Intraoperative Radiation Therapy Delivered by Brachytherapy in Breast Cancer: An Interim Analysis of a Phase 2 Trial.

PURPOSE: Intraoperative breast cancer radiotherapy (IORT) offers an alternative to external beam radiotherapy (EBRT) after breast-conserving surgery (BCS). The Intraoperative brachytherapy (IOBT) trial applies high dose rate (HDR) brachytherapy with a new applicator prototype as IORT after BCS. In this interim analysis of the IOBT trial, we present the oncological safety and toxicity of the method METHODS: Eligible patients were women, ≥ 50 years old with an unifocal nonlobular, estrogen-receptor-positive, HER2-negative breast cancer, cN0, ≤ 3 cm, treated with BCS and sentinel node biopsy (SNB). Toxicity was registered according to the LENT-SOMA scale. Cumulative incidence of local (LR) and regional recurrence (RR) were calculated through cumulative incidence function whereas overall survival (OS) was illustrated through Kaplan-Meier curve. RESULTS: Until February 2023, 155 women (median age 68 years) were included in the trial. Twenty-nine women (18.7%) received supplemental EBRT, mostly due to positive SNB. Three-year cumulative incidence of LR and RR were 1.0% (CI 95 % 0.1%-2.3%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five- year cumulative incidence of LR and RR were 3.9% (CI 95% 1.8%-6.4%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five-year OS was 96.3% (CI 95% 93.6%-98.4%). Side effects were limited, low grade, and transient. CONCLUSION: Acknowledging the short median follow-up time at interim analysis, our initial results indicate that delivering IORT through HDR brachytherapy in carefully selected breast cancer patients is feasible and oncological safe so far. A long-term follow-up is essential to confirm the initial results.

Brachytherapy in the Treatment of Soft-Tissue Sarcomas of the Extremities-A Current Concept and Systematic Review of the Literature.

INTRODUCTION: Evidence on the use of brachytherapy in soft-tissue sarcoma (STS) is sparse. Therapy regimens are determined more by local interdisciplinary tumor conferences than by standardized protocols. Patient-specific factors complicate the standardized application of therapy protocols. The individuality of the treatment makes it difficult to compare results. MATERIALS AND METHODS: A comprehensive literature search was conducted, whereby the literature from a period of almost 44 years (1977-2021) was graded and included in this systematic review. For this purpose, PubMed was used as the primary database. Search string included "soft-tissue sarcoma", "brachytherapy", and "extremity." Four independent researchers reviewed the literature. Only full-text articles written in English or German were included. RESULTS: Of the 175 identified studies, 70 were eligible for analysis based on the inclusion and exclusion criteria. The key points to compare were local complications, recurrence rate and correlation with margins of resection, and the use of brachytherapy regarding tumor grading. CONCLUSION: Brachytherapy represents an important subset of radiotherapy techniques used in STSs, whose indications and applications are constantly evolving, and for which a local control rate of 50% to 96% has been reported as monotherapy, depending on risk factors. However, the best benefit is seen in the combination of further resection and brachytherapy, and most authors at many other centers agree with this treatment strategy.

Midterm Results of High-Dose-Rate Intraoperative Brachytherapy in the Treatment of Soft Tissue Sarcomas.

INTRODUCTION: According to the literature only sparse data are available on the use of high-dose-rate intraoperative brachytherapy (IOHDR-BT) as a boost to external-beam irradiation (EBRT) in combination with a wide resection in patients with high-grade soft tissue sarcomas (STS). MATERIALS AND METHODS: Applying a retrospective study design, we investigated all patients who between 2010 and 2016 underwent marginal resection of a high-grade STS and intraoperative radiotherapy, followed by EBRT. We included only patients with a traceable follow-up time of at least two years. Of 89 patients, 35 met our inclusion criteria and showed an average follow-up of four years. RESULTS: We found an overall 2-year local control rate of 94.3%. The local recurrence rate for R0 resections was 6%, whereas recurrences occurred in 13% of R1 resections and in 100% of R2 resections. One affected patient received only intraoperative radiotherapy. The recurrence rate by tumour entity was 36% for LPS, 11% for myxofibrosarcoma and 17% for undifferentiated pleomorphic sarcoma. CONCLUSION: The treatment regimen consisting of limb-preserving surgery, IORT and pre- or postoperative radiotherapy consistently shows excellent local control rates.

Narrowing the difference in dose delivery for IOERT and IOBT for locally advanced and locally recurrent rectal cancer.

Purpose: Intra-operative radiotherapy (IORT) has been used as a tool to provide a high-dose radiation boost to a limited volume of patients with fixed tumors with a likelihood of microscopically involved resection margins, in order to improve local control. Two main techniques to deliver IORT include high-dose-rate (HDR) brachytherapy, termed 'intra-operative brachytherapy' (IOBT), and electrons, termed 'intra-operative electron radiotherapy' (IOERT), both having very different dose distributions. A recent paper described an improved local recurrence-free survival favoring IOBT over IOERT for patients with locally advanced or recurrent rectal cancer and microscopically irradical resections. Although several factors may have contributed to this result, an important difference between the two techniques was the higher surface dose delivered by IOBT. This article described an adaptation of IOERT technique to achieve a comparable surface dose as dose delivered by IOBT. Material and methods: Two steps were taken to increase the surface dose for IOERT: 1. Introducing a bolus to achieve a maximum dose on the surface, and 2. Re-normalizing to allow for the same prescribed dose at reference depth. Conclusions: We describe and propose an adaptation of IOERT technique to increase surface dose, decreasing the differences between these two techniques, with the aim of further improving local control. In addition, an alternative method of dose prescription is suggested, to consider improved comparison with other techniques in the future.

Rapid Interval Recurrence of Glioblastoma Following Gross Total Resection: A Possible Indication for GammaTileⓇ Brachytherapy.

Glioblastoma recurrence between initial resection and standard-of-care adjuvant chemoradiotherapy (CRT) is a negative prognostic factor in an already highly aggressive disease. Re-resection with GammaTileⓇ(GT Medical Technologies Inc., Tempe, AZ) placement affords expedited adjuvant radiation to mitigate the likelihood of such growth. Here, we report a glioblastoma patient who underwent re-resection and GammaTileⓇ (GT) placement within two months of the initial gross total resection due to regrowth that reached the size of the original presenting tumor. The patient subsequently received concurrent temozolomide and 60 Gy external beam to regions outside of the brachytherapy range, fulfilling the generally accepted Stupp regimen. The patient tolerated the treatment without complication. The dosimetrics and implications of the case presentation are reviewed.

Intraoperative high dose rate brachytherapy during breast-conserving surgery: A prospective pilot study.

PURPOSE: To evaluate feasibility, quality of life, toxicity, and cosmetic outcome for intraoperative breast cancer brachytherapy after breast-conserving surgery using high dose rate brachytherapy. METHODS: Fifty-two consecutive women, ⩾50 years old, diagnosed with a unifocal non-lobular breast cancer ⩽3 cm, N0, underwent breast-conserving surgery and sentinel node biopsy. Twenty-five women received intraoperative brachytherapy pre-pathology at primary surgery and the others post-pathology, during a second procedure. An applicator, connected to a high dose rate afterloader, was used. Two of the women were excluded due to metastases found per-operatively at a frozen section from the sentinel node. Quality of life was evaluated using two validated health questionnaires. Treatment toxicity was documented according to the LENT-SOMA scale by two oncologists. The cosmetic result was evaluated using the validated freely available software BCCT.core 2.0. RESULTS: The clinical procedure worked out well logistically. Seven women received supplementary external radiotherapy due to insufficient margins and, in one case, poor adaptation of the breast parenchyma to the applicator. No serious adverse effects from irradiation were registered. The results from the health questionnaires showed no major differences compared with reference groups from the Swedish population. Only two women were registered as having a "poor" cosmetic result while a majority of the women had a "good" outcome. CONCLUSIONS: This pilot study shows that intraoperative brachytherapy is a feasible procedure and encourages further trials evaluating its role in treatment of early breast cancer.

Sublobar resection with intraoperative brachytherapy versus sublobar resection alone for early-stage non-small-cell lung cancer: a meta-analysis.

OBJECTIVES: The purpose of this study was to compare the clinical outcomes for sublobar resection (SR) or SR plus intraoperative brachytherapy (SRB) for clinical stage I non-small-cell lung cancer. METHODS: A systematic search was performed in the EMBASE, PubMed and Cochrane Library databases to identify related studies comparing SR to SRB. Data were collected on local recurrence (LR) as a primary outcome and regional or distant recurrence, overall survival and disease-free survival (DFS) as secondary outcomes. Meta-analysis was carried out using Stata 12.0. RESULTS: A total of 476 patients received SRB, and 617 received SR across 5 studies. Meta-analysis of LR, regional or distant recurrence, overall survival and disease-free survival rates showed no significant difference between SRB and SR groups. However, when biologically effective dose (BED) was >100 Gy, LR rate was lower in the SRB group than in the SR group (Relative risk [RR] = 0.143, 95% confidence interval [CI]: 0.051-0.397) (p < 0.001). When BED was <100 Gy, no significant difference was found in LR rate between SRB and SR groups (SRB versus SR: RR = 1.132, 95%CI: 0.704-1.821) (p = 0.608). CONCLUSIONS: Intraoperative brachytherapy was not associated with reduced risk of regional or distant metastasis or improved outcomes for patients with clinical stage I non-small-cell lung cancer; however, it might reduce the LR rate when BED was >100 Gy.

A nomogram to determine required seed air kerma strength in planar 131Cesium permanent seed implant brachytherapy.

PURPOSE: Intraoperatively implanted Cesium-131 (131Cs) permanent seed brachytherapy is used to deliver highly localized re-irradiation in recurrent head and neck cancers. A single planar implant of uniform air kerma strength (AKS) seeds and 10 mm seed-to-seed spacing is used to deliver the prescribed dose to a point 5 mm or 10 mm perpendicular to the center of the implant plane. Nomogram tables to quickly determine the required AKS for rectangular and irregularly shaped implants were created and dosimetrically verified. By eliminating the need for a full treatment planning system plan, nomogram tables allow for fast dose calculation for intraoperative re-planning and for a second check method. MATERIAL AND METHODS: TG-43U1 recommended parameters were used to create a point-source model in MATLAB. The dose delivered to the prescription point from a single 1 U seed at each possible location in the implant plane was calculated. Implant tables were verified using an independent seed model in MIM Symphony LDR™. Implant tables were used to retrospectively determine seed AKS for previous cases: three rectangular and three irregular. RESULTS: For rectangular implants, the percent difference between required seed AKS calculated using MATLAB and MIM was at most 0.6%. For irregular implants, the percent difference between MATLAB and MIM calculations for individual seed locations was within 1.5% with outliers of less than 3.1% at two distal locations (10.6 cm and 8.8 cm), which have minimal dose contribution to the prescription point. The retrospectively determined AKS for patient implants using nomogram tables agreed with previous calculations within 5% for all six cases. CONCLUSIONS: Nomogram tables were created to determine required AKS per seed for planar uniform AKS 131Cs implants. Comparison with the treatment planning system confirms dosimetric accuracy that is acceptable for use as a second check or for dose calculation in cases of intraoperative re-planning.

Carotid stent extrusion following carotid blowout.

OBJECTIVE: We describe an unusual foreign body, a carotid stent extruded into the upper airway, and discuss the predisposing factors. METHODS: This is a single patient case report with review of the literature. RESULTS: Our patient is a 59 year old female treated for T3N2aM0 (stage IVa) left tonsil squamous cell carcinoma who experienced a carotid blowout treated by carotid stent placement with subsequent carotid coiling and vessel takedown. Approximately ten months later, she coughed and expelled approximately 3cm of tubular stent-appearing material into her airway causing acute stridor and dysphagia. CT angiography (CTA) showed the distal and proximal stent in proper position without evidence of extravasation. The stent was extracted transorally showing the distal end of the carotid to be patent and covered by fibrin within its lumen. Review of the literature shows that such stent extrusions, although rare, do occur. CONCLUSION: Carotid stents are a valuable tool in cases of carotid blowout. However, long-term data on patient prognosis is lacking. The foreign body response triggered by stent placement can cause dislodgement. The potential for stent extrusion is greatest in patients who have preexisting ulceration or who have undergone radiation, both common in head and neck cancer patients.

Primary Treatment Options for High-Risk/Medically Inoperable Early Stage NSCLC Patients.

Lung cancer is among the most common cancers worldwide and is the leading cause of cancer death in both men and women. For patients with early stage (American Joint Committee on Cancer T1-2, N0) non-small-cell lung cancer, the current standard of care is lobectomy with systematic lymph node evaluation. Unfortunately, patients with lung cancer often have medical comorbities, which may preclude the option of surgical resection. In such cases, a number of minimally invasive to noninvasive treatment options have gained popularity in the treatment of these high-risk patients. These modalities provide significant advantages, including patient convenience, treatment in an outpatient setting, and acceptable toxicities, including reduced impact on lung function and a modest risk of postprocedure chest wall pain. We provide a comprehensive review of the literature, including reported outcomes, complications, and limitations of sublobar resection with or without intraoperative brachytherapy, radiofrequency ablation, microwave ablation, percutaneous cryoablation, photodynamic therapy, and stereotactic body radiotherapy.