Stereotactic body proton therapy for liver tumors: Dosimetric advantages and their radiobiological and clinical implications.

BACKGROUND AND PURPOSE: Photon Stereotactic Body Radiotherapy (SBRT) for primary and metastatic tumors of the liver is challenging for larger lesions. An in silico comparison of paired SBRT and Stereotactic Body Proton Therapy (SBPT) plans was performed to understand the potential advantages of SBPT as a function of tumor size and location. METHODS AND MATERIALS: Theoretical tumor volumes with maximum diameter of 1-10 cm were contoured in the dome, right inferior, left medial, and central locations. SBRT and SBPT plans were generated to deliver 50 Gy in 5 fractions, max dose <135%. When organs-at-risk (OAR) constraints were exceeded, hypothetical plans (not clinically acceptable) were generated for comparison. Liver normal tissue complication probability (NTCP) models were applied to evaluate differences between treatment modalities. RESULTS: SBRT and SBPT were able to meet target goals and OAR constraints for lesions up to 7 cm and 9 cm diameter, respectively. SBPT plans resulted in a higher integral gross target dose for all lesions up to 7 cm (mean dose 57.8 ±â€¯2.3 Gy to 64.1 ±â€¯2.2 Gy, p < 0.01). Simultaneously, SBPT spared dose to the uninvolved liver in all locations (from 11.5 ±â€¯5.3 Gy to 8.6 ±â€¯4.4 Gy, p < 0.01), resulting in lower NTCP particularly for larger targets in the dome and central locations. SBPT also spared duodenal dose across all sizes and positions (from 7.3 ±â€¯1.1 Gy to 1.1 ±â€¯0.3 Gy, p < 0.05). CONCLUSION: The main advantages of SBPT over SBRT is meeting plan goals and constrains for larger targets, particularly dome and central locations, and sparing dose to uninvolved liver. For such patients, SBPT may allow improvements in tumor control and treatment safety.

Proton Therapy Reduces Normal Tissue Dose in Extended-Field Pelvic Radiation for Endometrial Cancer.

PURPOSE: We dosimetrically compared pencil beam scanning (PBS) proton therapy and intensity-modulated radiation therapy (IMRT) for pelvic and para-aortic lymph node disease in endometrial carcinoma and present acute toxicities associated with extended-field PBS. PATIENTS AND METHODS: Twenty-five patients with locally advanced endometrial malignancies were enrolled in an image-guided registry study. Seven of these patients were treated with PBS, and 18 patients were treated with IMRT. Organs at risk included pelvic bone marrow (PBM), small bowel (SB), large bowel (LB), rectum, bladder, and kidneys. The IMRT and PBS dosimetric parameters were compared using Wilcoxon rank-sum tests. RESULTS: Compared with IMRT PBM dose-volume histograms, PBS resulted in significantly lower dose volumes from 0 to 26.0 Gy (P < .05) and higher dose volumes from 33.9 to 42.9 Gy (P < .05). Overall, PBS resulted in 22% lower median PBM volume irradiated to 10 Gy (RBE) (PBS 71.3% versus IMRT 93.4%, P < .001) and 14% lower median volume irradiated to 20 Gy (RBE) (PBS 65.1% versus IMRT 79.4%, P < .001). Compared with IMRT, PBS also significantly reduced SB dose volumes from 0 to 27.5 Gy, LB dose volumes from 0 to 31.6 Gy, bladder dose volumes from 0 to 27.3 Gy, and rectal dose volumes from 0 to 7.6 Gy (all P < .05). However, PBS resulted in higher rectal dose volumes compared with IMRT from 26.0 to 48.4 Gy. Grade 3+ hematologic toxicities were present in 2 (11%) IMRT-treated patients and no PBS-treated patients. No grade 3+ gastrointestinal or genitourinary toxicities were present in either treatment group. CONCLUSION: In endometrial carcinoma, extended-field PBS is clinically feasible, resulting in statistically significant dose reduction to PBM as well as SB, LB, and bladder in the lower dose regions.

Proton therapy for pediatric head and neck malignancies.

PURPOSE: Pediatric head and neck malignancies are managed with intensive multimodality therapy. Proton beam therapy (PBT) may reduce toxicity by limiting exposure of normal tissue to radiation. In this study, we report acute toxicities and early outcomes following PBT for pediatric head and neck malignancies. MATERIALS AND METHODS: Between 2010 and 2016, pediatric patients with nonhematologic malignancies of the head and neck were treated with PBT. Clinical and dosimetric data were abstracted from the medical record and treatment planning system with institutional review board approval. RESULTS: Sixty-nine consecutive pediatric patients were treated with proton-based radiotherapy for head and neck malignancies. Thirty-five were treated for rhabdomyosarcoma to a median dose of 50.4 Gy relative biological effectiveness [RBE]. Ten patients were treated for Ewing sarcoma to a median dose of 55.8 Gy[RBE]. Twenty-four patients were treated for other histologies to a median dose of 63.0 Gy[RBE]. Grade 3 oral mucositis, anorexia, and dysphagia were reported to be 4, 22, and 7%, respectively. Actuarial 1-year freedom from local recurrence was 92% (95% CI 80-97). Actuarial 1-year overall survival was 93% (95% CI 79-98) in the entire cohort. Oral cavity mucositis was significantly correlated with oral cavity dose (D80 and D50 [P < 0.05], where D80 and D50 are dose to 50% of the volume and dose to 80% of the volume, respectively). CONCLUSIONS: In this study, we report low rates of acute toxicity in a cohort of pediatric patients with head and neck malignancies. PBT appears safe for this patient population, with local control rates similar to historical reports. Longer follow-up will be required to evaluate late toxicity and long-term disease control.

Superiority in Robustness of Multifield Optimization Over Single-Field Optimization for Pencil-Beam Proton Therapy for Oropharynx Carcinoma: An Enhanced Robustness Analysis.

PURPOSE: To compare the difference in robustness of single-field optimized (SFO) and robust multifield optimized (rMFO) proton plans for oropharynx carcinoma patients by an improved robustness analysis. METHODS AND MATERIALS: We generated rMFO proton plans for 11 patients with oropharynx carcinoma treated with SFO intensity modulated proton therapy with simultaneous integrated boost prescription. Doses from both planning approaches were compared for the initial plans and the worst cases from 20 optimization scenarios of setup errors and range uncertainties. Expected average dose distributions per range uncertainty were obtained by weighting the contributions from the respective scenarios with their expected setup error probability, and the spread of dose parameters for different range uncertainties were quantified. Using boundary dose distributions created from 56 combined setup error and range uncertainty scenarios and considering the vanishing influence of setup errors after 30 fractions, we approximated realistic worst-case values for the total treatment course. Error bar metrics derived from these boundary doses are reported for the clinical target volumes (CTVs) and organs at risk (OARs). RESULTS: The rMFO plans showed improved CTV coverage and homogeneity while simultaneously reducing the average mean dose to the constrictor muscles, larynx, and ipsilateral middle ear by 5.6 Gy, 2.0 Gy, and 3.9 Gy, respectively. We observed slightly larger differences during robustness evaluation, as well as a significantly higher average brainstem maximum and ipsilateral parotid mean dose for SFO plans. For rMFO plans, the range uncertainty-related spread in OAR dose parameters and many error bar metrics were found to be superior. The SFO plans showed a lower global maximum dose for single-scenario worst cases and a slightly lower mean oral cavity dose throughout. CONCLUSIONS: An enhanced robustness analysis has been proposed and implemented into clinical systems. The benefit of better CTV coverage and OAR dose sparing in oropharynx carcinoma patients by rMFO compared with SFO proton plans is preserved in a robustness analysis with consideration of setup error and range uncertainty.

Field-Specific Intensity-modulated Proton Therapy Optimization Technique for Breast Cancer Patients with Tissue Expanders Containing Metal Ports.

This report aims to propose and present an evaluation of a robust pencil beam scanning proton multi-field optimized treatment planning technique for postmastectomy radiation of breast cancer patients with implanted tissue expanders containing an internal metal port. Field-specific split targets were created for optimization to prevent spots from traveling through the metal port, while providing uniform coverage of the target with the use of a multi-field intensity modulated optimization approach. Two beam angles were strategically selected to provide complementary target coverage and plan robustness. The plan was compared with an independently developed photon plan and evaluated for robustness with respect to isocenter shifts, range shifts, and variation of the water-equivalent thickness of the port. The proton plan resulted in clinically acceptable target coverage and dosage to neighboring normal tissues. The D95% coverage was 95.3% in the nominal proton plan, with a worst-case coverage of 90.1% (when considering 0.3 cm isocenter shifts combined with 3.5% range uncertainty), and the coverage varied less than 1% under a hypothetically extreme variation of the port density. The proton plan had improved dose homogeneity compared with the photon plan, and reduced ipsilateral lung and mean heart doses. We demonstrated that a practical, field-specific intensity-modulated proton therapy (IMPT) optimization technique can be used to deal with the challenge of metal port in breast cancer patients with tissue expanders. The resulting proton plan has superior dosimetric characteristics over the best-case scenario photon plan, and is also robust to setup and proton range uncertainties.

Pencil beam scanning proton therapy vs rotational arc radiation therapy: A treatment planning comparison for postoperative oropharyngeal cancer.

Patients diagnosed with head and neck cancer are traditionally treated with photon radiotherapy. Proton therapy is currently being used clinically and may potentially reduce treatment-related toxicities by minimizing the dose to normal organs in the treatment of postoperative oropharyngeal cancer. The finite range of protons has the potential to significantly reduce normal tissue toxicity compared to photon radiotherapy. Seven patients were planned with both proton and photon modalities. The planning goal for both modalities was achieving the prescribed dose to 95% of the planning target volume (PTV). Dose-volume histograms were compared in which all cases met the target coverage goals. Mean doses were significantly lower in the proton plans for the oral cavity (1771cGy photon vs 293cGy proton, p < 0.001), contralateral parotid (1796cGy photon vs 1358 proton, p < 0.001), and the contralateral submandibular gland (3608cGy photon vs 3251cGy proton, p = 0.03). Average total integral dose was 9.1% lower in proton plans. The significant dosimetric sparing seen with proton therapy may lead to reduced side effects such as pain, weight loss, taste changes, and dry mouth. Prospective comparisons of protons vs photons for disease control, toxicity, and patient-reported outcomes are therefore warranted and currently being pursued.

Range optimization for mono- and bi-energetic proton modulated arc therapy with pencil beam scanning.

The development of rotational proton therapy plans based on a pencil-beam-scanning (PBS) system has been limited, among several other factors, by the energy-switching time between layers, a system-dependent parameter that ranges between a fraction of a second and several seconds. We are investigating mono- and bi-energetic rotational proton modulated arc therapy (PMAT) solutions that would not be affected by long energy switching times. In this context, a systematic selection of the optimal proton energy for each arc is vital. We present a treatment planning comparison of four different range selection methods, analyzing the dosimetric outcomes of the resulting treatment plans created with the ranges obtained. Given the patient geometry and arc definition (gantry and couch trajectories, snout elevation) our in-house treatment planning system (TPS) FoCa was used to find the maximum, medial and minimum water-equivalent thicknesses (WETs) of the target viewed from all possible field orientations. Optimal ranges were subsequently determined using four methods: (1) by dividing the max/min WET interval into equal steps, (2) by taking the average target midpoints from each field, (3) by taking the average WET of all voxels from all field orientations, and (4) by minimizing the fraction of the target which cannot be reached from any of the available angles. After the range (for mono-energetic plans) or ranges (for bi-energetic plans) were selected, the commercial clinical TPS in use in our institution (Varian Eclipse™) was used to produce the PMAT plans using multifield optimization. Linear energy transfer (LET) distributions of all plans were also calculated using FoCa and compared among the different methods. Mono- and bi-energetic PMAT plans, composed of a single 180° arc, were created for two patient geometries: a C-shaped target located in the mediastinal area of a thoracic tissue-equivalent phantom and a small brain tumor located directly above the brainstem. All plans were optimized using the same procedure to (1) achieve target coverage, (2) reduce dose to OAR and (3) limit dose hot spots in the target. Final outcomes were compared in terms of the resulting dose and LET distributions. Data shows little significant differences among the four studied methods, with superior results obtained with mono-energetic plans. A streamlined systematic method has been implemented in an in-house TPS to find the optimal range to maximize target coverage with rotational mono- or bi-energetic PBS rotational plans by minimizing the fraction of the target that cannot be reached by any direction.

Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial.

BACKGROUND AND PURPOSE: In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs). MATERIAL AND METHODS: Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT). RESULTS: When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D2) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org. CONCLUSIONS: In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation.

Technical Note: A treatment plan comparison between dynamic collimation and a fixed aperture during spot scanning proton therapy for brain treatment.

PURPOSE: To quantitatively assess the advantages of energy-layer specific dynamic collimation system (DCS) versus a per-field fixed aperture for spot scanning proton therapy (SSPT). METHODS: Five brain cancer patients previously planned and treated with SSPT were replanned using an in-house treatment planning system capable of modeling collimated and uncollimated proton beamlets. The uncollimated plans, which served as a baseline for comparison, reproduced the target coverage and organ-at-risk sparing of the clinically delivered plans. The collimator opening for the fixed aperture-based plans was determined from the combined cross sections of the target in the beam's eye view over all energy layers which included an additional margin equivalent to the maximum beamlet displacement for the respective energy of that energy layer. The DCS-based plans were created by selecting appropriate collimator positions for each row of beam spots during a Raster-style scanning pattern which were optimized to maximize the dose contributions to the target and limited the dose delivered to adjacent normal tissue. RESULTS: The reduction of mean dose to normal tissue adjacent to the target, as defined by a 10 mm ring surrounding the target, averaged 13.65% (range: 11.8%-16.9%) and 5.18% (2.9%-7.1%) for the DCS and fixed aperture plans, respectively. The conformity index, as defined by the ratio of the volume of the 50% isodose line to the target volume, yielded an average improvement of 21.35% (19.4%-22.6%) and 8.38% (4.7%-12.0%) for the DCS and fixed aperture plans, respectively. CONCLUSIONS: The ability of the DCS to provide collimation to each energy layer yielded better conformity in comparison to fixed aperture plans.

Quantitative assessment of anatomical change using a virtual proton depth radiograph for adaptive head and neck proton therapy.

The aim of this work is to demonstrate the feasibility of using water-equivalent thickness (WET) and virtual proton depth radiographs (PDRs) of intensity corrected cone-beam computed tomography (CBCT) to detect anatomical change and patient setup error to trigger adaptive head and neck proton therapy. The planning CT (pCT) and linear accelerator (linac) equipped CBCTs acquired weekly during treatment of a head and neck patient were used in this study. Deformable image registration (DIR) was used to register each CBCT with the pCT and map Hounsfield units (HUs) from the planning CT (pCT) onto the daily CBCT. The deformed pCT is referred as the corrected CBCT (cCBCT). Two dimensional virtual lateral PDRs were generated using a ray-tracing technique to project the cumulative WET from a virtual source through the cCBCT and the pCT onto a virtual plane. The PDRs were used to identify anatomic regions with large variations in the proton range between the cCBCT and pCT using a threshold of 3 mm relative difference of WET and 3 mm search radius criteria. The relationship between PDR differences and dose distribution is established. Due to weight change and tumor response during treatment, large variations in WETs were observed in the relative PDRs which corresponded spatially with an increase in the number of failing points within the GTV, especially in the pharynx area. Failing points were also evident near the posterior neck due to setup variations. Differences in PDRs correlated spatially to differences in the distal dose distribution in the beam's eye view. Virtual PDRs generated from volumetric data, such as pCTs or CBCTs, are potentially a useful quantitative tool in proton therapy. PDRs and WET analysis may be used to detect anatomical change from baseline during treatment and trigger further analysis in adaptive proton therapy.

Toward improved target conformity for two spot scanning proton therapy delivery systems using dynamic collimation.

PURPOSE: To quantify improvement in target conformity in brain and head and neck tumor treatments resulting from the use of a dynamic collimation system (DCS) with two spot scanning proton therapy delivery systems (universal nozzle, UN, and dedicated nozzle, DN) with median spot sizes of 5.2 and 3.2 mm over a range of energies from 100 to 230 MeV. METHODS: Uncollimated and collimated plans were calculated with both UN and DN beam models implemented within our in-house treatment planning system for five brain and ten head and neck datasets in patients previously treated with spot scanning proton therapy. The prescription dose and beam angles from the clinical plans were used for both the UN and DN plans. The average reduction of the mean dose to the 10-mm ring surrounding the target between the uncollimated and collimated plans was calculated for the UN and the DN. Target conformity was analyzed using the mean dose to 1-mm thickness rings surrounding the target at increasing distances ranging from 1 to 10 mm. RESULTS: The average reductions of the 10-mm ring mean dose for the UN and DN plans were 13.7% (95% CI: 11.6%-15.7%; p < 0.0001) and 11.5% (95% CI: 9.5%-13.5%; p < 0.0001) across all brain cases and 7.1% (95% CI: 4.4%-9.8%; p < 0.001) and 6.3% (95% CI: 3.7%-9.0%; p < 0.001), respectively, across all head and neck cases. The collimated UN plans were either more conformal (all brain cases and 60% of the head and neck cases) than or equivalent (40% of the head and neck cases) to the uncollimated DN plans. The collimated DN plans offered the highest conformity. CONCLUSIONS: The DCS added either to the UN or DN improved the target conformity. The DCS may be of particular interest for sites with UN systems looking for a more economical solution than upgrading the nozzle to improve the target conformity of their spot scanning proton therapy system.

Bag and loop small bowel contouring strategies differentially estimate small bowel dose for post-hysterectomy women receiving pencil beam scanning proton therapy.

Background Small bowel (SB) dose-volume relationships established during initial computed tomography (CT) simulations may change throughout therapy due to organ displacement and motion. We investigated the impact of organ motion on SB dose-volume histograms (DVHs) in women with gynecologic malignancies treated with pencil beam scanning (PBS) proton therapy and compared PBS SB DVHs to intensity-modulated radiation therapy (IMRT). Material and methods Post-hysterectomy patients (n = 11) treated for gynecologic cancers were enrolled on an image-guided proton therapy protocol involving CT simulation with full (CTF) and empty (CTE) bladders and weekly/biweekly on-treatment scans. IMRT plans were generated for comparative analysis. SB was contoured as bowel loops or bowel bag. Wilcoxon signed-rank tests were used for matched-pair comparisons of SB, bladder, and rectum dose-volumes between CT scans and between PBS and IMRT plans. Results In PBS loops analysis, on-treatment DVH was significantly higher than CTF for doses <45 Gy (p < 0.05), and not significantly different than CTE. Specifically, V15 for loops was higher on-treatment (median 240 cm(3)) compared to CTF (median 169 cm(3), p = 0.03). In PBS bag analysis, on-treatment DVH was not significantly different from CTF across all dose ranges. Bowel bag V45 was not significantly different between on-treatment (median 540 cm(3)) and CTF (median 499 cm(3), p = 0.53). Decreasing bladder volume was associated with increasing V15 for loops and V45 for bowel bag (p < 0.005, both). Comparing PBS and IMRT, PBS resulted in significantly lower DVHs at low dose regions (<38 Gy) and higher DVHs at high dose regions (42.5-45.5 Gy) in both loops and bag analysis. IMRT plans demonstrated higher on-treatment SB loop DVHs and only minimal differences in bowel bag DVHs compared to CTF. Conclusions SB DVHs were well estimated by CTF bowel bag and underestimated by CTF loops in the setting of inconsistent bladder filling. Verifying bladder filling prior to treatment or using CTE for planning may more conservatively estimate SB dose-volume relationships.

Theoretical Benefits of Dynamic Collimation in Pencil Beam Scanning Proton Therapy for Brain Tumors: Dosimetric and Radiobiological Metrics.

PURPOSE: To quantify the dosimetric benefit of using a dynamic collimation system (DCS) for penumbra reduction during the treatment of brain tumors by pencil beam scanning proton therapy (PBS PT). METHODS AND MATERIALS: Collimated and uncollimated brain treatment plans were created for 5 patients previously treated with PBS PT and retrospectively enrolled in an institutional review board-approved study. The in-house treatment planning system, RDX, was used to generate the plans because it is capable of modeling both collimated and uncollimated beamlets. The clinically delivered plans were reproduced with uncollimated plans in terms of target coverage and organ at risk (OAR) sparing to ensure a clinically relevant starting point, and collimated plans were generated to improve the OAR sparing while maintaining target coverage. Physical and biological comparison metrics, such as dose distribution conformity, mean and maximum doses, normal tissue complication probability, and risk of secondary brain cancer, were used to evaluate the plans. RESULTS: The DCS systematically improved the dose distribution conformity while preserving the target coverage. The average reduction of the mean dose to the 10-mm ring surrounding the target and the healthy brain were 13.7% (95% confidence interval [CI] 11.6%-15.7%; P<.0001) and 25.1% (95% CI 16.8%-33.4%; P<.001), respectively. This yielded an average reduction of 24.8% (95% CI 0.8%-48.8%; P<.05) for the brain necrosis normal tissue complication probability using the Flickinger model, and 25.1% (95% CI 16.8%-33.4%; P<.001) for the risk of secondary brain cancer. A general improvement of the OAR sparing was also observed. CONCLUSION: The lateral penumbra reduction afforded by the DCS increases the normal tissue sparing capabilities of PBS PT for brain cancer treatment while preserving target coverage.

Proton Therapy for Vaginal Reirradiation.

Primary or recurrent gynecologic cancers in operable patients with a history of prior pelvic radiation are typically treated with surgery based on the risk of late toxicities historically associated with reirradiation. A number of studies have demonstrated that, compared with conventional radiation therapy (RT) using photons, proton therapy (PT) offers dosimetric advantages for patients with gynecologic cancers by reducing radiation dose to healthy tissues. Thereby, we expect that, in appropriately selected cases, PT may reduce long-term treatment-related morbidities without compromising treatment efficacy. Herein, we describe the treatment planning, technique, and long-term follow-up of a patient who was treated with PT for a primary vaginal carcinoma nearly 30 years after a prior course of pelvic RT. Using this case, we illustrate the utility and advantages of PT in the treatment of cancers that occur at less favorable sites, adjacent to normal structures with low radiation tolerance, or in paients with a history of prior irradiation. Additionally, we provide a brief discussion and review of literature of prior case series of pelvic reirradiation, illustrating the value of identifying treatment approaches that can reduce treatment-related morbidities, particularly late treatment toxicities.

Comparison of Pencil Beam Scanning Proton- and Photon-Based Techniques for Carcinoma of the Parotid.

PURPOSE: To report the dosimetric advantages of a comparison between pencil beam scanning (PBS) proton therapy versus intensity-modulated radiation therapy (IMRT) for parotid gland cancers. PATIENTS AND METHODS: This was a retrospective, dosimetric comparison of 8 patients who received external beam radiation therapy at our institution between 2009 and 2011. Two separate plans were generated for each patient: 1 IMRT and 1 PBS plan. The prescription dose for each plan was 60 Gy for IMRT and 60 Gy (RBE) for PBS. We measured dose-volume relationships for target volumes and organs at risk with each treatment technique. Dosimetric comparisons for each organ at risk were made by using the Wilcoxon signed rank test. All tests were 2-tailed, with P values < .05 considered statistically significant. RESULTS: The mean patient planning target volume was 160.9 cm3 (SD 74.6). Pencil beam scanning, compared to IMRT, significantly reduced the mean dose to the following structures: ipsilateral temporal lobe (2.86 versus 9.59 Gy (RBE), P = .01), oral cavity (0.58 versus 13.48 Gy (RBE), P = .01), mandible (V50: 7.4% versus 12.8%, P = .01), contralateral parotid gland (0.003 versus 4.64 Gy (RBE), P = .01), ipsilateral submandibular gland (16.59 versus 38.94 Gy (RBE), P = .03), and contralateral submandibular gland (0.02 versus 5.34 Gy (RBE), P = .01). Pencil beam scanning also significantly reduced the maximum dose delivered to the brainstem (7.1 versus 30.9 Gy (RBE), P = .01). CONCLUSION: Pencil beam scanning allows for superior normal tissue sparing while still maintaining excellent target coverage in patients with resected parotid gland cancers. These findings suggest that PBS may allow for an improved therapeutic index for these patients. Clinical outcomes with PBS should be evaluated prospectively, with a focus on disease outcomes as well as treatment-related toxicities and patient quality of life.

Improving Head and Neck Cancer Treatments Using Dynamic Collimation in Spot Scanning Proton Therapy.

PURPOSE: Interest in using collimation for spot scanning proton therapy has recently increased in an attempt to improve the lateral penumbra. To investigate the advantages of such an approach for complex targets, a plan comparison between uncollimated and collimated beam spots was performed for patients with head and neck cancer. PATIENTS AND METHODS: For 10 patients with head and neck cancer, previously treated with spot scanning proton therapy, uncollimated and collimated treatment plans were created using an in-house treatment-planning system capable of modeling asymmetric-beamlet dose distributions resulting from the use of a dynamic collimation system. Both uncollimated and collimated plans reproduced clinically delivered plans in terms of target coverage. A relative plan comparison was performed using both physical and radiobiological metrics on the organs at risk. RESULTS: The dynamic collimation system improved dose-distribution conformity while preserving target coverage. The median reduction of the mean dose to the esophagus, uninvolved larynx, and uninvolved parotids were -11.9% (minimum to maximum, -6.4% to -24.1%), -7.2% (-0.8% to -60.1%), and -5.2% (-0.2% to -21.5%), respectively, and depended on the organ location relative to the target and radiation beam angle. The collimation did not improve dose to some organs at risk surrounded by the target or located upstream of Bragg peaks because of the priority on the target coverage. CONCLUSION: In spot scanning proton therapy, the dynamic collimation system generally affords better target conformity, which results in improvement in organ-at-risk sparing in the head and neck region while preserving target coverage. However, the benefits of collimation and the increased complexity should be considered for each patient. Patients with large bilateral targets or organs at risk surrounded by the target showed the least benefit.

Initial Report of Pencil Beam Scanning Proton Therapy for Posthysterectomy Patients With Gynecologic Cancer.

PURPOSE: To report the acute toxicities associated with pencil beam scanning proton beam radiation therapy (PBS) for whole pelvis radiation therapy in women with gynecologic cancers and the results of a dosimetric comparison of PBS versus intensity modulated radiation therapy (IMRT) plans. METHODS AND MATERIALS: Eleven patients with posthysterectomy gynecologic cancer received PBS to the whole pelvis. The patients received a dose of 45 to 50.4 Gy relative biological effectiveness (RBE) in 1.8 Gy (RBE) daily fractions. Acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 4. A dosimetric comparison between a 2-field posterior oblique beam PBS and an IMRT plan was conducted. The Wilcoxon signed rank test was used to assess the potential dosimetric differences between the 2 plans and PBS target coverage robustness relative to setup uncertainties. RESULTS: The median patient age was 55 years (range 23-76). The primary site was cervical in 7, vaginal in 1, and endometrial in 3. Of the 11 patients, 7 received concurrent cisplatin, 1 each received sandwich carboplatin and paclitaxel chemotherapy, both sandwich and concurrent chemotherapy, and concurrent and adjuvant chemotherapy, and 1 received no chemotherapy. All patients completed treatment. Of the 9 patients who received concurrent chemotherapy, the rate of grade 2 and 3 hematologic toxicities was 33% and 11%, respectively. One patient (9%) developed grade 3 acute gastrointestinal toxicity; no patient developed grade ≥3 genitourinary toxicity. The volume of pelvic bone marrow, bladder, and small bowel receiving 10 to 30 Gy was significantly lower with PBS than with intensity modulated radiation therapy (P<.001). The target coverage for all PBS plans was robust relative to the setup uncertainties (P>.05) with the clinical target volume mean dose percentage received by 95% and 98% of the target volume coverage changes within 2% for the individual plans. CONCLUSIONS: Our results have demonstrated the clinical feasibility of PBS and the dosimetric advantages, especially for the low-dose sparing of normal tissues in the pelvis with the target robustness maintained relative to the setup uncertainties. Future studies with larger patient numbers are planned to further validate our preliminary findings.

Adjuvant radiation therapy for bladder cancer: a dosimetric comparison of techniques.

Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to compare plans for bowel and rectal volumes exposed to 35% (V35%), 65% (V65%), and 95% (V95%) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V35% rectum, V65% rectum, and V95% rectum; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V95% bowel, V65% bowel, or V35% bowel). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V65% bowel and V95% bowel for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation. Using the IMRT or the SFUD plans instead of the 3-D conformal plan may improve both bowel and rectal toxicity.