NCCN Guidelines® Insights: Survivorship, Version 1.2023.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.

Radiotherapy for Atypical Teratoid/Rhabdoid Tumor (ATRT) on the Pediatric Proton/Photon Consortium Registry (PPCR).

PURPOSE: Atypical teratoid/rhabdoid tumors (ATRT) of the central nervous system (CNS) are rare tumors with a poor prognosis and variable use of either focal or craniospinal (CSI) radiotherapy (RT). Outcomes on the prospective Pediatric Proton/Photon Consortium Registry (PPCR) were evaluated according to RT delivered. METHODS: Pediatric patients receiving RT were prospectively enrolled on PPCR to collect initial patient, disease, and treatment factors as well as provide follow-up for patient outcomes. All ATRT patients with evaluable data were included. Kaplan-Meier analyses with log-rank p-values and cox proportional hazards regression were performed. RESULTS: The PPCR ATRT cohort includes 68 evaluable ATRT patients (median age 2.6 years, range 0.71-15.40) from 2012 to 2021. Median follow-up was 40.8 months (range 3.4-107.7). Treatment included surgery (65% initial gross total resection or GTR), chemotherapy (60% with myeloablative therapy including stem cell rescue) and RT. For patients with M0 stage (n = 60), 50 (83%) had focal RT and 10 (17%) had CSI. Among patients with M + stage (n = 8), 3 had focal RT and 5 had CSI. Four-year overall survival (OS, n = 68) was 56% with no differences observed between M0 and M + stage patients (p = 0.848). Local Control (LC) at 4 years did not show a difference for lower primary dose (50-53.9 Gy) compared to ≥ 54 Gy (73.3% vs 74.7%, p = 0.83). For patients with M0 disease, four-year OS for focal RT was 54.6% and for CSI was 60% (Hazard Ratio 1.04, p = 0.95. Four-year event free survival (EFS) among M0 patients for focal RT was 45.6% and for CSI was 60% (Hazard Ratio 0.71, p = 0.519). For all patients, the 4-year OS comparing focal RT with CSI was 54.4% vs 60% respectively (p = 0.944), and the 4-year EFS for focal RT or CSI was 42.8% vs 51.4% respectively (p = 0.610). CONCLUSION: The PPCR ATRT cohort found no differences in outcomes according to receipt of either higher primary dose or larger RT field (CSI). However, most patients were M0 and received focal RT. A lower primary dose (50.4 Gy), regardless of patient age, is appealing for further study as part of multi-modality therapy.

Delivery of re-irradiation and complex palliative radiotherapy using proton therapy in pediatric cancer patients.

BACKGROUND: The intent of this study is to characterize indications for pediatric palliative-intent proton radiation therapy (PIPRT). PROCEDURE: We retrospectively reviewed patients 21 years and younger who received PIPRT. We defined PIPRT as radiotherapy (RT) aimed to improve cancer-related symptoms/provide durable local control in the non-curative setting. Mixed proton/photon plans were included. Adjacent re-irradiation (reRT) was defined as a reRT volume within the incidental dose cloud of a prior RT target, whereas direct reRT was defined as in-field overlap with prior RT target. Acute toxicity during RT until first inspection visit was graded according to the Common Terminology Criteria for Adverse Events. The Kaplan-Meier method, measured from last PIPRT fraction, was used to assess progression-free survival (PFS) and overall survival (OS). RESULTS: Eighteen patients underwent PIPRT between 2014 and 2020. Median age at treatment start was 10 years [2-21]. Median follow-up was 8.2 months [0-48]. Treatment sites included: brain/spine [10], abdomen/pelvis [3], thorax [3], and head/neck [2]. Indications for palliation included: durable tumor control [18], neurologic symptoms [4], pain [3], airway compromise [2], and great vessel compression [1]. Indications for protons included: reRT [15] (three adjacent, 12 direct), craniospinal irradiation [4], reduction of dose to normal tissues [3]. Sixteen experienced grade (G) 1-2 toxicity; two G3. There were no reports of radionecrosis. Median PFS was 5.3 months [95% confidence interval (CI): 2.7-16.3]. Median OS was 8.3 months [95% CI: 5.5-26.3]. CONCLUSIONS: The most common indication for PIPRT was reRT to provide durable tumor control. PIPRT appears to be safe, with no cases of high-grade toxicity.

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.

NCCN Guidelines® Insights: Survivorship, Version 1.2022.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals who work with survivors to ensure that the survivors' complex and varied needs are addressed. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for the consequences of adult-onset cancer and its treatment; recommendations to help promote physical activity, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes updates to the NCCN Guidelines pertaining to preventive health for cancer survivors, including recommendations about alcohol consumption and vaccinations.

Sociodemographics, Health Competence, and Transition Readiness Among Adolescent/Young Adult Cancer Survivors.

OBJECTIVE: Fewer than one-third of childhood cancer survivors receive follow-up from an adult provider, and adolescent and young adults (AYAs) from structurally minoritized sociodemographic groups often face health disparities that can impact transition to adult-oriented care. The primary aim of this study was to determine the relation among sociodemographic factors, cumulative effects, and transition beliefs/expectations and goals, and the moderating role of health competence beliefs in AYA survivors of childhood cancer. METHODS: A total of 195 AYAs (aged 15-29) reported sociodemographic information, completed the Transition Readiness Inventory assessing positive beliefs/expectations and goals related to transition, and completed the Health Competence Beliefs Inventory assessing health perceptions, healthcare satisfaction, cognitive competence, and autonomy. A cumulative sociodemographic factor variable was computed to investigate the potential additive effects of multiple sociodemographic factors associated with disparities. T-tests, Pearson correlations, and multivariate linear regressions were used. RESULTS: Cumulative sociodemographic factors were not related to transition readiness, and insurance type was the only factor associated with health competence beliefs and transition readiness, such that AYAs with public insurance reported lower healthcare satisfaction, cognitive competence, and transition goals relative to those with private insurance. There were no interaction effects; however, health competence beliefs were significantly associated with transition beliefs/expectations and goals. CONCLUSION: Public insurance is a barrier to holding positive beliefs/expectations and goals about transition, yet other sociodemographic factors associated with risks for poor transfer were not related to transition readiness. Multi-level interventions to reduce disparities and improve transition readiness should target health competence beliefs and barriers created by insurance.

Survivorship, Version 1.2021.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor's complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.

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.

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.

Acceptability and feasibility of survivorship care plans and an accompanying mobile health intervention for adolescent and young adult survivors of childhood cancer.

BACKGROUND: Self-management interventions for adolescent and young adult (AYA) survivors of childhood cancer are needed. The present study reports on the acceptability and feasibility of delivering survivorship care plans (SCPs) and an accompanying app to AYA. PROCEDURE: AYA (n = 224) ages 15-29 who completed treatment for cancer were randomized and received a digital SCP only or an SCP plus a mobile app intended to enhance self-management. For 16 weeks, the app delivered one to two daily messages complementing information in their SCP and tailored based on age, treatment, and health goal. Data are presented on feasibility, self-reported acceptability (including satisfaction and perceived benefits) and its relationship to app engagement (for those in app group), and feedback from qualitative interviews conducted with 10 AYA. RESULTS: The SCP and app proved feasible as evidenced by high recruitment and retention, access to technology, time analysis, moderate app engagement, and minimal technical issues. However, 12% reported never reading the SCP and 8% never used the app. The app and SCP were acceptable to AYA, and SCP acceptability ratings did not differ between groups. For those with the app, acceptability was positively related to message engagement. AYA recommended enhanced individualization and design features of the SCP and app. CONCLUSIONS: Results support the use of tailored SCPs and mobile health interventions for most AYA, as well as the need for further refinement and research. Delivery of SCPs and digital interventions are acceptable and feasible to AYA survivors, and may help promote health-related knowledge and survivorship self-management.

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.

NCCN Guidelines Insights: Survivorship, Version 2.2020.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment, with the goal of helping healthcare professionals who work with survivors, including those in primary care. The guidelines also provide recommendations to help clinicians promote physical activity, weight management, and proper immunizations in survivors and facilitate care coordination to ensure that all of the survivors' needs are addressed. These NCCN Guidelines Insights summarize additions and changes made to the guidelines in 2020 regarding cardiovascular disease risk assessment and screening for subsequent primary malignancies.

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.

Tumor bed proton irradiation in young children with localized medulloblastoma.

BACKGROUND: Radiotherapy is often deferred in very young children with medulloblastoma, in favor of more intense chemotherapy and stem cell rescue; however, posterior fossa radiation has been shown to improve overall survival (OS) and event-free survival compared with adjuvant chemotherapy alone. This study was performed to assess the OS, recurrence-free survival (RFS), patterns of failure, and clinical toxicity for children aged five and under who received focal proton radiation to the tumor bed alone. PROCEDURE: From 2010 to 2017, 14 patients with newly diagnosed medulloblastoma at one institution received tumor bed irradiation following surgery and chemotherapy. The median age of the patients was 40 months (range, 10.9-62.9 months). RESULTS: With a median follow-up of 54 months, four patients relapsed: three within the central nervous system (CNS) outside of the posterior fossa, and one within the tumor bed after subtotal resection. All relapses occurred within 28 months after the completion of radiation therapy. Five-year OS and RFS for this cohort of patients were 84% (95% CI, 48%-96%) and 70% (95% CI, 38%-88%), respectively. One patient experienced significant tumor regrowth soon after completion of radiation, autopsy showed viable tumor and necrosis near and within the brainstem, with relation to radiation unknown; however, no other acute clinical toxicities greater than grade 2 were observed in this group of patients. In the nine patients with available performance status follow-up, no significant changes in Lansky performance status were observed. CONCLUSIONS: Five-year OS and RFS following tumor bed irradiation in young children with medulloblastoma appear to be improved compared with other studies that forego the use of radiation therapy in this patient population. This approach should be further investigated in young children with medulloblastoma.

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.

Insurance coverage decisions for pediatric proton therapy.

Proton beam therapy (PBT) holds promise for pediatric patients, but level 1 evidence is not available. In this context, we examined insurance coverage decisions at our facility from 2010 to 2015. PBT was initially denied for 11% of pediatric cases. However, nearly all denials were overturned on appeal-a process that often delayed care by more than a week. Despite unfavorable language in coverage policies, real-world decisions were eventual approval in >99% of cases. Payers appear to have largely accepted the current level-of-evidence for pediatric PBT, but all parties spend significant time and resources on appeals. Streamlined approval processes could align incentives among stakeholders.

Musculoskeletal complications following total body irradiation in hematopoietic stem cell transplant patients.

Total body irradiation (TBI) is commonly used in conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) to treat benign and malignant disease. Though life-saving, these therapies place patients at risk for important side effects, including musculoskeletal complications such as short stature, osteonecrosis, slipped capital femoral epiphysis, and the development of benign and malignant bone tumors. With an increasing number of HSCT survivors, there is a growing need for awareness of the musculoskeletal complications of HSCT and TBI.

Proton therapy for pediatric head and neck malignancies.

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

Cardiac Toxicity After Craniospinal Irradiation: A Late Effect That May be Eliminated With Proton Therapy.

BACKGROUND: Craniospinal irradiation (CSI) is commonly required for pediatric patients with central nervous system malignancies. Traditionally, CSI is given using x-rays to deliver radiation to the brain and spine, exposing normal anterior structures, including heart, to unnecessary radiation. OBSERVATIONS: We present a patient treated with x-ray CSI for medulloblastoma with spinal metastasis (3600 cGy CSI with focal boost to 5000 cGy), who subsequently developed significant cardiac toxicity, likely related to radiation exposure. CONCLUSIONS: Spinal irradiation can cause significant cardiac risk due to exit dose through anterior structures. This toxicity may be avoided with proton therapy, which eliminates visceral exit dose.