Late Effects Of Treatment Research Articles

Late effects of high-dose methotrexate treatment in childhood cancer survivors\u2014a systematic review

BackgroundHigh-dose methotrexate (HD-MTX) is used in the treatment of different childhood cancers, including leukemia, the most common cancer type and is commonly defined as an intravenous dose of at least 1 g/m2 body surface area per application. A systematic review on late effects on different organs due to HD-MTX is lacking.MethodWe conducted a systematic literature search in PubMed, including studies published in English or German between 1985 and 2020. The population of each study had to consist of at least 75% childhood cancer survivors (CCSs) who had completed the cancer treatment at least twelve months before late effects were assessed and who had received HD-MTX. The literature search was not restricted to specific cancer diagnosis or organ systems at risk for late effects. We excluded case reports, case series, commentaries, editorial letters, poster abstracts, narrative reviews and studies only reporting prevalence of late effects. We followed PRISMA guidelines, assessed the quality of the eligible studies according to GRADE criteria and registered the protocol on PROSPERO (ID: CRD42020212262).ResultsWe included 15 out of 1731 identified studies. Most studies included CCSs diagnosed with acute lymphoblastic leukemia (n = 12). The included studies investigated late effects of HD-MTX on central nervous system (n = 10), renal (n = 2) and bone health (n = 3). Nine studies showed adverse outcomes in neuropsychological testing in exposed compared to non-exposed CCSs, healthy controls or reference values. No study revealed lower bone density or worse renal function in exposed CCSs. As a limitation, the overall quality of the studies per organ system was low to very low, mainly due to selection bias, missing adjustment for important confounders and low precision.ConclusionsCCSs treated with HD-MTX might benefit from neuropsychological testing, to intervene early in case of abnormal results. Methodological shortcomings and heterogeneity of the tests used made it impossible to determine the most appropriate test. Based on the few studies on renal function and bone health, regular screening for dysfunction seems not to be justified. Only screening for neurocognitive late effects is warranted in CCSs treated with HD-MTX.

Measuring Clinical, Biological, and Behavioral Variables to Elucidate Trajectories of Patient-Reported Outcomes: The PROFILES Registry.

To take cancer survivorship research to the next level, it’s important to gain insight in trajectories of changing patient-reported outcomes and impaired recovery after cancer. This is needed as the number of survivors is increasing and a large proportion is confronted with changing health after treatment. Mechanistic research can facilitate the development of personalized risk-stratified follow-up care and tailored interventions to promote healthy cancer survivorship. We describe how these trajectories can be studied by taking the recently extended Dutch population-based Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship (PROFILES) registry as an example. PROFILES combines longitudinal assessment of patient-reported outcomes with novel, ambulatory and objective measures (eg, activity trackers, blood draws, hair samples, online food diaries, online cognitive tests, weighing scales, online symptoms assessment), and cancer registry and pharmacy databases. Furthermore, we discuss methods to optimize the use of a multidomain data collection–like return of individual results to participants, which may improve not only patient empowerment but also long-term cohort retention. Also, advanced statistical methods are needed to handle high-dimensional longitudinal data (with missing values) and provide insight into trajectories of changing patient-reported outcomes after cancer. Our coded data can be used by academic researchers around the world. Registries like PROFILES, which go beyond boundaries of disciplines and institutions, will contribute to better predictions of who will experience changes and why. This is needed to prevent and mitigate long-term and late effects of cancer treatment and to identify new interventions to promote health.

Late Effects of Cancer Treatment, Job Resources, and Burnout Complaints Among Employees With a Breast Cancer Diagnosis 2-10 Years Ago: A Longitudinal Study.

PurposeThe aim of this study was to investigate the effect of possible late effects of cancer treatment (physical complaints, fatigue, and cognitive complaints) and of two job resources (autonomy and supportive leadership style) on future burnout complaints, among employees living 2–10 years beyond breast cancer diagnosis.MethodsData at T1 (baseline questionnaire) and at T2 (9 months later) were collected in 2018 and 2019 (N = 287). These data were part of a longitudinal study among Dutch speaking workers with a cancer diagnosis 2–10 years ago. All complaints and job resources were self-reported. Longitudinal multivariate regression analyses were executed, controlling for years since diagnosis, living with cancer (recurrence or metastasis), and other chronic or severe diseases. Mediation by baseline burnout complaints was considered.ResultsA higher level of fatigue and cognitive complaints at baseline (T1) resulted in higher future burnout complaints (at T2), with partial mediation by baseline burnout complaints. No effect of physical complaints at T1 was observed. Higher levels of autonomy or a supportive leadership style resulted in lower burnout complaints, with full mediation by baseline burnout complaints. Buffering was observed by autonomy in the relationship of cognitive complaints with future burnout complaints. No moderation was observed by supportive leadership.ConclusionThe level of burnout complaints among employees 2–10 years beyond breast cancer diagnosis may be an effect of fatigue or cognitive complaints, and awareness of this effect is necessary. Interventions to stimulate supportive leadership and autonomy are advisable, the latter especially in the case of cognitive complaints.

Assessment of Quality of Life Following Radiotherapy in Patients with Rectum Cancer.

The aim of the present study is to investigate the effects of radiotherapy (RT) on quality of life (QoL) and influencing factors. Data of 106 patients who completely filled out the three questionnaires were evaluated in this prospective study. Quality of life was evaluated with cancer-specific QLQ-C30 and colorectal cancer module QLQ-CR29 created by European Organization for Research and Treatment of Cancer (EORTC). All statistical analyses were done with SPSS version 22 software. A p level of < 0.05 was accepted as statistically significant. Median age was 61 (27-86). Of the patients, 77 (72.6%) were male and 29 (27.4%) were female. When QLQ-C30 questionnaires were evaluated, it was observed that physical, role, cognitive, and emotional function scores were impaired following RT, however returned to pre-RT levels on control. According to the results of QLQ-CR29 questionnaire, after RT, impairment was observed in urination frequency, urinary incontinence, stool frequency, dysuria, fecal incontinence, embarrassment, and sexual interest in male scales; however, they returned to pre-RT values on control. When evaluated with regard to age, financial difficulty, global health score, mucus in stool, dysuria, dyspareunia, and abdominal pain were observed to be poorer in the young; urination frequency and urinary incontinence were observed to be poorer in the elderly. Although both functional and symptom scales were shown to impair, most of them were detected to be temporal and patients could well tolerate radiotherapy. Additional assessment is required for evaluating the late effects of treatments on QoL.

Incidence and time trends of second primary malignancies after non-Hodgkin lymphoma: a Swedish population-based study

AbstractConsidering treatment changes and an improved prognosis of non-Hodgkin lymphoma (NHL) over time, knowledge regarding long-term health outcomes, including late effects of treatment, has become increasingly important. We report on time trends of second primary malignancies (SPMs) in Swedish NHL patients, encompassing the years before as well as after the introduction of anti-CD20 antibody therapy. We identified NHL patients in the Swedish Cancer Register 1993 to 2014 and matched comparators from the Swedish Total Population Register. The matched cohort was followed through 2017. By linking to the Swedish Lymphoma Register, subcohort analyses by NHL subtype were performed. Flexible parametric survival models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of SPM among patients and comparators. Among 32 100 NHL patients, 3619 solid tumors and 217 myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) cases were observed, corresponding to a 40% higher rate of solid tumors (HRsolid tumors = 1.4; 95% CI, 1.4-1.5) and a 5-fold higher rate of MDS/AML (HRMDS/AML = 5.2; 95% CI, 4.4-6.2) than for comparators. Overall, the observed excess risks for solid tumors or MDS/AML remained stable over the study period, except for follicular lymphoma, where the excess rate of MDS/AML attenuated with time (P for trend = .012). We conclude that NHL survivors have an increased risk of both solid tumors and hematologic malignancies, in particular MDS/AML. Stable excess risks over time indicate that contemporary treatment standards are not associated with modified SPM risk. Encouragingly, decreasing rates of MDS/AML were noted among patients with follicular lymphoma, possibly due to the increasing use of nonchemotherapy-based treatments.

Measuring female breast cancer survivors' concerns about late effects of treatment: initial development of the Concerns about Late Effects in Oncology Questionnaire (CLEO).

While an increasing number of women are surviving breast cancer, survivors remain at risk of developing late effects. Late effects are long-term side effects which may emerge months to years after completing active treatment. Survivors may experience chronic worry and concern about the unpredictable and debilitating nature of late effects. This qualitative study aimed to explore the content validity of items included in the first patient-reported outcome measure (PROM) to quantify survivors' concerns about late effects: the Concerns about Late Effects in Oncology Questionnaire (CLEO). Items included in the CLEO were informed by a literature review and consultation with expert stakeholders. Breast cancer survivors completed "think aloud" interviews to explore the perceived acceptability, relevance, clarity, and feasibility of the CLEO. Interviews were transcribed verbatim and analyzed using framework analysis. Twenty-eight participants were interviewed. Participants indicated the CLEO was acceptable, relevant to women's experiences of late effects, and easy to use and understand. Of the 55 proposed items, participants endorsed 33 items across six domains and suggested to include one additional item. These findings suggest the CLEO captured concerns relevant to breast cancer survivors and provides initial validation of items for inclusion in the CLEO. The CLEO may improve communication about late effects in clinical settings and prompt future research into evidence-based interventions for survivors. Future research should assess the relevance of the CLEO items to other cancer populations. The psychometric properties of the CLEO will be evaluated in future stages of questionnaire development.

Muscle-specific functional deficits and lifelong fibrosis in response to paediatric radiotherapy and tumour elimination.

BackgroundAs paediatric cancer survivors are living into adulthood, they suffer from the age‐related, accelerated decline of functional skeletal muscle tissue, termed sarcopenia. With ionizing radiation (radiotherapy) at the core of paediatric cancer therapies, its direct and indirect effects can have lifelong negative impacts on paediatric growth and maintenance of skeletal muscle. Utilizing our recently developed preclinical rhabdomyosarcoma mouse model, we investigated the late effects of paediatric radiation treatment on skeletal muscles from late adolescent (8 weeks old) and middle‐aged (16 months old) mice.MethodsPaediatric C57BL/6J male mice (3 weeks old) were injected with rhabdomyosarcoma cells into their right hindlimbs, and then fractionated irradiation (3 × 8.2 Gy) was administered to those limbs at 4 weeks old to eliminate the tumours. Radiation‐alone and tumour‐irradiated mice were assessed at either 8 weeks (3 weeks post‐irradiation) or 16 months (14 months post‐irradiation) of age for muscle physiology, myofibre characteristics, cell loss, histopathology, fibrosis, inflammatory gene expression, and fibrotic gene expression.ResultsMice that received only paediatric radiation demonstrated reduced muscle mass (−17%, P < 0.001), muscle physiological function (−25%, P < 0.01), muscle contractile kinetics (−25%, P < 0.05), satellite cell number (−45%, P < 0.05), myofibre cross‐sectional area (−30%, P < 0.0001), and myonuclear number (−17%, P < 0.001). Paediatric radiation increased inflammatory gene expression, increased fibrotic gene expression, and induced extracellular matrix protein deposition (fibrosis) with tumour elimination exacerbating some phenotypes. Paediatric tumour‐eliminated mice demonstrated exacerbated deficits to function (−20%, P < 0.05) and myofibre size (−17%, P < 0.001) in some muscles as well as further increases to inflammatory and fibrotic gene expression. Examining the age‐related effects of paediatric radiotherapy in middle‐aged mice, we found persistent myofibre atrophy (−20%, P < 0.01), myonuclear loss (−18%, P < 0.001), up‐regulated inflammatory and fibrotic signalling, and lifelong fibrosis.ConclusionsThe results from this paediatric radiotherapy model are consistent and recapitulate the clinical and molecular features of accelerated sarcopenia, musculoskeletal frailty, and radiation‐induced fibrosis experienced by paediatric cancer survivors. We believe that this preclinical mouse model is well poised for future mechanistic insights and therapeutic interventions that improve the quality of life for paediatric cancer survivors.

Evaluation of Cardiotoxicity in HER-2-Positive Breast Cancer Patients Treated With Radiation Therapy and Trastuzumab

Trastuzumab is associated with cardiac dysfunction in patients with human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. The current study examines the effect of radiation therapy (RT) on cardiotoxicity in this patient population. The Herceptin Adjuvant (HERA) trial is a phase 3 prospective, randomized clinical trial that established the efficacy of trastuzumab in HER-2-positive breast cancer. The current study is a retrospective analysis of 3321 trial patients treated with trastuzumab, with or without RT. Cardiac function was closely monitored over a median follow-up period of 11 years. The primary endpoint of the current study was to determine the effect of RT on left ventricular ejection fraction (LVEF) and the occurrence of cardiovascular events. Patients were divided into 3 groups: 1270 patients received trastuzumab and left-sided RT (group 1); 1271 patients received trastuzumab and right-sided RT (group 2); and 780 patients received trastuzumab with no RT (group 3). The incidence of decline in LVEF documented by echocardiography was 9.18%, 8.99%, and 8.80%, respectively, with no significant differences among the 3 groups (P=.073). The incidence of cardiovascular events was low in all groups, with the lowest incidence noted in group 3 (0.62%) followed by group 2 (0.92%) and group 1 (1.08%) (P=.619). Univariate and multivariate competing-risks regression showed that left-sided and right-sided RT delivery did not significantly increase the risk of LVEF decline or cardiovascular events. Our analysis of the HERA trial suggests that RT does not significantly increase the risk of cardiotoxicity in HER-2-positive breast cancer patients treated with trastuzumab. Continued monitoring of patients is needed to investigate late effects of contemporary treatments for breast cancer patients.

Abstract PO-215: Racial disparities in proton beam therapy use for newly diagnosed cancer patients in the United States

Abstract Background: Black patients are less likely than White patients in the US to receive guideline-concordant cancer care, including radiation therapy. Proton Beam Therapy (PBT) is a potentially superior technology to photon radiotherapy for the treatment of pediatric cancers, where decreasing late effects of radiation treatment is a main concern, and in cancers where pituitary, visual, auditory, and intellectual functions might be disrupted because of radiation therapy. The aim of this study was to conduct a comprehensive evaluation of racial disparities in PBT use in the US. Methods: We identified 4,919,975 Black and White patients diagnosed between 2004 and 2018 in the National Cancer Database (NCDB) based on data collected from Commission on Cancer (CoC) accredited hospitals. Once a patient is diagnosed and/or treated at a CoC accredited facility, the patient is followed and all treatment is reported (including treatment received outside of the reporting facility). Therefore, NCDB captures PBT received both at CoC-accredited hospitals (59.5% of patients who received PBT in this study) and PBT received at hospitals not accredited by CoCs (40.5% of PBT patients in this study). American Society of Radiation Oncology (ASTRO) Model Policies were used to classify patients into Group 1, for which PBT is the recommended radiation therapy modality, and Group 2, for which evidence of PBT efficacy is still under investigation. Propensity score matching was used to ensure comparability of Black and White patients' clinical characteristics and regional availability of PBT. Results: Black cancer patients were less likely to be treated with PBT than White cancer patients with similar characteristics (Odds Ratios [OR]: 0.72; 95% Confidence Interval [CI]: 0.68, 0.76). Racial disparities were greater for Group 1 cancers (OR = 0.61; CI: 0.54, 0.69) than for Group 2 cancers (OR: 0.75; CI: 0.70, 0.81). Disparities were greatest for Group 1 cancers commonly diagnosed in children, such as central nervous system (OR: 0.54; CI: 0.46, 0.63) and rhabdomyosarcoma (OR: 0.47; CI: 0.31, 0.70). Racial disparities in PBT receipt among Group 1 cancers increased during the study period and were greatest in 2018 despite the increase in the number of facilities offering PBT from 4 to 28 during the corresponding period, Conclusion and Relevance: Racial disparities in PBT receipt are greatest for cancers for which PBT is the recommended radiation therapy modality. The racial disparities identified in our study suggest undertreatment of Black patients with the greatest need (e.g. children diagnosed with central nervous system cancers). Future studies are needed to identify modifiable factors contributing to the racial disparity in receipt of PBT as efforts other than increasing the number of facilities providing PBT will be needed to eliminate disparities. Citation Format: Leticia M. Nogueira, Ahmedin Jemal, Jason A. Efstathiou, K. Robin Yabroff. Racial disparities in proton beam therapy use for newly diagnosed cancer patients in the United States [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-215.

Late Effects of Childhood Cancer Treatment in Long-Term Survivors Diagnosed Before the Age of 3 Years - A Multicenter, Nationwide Study

Late Effects of Childhood Cancer Treatment in Long-Term Survivors Diagnosed Before the Age of 3 Years - A Multicenter, Nationwide Study

Reconstruction of spermatogonial niche for male fertility preservation

Infertility is one of the late side effects of cancer treatment. Expansion of anti-cancer treatment allow patients to have more life time, however infertility is becoming a matter damaging QOL during the young cancer survivors. The passive strategy such as avoiding the gonad-toxic drug or decreasing the total volume of them and shielding the gonads against cancer therapy has been conducted. To preserve the fertility of young female, ovary tissue cryopreservation is becoming a standard over the world after the success of offspring from cryopreserved ovary tissue autograft was reported. Sperm preservation method is established for the male fertility preservation method, however this is only applicable for sexually matured male patients. For the sake of preserving fertility of sexually immature male patients, many trials using cryopreserved testis tissues or testicular cells have been undergone. Recently, in vitro gametogenesis from stem cell of the human and the mouse to primordial germ cell like cell has been achieved. Here the previous challenges and the latest reports for obtaining functional sperm from immature testis and the reconstruction of spermatogonial niche as a potential approach for preserving fertility procedure are described.

Central Nervous System Tumors in Children.

Central Nervous System Tumors in Children.

All eyes on the EuroNet-PHL-C1 trial for paediatric classical Hodgkin lymphoma.

Combined-modality therapy has been the paradigm in the treatment of paediatric classical Hodgkin lymphoma for 15–20 years, leading to event-free survival rates of around 90% and overall survival rates of around 95%. 1 Mauz-Korholz C Metzger ML Kelly KM et al. Pediatric Hodgkin lymphoma. J Clin Oncol. 2015; 33: 2975-2985 Crossref PubMed Scopus (86) Google Scholar In the past two decades, however, the strategy has silently shifted towards a response-based approach with shrinking radiation fields and clearly characterised patients in whom radiotherapy could safely be either completely or partially omitted to minimise the radiation-induced late effects of therapy. 2 Ehrhardt MJ Flerlage JE Armenian SH Castellino SM Hodgson DC Hudson MM Integration of pediatric hodgkin lymphoma treatment and late effects guidelines: seeing the forest beyond the trees. JNCCN. 2021; 19: 755-764 PubMed Google Scholar Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trialOur results show that radiotherapy can be omitted in patients who adequately respond to treatment, when consolidated with COPP or COPDAC. COPDAC might be less effective, but is substantially less gonadotoxic than COPP. A high proportion of patients could therefore be spared radiotherapy, eventually reducing the late effects of treatment. With more refined criteria for response assessment, the number of patients who receive radiotherapy will be further decreased. Full-Text PDF Open Access

P-O01 A patient education video to support the management of post-gastrectomy / oesophagectomy syndromes

Abstract Background Oesophagectomy and gastrectomy result in profound and life-long changes in eating behaviour and appetite, and significant post-prandial symptoms. Despite decades of research, and recent advantages in the understanding of gut physiology, medical approaches to post-resectional patient care remain limited. The mainstay of treatment is patient education. Using clinical and lab-based studies, we investigated the effects of altered gut hormone secretion in patients after surgery for oesophageal and gastric cancer. We then produced a partially animated patient information video to better equip our patients to manage their altered alimentation. Methods The scientific background to the video was previously presented at AUGIS, and published. Studies included examination of eating behaviour, post-prandial symptoms, glucose homeostasis, gut hormone profiles and intestinal transcriptomic / peptidomic changes in a cohort of patients after oesophagectomy and gastrectomy. The movie storyboard and script were written by a team of surgeons, dietitians, patient representatives, clinical scientists and communications specialists. The goal was to communicate the physiological basis of altered eating in post-operative patients and appropriate nutritional strategies. Results The video is now freely available on Vimeo at: https://vimeo.com/356892336 It is in routine use for pre- and post-operative patient education. Conclusions Multimedia patient education is a useful tool to help manage the late effects of upper GI cancer treatment.

Endocrine late effects of cancer treatment.

Endocrine disorders are one of the common late complications of cancer treatment in childhood and adulthood. The incidence is more common in individuals who underwent oncology treatment in childhood in whom the estimated prevalence of these disorders is 20-50%. With improving treatment, there is an increasing number of people with a history of cancer treatment and thus persons who are potentially at risk of developing endocrine disorders. In adults, the prevalence of disorders is lower compared to those who had treatment in their childhood; however, endocrinological complications are relatively common even here, although the dia-gnosis is given less attention in adults compared to children. Endocrine disorders are possible complications of practically all treatment modalities used in oncology (radiotherapy, chemotherapy and immunotherapy). In terms of the type of disorders, these mainly include hypofunction or - more rarely - hyperfunction of the endocrine glands and secondary endocrine neoplasms, especially radiotherapy-induced thyroid tumors. The disadvantages of endocrine disorders are often non-specific and slowly developing symptoms. In addition to a clinical examination with an assessment of the presence of possible clinical manifestations, regular laboratory tests should also be performed to allow for early detection. The level of risk of developing endocrine disorders varies and depends on a number of factors, including the age at which the individual underwent treatment as well as the type of treatment: radiation dose, type of chemotherapy, etc. Based on these data, individualized monitoring plan for the individual needs should be made, allowing an early detection of these disorders. The advantage of endocrinological consequences is the fact that if properly and timely dia-gnosed, they are relatively easy to treat and the treatment often allows for full restitution of the condition. The purpose of this article is to present a brief overview about broad spectrum of various possible endocrine complications of cancer treatment, how to dia-gnose and treat them, aiming to increase awareness about this topic among the health care professionals who treat these patients.

Employment status and occupational positions of childhood cancer survivors from Denmark, Finland and Sweden: A Nordic register-based cohort study from the SALiCCS research programme.

SummaryBackgroundA childhood cancer diagnosis and late effects of treatment may affect survivors’ possibilities of employment or highly skilled occupations later in life. In this study, we compared the employment and occupational status of childhood cancer survivors with population comparisons and siblings.MethodsIn a cohort study based on Nordic registers, we identified 10 461 survivors of childhood cancer diagnosed before age 20 years in Denmark, Finland and Sweden since 1971. Survivors were compared with 48 928 population comparisons matched to survivors by age, sex and geographical region and 12 605 siblings of survivors. Annual outcome information on employment, unemployment, health-related unemployment and occupational position was obtained from the statistical institutes between 1980-2017 and assessed in multivariate logistic regression analyses from age 30 onwards.FindingsBy 30 years of age, 9.2% (95% CI, 8.6-9.9%) of survivors were unemployed for health reasons. Childhood cancer survivors had considerably higher odds of health-related unemployment at ages 30, 40 and 50 than population comparisons (ORage30, 2.57; 95% CI, 2.35-2.81) and siblings (ORage30, 2.50; 95% CI, 2.15-2.90). We observed no large difference in unemployment unrelated to health or in occupational position. Health-related unemployment was particularly pronounced among survivors of central nervous system tumours and survivors diagnosed below 15 years of age.InterpretationSurvivors at risk of health-related unemployment should be offered comprehensive survivorship care and interventions for obtaining and maintaining suitable employment.FundingNordForsk [76111], the Danish Childhood Cancer Foundation [2016-0293], Aarhus University [43239402], the Swedish Childhood Cancer Foundation [PR2020-0130] and [OB2019-0003], Tømrermester Jørgen Holm og Hustru Elisa F. Hansens Mindelegat [20088] and the Swiss National Science Foundation to LM [P2LUP3_175288].

Early parental knowledge of late effect risks in children with cancer.

Despite the pervasiveness of late effects in childhood cancer survivors, many parents feel inadequately informed about their child's risks. We assessed early parental knowledge of risks of late effects and predictors of increased knowledge. Parents of children receiving cancer treatment at Dana-Farber/Boston Children's Cancer and Blood Disorders Center were surveyed about their knowledge of their child's likelihood of eight late effects. Individual risk for each late effect (yes/no) was assessed using the Children's Oncology Group's Long-Term Follow-Up Guidelines v5 as a reference. Descriptive statistics were used to summarize knowledge scores; ordinal logistic regression was used to identify predictors of higher knowledge. Of 96 parent participants, 11 (11.46%) correctly identified all of their child's risks for the eight late effects. Five of eight was the median number of correctly identified late effect risks. Among 21 parents whose children were at risk for ototoxicity, 95% correctly identified this risk. Conversely, parents of at-risk children were less knowledgeable about risks of secondary malignancy (63% correct identification, of N=94 at risk), cardiac toxicity (61%; N=71), neurocognitive impairment (56%; N=63), and infertility (28%; N=61). Ordinal logistic regression analysis identified no significant differences in parental knowledge of late effect risks by any factors evaluated. Gaps in parental knowledge of potential late effects of childhood cancer treatment emerge early in a child's care, and parents are more knowledgeable about some late effects, such as ototoxicity, than others, such as infertility. As no child- or parent-specific factors were associated with increased knowledge of late effect risks, interventions must be applied broadly.

Distress, Health-Related Quality of Life (HQOL) and Confidence in Survivorship Information (CSI) in Older (≥60 Years) Hematopoietic Cell Transplant (HCT) Patients

Background: The use of HCT to treat older (≥60 years) patients with hematological malignancies has markedly increased in recent years, however, the long-term effects of HCT on distress, psychosocial functioning, and HQOL in older HCT survivors is largely unknown. Though older HCT survivors have a higher risk of disease recurrence, they may have less access to resources and subsequently experience more pronounced late effects of disease and treatment. Confidence in Survivorship Information (CSI) in this specific age group has not been reported.Methods: We conducted a secondary analysis on a subgroup of patients enrolled in INSPIRE (NCT01602211) and PCORI-SCP (NCT02200133) clinical trials. Eligibility criteria for inclusion include HCT patients who were ≥ 60 years at time of transplant performed in 2003-2014, survived ≥ 1 year post-transplant with no evidence of disease relapse or secondary cancers. Patients were eligible for inclusion irrespective of transplant type (autologous or allogeneic), diagnosis, donor source or conditioning regimen. Primary endpoint was distress level in older HCT survivors; secondary endpoints included CSI and HQOL outcomes. We collected baseline distress level as measured by Cancer and Treatment Distress (CTXD) score, HQOL (measured by SF-12 Mental and Physical Component Summaries (PCS/MCS) and CSI (measured by a 15-item CSI questionnaire). Sociodemographic, disease and transplant factors were extracted from medical databases. Nonparametric (Wilcoxon rank sum/Kruskal-Wallis) test was conducted for comparing 2 or 3 groups. Spearman correlation and univariate linear regression model were used to evaluate associations between CTXD/CSI and PCS/MCS. Bonferroni correlation was used to adjust for multiple pairwise comparisons within age group.Results: A total of 567 patients satisfied the eligibility criteria and were included in this analysis. Median age at time of HCT was 69 years with 57% male; two-thirds were autologous HCT recipients. Table 1 details patient characteristics. The median CTXD score for older HCT survivors was 0.7 (range 0-2.7, SD 0.6) indicating low/insignificant level of distress post-HCT. 20-30% of HCT survivors reported moderate distress when asked about concerns regarding relapse risk, loss of energy and functional decline. Type of transplant (auto vs allo), age group (<65 years, 65-70 years, ≥70 years), and time from HCT (≤2 years vs > 2 years) showed no apparent effect on reported distress level. CSI median score was 1.4 (range 0-2) which remains consistent with the score reported previously by the original trial including all age groups, indicating that older HCT survivors may have similar level of confidence in their survivorship information as their younger counterparts. Of note, close to 20% of the older HCT survivors reported poor CSI when asked about strategies for prevention and treatment of long-term effects of HCT and when asked about their confidence in availability of community resources to deal with long-term HCT complications. No statistically significant correlation was identified between CSI in older survivors and transplant type, time from HCT, or age group. HQOL outcomes indicated a median PCS of 48.2 (range 21.1 - 62.9) and a median MCS of 54.7 (range of 14.9 - 67.2). Interestingly, even though not reflected on the overall median CTXD and CSI scores for this cohort, a significant individual association between CTXD/CSI and PCS/MCS measures of HQOL was found (Figure 1). A subgroup analysis conducted on older alloHCT recipients confirmed the same findings of clinically insignificant distress level (mean CTXD ≤1.1) while having a similar level of CSI when compared to all age groups. Interestingly, time from HCT (≤2 years vs > 2 years) showed no significant effect on distress level reported by older alloHCT survivors, and cGVHD status did not correlate with CTXD or CSI scores nor with PCS/MCS in older alloHCT survivors.Conclusion: This is the largest study to date to investigate patient-reported distress, CSI and HQOL in older HCT survivors. Our data indicate that older HCT survivors have low levels of stress after HCT and had confidence in survivorship information in most aspects of their care. However, targeted interventions should focus on improving strategies for prevention, treatment and availability of community resources to deal with late effects of HCT; aspects reported as points of low CSI by older HCT survivors. [Display omitted] DisclosuresFarhadfar: Incyte: Consultancy. Shaw: Orca bio: Consultancy; mallinkrodt: Other: payments. Devine: Be the Match: Current Employment; Orca Bio: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy. Wingard: Merck: Consultancy; AlloVir: Consultancy; Celgene: Consultancy; Shire: Consultancy; Janssen: Consultancy; Cidara Therapeutics: Consultancy.

Meeting Challenges in the Long-Term Care of Children, Adolescents, and Young Adults with Acute Lymphoblastic Leukemia.

To discuss the long-term view of treating and following pediatric, adolescent, and young adult patients with acute lymphoblastic leukemia (ALL) - with review of what can be done to prevent, monitor for, and treat complications of therapy. Pediatric, adolescent, and young adult oncology patients, including those with ALL, are living longer with higher overall survival rates as treatments and supportive care for these patients continue to improve. These patients are burdened by the risk of significant health and quality of life consequences as a result of their treatment.. For these patients, the late effects of treatment can be life-threatening, such as secondary cancers or cardiotoxicity, or life-altering with respect to quality of life. The goal of this paper is to review the current literature, research, and surveillance guidelines regarding the late effects of ALL therapy, to outline what can be done to mitigate the toxic effects of oncology treatment, and to extend life expectancy and improve quality of life for our patients. We review risk factors and interventions available to prevent and treat cardiovascular disease, secondary malignancies, endocrine complications (obesity, osteoporosis, infertility, and premature menopause), cognitive effects, and effects on functioning and mortality.

Evaluation of Cardiotoxicity in HER-2 Positive Breast Cancer Patients Treated With Radiation Therapy and Trastuzumab

Trastuzumab is associated with cardiac dysfunction in HER-2 positive breast cancer patients. The current study examines the effect of radiation therapy on cardiotoxicity in this patient population.The HERA trial is a phase III prospective randomized clinical trial that established the efficacy of trastuzumab in HER-2 positive breast cancer. The current study is a retrospective analysis of 3,321 trial patients treated with trastuzumab with or without radiotherapy. Cardiac function was closely monitored over a median follow up period of 10 years. The primary endpoint of the study was to determine the effect of radiation therapy on left ventricular ejection fraction (LVEF) and the occurrence of cardiovascular events.Patients were divided to three groups: 1270 subjects received trastuzumab and left-sided radiation therapy (group 1), 1271 subjects received trastuzumab and right-sided radiation therapy (group 2) and 780 had trastuzumab with no radiation therapy (group 3). The incidence of significant LVEF decline was 28.22%, 29.54% and 26.85%, respectively with no significant differences among the three groups (P-value = 0.484). The incidence of cardiovascular events was low in all groups with the lowest incidence noted in group 3 (0.62%) followed by group 2 (0.92%) and group 1 (1.08%) (P-value = 0.619). Univariate and multivariate COX regression showed significant associations of age and hypertension with both LVEF decline and cardiovascular events. However, radiation therapy delivery and laterality were not significantly associated with either outcome.Our analysis of the HERA trial suggests that radiation therapy does not significantly increase the risk of cardiotoxicity in HER-2 positive breast cancer patients treated with trastuzumab. Continued monitoring of patients is needed to investigate late effects of contemporary treatments for breast cancer patients.