Impact of proton PBS machine operating parameters on the effectiveness of layer rescanning for interplay effect mitigation in lung SBRT treatment.

BACKGROUND: Rescanning is a common technique used in proton pencil beam scanning to mitigate the interplay effect. Advances in machine operating parameters across different generations of particle therapy systems have led to improvements in beam delivery time (BDT). However, the potential impact of these improvements on the effectiveness of rescanning remains an underexplored area in the existing research. METHODS: We systematically investigated the impact of proton machine operating parameters on the effectiveness of layer rescanning in mitigating interplay effect during lung SBRT treatment, using the CIRS phantom. Focused on the Hitachi synchrotron particle therapy system, we explored machine operating parameters from our institution's current (2015) and upcoming systems (2025A and 2025B). Accumulated dynamic 4D dose were reconstructed to assess the interplay effect and layer rescanning effectiveness. RESULTS: Achieving target coverage and dose homogeneity within 2% deviation required 6, 6, and 20 times layer rescanning for the 2015, 2025A, and 2025B machine parameters, respectively. Beyond this point, further increasing the number of layer rescanning did not further improve the dose distribution. BDTs without rescanning were 50.4, 24.4, and 11.4 s for 2015, 2025A, and 2025B, respectively. However, after incorporating proper number of layer rescanning (six for 2015 and 2025A, 20 for 2025B), BDTs increased to 67.0, 39.6, and 42.3 s for 2015, 2025A, and 2025B machine parameters. Our data also demonstrated the potential problem of false negative and false positive if the randomness of the respiratory phase at which the beam is initiated is not considered in the evaluation of interplay effect. CONCLUSION: The effectiveness of layer rescanning for mitigating interplay effect is affected by machine operating parameters. Therefore, past clinical experiences may not be applicable to modern machines.

Effect of the initial energy layer and spot placement parameters on IMPT delivery efficiency and plan quality.

PURPOSE: Improving efficiency of intensity modulated proton therapy (IMPT) treatment can be achieved by shortening the beam delivery time. The purpose of this study is to reduce the delivery time of IMPT, while maintaining the plan quality, by finding the optimal initial proton spot placement parameters. METHODS: Seven patients previously treated in the thorax and abdomen with gated IMPT and voluntary breath-hold were included. In the clinical plans, the energy layer spacing (ELS) and spot spacing (SS) were set to 0.6-0.8 (as a scale factor of the default values). For each clinical plan, we created four plans with ELS increased to 1.0, 1.2, 1.4, and SS to 1.0 while keeping all other parameters unchanged. All 35 plans (130 fields) were delivered on a clinical proton machine and the beam delivery time was recorded for each field. RESULTS: Increasing ELS and SS did not cause target coverage reduction. Increasing ELS had no effect on critical organ-at-risk (OAR) doses or the integral dose, while increasing SS resulted in slightly higher integral and selected OAR doses. Beam-on times were 48.4 ± 9.2 (range: 34.1-66.7) seconds for the clinical plans. Time reductions were 9.2 ± 3.3 s (18.7 ± 5.8%), 11.6 ± 3.5 s (23.1 ± 5.9%), and 14.7 ± 3.9 s (28.9 ± 6.1%) when ELS was changed to 1.0, 1.2, and 1.4, respectively, corresponding to 0.76-0.80 s/layer. SS change had a minimal effect (1.1 ± 1.6 s, or 1.9 ± 2.9%) on the beam-on time. CONCLUSION: Increasing the energy layers spacing can reduce the beam delivery time effectively without compromising IMPT plan quality; increasing the SS had no meaningful impact on beam delivery time and resulted in plan-quality degradation in some cases.

Adjuvant chemoradiation for high-grade cardiac leiomyosarcoma in a child: Case report and review of literature.

A 13-year-old healthy girl presented with dizziness and palpitations, found to have a left atrial mass. An 8-cm tumor was removed en bloc. Pathology confirmed grade 3 leiomyosarcoma with multifocal positive margins. She received adjuvant ifosfamide and doxorubicin, followed by concurrent proton radiotherapy and ifosfamide. Radiotherapy included 66 Gy (RBE) in 33 fractions to the operative bed. Prospectively graded toxicities included Grade 2 esophagitis and Grade 1 anorexia, dermatitis, and fatigue. She completed six cycles of ifosfamide. Two years post operation, she had no evidence of disease, intermittent palpitations with normal cardiac function, and no other cardiopulmonary or esophageal symptoms.

Proton therapy for adults with mediastinal lymphomas: the International Lymphoma Radiation Oncology Group guidelines.

Among adult lymphoma survivors, radiation treatment techniques that increase the excess radiation dose to organs at risk (OARs) put patients at risk for increased side effects, especially late toxicities. Minimizing radiation to OARs in adults patients with Hodgkin and non-Hodgkin lymphomas involving the mediastinum is the deciding factor for the choice of treatment modality. Proton therapy may help to reduce the radiation dose to the OARs and reduce toxicities, especially the risks for cardiac morbidity and second cancers. Because proton therapy may have some disadvantages, identifying the patients and the circumstances that may benefit the most from proton therapy is important. We present modern guidelines to identify adult lymphoma patients who may derive the greatest benefit from proton therapy, along with an analysis of the advantages and disadvantages of proton treatment.

Proton therapy for skull-base chondrosarcoma, a single-institution outcomes study.

BACKGROUND: We sought to evaluate the effectiveness of definitive or adjuvant external-beam proton therapy on local control and survival in patients with skull-base chondrosarcoma. METHODS: We reviewed the medical records of 43 patients with a median age of 49 years (range, 23-80 years) treated with double-scattered 3D conformal proton therapy for skull-base chondrosarcomas between January 2007 and February 2016. Proton therapy-related toxicities were scored using CTCAE v4.0. RESULTS: The median radiotherapy dose was 73.8 Gy(RBE) (range, 64.5-74.4 Gy[RBE]). Thirty-six (84%) and 7 (16%) patients underwent surgical resection or biopsy alone. Tumor grade distribution included: grade 1, 19 (44%) patients; grade 2, 22 (51%); and grade 3, 2 (5%). Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following surgery. The median follow-up was 3.7 years (range, 0.7-10.1 years). There were no acute grade 3 toxicities related to RT. At 4 years following RT, actuarial rates of overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were 95%, 100%, 89%, and 95%. CONCLUSION: High-dose, double-scattered 3D conformal proton therapy alone or following surgical resection for skull-base chondrosarcoma is an effective treatment with a high rate of local control with no acute grade 3 radiation-related toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Radiation doses to brain substructures associated with cognition in radiotherapy of pediatric brain tumors.

Background: Several brain substructures associated with cognition (BSCs) are located close to typical pediatric brain tumors. Pediatric patients therefore have considerable risks of neurocognitive impairment after brain radiotherapy. In this study, we investigated the radiation doses received by BSCs for three common locations of pediatric brain tumor entities. Material and methods: For ten patients in each group [posterior fossa ependymoma (PFE), craniopharyngioma (CP), and hemispheric ependymoma (HE)], the cumulative fraction of BSCs volumes receiving various dose levels were analyzed. We subsequently explored the differences in dose pattern between the three groups and used available dose response models from the literature to estimate treatment-induced intelligence quotient (IQ) decline. Results: Doses to BSCs were found to differ considerably between the groups, depending on their position relative to the tumor. Large inter-patient variations were observed in the ipsilateral structures of the HE groups, and at low doses for all three groups. IQ decline estimates differed depending on the model applied, presenting larger variations in the HE group. Conclusion: While there were notable differences in the dose patterns between the groups, the extent of estimated IQ decline depended more on the model applied. This inter-model variability should be considered in dose-effect assessments on cognitive outcomes of pediatric patients.

Impact of unfavorable factors on outcomes among inoperable stage II-IV Nonsmall cell lung cancer patients treated with proton therapy.

PURPOSE: To investigate the impact of unfavorable risk factors among patients with locally advanced nonsmall cell lung cancer (LA-NSCLC) treated with proton therapy (PT). MATERIAL AND METHODS: From May 2008 through July 2015, 90 consecutive patients with unresectable stage II-IV (oligometastatic) NSCLC were treated with PT. Unfavorable factors including age ≥80 years, stage IV, weight loss >10% in 3 months, performance status (PS) ≥2, FEV1 < 1.0 or O2 dependency, prior lung cancer, prior lung surgery, prior 2nd cancer in the past 3 years, and prior chest irradiation were evaluated. All patients received standard fractionation of 1.8-2 Gy(RBE) (median dose, 70 Gy[RBE]). Overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method. The impact of unfavorable factors was analyzed in Cox regression models. RESULTS: Twenty-six percent were favorable-risk, while 42%, 22%, and 10% had 1-, 2-, or ≥3 unfavorable factors. The 2-year OS was 52% and 45% (p = .8522), and 2-year PFS was 21% and 44% (p = .0207), for favorable and unfavorable risk patients, respectively. Among patients with stage III-IV, only PS ≥2 adversely impacted OS (p = .0015). CONCLUSION: Most patients treated with PT for LA-NSCLC have unfavorable risk factors. These patients had similar outcomes to favorable-risk patients. Enrollment in future clinical trials may improve if eligibility is less restrictive.

Impact of intrafraction prostate motion on clinical target coverage in proton therapy: A simulation study of dosimetric differences in two delivery techniques.

PURPOSE: To investigate the dosimetric impact of prostate intrafraction motion on proton double-scattering (DS) and uniform scanning (US) treatments using electromagnetic transponder-based prostate tracking data in simulated treatment deliveries. METHODS: In proton DS delivery, the spread-out Bragg peak (SOBP) is created almost instantaneously by the constant rotation of the range modulator. US, however, delivers each entire energy layer of the SOBP sequentially from distal to proximal direction in time, which can interplay with prostate intrafraction motion. This spatiotemporal interplay during proton treatment was simulated to evaluate its dosimetric impact. Prostate clinical target volume (CTV) dose was obtained by moving CTV through dose matrices of the energy layers according to prostate-motion traces. Fourteen prostate intrafraction motion traces of each of 17 prostate patients were used in the simulated treatment deliveries. Both single fraction dose-volume histograms (DVHs) and fraction-cumulative DVHs were obtained for both 2 Gy per fraction and 7.25 Gy per fraction stereotactic body radiotherapy (SBRT). RESULTS: The simulation results indicated that CTV dose degradation depends on the magnitude and direction of prostate intrafraction motion and is patient specific. For some individual fractions, prescription dose coverage decreased in both US and DS treatments, and hot and cold spots inside the CTV were observed in the US results. However, fraction-cumulative CTV dose coverage showed much reduced dose degradation for both DS and US treatments for both 2 Gy per fraction and SBRT simulations. CONCLUSIONS: This study indicated that CTV dose inhomogeneity may exist for some patients with severe prostate intrafraction motion during US treatments. However, there are no statistically significant dose differences between DS and US treatment simulations. Cumulative dose of multiple-fractions significantly reduced dose uncertainties.

Five-year outcomes from a prospective trial of image-guided accelerated hypofractionated proton therapy for prostate cancer.

PURPOSE: To report 5-year outcomes of a prospective trial of image-guided accelerated hypofractionated proton therapy (AHPT) for prostate cancer. PATIENTS AND METHODS: 215 prostate cancer patients accrued to a prospective institutional review board-approved trial of 70Gy(RBE) in 28 fractions for low-risk disease (n = 120) and 72.5Gy(RBE) in 29 fractions for intermediate-risk disease (n = 95). This trial excluded patients with prostate volumes of ≥60 cm3 or International Prostate Symptom Scores (IPSS) of ≥15, patients on anticoagulants or alpha-blockers, and patients in whom dose-constraint goals for organs at risk (OAR) could not be met. Toxicities were graded prospectively according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. This trial can be found on ClinicalTrials.gov (NCT00693238). RESULTS: Median follow-up was 5.2 years. Five-year rates of freedom from biochemical and clinical disease progression were 95.9%, 98.3%, and 92.7% in the overall group and the low- and intermediate-risk subsets, respectively. Actuarial 5-year rates of late radiation-related CTCAE v3.0 grade 3 or higher gastrointestinal and urologic toxicities were 0.5% and 1.7%, respectively. Median IPSS before treatment and at 4+ years after treatment were 6 and 5 for low-risk patients and 4 and 6 for intermediate-risk patients. CONCLUSIONS: Image-guided AHPT 5-year outcomes show high efficacy and minimal physician-assessed toxicity in selected patients. These results are comparable to the 5-year results of our prospective trials of standard fractionated proton therapy for patients with low-risk and intermediate-risk prostate cancer. Longer follow-up and a larger cohort are necessary to confirm these findings.

Biological dose and complication probabilities for the rectum and bladder based on linear energy transfer distributions in spot scanning proton therapy of prostate cancer.

BACKGROUND: The increased linear energy transfer (LET) at the end of the Bragg peak causes concern for an elevated and spatially varying relative biological effectiveness (RBE) of proton therapy (PT), often in or close to dose-limiting normal tissues. In this study, we investigated dose-averaged LET (LETd) distributions for spot scanning PT of prostate cancer patients using different beam angle configurations. In addition, we derived RBE-weighted (RBEw) dose distributions and related normal tissue complication probabilities (NTCPs) for the rectum and bladder. MATERIAL AND METHODS: A total of 21 spot scanning proton plans were created for each of six patients using a prescription dose of 78 Gy(RBE1.1), with each plan using two 'mirrored' beams with gantry angles from 110°/250° to 70°/290°, in steps of 2°. Physical dose and LETd distributions were calculated as well as RBEw dose distributions using either RBE = 1.1 or three different variable RBE models. The resulting biological dose distributions were used as input to NTCP models for the rectum and bladder. RESULTS: For anterior oblique (AO) configurations, the rectum LETd volume and RBEw dose increased with increasing angles off the lateral opposing axis, with the RBEw rectum dose being higher than for all posterior oblique (PO) configurations. For PO configurations, the corresponding trend was seen for the bladder. Using variable RBE models, the rectum NTCPs were highest for the AO configurations with up to 3% for the 80°/280° configuration while the bladder NTCPs were highest for the PO configurations with up to 32% for the 100°/260°. The rectum D1cm3 constraint was fulfilled for most patients/configurations when using uniform RBE but not for any patient/configuration with variable RBE models. CONCLUSIONS: Compared to using constant RBE, the variable RBE models predicted increased biological doses to the rectum, bladder and prostate, which in turn lead to substantially higher estimated rectum and bladder NTCPs.

Linear energy transfer distributions in the brainstem depending on tumour location in intensity-modulated proton therapy of paediatric cancer.

BACKGROUND: For tumours near organs at risk, there is concern about unintended increase in biological dose from elevated linear energy transfer (LET) at the distal end of treatment fields. The objective of this study was therefore to investigate how different paediatric posterior fossa tumour locations impact LET and biological dose to the brainstem during intensity-modulated proton therapy (IMPT). MATERIAL AND METHODS: Multiple IMPT plans were generated for four different simulated tumour locations relative to the brainstem for a five-year-old male patient. A prescribed dose of 59.4 Gy(RBE) was applied to the planning target volumes (PTVs). Plans with two lateral and one posterior non-coplanar fields were created, along with plans with modified field arrangements. The dose-averaged LET (LETd) and the physical dose × RBELET (D × RBELET), where RBELET=1+c × LETd, were calculated using the FLUKA Monte Carlo code. A scaling parameter c was applied to make the RBELET represent variations in the biological effect due to LET. RESULTS: High LETd values surrounded parts of the PTV and encompassed portions of the brainstem. Mean LETd values in the brainstem were 3.2-6.6 keV/µm. The highest absolute brainstem LETd values were seen with the tumour located most distant from the brainstem, whereas lower and more homogeneous LETd values were seen when the tumour invaded the brainstem. In contrast, the highest mean D × RBELET values were found in the latter case (54.0 Gy(RBE)), while the case with largest distance between tumour and brainstem had a mean D × RBELET of 1.8 Gy(RBE). CONCLUSIONS: Using IMPT to treat posterior fossa tumours may result in high LETd values within the brainstem, particularly if the tumour volume is separated from the brainstem. However, the D × RBELET was greater for tumours that approached or invaded the brainstem. Changing field angles showed a reduction of LETd and D × RBELET in the brainstem.

Proton Therapy for Pediatric Hodgkin Lymphoma.

BACKGROUND: Compared to X-ray radiation therapy, proton therapy (PT) reduces the radiation dose to organs at risk, which is expected to translate into fewer second cancers and less cardiac morbidity decades after treatment. The Children's Oncology Group high-risk pediatric Hodgkin lymphoma (PHL) protocol, AHOD1331, allows the use of PT, yet limited data exist on the use of PT in PHL. PROCEDURE: Between 2010 and 2014, 22 pediatric patients were treated with PT for PHL at our institution: 7 intermediate-risk patients, 11 high-risk patients, and 4 relapsed patients. The patients' age ranged from 6 to 18 years old. Median follow-up was 36 months. All patients received chemotherapy before PT. RESULTS: The 2-year and 3-year overall survival rates were both 94%, and the progression-free survival rate was 86%. Recurrences occurred in three high-risk patients: one isolated in-field cervical lymph node and two in-field and out-of-field. All recurrences occurred within 5 months of completing PT. No PT-related grade 3 or higher acute or late complications were observed. CONCLUSION: PT for PHL showed no short-term severe toxicity and yields similar short-term control to recently published large multi-institutional clinical trials.

Incidence and dosimetric parameters of pediatric brainstem toxicity following proton therapy.

BACKGROUND: Proton therapy offers superior low and intermediate radiation dose distribution compared with photon-based radiation for brain and skull base tumors; yet tissue within and adjacent to the target volume may receive a comparable radiation dose. We investigated the tolerance of the pediatric brainstem to proton therapy and identified prognostic variables. MATERIAL AND METHODS: All patients < 18 years old with tumors of the brain or skull base treated from 2007 to 2013 were reviewed; 313 who received > 50.4 CGE to the brainstem were included in this study. Brainstem toxicity was graded according to the NCI Common Terminology Criteria for Adverse Events v4.0. RESULTS: The three most common histologies were ependymoma, craniopharyngioma, and low-grade glioma. Median patient age was 5.9 years (range 0.5-17.9 years) and median prescribed dose was 54 CGE (range 48.6-75.6 CGE). The two-year cumulative incidence of toxicity was 3.8% ± 1.1%. The two-year cumulative incidence of grade 3 + toxicity was 2.1% ± 0.9%. Univariate analysis identified age < 5 years, posterior fossa tumor location and specific dosimetric parameters as factors associated with an increased risk of toxicity. CONCLUSION: Utilization of current national brainstem dose guidelines is associated with a low risk of brainstem toxicity in pediatric patients. For young patients with posterior fossa tumors, particularly those who undergo aggressive surgery, our data suggest more conservative dosimetric guidelines should be considered.

Proton Pencil Beam Scanning Facilitates the Safe Treatment of Extended Radiation Targets for Hodgkin Lymphoma: A Report from the Proton Collaborative Group Registry.

Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT.

A review of the clinical introduction of 4D particle therapy research concepts.

Background and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments. Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic. Results: Available technological capabilities for motion surveillance and compensation determined the course of each 4D particle treatment. 4D motion management, delivery techniques and strategies including imaging were diverse and depended on many factors. These included aspects of motion amplitude, tumour location, as well as accelerator technology driving the necessity of centre-specific dosimetric validation. Novel methodologies for X-ray based image processing and MRI for real-time tumour tracking and motion management were shown to have a large potential for online and offline adaptation schemes compensating for potential anatomical changes over the treatment course. The latest research developments were dominated by particle imaging, artificial intelligence methods and FLASH adding another level of complexity but also opportunities in the context of 4D treatments. Conclusion: This review showed that the rapid technological advances in radiation oncology together with the available intrafractional motion management and adaptive strategies paved the way towards clinical implementation.

Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). MATERIAL AND METHODS: Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. RESULTS: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. CONCLUSION: In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.

Risks of Spinal Abnormalities and Growth Impairment After Radiation to the Spine in Childhood Cancer Survivors: A PENTEC Comprehensive Review.

PURPOSE: A PENTEC (Pediatric Normal Tissue Effects in the Clinic) review was performed to estimate the dose-volume effects of radiation therapy on spine deformities and growth impairment for patients who underwent radiation therapy as children. METHODS AND MATERIALS: A systematic literature search was performed to identify published data for spine deformities and growth stunting. Data were extracted from 12 reports of children irradiated to the spine (N = 603 patients). The extracted data were analyzed to find associations between complication risks and the radiation dose (conventional fractionation throughout) as impacted by exposed volumes and age using the mixed-effects logistic regression model. When appropriate, corrections were made for radiation modality, namely orthovoltage beams. RESULTS: In the regression analysis, the association between vertebral dose and scoliosis rate was highly significant (P < .001). Additionally, young age at time of radiation was highly predictive of adverse outcomes. Clinically significant scoliosis can occur with doses ≥15 Gy to vertebrae during infancy (<2 years of age). For children irradiated at 2 to 6 years of age, overall scoliosis rates of any grade were >30% with doses >20 Gy; grade 2 or higher scoliosis was correlated with doses ≥30 Gy. Children >6 years of age remain at risk for scoliosis with doses >30 Gy; however, most cases will be mild. There are limited data regarding the effect of dose gradients across the spine on degree of scoliosis. The risk of clinically meaningful height loss was minimal when irradiating small volumes of the spine up to 20 Gy (eg, flank irradiation), except in infants who are more vulnerable to lower doses. Growth stunting was more frequent when larger segments of the spine (eg, the entire spine or craniospinal irradiation) were irradiated before puberty to doses >20 Gy. The effect was modest when patients were irradiated after puberty to doses >20 Gy. CONCLUSIONS: To reduce the risk of kyphoscoliosis and growth impairment, the dose to the spine should be kept to <20 Gy for children <6 years of age and to <10 to 15 Gy in infants. The number of vertebral bodies irradiated and dose gradients across the spine should also be limited when possible.

Proton therapy dose distribution comparison between Monte Carlo and a treatment planning system for pediatric patients with ependymoma.

PURPOSE: Compare dose distributions for pediatric patients with ependymoma calculated using a Monte Carlo (MC) system and a clinical treatment planning system (TPS). METHODS: Plans from ten pediatric patients with ependymoma treated using double scatter proton therapy were exported from the TPS and calculated in our MC system. A field by field comparison of the distal edge (80% and 20%), distal fall off (80% to 20%), field width (50% to 50%), and penumbra (80% to 20%) were examined. In addition, the target dose for the full plan was compared. RESULTS: For the 32 fields from the 10 patients, the average differences of distal edge at 80% and 20% on central axis between MC and TPS are -1.9 ± 1.7 mm (p < 0.001) and -0.6 ± 2.3 mm (p = 0.13), respectively. Excluding the fields that ranged out in bone or an air cavity, the 80% difference was -0.9 ± 1.7 mm (p = 0.09). The negative value indicates that MC was on average shallower than TPS. The average difference of the 63 field widths of the 10 patients is -0.7 ± 1.0 mm (p < 0.001), negative indicating on average the MC had a smaller field width. On average, the difference in the penumbra was 2.3 ± 2.1 mm (p < 0.001). The average of the mean clinical target volume dose differences is -1.8% (p = 0.001), negative indicating a lower dose for MC. CONCLUSIONS: Overall, the MC system and TPS gave similar results for field width, the 20% distal edge, and the target coverage. For the 80% distal edge and lateral penumbra, there was slight disagreement; however, the difference was less than 2 mm and occurred primarily in highly heterogeneous areas. These differences highlight that the TPS dose calculation cannot be automatically regarded as correct.

Improving the therapeutic ratio in Hodgkin lymphoma through the use of proton therapy.

The risk of serious late complications in Hodgkin lymphoma (HL) survivors has led to a variety of strategies for reducing late treatment effects from both chemotherapy and radiation therapy. With radiation therapy, efforts have included reductions in dose, reductions in the size of the target volume, and most recently, significant reductions in the dose to nontargeted normal tissues at risk for radiation damage, achieved by using the emerging technologies of intensity-modulated radiation therapy and proton therapy (PT). PT is associated with a substantial reduction in radiation dose to critical organs, such as the heart and lungs, and has the potential to improve not only the therapeutic ratio, but also both event-free and overall survival. This review addresses the rationale and evidence for--and the challenges, cost implications, and future development of--PT as an important part of the treatment strategy in HL.