Long-term outcomes following proton therapy for prostate cancer in young men with a focus on sexual health.

BACKGROUND: We investigated long-term outcomes for men ≤60 years old treated with proton therapy (PT). METHODS: Of 254 men ≤60 years old were treated with proton therapy alone for prostate cancer. Risk stratification included 56% with low-, 42% with intermediate- and 2% with high-risk disease. Patients received 76-82 Gy at 2 Gy/fraction or 70-72.5 Gy at 2.5 Gy/fraction. Before treatment and every 6-12 months for 5 years, patients were evaluated by a physician, answered health-related quality of life surveys, including the EPIC, IIEF and IPSS, and had PSA evaluated. RESULTS: Median follow-up for the cohort was 7.1 years; 7-year biochemical-free survival was 97.8%. Eight men (one high-risk; five intermediate-risk and two low-risk) experienced biochemical progression, including one who died of disease 9 years after treatment. Potency (erections firm enough for sexual intercourse) was 90% at baseline and declined to 72% at the first-year follow-up, but declined to only 67% at 5 years. Only 2% of patients developed urinary incontinence requiring pads. The bowel habits mean score declined from a baseline of 96 to 88 at 1 year, which improved over the following years to 93 at 5 years. CONCLUSIONS: Young men with prostate cancer continue to have excellent results with respect to 7-year biochemical control and 5-year erectile function, without clinically significant urinary incontinence 5 years after proton therapy. Comparative effectiveness studies of proton therapy with surgery and IMRT are needed.

A neural network-based 2D/3D image registration quality evaluator for pediatric patient setup in external beam radiotherapy.

Our purpose was to develop a neural network-based registration quality evaluator (RQE) that can improve the 2D/3D image registration robustness for pediatric patient setup in external beam radiotherapy. Orthogonal daily setup X-ray images of six pediatric patients with brain tumors receiving proton therapy treatments were retrospectively registered with their treatment planning computed tomography (CT) images. A neural network-based pattern classifier was used to determine whether a registration solution was successful based on geometric features of the similarity measure values near the point-of-solution. Supervised training and test datasets were generated by rigidly registering a pair of orthogonal daily setup X-ray images to the treatment planning CT. The best solution for each registration task was selected from 50 optimizing attempts that differed only by the randomly generated initial transformation parameters. The distance from each individual solution to the best solution in the normalized parametrical space was compared to a user-defined error tolerance to determine whether that solution was acceptable. A supervised training was then used to train the RQE. Performance of the RQE was evaluated using test dataset consisting of registration results that were not used in training. The RQE was integrated with our in-house 2D/3D registration system and its performance was evaluated using the same patient dataset. With an optimized sampling step size (i.e., 5 mm) in the feature space, the RQE has the sensitivity and the specificity in the ranges of 0.865-0.964 and 0.797-0.990, respectively, when used to detect registration error with mean voxel displacement (MVD) greater than 1 mm. The trial-to-acceptance ratio of the integrated 2D/3D registration system, for all patients, is equal to 1.48. The final acceptance ratio is 92.4%. The proposed RQE can potentially be used in a 2D/3D rigid image registration system to improve the overall robustness by rejecting unsuccessful registration solutions. The RQE is not patient-specific, so a single RQE can be constructed and used for a particular application (e.g., the registration for images acquired on the same anatomical site). Implementation of the RQE in a 2D/3D registration system is clinically feasible.

Temporal lobe sparing radiotherapy with photons or protons for cognitive function preservation in paediatric craniopharyngioma.

BACKGROUND AND PURPOSE: Reducing radiation exposure to the temporal lobes could be beneficial to preserve cognitive function in paediatric brain tumour patients. The distribution of doses to brain substructures associated with cognition (BSCs) both within and outside of the temporal lobe have not been reported. The aim of this study was therefore to investigate temporal lobe sparing photon vs. proton therapy for paediatric suprasellar tumours. MATERIAL AND METHODS: Data from ten anonymized craniopharyngioma patients were used in this study. Temporal lobe sparing volumetric modulated arc therapy (VMAT) and pencil beam scanning (PBS) proton therapy plans were optimized to maintain consistent target metrics as in the delivered double scattering proton therapy (DSPT) plans. Thirty BSCs were delineated, including temporal lobe substructures (i.e. amygdala, hippocampus, entorhinal cortex). The dose/volume fractions to each BSC were analysed, and intelligence quotient (IQ) as well as memory scores were estimated to compare the different modalities. RESULTS: The exposed volumes of the temporal lobes and their substructures were consistently reduced with PBS compared to DSPT and VMAT, e.g. the left hippocampus V10Gy from 100% (VMAT) or 41% (DSPT) to 5% with PBS (p = 0.002). Some of the ventricular substructures were better spared with VMAT compared to both proton modalities. The reduced doses to the temporal lobes achieved with PBS translated into improved predicted memory outcomes, but not for the estimated IQ. CONCLUSION: The irradiated volumes of temporal lobe BSCs were consistently the lowest with PBS, whereas the model-based estimates of cognitive outcomes were less consistent.

PTV margin analysis for prostate patients treated with initial pelvic nodal IMRT and prostate proton boost.

To evaluate the planning target volume (PTV) margins for prostate cancer patients treated with initial intensity-modulated radiation therapy (IMRT) to pelvic lymph nodes and a proton boost to the prostate using cone-beam computed tomography (CBCT) and radiographs as image guidance. We analyzed data from prostate patients (n = 15) treated with initial pelvic IMRT and a proton boost to the prostate. CBCT and 2-dimensional (2D) radiographs were used for IMRT and proton pre-treatment alignments, respectively. Translations from bony-matching, implanted marker seed matching, and seed-bony differences were obtained from CBCTs. Pretreatment and post-treatment 2D radiographs were analyzed for residual setup errors and intrafractional organ motion. PTV margins of prostate and pelvic lymph nodes for seed-matching, bony-matching and the skin mark-matching approach were obtained using 2.5 * Σ + 0.7 * σ formula, where Σ is the systematic error and σ is the random error summed in quadrature of various error components. For the seed-matching approach, the prostate margins were 1.5 mm, 3.5 mm, and 2.7 mm for the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, respectively; pelvic lymph node margins were 2.3 mm, 7.1 mm, and 7.0 mm. For the bony-matching approach, the prostate margins were 2.7 mm, 7.8 mm, and 7.5 mm for the LR, SI, and AP directions, respectively; pelvic lymph node margins were 0.7 mm, 1.5 mm, and 1.4 mm. For the skin mark-matching approach, the prostate margins were 7.6 mm, 13.4 mm, and 11.4 mm for the LR, SI, and AP directions, respectively; pelvic lymph node margins were 8.2 mm, 12.6 mm, and 12.3 mm. The seed-matching approach, as compared to the bony-matching approach, reduced prostate margins, which may in turn reduce dose to the bladder and rectum at the expense of increased but acceptable margins for the pelvic lymph nodes.

Dose-volume comparison of proton therapy and intensity-modulated radiotherapy for prostate cancer.

PURPOSE: The contrast in dose distribution between proton radiotherapy (RT) and intensity-modulated RT (IMRT) is unclear, particularly in regard to critical structures such as the rectum and bladder. METHODS AND MATERIALS: Between August and November 2006, the first 10 consecutive patients treated in our Phase II low-risk prostate proton protocol (University of Florida Proton Therapy Institute protocol 0001) were reviewed. The double-scatter proton beam plans used in treatment were analyzed for various dosimetric endpoints. For all plans, each beam dose distribution, angle, smearing, and aperture margin were optimized. IMRT plans were created for all patients and simultaneously analyzed. The IMRT plans were optimized through multiple volume objectives, beam weighting, and individual leaf movement. The patients were treated to 78 Gray-equivalents (GE) in 2-GE fractions with a biologically equivalent dose of 1.1. RESULTS: All rectal and rectal wall volumes treated to 10-80 GE (percentage of volume receiving 10-80 GE [V(10)-V(80)]) were significantly lower with proton therapy (p < 0.05). The rectal V(50) was reduced from 31.3% +/- 4.1% with IMRT to 14.6% +/- 3.0% with proton therapy for a relative improvement of 53.4% and an absolute benefit of 16.7% (p < 0.001). The mean rectal dose decreased 59% with proton therapy (p < 0.001). For the bladder and bladder wall, proton therapy produced significantly smaller volumes treated to doses of 10-35 GE (p < 0.05) with a nonsignificant advantage demonstrated for the volume receiving < or =60 GE. The bladder V(30) was reduced with proton therapy for a relative improvement of 35.3% and an absolute benefit of 15.1% (p = 0.02). The mean bladder dose decreased 35% with proton therapy (p = 0.002). CONCLUSION: Compared with IMRT, proton therapy reduced the dose to the dose-limiting normal structures while maintaining excellent planning target volume coverage.

Proton therapy in the management of non-Hodgkin lymphoma.

Proton therapy (PT) is a highly conformal type of radiation therapy that can target the tumor while sparing dose to surrounding normal tissues. This study reviews a single institution's experience managing patients with non-Hodgkin lymphoma (NHL) treated with PT. Eleven patients with NHL were treated with PT from January 2008 to January 2014 on an institutional review board-approved outcomes tracking protocol, and included patients with indolent orbital lymphoma (n = 4), primary mediastinal B-cell lymphoma (n = 3), plasmablastic lymphoma (n = 2) and natural killer (NK) T-cell lymphoma (n = 2). The median follow-up was 38 months. The 2-year rate of local control was 91%, with one patient with NK T-cell lymphoma having recurrence in-field. Toxicities were limited to grade 2 at highest, during follow-up. PT is a feasible and effective treatment for NHL. Early outcomes are favorable. Longer follow-up and more patients are needed to confirm our findings.

Improving the therapeutic ratio by using proton therapy in patients with stage I or II seminoma.

OBJECTIVES: The goal of the present study was to evaluate possible dosimetric advantages of proton therapy (PT) compared with 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in the treatment of patients with stage I and II seminoma. METHODS: Two representative patients (1 with left-sided and 1 with right-sided seminoma) underwent treatment planning for stage I seminoma (paraaortic lymph nodes alone) with 3DCRT (PA3d), IMRT (PAimrt) double-scatter protons (PAPds), and uniform-scanning protons (PAPus) and for stage II seminoma (paraaortics lymph nodes and iliac nodes) with 3DCRT (PI3d) , IMRT (PIimrt) double-scatter protons (PIPds), and uniform-scanning protons (PIPus). The doses to the organs at risk were compared for photons and protons. RESULTS: For stage I seminoma, PT reduced the mean dose to the stomach, ipsilateral kidney, pancreas, bowel space, small bowel, and colon compared with 3DCRT and IMRT. For stage II seminoma, PT reduced the mean dose to the same organs as in stage I seminoma with additional reductions in mean dose to the bladder and rectum compared with 3DCRT and IMRT. Uniform-scanning protons further reduced the dose to the organs at risk compared with double-scatter protons. CONCLUSIONS: PT may offer an improvement in the therapeutic ratio in patients with seminoma by reducing the dose to normal tissue. This improvement may translate into lower risks of acute gastrointestinal side effects, infertility, and secondary malignancies, which should be explored in a prospective study.

Effective dose reduction to cardiac structures using protons compared with 3DCRT and IMRT in mediastinal Hodgkin lymphoma.

PURPOSE: We investigated the dosimetric impact of proton therapy (PT) on various cardiac subunits in patients with Hodgkin lymphoma (HL). METHODS AND MATERIALS: From June 2009 through December 2010, 13 patients were enrolled on an institutional review board-approved protocol for consolidative involved-node radiotherapy (INRT) for HL. Three separate treatment plans were developed prospectively by using three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and PT. Cardiac subunits were retrospectively contoured on the 11 patients with intravenous-contrast simulation scans, and the doses were calculated for all treatment plans. A Wilcoxon paired test was performed to evaluate the statistical significance (p < 0.05) of 3DCRT and IMRT compared with PT. RESULTS: The mean heart doses were 21 Gy, 12 Gy, and 8 Gy (relative biologic effectiveness [RBE]) with 3DCRT, IMRT, and PT, respectively. Compared with 3DCRT and IMRT, PT reduced the mean doses to the left and right atria; the left and right ventricles; the aortic, mitral, and tricuspid valves; and the left anterior descending, left circumflex, and right circumflex coronary arteries. CONCLUSIONS: Compared with 3DCRT and IMRT, PT reduced the radiation doses to all major cardiac subunits. Limiting the doses to these structures should translate into lower rates of cardiac toxicities.

Protons offer reduced normal-tissue exposure for patients receiving postoperative radiotherapy for resected pancreatic head cancer.

PURPOSE: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. METHODS AND MATERIALS: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. RESULTS: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). CONCLUSIONS: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

Dosimetric study of pelvic proton radiotherapy for high-risk prostate cancer.

PURPOSE: To compare dose distributions in targeted tissues (prostate, seminal vesicles, pelvic regional nodes) and nontargeted tissues in the pelvis with intensity-modulated radiotherapy (IMRT) and forward-planned, double-scattered, three-dimensional proton radiotherapy (3D-PRT). METHODS AND MATERIALS: IMRT, IMRT followed by a prostate 3D-PRT boost (IMRT/3D-PRT), and 3D-PRT plans were created for 5 high-risk prostate cancer patients (n = 15 plans). A 78-CGE/Gy dose was prescribed to the prostate and proximal seminal vesicles and a 46-CGE/Gy was prescribed to the pelvic nodes. Various dosimetric endpoints were compared. RESULTS: Target coverage of the prostate and nodal planning target volumes was adequate for all three plans. Compared with the IMRT and IMRT/3D-PRT plans, the 3D-PRT plans reduced the mean dose to the rectum, rectal wall, bladder, bladder wall, small bowel, and pelvis. The relative benefit of 3D-PRT (vs IMRT) at reducing the rectum and rectal wall V5-V40 was 53% to 71% (p < 0.05). For the bladder and bladder wall, the relative benefit for V5 to V40 CGE/Gy was 40% to 63% (p < 0.05). The relative benefit for reducing the volume of small bowel irradiated from 5 to 30 CGE/Gy in the 3D-PRT ranged from 62% to 69% (p < 0.05). Use of 3D-PRT did not produce the typical low-dose "bath" of radiation to the pelvis seen with IMRT. Femoral head doses were higher for the 3D-PRT. CONCLUSIONS: Use of 3D-PRT significantly reduced the dose to normal tissues in the pelvis while maintaining adequate target coverage compared with IMRT or IMRT/3D-PRT. When treating the prostate, seminal vesicles, and pelvic lymph nodes in prostate cancer, proton therapy may improve the therapeutic ratio beyond what is possible with IMRT.