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Targeting Accuracy Considerations for Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy.

ABSTRACT: Purpose: Tumor treating fields (TTFields) is a novel antimitotic treatment that was first proven effective for glioblastoma multiforme, now with trials for several extracranial indications underway. Several studies focused on concurrent TTFields therapy with radiation in the same time period, but were not given simultaneously. This study evaluates the targeting accuracy of simultaneous radiation therapy while TTFields arrays are in place and powered on, ensuring that radiation does not interfere with TTFields and TTFields does not interfere with radiation. This is one of several options to enable TTFields to begin several weeks sooner, and opens potential for synergistic effects of combined therapy. Methods: TTFields arrays were attached to a warm saline water bath and salt was added until the TTFields generator reached the maximal 2000 mA peak-to-peak current. A ball cube phantom containing 2 orthogonal films surrounded by fiducials was placed in the water phantom, CT scanned, and a radiation treatment plan with 58 isocentric beams was created using a 3 cm circular collimator. Fiducial tracking was used to deliver radiation, the films were scanned, and end-to-end targeting error was measured with vendor-supplied software. In addition, radiation effects on electric fields generated by the TTFields system were assessed by examining logfiles generated from the field generator. Results: With TTFields arrays in place and powered on, the robotic radiosurgery system achieved a final targeting result of 0.47 mm, which was well within the submillimeter specification. No discernible effects on TTFields current output beyond 0.3% were observed in the logfiles when the radiation beam pulsed on and off. Conclusion: A robotic radiosurgery system was used to verify that radiation targeting was not adversely affected when the TTFields arrays were in place and the TTFields delivery device was powered on. In addition, this study verified that radiation delivered simultaneously with TTFields did not interfere with the generation of the electric fields.

SUBMITTER: Biswas S

PROVIDER: S-EPMC8504228 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Little is known about the effectiveness of hypofractionated radiation therapy (HFRT) or stereotactic body radiation therapy (SBRT) for the treatment of patients with oligometastatic (OM) or oligoprogressive (OP) thymic malignancies. Methods We retrospectively reviewed Stage IV patients with OM or OP thymic malignancies treated with HFRT or SBRT between 2009–2021. We defined OM as 5 or fewer sites of metastatic disease and OP as 5 or fewer sites of metastatic disease increasing in radiological size at the time of radiation. Analysis of local failure (LF, defined as failure within a treated lesion) and distant failure (DF, defined as failure outside the treated lesion) was done at the treatment course level using univariate analysis Fine-Gray regression adjusted for clustering. Analysis of overall survival (OS) and progression-free survival (PFS) was done at the patient level utilizing only the first course of treatment for each patient. Results Our analysis included 50 patients with 92 treatment courses. Patients had thymoma (50%), thymic carcinoma (TC, 40%), or atypical thymic carcinoid (ATC, 10%). The median biologic effective dose (BED) was 51 Gy (range, 38–106 Gy). With a median follow-up of 36 months, the median OS and PFS were 50 and 6.5 months, respectively. Patients with TC or ATC had significantly worse PFS than those with thymoma [hazard ratio (HR) 2.37; 95% confidence interval (CI): 1.18–4.76, P=0.013], but similar OS (P=0.55) and LF (P=0.729). Treated thymoma lesions had a lower hazard of DF than TC/ATC lesions, but this was not statistically significant (HR 0.59; 95% CI: 0.34–1.03, P=0.065). Lesions treated to a BED higher than 60 Gy had lower hazards of LF and DF, although this was not statistically significant (HR 0.29; 95% CI: 0.05–1.68, P=0.166 and HR 0.58; 95% CI: 0.3–1.1, P=0.096, respectively). Conclusions In our analysis, patients with TC or ATC had worse PFS than those with thymoma. Treated thymoma and TC/ATC lesions had similar hazards of LF, indicating similar radiation sensitivity in thymic lesions regardless of histology. There was a trend towards increased local control with higher BED regimens, but this did not reach statistical significance. Overall, our analysis points to the need for clinical trials on HFRT/SBRT for the treatment of these rare malignancies.

Project description:PurposeThis phase 1 trial aimed to identify the maximally tolerated hypofractionated dose schedule for postoperative radiation therapy (PORT) after radical prostatectomy. Secondary objectives included biochemical control and quality of life (QoL) measures.Methods and materialsPatients were treated on 1 of 3 dose levels (DLs): 56.4 Gy in 20 fractions (DL1), 51.2 Gy in 15 fractions (DL2), and 44.2 Gy in 10 fractions (DL3). Treatment was delivered to the prostate bed without pelvic nodal irradiation. Dose escalation followed a standard 3 + 3 design with an expansion for 6 additional patients at the maximally tolerated hypofractionated dose schedule. Acute dose-limiting toxicity (DLT) was defined as grade 3 toxicity lasting >4 days within 21 days of PORT completion; late DLT was defined as grade 4 gastrointestinal (GI) or genitourinary (GU) toxicity.ResultsBetween January 2018 and August 2019, 15 patients underwent radiation treatment: 3 on DL1, 3 on DL2, and 9 on DL3. The median follow-up was 24 months. There were no DLTs, and the maximally tolerated hypofractionated dose schedule was identified as DL3. Two of the 15 patients (13.3%) experienced biochemical failure (prostate-specific antigen >0.1). Ten of 15 patients (67%) had grade 2+ acute toxicities, consisting of transient GI toxicities. Three patients experienced late grade 2+ GI toxicity, and 5 patients experienced late grade 2+ GU toxicity. Late grade 3 GU toxicity occurred in 2 patients. There were no grade 4+ acute or late toxicities. There were no significant differences in GI measures of QoL, however, there was an increase in GU symptoms and corresponding decrease in GU QoL between 12 and 24 months.ConclusionsThe maximum tolerated hypofractionated dose schedule for hypofractionated PORT to the prostate bed was determined to be 44.2 Gy in 10 daily fractions. The most frequent clinically significant toxicities were late grade 2+ GU toxicities, which corresponded to a worsening of late GU QoL.

Project description:BackgroundResults from numerous clinical trials have led to a consensus that moderately hypofractionated radiation therapy is the ideal postoperative irradiation treatment plan in patients with breast cancer (BC). However, there are specific situations such as chest wall (with or without breast reconstruction) and regional node irradiation that still face obstacles in its widespread use. There is a lack of evidence supporting the use of moderately hypofractionated irradiation from the Latin American context. This study aims to describe the profile and clinical outcomes of patients treated with moderate hypofractionation for both early-stage (Stage I and II) and locally advanced BC (Stage III) regardless of the type of surgery in a Brazilian Oncology Center.MethodsAll patients with non-metastatic BC who were treated with moderately hypofractionated schedules of 40Gy in 15 fractions or 42.4Gy in 16 fractions between 2010 to 2019 at Hospital Sírio-Libanês, Brazil were retrospectively analyzed. The rates of local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distance recurrence-free survival (DRFS) and overall survival (OS) were estimated. Acute and late toxicity profiles were accessed for the entire cohort.FindingsA total of 670 patients were included. The median age was 57 years and the median follow-up time was 31 months. Most of the patients had stage I and II breast cancer, and 81.6% underwent breast-conserving surgery. Of the 123 women who underwent mastectomy treatment, 29% (n = 37) had immediate reconstruction with implants and 28% (n = 35) with autologous tissue. Seventy-one per cent of the patients presented luminal subtype tumour and 84.3% received adjuvant hormonal therapy. Chemotherapy was administered to almost half of the patients and all 80 patients with Her-2 positive disease received trastuzumab-based systemic therapy. One-third of patients received regional node irradiation; boost was performed in 41.1% of treatments. The 5-year LRFS, RRFS, DRFS and OS was 95.6%, 97.6%,92.2% and 95.9%, respectively. Acute and late side effects profile were mild and only 2.9% of patients developed grade 3 dermatitis. Among patients with breast implants, 11.4% had capsular contracture.InterpretationIn this Brazilian institution experience, moderately hypofractionated irradiation to the breast, chest wall (with or without breast reconstruction), and regional lymph nodes was safe and with an acceptable toxicity profile.FundingNone.

Project description:IntroductionThe recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or hypofractionated radiation therapy (MRgHRT) enables the safe delivery of high-dose radiation to central and UC lung lesions.MethodsPatients with UC or central lesions were treated with MRgSBRT/MRgHRT with real-time gating or adaptation. Central lesions were defined as per the Radiation Therapy Oncology Group and UC as per the HILUS study definitions: (1) group A or tumors less than 1 cm from the trachea and/or mainstem bronchi; or (2) group B or tumors less than 1 cm from the lobar bronchi. The Kaplan-Meier estimate and log-rank test were used to estimate survival. Associations between toxicities and other patient factors were tested using the Mann-Whitney U test and Fisher's exact test.ResultsA total of 47 patients were included with a median follow-up of 22.9 months (95% confidence interval: 16.4-29.4). Most (53%) had metastatic disease. All patients had central lesions and 55.3% (n = 26) had UC group A. The median distance from the proximal bronchial tree was 6.0 mm (range: 0.0-19.0 mm). The median biologically equivalent dose (α/β = 10) was 105 Gy (range: 75-151.2). The most common radiation schedule was 60 Gy in eight fractions (40.4%). Most (55%) had previous systemic therapy, 32% had immunotherapy and 23.4% had previous thoracic radiation therapy. There were 16 patients who underwent daily adaptation. The 1-year overall survival was 82% (median = not reached), local control 87% (median = not reached), and progression-free survival 54% (median = 15.1 mo, 95% confidence interval: 5.1-25.1). Acute toxicity included grade 1 (26%) and grade 2 (21%) with only two patients experiencing grade 3 (4.3%) in the long term. No grade 4 or 5 toxicities were seen.ConclusionsPrevious studies noted high rates of toxicity after SBRT to central and UC lung lesions, with reports of grade 5 toxicities. In our cohort, the use of MRgSBRT/MRgHRT with high biologically effective doses was well tolerated, with two grade 3 toxicities and no grade 4/5.

Project description:PURPOSE:Treatment strategies in palliation of pediatric cancer remain a significant challenge. In this study, we aimed to assess the efficacy and safety of a short course of hypofractionated radiation therapy (RT) for metastatic or recurrent childhood tumors. METHODS AND MATERIALS:A total of 104 lesions in 62 pediatric patients with metastatic or recurrent cancer were treated with a short hypofractionation schedule (>1 but ?5 fractions; ?3 Gy per fraction) between 2007 and 2017 in our institution. The primary endpoint was local control (LC). Other endpoints included treatment response, overall survival, progression-free survival, and toxicity. Toxicities were assessed using the Common Terminology Criteria for Adverse Events v.4.0. RESULTS:The most common histologies were neuroblastoma, comprising 50 of the 104 lesions (48.1%); osteosarcoma, 17 lesions (16.4%); and Ewing sarcoma, 13 lesions (12.5%). A median total dose of 24 Gy was delivered in a median of 5 fractions. Of 104 lesions, 26 (25.0%) were treated with stereotactic body radiation therapy, 24 (23.1%) with intensity modulated RT, and 48 (46.2%) with 2-dimensional RT or 3-dimensional conformal RT. A complete or partial response was observed in 63 (60.6%) of lesions, and stable disease was observed in 34 (32.7%). At a median follow-up of 8.7 months, 21 local failures occurred (20.2%). The 1- and 2-year LC rates were 74% and 68%, respectively. LC was better for tumors without previous irradiation (83% vs 57% with previous RT; P = .004). LC rates did not differ between RT techniques or total biologically effective dose with ?/? ratio of 10 (BED10) (?30 vs >30 Gy). At the time of analysis, 38 deaths in the cohort of 62 patients (61.3%) were recorded. The 1-year progression-free survival and overall survival rates were 31% and 44%, respectively. Incidence of any grade ?3 toxicity was 6.7% (7 of 104). No grade 5 events occurred. CONCLUSIONS:A short hypofractionation scheme yields effective disease control and treatment response with a favorable side effect profile. Select pediatric patients with symptomatic metastases or recurrent disease can be considered for a short course of palliative RT.

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Targeting Accuracy Considerations for Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy.

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