Evaluation of results and costs of high precision radiotherapy (VMAT) compared with conventional radiotherapy (3D) in the treatment of cancer patients with spinal cord compression of metastatic origin.

Background: The aim of this study was to evaluate the results and economic costs of using volumetric modulated arc therapy (VMAT) (5 fr × 5 Gy), compared with other conventional 3D radiotherapy schemes such as "5 × 4 Gy" and "10 × 3 Gy". Materials and methods: The data about the direct costs for the public health system was obtained from the Economic Information "Management per Patient" System available at the Integrated Health Organization Ezkerraldea Enkarterri Cruces. It is a model of real costs per patient which uses a bottom-up methodology which connects all sources of information generated in clinical practice, integrating healthcare information with economic information. This system presents the real cost per individualized patient, and shows the traceability of all clinical care. The costs of "typical patients" requiring hospital admission were identified for each of the three radiotherapy schemes based on the clinical activity and the material and human resources that were used. Results: The 5 × 5 Gy scheme has a cost of EUR 4,801.48, which is 1.64% higher (EUR 77) than the "5 × 4 Gy" scheme (EUR 4,724.05). The "10 × 3 Gy" scheme has a cost of EUR 8,394.61, which is 74.8% higher (EUR 3,593) than the "5 × 5 Gy" scheme. The main cost factor in the "10 × 3 Gy" scheme is hospitalization, since patients are at hospital for 2 weeks compared with 1 week in the "5 × 5 Gy" scheme. Conclusions: The cost per patient of the VMAT "5 × 5 Gy" radiotherapy scheme is notably lower than that of the "10 × 3 Gy" scheme (conventional 3D radiotherapy), with the advantage of being administered in half the time. In relation to the scheme with 5 Gy × 4 sessions, the cost is similar to that of the "5 × 5 Gy" scheme.

Dosimetric Evaluation of Commercially Available Flat vs. Self-Produced 3D-Conformal Silicone Boluses for the Head and Neck Region.

Background: Boluses are routinely used in radiotherapy to modify surface doses. Nevertheless, considerable dose discrepancies may occur in some cases due to fit inaccuracy of commercially available standard flat boluses. Moreover, due to the simple geometric design of conventional boluses, also surrounding healthy skin areas may be unintentionally covered, resulting in the unwanted dose buildup. With the fused deposition modeling (FDM) technique, there is a simple and possibly cost-effective way to solve these problems in routine clinical practice. This paper presents a procedure of self-manufacturing bespoke patient-specific silicone boluses and the evaluation of buildup and fit accuracy in comparison to standard rectangular commercially available silicone boluses. Methods: 3D-conformal silicone boluses were custom-built to cover the surgical scar region of 25 patients who received adjuvant radiotherapy of head and neck cancer at the University Hospital Würzburg. During a standard CT-based planning procedure, a 5-mm-thick 3D bolus contour was generated to cover the radiopaque marked surgical scar with an additional safety margin. From these digital contours, molds were 3D printed and poured with silicone. Dose measurements for both types of boluses were performed with radiochromic films (EBT3) at three points per patient-at least one aimed to be in the high-dose area (scar) and one in the lower-dose area (spared healthy skin). Surface-bolus distance, which ideally should not be present, was determined from cone-beam CT performed for positioning control. The dosimetric influence of surface-bolus distance was also determined on slab phantom for different field sizes. The trial was performed with hardware that may be routinely available in every radiotherapy department, with the exception of the 3D printer. The required number of patients was determined based on the results of preparatory measurements with the help of the statistical consultancy of the University of Würzburg. The number of measuring points represents the total number of patients. Results: In the high-dose area of the scar, there was a significantly better intended dose buildup of 2.45% (95%CI 0.0014-0.0477, p = 0.038, N = 30) in favor of a 3D-conformal bolus. Median distances between the body surface and bolus differed significantly between 3D-conformal and commercially available boluses (3.5 vs. 7.9 mm, p = 0.001). The surface dose at the slab phantom did not differ between commercially available and 3D-conformal boluses. Increasing the surface-bolus distance from 5 to 10 mm decreased the surface dose by approximately 2% and 11% in the 6 × 6- and 3 × 3-cm2 fields, respectively. In comparison to the commercially available bolus, an unintended dose buildup in the healthy skin areas was reduced by 25.9% (95%CI 19.5-32.3, p < 0.01, N = 37) using the 3D-conformal bolus limited to the region surrounding the surgical scar. Conclusions: Using 3D-conformal boluses allows a comparison to the commercially available boluses' dose buildup in the covered areas. Smaller field size is prone to a larger surface-bolus distance effect. Higher conformity of 3D-conformal boluses reduces this effect. This may be especially relevant for volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) techniques with a huge number of smaller fields. High conformity of 3D-conformal boluses reduces an unintended dose buildup in healthy skin. The limiting factor in the conformity of 3D-conformal boluses in our setting was the immobilization mask, which was produced primarily for the 3D boluses. The mask itself limited tight contact of subsequently produced 3D-conformal boluses to the mask-covered body areas. In this respect, bolus adjustment before mask fabrication will be done in the future setting.

Sparing the hippocampus and the hypothalamic- pituitary region during whole brain radiotherapy: a volumetric modulated arc therapy planning study.

BACKGROUND: Feasibility testing of a simultaneous sparing approach of hippocampus, hypothalamus and pituitary gland in patients undergoing whole-brain radiotherapy (WBRT) with and without a concomitant boost to metastatic sites. INTRODUCTION: Cognitive impairment and hormonal dysfunction are common side effects of cranial radiotherapy. A reduced dose application to the patho-physiologically involved functional brain areas, i.e. hippocampus, hypothalamus and pituitary gland, could reduce these common side effects. While hippocampal sparing is already a common practice to improve cognitive outcome, technical experience of additional combined sparing of the hypothalamus/pituitary gland (HT-P) is insufficient. METHODS: Twenty patients were included in the planning study. In 11 patients, a total dose of 36 Gy of WBRT (2 Gy per fraction) plus a simultaneous integrated boost (SIB) of 9 Gy (0.5 Gy per fraction, total dose: 45 Gy) to the brain metastases was applied. In 9 patients, prophylactic cranial irradiation (PCI) was simulated with a total dose of 30 Gy (2 Gy per fraction). In both patient cohorts, a sparing approach of the hippocampus and the HT-P area was simulated during WBRT. For all treatment plans, volumetric modulated arc therapy (VMAT) was used. Quality assurance included assessment of homogeneity, conformality and target coverage. RESULTS: The mean dose to the hippocampus and HT-P region was limited to less than 50% of the prescribed dose to the planning target volume (PTV) in all treatment plans. Dose homogeneity (HI) of the target volume was satisfying (median HI = 0.16 for WBRT+SIB and 0.1 for PCI) and target coverage (conformation number, CN) was not compromised (median CN = 0.82 for SIB and 0.86 for PCI). CONCLUSION: Simultaneous dose reduction to the hippocampus and the HT-P area did not compromise the PTV coverage in patients undergoing WBRT+SIB or PCI using VMAT. While the feasibility of the presented approach is promising, prospective neurologic, endocrine outcome and safety studies are required.

Linac-based SBRT as a feasible salvage option for local recurrences in previously irradiated prostate cancer.

BACKGROUND AND OBJECTIVE: The optimal management of prostate cancer (PC) recurrences after definitive or postoperative radiotherapy (RT) is still controversial. The aim of the present retrospective study was to report the preliminary clinical results and toxicity of a mono-institutional series of patients re-irradiated with linac-based SBRT in recurrent prostate cancer. METHODS: Inclusion criteria were previous definitive or adjuvant/salvage RT, evidence of biochemical recurrence and radiological detection of local relapse (Magnetic Resonance Imaging or PSMA/choline-Positron Emission Tomography), and IPSS <10. Toxicity was assessed according to Common Terminology Criteria for Adverse Events v4.0. RESULTS: Between 12/2014 and 12/2019, 24 patients with median age 75 years (65-89) underwent re-RT for PC recurrence. Median follow-up was 21 months (2-68). The recurrences occurred in 13 cases within the prostate and in 11 cases within the prostate bed. All patients were treated with SBRT to a median total dose of 30 Gy (25-36 Gy) in 5-6 fractions, and simultaneous androgen deprivation therapy was administered in 4 patients. Acute toxicity was G1 in 8.3% and G2 in 12.5% for genitourinary (GU), no acute gastrointestinal (GI) toxicity occurred. Concerning late side effects, 19.7% of patients were found to have ≥G2 GU toxicity, including one G3 urethral stenosis. Only one case of G1 late GI toxicity occurred and no ≥G2. The 2­year overall survival was 95%. The 1­ and 2­year biochemical relapse-free survival (BRFS) and progression-free survival (PFS) rates were 80 and 54.9%, respectively. CONCLUSION: Despite of the heterogeneity of the sample, linac-based SBRT as a salvage treatment in previously irradiated locally recurrent PC patients seems to be a safe and feasible treatment option. Long-term data are pending.

Dose escalation (81 Gy) with image-guided radiation therapy and volumetric-modulated arc therapy for localized prostate cancer: A retrospective preliminary result.

OBJECTIVES: The objective of the study is to report the acute and late toxicity and preliminary results of localized prostate cancer treated with high-dose radiation therapy (RT). MATERIALS AND METHODS: Between March 2010 and October 2018, a total of 53 patients with clinically localized prostate cancer were treated with definitive RT at our institution. All patients were planned to receive a total dose of 81 Gy with the volumetric-modulated arc therapy technique. Patients were stratified by prognostic risk groups based on the National Comprehensive Cancer Network risk classification criteria. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. The definition of biochemical failure was using the 2005 ASTRO Phoenix consensus definition. Median follow-up time was 46.5 months (range: 4.7-81.0 months). RESULTS: The 3-year biochemical failure-free survival rates for low-, intermediate-, and high-risk group patients were 100%, 87.5%, and 84%, respectively. The 3- and 5-year overall survival rates were 83% and 62%, respectively. Three (5.6%) patients developed Grade II acute gastrointestinal (GI) toxicity. Four (7.5%) patients developed Grade II acute genitourinary (GU) toxicity, and none experienced Grade III or higher acute GI or GU symptoms. One (1.8%) patient developed Grade II or higher late GI toxicity. Six (11.3%) patients experienced Grade II late GU toxicity. No Grade III or higher late GI and GU complications have been observed. CONCLUSIONS: Data from the current study demonstrated the feasibility of dose escalation with image-guided and volumetric-modulated arc therapy techniques for the treatment of localized prostate cancer. Minimal acute and late toxicities were observed from patients in this study. Long-term prostate-specific antigen controls are comparable to previously published results of high-dose intensity-modulated RT for localized prostate cancer. Based on this favorable outcome, dose escalation (81 Gy) has become the standard treatment for localized prostate cancer at our institution.

Concurrent chemoradiotherapy by simultaneously integrated boost volumetric-modulated arc therapy for nasopharyngeal carcinoma-toxicity/quality of life and survival.

BACKGROUND: To investigate the toxicity, changes of quality of life (QOL), and survival for patients with nasopharyngeal cancer (NPC) treated by concurrent chemoradiotherapy (CCRT) with simultaneously integrated boost volumetric-modulated arc therapy (SIB-VMAT). METHODS: A total of 68 NPC patients treated by CCRT with SIB-VMAT technique were collected. QOL was longitudinally assessed by the EORTC QLQ-C30 and HN35 questionnaires at the 4 time points: baseline, 42.4 Gy (20 fractions), and 3, 12 months after CCRT. RESULTS: The 4-year locoregional relapse free, distant metastasis free, failure free, and overall survival rates were 97.0%, 86.4%, 82.0%, and 88.1%, respectively. The 4-year cumulative incidence rate of late toxicities with grade 3 or more was 3.0%. One year after CCRT, most QOL scales, except some oral related symptoms, recovered to baseline level. CONCLUSION: CCRT with SIB-VMAT produces excellent locoregional control, few severe late toxicity, and good general health status for NPC patients.

Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer.

PURPOSE: This study aimed at investigating whether the irradiated volume of pelvic bone marrow (PBM) and specific subsites may predict the occurrence of acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. METHODS: 50 patients, submitted to IMRT and concurrent chemotherapy, were analyzed. Several bony structures were defined on planning-CT: PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring scale. Generalized linear modeling was used to find correlations between dosimetric variables and blood cell nadirs, while logistic regression analysis was used to test correlation with ≥G3 HT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the optimal cut-off points for predictive dosimetric variables with the Youden method. RESULTS: Maximum detected acute HT comprised 38 % of ≥G3 leukopenia and 32 % of ≥G3 neutropenia. Grade 2 anemia was observed in 4 % of patients and ≥G3 thrombocytopenia in 10 %. On multivariate analysis a higher PBM-V 20 was associated with lower WBC nadir. Increased LSBM-V 40 was correlated with a higher likelihood to develop ≥G3 HT. A cut-off point at 41 % for LSBM-V 40 was found. Patients with LSBM-V 40 ≥41 % were more likely to develop ≥G3 HT (55.3 vs. 32.4 %; p < 0.01). CONCLUSIONS: Increased low-dose to pelvic bony structures significantly predicted for WBC decrease. Medium-high dose to specific osseous subsites was associated with a higher probability of HT. LSBM-V 40 was a strong predictor of ≥G3 HT. A threshold at 41 % for LSBM-V 40 could be used to limit HT.

A dosimetric study of volumetric modulated arc therapy with a simultaneous integrated boost for preoperative chemoradiotherapy in patients with locally advanced rectal cancer / 中华放射肿瘤学杂志

Objective To investigate the dosimetric feasibility of volumetric modulated arc therapy (VMAT)with a simultaneous integrated boost(SIB-VMAT58.75 Gy)for preoperative chemoradiotherapy in patients with locally advanced rectal cancer(LARC),and to provide a basis for clinical practice.Methods Nine patients with stage Ⅱ-Ⅲ rectal cancer who underwent preoperative concurrent chemoradiotherapy were involved in the study,and two plans were performed for each patient:SIB-VMAT58.75 Gy and VMAT50.00 Gy. For the SIB-VMAT58.75 Gy plan,the prescribed dose was 58.75 Gy(2.35 Gy/fraction)for the local rectal tumor and positive lymph nodes(GTV 58.75 Gy),and 50 Gy(2 Gy/fraction)for the regions at high risk of harboring microscopic disease(pelvic lymphatic drainage area)(PTV 50Gy).For the VMAT50.00 Gy plan,the prescribed dose was 50 Gy(2 Gy/fraction)for the regions at high risk of harboring microscopic disease(pelvic lymphatic drainage area)without a boost. The conformity index(CI),homogeneity index (HI),and dose for target areas and organs at risk(OAR)were assessed according to the dose-volume histogram. The paired t-test or nonparametric rank test was used to compare the differences between the two plans. Results Both plans met the prescription goal for PTV dose coverage. There was no significant difference in CI for the PTV between the two plans(1.0±0.0 vs. 1.0±0.0,P>0.05).The SIB-VMAT58.75 Gy plan had a worse HI than the VMAT50.00 Gy plan(0.2± 0.2 vs. 0.1± 0.0,P<0.05).There was no significant difference in V10-V50of the small intestine,bladder,femoral heads,and pelvis between the two plans(P>0.05),but D 2 cm3of the small intestine was significantly higher in the SIB-VMAT58.75 Gy plan than in the VMAT50.00 Gy plan(P=0.038). Conclusions The SIB-VMAT58.75 Gy plan for LARC achieves required target volume dose coverage and OAR dose constraints,which is safe and feasible in terms of dosimetry,and its clinical efficacy and adverse effects need further evaluation.

Selection of Proper Modality in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

BACKGROUND/AIMS: As the optimal stereotactic body radiation therapy (SBRT) modality for hepatocellular carcinoma (HCC) has not been confirmed, we aimed herein to provide a practical guideline by our retrospective review. METHODS: Thirty-nine patients with primary HCC who underwent liver SBRT via 3 modalities (helical tomotherapy [HT]: 22, volumetric modulated arc therapy [VMAT]: 13, Cyberknife: 4) at our institution between July 2014 and July 2015 were included. Modalities were compared with regard to dose conformity index (CI), homogeneity index (HI), clinical results, and patient compliance. RESULTS: VMAT SBRT had favorable conformity (CI: 0.7±0.2), homogeneity (HI: 1.1±0.0), and shortest treatment time (100.2±26.1 seconds). HT SBRT yielded good dosimetric outcomes, especially in conformity (CI: 1.0±0.2). Although the Cyberknife SBRT synchrony system allowed real-time tumor targeting, the treatment time was longest (3,015.0±447.3 seconds), invasive pre-treatment procedures were required, and the HI (1.3±0.0) was lowest. CONCLUSIONS: All 3 modalities yielded competent dosimetric planning parameters. VMAT SBRT was most appropriate for tumors with residual lipiodol or patients with poor conditions. HT SBRT is available for multiple or irregular targets. Cyberknife SBRT is recommended for carefully selected patients and tumors indicated for sono-guided fiducial insertion.

Treatment: Outcome and Toxicity of Volumetric Modulated Arc Therapy in Oropharyngeal Carcinoma.

BACKGROUND/AIM: Radiotherapy is a common approach for treating squamous cell carcinoma (SCC) of the oropharynx. We aimed to analyze toxicity and outcome of patients affected by oropharyngeal SCC treated with volumetric modulated arc therapy (VMAT). PATIENTS AND METHODS: Fifty-four patients presenting advanced orophayngeal carcinoma who were treated with radical radiotherapy were analyzed. All patients were treated with VMAT-RapidArc, with simultaneous integrated boost in 33 fractions for a dose of 69.96 Gy to the high-risk, and of 54.45 Gy to the low-risk volume. RESULTS: Median follow-up was 23 months. In eight cases, locoregional relapse was observed (median time to relapse=10.7 months). Four among eight local recurrences appeared in the high-dose target volume. The 1- and 2-year actuarial disease-free survival rates were 88% and 80%, respectively. The 1- and 2-year actuarial overall survival rates were 94% and 87%, respectively. CONCLUSION: VMAT for oropharyngeal SCC treatment is effective and safe, with interesting rates of control of disease and survival.