Selection of motion management in liver stereotactic body radiotherapy and its impact on treatment time.

Background and purpose: Reduction of respiratory tumour motion is important in liver stereotactic body radiation therapy (SBRT) to reduce side effects and improve tumour control probability. We have assessed the distribution of use of voluntary exhale breath hold (EBH), abdominal compression (AC), free breathing gating (gating) and free breathing (FB), and the impact of these on treatment time. Materials and Methods: We assessed all patients treated in a single institution with liver SBRT between September 2017 and September 2021. Data from pre-simulation motion management assessment using fluoroscopic assessment of liver dome position in repeat breath holds, and motion with and without AC, was reviewed to determine liver dome position consistency in EBH and the impact of AC on motion. Treatment time was assessed for all fractions as time from first image acquisition to last treatment beam off. Results: Of 136 patients treated with 145 courses of liver SBRT, 68 % were treated in EBH, 20 % with AC, 7 % in gating and 5 % in FB. AC resulted in motion reduction < 1 mm in 9/26 patients assessed. Median treatment time was higher using EBH (39 min) or gating (42 min) compared with AC (30 min) or FB (24 min) treatments. Conclusions: Motion management in liver SBRT needs to be assessed per-patient to ensure appropriate techniques are applied. Motion management significantly impacts treatment time therefore patient comfort must also be taken into account when selecting the technique for each patient.

High-dose-rate brachytherapy boost for locally advanced cervical cancer: Oncological outcome and toxicity analysis of 4 fractionation schemes.

PURPOSE: Brachytherapy (BT) boost after radio-chemotherapy (RCT) is a standard of care in the management of locally advanced cervical cancer (LACC). As there is no consensus on high-dose-rate (HDR) BT fractionation schemes, our aim was to report the oncological outcome and toxicity profile of four different schemes using twice-a-day (BID) HDR-BT. PATIENTS AND METHODS: This was an observational, retrospective, single institution study for patients with LACC receiving a HDR-BT boost. The latter was performed with a single implant and single imaging done on day 1. The different fractionation schemes were: 7 Gy + 4x3.5 Gy (group 1); 7 Gy + 4x4.5 Gy (group 2); 3x7Gy (group 3) and 3x8Gy (group 4). Local (LFS), nodal (NFS) and metastatic (MFS) recurrence-free survival as well as progression-free survival (PFS) and overall survival (OS) were analyzed. Acute (≤6 months) and late toxicities (>6 months) were reported. RESULTS: From 2007 to 2018, 191 patients were included. Median follow-up was 57 months [45-132] and median EQD210D90CTVHR was 84, 82 and 90 Gy for groups 2, 3 and 4 respectively (dosimetric data missing for group 1). The 5-year LFS, NFS, MFS, PFS and OS were 85% [81-90], 83% [79-86], 70% [67-73], 61% [57-64] and 75% [69-78] respectively, with no significant difference between the groups. EQD210D90CTVHR < 85 Gy was a prognostic factor for local recurrence in univariate analysis (p = 0.045). The rates of acute/late grade ≥ 2 urinary, digestive and gynecological toxicities were 9%/15%, 3%/15% and 9%/25% respectively. CONCLUSION: Bi-fractionated HDR-BT boost seems feasible with good oncological outcome and slightly more toxicity after dose escalation.

Intensity modulated radiotherapy for anal canal squamous cell carcinoma: A 16-year single institution experience.

INTRODUCTION: To report long-term efficacy and adverse events (AEs) associated with intensity modulated radiotherapy (IMRT) for patients with anal canal squamous cell carcinoma (ASCC). MATERIALS AND METHODS: This was a retrospective review of patients with ASCC who received curative-intent IMRT and concurrent chemotherapy (98%) between 2003 and 2019. Overall survival (OS), colostomy-free survival (CFS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The cumulative incidence of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. Acute and late AEs were recorded per National Cancer Institute Common Terminology Criteria for AEs. RESULTS: 127 patients were included. The median patient age was 63 years (interquartile range [IQR] 55-69) and 79% of patients were female. 33% of patients had T3-4 disease and 68% had clinically involved pelvic or inguinal lymph nodes (LNs).The median patient follow-up was 47 months (IQR: 28-89 months). The estimated 4-year OS, CFS, and PFS were 81% (95% confidence interval [CI]: 73%-89%), 77% (95% CI: 68%-86%), and 78% (95% CI: 70%-86%), respectively. The 4-year cumulative incidences of LR, LRR, and DM were 3% (95% CI: 1%-9%), 9% (95% CI: 5%-17%), and 10% (95% CI: 6%-18%), respectively. Overall treatment duration greater than 39 days was associated with an increased risk of LRR (Hazard Ratio [HR]: 5.2, 95% CI: 1.4-19.5, p = 0.015). The most common grade 3+ acute AEs included hematologic (31%), gastrointestinal (GI) (17%), dermatologic (16%), and pain (15%). Grade 3+ late AEs included: GI (3%), genitourinary (GU) (2%), and pain (1%). Current smokers were more likely to experience grade 3+ acute dermatologic toxicity compared to former or never smokers (34% vs. 7%, p < 0.001). CONCLUSIONS: IMRT was associated with favorable toxicity rates and long-term efficacy. These data support the continued utilization of IMRT as the preferred treatment technique for patients with ASCC.

Multiple sclerosis as differential diagnosis of radionecrosis for post-irradiation brain lesions: A case report.

INTRODUCTION: Demyelination can occur after brain radiotherapy in tissue adjacent to irradiated tumours. To date, no correlation has been found between conventional-dose radiotherapy and the development of multiple sclerosis, but radiotherapy could be a triggering factor among women with known multiple sclerosis. To the best of our knowledge, this is the first well-documented case of this association with a dosimetric analysis. CASE PRESENTATION: The case we report here describes the development of multiple sclerosis in a 36-year-old woman without significant past medical history 3 months after the last session of fractionated stereotactic radiotherapy for a pituitary macroadenoma. Our dosimetric analysis suggests that all the multiple sclerosis lesions occurred in the brain regions irradiated with a mean biologically effective dose (BED2) of 33.9 Gy (27.3-49.6 Gy). CONCLUSION: Consequently special caution towards radiotherapy is required among patients with demyelinating illnesses or for 35-45-year-old women who are at risk. In addition, multiple sclerosis lesions can look like metastases. We should therefore keep differential diagnoses in mind in order not to make mistakes that would delay treatment.

Determining RBE for development of lung fibrosis induced by fractionated irradiation with carbon ions utilizing fibrosis index and high-LET BED model.

BACKGROUND AND PURPOSES: Carbon ion radiotherapy (CIRT) with raster scanning technology is a promising treatment for lung cancer and thoracic malignancies. Determining normal tissue tolerance of organs at risk is of utmost importance for the success of CIRT. Here we report the relative biological effectiveness (RBE) of CIRT as a function of dose and fractionation for development of pulmonary fibrosis using well established fibrosis index (FI) model. MATERIALS AND METHODS: Dose series of fractionated clinical quality CIRT versus conventional photon irradiation to the whole thorax were compared in C57BL6 mice. Quantitative assessment of pulmonary fibrosis was performed by applying the FI to computed tomography (CT) data acquired 24-weeks post irradiation. RBE was calculated as the ratio of photon to CIRT dose required for the same level of FI. Further RBE predictions were performed using the derived equation from high-linear energy transfer biologically effective dose (high-LET BED) model. RESULTS: The averaged lung fibrosis RBE of 5-fraction CIRT schedule was determined as 2.75 ±â€¯0.55. The RBE estimate at the half maximum effective dose (RBEED50) was estimated at 2.82 for clinically relevant fractional sizes of 1-6 Gy. At the same dose range, an RBE value of 2.81 ±â€¯0.40 was predicted by the high-LET BED model. The converted biologically effective dose (BED) of CIRT for induction of half maximum FI (BEDED50) was identified to be 58.12 Gy3.95. In accordance, an estimated RBE of 2.88 was obtained at the BEDED50 level. The LQ model radiosensitivity parameters for 5-fraction was obtained as αH = 0.3030 ±â€¯0.0037 Gy-1 and ßH = 0.0056 ±â€¯0.0007 Gy-2. CONCLUSION: This is the first report of RBE estimation for CIRT with the endpoint of pulmonary fibrosis in-vivo. We proposed in present study a novel way to mathematically modeling RBE by integrating RBEmax and α/ßL based on conventional high-LET BED conception. This model well predicted RBE in the clinically relevant dose range but is sensitive to the uncertainties of α/ß estimates from the reference photon irradiation (α/ßL). These findings will assist to eliminate current uncertainties in prediction of CIRT induced normal tissue complications and builds a solid foundation for development of more accurate in-vivo data driven RBE estimates.

Stereotactic Body Radiotherapy for Medically Inoperable Stage I-II Non-Small Cell Lung Cancer: The Mayo Clinic Experience.

OBJECTIVE: To examine disease control and survival after stereotactic body radiotherapy (SBRT) for medically inoperable, early-stage non-small cell lung cancer (NSCLC) and determine associations of pretreatment 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) maximum standardized uptake values (SUVmax), biologically effective dose, and mediastinal staging with disease control and survival outcomes. PATIENTS AND METHODS: We retrospectively reviewed the cases of consecutive patients with FDG-PET-staged, medically inoperable NSCLC treated with SBRT at our institution between January 1, 2008, and August 4, 2014. Cumulative incidences of recurrence were estimated, accounting for the competing risk of death. Associations of SUVmax, biologically effective dose, and mediastinal staging with outcomes were evaluated using Cox proportional hazards regression models. RESULTS: Among 282 patients, 2-year cumulative incidences of recurrence were 4.9% (95% CI, 2.6%-8.3%) for local, 9.8% (95% CI, 6.3%-14.2%) for nodal, 10.8% (95% CI, 7.0%-15.5%) for ipsilateral lung, 6.0% (3.3%-9.8%) for contralateral lung, 9.7% (95% CI, 6.3%-14.0%) for distant recurrence, and 26.1% (95% CI, 20.4%-32.0%) for any recurrence. The 2-year overall survival was 70.4% (95% CI, 64.5%-76.8%), and the 2-year disease-free survival was 51.2% (95% CI, 44.9%-58.5%). Risk of any recurrence was significantly higher for patients with higher SUVmax (hazard ratio [per each doubling], 1.29 [95% CI, 1.05-1.59]; P=.02). A similar association with SUVmax was observed when considering the composite outcome of any recurrence or death (hazard ratio, 1.23 [95% CI, 1.05-1.44]; P=.01). The SUVmax was not significantly associated with other outcomes (P≥0.69). Two-year cumulative incidences of local recurrence for patients receiving 48 Gy in 4 fractions, 54 Gy in 3 fractions, or 50 Gy in 5 fractions were 1.7% (95% CI, 0.3%-5.6%), 3.7% (95% CI, 0.7%-11.4%), and 15.3% (95% CI, 5.9%-28.9%), respectively (P=.02); this difference was independent of lesion size (P=.02). CONCLUSION: Disease control was excellent for patients who received SBRT for early-stage NSCLC, and this series represents the largest single-institution experience from the United States on SBRT for early-stage inoperable NSCLC. Higher pretreatment FDG-PET SUVmax was associated with increased risk of any recurrence, and the 50 Gy in 5 fractions dose prescription was associated with increased risk of local recurrence.