Gamma Knife Radiosurgery for Treatment of Brain Metastases during the COVID-19 Outbreak.

INTRODUCTION: The WHO declared 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a public health emergency of international concern. The National and Regional Health System has been reorganized, and many oncological patients died during this period or had to interrupt their therapies. This study summarizes a single-centre experience, during the COVID-19 period in Italy, in the treatment of brain metastases with Gamma Knife stereotactic radiosurgery (GKRS). METHODS: We retrospectively analysed our series of patients with brain metastases who underwent GKRS at the Niguarda Hospital from February 24 to April 24, 2020. RESULTS: We treated 30 patients with 66 brain metastases. A total of 22 patients came from home and 8 patients were admitted to the emergency room for urgent neurological symptoms. Duration of stay was limited to 0-1 day in 17 patients. We chose to treat a cluster of 9 patients, whose greater lesion exceeded 10 cm3, with 2-stage modality GKRS to minimize tumour recurrence and radiation necrosis. CONCLUSION: Due to the COVID-19 pandemic, the whole world is at a critical crossroads about the use of health care resources. During the COVID-19 outbreak, the deferral of diagnostic and therapeutic procedures and a work backlog in every medical specialty are the natural consequences of reservation of resources for COVID-19 patients. GKRS improved symptoms and reduced the need for open surgeries, allowing many patients to continue their therapeutic path and sparing beds in ICUs. Neurosurgeons have to take into account the availability of stereotactic radiosurgery to reduce hospital stay, conciliating safety for patients and operators with the request for health care coming from the oncological patients and their families.

Set-up errors and planning target volume margins in head and neck cancer radiotherapy: a clinical study of image guidance with on-line cone-beam computed tomography.

BACKGROUND: Set-up errors represent a source of uncertainty in head and neck (H&N) cancer radiotherapy. The present study evaluated set-up accuracy with the use of cone-beam computed tomography (CBCT) in order to establish the proper clinical target volume (CTV) to planning target volume (PTV) margins to be adopted. METHODS: Local set-up accuracy was analysed for 44 H&N cancer patients since the implementation of CBCT. An on-line correction protocol was adopted, with the first 3 scans used to correct systematic errors with a 3-mm action level. The overall mean displacement (M), the population systematic (Σ) and random (σ) errors and the 3D vector length were calculated. PTV margins were calculated according to the van Herk formula (2.5Σ + 0.7σ). RESULTS: A total of 420 CBCT scans were analysed. A systematic correction was needed in 43% of patients. The value of M was <1 mm in all directions; the values of Σ and σ ranged over 1-1.2 and 1.4-1.9 mm, respectively. Pre-correction PTV margins were 3.48, 4.08 and 4.33 mm along the 3 axes. The PTV margins calculated after online correction were <2.5 mm in all directions. CONCLUSIONS: Kilovoltage CBCT is effective in evaluating set-up accuracy in H&N patients. CTV-PTV margins of 5 mm are safe and are currently adopted at our centre; however, some special situations, such as re-irradiation or the close proximity of organs at risk and high-dose regions, could benefit from daily image registration and lower (i.e., 3 mm) margins.

MRI only in a patient with prostate cancer with bilateral metal hip prostheses: case study.

OBJECTIVE: To outline a practical method of performing prostate cancer radiotherapy in patients with bilateral metal hip prostheses with the standard resources available in a modern general hospital. The proposed workflow is based exclusively on magnetic resonance imaging (MRI) to avoid computed tomography (CT) artifacts. CASE DESCRIPTION: This study concerns a 73-year-old man with bilateral hip prostheses with an elevated risk prostate cancer. Magnetic resonance images with assigned electron densities were used for planning purposes, generating a synthetic CT (sCT). Imaging acquisition was performed with an optimized Dixon sequence on a 1.5T MRI scanner. The images were contoured by autosegmentation software, based on an MRI database of 20 patients. The sCT was generated assigning averaged electron densities to each contour. Two volumetric modulated arc therapy plans, a complete arc and a partial one, where the beam entrances through the prostheses were avoided for about 50° on both sides, were compared. The feasibility of matching daily cone beam CT (CBCT) with MRI reference images was also tested by visual evaluations of different radiation oncologists. CONCLUSIONS: The use of magnetic resonance images improved accuracy in targets and organs at risk (OARs) contouring. The complete arc plan was chosen because of 10% lower mean and maximum doses to prostheses with the same planning target volume coverage and OAR sparing. The image quality of the match between performed CBCTs and MRI was considered acceptable. The proposed method seems promising to improve radiotherapy treatments for this complex category of patients.

Gantry angle dependence in IMRT pre-treatment patient-specific quality controls.

Intensity Modulated Radiation Therapy (IMRT) is a complex treatment modality that requires pre-treatment patient-specific quality control (QC) in order to assess a correct treatment delivery. The aim of this work is to investigate pre-treatment patient-specific per-field QCs performed with an on-board EPID at the gantry angle of 0° and at the treatment ones, and to asses if measurements executed at 0° are able to guarantee a correct treatment. Ten patients with prostate cancer were evaluated. Two "verification" plans were created for each patient in order to calculate the dose at the EPID surface: one with all fields positioned at 0° and one with all fields at the actual treatment angles. EPID's mechanical shifts due to gravity effects were always taken into account and corrected. 0 and no-0 plans were compared using a gamma-index method (3%, 3 mm). The gamma index was found dependent on gantry angles but the difference between 0 and no-0 samples was small (-0.3% mean value) and the criteria of acceptability of the gamma method was always satisfied for every field delivered at angles different from 0. Therefore patient-specific pre-treatment QCs should be done at treatments angles, but, if periodical quality assurance is performed on dynamic MLC for different gantry angles, this requirement was shown not strictly mandatory and pre-treatment IMRTQC can be reasonably executed at 0° angles too.

Late fecal incontinence after high-dose radiotherapy for prostate cancer: better prediction using longitudinal definitions.

PURPOSE: To model late fecal incontinence after high-dose prostate cancer radiotherapy (RT) in patients accrued in the AIROPROS (prostate working group of the Italian Association of Radiation Oncology) 0102 trial using different endpoint definitions. METHODS AND MATERIALS: The self-reported questionnaires (before RT, 1 month after RT, and every 6 months for ≤3 years after RT) of 586 patients were available. The peak incontinence (P_INC) and two longitudinal definitions (chronic incontinence [C_INC], defined as the persistence of Grade 1 or greater incontinence after any Grade 2-3 event; and mean incontinence score [M_INC], defined as the average score during the 3-year period after RT) were considered. The correlation between the clinical/dosimetric parameters (including rectal dose-volume histograms) and P_INC (Grade 2 or greater), C_INC, and M_INC of ≥1 were investigated using multivariate logistic analyses. Receiver operating characteristic curves and the area under the curve were used to assess the predictive value of the different multivariate models. RESULTS: Of the 586 patients, 36 with a Grade 1 or greater incontinence score before RT were not included in the present analysis. Of the 550 included patients, 197 (35.8%) had at least one control with a Grade 1 or greater incontinence score (M_INC >0). Of these 197 patients, 37 (6.7%), 22 (4.0%), and 17 (3.1%) were scored as having P_INC, M_INC ≥1, and C_INC, respectively. On multivariate analysis, Grade 2 or greater acute incontinence was the only predictor of P_INC (odds ratio [OR], 5.9; p = .0009). Grade 3 acute incontinence was predictive of C_INC (OR, 9.4; p = .02), and percentage of the rectal volume receiving >40 Gy of ≥80% was predictive of a M_INC of ≥1 (OR, 3.8; p = .008) and of C_INC (OR, 3.6; p = .03). Previous bowel disease, previous abdominal/pelvic surgery, and the use of antihypertensive (protective factor) correlated highly with both C_INC and M_INC ≥1. The predictive values of the models for C_INC (area under the curve, 0.83) and M_INC ≥1 (area under the curve, 0.73) were greater than the ones for P_INC (area under the curve, 0.62) and more reliable (p = .0001-.0003 against p = .02). Nomograms for the two longitudinal definitions were derived. CONCLUSIONS: The longitudinal definitions of fecal incontinence (C_INC and M_INC ≥1) were helpful in accounting for both the persistence and the severity of the incontinence. A significant fraction of peak events was consequential to acute incontinence, and a longer duration of symptoms mainly depended on the rectal dose bath (percentage of rectal volume receiving >40 Gy), and pretreatment clinical factors.

Increasing the risk of late rectal bleeding after high-dose radiotherapy for prostate cancer: the case of previous abdominal surgery. Results from a prospective trial.

PURPOSE: To evaluate and discuss the role of specific types of abdominal surgery (SURG) before radical radiation therapy as a risk factor for late rectal toxicity in prostate cancer patients. METHODS: Results concerning questionnaire-based scored late bleeding and faecal incontinence in 718 patients with a complete follow-up of 36 months were analysed, focusing on the impact of specific pre-radiotherapy abdominal/pelvic surgery procedures. Patients were accrued in the prospective study AIROPROS 0102. Different types of surgery (rectum-sigma resection, kidney resection, cholecystectomy or appendectomy) were considered as covariates together with a number of different parameters previously found to be predictive of late toxicity and including clinical as well as dosimetric parameters. Univariate (UVA) and multivariate (MVA) logistic analyses were carried out. RESULTS: In total 69/718 patients were previously submitted to one or more surgical procedures, mostly cholecystectomy (n=21) and appendectomy (n=27). Actuarial incidences of G2-G3 and G3 bleeding were 52 (7.2%) and 24 (3.3%) respectively; 19 (2.6%) chronic incontinence events were registered. Cholecystectomy was found to be highly correlated with late rectal bleeding at UVA: OR=4.3 and p=0.006 for G2-G3 and OR=5.4 and p=0.01 for G3. Considering MVA (including dosimetric and clinical factors), G2-G3 bleeding was significantly correlated to cholecystectomy (OR=6.5, p=0.002), V75 Gy (OR=1.074, p=0.003) and secondarily with appendectomy (OR=2.7, p=0.10), presence of acute radioinduced rectal bleeding (OR=1.70, p=0.21) and androgen deprivation (OR=0.67, p=0.25). Appendectomy (OR=5.9, p=0.004) and cholecystectomy (OR=5.5, p=0.016) were very strong predictors of G3 bleeding with V75 Gy playing a less significant role (OR=1.037, p=0.26). Conversely, no specific surgery was correlated with actuarial or chronic incontinence. CONCLUSIONS: This analysis highlights previous SURG as the best predictor of late rectal bleeding. Among the different types of abdominal surgery, cholecystectomy and appendectomy play the major role, especially for severe late bleeding.

Inclusion of clinical risk factors into NTCP modelling of late rectal toxicity after high dose radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: To fit an NTCP model including clinical risk factors to late rectal toxicities after radiotherapy for prostate cancer. METHODS AND MATERIALS: Data of 669 patients were considered. The probability of late toxicity within 36months (bleeding and incontinence) was fitted with the original and a modified Logit-EUD model, including clinical factors by fitting a subset specific TD(50)s: the ratio of TD(50)s with and without including the clinical variable was the dose-modifying factor (D(mod)). RESULTS: Abdominal surgery (surg) was a risk factor for G2-G3 bleeding, reflecting in a TD(50)=82.7Gy and 88.4Gy for patients with and without surg (D(mod)=0.94; 0.90 for G3 bleeding); acute toxicity was also an important risk factor for G2-G3 bleeding (D(mod)=0.93). Concerning incontinence, surg and previous diseases of the colon were the clinical co-factors. D(mod)(surg) and D(mod)(colon) were 0.50 and 0.42, respectively for chronic incontinence and 0.73 and 0.64, respectively for mean incontinence score ⩾1. Best-fit n values were 0.03-0.05 and 1 for bleeding and incontinence, respectively. The inclusion of clinical factors always improved the predictive value of the models. CONCLUSIONS: The inclusion of predisposing clinical factors improves NTCP estimation; the assessment of other clinical and genetic factors will be useful to reduce parameter uncertainties.

Clinical and dosimetric predictors of late rectal toxicity after conformal radiation for localized prostate cancer: results of a large multicenter observational study.

PURPOSE: Assessing the predictors of late rectal toxicity after high-dose conformal radiotherapy for prostate cancer. METHODS: One thousand one hundred thirty-two patients entered a prospective observational multicentric study; late rectal toxicity was evaluated by a self-reported questionnaire. Results concerning bleeding and faecal incontinence of 718/1132 patients with a complete follow-up at 36 months were analysed. The correlation between a number of clinical-dosimetric parameters and moderate/severe toxicity was investigated by univariate and multivariate logistic analyses. RESULTS: Fifty-two (7.2%) and 57/718 (7.9%) patients were scored as moderate/severe bleeders and faecal incontinents, respectively; 19/57 incontinent patients showed persistent incontinence at 36 months. Bleeding was mainly correlated with V75 Gy while severe bleeding was mainly correlated with the previous abdominal/pelvic surgery; a different rectal dose-volume relationship in the two groups of patients (with/without surgery) was found. Moderate/severe acute toxicity was weakly correlated to late bleeding. The best predictor of faecal incontinence was acute toxicity (OR=4 and 7 for chronic and actuarial incontinence, respectively). CONCLUSION: The application of rectal dose-volume constraints limited the incidence of rectal bleeding. The risk of bleeding may be further reduced by limiting V75 Gy<5% and, in the case of patients previously submitted to abdominal/pelvic surgery, V70 Gy<15-20%. Faecal incontinence seems to be mainly a consequential effect after acute toxicity.