How LEM-based RBE and dose-averaged LET affected clinical outcomes of sacral chordoma patients treated with carbon ion radiotherapy.

PURPOSE/OBJECTIVE: To understand the role of relative biological effectiveness (RBE) and dose-averaged linear energy transfer (LETd) distributions in the treatment of sacral chordoma (SC) patients with carbon ion radiotherapy (CIRT). MATERIAL/METHODS: Clinical plans of 50 SC patients consecutively treated before August 2018 with a local effect model-based optimization were recalculated with the modified microdosimetric kinetic RBE model (mMKM). Twenty-six patients were classified as progressive disease and the relapse volume was contoured on the corresponding follow-up diagnostic sequence. The remaining 24 patients populated the control group. Target prescription dose (DRBE|50%), near-to-minimum- (DRBE|95%) and near-to-maximum- (DRBE|2%) doses were compared between the two cohorts in both RBE systems. LETd distribution was evaluated for in-field relapsed cases with respect to the control group. RESULTS: Target DMKM|50% and DMKM|95% were respectively 10% and 18% lower than what we aimed at. Dosimetric evaluators showed no significant difference, in neither of the RBE frameworks, between relapsed and control sets. Half of the relapse volumes were located in a well-covered high dose region. On average, over these cases, median target LETd was significantly lower than the control cohort mean value (27 vs 30 keV/µm). Most notably, the volume receiving dose from high-LET particles (>50 keV/µm) lay substantially below recently reported data in the literature. CONCLUSION: A combined multi model RBE- and LET-based optimization could play a key role in the enhancement of the therapeutic ratio of CIRT for large radioresistant tumors such as sacral chordomas.

Quality of Life in Early Breast Cancer Patients: A Prospective Observational Study Using the FACT-B Questionnaire.

BACKGROUND/AIM: Quality of life (QoL) in early breast cancer (BC) treatment may be affected by acute and late toxicities. This study evaluated the impact of radiotherapy (RT) schedules, treatment-related toxicities, hormone therapy (HT) and age on QoL. PATIENTS AND METHODS: Ninety-five patients answered the FACT-B 4.0 questionnaire. Acute or late toxicities were recorded at each follow-up visit. RESULTS: The median trend of the QoL subscales was stable during all questionnaires. HT negatively impacted on Functional Assessment of Cancer Therapy-General-Total, functional and emotional wellbeing. No difference was recorded between RT schedules and toxicity. No significant differences for age were detected in QoL. CONCLUSION: RT seems not to influence QoL of BC patients, in terms of fractionation regimen or RT-related side-effects. Moreover, women having systemic HT experienced a QoL worse than patients treated with RT only. Further and long-term protocols are needed to improve the validity of the tool.

Multimodal Evaluation of Voice Outcome in Early Glottic Cancers Treated With Definitive Radiotherapy.

Background/Aim: We employed a multimodal evaluation of voice outcome (MEVO) model to assess long-term voice outcome in early glottic cancer (EGC) patients treated with primary radiotherapy (RT). The model consisted of objective and subjective vocal evaluation during follow-up, by a dedicated Speech Pathologist and Speech Therapist. Patients and Methods: MEVO methodology includes Self-perception Voice Handicap Index (VHI-30), evaluation of parameters Grade (G), Roughness (R), Breathiness (B), Asthenia (A) and Strain (S) according to GRBAS scale, objective analysis and aerodynamics using the PRAAT software and laryngeal evaluation with videostroboscope (VS). Results: The MEVO methodology was described and tested on a sample of 10 EGCs submitted to definitive RT (total dose 66-70 Gy). Mean follow-up was 48.9 months (range=9-115). VHI was mild-moderate in 90% of patients; overall voice function (GRBAS) was normal-mildly impaired in 70% of patients; VS evaluation showed normal vocal cord motion in 90% of patients, but complete glottic closure in 60%. PRAAT scores confirmed these findings. Conclusion: A multidimensional voice evaluation is time consuming, but useful to objectify vocal impact of radiotherapy. The MEVO model allowed to quantify vocal dysfunction, showing a good objective vocal outcome.

A Feasibility Study for in vivo Dosimetry Procedure in Routine Clinical Practice.

PURPOSE: The aim of the in vivo dosimetry, during the fractionated radiation therapy, is the verification of the correct dose delivery to patient. Nowadays, in vivo dosimetry procedures for photon beams are based on the use of the electronic portal imaging device and dedicated software to elaborate electronic portal imaging device images. METHODS: In total, 8474 in vivo dosimetry tests were carried out for 386 patients treated with 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and volumetric modulated arc therapy techniques, using the SOFTDISO. SOFTDISO is a dedicated software that uses electronic portal imaging device images in order to (1) calculate the R index, that is, the ratio between daily reconstructed dose and the planned one at isocenter and (2) perform a γ-like analysis between the signals, S, of a reference electronic portal imaging device image and that obtained in a daily fraction. It supplies 2 indexes, the percentage γ% of points with γ < 1 and the mean γ value, γmean. In γ-like analysis, the pass criteria for the signals agreement ΔS% and distance to agreement Δd have been selected based on the clinical experience and technology used. The adopted tolerance levels for the 3 indexes were fixed in 0.95 ≤ R ≤ 1.05, γ% ≥ 90%, and γmean ≤ 0.5. RESULTS: The results of R ratio, γ-like, and a visual inspection of these data reported on a monitor screen permitted to individuate 2 classes of errors (1) class 1 that included errors due to inadequate standard quality controls and (2) class 2, due to patient morphological changes. Depending on the technique and anatomical site, a maximum of 18% of tests had at least 1 index out of tolerance; once removed the causes of class-1 errors, almost all patients (except patients with 4 lung and 2 breast cancer treated with 3-dimensional conformal radiotherapy) presented mean indexes values ([Formula: see text], [Formula: see text]%, and [Formula: see text] ) within tolerance at the end of treatment course. Class-2 errors were found in some patients. CONCLUSIONS: The in vivo dosimetry procedure with SOFTDISO resulted easily implementable, able to individuate errors with a limited workload.

Assessment of bowel and anal sphincter function after neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

PURPOSE: To report long-term effects on anorectal function and bowel disorders and late toxicity rate of preoperative chemoradiotherapy in patients with locally advanced rectal cancer. METHODS: Between 2000 and 2016, 201 patients treated with different neoadjuvant schedules of chemotherapy and radiotherapy doses were retrospectively analyzed. The Memorial Sloan-Kettering Cancer Center score was used for the evaluation of anal sphincter function. RESULTS: The median follow-up time was 68 months (interquartile range 35-113 months). Radical resection was performed in 188 (93.5%) patients with a pathologic complete response rate of 26.4%. Overall sphincter function resulted excellent in 105 (52.2%) patients, good in 13 (6.5%), fair in 10 (5.0%), and poor (incontinence) in 40 (19.9%), with a persistent stoma rate of 16.4%. A further evaluation on 194 patients showed an improvement of sphincter function after 2 years in 11.9% of them. Seventy-three patients presenting stoma or poor sphincter function were re-evaluated for quality of life (QoL) indexes. Twenty-one (29%), 19 (26%), and 24 (33%) of them declared some variations concerning well-being, fatigue, and ability to perform daily activities. The 5-year overall survival, disease-free survival, and local recurrence rates were 88.0% ± 2.6%, 86.3% ± 2.5%, and 94.6% ± 1.9%, respectively. CONCLUSIONS: In our study, neoadjuvant chemoradiotherapy was associated with good results in terms of sphincter function, late toxicities, and QoL indexes. A routine use of assessment scales could contribute to a better selection of patients with increased risk of developing functional disorders who could benefit from neoadjuvant therapy.

Hippocampal sparing approach in fractionated stereotactic brain VMAT radio therapy: A retrospective feasibility analysis.

Volumetric Modulated Arc Therapy (VMAT) techniques for fractioned stereotactic brain radiotherapy (FSBRT) can achieve highly conformal dose distribution to intracranial lesions. However, they can potentially increase the dose to hippocampus (H) causing neurocognitive toxicity during the first four months after irradiation. The purpose of this study was to assess the feasibility of hippocampal-sparing (HS) treatment plans in 22 patients with brain metastasis treated with VMAT technique. Firstly, we retrospectively analyzed hippocampal doses in all 22 VMAT original (not hippocampal-sparing, NHS) plans. Plans with hippocampal dose exceeding constraints (9 out of 22) were re-planned considering dose constraints on the hippocampus (H) and on hippocampal avoidance zone (HAZ) generated using 5 mm isotropic margin to the hippocampus. Conformity (CI) and homogeneity indexes (HI) on the target and MUs, were maintained as close as possible to the original plans. Mean CINHS and CIHS obtained were: 0.79 ± 0.11 and 0.81 ± 0.10, respectively (P = 0.75); mean HINHS and HIHS were 1.05 ± 0.02 and 1.04 ± 0.01 respectively (P = 0.72). In both sets of plans, the mean MU values were similar: 1033 ± 275 and 1022 ± 234 for NHS and HS respectively. In HS plans, the mean hippocampal dose was decreased by an average of 35%. After replanning, the Dmax (21.3 Gy) for HAZ and H was met by 45% (4/9) and 78% (7/9) of the NHS plans, respectively. The worst results were obtained for cases with target volumes extention closer than 12 mm to H, because of the difficulty to spare hippocampus without compromising target coverage. After replanning D40% constraint value (7.3 Gy) was met by all the 9 NHS plans. In conclusion, this study suggests that an hippocampal-sparing approach to FSBRT is feasible resulting in a decrease in the dose to the hippocampus without any loss in conformity or increase in treatment time.