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.

Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders.

BACKGROUND: Allogeneic hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis (HLH) disorders is associated with substantial morbidity and mortality. OBJECTIVE: The effect of conditioning regimen groups of varying intensity on outcomes after transplantation was examined to identify an optimal regimen or regimens for HLH disorders. METHODS: We studied 261 patients with HLH disorders transplanted between 2005 and 2018. Risk factors for transplantation outcomes by conditioning regimen groups were studied by Cox regression models. RESULTS: Four regimen groups were studied: (1) fludarabine (Flu) and melphalan (Mel) in 123 subjects; (2) Flu, Mel, and thiotepa (TT) in 28 subjects; (3) Flu and busulfan (Bu) in 14 subjects; and (4) Bu and cyclophosphamide (Cy) in 96 subjects. The day 100 incidence of veno-occlusive disease was lower with Flu/Mel (4%) and Flu/Mel/TT (0%) compared to Flu/Bu (14%) and Bu/Cy (22%) (P < .001). The 6-month incidence of viral infections was highest after Flu/Mel (72%) and Flu/Mel/TT (64%) compared to Flu/Bu (39%) and Bu/Cy (38%) (P < .001). Five-year event-free survival (alive and engrafted without additional cell product administration) was lower with Flu/Mel (44%) compared to Flu/Mel/TT (70%), Flu/Bu (79%), and Bu/Cy (61%) (P = .002). The corresponding 5-year overall survival values were 68%, 75%, 86%, and 64%, and did not differ by conditioning regimen (P = .19). Low event-free survival with Flu/Mel is attributed to high graft failure (42%) compared to Flu/Mel/TT (15%), Flu/Bu (7%), and Bu/Cy (18%) (P < .001). CONCLUSIONS: Given the high rate of graft failure with Flu/Mel and the high rate of veno-occlusive disease with Bu/Cy and Flu/Bu, Flu/Mel/TT may be preferred for HLH disorders. Prospective studies are warranted.

Late health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group.

BACKGROUND: The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials. METHODS: P9404 (acute lymphoblastic leukemia/lymphoma [ALL]), P9425 and P9426 (Hodgkin lymphoma), P9754 (osteosarcoma), and Dana-Farber Cancer Institute 95-01 (ALL) enrolled 1308 patients between 1996 and 2001: 1066 were randomized (1:1) to doxorubicin with or without dexrazoxane, and 242 (from P9754) were nonrandomly assigned to receive dexrazoxane. Trial data were linked with the National Death Index, the Organ Procurement and Transplantation Network, the Pediatric Health Information System (PHIS), and Medicaid. Osteosarcoma survivors from the Childhood Cancer Survivor Study (CCSS; n = 495; no dexrazoxane) served as comparators in subanalyses. Follow-up events were assessed with cumulative incidence, Cox regression, and Fine-Gray methods. RESULTS: In randomized trials (cumulative prescribed doxorubicin dose, 100-360 mg/m2 ; median follow-up, 18.6 years), dexrazoxane was not associated with relapse (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63-1.13), second cancers (HR, 1.19; 95% CI, 0.62-2.30), all-cause mortality (HR, 1.07; 95% CI, 0.78-1.47), or cardiovascular mortality (HR, 1.45; 95% CI, 0.41-5.16). Among P9754 patients (all exposed to dexrazoxane; cumulative doxorubicin, 450-600 mg/m2 ; median follow-up, 16.6-18.4 years), no cardiovascular deaths or heart transplantation occurred. The 20-year heart transplantation rate among CCSS osteosarcoma survivors (mean doxorubicin, 377 ± 145 mg/m2 ) was 1.6% (vs 0% in P9754; P = .13). Among randomized patients, serious cardiovascular outcomes (cardiomyopathy, ischemic heart disease, and stroke) ascertained by PHIS/Medicaid occurred less commonly with dexrazoxane (5.6%) than without it (17.6%; P = .02), although cardiomyopathy rates alone did not differ (4.4% vs 8.1%; P = .35). CONCLUSIONS: Dexrazoxane did not appear to adversely affect long-term mortality, event-free survival, or second cancer risk.

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.

The Role of Follicle-stimulating Hormone in Vascular Dysfunction Observed in Hematopoietic Cell Transplant Recipients.

Childhood cancer survivors who receive a hematopoietic cell transplantation (HCT) are at increased risk for follicle-stimulating hormone (FSH) abnormalities, which may have a substantial negative impact on vascular function. The purpose of this study was to examine the association of vascular function with FSH in HCT recipients, non-HCT recipients and healthy controls. The study included childhood cancer survivors who were HCT recipients (n=24) and non-HCT recipients (n=308), and a control group of healthy siblings (n=211) all between 9 and 18 years old. Vascular measures of carotid artery structure and function (compliance and distensibility), brachial artery flow-mediated dilation and endothelial-independent dilation were measured using ultrasound imaging. A fasting blood sample was collected to measure hormone levels. FSH was significantly higher in HCT recipients compared with non-HCT recipients and healthy controls (P<0.01). Carotid compliance and distensibility were significantly lower in HCT and non-HCT recipients compared with healthy controls (P<0.05). Higher FSH was associated with decreased carotid compliance (P<0.05). This study's results suggest that higher levels of FSH in HCT recipients may result in significant reductions in vascular function compared with non-HCT recipients and healthy controls. Therefore, gonadotropin endocrine dysfunction, particularly abnormal FSH levels, may be an underlying mechanism of vascular dysfunction.

Prediction of Acute Graft versus Host Disease and Relapse by Endogenous Metabolomic Compounds in Patients Receiving Personalized Busulfan-Based Conditioning.

Busulfan-based conditioning is the most commonly used high-dose conditioning regimen for allogeneic hematopoietic cell transplant (HCT). The alkylating agent busulfan has a narrow therapeutic index, with busulfan doses personalized to a target plasma exposure (targeted busulfan). Using a global pharmacometabonomics approach, we sought to identify novel biomarkers of relapse or acute graft versus host disease (GVHD) in a cohort of 84 patients receiving targeted busulfan before allogeneic HCT. A total of 763 endogenous metabolomic compounds (EMCs) were quantitated in 230 longitudinal blood samples before, during, and shortly after intravenous busulfan administration. We performed both univariate linear regression and pathway enrichment analyses using global testing. The cysteine/methionine pathway and the glycine, serine, and threonine metabolism pathway were most associated with relapse. The latter be explained by the fact that glutathione S-transferases conjugate both busulfan and glutathione, which contains glycine as a component. The d-arginine and d-ornithine metabolism pathway and arginine and proline metabolism pathway were most associated with acute GVHD. None of these associations were significant after correcting for false discovery rate (FDR) with a strict cutoff of FDR-adjusted p < 0.1. Although larger studies are needed to substantiate these findings, the results show that EMCs may be used as predictive biomarkers in HCT patients.

Total body irradiation dose and risk of subsequent neoplasms following allogeneic hematopoietic cell transplantation.

We examined the impact of total body irradiation (TBI) dose and fractionation on risk of subsequent malignant neoplasms (SMNs) in the era of reduced-intensity and nonmyeloablative conditioning regimens for hematopoietic cell transplantation (HCT). Among 4905 1-year survivors of allogeneic HCT for hematologic malignancies (N = 4500) or nonmalignant disorders (N = 405) who received transplants between 1969 and 2014, we identified 581 SMNs (excluding squamous and basal cell of skin) in 499 individuals. With a median length of follow-up of 12.5 years, the cumulative incidence of SMNs by 30 years after HCT was 22.0%. Compared with age-, sex-, and calendar year-matched Surveillance, Epidemiology, and End Results (SEER) population rates, the standardized incidence ratio (SIR) of SMNs was increased 2.8-fold. The highest SIRs were for SMNs of bones (SIR, 28.8), oral cavity (SIR, 13.8), skin (SIR, 7.3), central nervous system (SIR, 6.0), and endocrine organs (SIR, 4.9). The highest excess absolute risks (EARs) were seen with breast cancer (EAR, 2.2) and cancers of the oral cavity (EAR, 1.5) and skin (EAR, 1.5) per 1000 person-years. The highest incidence of SMNs was in survivors exposed to unfractionated (600-1000 cGy) or high-dose fractionated (1440-1750 cGy) TBI. For patients receiving low-dose TBI, the incidence was comparable to myeloablative chemotherapy alone, although still twofold higher than in the general population. These data demonstrate a strong effect of TBI dose, dose fractionation, and risk of SMNs after HCT. The cumulative incidence of SMNs increases with follow-up time; thus, HCT survivors require lifetime monitoring for early detection and effective therapy of SMNs.

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.

Feasibility and acceptability of a home-based resistance training intervention in adolescent and young adult hematopoietic cell transplant survivors.

BACKGROUND: Adolescent and young adult (AYA) hematopoietic cell transplantation (HCT) survivors are at increased risk of metabolic syndrome and lean body mass (LBM) deficits. Resistance training (RT) is a potential intervention to improve LBM, metabolic fitness, and reduce risk of cardiovascular disease. PROCEDURE: Eligible participants ages 13-39 years, 80-120 days post-HCT, transfusion independent, and prednisone dose ≤1 mg/kg/day were approached. Baseline assessments of body composition (DXA), anthropometrics, and strength testing were completed and participants were taught a 12-week, home-based RT intervention with weekly remote coaching. Follow-up assessments were at day +200 (FU1) and +365 post-HCT (FU2). Feasibility targets were (a) 60% enrollment of approached patients, (b) 80% completion of weekly phone calls, and (c) 80% completion of the RT intervention and FU1 assessments. Acceptability was based on positive responses in qualitative interviews. RESULTS: Twenty of 31 (65%) eligible AYAs enrolled. Three participants failed to complete baseline measurements (2 = scheduling barriers, 1 = passive refusal) and four participants who completed baseline assessments did not receive the intervention (1 = medical reasons, 2 = no longer interested). Of those who completed baseline assessments, 13 received the intervention, completed 88.5% of coaching calls, and 11 (65%) completed FU1. LBM (kg) increased or remained unchanged in nine of nine participants with complete body composition data at FU1 (mean 1.1 kg; 95%CI: 0.4, 1.9). All participants who completed FU1 reported they would recommend the intervention to an AYA HCT survivor. CONCLUSIONS: A home-based RT intervention in AYA HCT survivors early post HCT is both feasible and acceptable and may maintain or increase LBM.

HLA-Haploidentical Hematopoietic Cell Transplantation for Treatment of Nonmalignant Diseases Using Nonmyeloablative Conditioning and Post-Transplant Cyclophosphamide.

Allogeneic hematopoietic cell transplant (HCT) is often the only curative therapy for patients with nonmalignant diseases; however, many patients do not have an HLA-matched donor. Historically, poor survival has been seen after HLA-haploidentical HCT because of poor immune reconstitution, increased infections, graft-versus-host disease (GVHD), and graft failure. Encouraging results have been reported using a nonmyeloablative T cell-replete HLA-haploidentical transplant approach in patients with hematologic malignancies. Here we report the outcomes of 23 patients with various nonmalignant diseases using a similar approach. Patients received HLA-haploidentical bone marrow (n = 17) or granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (n = 6) grafts after conditioning with cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, and 2 or 4 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, tacrolimus, ± sirolimus. Median patient age at HCT was 10.8 years. Day 100 transplant-related mortality (TRM) was 0%. Two patients died at later time points, 1 from intracranial hemorrhage/disseminated fungal infection in the setting of graft failure and 1 from infection/GVHD. The estimated probabilities of grades II to IV and III to IV acute GVHD at day 100 and 2-year National Institutes of Health consensus chronic GVHD were 78%, 26%, and 42%, respectively. With a median follow-up of 2.5 years, the 2-year overall and event-free rates of survival were 91% and 78%, respectively. These results are encouraging and demonstrate favorable disease-specific lineage engraftment with low TRM in patients with nonmalignant diseases using nonmyeloablative conditioning followed by T cell-replete HLA-haploidentical grafts. However, additional strategies are needed for GVHD prevention to make this a viable treatment approach for patients with nonmalignant diseases.

Reduced-intensity conditioning for hematopoietic cell transplant for HLH and primary immune deficiencies.

Allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning for disorders associated with excessive inflammation such as hemophagocytic lymphohistiocytosis (HLH) is associated with early mortality. A multicenter prospective phase 2 trial of reduced-intensity conditioning with melphalan, fludarabine, and intermediate-timing alemtuzumab was conducted for HLA matched or single HLA locus mismatched related or unrelated donor HCT in a largely pediatric cohort. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine with methylprednisolone. The primary end point was 1-year overall survival (OS). Thirty-four patients with HLH and 12 with other primary immune deficiencies were transplanted. With a median follow-up of 20 months, the 1-year OS for transplanted patients was 80.4% (90% confidence interval [CI], 68.6%-88.2%). Five additional deaths by 16 months yielded an 18-month OS probability of 66.7% (90% CI, 52.9%-77.3%). Two patients experienced primary graft failure, and 18 patients either experienced a secondary graft failure or required a second intervention (mostly donor lymphocyte infusion [DLI]). At 1 year, the proportion of patients alive with sustained engraftment without DLI or second HCT was 39.1% (95% CI, 25.2%-54.6%), and that of being alive and engrafted (with or without DLI) was 60.9% (95% CI, 45.4 %-74.9%). The day 100 incidence of grade II to IV acute GVHD was 17.4% (95% CI, 8.1%-29.7%), and 1-year incidence of chronic GVHD was 26.7% (95% CI, 14.6%-40.4%). Although the trial demonstrated low early mortality, the majority of surviving patients required DLI or second HCT. These results demonstrate a need for future approaches that maintain low early mortality with improved sustained engraftment. The trial was registered at Clinical Trials.gov (NCT 01998633).

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.

Engaging hematopoietic cell transplantation patients and caregivers in the design of print and mobile application individualized survivorship care plan tools.

PURPOSE: INSPIRE (INteractive Survivorship Program with Information and REsources) is an online health program that includes a mobile app, website, health action plan, and individualized survivorship care plans for adult hematopoietic cell transplant (HCT) survivors. The INSPIRE program integrates two previously effective randomized control trials that tested an internet-based program and patient-centered survivorship care plans for HCT survivors. METHODS: Three focus groups were conducted with a total of 22 participants (20 patients, 2 caregivers/patient advocates) to explore patient and caregiver preferences and to optimize the patient-centered emphasis of INSPIRE. Adult (age > 18 years at the time of study entry) HCT recipients had to be at least 1-year post-HCT to participate; caregivers/patient advocates were also eligible. Participants had to be able to communicate in English, could have any diagnosis, transplant type, or donor source, and could have had multiple transplants. RESULTS: All patient participants received an allogeneic HCT; average time since HCT was 8 years (range 2-22 years). The majority of participants were female (77.3%). Overall, the tools were well received by participants in this study, particularly the personalized features of all the tools. Major themes included interest in having the ability to tailor features to individual needs, and an interest in tracking information over time. DISCUSSION: Engaging patients and caregivers is invaluable to optimize tools designed to improve HCT survivorship care. Print, online, and mobile-based tools, tailored to individual patients' treatment history and requisite follow-up care, can provide otherwise unavailable expertise and guidelines for care.

Distress and resilience among adolescents and young adults with cancer and their mothers: An exploratory analysis.

The aim of this analysis was to explore intra-family longitudinal relationships in psychosocial well-being among adolescent and young adults (AYAs, Mage = 17, SD = 2.1) with cancer and their mothers using data from a multi-site, prospective, survey-based study. AYA-mother dyads (n = 14 dyads) completed validated patient reported outcome (PRO) measures of self-perceived resilience [Connor-Davidson resilience scale (CD-RISC-10)] and distress [Kessler-6 psychological distress scale (K6)] at baseline (14-60 days following diagnosis) and follow-up (3-6 months later). Higher AYA distress predicted better maternal resilience, whereas higher maternal distress predicted worse AYA resilience. Thus, processes of resilience between AYAs and their mothers may differ.

Vascular Structure and Function in Cancer Survivors after Hematopoietic Stem Cell Transplantation.

This study examined the effects of hematopoietic cell transplantation (HCT) and associated preparative regimens on vascular structure and function. Measures of carotid artery stiffness and brachial artery endothelial-dependent dilation were obtained in patients who had survived ≥ 2 years after HCT for hematologic malignancy and were diagnosed at ≤21 years. HCT survivors (n = 108) were examined: 66 received total body irradiation (TBI) alone or with a low-dose cranial radiation boost (TBI±LD-CRT), 19 received TBI plus high-dose cranial radiation (TBI+HD-CRT), and 23 received a chemotherapy-only preparative regimen (CHEMO). Siblings (n = 83) were invited to participate as control subjects. Although endothelial-dependent dilation did not differ between siblings and HCT survivors, carotid cross-sectional compliance, cross-sectional distensibility, diameter compliance, and diameter distensibility were greater in siblings than HCT survivors. Comparing the HCT preparative regimens, carotid cross-sectional compliance, cross-sectional distensibility, diameter compliance, diameter distensibility, and incremental elastic modulus were significantly lower in the TBI+HD-CRT group compared with siblings or with TBI±LD-CRT and CHEMO treatment groups. Cross-sectional distensibility and diameter compliance were significantly lower in the TBI±LD-CRT group compared with siblings. TBI±LD-CRT and CHEMO groups did not differ from each other in these vascular measures. HCT preparative regimens containing TBI+HD-CRT resulted in greater arterial decrements, indicating increased risk for cardiovascular disease.

Tailoring a Survivorship Care Plan: Patient and Provider Preferences for Recipients of Hematopoietic Cell Transplantation.

This study aimed to develop a survivorship care plan (SCP) that can be individualized to facilitate long-term follow-up care of hematopoietic cell transplantation (HCT) survivors. A sample SCP was developed that included 2 documents: a treatment summary and preventive care recommendations that combined data on treatment exposures routinely submitted by HCT centers to the Center for International Blood and Marrow Transplant Research (CIBMTR) with long-term follow-up guidelines. Focus groups were conducted by phone to characterize the critical patient-centered elements of the SCP. Focus group eligibility criteria included (1) adult patients >1 year post-HCT and their caregivers (3 groups; n = 22), (2) HCT physicians and advanced practice providers (APPs) (2 groups; n = 14), (3) HCT nurses and social workers (4 groups; n = 17), and (4) community health care professionals (3 groups; n = 24). Transcripts were analyzed for saturation of key themes using NVivo 10 software. Patients and caregivers suggested combining the treatment summary and care guidelines into a single document. They also requested sections on sexual and emotional health and the immune system. Providers wanted the treatment summary to focus only on what they absolutely must know. Themes were similar across healthcare professionals, although screening for psychosocial issues was emphasized more by the nurses and social workers. All preferred to receive the SCP electronically; however, hardcopy was considered necessary for some patients. All felt that the SCP would facilitate appropriate post-HCT care. This study highlights the need for an SCP instrument to facilitate HCT survivorship care. Furthermore, it demonstrates the feasibility and value of engaging HCT recipients, caregivers, and providers in developing an SCP. Their feedback was incorporated into a final SCP that was subsequently tested in a randomized trial.

Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study.

Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by chromosomal fragility, progressive marrow failure, and cancer predisposition. Hematopoietic cell transplantation (HCT) is curative for FA-related marrow failure or leukemia, but both radiation exposure during transplant and graft-versus-host disease (GVHD) may increase risk of later malignancies of the head and neck and anogenital area. In this study, we tested a radiation-free conditioning regimen with a T-cell-depleted graft to eliminate radiation exposure and minimize early and late toxicities of transplant. Forty-five patients (median age, 8.2 years; range 4.3-44) with FA underwent HCT between June 2009 and May 2014. The preparative regimen included busulfan, cyclophosphamide, fludarabine, and rabbit anti-thymocyte globulin. Busulfan levels were monitored to avoid excess toxicity. All grafts were CD34-selected/T-cell-depleted using the CliniMacs CD34 columns (Miltenyi). Thirty-four patients (75.6%) with marrow failure and 11 (24.4%) with myelodysplastic syndrome underwent HCT using matched unrelated (n = 25, 55.5%), mismatched unrelated (n = 14, 31.1%), or mismatched related donors (n = 6, 13.4%). One year probabilities of overall and disease-free survival for the entire cohort, including patients with myeloid malignancy and those receiving mismatched related/haploidentical grafts, were 80% (±6%) and 77.7% (±6.2%), respectively (median follow-up 41 months). All young children (<10 years of age) undergoing HCT for marrow failure using low-dose busulfan-containing regimen survived. No patients developed acute grade 3-4 GVHD. Sequential reduction of busulfan dose was successfully achieved per study design. Our results show excellent outcomes in patients with FA undergoing alternative donor HCT without radiation exposure. The study is registered to www.clinicaltrials.gov as #NCT01082133.

Randomized controlled trial of individualized treatment summary and survivorship care plans for hematopoietic cell transplantation survivors.

Survivorship Care Plans (SCPs) may facilitate long-term care for cancer survivors, but their effectiveness has not been established in hematopoietic cell transplantation recipients. We evaluated the impact of individualized SCPs on patient-reported outcomes among transplant survivors. Adult (≥18 years at transplant) survivors who were 1-5 years post transplantation, proficient in English, and without relapse or secondary cancers were eligible for this multicenter randomized trial. SCPs were developed based on risk-factors and treatment exposures using patient data routinely submitted by transplant centers to the Center for International Blood and Marrow Transplant Research and published guidelines for long-term follow up of transplant survivors. Phone surveys assessing patient-reported outcomes were conducted at baseline and at 6 months. The primary end point was confidence in survivorship information, and secondary end points included cancer and treatment distress, knowledge of transplant exposures, health care utilization, and health-related quality of life. Of 495 patients enrolled, 458 completed a baseline survey and were randomized (care plan=231, standard care=227); 200 (87%) and 199 (88%) completed the 6-month assessments, respectively. Patients' characteristics were similar in the two arms. Participants on the care plan arm reported significantly lower distress scores at 6 months and an increase in the Mental Component Summary quality of life score assessed by the Short Form 12 (SF-12) instrument. No effect was observed on the end point of confidence in survivorship information or other secondary outcomes. Provision of individualized SCPs generated using registry data was associated with reduced distress and improved mental domain of quality of life among 1-5 year hematopoietic cell transplantation survivors. Trial registered at clinicaltrials.gov 02200133.

NCCN Guidelines Insights: Survivorship, Version 2.2019.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors and to facilitate care coordination to ensure that all needs are addressed. These NCCN Insights summarize some of the topics discussed by the NCCN Survivorship Panel during the 2019 update of the guidelines, including the survivorship population addressed, ways to improve care coordination, and pain management.

Hope and benefit finding: Results from the PRISM randomized controlled trial.

BACKGROUND: Adolescents and young adults (AYAs) with cancer are at risk for poor psychosocial outcomes, perhaps because they have not acquired skills to navigate the adversities of illness. In a recent phase II randomized controlled trial (RCT), the "Promoting Resilience in Stress Management" (PRISM) intervention was associated with improved patient-reported resilience, quality of life, and distress. In this planned analysis of secondary aims, we hypothesized PRISM would also improve targeted coping skills of hopeful thinking, benefit finding, and goal setting. METHODS: We conducted this parallel RCT at Seattle Children's Hospital from January 2015 to October 2016. English-speaking AYAs (12-25 years old) with cancer were randomized one-to-one to PRISM or usual care (UC). PRISM teaches stress-management, goal-setting, cognitive-reframing, and meaning-making skills in four sessions delivered in-person every other week. Participants completed surveys at enrollment and 6 months later. Mixed effects linear regression models evaluated associations between PRISM and benefit finding (Benefit-Finding Scale for Children), hopeful thinking (Hope Scale), and an exploratory outcome of goal setting (queried with open-ended items about participant's goals, measured qualitatively by three blinded reviewers). RESULTS: Of N = 92 AYAs (48 PRISM, 44 UC), 73% were 12-17 years old, 43% female, and 62% diagnosed with leukemia or lymphoma. PRISM was associated with improved benefit finding and hope with moderate-to-large effect sizes-benefit finding: +3.1 points, 95% CI 0.0, 6.2, d = 0.4, and P = 0.05; and hope: +3.6 points, 95% CI 0.7, 6.4, d = 0.6, and P = 0.01. We did not detect changes in goal setting (-0.5 points, 95% CI -1.2, 0.3, d = -0.3, P = 0.23). CONCLUSIONS: PRISM was associated with improvements in benefit finding and hopeful thinking, two adaptive coping skills which may mitigate long-term psychosocial risk.