Future of Telemedicine in Radiation Oncology.

Telemedicine allows providers and patients to communicate without being in the same room through video platforms or telephone. Like the increased use of telework for businesses, telemedicine exploded during the pandemic. While many workplaces and clinics have returned to some level of in-person interactions, the convenience and comfort have given telemedicine staying power. Patients can be seen from the comfort of their homes; family members can join from the same or a different location. Driving, obtaining childcare, or taking time off from work is unnecessary. Pediatric patients' parents can pull them into the conversation at appropriate times and avoid the awkwardness of having them leave for portions of the discussion. Because virtual visits are more efficient for everyone, they can often be scheduled sooner than an in-person visit. While not every visit can be done without the patient physically with the provider, many can. This is particularly true for cancer patients, who often have several visits with multiple providers. For immunocompromised patients, there is an added benefit of avoiding exposure from travel and a hospital visit. Oncology and radiation oncology practices have widely adopted telemedicine. While legal and logistical barriers exist in some areas of the world, these are sure to be resolved to make this medicine feasible for all in the modern era.

PTCOG international survey of practice patterns and trends in utilization of proton therapy for breast cancer.

Purpose/objectives: The indications, techniques, and extent to which proton beam therapy (PBT) is employed for breast cancer are unknown. We seek to determine PBT utilization for breast cancer. Materials/methods: The Particle Therapy Co-Operative Group (PTCOG) Breast Subcommittee developed an IRB-approved 29-question survey and sent it to breast cancer radiation oncologists at all active PBT centers worldwide in June 2023. Descriptive statistics were used to summarize responses, and comparisons by continent were performed using Fisher's exact tests. Results: Of 79 surveys distributed, 28 recipients submitted responses (35 % response rate) representing fifteen U.S., 8 European, and 5 Asian centers (continent response rate 50 %, 38 %, and 18 %, respectively). Overall, 93 % reported treating breast cancer patients with PBT; 13 (50 %) have treated ≥100 breast cancer patients at their center since opening. Most (89 %) have pencil beam scanning technology. Nearly half (46 %) use moderate hypofractionation (15-20 fractions) for regional nodal irradiation and 42 % conventional fractionation (25-30 fractions). More European centers prefer hypofractionation (88 %) vs. Asian (50 %) and U.S. (21 %) centers (p = 0.003). Common patient selection methods were practitioner determination/patient preference (n = 16) and comparative plan evaluation (n = 15). U.S. centers reported the most experience with breast PBT, with 71 % having treated ≥100 breast cancer patients vs. 38 % in Europe and none in Asia (p = 0.001). Of respondent centers, 39 % enrolled ≥75 % of breast PBT patients on a research study. Conclusion: Utilization, patient selection methods, and dose-fractionation approaches for breast cancer PBT vary worldwide. These survey data serve as a benchmark from which successor surveys can provide insight on practice pattern evolution.

Proton-Based Radiation Therapy for Skull Base Chondrosarcomas in Children and Adolescents: 40-Year Experience From the Massachusetts General Hospital.

PURPOSE: The literature on skull base chondrosarcoma (CHS) is scarce. We report outcomes for pediatric and young patients ≤22 years with base of skull CHSs treated with proton-based radiation therapy (PBRT). METHODS AND MATERIALS: We retrospectively reviewed all patients treated with PBRT between 1981 and 2023. Primary endpoints were overall survival (OS), chondrosarcoma-specific survival (CSS), progression-free survival (PFS), local control, and distal control. RESULTS: Eighty-four patients were identified. Median age at diagnosis was 19 years (range, 6-22). Most patients (n = 79, 94%) had conventional CHS, whereas 5 (6%) had mesenchymal CHS. Nine patients (11%) underwent gross total resection, 64 (76%) subtotal resection, and 11 patients (13%) underwent biopsy. Twenty-four (29%) patients progressed before radiation therapy. The median prescription dose was 70 Gy (relative biological equivalent) (range, 50-79.7). At a median follow-up of 18.0 years (IQR, 9.2-26.2) from diagnosis, 11 patients recurred (7 local, 4 distant). Six patients died of disease. Five patients died of other causes. Ten-year OS, CSS, and PFS rates for all patients were 93.3%, 94.7%, and 88%, respectively. Twenty-year OS, CSS, and PFS rates for conventional CHS (n = 79) were 93.1%, 97.1%, and 89.2%, respectively. Mesenchymal histology was significantly associated with worse OS and PFS. Preradiation therapy tumor progression portended worse OS and CSS. Eight patients (9.9 %) experienced a late toxicity grade 3 or greater. CONCLUSIONS: This is the largest cohort of pediatric base of skull CHSs in literature to date. High-dose PBRT after surgical resection achieves excellent disease control with minimal toxicity.

Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field.

BACKGROUND: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields. METHODS: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event-free survival (EFS) and OS were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse and death with Gray's test. RESULTS: Median follow-up was 7.0 years (range: 0.01-22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in-field recurrences (>12 Gy), 6 (19.4 %) had marginal failures (≤12 Gy), and 10 (32.3 %) had both in-field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal-only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06-5.50, p = 0.035) and post-consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19-0.94, p = 0.035) had lower risk of LRR. CONCLUSIONS: Despite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy.

Chondrosarcoma of the Mobile Spine: An Update on Patients Treated at a Single Institution.

STUDY DESIGN: Retrospective study. OBJECTIVE: The objective of this study was to report the clinical data for patients treated with mobile spine chondrosarcoma. SUMMARY OF BACKGROUND DATA: Chondrosarcoma of the mobile spine is a rare and challenging entity. A handful of case series have been published that report the clinical results of treatment, largely influenced by chondrosarcoma of the appendicular skeleton and pelvis. The clinical results of patients treated for chondrosarcoma of the mobile spine from our institution were published over 10 years ago and this represents and update since that publication. METHODS: Inclusion criteria were adults patients treated for chondrosarcoma of the mobile spine at Massachusetts General Hospital between 2007 and 2020. Patients with large sacral tumors extending into the lumbar spine were excluded. Furthermore, we excluded patients with metastatic chondrosarcoma undergoing palliative decompressions for neurological instability or instrumented procedures for biomechanical instability. Therefore, only patients undergoing definitive surgery at the primary site of disease in the mobile spine were included. RESULTS: A total of 24 patients were included for review in this series. Seventeen of the 24 patients had their tumors excised with negative (R0) margins. Three of these 17 patients (18%) were dead of disease at final follow-up. There were two patients with R1 resections and five patients with R2 resections. Three of the seven patients (43%) with positive margins were dead of disease at final follow-up. A Cox proportional hazard analysis indicated total radiation dose was a significant covariate (HR=1.18, 95% CI: 1.01-1.39, P =0.03). CONCLUSIONS: We found higher percentages of overall survival with R0 tumor resection and lower histologic grade, whereas development of metastatic disease was closely associated with local recurrence and poor survival. Despite the improvements in treatment paradigms, it is sobering that our findings largely mirror those of previous work considering patients treated between 1984 and 2006.

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

Unraveling molecular advancements in chordoma tumorigenesis and treatment response: a review of scientific discoveries and clinical implications.

Chordomas are tumors thought to originate from notochordal remnants that occur in midline structures from the cloves of the skull base to the sacrum. In adults, the most common location is the sacrum, followed by the clivus and then mobile spine, while in children a clival origin is most common. Most chordomas are slow growing. Clinical presentation of chordomas tend to occur late, with local invasion and large size often complicating surgical intervention. Radiation therapy with protons has been proven to be an effective adjuvant therapy. Unfortunately, few adjuvant systemic treatments have demonstrated significant effectiveness, and chordomas tend to recur despite intensive multimodal care. However, insight into the molecular underpinnings of chordomas may guide novel therapeutic approaches including selection for immune and molecular therapies, individualized prognostication of outcomes, and real-time noninvasive assessment of disease burden and evolution. At the genomic level, elevated levels of brachyury stemming from duplications and mutations resulting in altered transcriptional regulation may introduce druggable targets for new surgical adjuncts. Transcriptome and epigenome profiling have revealed promoter- and enhancer-dependent mechanisms of protein regulation, which may influence therapeutic response and long-term disease history. Continued scientific and clinical advancements may offer further opportunities for treatment of chordomas. Single-cell transcriptome profiling has further provided insight into the heterogeneous molecular pathways contributing to chordoma propagation. New technologies such as spatial transcriptomics and emerging biochemical analytes such as cell-free DNA have further augmented the surgeon-clinician's armamentarium by facilitating detailed characterization of intra- and intertumoral biology while also demonstrating promise for point-of-care tumor quantitation and assessment. Recent and ongoing clinical trials highlight accelerating interest to translate laboratory breakthroughs in chordoma biology and immunology into clinical care. In this review, the authors dissect the landmark studies exploring the molecular pathogenesis of chordoma. Incorporating this into an outline of ongoing clinical trials and discussion of emerging technologies, the authors aimed to summarize recent advancements in understanding chordoma pathogenesis and how neurosurgical care of chordomas may be augmented by improvements in adjunctive treatments.

The Use of Proton and Carbon Ion Radiation Therapy for Sarcomas.

The unique physical and biological characteristics of proton and carbon ions allow for improved sparing of normal tissues, decreased integral dose to the body, and increased biological effect through high linear energy transfer. These properties are particularly useful for sarcomas given their histology, wide array of locations, and age of diagnosis. This review summarizes the literature and describes the clinical situations in which these heavy particles have advantages for treating sarcomas.

Phantosmia during proton radiation and differences in frequency of phantosmia rates based on proton craniospinal irradiation technique for pediatric brain tumor patients.

BACKGROUND: Unusual olfactory perception, often referred to as "phantosmia" or "cacosmia" has been reported during brain radiotherapy (RT), but is infrequent and does not typically interfere with the ability to deliver treatment. We seek to determine the rate of phantosmia for patients treated with proton craniospinal irradiation (CSI) and identify any potential clinical or treatment-related associations. METHODS: We performed a retrospective review of 127 pediatric patients treated with CSI, followed by a boost to the brain for primary brain tumors in a single institution between 2016 and 2021. Proton CSI was delivered with passive scattering (PS) proton technique (n = 53) or pencil beam scanning technique (PBS) (n = 74). Within the PBS group, treatment delivery to the CSI utilized a single posterior (PA) field (n = 24) or two posterior oblique fields (n = 50). We collected data on phantom smell, nausea/vomiting, and the use of medical intervention. RESULTS: Our cohort included 80 males and 47 females. The median age of patients was 10 years (range: 3-21). Seventy-one patients (56%) received concurrent chemotherapy. During RT, 104 patients (82%) developed worsening nausea, while 63 patients (50%) reported episodes of emesis. Of those patients who were awake during CSI (n = 59), 17 (29%) reported phantosmia. In the non-sedated group, we found a higher rate of phantosmia in patients treated with PBS (n = 16, 42%) than PS (n = 1, 4.7%) (p = .002). Seventy-eight patients (61%) required medical intervention after developing nausea/vomiting or phantosmia during RT. Two patients required sedation due to the malodorous smell during CSI. We did not find any significant difference in nausea/vomiting based on treatment technique. CONCLUSION: Proton technique significantly influenced olfactory perception with greater rates of phantosmia with PBS compared to PS. Prospective studies should be performed to determine the cause of these findings and determine techniques to minimize phantosmia during radiation therapy.

Genetic architecture of the acute and persistent immune cell response after radiation exposure.

Hematologic toxicity is a common side effect of multimodal cancer therapy. Nearly all animal studies investigating the causes of radiotherapy-induced hematologic toxicity use inbred strains with limited genetic diversity and do not reflect the diverse responses observed in humans. We used the population-based Collaborative Cross (CC) mouse resource to investigate the genetic architecture of the acute and persistent immune response after radiation exposure by measuring 22 immune parameters in 1,720 CC mice representing 35 strains. We determined relative acute and persistent radiation resistance scores at the individual strain level considering contributions from all immune parameters. Genome-wide association analysis identified quantitative trait loci associated with baseline and radiation responses. A cross-species radiation resistance score predicted recurrence-free survival in medulloblastoma patients. We present a community resource of immune parameters and genome-wide association analyses before and after radiation exposure for future investigations of the contributions of host genetics on radiosensitivity.

Multi-institutional Characterization of Outcomes for Pediatric and Young Adult Patients With High-Risk Myxopapillary Ependymoma After Radiation Therapy.

PURPOSE: Myxopapillary ependymoma (MPE) is a rare, typically slow-growing subtype of spinal ependymomas. There are no standard guidelines for radiotherapy and long-term outcomes after radiation, particularly patterns of relapse, for pediatric and young adult (YA) patients with MPE remain under-characterized. METHODS AND MATERIALS: This is an Institutional Review Board-approved multi-institutional retrospective cohort study of 60 pediatric and YA patients diagnosed with MPE and received radiotherapy between 2000-2020. Clinical and treatment characteristics, and long-term outcomes were recorded. Site(s) of progression was compared to radiation fields. Survival outcomes were analyzed using Kaplan-Meier method. Cumulative incidence of local in-field progression (CILP) after initial radiotherapy was analyzed using Gray's method with out-of-field-only progression as a competing risk. Univariate analyses were performed using Cox proportional hazard's model. RESULTS: The median age at radiation was 14.8 years (range: 7.1-26.5). At time of radiotherapy, 45 (75.0%) and 35 (58.3%) patients had gross residual and multifocal disease, respectively. Forty-eight (80.0%), seven (11.7%) and five (8.3%) patients received involved field radiotherapy, craniospinal irradiation, and whole spine radiation, respectively. Median follow-up from end of radiotherapy was 6.2 years (range: 0.6-21.0). Five-year overall survival, progression-free survival, and CILP were 100%, 60.8% and 4.1%, respectively. Both local recurrences were at sites of gross residual disease. Of the eighteen out-of-field first recurrences after radiotherapy, all were superior to the initial treatment field and nine had intracranial relapse. On univariate analyses, distant-only recurrence before radiation (HR: 4.00, 95% CI: 1.54-10.43, p = 0.005) was significantly associated with shorter time to progression. CONCLUSIONS: While the risk of recurrence within the radiation field is low, pediatric and YA patients with high-risk MPE remain at risk for recurrences in the spine above the radiation field and intracranially after radiotherapy. Future prospective studies are needed to investigate the appropriate radiation field and dose based on the extent of metastases.

Surgery and proton radiation therapy for pediatric base of skull chordomas: Long-term clinical outcomes for 204 patients.

BACKGROUND: Data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population is limited. We report patient outcomes after surgery and proton radiotherapy (PRT). METHODS: Pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (proton-based; for most, 80% proton/20% photon) at the Massachusetts General Hospital from 1981 to 2021. Endpoints of interest were overall survival (OS), disease-specific survival, progression-free survival (PFS), freedom from local recurrence (LC), and freedom from distant failure (DC). RESULTS: Of 204 patients, median age at diagnosis was 11.1 years (range, 1-21). Chordoma location included 59% upper and/or middle clivus, 36% lower clivus, 4% craniocervical junction, and 1% nasal cavity. Fifteen (7%) received pre-RT chemotherapy. Forty-seven (23%) received PRT, and 157 (77%) received comboRT. Median total dose was 76.7 Gy (RBE) (range, 59.3-83.3). At a median follow-up of 10 years (interquartile range, 5-16 years), 56 recurred. Median OS and PFS were 26 and 25 years, with 5-, 10-, and 20-year OS and PFS rates of 84% and 74%, 78% and 69%, and 64% and 64%, respectively. Multivariable actuarial analyses showed poorly differentiated subtype, radiographical progression prior to RT, larger treatment volume, and lower clivus location to be prognostic factors for worse OS, PFS, and LC. RT was well tolerated at a median follow-up of 9 years (interquartile range, 4-16 years). Side effects included 166 patients (80%) with mild/moderate acute toxicities, 24 (12%) patients with late toxicities, and 4 (2%) who developed secondary radiation-related malignancies. CONCLUSION: This is the largest cohort of BOS chordomas in the literature, pediatric and/or adult. High-dose PRT following surgical resection is effective with low rates of late toxicity.

Toward Systematic Assessment and Improvement of Radiation Therapy Plan Quality of Cooperative Group Trial Submissions: A Report From the Children's Oncology Group.

PURPOSE: This study evaluates the quality of plans used for the treatment of patients in the Children's Oncology Group study ACNS1123. Plan quality is quantified based on a scoring system specific to the protocol. In this way, the distribution of plan quality scores is determined that can be used to identify plan quality issues for this study and for future plan quality improvement. METHODS AND MATERIALS: ACNS1123 stratum 1 patients (70) were evaluated. This included 50 photon and 20 proton plans. Digital Imaging and Communications in Medicine (DICOM) structure and dose data were obtained from the Children's Oncology Group. A commercially available plan quality scoring algorithm was used to create a scoring system we designed using the protocol dosimetric requirements. The whole ventricle and boost planning target volumes (PTVs) could earn a maximum of 70 points, whereas the organs at risk could earn 30 points (total maximum score of 100 points). The scoring algorithm adjusted scores based on the difficulty in achieving the structure dose requirements, which depended on the proximity of the PTVs and the dose gradients achieved relative to the organs at risk. The distribution of plan scores was used to determine the mean, median, and range of scores. RESULTS: The median adjusted plan quality scores for the 20 proton and 50 photon plans were 83.3 and 86.9, respectively. The range of adjusted scores (maximum to minimum) was 50 points. The average score adjustment was 7.4 points. Photon and proton plans performed almost equally. Average plan quality by individual structure revealed that the brain stem, PTV boost, and cochlea lost the most points. CONCLUSIONS: This report is the first to systematically analyze overall radiation therapy plan quality scores for an entire cohort of patients treated in a cooperative group clinical trial. The methodology demonstrated a large variation in plan quality in this trial. Future clinical trials could potentially use this method to reduce plan quality variability, which may improve outcomes.

Prognostic Significance of Percentage and Size of Dedifferentiation in Dedifferentiated Chondrosarcoma.

Dedifferentiated chondrosarcoma is rare, aggressive, and microscopically bimorphic. How pathologic features such as the amounts of dedifferentiation affect prognosis remains unclear. We evaluated the percentages and sizes of dedifferentiation in a consecutive institutional series of dedifferentiated chondrosarcomas from 1999 to 2021. The statistical analysis included cox proportional hazard models and log-rank tests. Of the 67 patients (26 women, 41 men; age, 39 to >89 [median 61] years; 2 with Ollier disease), 58 presented de novo; 9 were identified with conventional chondrosarcomas 0.6-13.2 years (median, 5.5 years) prior. Pathologic fracture and distant metastases were noted in 27 and 7 patients at presentation. The tumors involved the femur (n = 27), pelvis (n = 22), humerus (n = 7), tibia (n = 4), scapula/ribs (n = 4), spine (n = 2), and clivus (n = 1). In the 56 resections, the tumors ranged in size from 3.5 to 46.0 cm (median, 11.5 cm) and contained 1%-99.5% (median, 70%) dedifferentiated components that ranged in size from 0.6 to 24.0 cm (median, 7.3 cm). No correlation was noted between total size and percentage of dedifferentiation. The dedifferentiated components were typically fibrosarcomatous or osteosarcomatous, whereas the associated cartilaginous components were predominantly grade 1-2, rarely enchondromas or grade 3. The entire cohort's median overall survival and progression-free survival were 11.8 and 5.4 months, respectively. In the resected cohort, although the total size was not prognostic, the percentage of dedifferentiation ≥20% and size of dedifferentiation >3.0 cm each predicted worse overall survival (9.9 vs 72.5 months; HR, 3.76; 95% CI, 1.27-11.14; P = .02; 8.7 vs 58.9 months; HR, 3.03; 95% CI, 1.21-7.57; P = .02, respectively) and progression-free survival (5.3 vs 62.1 months; HR, 3.05; 95% CI, 1.13-8.28; P = .03; 5.3 vs 56.6 months; HR, 2.50; 95% CI, 1.06-5.88; P = .04, respectively). In conclusion, both the percentages and sizes of dedifferentiation were better prognostic predictors than total tumor sizes in dedifferentiated chondrosarcomas, highlighting the utility of their pathologic evaluations.

Late Radiation-Induced Carotid Artery Stenosis and Stroke in Pediatric Patient Treated With Proton Radiation Therapy for Skull-Base Chordoma.

Radiation vasculopathy is a well-recognized late complication of radiation therapy. We present a case of a stroke 29 years after high-dose proton radiation therapy for skull-base chordoma due to occlusion of bilateral internal carotid arteries.

Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing.

BACKGROUND: Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB). METHODS AND MATERIALS: We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10 mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans. RESULTS: Thirty-eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy. CONCLUSIONS: Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB. PLAIN LANGUAGE SUMMARY: In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.

Effects of Proton Craniospinal Radiation on Vertebral Body Growth Retardation in Children.

PURPOSE: It is of great interest to physicians and patients/patients' families to be able to predict the amount of growth decrement after craniospinal irradiation (CSI). Little data exist on the effect of proton CSI. Our aim was to determine the effect of proton CSI on vertebral body (VB) growth retardation, and to identify factors associated with growth delay. METHODS AND MATERIALS: We performed a retrospective outcome data analysis of 80 patients <16 years old with central nervous system tumors who received proton radiation therapy (PRT) at the Massachusetts General Hospital between 2002 and 2010 with available spinal magnetic resonance imaging. Forty-eight patients received CSI, and 32 patients with brain tumors who received focal cranial irradiation served as controls. VB height was measured midline using sagittal T1-weighted contrast or noncontrast enhanced magnetic resonance imaging of the spine. Measurements were repeated at multiple levels (C3, C3-C4, T4, T4-T5, C3-T6, T4-T7, L3, L1-L5) on available scans for the duration of follow-up. Data were fitted using a mixed-effects multivariable regression model, including follow-up time, CSI dose, age at CSI, and pretreatment VB percentile as parameters. RESULTS: Median follow-up was 69.6 months for patients treated with proton CSI and 52.9 months for the control group. There was a significant association of CSI dose, follow-up time, age at treatment, and pretreatment VB percentile with VB growth retardation. Growth retardation was shown to be independent of gender or growth hormone deficiency. CONCLUSIONS: Although the current practice of PRT CSI delivery allows for sparing of the organs anterior to the spine, the vertebral column receives radiation therapy because of its close proximity to the targeted spinal canal. In growing children, the whole VB has generally been included so that growth impairment is even across the VB. We present a quantitative model predicting the growth retardation of patients treated with PRT CSI based on age at treatment, CSI dose, follow-up time, and pretreatment growth percentile.

Serial Measurement of Global Longitudinal Strain Among Women With Breast Cancer Treated With Proton Radiation Therapy: A Prospective Trial for 70 Patients.

PURPOSE: Conventional photon radiation therapy (RT) for breast cancer is associated with a reduction in global longitudinal strain (GLS) and an increase in troponin, N-terminal pro hormone B-type natriuretic peptide (NT-proBNP), and incident heart failure. The cardiac radiation exposure with proton-RT is much reduced and thus may be associated with less cardiotoxicity. The objective was to test the effect of proton-RT on GLS, troponin, and NT-proBNP. METHODS AND MATERIALS: We conducted a prospective, observational, single-center study of 70 women being treated with proton-RT for breast cancer. Serial measurements of GLS, high-sensitivity troponin I, and NT-proBNP were performed at prespecified intervals (before proton-RT, 4 weeks after completion of proton-RT, and again at 2 months after proton-RT). RESULTS: The mean age of the patients was 46 ± 11 years, and the mean body mass index was 25.6 ± 5.2 kg/m2; 32% of patients had hypertension, and the mean radiation doses to the heart and the left ventricle (LV) were 0.44 Gy and 0.12 Gy, respectively. There was no change in left ventricular ejection fraction (65 ± 5 vs 66 ± 5 vs 64 ± 4%; P = .15), global GLS (-21.7 ± 2.7 vs -22.7 ± 2.3 vs -22.8 ± 2.1%; P = .24), or segmental GLS from before to after proton-RT. Similarly, there was no change in either high-sensitivity troponin or NT-proBNP with proton-RT. However, in a post hoc subset analysis, women with hypertension had a greater decrease in GLS after proton-RT compared with women without hypertension (-21.3 ± 3.5 vs -24.0 ± 2.4%; P = .006). CONCLUSIONS: Proton-RT did not affect LV function and was not associated with an increase in biomarkers. These data support the potential cardiac benefits of proton-RT compared with conventional RT.

The impact of radiotherapy on survival after surgical resection of chordoma with minimum five-year follow-up.

BACKGROUND CONTEXT: Local control remains a vexing problem in the management of chordoma despite advances in operative techniques and radiotherapy (RT) protocols. Existing studies show satisfactory local control rates with different treatment modalities. However, those studies with minimum follow-up more than 4 years demonstrate increasing rates of local failure. Therefore, mid-term local survival rates may be inadvertently elevated by studies with less than 4 years follow-up. PURPOSE: The purpose of this study is to report the mid-term results of primary spinal chordoma treated with en bloc resection and proton-based RT with minimum 5 years of follow-up. STUDY DESIGN/SETTING: Retrospective, single-center, cohort study. PATIENT SAMPLE: Patients undergoing primary surgical excision of a spine or sacral chordoma tumor between 1990 and 2016 at a single-institution were included. Patients were included if they had a local failure at any time, or they had a minimum of 5 years of follow up with no local failure. Patients were excluded if a prior surgical excision was performed or metastases were present at the time of referral. OUTCOME MEASURES: The outcome measures were local recurrence-free interval (LRFI) and overall survival (OS). METHODS: Demographic, clinical, oncologic and surgical variables, including margin status, as well as radiation doses and schedule (neoadjuvant, adjuvant, or both) were compared using Wilcoxon rank-sum or chi-squared testing. The goal RT dose was 70 Gray (total) and patients were stratified based on completing (C70) or receiving incomplete (I70) dosing. Overall survival (OS) and local-recurrence free interval (LRFI) were calculated using the Kaplan-Meier method. FUNDING STATEMENT: No funding was obtained for this work. RESULTS: Seventy-six patients were included in the final analysis. All patients had a minimum of 5-year follow-up (median 9.3 years, range 5.1-24.7 years). There were no significant clinical differences between the C70 and I70 RT groups. OS was greater for the C70 RT group (5-year OS 82% vs. 63%, p=.001). There was similar OS for the positive margin group (5-year OS 70% vs. 61%, p=.266). LRFI was greater for the C70 RT group (5-year OS 93% vs. 78%, p=.017). There was similar LRFI for the positive margin group (5-year OS 90% versus 87%, p=.810). CONCLUSION: Chordoma outcomes trend towards diminishing LRFI rates in the literature. Here we report the results of the operative management of primary spinal chordoma with minimum five year follow-up, the addition of C70 RT to surgical excision conferred a benefit to OS and local recurrence.