On the need of in vivo verifications as quality control for intraoperative electron radiotherapy in breast cancer.

INTRODUCTION: Intraoperative electron radiotherapy (IOERT) is a technique aiming to deliver radiotherapy during oncological surgery. In breast IOERT, the applicator and shielding disc placement are correlated with organs at risk (OAR) irradiation, in vivo verification of these parameters is scarcely reported. The aim of our study is to report and analyze possible causes of the misalignment using radiochromic films and compare our results to others reported in the bibliography. METHODS: From November 2019 to April 2023, in vivo verifications were performed for 33 patients. IOERT was performed using a LIAC 10 MeV (Sordina, Italy) electron accelerator. We attached a radiochromic film to the upper side of the polytetrafluoroethylene cover of the shielding disc. The percentage of the irradiation area outside the disc was recorded and various parameters (applicator angulations, prescription depth, tumor location and breast size) were analyzed to find possible correlations. RESULTS: For 29 patients, 20 Gy were prescribed while 10 Gy were prescribed to 4 patients. The average irradiated area outside the disc was 19% (0-56%) corresponding to a surface of 4.5 cm2 (0-17.4 cm2). The applicator of 5 cm was used for most of the patients. The mean prescription depth was 1.4 cm (0.5-2.5 cm). We found no correlation between the analyzed parameters and misalignment. CONCLUSION: This study confirms the presence and magnitude of the misalignments. We strongly recommend in vivo verifications as a quality check during IOERT procedures. The misalignment has no correlation with tumor localization parameters, so the solution could be based on technical improvements of the applicator.

Clinical outcomes and timing on the combination of focal radiation therapy and immunotherapy for the treatment of brain metastases.

Introduction: Radiotherapy is one of the standard treatments for brain metastases (BM). Over the past years, the introduction of immunotherapy as routine treatment for solid tumors has forced investigators to review and evaluate how it would interact with radiation. Radiation and Immunotherapy have shown a synergic effect activating the host's immune system and enhancing treatment response. The combinatory effect on BM is currently under investigation. Methods: Data published on Pubmed to determine toxicity, survival, treatment characteristics and timing on the combination of radiotherapy and immunotherapy for the treatment of BM has been reviewed. Results: Mostly retrospective reviews report an improvement of intracranial progression free survival (iPFS) when combining radioimmunotherapy for BM patients. Two systematic reviews and meta-analysis and one phase II prospective trial also report a benefit on iPFS without an increase of toxicity. Among the published literature, the definition of concurrency is heterogeneous, being one month or even narrowed intervals correlated to better clinical outcomes. Toxicity due to concurrent radioimmunotherapy, specifically symptomatic radionecrosis, is also directly analyzed and reported to be low, similar to the toxicity rates secondary to stereotactic radiosurgery alone. Conclusion: Radiation combined with immunotherapy has shown in predominantly retrospective reviews a synergic effect on the treatment of BM. The concurrent combination of radioimmunotherapy is a feasible therapeutic strategy and seems to improve clinical outcomes, especially iPFS, when delivered within <30 days. Larger prospective and randomized studies are needed to establish reliable outcomes, best delivery strategies and toxicity profile.

Hypofractionated whole breast irradiation in association with hypofractionated or normofractionated boost to the tumor bed in early breast cancer: tolerance and efficacy analysis

Background The boost to the tumor bed improves local control in breast cancer and it is an important part of the breast conserving therapy. However, information about the use of a hypofractionated boost is sparse, thus further studies are needed. We conducted a retrospective study with the aim of comparing hypofractionated boost (HB) and normofractionated boost (NB) on skin toxicity and local control. Materials and methods A total of 96 women with early breast cancer undergoing breast-conserving surgery and hypofractionated whole breast irradiation (WBI) were retrospectively analyzed divided into hypofractionated boost group and conventional fractionation boost group. Forty-nine patients were treated with NB with 16 Gy in 8 fractions and 47 patients were treated with HB with 13.35 Gy in 5 fractions. We examined acute and chronic toxicity with CTCAE version 5. Results The median follow-up was 49.5 months (26–67). Median age was 57 years (36–82). Sixty-six patients (68.7%) were younger than 60 years at the time of boost and 30 (31.2%) were older than 60 years who received the boost due to poor prognostic factors. No differences were found between the two groups in terms of patient, tumor or treatment characteristics. Grade 2 acute skin toxicity was 6.3% in the NB group and 4.2% in the HB group. Chronic skin induration was 4.2% in the NB group and 1% in the HB group. They did not show grade 3 skin toxicity. There were also no differences in acute or late skin toxicity between the two groups. No local recurrences were evidenced. Conclusions Hypofractionated WBI associated with HB treatment is a viable option in the management of conservative breast therapy given the good tolerance and similar local control (AU)

Analysis of Local Recurrence Risk in Ductal Carcinoma In Situ and External Validation of the Memorial Sloan Kettering Cancer Center Nomogram.

BACKGROUND: Adjuvant radiotherapy and hormonotherapy after breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) have been shown to reduce the risk of local recurrence. To predict the risk of ipsilateral breast tumor relapse (IBTR) after BCS, the Memorial Sloan Kettering Cancer Center (MSKCC) developed a nomogram to analyze local recurrence (LR) risk in our cohort and to assess its external validation. METHODS: A historical cohort study using data from 296 patients treated for DCIS at the Hospital Clínic of Barcelona was carried out. Patients who had had a mastectomy were excluded from the analysis. RESULTS: The mean age was 58 years (42-75), and the median follow-up time was 10.64 years. The overall local relapse rate was 13.04% (27 patients) during the study period. Actuarial 5- and 10-year IBTR rates were 5.8 and 12.9%, respectively. The external validation of the MSKCC nomogram was performed using a multivariate logistic regression analysis on a total of 207 patients, which did not reach statistical significance in the studied population for predicting LR (p = 0.10). The expression of estrogen receptors was significantly associated with a decreased risk of LR (OR: 0.25; p = 0.004). CONCLUSIONS: In our series, the LR rate was 13.4%, which was in accordance with the published series. The MSKCC nomogram did not accurately predict the IBTR in this Spanish cohort of patients treated for DCIS (p = 0.10).

Hypofractionated whole breast irradiation in association with hypofractionated or normofractionated boost to the tumor bed in early breast cancer: tolerance and efficacy analysis.

BACKGROUND: The boost to the tumor bed improves local control in breast cancer and it is an important part of the breast conserving therapy. However, information about the use of a hypofractionated boost is sparse, thus further studies are needed. We conducted a retrospective study with the aim of comparing hypofractionated boost (HB) and normofractionated boost (NB) on skin toxicity and local control. MATERIALS AND METHODS: A total of 96 women with early breast cancer undergoing breast-conserving surgery and hypofractionated whole breast irradiation (WBI) were retrospectively analyzed divided into hypofractionated boost group and conventional fractionation boost group. Forty-nine patients were treated with NB with 16 Gy in 8 fractions and 47 patients were treated with HB with 13.35 Gy in 5 fractions. We examined acute and chronic toxicity with CTCAE version 5. RESULTS: The median follow-up was 49.5 months (26-67). Median age was 57 years (36-82). Sixty-six patients (68.7%) were younger than 60 years at the time of boost and 30 (31.2%) were older than 60 years who received the boost due to poor prognostic factors. No differences were found between the two groups in terms of patient, tumor or treatment characteristics. Grade 2 acute skin toxicity was 6.3% in the NB group and 4.2% in the HB group. Chronic skin induration was 4.2% in the NB group and 1% in the HB group. They did not show grade 3 skin toxicity. There were also no differences in acute or late skin toxicity between the two groups. No local recurrences were evidenced. CONCLUSIONS: Hypofractionated WBI associated with HB treatment is a viable option in the management of conservative breast therapy given the good tolerance and similar local control.

Intraoperative electron radiation therapy after salvage surgery in gynecological cancers and retroperitoneal sarcomas: outcomes and adverse effects.

Background: Salvage surgery is considered an option for isolated recurrences of retroperitoneal and pelvic tumors, in patients who have undergone previous radiotherapy. In order to increase local control intra operative electron radiation therapy (IOERT) can be used in these patients to administer additional radiation dose. We evaluated the outcomes and adverse effects in patients with retroperitoneal sarcoma and gynecologic tumors after salvage surgery and IOERT. Materials and methods: Twenty patients were retrospectively analyzed. Twenty-three IOERT treatments were performed after surgery. Six (30%) were sarcoma and 14 (70%) were gynecological carcinoma. Administered dose depended on previous dose received with external beam radiotherapy (EBRT) and proximity to critical structures. The toxicities were scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: The median age of the patients was 51 years (range 34-70). After a median follow-up of 32 months (range 1-68), in the sarcoma group the local control rate was 66.6%; while in the gynecological group the local control rate was 64.3%. In relation to late toxicity, one patient had a Grade 2 vesicovaginal fistula, and one patient presented Grade 4 enterocolitis and enteric intestinal fistula. Conclusions: IOERT could have a role in the treatment of retroperitoneal sarcomas in primary tumors after EBRT, as it may suggest a benefit in local control or recurrences after surgical resection in those at high risk of microscopic residual disease. The addition of IOERT to salvage resection for isolated recurrence of gynecologic cancers suggest favorable local control in cases with concern for residual microscopic disease.

Analgesic effects of low-dose radiotherapy in greater trochanteric pain syndrome: results in a clinical series of 155 patients with recurrent or refractory symptoms

PurposeThis prospective study assessed the effects of low-dose radiotherapy in patients diagnosed with greater trochanteric pain syndrome (GTPS) with recurrent symptoms or refractory to previous conservative measures.MethodsWe evaluated a total of 155 patients (90.3% women, mean age 69 years). Most patients (n = 136) received 10 Gy (1 Gy/day/3 fractions per week on alternate days), but after recommendations of DEGRO guidelines published in 2015, the remaining 19 patients (12.2%) received 6 Gy (1 Gy/day/3 fractions per week on alternate days).ResultsAt the pre-treatment visit, the mean (standard deviation, SD) visual analog scale (VAS) score was 8), which decreased to 5 (SD 2.2) after 1 month of the end of treatment and to 4 (SD 2.3) after 4 months. An objective symptom response with increased mobility, better sleep quality, and reduction of analgesic medication was found in 56% of patients at 1 month. In 129 patients (83.2%), there was a decrease of at least 1 point in the VAS score, and in 49 patients (29.0%), the VAS score was lower than 3. The mean length of follow-up was 45 months. The probability of maintaining the analgesic response estimated by the Kaplan-Meier method was 53% at 5 years.ConclusionLow dose radiotherapy effectively improved pain in the trochanteric area in most patients with recurrent or refractory GTPS, allowing a reduction in the need for analgesic medications and, more, importantly, better functioning and mobility. Further randomized studies in selected populations of GTPS are needed to define the treatment position of low-dose radiotherapy in this clinical setting.

Magnetic Resonance Imaging Assessment of Radial Scars/complex Sclerosing Lesions of the Breast.

PURPOSE: To describe the magnetic resonance characteristics of radial scars/complex sclerosing lesions (RS/CSL) of the breast using the current BI-RADS lexicon. To investigate the value of diffusion weighted imaging to predict malignancy. PATIENTS AND METHODS: From 2010 to 2017, we have found 25 women with architectural distortion at mammography who underwent surgical resection with a final hystopathologic report of RS/CSL. For the description of MRI findings, we adhered to BI-RADS classification (5th edition). RESULTS: The final pathological diagnosis was: "pure" RS/CSL in 7 cases (28%), RS/CSL with associated high risk lesions in 12 (48%) and 6 cases (24%) were associated with malignancy. Magnetic resonance findings: four of 25 negative or focus. Five of 25 mass enhancement: irregular, non circumscribed spiculated mass with heterogeneous or rim enhancement and most with type II curves. Sixteen of 25 non mass enhancement: focal or linear distribution and heterogeneous internal enhancement most with type I curves. Six of 25 had cancer associated with the complex sclerosing lesion. All six showed non-mass enhancement. Two cases with invasive breast carcinoma had ADC values under 1.15 x10-3 mm/s while most of the rest had the values above. CONCLUSION: Most RS/CSL showed enhancement at MR. The predominant pattern was a non-mass, focal, heterogeneous internal enhancement with type 1 curves. All cases with associated cancer showed non mass enhancement. Invasive breast cancers had ADC values < 1.15 10-3 s/mm2.

Analgesic effects of low-dose radiotherapy in greater trochanteric pain syndrome: results in a clinical series of 155 patients with recurrent or refractory symptoms.

PURPOSE: This prospective study assessed the effects of low-dose radiotherapy in patients diagnosed with greater trochanteric pain syndrome (GTPS) with recurrent symptoms or refractory to previous conservative measures. METHODS: We evaluated a total of 155 patients (90.3% women, mean age 69 years). Most patients (n = 136) received 10 Gy (1 Gy/day/3 fractions per week on alternate days), but after recommendations of DEGRO guidelines published in 2015, the remaining 19 patients (12.2%) received 6 Gy (1 Gy/day/3 fractions per week on alternate days). RESULTS: At the pre-treatment visit, the mean (standard deviation, SD) visual analog scale (VAS) score was 8), which decreased to 5 (SD 2.2) after 1 month of the end of treatment and to 4 (SD 2.3) after 4 months. An objective symptom response with increased mobility, better sleep quality, and reduction of analgesic medication was found in 56% of patients at 1 month. In 129 patients (83.2%), there was a decrease of at least 1 point in the VAS score, and in 49 patients (29.0%), the VAS score was lower than 3. The mean length of follow-up was 45 months. The probability of maintaining the analgesic response estimated by the Kaplan-Meier method was 53% at 5 years. CONCLUSION: Low dose radiotherapy effectively improved pain in the trochanteric area in most patients with recurrent or refractory GTPS, allowing a reduction in the need for analgesic medications and, more, importantly, better functioning and mobility. Further randomized studies in selected populations of GTPS are needed to define the treatment position of low-dose radiotherapy in this clinical setting.

Intraoperative radiation therapy in uterine cervical cancer: A review.

Locally advanced uterine cervical cancer continues to present a high number of pelvic relapses. Intraoperative radiation therapy (IORT) allows a precise therapeutic intensification in the surgical area in cases in which removal of the tumour recurrence is feasible. At the same time, IORT excludes the radiosensitive organs from the field of irradiation. While the first gynecological IORT took place in 1905, procedures have been limited over the years and the series are retrospective, including few patients. At the same, time recurrences are located at different pelvic areas. Both heterogeneity and the long recruiting time make it difficult to correctly interpret the published results. Despite this, we have reviewed the most relevant publications. Some institutions indicated IORT as a boost on the surgical bed of the excised tumor recurrence. In others, IORT permits an extra radiation dose after radical surgery of the primary tumor, usually in stage IIB. Most studies conclude that the addition of IORT increases the local control but probably with little impact on survival. On the other hand, there is a controversy in the indication of IORT in surgically resectable primary tumours. No clear advantage over the usual scheme of chemoradiation and brachytherapy has been detected. Randomized studies that allow a breakthrough in the conclusions are highly unlikely to be performed in this area.

A new short daily brachytherapy schedule in postoperative endometrial carcinoma. Preliminary results.

PURPOSE: To evaluate the preliminary results of vaginal-cuff relapses (VCR) and complications of a short brachytherapy (BT) schedule in postoperative endometrial carcinoma. METHODS AND MATERIALS: From September 2011 to December 2014, 102 patients were treated with postoperative BT for endometrial carcinoma. Seventy-four patients received a single 7 Gy dose after external beam irradiation (Group 1), and 28 intermediate-risk patients received three daily fractions of 6 Gy (Group 2). The dose was prescribed at 5 mm from the applicator surface. Toxicity was prospectively evaluated after the objective late effects of normal tissues-subjective, objective, management, analytic scores for vagina and RTOG scores for rectum and bladder. STATISTICS: χ2 and Student's t tests. RESULTS: The mean followup was 28.85 months (9.6-58.5) in Group 1 and 31.19 months (7.7-62.3) in Group 2. No VCR was found during followup. Late toxicity: vagina toxicity was developed in 24.32% of the patients in Group 1 (G1-G2) and in 21.4% in Group 2 (G1-G2 but 1 G3). Rectal toxicity appeared in only 2.7% of patients in Group 1 (G1). Neither Group 1 nor Group 2 presented late bladder toxicity. No differences were found in late toxicity between Groups 1 and 2. CONCLUSIONS: The present short BT schedule was safe in relation to VCR and late toxicity for the followup period studied. These results are similar to those of two larger previous schedules performed in our center in relation to the same point of followup.