Search

Background: Because the occurrence of metabolic syndrome (MetS) might contribute to childhood cancer survivor's excess risk of cardiovascular disease, the authors assessed the prevalence and determinants of MetS in the Dutch Childhood Cancer Survivor Study (DCCSS‐LATER2) cohort. Methods: In total, 2338 adult childhood cancer survivors (CCS) were cross‐sectionally assessed for the prevalence of MetS, using the Lifelines cohort (N = 132,226 adults without a history of cancer) as references. The prevalence of MetS was clinically assessed using existing classifications, as well as an alternative method using dual‐energy x‐ray absorptiometry fat% instead of waist circumference to define abdominal adiposity. Logistic regression models, adjusted for age and sex, were used to investigate the association between the presence of MetS and both cohorts. Demographic, lifestyle, and treatment determinants of MetS were identified through multivariable logistic regression. Results: The survivor cohort (median age, 34.7 years, median follow‐up time, 27.1 years) showed increased adjusted odds ratio (aOR) for MetS (modified National Cholesterol Education Program Adult Treatment Panel III criteria), as compared to the reference cohort (aOR, 2.07; 95% confidence interval [CI], 1.85–2.32). Compared to these criteria, the alternative method identified 57 additional survivors with MetS (395 of 2070 [19.1%] vs. 452 of 1960 [23.1%], respectively). Age (odds ratio [OR], 1.07; 95% CI, 1.04–1.10, per year increase), smoking (OR, 1.46; 95% CI, 1.04–2.04), low physical activity (OR, 1.48; 95% CI, 1.05–2.09), abdominal radiotherapy (OR, 2.13; 95% CI, 1.01–4.31; >30 Gy), cranial radiotherapy (OR, 2.89; 95% CI, 1.67–4.96; 1–25 Gy; and OR, 2.44; 95% CI, 1.30–4.47; >25 Gy), total body irradiation (OR, 6.17; 95% CI, 3.20–11.76), and underlying central nervous system tumor (OR, 1.78; 95% CI, 1.21–2.60) were associated with MetS. Conclusion: The high risk of MetS in CCS, combined with several potential modifiable factors, underscores the need for timely identification and intervention strategies to mitigate the long‐term cardiovascular risks in CCS. The prevalence of metabolic syndrome in the recruited nationwide childhood cancer survivor cohort was high and inconsistent with the chronological age, suggesting a substantial future health burden. Nonmodifiable determinants, including cranial, abdominal, and total body irradiation, as well as modifiable determinants, including smoking and physical activity, were associated with metabolic syndrome in this nationwide childhood cancer survivor cohort. [ABSTRACT FROM AUTHOR]

Introduction: Severe combined immunodeficiency (SCID) is an inborn error of immunity that is fatal without hematopoietic cell transplantation (HCT) or gene therapy (GT). Survival outcomes have improved, largely due to implementation of SCID newborn screening. A better understanding of the long-term outcomes and late effects to address critical aspects of monitoring immune and general health life-long is needed. Areas covered: In a comprehensive review of PubMed indexed articles with publication dates 2008–2024 we describe the current knowledge of chronic and late effects (CLE) of HCT survivors for SCID as well as the role of GT and advances for specific SCID genotypes. We review factors affecting the development of CLE including disease related factors (genotype, trigger for diagnosis and presence of infection prior to HCT), transplant related factors (type of donor, conditioning regimen, immune reconstitution and graft versus host disease (GVHD) and describe causes and factors associated with higher risk for late mortality in this unique population. We further describe monitoring and potential therapeutic strategies for management of common CLE in this patient population. Expert opinion: Ongoing research efforts are needed to better describe CLE in survivors, to develop prospective clinical trials aimed at mitigating these CLE, and developing genotype-based approaches for management and follow-up of these patients. [ABSTRACT FROM AUTHOR]

Purpose: Adolescent and young adult (AYA) malignant brain tumour (BT) survivors are at risk of adverse health outcomes, which may impact their health-related quality of life (HRQoL). This study aimed to investigate the (1) prevalence of physical and psychological adverse health outcomes, (2) the HRQoL, and (3) the association of adverse health outcomes and HRQoL among long-term AYA-BT survivors. Adverse health outcomes and HRQoL were compared to other AYA cancer (AYAC) survivors. Methods: A cross-sectional secondary data analysis of the SURVAYA study among 133 AYA-BT and 3877 AYAC survivors was conducted. Participant self-reported adverse health outcomes and HRQoL scores were analysed and compared between the two populations. Associations with HRQoL were assessed using linear regression modelling with AIC-based backward elimination. Results: AYA-BT survivors faced significant issues of fatigue (47.6%), future uncertainty (45.2%), and medical conditions like vision (34.4%), speech, taste, or smell (26.2%) impairments, cancer recurrence, and metastasis (25.4%). Neurocognitive symptoms were identified as BT-specific issues (13.6–33.6%). Compared to AYAC survivors, AYA-BT survivors reported significantly (p < 0.05) lower functioning scores on the role, cognitive, emotional, and social HRQoL, with cognitive (56.0%) and emotional (40.0%) domains being the most affected. Adverse health outcomes were negatively associated with HRQoL, ranging from small to large clinical relevance. Conclusion: Long-term AYA-BT survivors were identified as a highly burdened population, affected by multifaceted issues and multidimensional detriments in HRQoL years beyond their cancer diagnosis. This study highlights the necessity of long-term follow-up and a holistic, multidisciplinary approach to survivorship care to ultimately improve the quality of AYA-BT survivorship. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors face high risks of adverse late health effects. Long‐term follow‐up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high‐quality long‐term follow‐up care, we explored expected barriers and facilitators for establishing this follow‐up care among healthcare providers from four European clinics. Methods: A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi‐structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political. Results: Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long‐term follow‐up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long‐term follow‐up care results to convince hospital managers. Conclusion: This study identified several factors for successful implementation of long‐term follow‐up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors. [ABSTRACT FROM AUTHOR]

Background: Low-grade glioma is the most common brain tumor in children with different modes of treatment and a high overall survival. Low-grade glioma is considered a chronic disease, since residual tumor is present in many children. The tumor and its treatment lead to acquired brain injury with diverse consequences for later life based on factors like the diverse tumor locations, treatment(s) applied, neurofibromatosis type 1, and age at diagnosis. Methods: An overview of affected domains is provided based upon cohort studies from literature and partially based on clinical experience with a practical approach regarding each domain of functioning in order to provide insight in the requirements for long-term care assistance after childhood low-grade glioma. Results: The diverse domains that can potentially be affected are described as follows: motor function, speech, eating and swallowing, sensory functions, seizures, neuropathy, organ function after systemic treatment, late effects due to cranial radiation (vascular changes and secondary tumors, endocrine and hypothalamic function, sleep and energy, neuro-cognition and education, psychosocial effects, and quality of life. Conclusion: Insight in affected domains guides advices for medical follow-up, diagnostics, supportive instructions, and assistive measures per domain of functioning and provide insight in the requirements for long-term care assistance after childhood low-grade glioma. [ABSTRACT FROM AUTHOR]

Summary: The documented treatment‐induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995–2015 and aged 15–40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I–II and 33.5% had stage III–IV disease. With a median follow‐up of 14.76 years, 139 deaths occurred, yielding a 5‐year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL‐related death showed an initial sharp rise, with a plateau at 5.3% 10‐year post‐diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20‐year mark respectively. HL cases had a 7.5‐fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause‐specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches. [ABSTRACT FROM AUTHOR]

Purpose: Despite a haematopoietic stem cell transplant (HSCT) being a potentially curative treatment option for malignant and non-malignant disorders, patients may develop complex physical and psychological post-transplant complications. Consequently, transplant centres remain responsible for patients' life-long monitoring and screening practices. We sought to describe how HSCT survivors experience long-term follow-up (LTFU) monitoring clinics in England. Method: A qualitative approach was adopted with data collected from written accounts. Seventeen transplant recipients were recruited from across England, and the data was analysed using thematic analysis. Results: Data analysis elicited four themes: Transfer to LTFU care: 'will there be a change in my care, or will appointments just become less frequent?'; Care Coordination: 'it is good to know I am still in the system'; Relationship continuity: 'a good knowledge of me, my health and what is important to me'; and Late-effects Screening: 'there was not much information about what to expect or be aware of'. Conclusions: HSCT survivors in England experience uncertainty and lack of information regarding the transfer from acute to long-term care and clinic screening practices. However, patients gain reassurance from remaining on a healthcare pathway and maintaining relationships with healthcare professionals. Implications for cancer survivors: HSCT recipients entering LTFU monitoring clinics are a growing population of cancer survivors. Understanding and acknowledging this cohort of patients' needs may inform the development of tailored support to help patients navigate the complicated healthcare pathway. [ABSTRACT FROM AUTHOR]

Background: Parameningeal rhabdomyosarcoma (PM-RMS) is a rare and aggressive soft tissue malignancy that primarily occurs in the head and neck region. The standard treatment approach for RMS involves a multimodal therapy regimen, which includes surgery, chemotherapy, and radiotherapy. However, the routine use of radiotherapy and chemotherapy in young patients with RMS in the head and neck region can lead to adverse effects on dental development and thereby, pose a challenge in planning dental intervention. Case presentation: This case report outlines the dental and facial developmental consequences in a 13-year-old child, who received chemo-radiotherapeutic intervention at the age of 7 years for the management of PM-RMS. Following treatment, the child exhibited significant dental complications, including arrested root growth and restricted mouth opening. Conclusions: This case highlights the necessity for interdisciplinary collaboration between oncologists, dentists, and other healthcare professionals to mitigate the adverse effects on dental health and overall quality of life in patients undergoing chemo-radiotherapy for rhabdomyosarcoma. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to examine the prevalence of unhealthy lifestyle behaviors, overweight, and obesity in Dutch childhood cancer survivors (CCSs) compared with sibling controls and the Dutch general population. Other aims were to assess associated factors of unhealthy lifestyle behaviors, overweight, and obesity and to identify subgroups of CCSs at risk for these unhealthy statuses. Methods: The authors included 2253 CCSs and 906 siblings from the Dutch Childhood Cancer Survivor Study‐Late Effects After Childhood Cancer cohort, part 1, and added data from the Dutch general population. Questionnaire data were collected on overweight and obesity (body mass index >25.0 kg/m2), meeting physical activity guidelines (>150 minutes per week of moderate or vigorous exercises), excessive alcohol consumption (>14 and >21 alcoholic consumptions per week for women and men, respectively), daily smoking, and monthly drug use. Multivariable logistic regression analyses and two‐step cluster analyses were performed to examine sociodemographic‐related, health‐related, cancer‐related, and treatment‐related associated factors of unhealthy lifestyle behaviors and to identify subgroups of CCSs at risk for multiple unhealthy behaviors. Results: CCSs more often did not meet physical activity guidelines than their siblings (30.0% vs. 19.3%; p <.001). Married as marital status, lower education level, nonstudent status, and comorbidities were common associated factors for a body mass index ≥25.0 kg/m2 and insufficient physical activity, whereas male sex and lower education were shared associated factors for excessive alcohol consumption, daily smoking, and monthly drug use. A subgroup of CCSs was identified as excessive alcohol consumers, daily smokers, and monthly drug users. Conclusions: The current results emphasize the factors associated with unhealthy behaviors and the potential identification of CCSs who exhibit multiple unhealthy lifestyle behaviors. The results of this study indicate a higher prevalence of physical inactivity in childhood cancer survivors compared with sibling controls and the Dutch population, emphasizing the necessity for personalized health behavior interventions in childhood cancer survivors. These findings can be used in clinical practice to create awareness and to identify subgroups of childhood cancer survivors who need special attention regarding health behaviors. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)? SUMMARY ANSWER Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL. WHAT IS KNOWN ALREADY Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol. STUDY DESIGN, SIZE, DURATION This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatment-levels (TL1, TL2, and TL3) and treatment-arms (OEPA-COPDAC-28 and OEPA-DECOPDAC-21). Serum samples obtained from patients after receiving pelvic radiotherapy were excluded from the main analyses. MAIN RESULTS AND THE ROLE OF CHANCE A total of 104 females, with median age at diagnosis of 15.6 years (IQR 13.7; 17.0), were included in the analysis. Ninety-nine were (post)pubertal. Eighteen girls were diagnosed with an early stage of cHL (TL1) and 86 with intermediate or advanced stage disease (50 TL2 and 36 TL3, 66% received COPDAC-28 and 34% DECOPDAC-21). Five patients received pelvic radiotherapy. Median AMH level at diagnosis was 1.7 µg/l (IQR 0.9; 2.7). After two courses of OEPA chemotherapy, AMH levels decreased substantially in all patients (98% <0.5 µg/l), followed by a significant increase during the consolidation treatment and follow-up. After 2 years, 68% of patients reached their baseline AMH value, with overall median recovery of 129% (IQR 75.0; 208.9) compared to baseline measurement. Five patients (7%) had AMH <0.5 µg/l. In patients treated for advanced stage disease, AMH levels remained significantly lower compared to early- or intermediate stage disease, with median serum AMH of 1.3 µg/l (IQR 0.8; 2.1) after 2 years. Patients who received DECOPDAC-21 consolidation had lower AMH levels during treatment than patients receiving COPDAC-28, but the difference was no longer statistically significant at 2 years post-diagnosis. Of the 35 postmenarchal girls who did not receive hormonal co-treatment, 19 (54%) experienced treatment-induced amenorrhea, two girls had persisting amenorrhea after 2 years. LIMITATIONS, REASONS FOR CAUTION The studied population comprises young girls with diagnosis of cHL often concurring with pubertal transition, during which AMH levels naturally rise. There was no control population, while the interpretation of AMH as a biomarker during childhood is complex. The state of cHL disease may affect AMH levels at diagnosis, potentially complicating assessment of AMH recovery as a comparison with baseline AMH. The current analysis included data up to 2–5 years post-diagnosis. WIDER IMPLICATIONS OF THE FINDINGS The current PANCARE guideline advises to use the cyclophosphamide-equivalent dose score (CED-score, as an estimation of cumulative alkylating agent exposure) with a cut-off of 6000 mg/m2 to identify females aged <25 years at high risk of infertility. All treatment-arms of the EuroNet-PHL-C2 protocol remain below this cut-off, and based on this guideline, girls treated for cHL should therefore be considered low-risk of infertility. However, although we observed an increase in AMH after chemotherapy, it should be noted that not all girls recovered to pre-treatment AMH levels, particularly those treated for advanced stages of cHL. It remains unclear how our measurements relate to age-specific expected AMH levels and patterns. Additional (long-term) data are needed to explore clinical reproductive outcomes of survivors treated according to the EuroNet-PHL-C2 protocol. STUDY FUNDING/COMPETING INTEREST(S) The fertility add-on study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M-K. D.K. W.H.W. D.H. M.C. A.U. and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors indicated no potential conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Summary: Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin‐containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population‐based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age‐ and sex‐matched comparators from the background population. Median follow‐up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30–3.68]), with a 10‐year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35–26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43–2.76]), with a 10‐year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43–1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B‐symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work‐up of pulmonary symptoms. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can human pre- and peri-pubertal testicular cells obtained from childhood cancer patients, previously treated with chemotherapy, form testicular organoids (TOs)? SUMMARY ANSWER Organoid formation from testicular tissue collected from childhood cancer patients positively correlates with SRY-Box transcription factor 9 (SOX9) expression in Sertoli cells, which in turn negatively correlates with previous exposure to alkylating chemotherapy. WHAT IS KNOWN ALREADY Pre- and peri-pubertal boys exposed to highly gonadotoxic therapies can only safeguard their fertility potential through testicular tissue cryopreservation. Today, there is no established clinical tool to restore fertility using these testicular samples. Organoids hold promise in providing fundamental early insights in creating such platforms. However, the generation of TOs that closely resemble the innate testis, to enable a thorough monitoring of the necessary steps for germ cell differentiation and somatic functionalities, remains a challenge. STUDY DESIGN, SIZE, DURATION We used a Matrigel-based three-layer gradient culture system to generate human TOs and to reveal whether chemotherapy exposure affects TO formation capacity and the functionality of pre- and peri-pubertal testicular somatic cells. Testicular cells of 11 boys (aged 7.7 ± 4.1 (mean ± SD) years) were assessed for TO formation in relation to previous chemotherapy exposure and SOX9 expression in histological sections of paraffin-embedded testicular tissue samples collected on the day of biopsy and compared with testicular tissue samples obtained from 28 consecutive patients (aged 6.9 ± 3.8 (mean ± SD) years). All 39 patients were part of the fertility preservation project NORDFERTIL; an additional 10 samples (from boys aged 5.5 ± 3.5 (mean ± SD) years, without an underlying pathology) in an internal biobank collection were used as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS We obtained 49 testicular tissue samples from boys aged 0.8–13.4 years. Fresh samples (n = 11) were dissociated into single-cell suspensions and applied to a three-layer gradient culture system for organoid formation. Histological sections of another 28 samples obtained as part of the fertility preservation project NORDFERTIL, and 10 samples from a sample collection of a pathology biobank were used to evaluate the effects of prior exposure to alkylating agents on testicular samples. Testicular organoid formation was defined based on morphological features, such as compartmentalized structures showing cord formation, and protein expression of testicular cell-specific markers for germ and somatic cells was evaluated via immunohistochemical staining. Hormone secretion was analysed by specific enzyme-linked immunosorbent assays for testosterone and anti-Müllerian hormone (AMH) production. MAIN RESULTS AND THE ROLE OF CHANCE Our results revealed that 4 out of 11 prepubertal testicular samples formed TOs that showed compartmentalized cord-like structures surrounded by interstitial-like areas and increasing levels of both testosterone as well as AMH over a 7-day culture period. We observed that SOX9 expression was correlated positively with TO formation. Moreover, exposure to alkylating agents before biopsy was inversely correlated with SOX9 expression (P  = 0.006). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Due to the limited amount of material available, only 11 out of the 39 pre- and peri-pubertal testicular tissue samples could be used for the organoid formation experiments. The testicular tissue samples obtained from a sample collection of the internal biobank of Department of Pathology, Karolinska University Hospital were considered normal and included in the study if no testicular pathology was reported. However, detailed information regarding previous medical treatments and/or testicular volumes of the patients included in this biobank was not available. WIDER IMPLICATIONS OF THE FINDINGS Our observations suggest that SOX9 expression may serve as a putative indicator of TO formation, indicating a critical role of Sertoli cells in promoting organoid formation, seminiferous tubule integrity, and testicular function in pre- and peri-pubertal testicular tissue. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115; TJ2020-0023) (J.-B.S.), Finnish Cancer Society (K.J.), Finnish Foundation for Paediatric Research (K.J.), Swedish Research Council (2018-03094; 2021-02107) (J.-B.S.), and Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2020-00335; 2021-00073; 2022-00317) (J.-B.S. and K.J.). Y.C. and Y.Y. received a scholarship from the Chinese Scholarship Council. J.P.A-L. was supported by a Starting Grant in Medicine and Health (2022-01467) from the Swedish Research Council. R.T.M. was supported by a UKRI Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health was supported by an MRC Centre Grant (MR/N022556/1). The authors declare no competing interests. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors are at risk of various endocrine late effects affecting their quality of life. The aim of this study was to assess the prevalence and predictors of endocrine and reproductive outcomes in young adult survivors. A secondary aim was to assess possible associations between testosterone replacement therapy (TRT) and other endocrine, cardiovascular and psychosocial late effects. This nationwide study comprised 1212 male childhood cancer survivors aged 19–40 years, identified through the National Quality Registry for Childhood Cancer in Sweden. Median age at diagnosis during 1981–2017 was 7 (range 0–17) and at study 29 (19–40) years. The study combined self‐report survey data with cancer treatment data from the national registry. Hormone‐induced puberty was self‐reported by 3.8% of the survivors and ongoing TRT by 6.0%. In separate logistic regression analyses, these treatments were associated with hematopoietic stem cell transplantation and cranial radiotherapy. Hormone‐induced puberty was additionally associated with younger age at diagnosis. Men with TRT had a higher prevalence of other endocrine deficiencies, cholesterol medication, depressive symptoms and fatigue as well as a lower probability of living with a partner, having a biological child or current occupation. In the total male cohort, 28.2% reported having a biological child. Reassuring reproductive outcomes after less intensive therapies and low frequency of TRT were observed in young adult male childhood cancer survivors treated in the most recent treatment era. However, men with TRT suffered from several other endocrine, cardiovascular and psychosocial late effects, indicating a need for long‐term monitoring of this high‐risk group. [ABSTRACT FROM AUTHOR]

Introduction: Cancer therapies predispose childhood cancer survivors to various treatment-related late effects, which contribute to a higher symptom burden, chronic health conditions (CHCs), and premature mortality. Regular monitoring of symptoms between clinic visits is useful for timely medical consultation and interventions that can improve quality of life (QOL). The Health Share Study aims to utilize mHealth to collect patient-generated health data (PGHD; daily symptoms, momentary physical health status) and develop survivor-specific risk prediction scores formitigating adverse health outcomes including poor QOL and emergency roomadmissions. These personalized risk scoreswill be integrated into the hospital-based electronic health record (EHR) system to facilitate clinician communications with survivors for timely management of late effects. Methods: This prospective study will recruit 600 adult survivors of childhood cancer from the St. Jude Lifetime Cohort study. Data collection include 20 daily symptoms via a smartphone, objective physical health data (physical activity intensity, sleep performance, and biometric data including resting heart rate, heart rate variability, oxygen saturation, and physical stress) via a wearable activity monitor, patient-reported outcomes (poor QOL, unplanned healthcare utilization) via a smartphone, and clinically ascertained outcomes (physical performance deficits, onset of/worsening CHCs) assessed in the survivorship clinic. Participants will complete health surveys and physical/functional assessments in the clinic at baseline, 2) report daily symptoms, wear an activity monitor, measure blood pressure at home over 4 months, and 3) complete health surveys and physical/functional assessments in the clinic 1 and 2 years from the baseline. Socio-demographic and clinical data abstracted from the EHR will be included in the analysis. We will invite 20 cancer survivors to investigate suitable formats to display predicted risk information on a dashboard and 10 clinicians to suggest evidence-based risk management strategies for adverse health outcomes. Analysis: Machine and statistical learning will be used in prediction modeling. Both approaches can handle a large number of predictors, including longitudinal patterns of daily symptoms/other PGHD, along with cancer treatments and socio-demographics. Conclusion: The individualized risk prediction scores and added communications between providers and survivors have the potential to improve survivorship care and outcomes by identifying early clinical presentations of adverse events. [ABSTRACT FROM AUTHOR]

Background/Objectives: The survival rate among pediatric cancer patients has reached 80%; however, these childhood cancer survivors (CCSs) are at a heightened risk of developing chronic conditions in adulthood, particularly kidney and cardiovascular diseases. The aims of this study were to assess the serum α-Klotho and FGF23 levels in CCSs and to determine their association with nephro- and cardiotoxicity. Methods: This study evaluated a cohort of 66 CCSs who remained in continuous remission, with a mean follow-up of 8.41 ± 3.76 years. Results: The results of this study revealed that CCSs exhibited significantly higher levels of soluble α-Klotho compared to healthy peers (1331.4 ± 735.5 pg/mL vs. 566.43 ± 157.7 pg/mL, p < 0.0001), while no significant difference was observed in their FGF23 levels. Within the participant cohort, eight individuals (12%) demonstrated a reduced estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73 m2. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed (p < 0.05). No correlations were found between potential treatment-related risk factors, such as chemotherapy or radiation therapy, serum levels of α-Klotho and FGF23, and nephro- and cardiotoxicity. Conclusions: In conclusion, this preliminary cross-sectional study revealed elevated levels of α-Klotho among childhood cancer survivors but did not establish a direct association with anticancer treatment. The significance of elevated α-Klotho protein levels among CCSs warrants further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Childhood cancer survivors (CCS) are at risk of experiencing lower quality-of-life, fatigue, and depression. Few randomized controlled trials have studied the effect of physical activity (PA) on these in adult long-term CCS. This study investigated the effect of a 1-year individualized PA intervention on healthrelated quality-of-life (HRQOL), fatigue, and distress symptoms in adult CCS. Methods: The SURfit trial randomized 151 CCS =16 years old, <16 at diagnosis and =5 years since diagnosis, identified through the Swiss Childhood Cancer Registry. Intervention participants received personalized PA counselling to increase intense PA by =2.5 h/week for 1 year. Controls maintained usual PA levels. The authors assessed physical- and mental-HRQOL, fatigue, and distress symptoms at baseline, 3, 6, and 12 months. T-scores were calculated using representative normative populations (mean = 50, standard deviation = 10). Generalized linear mixed-effects models with intention-to-treat (ITT, primary), and three per-protocol allocations were used. Results: At 12 months, ITT (-3.56 larger decrease, 95% confidence interval -5.69 to -1.43, p = .001) and two per-protocol analyses found significantly lower fatigue. Physical-HRQOL improved significantly in two per-protocol analyses at 12 months. No other effects were found. Conclusion: SURfit showed that increased intense PA over 1 year improved fatigue in adult CCS. Survivors should be recommended PA to reduce the burden of late-effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Understanding the age-specific effects of proton beam therapy (PBT) on kidney function is crucial for personalized treatment. This study compared the long-term impact of PBT on kidneys in pediatric and adult patients with adjacent malignancies. Findings reveal that children are more prone to renal atrophy post-PBT compared to adults, who experience minimal changes in kidney morphology. The percentage of irradiated volume receiving 10 Gy (RBE) and 20 Gy (RBE) may predict the degree of renal atrophy, especially in children. PBT has minimal impact on renal function deterioration in both age groups. This research informs treatment plans for patients in different ages, aiming to minimize renal complications and provide insights for personalized cancer care, ensuring better long-term kidney health outcomes and overall quality of life. To compare late renal effects in pediatric and adult patients with malignancies after PBT involving part of the kidney. A retrospective study was conducted to assess changes in renal volume and function in 24 patients, including 12 children (1–14 years old) and 12 adults (51–80 years old). Kidney volumes were measured from CT or MRI images during follow-up. Dose-volume histograms were calculated using a treatment planning system. In children, the median volume changes for the irradiated and control kidneys were −5.58 (−94.95 to +4.79) and +14.92 (−19.45 to +53.89) mL, respectively, with a relative volume change of −28.38 (−119.45 to −3.87) mL for the irradiated kidneys. For adults, these volume changes were −22.43 (−68.7 to −3.48) and −21.56 (−57.26 to −0.16) mL, respectively, with a relative volume change of −5.83 (−28.85 to +30.92) mL. Control kidneys in children exhibited a marked increase in size, while those in adults showed slight volumetric loss. The percentage of irradiated volume receiving 10 Gy (RBE) (V10) and 20 Gy (RBE) (V20) were significantly negatively associated with the relative volume change per year, especially in children. The CKD stage based on eGFR for all patients ranged from 1 to 3 and no cases with severe renal dysfunction were found before or after PBT. Late effects on the kidneys after PBT vary among age groups. Children are more susceptible than adults to significant renal atrophy after PBT. V10 and V20 might serve as predictors of the degree of renal atrophy after PBT, especially in children. PBT has a minimal impact on deterioration of renal function in both children and adults. [ABSTRACT FROM AUTHOR]

For many cancer survivors, toxic side effects of treatment, lingering effects of the aftermath of disease and cancer recurrence adversely affect quality of life (QoL) and reduce healthspan. Data−driven approaches for quantifying and improving wellness in healthy individuals hold great promise for improving the lives of cancer survivors. The data-driven strategy will also guide personalized nutrition and exercise recommendations that may help prevent cancer recurrence and secondary malignancies in survivors. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate how cumulative burden of clinically relevant, self‐reported outcomes in childhood cancer survivors (CCSs) compares to a sibling control group and to explore how the burden corresponds to levels of care proposed by existing risk stratifications. Methods: The authors invited 5925 5‐year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS LATER) cohort and their 1066 siblings to complete a questionnaire on health outcomes. Health outcomes were validated by self‐reported medication use or medical record review. Missing data on clinically relevant outcomes in CCSs for whom no questionnaire data were available were imputed with predictive mean matching. We calculated the mean cumulative count (MCC) for clinically relevant outcomes. Furthermore, we calculated 30‐year MCC for groups of CCSs based on primary cancer diagnosis and treatment, ranked 30‐year MCC, and compared the ranking to levels of care according to existing risk stratifications. Results: At median 18.5 years after 5‐year survival, 46% of CCSs had at least one clinically relevant outcome. CCSs experienced 2.8 times more health conditions than siblings (30‐year MCC = 0.79; 95% confidence interval [CI], 0.74–0.85 vs. 30‐year MCC = 0.29; 95% CI, 0.25–0.34). CCSs' burden of clinically relevant outcomes consisted mainly of endocrine and vascular conditions and varied by primary cancer type. The ranking of the 30‐year MCC often did not correspond with levels of care in existing risk stratifications. Conclusions: CCSs experience a high cumulative burden of clinically relevant outcomes that was not completely reflected by current risk stratifications. Choices for survivorship care should extend beyond primary tumor and treatment parameters, and should consider also including CCSs' current morbidity. Survivors of childhood cancer experience a high cumulative burden of clinically relevant outcomes. Choices for survivorship care should extend beyond primary tumor and treatment parameters and should also consider including the current morbidity of childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Copyright of Paediatria Croatica is the property of Paediatria Croatica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Survivors of childhood neuroblastoma are at risk of multiple treatment-related health problems (late effects), impacting their quality of life. While late effects and quality of life among Australia and New Zealand (ANZ) childhood cancer survivors have been reported, the outcomes of neuroblastoma survivors specifically have not been reported, limiting critical information to inform treatment and care. Methods: Young neuroblastoma survivors or their parents (as proxy for survivors <16 years) were invited to complete a survey and optional telephone interview. Survivors' late effects, risk perceptions, health-care use, and health-related quality of life were surveyed and analyzed using descriptive statistics and linear regression analyses. In-depth interviews explored participants' experiences, knowledge, and perception of late effects and information needs. Thematic content analysis was used to summarize the data. Results: Thirty-nine neuroblastoma survivors or parents completed questionnaires (median age = 16 years, 39% male), with 13 also completing interviews. Thirty-two participants (82%) reported experiencing at least 1 late effect, most commonly dental problems (56%), vision/hearing problems (47%), and fatigue (44%). Participants reported high overall quality of life (index = 0.9, range = 0.2–1.0); however, more participants experienced anxiety/depression compared to the population norm (50% met criteria versus 25%, χ 2 = 13, p  < 0.001). Approximately half of participants (53%) believed they were at risk of developing further late effects. Qualitatively, participants reported knowledge gaps in understanding their risk of developing late effects. Conclusion: Many neuroblastoma survivors appear to experience late effects, anxiety/depression and have unmet cancer-related information needs. This study highlights important areas for intervention to reduce the impact of neuroblastoma and its treatment in childhood and young adulthood. [ABSTRACT FROM AUTHOR]

Purpose: The study aims to describe work status at diagnosis and 8 years post-diagnosis in a nationwide sample of breast cancer survivors (BCSs), and investigate associated and self-reported factors of reduced work status. Methods: Women aged 20–65 years when diagnosed with stage I–III breast cancer (BC) in 2011 or 2012 were invited to participate in a questionnaire study in 2019 (n = 2803), of whom 49% (n = 1361) responded. For this sub-study, we included 974 BCSs below the legal retirement age in Norway (< 67 years) at survey and with complete work status data. Reduced work status was defined as being in paid work at BC diagnosis and not working at time of survey. Logistic regression analyses were applied to identify factors associated with reduced work status. Results: Of BCSs who were in paid work at diagnosis (n = 845), 63% maintained their work status to 8 years later. Reduced work status was associated with not living with children (OR.44, 95% CI.24–.82), age (OR 1.16, 95% CI 1.11–1.21), chemotherapy (OR 2.83, 95% CI 1.24–6.61), > 2 comorbid conditions (OR 2.27, 95% CI 1.16–4.32), cognitive function (OR.99, 95% CI.98–.99), fatigue (OR 1.02, 95% CI 1.01–1.03), and neuroticism (OR 1.57, 95% CI 1.00–2.46). BC and late effects were reported as reasons for reduced work status and disability. Conclusions: The majority of BCSs who were in paid work at diagnosis were working 8 years later. Implications for Cancer Survivors: Our results suggest a need to focus on fatigue and reduced cognitive function among long-term BCSs, with the ultimate aim of improving work sustainability. [ABSTRACT FROM AUTHOR]

Background: Due to late effects, childhood cancer survivors (CCS) are more likely to have multiple chronic conditions than the general population. However, little is known about the economic burden of care of CCS in the long term. Objectives: To estimate excess healthcare expenditure for long-term CCS in France compared to the general population and to investigate the associated factors. Methods: We included 5353 5-year solid CCS diagnosed before the age of 21 years before 2000 from the French CCS cohort and obtained a random reference sample from the general population for each CCS, matched on age, gender and region of residence. We used the French national health data system to estimate annual healthcare expenditure between 2011 and 2018 for CCS and the reference sample, and computed the excess as the net difference between CCS expenditure and the median expenditure of the reference sample. We used repeated-measures linear models to estimate associations between excess healthcare expenditure and CCS characteristics. Results: Annual mean (95% CI) excess healthcare expenditure was €3920 (3539; 4301), mainly for hospitalization (39.6%) and pharmacy expenses (17%). Higher excess was significantly associated with having been treated before the 1990s and having survived a central nervous system tumor, whereas lower excess was associated with CCS who had not received treatment with radiotherapy. Conclusions: Of the variables that influence excess healthcare expenditure, a lever for action is the type of treatment administered. Future research should focus on addressing the long-term cost-effectiveness of new approaches, especially those related to radiotherapy. [ABSTRACT FROM AUTHOR]

Retardation of growth and development is a well-known late effect after radiotherapy for pediatric patients. The goal of the study was to examine the effect of proton beam therapy (PBT) on the growth of muscles included in the irradiated area. The subjects were 17 pediatric patients (age ≤ 5 years) who received PBT with a treatment field including a muscle on only one side out of a pair of symmetrical bilateral muscles and had imaging evaluations for at least 1 year after PBT. The thicknesses of the irradiated and non-irradiated (contralateral) muscles were measured retrospectively on CT or MRI axial images collected before and after PBT. The change of thickness divided by the period (years) for each muscle was compared between the irradiated and contralateral sides. Correlations of muscle growth with irradiation dose and age at the start of treatment were also evaluated. The median observation period was 39.2 months. The measurement sites included the erector spinae (n  = 9), gluteus maximus (n  = 5) and rhomboids + trapezius (n  = 3) muscles. The average changes in muscle thickness were 0.24 mm/year on the irradiated side and 1.19 mm/year on the contralateral side, showing significantly reduced growth on the irradiated side (P  = 0.001). Younger patients had greater muscle growth. Irradiation dose was not significant, but muscle growth tended to decrease as the dose increased, and muscles irradiated at >50 Gy (RBE) showed little growth. These results show that muscle growth is affected by PBT and that long-term follow-up is needed to evaluate muscle growth retardation. [ABSTRACT FROM AUTHOR]

Simple Summary: Sexuality remains an unspoken topic in the consulting room regarding testicular germ cell tumor (TGCT) patients in the adolescent and young adult (AYA) age. Little is known about the perspectives and concerns of these patients regarding sexuality. The PRICELESS-study explored these perspectives and concerns through individual interviews with 13 AYA patients treated for TGCT. Interviews revealed seven interacting and interconnected themes: desire to have children, rediscovering sexuality, insecurity about sexual performance, acceptance of physical change, loss of masculinity, burden on relationship, and openness in discussing sexuality. TGCT patients face multiple changes (physical, emotional, relational, and sexual), followed by a difficult period of acceptance, after which a new phase of rediscovering sexuality appears. Insights from this study can help healthcare professionals understand the underlying mechanisms and help to define topics for instrument development to support discussing sexuality. This study aimed to explore perspectives and concerns regarding sexuality among adolescents and young adults (AYAs) possibly experiencing late effects after testicular germ cell tumor (TGCT) treatment. A qualitative study was performed in which semi-structured interviews were held with thirteen AYAs from a center of expertise for TGCT in the Netherlands. Data were analyzed using Braun and Clark's thematic analysis method. Seven interacting and interconnected themes were found: desire to have children, rediscovering sexuality, insecurity about sexual performance, acceptance of physical change, loss of masculinity, burden on relationship, and openness in discussing sexuality. Concerns about the desire to have children seem to play a significant role. In conclusion, TGCT patients face multiple changes (physical, emotional, relational, and sexual), followed by a difficult period of acceptance, after which a new phase of rediscovering sexuality appeared. These findings can help to make healthcare professionals aware of the underlying mechanisms and concerns about sexuality. Furthermore, insights can help to develop sexuality-themed items for a broader monitoring tool to structurally assess the late effects to support discussing sexuality. [ABSTRACT FROM AUTHOR]

Objectives: Childhood cancer survivors are at risk of developing primary recurrences and new second cancers. Experiencing a recurrence and/or second cancer can be highly distressing for survivors and families. We aimed to understand the psychological impacts of experiencing a recurrence or second cancer and how this potentially influences survivors' engagement with survivorship care. Methods: We invited childhood cancer survivors or their parents if survivors were ≤16 years of age from 11 tertiary pediatric oncology hospitals across Australia and New Zealand to complete interviews. We conducted a thematic analysis facilitated by NVivo12. Results: We interviewed 21 participants of whom 16 had experienced a recurrence, 3 had a second cancer, and 2 had both a recurrence and second cancer. Participants reported that a recurrence/second cancer was a stressful sudden disruption to life, accompanied by strong feelings of uncertainty. Participants tended to be less aware of their second cancer risk than recurrence risk. Some participants reported feelings of anxiousness and despair, describing varying responses such as gratitude or avoidance. Participants shared that the fear of cancer recurrence either motivated them to adopt protective health behaviors or to avoid information and disengage from survivorship care. Significance of results: Some survivors and their parents have a poor understanding and expressed reluctance to receive information about their risk of second cancer and other treatment-related late effects. Improving the delivery of information about late effects to families may improve their engagement with survivorship care and surveillance, although care must be taken to balance information provision and survivors' anxieties about their future health. [ABSTRACT FROM AUTHOR]

The Cancer Survivorship Program was established at the University of Pennsylvania Cancer Center in 2001. The Cancer Center was renamed the Abramson Cancer Center of the University of Pennsylvania in 2002 and the survivorship program was henceforth known as the ACC Survivorship Program. The program was supported from 2001 to 2004 in part by a seed grant from the Lance Armstrong Foundation (LAF). The LIVESTRONG Survivorship Centers of Excellence Network was created by the LAF in 2005 and the ACC Survivorship Program joined the Network in 2007. The seven nationwide Cancer Centers that comprised the Network were supported by the LAF through 2015. A focus on clinical care, research, and education led the development of the ACC Survivorship Program. The program is currently led by an advanced practice provider (APP) and staffed by medical, surgical, and radiation oncology APPs and collaborating oncologists. This program provides care to adult survivors of pediatric cancers, as well as survivors of adult-onset cancers such as breast, genitourinary/prostate, lymphoma, head and neck, gastrointestinal, thoracic, sarcoma, and central nervous system. Research protocols for survivors of specific cancer diagnoses have been developed and have resulted in collaborative research, publications, and conference presentations. Sustaining the ACC Survivorship Program has been challenging despite strong endorsement of services by patients, families, and providers. Challenges include barriers such as cost restraints, changing cancer center priorities, and a reduced oncology workforce, issues experienced across the country that must be addressed in the years to come. [ABSTRACT FROM AUTHOR]

Purpose: Reported prevalence of cancer-related fatigue (CRF) among childhood cancer survivors (CCS) varies widely, and evidence on factors associated with CRF among CCS is limited. We aimed to investigate the prevalence of CRF and its associated factors among adult CCS in Switzerland. Methods: In a prospective cohort study, we invited adult CCS who survived at least 5 years since last cancer diagnosis, and were diagnosed when age 0–20 years and treated at Inselspital Bern between 1976 and 2015 to complete two fatigue-measuring instruments: the Checklist Individual Strength subjective fatigue subscale (CIS8R; increased fatigue 27–34, severe fatigue ≥ 35) and the numerical rating scale (NRS; moderate fatigue 4–6, severe fatigue 7–10). We collected information about previous cancer treatment and medical history, and calculated β coefficients for the association between CIS8R/NRS fatigue scores and potential determinants using multivariable linear regression. Results: We included 158 CCS (participation rate: 30%) with a median age at study of 33 years (interquartile range 26–38). Based on CIS8R, 19% (N = 30) of CCS reported increased fatigue, yet none reported severe fatigue. CRF was associated with female sex, central nervous system (CNS) tumors, sleep disturbance, and endocrine disorders. Lower CRF levels were observed among CCS age 30–39 years compared to those younger. Conclusions: A considerable proportion of adult CCS reported increased levels of CRF. Implications for Cancer Survivors: CCS who are female and < 30 years old, have a history of CNS tumor, report sleep disturbance, or have an endocrine disorder should be screened for CRF. [ABSTRACT FROM AUTHOR]

With diagnostic and therapeutic advances, over 80% of children diagnosed with cancer become long-term survivors. As the number of childhood cancer survivors (CCS) continues to increase, dental practitioners become more likely to have CCS among their patients. CCS may develop late complications from damage caused by their cancer treatment to endocrine, cardiovascular, musculoskeletal, and other organ systems. These complications may surface decades after the completion of treatment. Adverse outcomes of childhood cancer treatment frequently involve oral and craniofacial structures including the dentition. Tooth development, salivary gland function, craniofacial growth, and temporomandibular joint function may be disturbed, increasing oral health risks in these individuals. Moreover, CCS are at risk of developing subsequent malignancies, which may manifest in or near the oral cavity. It is important that dental practitioners are aware of the childhood cancer history of their patients and have knowledge of potential late complications. Therefore, this narrative review aims to inform dental practitioners of late oral complications of cancer treatment modalities commonly used in pediatric oncology. Furthermore, selected common non-oral late sequelae of cancer therapy that could have an impact on oral health and on delivering dental care will be discussed. [ABSTRACT FROM AUTHOR]

Targeting the microbiome, microbiota-derived metabolites, and related pathways represents a significant challenge in oncology. Microbiome analyses have confirmed the negative impact of cancer treatment on gut homeostasis, resulting in acute dysbiosis and severe complications, including massive inflammatory immune response, mucosal barrier disruption, and bacterial translocation across the gut epithelium. Moreover, recent studies revealed the relationship between an imbalance in the gut microbiome and treatment-related toxicity. In this review, we provide current insights into the role of the microbiome in tumor development and the impact of gut and tumor microbiomes on chemo- and immunotherapy efficacy, as well as treatment-induced late effects, including cognitive impairment and cardiotoxicity. As discussed, microbiota modulation via probiotic supplementation and fecal microbiota transplantation represents a new trend in cancer patient care, aiming to increase bacterial diversity, alleviate acute and long-term treatment-induced toxicity, and improve the response to various treatment modalities. However, a more detailed understanding of the complex relationship between the microbiome and host can significantly contribute to integrating a microbiome-based approach into clinical practice. Determination of causal correlations might lead to the identification of clinically relevant diagnostic and prognostic microbial biomarkers. Notably, restoration of intestinal homeostasis could contribute to optimizing treatment efficacy and improving cancer patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Long‐term breast cancer survivors (BCSs) may experience several late effects (LEs) simultaneously. This study aimed to identify subgroups of 8‐year BCSs with higher burden of LEs who could benefit from closer survivorship care, explore variables associated with higher symptom burden, and describe how symptom burden may affect general functioning. Methods: All Norwegian women aged 20 to 65 years when diagnosed with stage I‐III breast cancer in 2011 and 2012 were invited (n = 2803). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire/BR23, the Fatigue Questionnaire, Assessment of Survivor Concerns, and Scale for Chemotherapy Induced Long‐term Neurotoxicity were used to assess 10 common LEs and general functioning. Using latent class analysis, subgroups of BCSs with similar burden of LEs were identified. Multinominal regression analysis were performed to examine variables associated with higher symptom burden. Results: The final sample consisted of 1353 BCSs; 46% had low, 37% medium, and 17% high symptom burden. Younger age, short education, axillary dissection, higher systemic treatment burden, higher body mass index, and physical inactivity were associated with higher symptom burden. General functioning scores were lower, and the proportion on disability pension were higher among BCSs in the two most burdened subgroups compared with those in the low burden subgroup. Conclusion: More than half of long‐term BCSs suffered from medium or high symptom burden and experienced impaired general functioning compared with BCS with low symptom burden. Younger age and systemic treatment were important risk factors for higher symptom burden. BCSs at risk of higher symptom burdens should be identified and offered closer and extended survivorship care. More than half of long‐term breast cancer survivors suffer from medium or high burden of late effects. Younger age and systemic treatments are important risk factors for experiencing a higher symptom burden, and breast cancer survivors with these risk factors should be prioritized for closer follow‐up care. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively assess the incidence of Dropped Head Syndrome (DHS) in childhood cancer survivors (CCS) and to develop and evaluate a diagnostic algorithm for DHS. Methods: A systematic literature search for DHS in combination with neck radiotherapy (RT) exposure was performed. Analyses and a combination of the most common examination methods were integrated into a diagnostic algorithm. Almost all CCSs visiting the local late effects clinic between May 2020 and April 2022 were included in the study. CCS exposed to neck RT with doses ≥ 19 Gy received standardized clinical and neurological assessment and, in case of abnormal results, an MRI scan to confirm muscle atrophy. Results: Two hundred and five CCS were included of whom 41 received RT to the neck with ≥ 19 Gy. In the entire cohort and in the subgroup receiving RT, 2.4% and 12% of CCS were affected by DHS, respectively. Results of clinical and neurological assessment correlated well with MRI results. Neck circumference and neck/thigh ratio were lower after neck RT. Over 50% of CCS experienced neck disability and pain. Conclusions: A relevant proportion of CCS exposed to neck RT is affected by DHS. High concordance of MRI results with the neurological examination supports the clinical value of the diagnostic algorithm. Measurement of neck circumference might be an easy tool for assessment of neck muscle atrophy in survivors at risk. Implications for cancer survivors: Integration of a diagnostic algorithm for DHS in standard long-term follow-up care facilitates diagnosis as well as initiation of early treatment and obviates the need for invasive examinations. [ABSTRACT FROM AUTHOR]

Purpose: The standard treatment of non-Hodgkin lymphoma (NHL) comprises combined modality treatment, radiotherapy (RT), and chemotherapy with rituximab which has significantly improved both disease-free survival (DFS) and overall survival (OS). However, there is no uniformity in radiation dose usage in these patients. In this retrospective study, we compared lower radiation dose with higher in patients with aggressive NHL. Materials and Methods: From 2007 to 2017, treatment records of all high-grade NHL or diffuse large B-cell lymphoma and non-central nervous system NHL were included. We compared response rates, OS and DFS of patients who received =30 Gy RT to those with >30 Gy. Univariate and multivariate analyses were done to determine factors affecting prognosis, i.e., age, sex, stage, International Prognostic Index (IPI), adding rituximab, and radiation dose. Results: A total of 184 NHL patients treated with combined modality or radiation alone having complete follow-up details were analyzed. At median follow-up of 66.8 months, 5-year OS was 72.8% in high-dose group versus 69.9% in low-dose group (p = 0.772) and 5-year DFS 64.7% versus 64.1% (p = 0.871). Patients having early-stage disease receiving low dose and those with advanced disease treated with >30 Gy had better OS and DFS though not statistically significant. Adding rituximab was associated with significantly better OS and DFS irrespective of radiation dose delivered. High IPI score and omitting rituximab were the only factors that significantly worsened both OS and DFS. Acute radiation toxicities were comparable in both groups (p = 0.82). Among late toxicities, no patient developed a second malignancy and 5% died due to cardiovascular complications (p = 0.595) though only two patients (1.1%) had received thoracic radiation. Conclusion: The two groups had comparable response rates, acute toxicities, DFS and OS. This study suggests that RT dose reduction may be possible in high-grade NHL without compromising the DFS and OS. [ABSTRACT FROM AUTHOR]

Purpose: Childhood cancer survivors (CCS) are at risk for increased morbidity and reduced quality of life associated with treatment-related late effects. In Germany, however, only a few of the more than 40,000 CCS registered in the German Childhood Cancer Registry (GCCR) currently benefit from adequate clinical long-term follow-up (LTFU) structures. To establish a comprehensive knowledge base on CCS' long-term health in Germany, a database was developed in cooperation with the GCCR. Following a first evaluation phase at two German university centres, this database will be implemented more widely within Germany allowing longitudinal documentation of clinical LTFU data. Methods: The feasibility study cohort comprised 208 CCS aged 18 or older whose medical, mental and psychosocial health data were collected during routine LTFU or first clinic visits in adult care. CCS were enrolled from 04/2021 to 12/2022, and data entry was completed by 03/2023. Descriptive data analysis was conducted. All CCS were stratified into three risk groups (RG) based on their individual risk for developing late effects resulting from their respective diagnoses and treatments. Results: Chronic health conditions of various organ systems associated with late and long-term effects of cancer therapy affected CCS in all RG supporting the clinical relevance of risk-adapted LTFU. Enrolment into the database was feasible and broadly accepted amongst CCS. Conclusion: Implementation of a clinical follow-up care infrastructure and database in Germany will pave the way to collect clinically evaluated and regularly updated health data of potentially over 40,000 German CCS and facilitate future national and international cooperation. [ABSTRACT FROM AUTHOR]

Aim: Nutrition challenges are common during childhood cancer treatment and can persist into survivorship, increasing the risk of non‐communicable diseases. Evidence‐based practice and implementation of nutrition interventions/education for childhood cancer survivors has been poorly investigated and may influence their future health. This study aimed to explore the nutrition interventions/education needs of childhood cancer survivors and the barriers and facilitators to delivering follow‐up services in New Zealand. Methods: Semi structured interviews were conducted with childhood cancer survivors and/or their families (n=22) and health professionals (n=9) from a specialist paediatric oncology centre in New Zealand. Interviews were audio‐recorded and transcribed verbatim. Transcripts were analysed inductively using thematic analysis. A multi‐level consensus coding methodology was used where each theme and associated subthemes were discussed with the study team for confirmation to ensure accurate coding and analysis. Results: Three themes emerged from the analysis: (1) the current survivorship care pathway does not provide adequate interventions/education, (2) weight and dietary changes are common challenges and (3) requirements for interventions/education in survivorship are varied. Common nutrition‐related concerns included fussy eating/limited dietary intake, poor diet quality, difficulties with tube weaning, and challenges with weight gain. Participants expressed a desire for education on healthy eating alongside information about cancer‐related nutrition issues, such as learned food aversions. A preference for clear referral pathways and multifaceted interventions tailored to individual patient needs was identified. Conclusion: The trifecta of treatment side effects, negative feeding practices and poor messaging from health professionals creates a challenging environment to optimise nutrition. A stepped care model matching the intervention intensity with the childhood cancer survivors is required. Education for healthcare professionals will improve the delivery of timely interventions/education and monitoring practices. [ABSTRACT FROM AUTHOR]

Simple Summary: Advanced juvenile nasopharyngeal angiofibroma (JNA) can present a considerable therapeutic challenge. Photon radiotherapy has been recognized as an effective treatment approach for recurrent or inoperable advanced JNA in an additive or definitive setting. However, due to the benign nature of JNA and the young age of the affected patients, concerns about long-term radiation-induced morbidity have led to a certain hesitance towards this treatment modality. Proton therapy (PRT) presents a promising alternative for treating benign conditions in young patients, yet there remains a gap in the literature regarding its application to JNA. We retrospectively examined the outcomes of patients with JNA who underwent PRT in our center and evaluated the dosimetric advantages of PRT over conformal radiotherapy. This study is the first report investigating PRT for advanced JNA, highlighting PRT's safety and effectiveness as a viable therapeutic option. Dosimetric and complication risk evaluations suggest that PRT holds the potential to reduce long-term radiation-induced complications, including the development of secondary neoplasms or decline in neurocognitive function. Purpose: To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT). Methods: We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive or postoperative setting with a relative biological effectiveness weighted dose of 45 Gy in 25 fractions between 2012 and 2022 at the Heidelberg Ion Beam Therapy Center. Furthermore, dosimetric comparisons and risk estimations for short- and long-term radiation-induced complications between PRT plans and helical XRT plans were conducted. Results: PRT was well tolerated, with only low-grade acute toxicities (CTCAE I–II) being reported. The local control rate was 100% after a median follow-up of 27.0 (interquartile range 13.3–58.0) months. PRT resulted in considerable tumor shrinkage, leading to complete remission in five patients and bearing the potential to provide partial or complete symptom relief. Favorable dosimetric outcomes in critical brain substructures by the use of PRT translated into reduced estimated risks for neurocognitive impairment and radiation-induced CNS malignancies compared to XRT. Conclusions: PRT is an effective treatment option for advanced JNA with minimal acute morbidity and the potential for reduced radiation-induced long-term complications. [ABSTRACT FROM AUTHOR]

Purpose: Male breast cancer accounts for approximately 1% of all breast cancer diagnoses. Unfortunately, a lack of information exists regarding late effects of breast cancer treatment in men. Methods: An online survey directed towards male breast cancer patients was distributed via social medial and emails from June to July 2022. Participants were asked about their disease characteristics, treatments and side effects from the disease or treatment. Patients and treatment variables were reported via descriptive statistics. Univariate logistic regression was performed to evaluate associations between different treatment variables and outcomes expressed by odds ratio. Results: A total of 127 responses were analyzed. Median age of the participants was 64 years (range 56–71 years). A total of 91 participants (71.7%) revealed they experienced late effects secondary to their cancer or cancer treatment. The most concerning physical and psychological symptoms reported were fatigue and fear of recurrence respectively. Axillary lymph node dissection was associated with swollen arm and with difficulty in arm or shoulder movement. Systemic chemotherapy was related to bothersome hair loss and changes on interest in sex; and endocrine therapy was associated with feeling less masculine. Conclusion: Our study showed that men suffer several late effects from treatments for breast cancer. Lymphedema, difficulty with arm and shoulder movement, sexual dysfunction and hair loss should be discussed with males as it can be distressing for some patients and decrease their quality of life. [ABSTRACT FROM AUTHOR]

Treatment gaps in meeting the neuropsychological needs of young adult (YA) cancer survivors can be attributed to several clinical and systemic reasons. Access to neurocognitive care can be increased through the effective integration of neuropsychological monitoring and intervention in survivorship care. In this brief report, we aim to compare the efficacy of a brief neuropsychological screener (DIVERGT) in meeting the assessment and referral needs of pediatric and YA cancer survivors (n = 40) as part of a wellness and survivorship clinic. Participants (n = 40) were patients who presented to a pediatric oncology survivorship clinic over the span of 15 months. [ABSTRACT FROM AUTHOR]

Copyright of Tijdschrift voor Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019. Material and Methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position. Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each). Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice. [ABSTRACT FROM AUTHOR]

By 2040, an anticipated 26.1 million people with a history of cancer will be part of the healthcare system. The purpose of this study was to explore Missouri-based non-oncology clinicians' perspectives on caring for patients with a history of cancer to identify needs of rural-based clinicians to optimize their patients' survivorship care. Using an interpretive qualitative descriptive approach, we conducted semi-structured interviews with 17 non-oncology clinicians. We encouraged clinicians to discuss their approach to caring for patients with a history of cancer and invited them to talk about what might help them increase their knowledge of survivorship care best practices. Through interpretive qualitative descriptive analysis methods including first level coding and constant comparison, we found there is consensus that cancer survivorship care is important; however, training that now guides our clinicians occurred mostly during residency, if at all. Clinicians relied on previous patient encounters and oncology notes combined with their patients' personal account of treatment history to inform the best next steps. Clinicians expressed strong interest in having a simple protocol of their patient's treatment with prompts of known long-term cancer treatment–related effects and a patient-centric follow-up monitoring schedule (mandatory vs recommended vs optional). Clinicians expressed interest in educational opportunities about cancer care and ability for curbside consults with oncologists. They consistently noted the limited resources available in rural areas and that rural patients may have different preferences and approaches to cancer survivorship. There is a clear opportunity to improve non-oncology clinicians' knowledge of the needs of people with a history of cancer as well as their own knowledge base and self-efficacy, especially in rural settings. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to examine the association between the conditioning intensity and height growth in pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Methods: We reviewed the clinical records of 89 children with malignant diseases who underwent initial allo‐HSCT between 2003 and 2021. Height measurements were standardized using standard height charts prepared by the Japanese Society for Pediatric Endocrinology to calculate standard deviation score (SDS). We defined short stature as a height SDS less than −2.0 in that reference. Myeloablative conditioning (MAC) comprised total‐body irradiation at more than 8 Gy and busulfan administration at more than 8 mg/kg (more than 280 mg/m2). Other conditioning regimens were defined as reduced intensity conditioning (RIC). Results: A total of 58 patients underwent allo‐HSCT with MAC, and 31 patients received allo‐HSCT with RIC. There were significant differences in the height SDS at 2 and 3 years after allo‐HSCT between MAC and RIC group (−1.33 ± 1.20 vs. −0.76 ± 1.12, p = 0.047, −1.55 ± 1.28 vs. −0.75 ± 1.11, p = 0.022, respectively). Multivariate logistic regression analysis with the adjustments for potential confounding factors of patients less than 10 years of age at allo‐HSCT and chronic graft‐versus host disease demonstrated that MAC regimen was associated with a markedly increased risk of a short stature at 3 years after allo‐HSCT (adjusted odds ratio, 5.61; 95% confidence interval, 1.07–29.4; p = 0.041). Conclusion: The intensity of conditioning regimen may be associated with short statures after allo‐HSCT. [ABSTRACT FROM AUTHOR]

Objective: Improved survival rates have made it increasingly important for clinicians to focus on cancer survivorship issues affecting the quality of life of melanoma patients. To provide a comprehensive overview of the disease and treatment‐related issues affecting such patients, we conducted a systematic review and meta‐analysis of the literature to estimate the prevalence of symptoms of depression, anxiety, fatigue, sleep disturbance, and cognitive problems among melanoma patients, both uveal and cutaneous, before, during and after treatment. Methods: The review was preregistered with PROSPERO (#CRD42020189847) and reported following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. A comprehensive search of the literature published up until June 2022 was undertaken using PubMed, PsycInfo, the Cochrane Library, and CINAHL. Two independent reviewers screened 1418 records and quality‐rated included studies. The reported prevalence rates of symptoms were pooled using a random‐effects model. Results: Sixty‐six studies including a total of 12,400 melanoma patients published between 1992 and 2022 were included. Pooled prevalence rates ranged from 6% to 16% for depression and 7%–30% for anxiety across diagnoses (uveal and cutaneous melanoma) and assessment time points. One third of the patients (35%) reported clinically significant fatigue, 20%–44% had cognitive complaints, while prevalence of sleep disturbance was not reported. Quality assessment indicated that 80% of the studies were of good quality. Conclusion: A large body of research shows that depression and anxiety symptoms are prevalent in melanoma patients before, during and after treatment. However, research examining other symptoms known to affect quality of life, such as fatigue, sleep disturbances, and cognitive problems, is still needed. [ABSTRACT FROM AUTHOR]

Purpose: Head and neck cancer (HNC) treatment may lead to late effects and impaired health-related quality of life of survivors. Knowledge on long-term late effects after radiotherapy (RT) and potential underlying biological mechanisms is lacking. We assessed the prevalence of xerostomia, dysphagia, and chronic fatigue (CF) in HNC survivors ≥ 5 years post-RT, and examined associations between pro-inflammatory cytokines and late effects. Methods: In a cross-sectional study, 263 HNC survivors treated between 2007 and 2013 were enrolled. They completed validated questionnaires assessing xerostomia and dysphagia (the EORTC QLQ-H&N35), and CF (the Fatigue Questionnaire), and underwent blood sampling and clinical examination. Pro-inflammatory cytokines were analyzed in 262 survivors and 100 healthy age- and gender-matched controls. Results: Median time since treatment was 8.5 years. The proportions of survivors reporting xerostomia, dysphagia, and CF were 58%, 31%, and 33%, respectively, with a preponderance of females. We found no significant associations between IL-6, IL-8, IP-10, TARC, TNF, or ENA-78 and the three late effects. The odds of having elevated levels of IL-6 and IP-10 were significantly higher in the survivors compared to the controls. Conclusions: More than one-third of long-term HNC survivors experienced xerostomia, dysphagia, and CF. Persistent inflammation, with elevated systemic cytokines, was not associated with these late effects, although HNC survivors had higher levels of some cytokines than the controls. Implications for Cancer Survivors: This study provides new knowledge on late effects that can serve as grounds for informing patients with HNC about risk of late effects more than 5 years after RT. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are atrisk of developing cognitive impairment and neurobehavioral symptoms. Inflammation induced by a compromised health status during cancer survivorship is proposed as a pathophysiological mechanism underlying cognitive impairment in cancer survivors. Objectives: To evaluate the associations of biomarkers of inflammation with attention and neurobehavioral outcomes in survivors of childhood ALL, and to identify clinical factors associated with biomarkers of inflammation in this cohort. Methods: We recruited patients who were diagnosed with ALL at = 18 years old and were currently =5 years post-cancer diagnosis. The study outcomes were attention (Conners Continuous Performance Test) and self-reported behavioral symptoms (Adult Self-Report [ASR] checklist). Using a commercial screening kit, survivors' plasma (5ml) was assayed for 17 cytokines/chemokine cell-signaling molecules that are associated with neurodegenerative diseases. The final panel of the targeted markers included interleukin (IL)-8, IL-13, interferon-gamma (IFN-g), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1b, and tumor necrosis factor-a. Biomarker levels were rank-ordered into tertiles based on the sample distribution. Multivariable general linear modeling was used to test for associations between biomarkers and study outcomes in the overall cohort and stratified by gender. Conclusion: Inflammation due to cancer-related late effects may potentially be mechanistic mediators of neurobehavioral problems in pediatric ALL survivors. Markers of inflammation can potentially be applied to assess or monitor the effectiveness of interventions, particularly behavioral interventions, in improving cognitive outcomes in survivors. Future work includes understanding the underlying gender-specific pathophysiology behind functional outcomes in the population. [ABSTRACT FROM AUTHOR]

Background: Treatment‐related late effects can worsen over time among cancer survivors. Such worsening health states may trigger changes in internal standards, values, or conceptualization of quality‐of‐life (QOL). This "response‐shift" phenomenon can jeopardize the validity of QOL assessment, and misrepresent QOL comparisons over time. This study tested response‐shift effects in reporting future‐health concerns among childhood cancer survivors who experienced progression in chronic health conditions (CHCs). Methods: 2310 adult survivors of childhood cancer from St. Jude Lifetime Cohort Study completed a survey and clinical assessment at two or more timepoints. Based on 190 individual CHCs graded for adverse‐event severity, global CHC burden was classified as "progression" or "non‐progression". QOL was assessed using the SF‐36TM eight domains and physical‐ and mental‐component summary scores (PCS, MCS). A single global item measured concerns about future health. Random‐effects models comparing survivors with and without progressive global CHC burden (progressors vs. non‐progressors) evaluated response‐shift effects (recalibration, reprioritization, reconceptualization) in reporting future‐health concerns. Results: Compared with non‐progressors, progressors were more likely to de‐emphasize (or downplay) overall physical and mental health in evaluating future‐health concerns (p‐values<0.05), indicating recalibration response‐shift, and more likely to de‐emphasize physical health earlier rather than later in follow‐up (p‐value<0.05), indicating reprioritization response‐shift. There was evidence for a reconceptualization response‐shift with progressor classification associated with worse‐than‐expected future‐health concerns and physical health, and better‐than‐expected pain and role‐emotional functioning (p‐values<0.05). Conclusion: We identified three types of response‐shift phenomena in reporting concerns about future health among childhood cancer survivors. Survivorship care or research should consider response‐shift effects when interpreting changes in QOL over time. [ABSTRACT FROM AUTHOR]

Purpose: Studies indicate that adult childhood cancer survivors do not achieve recommended physical activity levels. A deeper understanding of factors that influence their ability to be physically active is essential to identify individuals in need of support. The aim was to explore factors that influence adult childhood cancer survivor’s ability to be physically active. Method: Semi-structured interviews were conducted from June to October 2020 with 20 adult childhood cancer survivors with a median age of 31 (min–max 20–47) years. Interviews were transcribed verbatim and analyzed with qualitative content analysis. Results: Four main categories: “The impact of environmental factors,” “Personal factors of importance,” “Consequences of the treatment or disease,” and “The impact of support from healthcare” and 10 sub-categories, were identified. Participants described how family habits and encouragement from others influenced their present ability to be physically active. Experienced benefits of physical activity were described as a facilitator for current physical activity while suffering from late complications was identified as a barrier. Participants highlighted the importance of specific and individualized physical activity recommendations. Conclusion: This study includes adult childhood cancer survivors several years after completion of treatment, hence highlighting the importance for support both during treatment and follow-up to sustain their physical activity. Healthcare providers need to identify individuals suffering from late complications, even several years after treatment; provide individualized physical activity recommendations; and educate families and schools about the importance of physical activity in childhood cancer survivorship. Trial registration: This research project was registered in the Swedish National Database of Research and Development, identifier 273320, December 6, 2019 () [ABSTRACT FROM AUTHOR]

Osteonecrosis (ON) is a known complication of acute leukemia (AL) management, affecting 1%–10% of young patients and resulting in long-term morbidity. Widespread access to MRI over the past decade has allowed earlier detection and more accurate assessment. This study investigated clinical and MRI features of the 129 (2.5%) patients with symptomatic ON retrospectively recruited from the French LEA (Leucémies de l'Enfant et de l'Adolescent, or child and adolescent leukemias) cohort (n = 4,973). We analyzed data concerning ON risk factors, multifocal involvement, severe lesions detected by MRI, and patient quality of life (QoL). ON patients tended to be >10 years old at the time of AL diagnosis (odds ratio [OR]: 22.46; p < 10−6), female (OR: 1.8; p = 0.002), or treated for relapse (OR: 1.81; p = 0.041). They more frequently suffered from other sequelae (p < 10−6). Most necroses involved weight-bearing joints, and they were multifocal in 69% of cases. Double-blinded review of MRIs for 39 patients identified severe lesions in 14, usually in the hips. QoL of adolescents and adults was poor and permanently impacted after onset of ON. In conclusion, age >10 at time of AL diagnosis, female sex, and relapse occurrence were risk factors for multifocal ON; MRI revealed severe ON in a third of the patients considered; and ON was associated with persistently poor QoL affecting multiple domains. Future studies should include prospective data addressing ON management and seek to identify genetic markers for targeted screening enabling early ON detection and treatment. [ABSTRACT FROM AUTHOR]

Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): −0.01 − 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: −0.01–0.03), BMD of the left femoral neck: 0.00, (95% CI: −0.01–0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort. [ABSTRACT FROM AUTHOR]

The risk of cardiovascular events in patients treated for colorectal cancer is debated due to diverging results in previous studies. Colorectal cancer and cardiovascular disease share several risk factors such as physical inactivity, obesity, and smoking. Information about confounding covariates and follow-up time are therefore essential to address the issue. This study aims to investigate the risk of new-onset cardiovascular events for patients with stage I-III colorectal cancer receiving elective surgery compared to a matched population. Using a prospective cohort, we compared cardiovascular events among 876 patients treated with elective surgery for incident stage I-III colorectal cancer diagnosed between January 1st, 2001 and December 31st, 2016 to a cancer-free cohort matched by age, sex, and time since enrollment (N = 3504). Regression analyses were adjusted for lifestyle, cardiovascular risk factors, and comorbidity. Multivariable analyses were used to identify risk factors associated with cardiovascular events in the postoperative (<90 days of elective surgery) and long-term phase (>90 days after elective surgery). After a median follow-up of 3.9 years, the hazard ratio (HR) for incident heart failure was 1.53 (95% CI 1.02–2.28) among patients operated for colorectal cancer. The postoperative risk of myocardial infarction or angina pectoris was associated with the use of lipid-lowering drugs. Long-term risks of cardiovascular events were ASA-score of III+IV and lipid-lowering drugs with HRs ranging from 2.20 to 15.8. Further, the use of antihypertensive drugs was associated with an HR of 2.09 (95% CI 1.06–4.13) for angina pectoris or acute myocardial infarction. Heart failure was associated with being overweight, diabetes, and anastomosis leakage. We observed an increased hazard of heart failure in patients operated on for stage I-III colorectal cancer compared to cancer-free comparisons. We identified several potential risk factors for cardiovascular events within and beyond 90 days of elective surgery. [ABSTRACT FROM AUTHOR]