smaller than both PTV DIBH-SRS [30.74 cm3 (SD, 24.64), p = 0.002] and PTV FB-SRS [75.82 cm3 (SD, 45.65), p = 0.002]. The median applicator size was 3 cm (1.5–4.5), and the mean IORT simulated delivery time was 45.45 min (SD, 19.88). All constraints were met in all modalities. Liver V9.1 showed significantly smaller volumes with IORT [63.39 cm3 (SD, 35.67)] when compared to DIBH-SRS [150.12 cm3 (SD, 81.43), p = 0.002] or FB-SRS [306.13 cm3 (SD, 128.75), p = 0.002]. No other statistical or dosimetrically relevant difference was observed for stomach, spinal cord, or biliary tract. Mean IORT D90 was 85.3% (SD, 6.05), whereas D95 for DIBH-SRS and FB-SRS were 99.03% (SD, 1.71; p = 0.042) and 98.04% (SD, 3.46; p = 0.036), respectively.ConclusionKilovoltage IORT bears the potential as novel add-on treatment for resectable liver metastases, significantly reducing healthy liver exposure to radiation in comparison to SRS. Prospective clinical evidence is required to confirm this hypothesis.

P-P57 The first experience of intraoperative radiotherapy for pancreatic cancer in the UK

Background Intraoperative radiotherapy (IORT) involves giving a targeted single fraction of high dose radiation to the resection bed. The main advantages are exclusion of vulnerable structures from the radiation field and ability to direct the electron beam to threatened margins. IORT in pancreatic cancer is not new, with Japanese centres reporting series from the 1970s. Early reports were exciting, suggesting that IORT was useful in reducing visceral pain, achieving local control and improving survival in locally advanced and unresectable patients. However, paucity of randomised trials in the ensuing decades has limited its widespread adoption. Methods With funding from the PLANETS charity (www.planetscharity.org), University Hospitals Southampton acquired a Mobetron 2000 linear accelerator (IntraOp, USA) in 2016. Testing was done at the National Physical Laboratory (Teddington, UK) over two months to collect beam data and ensure consistency in treatment delivery. Staff training included visits to the Heidelberg Cancer Centre and several dry runs. Inclusion criteria were: (i) patients with pancreatic head adenocarcinomas; (ii) threatened vascular margins; (iii) WHO performance status 1-2; (iv) no evidence of distant metastasis. Results Nineteen patients had pancreaticoduodenectomy (traditional or pylorus preserving) combined with IORT. Median age was 66 (42-81) years. Median ASA grade was 2 (2-3). 16/19 had locally advanced pancreatic cancer and 18/19 had neoadjuvant chemotherapy. Median IOERT dose was 15 (10-15) Gy, energy 7.5 (6-12) MeV, to a mean depth of 1.6 +/- 0.8 cm, with median cone size 5 (4-6) cm and bevel angle 15 (0-30) degrees. All tumours were pT1-T3 and 10/19 had positive regional nodes. 10/19 were R1 resections, with 4/19 specimens exhibiting vascular invasion and 6/19 perineural invasion. Mean operating time (including IOERT) was 534 +/- 77 min. Median length of stay was 8.5 (6-41) days. 30-day mortality was zero. 6/19 patients had post-operative complications (Clavien-Dindo 1-2 only), with clinically detectable pancreatic fistula in 1/19. Conclusions This is the first UK experience of IORT for pancreatic cancer, showing that this treatment modality is safe and feasible. With the appropriate expertise, an IORT service can be implemented within 12 months of acquiring the Mobetron system. We hope that these data will encourage other UK and European HPB units to consider setting up regional IORT services, such that larger scale prospective trials can be initiated to demonstrate its efficacy.