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.

Children's Oncology Group's 2023 blueprint for research: Radiation oncology.

Radiation oncology is an integral part of the multidisciplinary team caring for children with cancer. The primary goal of our committee is to enable the delivery of the safest dose of radiation therapy (RT) with the maximal potential for cure, and to minimize toxicity in children by delivering lower doses to normal tissues using advanced technologies like intensity-modulated RT (IMRT) and proton therapy. We provide mentorship for y ators and are actively involved in educating the global radiation oncology community. We are leaders in the effort to discover novel radiosensitizers, radioprotectors, and advanced RT technologies that could help improve outcomes of children with cancer.

General Anesthesia for Pediatric Radiation Therapy in the Era of COVID-19.

Purpose: Managing pediatric patients requiring daily general anesthesia (GA) for radiation therapy (RT) in the setting of COVID-19 is complex, owing to the aerosolizing nature of GA procedures, the risk of cardiopulmonary complications for infected patients, and the treatment of immunocompromised oncology patients in a busy, densely populated radiation oncology clinic. Methods and Materials: We developed an institutional protocol to define procedures for COVID-19 testing and protection of patients, caregivers, and staff, hypothesizing that this protocol would allow patients requiring GA to be safely treated, minimizing COVID-19 transmission risk to both patients and staff, and at the same time maintaining pre-COVID-19 patient volumes. All patients underwent COVID-19 testing before their first treatment and thrice weekly during treatment. For patients who tested positive for COVID-19, RT was delivered in the last end-of-day treatment appointment. A negative pressure room was used for GA induction and recovery, and separate physician/nurse teams were designated for in-room versus out-of-room patient management. Results: Seventy-eight pediatric patients received RT under GA, versus 69 over the same prior year timeframe, and 2 patients received 2 courses of RT under GA, for a total of 80 courses. The mean age was 4.9 years (range, 0.5-19.0 years) and 41 of 78 (52.6%) were male. Two patients (2.6%) received 2 courses of RT under GA, establishing a total of 80 courses. The mean number of treatment fractions was 22.2 (range, 1-40). Two of 78 patients (2.6%) tested positive for COVID-19; both were asymptomatic. Both patients completed treatment as prescribed. Neither patient developed cardiopulmonary symptoms complicating anesthesia, and neither patient experienced grade 3+ acute radiation toxicity. Conclusions: With careful multidisciplinary planning to mitigate COVID-19 risk, pediatric RT with GA was carried out for a large patient volume without widespread infection and without increased toxic effects from either GA or RT.

Neuroblastoma.

The survival of patients with high-risk neuroblastoma has improved significantly with the use of intensive multimodality treatment regimens, including chemotherapy, surgery, radiation therapy, myeloablative chemotherapy followed by stem cell rescue, and immunotherapy. This report summarizes the current treatment strategies used in the COG and SIOP for children with neuroblastoma. The improved global collaboration and the adoption of a uniform International Neuroblastoma Risk Group Staging System will help facilitate comparison of homogeneous pretreatment cohorts across clinical trials. Future research strategies regarding the indications for and dosages of radiation therapy to the primary and metastatic sites, and the integration of meta-iodobenzyl guanidine therapy into the multimodal treatment program, are discussed.

Psychosocial impact of the COVID-19 pandemic on cancer patients, survivors and caregivers.

Objective: This study aimed to increase understanding of the effects of the pandemic on cancer patients, survivors and caregivers.Methods: An Internet-based survey was accessed over 2 months by individuals diagnosed with cancer or caregivers (N = 281), with descriptive statistics and chi square analysis used to compare subsets.Results: Most participants reported social isolation (76%) and mental health impact (70%) since the beginning of the COVID19 pandemic; isolation appeared to correlate with mental health impact (p < .00001). Food insecurity and financial hardship correlated significantly with mental health impact; food insecurity also correlated with social isolation.Conclusions: Our findings suggest that mental health during the pandemic in the cancer population may be impacted by social isolation, financial stress, and food insecurity, as well as stress regarding accessing cancer treatments. Awareness by psychosocial healthcare providers of need for resources to support these hardships, as well as framework to identify them, are essential elements of cancer-related care.

Contextual Predictors of Engagement in a Tailored mHealth Intervention for Adolescent and Young Adult Cancer Survivors.

BACKGROUND: Despite the promise of mobile health (mHealth), engagement is often too low for durable health behavior change, and little is known regarding why certain individuals abandon mHealth tools. PURPOSE: Guided by a mHealth engagement framework, we evaluated contextual predictors of objective engagement with an app for adolescents and young adults (AYA) who survived cancer. METHODS: One hundred and ten AYA survivors (M age = 20.5, 43% female, 30% racial/ethnic minority) were randomized to receive a disease self-management app that delivered 1-2 tailored messages/day for 16 weeks, and contained a survivorship care plan (SCP). Demographic, disease, psychosocial, and setting characteristics were examined as predictors of three objective engagement outcomes: (a) % of active app days, (b) % of messages read, and (c) viewed SCP in the app versus not. A subsample (n = 10) completed qualitative interviews to further assess engagement barriers. RESULTS: Self-reported uninterrupted app access (ß = -0.56, p < .001), iPhone (vs. Android) ownership (ß = 0.30, p < .001), and receiving the intervention in the summer (ß = -0.20, p = .01) predicted more active days. Lower depressed mood (ß = -0.30, p = .047) and uninterrupted app access (ß = -0.50, p < .001) predicted more messages read. Qualitatively, technical glitches and competing priorities were described as engagement barriers, whereas certain types of messages (e.g., health goal messages) were perceived as engaging. Among participants who had uninterrupted app access (n = 76), higher baseline motivation to change, better health perceptions, using the app during the summer, and iPhone ownership predicted higher engagement. CONCLUSIONS: Findings demonstrate the importance of comprehensively assessing and planning for multi-level ecological determinants of mHealth engagement in future trials. CLINICALTRIALS.GOV IDENTIFIER: NCT03363711.

Risk of Pneumonitis and Outcomes After Mediastinal Proton Therapy for Relapsed/Refractory Lymphoma: A PTCOG and PCG Collaboration.

PURPOSE: Despite high response rates, there has been reluctance to use radiation therapy for patients with relapsed/refractory (r/r) Hodgkin (HL) or aggressive non-Hodgkin lymphoma (NHL) given concerns for subacute and late toxicities. Symptomatic pneumonitis, a subacute toxicity, has an incidence of 17% to 24% (≥grade 2) even with intensity modulated radiation therapy. Proton therapy (PT), which has no exit radiation dose, is associated with a lower dose to lung compared with other radiation techniques. As risk of radiation pneumonitis is associated with lung dose, we evaluated whether pneumonitis rates are lower with PT. METHODS AND MATERIALS: Within an international, multi-institutional cohort, we retrospectively evaluated the incidence and grade of radiation pneumonitis (National Cancer Institute Common Terminology Criteria for Adverse Events v4) among patients with r/r HL or NHL treated with PT. RESULTS: A total of 85 patients with r/r lymphoma (66% HL, 34% NHL; 46% primary chemorefractory) received thoracic PT from 2009 to 2017 in the consolidation (45%) or salvage (54%) setting. Median dose was 36 Gy(RBE). Before PT, patients underwent a median of 1 salvage systemic therapy (range, 0-4); 40% received PT within 4 months of transplant. With a median follow-up of 26.3 months among living patients, 11 patients developed symptomatic (grade 2) pneumonitis (12.8%). No grade 3 or higher pneumonitis was observed. Dose to lung, including mean lung dose, lung V5, and V20, significantly predicted risk of symptomatic pneumonitis, but not receipt of brentuximab, history of bleomycin toxicity, sex, or peritransplant radiation. CONCLUSIONS: PT for relapsed/refractory lymphoma was associated with favorable rates of pneumonitis compared with historical controls. We confirm that among patients treated with PT, pneumonitis risk is associated with mean lung and lung V20 dose. These findings highlight how advancements in radiation delivery may improve the therapeutic ratio for patients with relapsed/refractory lymphoma. PT may be considered as a treatment modality for patients with relapsed/refractory lymphoma in the consolidation or salvage setting.

Role of Metastatic Site Irradiation in Pediatric Patients With Metastatic Ewing Sarcoma.

BACKGROUND: The use of radiation therapy to treat metastases in patients with metastatic Ewing sarcoma (MES) has been controversial and variable. The authors report outcomes and patterns of failure after metastatic site irradiation (MSI). PROCEDURE: A total of 27 pediatric patients with MES were treated with chemotherapy and received radiation therapy to their primary site. Ten patients additionally received MSI, which consisted of whole-lung irradiation (WLI) in patients with lung metastases. Metastatic sites were followed from diagnosis to the first relapse. RESULTS: Median follow-up was 29 months. Seventy-eight percent of patients relapsed. Two-year progression-free survival (PFS) and overall survival with and without MSI were 30 versus 29% (log rank P=0.38) and 60 versus 70% (log rank P=0.11), respectively. The median time to relapse among patients who relapsed was 19.5 versus 12.3 months for those receiving MSI versus those who did not (P=0.04).Seven of 20 (35%) patients with lung metastases received WLI±other MSI. Two-year PFS with and without MSI was 43% versus 23% (log rank P=0.02). Among patients with a complete response to computed tomography, 5 of 14 (36%) patients received MSI. Two-year PFS with and without MSI was 60% versus 33% (log rank P=0.04).In the cohort of patients who relapsed, among all metastatic sites at diagnosis, the disease recurred at 15% of irradiated sites and 31% of unirradiated sites. On logistic regression, no factors were statistically associated with increased risk of recurrence at initial sites of metastases. CONCLUSIONS: Relapses frequently occur at sites of prior unirradiated disease in patients with MES. WLI may improve 2-year PFS, regardless of chemotherapy response. Further investigation of the role of MSI is warranted.

An open invitation to join the Pediatric Proton/Photon Consortium Registry to standardize data collection in pediatric radiation oncology.

OBJECTIVE: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. METHODS AND MATERIALS: Current eligibility criteria are radiotherapy patients < 22 years treated at one of the 15 US participating institutions. Detailed health and treatment data are collected about the disease presentation and treatment exposures, and annually thereafter, in REDCap (Research Electronic Data Capture). DICOM (Digital Imaging and Communications in Medicine) imaging and radiation plans are collected through MIM/MIMcloud. An optional patient-reported quality-of-life (PedsQL) study is administered at 10 sites. RESULTS: Accrual started October 2012 with 2,775 participants enrolled as of 25 July 2019. Most patients, 62.0%, were treated for central nervous system (CNS) tumors, the most common of which are medulloblastoma (n = 349), ependymoma (n = 309), and glial/astrocytoma tumors (n = 279). The most common non-CNS diagnoses are rhabdomyosarcoma (n = 284), Ewing's sarcoma (n = 153), and neuroblastoma (n = 130). While the majority of participants are US residents, 18.7% come from 36 other countries. Over 685 patients participate in the PedsQL study. CONCLUSIONS: The PPCR is a valuable research platform capable of answering countless research questions that will ultimately improve patient care. Centers outside of the USA are invited to participate directly or may engage with the PPCR to align data collection strategies to facilitate large-scale international research. ADVANCES IN KNOWLEDGE: For investigators looking to carry out research in a large pediatric oncology cohort or interested in registry work, this paper provides an updated overview of the PPCR.

Proton Therapy.

Proton therapy is a form of external beam radiotherapy that has several advantages over conventional photon (x-ray) radiotherapy. Protons are useful in 2 scenarios that apply to a large proportion of cancer patients: lack of exit dose allows for delivery of a therapeutic radiation dose to tumors in challenging anatomic locations, and reduction in integral dose (low-dose bath) to normal tissues that may reduce the risk of late toxicities and secondary cancers. The emergence of smaller, more economically viable single-room proton units has led to the expansion in use of this technology across the world.

Outcomes After Proton Therapy for Treatment of Pediatric High-Risk Neuroblastoma.

PURPOSE: Patients with high-risk neuroblastoma (HR-NBL) require radiation to the primary tumor site and sites of persistent metastatic disease. Proton radiation therapy (PRT) may promote organ sparing, but long-term outcomes have not been studied. METHODS AND MATERIALS: Sequential patients with HR-NBL received PRT: 2160 cGy (relative biological effectiveness) to primary tumor bed and persistent metastatic sites, with 3600 cGy (relative biological effectiveness) to gross residual disease. RESULTS: From September 2010 through September 2015, 45 patients with HR-NBL received PRT after systemic therapy, primary tumor resection, and high-dose chemotherapy with stem cell rescue. Median age was 46 months at the time of PRT (range, 10 months to 12 years); 23 patients (51%) were male. Primary tumors were adrenal in 40 (89%); 11 (24%) received boost. Ten metastatic sites in 8 patients were radiated. Double scattered proton beams were used for 19 (42%) patients, in combination with x-rays for 2 (5%). The remaining 26 (58%) received pencil beam scanning, available since January 2013. We observed 97% freedom from primary site recurrence at 3, 4, and 5 years. Overall survival rates were 89%, 80%, and 80% and disease-free survival rates were 77%, 70%, and 70%, at 3, 4, and 5 years, respectively. With median follow-up of 48.7 months from diagnosis (range, 11-90 months) for all patients (57.4 months for those alive), 37 (82%) patients are alive, and 32 (71%) are without evidence of disease. One patient experienced locoregional recurrence; the remaining 12 (27%) experienced relapse at distant, nonradiated sites. Acute toxicities during treatment were mainly grade 1. No patient has experienced World Health Organization grade 3 or 4 long-term renal or hepatic toxicity. Pencil beam scanning plans required less planning time and resources than double scattered plans. CONCLUSIONS: We observe excellent outcomes in patients treated with PRT for HR-NBL from 2010 through 2015, with 82% of patients alive and 97% free of primary site recurrence. No patient has experienced long-term renal or liver toxicity. This treatment maximizes normal tissue preservation and is appropriate for this patient population.

Factors Influencing Delivery of Cancer Survivorship Care Plans: A National Patterns of Care Study.

Nearly half of all Americans will develop cancer at least once in their lifetime. Through improved screening and treatments, the number of cancer survivors is reaching all-time highs. However, survivorship care plans (SCPs) are inconsistently used, denying many survivors access to critical information. This study used 46,408 SCPs generated from 2007 to 2016 and applied machine learning to identify predictors of SCP creation, including cancer type, type of physician, and healthcare center where they received care, as well as regional variations in care plan creation. Identifying these disparities in SCP use is a critical first step in efforts toward expanding access to survivorship care planning. Using a convenience sample of survivors, it is possible to model the factors that predict generation of SCPs either by the survivor or by a healthcare provider. This study identifies several important disparities both survivor intrinsic such as cancer type, as well as treatment associated and geographic differences in SCP generation. Identifying these disparities at the national level across cancer types will allow for more targeted recommendations to improve SCP creation and dissemination in underserved groups.

Iterative Development of a Tailored mHealth Intervention for Adolescent and Young Adult Survivors of Childhood Cancer.

Objectives: Methods for developing mobile health (mHealth) interventions are not well described. To guide the development of future mHealth interventions, we describe the application of the agile science framework to iteratively develop a mHealth intervention for adolescent and young adult (AYA) survivors of childhood cancer. Methods: We created the AYA STEPS mobile app (AYA Self-management via Texting, Education, and Plans for Survivorship) by modifying and integrating two existing programs: an online survivorship care plan (SCP) generator and a text messaging self-management intervention for AYA off treatment. The iterative development process involved three stages of agile science: 1) Formative work, 2) Obtaining feedback about the first AYA STEPS prototype, and 3) Pilot testing and finalization of a prototype. We determined preferences of AYA stakeholders as well as discovered and addressed technology problems prior to beginning a subsequent randomized controlled trial. Results: AYA survivors reported that the app and the embedded tailored messages related to their health and SCP, were easy to use and generally satisfying and beneficial. Usage data supported that AYA were engaged in the app. Technology glitches were discovered in the pilot and addressed. Conclusions: The iterative development of AYA STEPS was essential for creating a consistent and acceptable end user experience. This study serves as one example of how behavioral scientists may apply agile science to their own mHealth research.

Patient-reported outcomes in head and neck cancer: prospective multi-institutional patient-reported toxicity.

PURPOSE: Head and neck cancer is occurring in an increasingly younger patient population, with treatment toxicity that can cause significant morbidity. Using a patient guided, Internet-based survivorship care plan program, we obtained and looked at patterns of patient-reported outcomes data from survivors seeking information after treatment for head and neck cancer. METHODS: The Internet-based OncoLife and LIVESTRONG Care Plan programs were employed, which design unique survivorship care plans based on patient-reported data. Care plans created for survivors of head and neck cancer were used in this evaluation. Demographics, treatment modality, and toxicity were included in this evaluation. Toxicity was further analyzed, grouped into system-based subsets. RESULTS: A total of 602 care plans were created from self-identified head and neck cancer survivors, from which patient-reported outcome data were attained. A majority of patients were Caucasian (96.2%) with median age at diagnosis of 55 years, living in suburban locations (39.9%), with ~50% receiving care within 20 miles of their residence. There was an equal distribution of education levels from high school only to graduate school. The majority of patients received care through cancer centers (96.7%), with a split between academic and non-academic centers. Ninety-three percent of patients had radiation therapy as part of their treatment modality, with 70.3% having chemotherapy and 60.1% having surgery. The most common system toxicities affected the oropharynx, followed by epithelium (skin/hair/nail), and then general global health. Specifically, the most common side effects were difficulty swallowing (61.5%) and changes in skin color/texture (49.7%). One third of patients experienced hearing/tinnitus/vertigo, xerostomia, loss of tissue flexibility, or fatigue. CONCLUSION: The current work demonstrates the ability to obtain patient-reported outcomes of head and neck cancer survivors through an Internet-based survivorship care plan program. For this group dysphagia and dermatitis were the most commonly reported toxicities, as was expected; however, global effects of therapy, such as fatigue, were also significant and should be addressed in future survivorship planning.

Identifying barriers to cancer survivors sharing their survivorship care plans with their healthcare provider.

PURPOSE: To understand what factors influence whether a cancer survivor will share their survivorship care plan (SCP) with their healthcare provider (HCP). METHODS: We used data from 3231 cancer survivors who utilized the OncoLink SCP resource between 2009 and 2016. Random forest and stepwise regression were used to identify predictors of SCP satisfaction and barriers to survivors sharing their care plans with their HCPs. RESULTS: Eighty-seven percent of users rated their satisfaction with their SCP as good or better; however, only 70% of survivors planned to share their SCP with their HCP. The most commonly reported reason for not sharing was a feeling that their HCP would not care. Self-reported satisfaction with their SCP was strongest predictor of whether a survivor would share their SCP. Gender, cancer status, number of chemotherapies received, and who was managing their healthcare were all associated with self-reported survivor satisfaction with their SCP. CONCLUSIONS: Survivor satisfaction with SCPs was high, but there was a disconnect in the number of satisfied survivors and the number of survivors planning to share their SCP with their HCP. To bridge this gap, additional prompts that HCPs are expecting this information should be added to the care plans. IMPLICATIONS FOR CANCER SURVIVORS: One of the primary functions of survivorship care plans is to improve communication between survivor and healthcare provider. While survivors are overwhelmingly satisfied with their SCP, additional steps are necessary to get survivors to share their SCP with their HCP.

An Update From the Pediatric Proton Consortium Registry.

BACKGROUND/OBJECTIVES: The Pediatric Proton Consortium Registry (PPCR) was established to expedite proton outcomes research in the pediatric population requiring radiotherapy. Here, we introduce the PPCR as a resource to the oncology community and provide an overview of the data available for further study and collaboration. DESIGN/METHODS: A multi-institutional registry of integrated clinical, dosimetric, radiographic, and patient-reported data for patients undergoing proton radiation therapy was conceived in May 2010. Massachusetts General Hospital began enrollment in July of 2012. Subsequently, 12 other institutions joined the PPCR and activated patient accrual, with the latest joining in 2017. An optional patient-reported quality of life (QoL) survey is currently implemented at six institutions. Baseline health status, symptoms, medications, neurocognitive status, audiogram findings, and neuroendocrine testing are collected. Treatment details of surgery, chemotherapy, and radiation therapy are documented and radiation plans are archived. Follow-up is collected annually. Data were analyzed 25 September, 2017. RESULTS: A total of 1,854 patients have consented and enrolled in the PPCR from October 2012 until September 2017. The cohort is 55% male, 70% Caucasian, and comprised of 79% United States residents. Central nervous system (CNS) tumors comprise 61% of the cohort. The most common CNS histologies are as follows: medulloblastoma (n = 276), ependymoma (n = 214), glioma/astrocytoma (n = 195), craniopharyngioma (n = 153), and germ cell tumors (n = 108). The most common non-CNS tumors diagnoses are as follows: rhabdomyosarcoma (n = 191), Ewing sarcoma (n = 105), Hodgkin lymphoma (n = 66), and neuroblastoma (n = 55). The median follow-up is 1.5 years with a range of 0.14 to 4.6 years. CONCLUSION: A large prospective population of children irradiated with proton therapy has reached a critical milestone to facilitate long-awaited clinical outcomes research in the modern era. This is an important resource for investigators both in the consortium and for those who wish to access the data for academic research pursuits.

Survivorship care planning in skin cancer: An unbiased statistical approach to identifying patterns of care-plan use.

BACKGROUND: Nearly 1 in 5 Americans will develop skin cancer, and as a result, survivors of skin cancer compose one of the largest groups of cancer survivors. Survivorship care plans (SCPs) are an important tool for improving patient outcomes and provide critical information to both survivors and health care professionals. Recent efforts have been made to expand SCP utilization; however, which patients currently receive SCPs is poorly understood. METHODS: This study used 596 individuals with a diagnosis of melanoma (n = 391) or nonmelanoma skin cancer (n = 205) who had used an Internet-based SCP tool from May 2010 to December 2016 to model the patient and provider characteristics that determine SCP utilization. RESULTS: Survivors were predominantly white (95.3%) and female (56.5%). Survivors who received a treatment summary were more likely to also receive an SCP. University and nonuniversity cancer centers used SCPs at a higher rate than other care settings. Survivors whose care was managed by a team rather than just an individual physician were also more likely to receive an SCP. Survivors older than 70 years at diagnosis were almost twice as likely to receive a plan as survivors who were diagnosed at a younger age. CONCLUSIONS: With a convenience sample of skin cancer survivors, it is possible to model factors that predict the receipt of SCPs. Important variables include the diagnosis age, treatment setting, physician type, and treatment-summary utilization. A closer examination of these variables identified several disparities in care-plan use and, therefore, opportunities to improve the distribution of SCPs. Further validation in additional cohorts of survivors is necessary to confirm these conclusions. Cancer 2018;124:183-91. © 2017 American Cancer Society.