Clinical Implementation of a Model-Based In Vivo Dose Verification System for Stereotactic Body Radiation Therapy-Volumetric Modulated Arc Therapy Treatments Using the Electronic Portal Imaging Device.

PURPOSE: To report findings from an in vivo dosimetry program implemented for all stereotactic body radiation therapy patients over a 31-month period and discuss the value and challenges of utilizing in vivo electronic portal imaging device (EPID) dosimetry clinically. METHODS AND MATERIALS: From December 2013 to July 2016, 117 stereotactic body radiation therapy-volumetric modulated arc therapy patients (100 lung, 15 spine, and 2 liver) underwent 602 EPID-based in vivo dose verification events. A developed model-based dose reconstruction algorithm calculates the 3-dimensional dose distribution to the patient by back-projecting the primary fluence measured by the EPID during treatment. The EPID frame-averaging was optimized in June 2015. For each treatment, a 3%/3-mm γ comparison between our EPID-derived dose and the Eclipse AcurosXB-predicted dose to the planning target volume (PTV) and the ≥20% isodose volume were performed. Alert levels were defined as γ pass rates <85% (lung and liver) and <80% (spine). Investigations were carried out for all fractions exceeding the alert level and were classified as follows: EPID-related, algorithmic, patient setup, anatomic change, or unknown/unidentified errors. RESULTS: The percentages of fractions exceeding the alert levels were 22.6% for lung before frame-average optimization and 8.0% for lung, 20.0% for spine, and 10.0% for liver after frame-average optimization. Overall, mean (± standard deviation) planning target volume γ pass rates were 90.7% ± 9.2%, 87.0% ± 9.3%, and 91.2% ± 3.4% for the lung, spine, and liver patients, respectively. CONCLUSIONS: Results from the clinical implementation of our model-based in vivo dose verification method using on-treatment EPID images is reported. The method is demonstrated to be valuable for routine clinical use for verifying delivered dose as well as for detecting errors.

Stereotactic radiosurgery does not appear to impact cochlear implant performance in patients with neurofibromatosis type II.

INTRODUCTION: Neurofibromatosis Type 2 (NF2) is a genetic condition associated with the presence of bilateral vestibular schwannoma and progressive sensorineural hearing loss. Treatment options include observation, stereotactic radiosurgery (SRS) or surgical resection. Historically, retrocochlear pathology was a contraindication to cochlear implantation (CI). However it is now recognized as viable, in an attempt to restore hearing and improve communication.Thus, the aim of this study was to contrast auditory function in CI recipients with NF2 whose tumors were either observed versus initially treated with SRS. METHODS: A local review of hearing outcomes in 2 CI patients (3 ears total) with NF2 was undertaken and then pooled with the existing medical literature. Comparative post-implant outcome data, including pure-tone average and aided speech perception measurements was analyzed and compared between 8 subjects whose tumors were observed and 11 subjects who received pre-implantation SRS. RESULTS: Mean tumor size in the observation cohort was 0.81cm (.13cm to 1.50cm), and 2.34cm in the SRS group (0.10cm to 3.7cm). The mean reported duration of deafness was 22 months as compared to 71 months in the SRS cohort. Both groups demonstrated similar pre-implant candidacy criteria, average age and open-set speech recognition. Although disparate outcome measurements were utilized across studies, an analysis of post-implant open-set speech perception found no significant differences between groups. CONCLUSION: Despite a small sample size and highly variable post implantation testing methods, patients who undergo SRS for NF2 associated Schwannoma prior to CI have similar hearing performance and benefit by having already completed definitive tumor management.

Effect of Standard Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma: A Randomized Clinical Trial.

IMPORTANCE: The Canadian Cancer Trials Group study HN.6 is the largest randomized clinical trial to date comparing the concurrent administration of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies with radiotherapy (RT) to standard chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). OBJECTIVE: To compare progression-free survival (PFS) in patients with LA-SCCHN treated with standard-fractionation RT plus high-dose cisplatin vs accelerated-fractionation RT plus the anti-EGFR antibody panitumumab. DESIGN, SETTING, AND PARTICIPANTS: A randomized phase 3 clinical trial in 17 Canadian centers. A total of 320 patients were randomized between December 2008 and November 2011. INTERVENTIONS: Patients with TanyN+M0 or T3-4N0M0 LA-SCCHN were randomized 1:1 to receive standard-fractionation RT (70 Gy/35 over 7 weeks) plus cisplatin at 100 mg/m2 intravenous for 3 doses (arm A) vs accelerated-fractionation RT (70 Gy/35 over 6 weeks) plus panitumumab at 9 mg/kg intravenous for 3 doses (arm B). MAIN OUTCOMES AND MEASURES: Primary end point was PFS. Due to an observed declining event rate, the protocol was amended to a time-based analysis. Secondary end points included overall survival, local and regional PFS, distant metastasis-free survival, quality of life, adverse events, and safety. RESULTS: Of 320 patients randomized (268 [84%] male; median age, 56 years), 156 received arm A and 159 arm B. A total of 93 PFS events occurred. By intention-to-treat, 2-year PFS was 73% (95% CI, 65%-79%) in arm A and 76% (95% CI, 68%-82%) in arm B (hazard ratio [HR], 0.95; 95% CI, 0.60-1.50; P = .83). The upper bound of the HR 95% CI exceeded the prespecified noninferiority margin. Two-year overall survival was 85% (95% CI, 78%-90%) in arm A and 88% (95% CI, 82%-92%) in arm B (HR, 0.89; 95% CI, 0.54-1.48; P = .66). Incidence of any grade 3 to 5 nonhematologic adverse event was 88% in arm A and 92% in arm B (P = .25). CONCLUSIONS AND RELEVANCE: With a median follow-up of 46 months, the PFS of panitumumab plus accelerated-fractionation RT was not superior to cisplatin plus standard-fractionation RT in LA-SCCHN and noninferiority was not proven. Despite having negative results, HN.6 has contributed important data regarding disease control and toxic effects of these treatment strategies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00820248.

Total body irradiation compared with BEAM: Long-term outcomes of peripheral blood autologous stem cell transplantation for non-Hodgkin's lymphoma.

PURPOSE: The optimal preparative regimen for non-Hodgkin's lymphoma patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) is unknown. We compared a total body irradiation (TBI)-based regimen with a chemotherapy-alone regimen. METHODS AND MATERIALS: A retrospective cohort study was performed at a Canadian cancer center. The TBI regimen consisted of cyclophosphamide, etoposide, and TBI 12 Gy in six fractions (CY/E/TBI). The chemotherapy-alone regimen consisted of carmustine, etoposide, cytarabine, and melphalan (BEAM). We compared the acute and long-term toxicities, disease relapse-free survival, and overall survival (OS). RESULTS: Of 73 patients, 26 received CY/E/TBI and 47 received BEAM. The median follow-up for the CY/E/TBI group was 12.0 years and for the BEAM group was 7.3 years. After PBSCT, no differences in acute toxicity were seen between the two groups. The 5-year disease relapse-free survival rate was 50.0% and 50.7% in the CY/E/TBI and BEAM groups, respectively (p = .808). The 5-year OS rate was 53.9% and 63.8% for the CY/E/TBI and BEAM groups, respectivey (p = .492). The univariate analysis results indicated that patients with Stage IV, with chemotherapy-resistant disease, and who had received PBSCT before 2000 had inferior OS. A three-way categorical analysis revealed that transplantation before 2000, rather than the conditioning regimen, was a more important predictive factor of long-term outcome (p = .034). CONCLUSION: A 12-Gy TBI-based conditioning regimen for PBSCT for non-Hodgkin's lymphoma resulted in disease relapse-free survival and OS similar to that after BEAM. PBSCT before 2000, and not the conditioning regimen, was an important predictor of long-term outcomes. TBI was not associated with more acute toxicity or pneumonitis. We found no indication that the TBI regimen was inferior or superior to BEAM.

Improving intensity-modulated radiation therapy using the anatomic beam orientation optimization algorithm.

A novel, anatomic beam orientation optimization (A-BOO) algorithm is proposed to significantly improve conventional intensity-modulated radiation therapy (IMRT). The A-BOO algorithm vectorially analyses polygonal surface mesh data of contoured patient anatomy. Five optimal (5-opt) deliverable beam orientations are selected based on (1) tangential orientation bisecting the target and adjacent organ's-at-risk (OARs) to produce precipitous dose gradients between them and (2) parallel incidence with polygon features of the target volume to facilitate conformal coverage. The 5-opt plans were compared to standard five, seven, and nine equiangular-spaced beam plans (5-equi, 7-equi, 9-equi) for: (1) gastric, (2) Radiation Therapy Oncology Group (RTOG) P-0126 prostate, and (3) RTOG H-0022 oropharyngeal (stage-III, IV) cancer patients. In the gastric case, the noncoplanar 5-opt plan reduced the right kidney V 20 Gy by 32.2%, 23.2%, and 20.6% compared to plans with five, seven, and nine equiangular-spaced beams. In the prostate case, the coplanar 5-opt plan produced similar rectal sparing as the 7-equi and 9-equi plans with a reduction of the V 75, V 70, V 65, and V 60 Gy of 2.4%, 5.3%, 7.0%, and 9.5% compared to the 5-equi plan. In the stage-III and IV oropharyngeal cases, the noncoplanar 5-opt plan substantially reduced the V 30 Gy and mean dose to the contralateral parotid compared to plans with five, seven, and nine equiangular-spaced beams: (stage-III) 7.1%, 5.2%, 6.8%, and 5.1, 3.5, 3.7 Gy and (stage-IV) 10.2%, 10.2%, 9.8% and 7.0, 7.1, 7.2 Gy. The geometry-based A-BOO algorithm has been demonstrated to be robust for application to a variety of IMRT treatment sites. Beam orientations producing significant improvements in OAR sparing over conventional IMRT can be automatically produced in minutes compared to hours with existing dose-based beam orientation optimization methods.

A simple geometric algorithm to predict optimal starting gantry angles using equiangular-spaced beams for intensity modulated radiation therapy of prostate cancer.

A fast, geometric beam angle optimization (BAO) algorithm for clinical intensity-modulated radiation therapy (IMRT) was implemented on ten localized prostate cancer patients on the Radiation Therapy Oncology Group (RTOG) 0126 protocol. The BAO algorithm computed the beam intersection volume (BIV) within the rectum and bladder using five and seven equiangular-spaced beams as a function of starting gantry angle for comparison to the V 75 Gy and V 70 Gy. A mathematical theory was presented to explain the correlation of BIV with dose and dose-volume metrics. The class solution 'W' pattern in the rectal V 75 Gy and V 70 Gy as a function of starting gantry angle using five equiangular-spaced beams (with two separate minima centered near 20 degrees and 50 degrees) was reproduced by the 5 BIV within the rectum. A strong correlation was found between the rectal 5 BIV and the rectal V 75 Gy and V 70 Gy as a function of starting gantry angle. The BAO algorithm predicted the location of the two dosimetric minima in rectal V 75 Gy and V 70 Gy (optimal starting gantry angles) to within 5 degrees. It was demonstrated that the BIV geometric variations for seven equiangular-spaced beams were too small to translate into a strong dosimetric effect in the rectal V 75 Gy and V 70 Gy. The relatively flat distribution with starting gantry angle of the bladder V 75 Gy and V 70 Gy was reproduced by the bladder five and seven BIV for each patient. A geometric BAO method based on BIV has the advantage over dosimetric BAO methods of simplicity and rapid computation time. This algorithm can be used as a standalone optimization method or act as a rapid calculation filter to reduce the search space for a dosimetric BAO method. Given the clinically infeasible computation times of many dosimetric beam orientation optimization algorithms, this robust geometric BIV algorithm has the potential to facilitate beam angle selection for prostate IMRT in clinical practice.

Optimal starting gantry angles using equiangular-spaced beams with intensity modulated radiation therapy for prostate cancer on RTOG 0126: a clinical study of 5 and 7 fields.

BACKGROUND AND PURPOSE: To investigate the effects of starting gantry angle and number of equiangular-spaced beams for prostate cancer radiotherapy on the Radiation Therapy Oncology Group (RTOG) 0126 protocol using intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: Ten localized prostate cancer patients were prescribed to 79.2Gy in 44 fractions. Static IMRT plans using five and seven equiangular-spaced beams were generated. The starting gantry angles were incremented by 5 degrees resulting in 15 (5 beams) and 11 (7 beams) plans per patient. Constant target coverage was ensured for all plans in order to isolate the variation in the rectal and bladder metrics as a function of starting gantry angle. RESULTS: The variation with starting gantry angle in rectal metrics using 5 beams was statistically significant (p<0.001) with dosimetric importance. The 5-beam rectal V 75Gy and V 70Gy demonstrated a class solution with a characteristic 'W' pattern and two optimal starting gantry angles near 20 degrees and 50 degrees . Statistically insignificant differences were observed for the bladder metrics using 5 beams. There was little dosimetric variation in the rectal and bladder metrics with 7 beams. Nearly equivalent rectal V 75Gy was achieved between 5 optimal equiangular-spaced beams starting at 20 degrees (class solution) and 7 equiangular-spaced beams starting at 0 degrees for most patients. CONCLUSIONS: The use of an optimal starting gantry angle for 5 equiangular-spaced beams, as indicated by a class solution in this study, will facilitate rectal sparing and can produce plans that are equivalent to those employing 7 equiangular-spaced beams.

Cardiac chamber and coronary artery doses associated with postmastectomy radiotherapy techniques to the chest wall and regional nodes.

PURPOSE: To compare the estimated radiation doses delivered to the cardiac chambers (CC) and coronary arteries (CA) for 5 postmastectomy radiotherapy (PMRT) techniques. METHODS AND MATERIALS: A dosimetry study of 20 left-sided PMRT cases was conducted. Cardiac chambers (left and right atria [LA/RA] and left and right ventricles [LV/RV]) and coronary vessels (left main [LM], left anterior descending [LAD], left circumflex [LCX], right coronary [RCA] and posterior descending [PDA] arteries) were contoured on contrast-enhanced CT scans and verified by a cardiologist (T.K.). Five PMRT techniques were applied to each case; 50 Gy in 2 Gy fractions was delivered to the chest wall +/- internal mammary node targets. The techniques were: (1) standard tangents (TAN); (2) cobalt (Co); (3) reverse hockey stick (RHS); (4) mixed photon/electron beam (20/80); and (5) partially wide tangent fields (PWTF). Three-dimensional dose calculations for 100 plans were performed for all structures. Plans were compared by using the mean dose (Dmean) and the volume that received more than 30 Gy (V(30)) and 45 Gy (V(45)) for each structure. RESULTS: Cobalt and 20/80 techniques delivered higher Dmeans to the whole heart and individual cardiac chambers (RA, RV, LA, and LV) as compared with the other three techniques. The heart received a Dmean of 21.03 +/- 3.5 Gy from Co and 11.87 +/- 5.22 Gy from 20/80. The remaining techniques delivered heart Dmeans of 2.90-4.94 Gy. When V(30) was used as a metric, all techniques had comparably low V(30) to the heart, except for Co, which resulted in a significantly higher irradiated volume of right-sided cardiac chambers (59.06% +/- 30.7 for RA F-test < 0.0001; and 61.46% +/- 22.13 for RV, F-test < 0.0001). Dmean to the proximal LAD (LAD_p) was significantly higher for RHS (17.64 +/- 7.43 Gy) and 20/80 (20.52 +/- 8.36 Gy) and lowest for PWTF (9.5 +/- 4.16 Gy). The Dmean for the distal LAD (LAD_d) was significantly lower with PWTF (11.02 +/- 7.34 Gy) than with all other techniques, including TAN (p < 0.0001). Similar results for PWTF and TAN were observed when V30 and V45 were used. CONCLUSIONS: Cardiac substructures receive the most radiation exposure after PMRT with CO, 20/80 or both and least exposure with PWTF. Although TAN resulted in significant sparing of the majority of the cardiac structures, a significantly higher dose and volume of LAD was exposed when compared with PWTF. Although the clinical relevance of these dose differences is not clearly understood, these dosimetric estimates can serve as a baseline in the development of new techniques for locoregional treatment that will further reduce cardiac exposure.

Postmastectomy radiotherapy of the chest wall: dosimetric comparison of common techniques.

PURPOSE: To compare seven techniques for irradiation of the postmastectomy chest wall (CW) using normal tissue complication probability (NTCP) predictions for pneumonitis and ischemic heart disease and dose-volume histogram analyses for normal and target tissues. METHODS AND MATERIALS: Plan comparisons were performed for 20 left-sided postmastectomy CW RT cases using target volumes based on clinical delineation of standard field borders. Seven common treatment techniques were planned for each case, using a prescription of 50 Gy in 25 fractions to the CW and internal mammary node (IMN) targets. NTCP model metrics were used to quantify the risks of pneumonitis and ischemic heart disease, supplemented by dose-volume metrics to assess the target coverage to the CW and IMNs, as well as normal tissue dose (lung and heart). RESULTS: Overlap in the distributions of the CW mean dose for all plans was found, except cobalt, which was significantly less than the remaining techniques (global F test, F = 21.90, p <0.0001). Standard tangents produced a significantly lower IMN mean dose than all other methods, as expected (F = 59.55, p < 0.0001); the reverse hockey stick and cobalt techniques were lower than the other methods, which were statistically similar. Cobalt produced a significantly higher percentage of the heart that received >30 Gy (V30) than the other methods (F = 49.76, p <0.0001). Use of partially wide tangent fields (PWTFs) resulted in the smallest heart V30. Use of cobalt fields resulted in a significantly greater NTCP estimate for ischemic heart disease than all the remaining techniques (F = 70.39, p <0.0001). Standard tangents resulted in a percentage of the lung receiving >20 Gy (V20) significantly less than with PWTFs, 30/70 and 20/80 photon/electron mix, and reverse hockey stick techniques. NTCP estimates for pneumonitis revealed significantly better results with standard tangents (F = 6.57, p <0.0001). CONCLUSION: No one technique studied combines the best CW and IMN coverage with minimal lung and heart complication probabilities. The choice of technique should be based on clinical discretion and the technical expertise available to implement these complex plans. Of the seven techniques studied, this analysis supports PWTFs as the most appropriate balance of target coverage and normal tissue sparing when irradiating the CW and IMN.