While cancer survival has steadily improved over time for adolescents and young adults (AYAs), previous studies have shown poorer survival in AYAs compared to children with leukaemia and lymphomas. In this study, we provided updated European 5-year relative survival (RS) estimates for AYAs with haematologic malignancies compared to children and assessed improvements in survival over time.

We used the EUROCARE-6 database, with population-based cancer registries data from 29 European countries. Using the period approach, we calculated 5-year RS for European children (0-14 years) and AYAs (15-39 years) in the follow-up period 2010- 2014 separately for leukaemia, lymphomas, relevant morphological subgroups, age- subgroups, and sex. We estimated 5-year RS time trends between 2000 and 2013.

Compared to children, AYAs had a worse RS for all acute lymphoblastic leukaemias (ALL) and acute myeloid leukaemia (AML), but a better survival for chronic myeloid leukaemia (CML). No differences in RS were observed between children and AYAs with acute promyelocytic leukaemia (APL). Compared to children, AYAs had a worse RS for HL and NHL in general, and specifically for lymphoblastic, Burkitt, follicular and NK/T cell lymphomas. In AYAs, RS increased between 2000-2013 for leukaemia overall (by 9% points), ALL (by 11% points), AML (by 8% points) and CML (by 11% points).

Despite increasing European survival for AYAs with haematological malignancies, we showed poorer survival in AYAs than in children for most types of leukaemia and lymphomas. These results reflect that further efforts are needed to improve the survival for this distinctive patient group.

As the prognosis for adolescents and young adults (AYAs) with breast cancer has improved, long-term health-related quality of life (HRQoL) has become increasingly important. This study aimed to analyze the long-term HRQoL of AYA breast cancer survivors compared to an age-matched normative population and to identify factors associated with HRQoL.

Secondary analyses were conducted using data from the SURVAYA study. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) was used to assess HRQoL. The Mann-Whitney U test was used to compare HRQoL scores of AYA breast cancer survivors with those of the normative population (n = 409). Linear regression models were constructed to identify patient and treatment characteristics associated with HRQoL.

A total of 944 female AYA breast cancer survivors were included, with a median age of 36.0 years and a median follow-up of 12.2 years. AYA breast cancer survivors scored significantly lower on five functional scales: physical, role, emotional, cognitive, and social, and higher on five symptom scales: fatigue, pain, dyspnea, insomnia, and financial impact compared to the normative population. Being in a relationship, having a positive body image, and adaptive coping were positively associated with HRQoL, while older age, chemotherapy, unemployment, and maladaptive coping were negatively associated.

AYA breast cancer survivors experience significantly compromised long-term HRQoL compared to an age-matched normative population. These results highlight the need for tailored follow-up care and long-term support, as well as the importance of shared decision-making about the benefits and risks of treatments before initiation.

We review the primary orbital, ocular, and adnexal rhabdomyosarcoma (RMS) spectrum of tumors and describe its clinicoradiological and histopathological features, molecular updates, management protocols, outcomes, and challenges. Despite being a favorable site, the prognosis remains dismal for cases of relapsing, refractory, and metastatic orbital RMS. A wide heterogeneity of data exists in terms of survival rates and treatment regimens spread across various geographic locations and age groups. Molecular cytogenetics is a crucial factor in both the diagnosis and effective management of RMS. Novel targeted therapy may play an integral role in avoiding treatment-related morbidity and mortality. Large-scale studies are warranted to formulate standardized regimens and uniformity, especially for advanced and metastatic cases.

Lymphoma is the most common cancer in adolescents. Outcome disparities based on the locus of care are increasingly recognized in this age group.

We report outcomes of LBCL patients between 14 and 21 who were treated at an adult center using adult type chemotherapy.

Sixty-four patients, median age 19 were analyzed. 82.8% were DLBCL, 17.2% were PMBCL; 21.9% stage I, 31.3% stage II, 7.8% stage III, and 39 % stage IV; 18.8% "very good", 62.5% "good" and 18.8% "poor" RIPI score. The median follow-up period was 68.8 months. The 5 years OS was 94.3%, and the 5 years EFS was 78.3%. High RIPI patients had a worse OS. High RIPI, B symptoms, ABC cell of origin and PMBCL had worse EFS.

Pediatric protocol use should be restricted to patients at higher risk of events rather than to all these patients.

Epidemiological data for sarcoma in adolescents and young adults (AYAs) and across age groups are limited. We aim to: 1) update sarcoma incidence, survival, and changes over time in European AYAs; 2) provide an updated comparison of sarcoma survival in AYAs versus children and mature adults.

We calculated crude incidence rates (IR) per 100,000 European population per year from 2006 to 2013. Using the period approach, we calculated 5-year relative survival (RS) for the follow-up period 2010-2014. We estimated changes in incidence and survival for bone sarcoma (BS) and soft tissue sarcoma (STS) subtypes in AYAs in the years 2000-2013.

In European AYAs, the IR was 0.81/100,000 for BS and 1.45/100,000 for STS. Five-year RS was 69 % and 65 % for BS and STS, respectively. Compared to children, AYAs had poorer survival for Ewing sarcoma of bone, synovial sarcoma, Ewing sarcoma of soft tissue and rhabdomyosarcoma. Compared to mature adults, AYAs had higher 5-year RS for all BS and for most of the STS subtypes. In AYAs, incidence increased for a few bone and soft tissue subtypes. Survival increased mainly for BS.

The reason for the better survival observed in AYAs compared to mature adults is probably multifactorial. The limited improvement of STS survival in AYAs may reflect the relative absence of new drugs for STS during the study period. The increase in RS for BS might relate to general improvements in radiological and surgical approaches and radiotherapy techniques.

Background: Evidence suggests the importance of cancer supportive care for adolescents and young adults (AYAs), and digital technology may provide tailored care that is flexible, affordable and accessible. However, AYAs' experiences with these digital cancer supportive care interventions are currently unclear. Objective: The aim of this review is to systematically identify and explore potential intervention facilitators, barriers and areas of improvement. Methods: We conducted a comprehensive search of MEDLINE (Ovid), EMBASE, PsycINFO and CINAHL for mixed methods and qualitative studies, published between 2000 and 2023, focusing on the experiences of AYAs between the ages of 15 and 39 years using digital supportive care interventions for cancer. Studies involving only pediatric and older populations were excluded. The identified studies were critically appraised and thematically analyzed. Results: Twenty-three digital interventions were identified. They varied in modality and addressed different aspects of supportive care (e.g., physical activity, psychological well-being and symptom management). Participants' experiences with the intervention attributes (e.g., appropriate content, flexible choices, seamless technology and inclusive environment) influenced their physical and psychological health, connections and communication skills, and autonomy. Conclusions: Overall, AYAs reported favorable experiences with digital interventions when provided with tailored supportive care for cancer. Digital interventions may help to increase reach and access to supportive care for cancer; however, barriers to delivery, such as faulty technology or cumbersome intervention features, can negatively impact participant experiences and may reduce engagement.

The registry-based collection of detailed cancer and late effect (LE) data in childhood and adolescent cancer (CAC) is rarely explored.

We aimed to provide an overview of CAC registration practices in Europe and share a Slovenian example.

We distributed a questionnaire among European cancer registries on disease, treatment and LE registration and present the system at the Slovenian Cancer Registry along with an example of retrospectively collected LE data from a cohort of central nervous system tumour survivors from 1983 to 2000. Kaplan-Meier and Cox regression were used to calculate the LE incidence.

Out of 27 responding registries, over 80% registered cancer type, vital status, death and second primary cancer data. Less than 20% registered cumulative doses of radiation and systemic therapy or progressions. Only three registered LEs. The obstacles in setting up LE collection in registries are a lack of standardization in the variable sets, definitions and methods of collection. In the retrospective cohort, neurological and endocrine LEs were most common. Females had a higher risk of endocrine LEs (HR of 1.89; 95% CI of 1.08-3.31), while patients treated with radiotherapy had higher risks of endocrine (3.47; 1.80-6.69), musculoskeletal and skin LEs (3.16; 1.60-6.26) and second primary cancers (2.85; 1.18-6.75).

Standardization and harmonization are necessary to promote detailed CAC and LE registration.

To investigate the in vitro impact of bleomycin on human sperm deoxyribonucleic acid (DNA) integrity, functionality, and morphology, with the aim of elucidating the underlying mechanism and anticipating potential repercussions on patients' reproductive function.

Controlled laboratory-based in vitro investigation.

Surplus human ejaculate donated for research by 45 reproductive-age participants exhibiting normozoospermic sperm parameters after clinical semen analysis. None of the participants had received a cancer diagnosis or undergone radiotherapy, chemotherapy, or both.

After clinical semen analysis, sperm samples were centrifuged, diluted in sperm preparation medium, and exposed to bleomycin (100 μg/mL) for 2 hours at 37 °C in a humidified incubator with 5% CO2.

In vitro human sperm competence was evaluated by comparing raw sperm, sperm incubated with sperm preparation medium, and sperm exposed to bleomycin. Competence indicators included sperm motility, vitality, DNA and acrosome integrity, and mitochondrial membrane potential. Transmisson electron microscopy was employed to correlate the ultrastructural morphological findings with functional assays.

Exposure to bleomycin for 2 hours in vitro significantly decreased sperm vitality, motility, and chromatin condensation compared with raw and control sperm. It also significantly increased sperm DNA fragmentation and the proportion of sperm with low mitochondrial membrane potential. Additionally, bleomycin significantly retarded the acrosomal response compared with control but did not affect the formation of intracellular and extracellular reactive oxygen species. Bleomycin-induced ultrastructural morphological changes supported the detected functional alterations.

Bleomycin negatively impacts male gamete competency in humans. Healthcare professionals should vigilantly monitor and further investigate the gonadotoxicity effects of bleomycin, in addition to its recognized lung toxicity. Meanwhile, it is recommended that patients with cancer undergoing bleomycin-containing chemotherapy regimens receive guidance on fertility preservation strategies.

The aim of this study was to determine the incidence of hypophosphatemia and identify factors associated with high-risk hypophosphatemia in children and adolescents with cancer. Patients aged 0-18 years who developed hypophosphatemia during treatment for cancer in our hospital between January 2021 and March 2023 were enrolled. Hypophosphatemia was defined as a serum phosphorus level < 2.5 mg/dL. The high-risk group for symptomatic hypophosphatemia was defined as patients with a serum phosphorus level of 1.5-1.9 mg/dL lasting for 2 weeks or more and patients with a serum phosphorus level < 1.5 mg/dL. During the study period, 48 of 253 (19%) patients developed a total of 108 episodes of hypophosphatemia. Symptomatic episodes were more frequent in the high-risk group (n = 31; 84% vs. 39%). Elevated total bilirubin level (> 0.50 mg/dL) (adjusted odds ratio (OR), 3.60; 95% confidence interval (CI), 1.37-9.48) and stem cell transplantation (adjusted OR, 4.83; 95% CI, 1.69-13.81) were found to be potential baseline predictors of high-risk hypophosphatemia in the logistic regression model. Fasting, diarrhea, and vomiting after initiation of treatment were also associated with the development of high-risk hypophosphatemia.

The incidence of hypophosphatemia was relatively high in children and adolescents receiving treatment for cancer. The results suggest that baseline characteristics and therapy-related toxicities may be associated with the development of high-risk hypophosphatemia.

• Patients with cancer are at increased risk of hypophosphatemia in adults. • Hypophosphatemia may be a factor associated with a poor prognosis in hospitalized patients.

• The incidence of hypophosphatemia was relatively high in children and adolescents receiving treatment for cancer. • Both baseline characteristics and therapy-related factors may be associated with the development of high-risk hypophosphatemia.

Purpose: Childhood cancer survivors (CCS) represent a growing population worldwide, and lifelong follow-up care is recommended for most. Once CCS become adults, the transition to adult care is emerging. Today, there is no transition or long-term follow-up care model in the adult setting that clearly outweighs others. We therefore aimed to evaluate the transition to physicians outside the hospital. Methods: In this single-center, cross-sectional, questionnaire-based study, we assessed in 2022 the current follow-up care situation of CCS who already transitioned to physicians outside the hospital (family physicians, pediatricians). We asked CCS about cancer knowledge, worries, self-management skills, and expectations and physicians about their experience with CCS and their needs when caring for CCS. We included physicians where a CCS was transitioned to. We compared the results with CCS transitioned in a hospital setting and used descriptive statistics. Results: Twenty-three CCS responded to the questionnaire (median age at questionnaire of 22 years, median 14 years since diagnosis). Nearly two-thirds reported not being in follow-up care anymore. The cancer knowledge was good, and cancer worries were low. Twenty-eight physicians responded with 21 reporting that they care for CCS. Half of them see CCS for acute problems only. Physicians are open to care for CCS but request the necessary recommendations and would also be available for respective training. Conclusion: Transition to physicians might be an option for selected CCS. However, education and empowerment of CCS early on and education of physicians is urgently needed to prevent loss to follow-up, which may lead to lifelong nonengagement and incorrect perceptions about future health.

Extreme hyperleukocytosis (Leukocyte count >200 × 109/L) in an adolescent young adult (AYA) patient with B-ALL could result in mild symptoms of leukostasis. Hyperleukocytosis requires prompt initiation of therapy with adequate hydration, cytoreduction and prevention of tumor lysis. Ph + B-ALL may present with extreme hyperleukocytosis and may be resistant to initial pre-phase therapy. In such cases, leukocytapheresis is beneficial in reducing the leukocyte count as well as controlling the symptoms.

Changes in bone age and tooth development are late side effects of cancer therapy and can be identified by imaging examination.

To evaluate the late effects of antineoplastic treatment on bone age and dental development in childhood cancer survivors.

This is a retrospective case-control study on paediatric cancer survivors of both sexes who underwent antineoplastic treatment with 5-15 years of survival. Carpal radiographs were assessed for bone age and growth curve, and panoramic radiographs were used to evaluate dental development and alterations. Carpal radiographs were analyzed using the Greulich and Pyle inspection method, and the Martins and Sakima method was used to analyze the growth curve. All tests were applied with a confidence level of 95%.

The study and control groups comprised 28 and 56 patients, respectively. There was no significant difference in bone age and growth curve between the study and control groups. Nonetheless, when sex was compared to chronological and bone ages, there was a significant difference in bone age (p = 0.019) and an underestimation in both groups and sexes in the Greulich and Pyle method. As to late dental effects, dental agenesia, microdontia, gyroversion, and unerupted teeth were found. Dental shape alterations mainly involve the root region.

Close multidisciplinary collaboration is necessary during the follow-up period of young patients who have survived cancer.

Survival from childhood and adolescent cancer has increased, but the chance of a livebirth in female survivors under 18 years at diagnosis may be reduced.

We performed a national population-based analysis, including all female cancer survivors diagnosed in Scotland before the age of 18 years between 1981 and 2012. Scottish Cancer Registry records were linked to Scottish maternity records. Females from the exposed group with no pregnancies before cancer diagnosis (n = 2118) were compared with three general population controls matched for age and year of diagnosis.

The cumulative incidence of a livebirth for all diagnoses was reduced to 37% (95% CI 33-40%) for cancer survivors at 30 years of age vs 58% (57-60%) for controls. The deficit varying by diagnosis: for lymphoid leukaemia, the cumulative incidence at 30 years was 29% (23-36%) vs 57% (52-61%) for controls with similar deficits in CNS tumours and retinoblastoma. There was a steady improvement in the chance of livebirth in those diagnosed more recently.

We have shown a reduced chance of livebirth in female survivors of cancer diagnosed before age 18. The deficit is present for all diagnoses.

With the advancements in conventional treatment modalities such as radiation, chemotherapy, and surgery, as well as the emergence of immunotherapy, the overall cure rate for solid tumor malignancies has experienced a significant increase. However, it is unfortunate that exposure to cancer treatments can have detrimental effects on the function of osteoblasts and osteoclasts, disturbing bone metabolic homeostasis in patients, as well as causing damage to bone marrow cells and other bone tissues. Consequently, certain tumor treatment options may pose a risk for subsequent bone diseases. Common bone disorders associated with cancer treatment include osteonecrosis, bone loss, and secondary bone tumors. (1)Cancer treatment-related osteonecrosis is primarily linked to the use of radiation therapy and certain chemicals, such as bisphosphonates, denosumab, antiangiogenic agents, and immunomodulators. It has been observed that high-dose radiation therapy is more likely to result in osteonecrosis. (2)Chemicals and hormones, particularly sex hormones, glucocorticoids, and thyroid hormones or thyrotropic hormones, are among the factors that can contribute to cancer treatment-related bone loss. (3)Secondary bone tumors differ from metastases originating from primary tumors, and radiotherapy plays a significant role in their development, while chemotherapy may also exert some influence. Radiogenic secondary bone tumors are predominantly malignant, with osteosarcoma being the most common type. Chemotherapy may be a risk factor for the relatively rare occurrence of secondary Ewing sarcoma of the bone. These treatment-related bone disorders have a considerable adverse impact on the prognosis of cancer patients. Hence, it is imperative to prioritize the bone health of patients undergoing cancer treatment and give it further attention.

Accurate and up-to-date estimates of the global cancer burden in adolescents and young adults (AYA) are scarce. This study aims to assess the global burden and trends of AYA cancer, with a focus on socioeconomic disparities, to inform global cancer control strategies.

AYA cancer, defined as cancer occurring in individuals aged 15-39, was analyzed using data from the Global Burden of Disease (GBD) 2021 study and the Global Cancer Observatory (GLOBOCAN) 2022 project. We examined the global burden by age, sex, geographic location, and Human Development Index (HDI), as well as its temporal trends. Primary outcomes included age-standardized incidence and mortality rates (ASIR, ASMR) and the average annual percent change (AAPC).

In 2022, an estimated 1,300,196 incidental cases and 377,621 cancer-related deaths occurred among AYAs worldwide, with an ASIR of 40.3 per 100,000 and an ASMR of 11.8 per 100,000. The most common cancers were breast, thyroid, and cervical, while the leading causes of death were breast, cervical, and leukemia. The incidence and mortality were disproportionately higher among females (ASIR: 52.9 for females vs. 28.3 for males; ASMR: 13.1 for females vs. 10.6 for males). Countries with higher HDI experienced a higher incidence of AYA cancers (ASIR: 32.0 [low HDI] vs. 54.8 [very high HDI]), while countries with lower HDI faced a disproportionately higher mortality burden (ASMR: 17.2 [low HDI] vs. 8.4 [very high HDI]) despite their relatively low incidence. Disproportionality and regression measures highlighted significant HDI-related inequalities. AYA cancer incidence was stable from 2000 to 2011 (AAPC: - 0.04) but increased from 2012 to 2021 (AAPC: 0.53), driven by growing gonadal and colorectal cancers. Mortality decreased substantially from 2000 to 2011 (AAPC: - 1.64), but the decline slowed from 2012 (AAPC: - 0.32) probably due to increased deaths from gonadal cancers. These trends varied by sex, cancer type, geography, and HDI.

AYA cancers present a significant and growing global burden, with marked disparities across sex, geographic locations, and HDI levels. Policymakers should prioritize equitable resource allocation and implement targeted interventions to reduce these inequalities, particularly in low-HDI regions and with regard to gonadal cancers.

Adolescents (15-19 years) with sarcoma are known to have significantly worse survival than children (0-14 years). One possible reason may be that the adolescent sarcomas exhibit specific biological characteristics resulting in differences in clinical presentation and treatment resistance behaviors. The BIOSCA project aims to further explore these age-related differences in survival accounting for molecular tumor characteristic in children and adolescents with sarcoma.

A retrospective national population-based observational study with documented somatic genetic analyses was conducted between 2011 and 2016 of all patients aged from 0 to 17 years with a diagnosis of sarcoma using the National Registry of Childhood Cancers Database.

A total of 1637 children (0-9years: 40%), preadolescents (10-14years: 35%) and adolescents (15-17 years: 25%) with a diagnosis of bone (N = 845) or soft-tissue (N = 792) sarcoma were included. Adolescents had significantly worse outcome for undifferentiated small round cell sarcoma (USRCS), alveolar rhabdomyosarcoma (ARMS), and epithelioid sarcoma. Five-year overall survivals were worse among CIC-rearranged USRCS cases (47% [95%CI:21-69]) as compared to other USRCS, and PAX3::FOXO1 ARMS patients (44% [95%CI:32-55]) as compared to other ARMS. Adjusting for stage and genomic-profiling status, adolescents with USRCS were 1.6-fold more likely to die than children (P = 0.05), while the difference in survival between age of ARMS patients was weaken. Indeed, the prevalence of PAX3::FOXO1 increased significantly with age.

Age was an independent prognostic factor of outcome only in patients with USRCS, while the association between age and survival of patients with ARMS could be partly explained by differences in prevalence of PAX3::FOXO1.

Introduction Acute lymphoblastic leukemia (ALL) has suboptimal survival rates for adolescents and young adults (AYA) as compared to children. Very limited studies have been conducted on AYA patients in India. This study aimed to identify the cytogenetic and immunophenotype characteristics of B-cell ALL (B-ALL) in AYA patients and determine its correlation with clinicopathological parameters in the Southern India region. Method The study was a prospective study conducted for three years, from June 2019 to May 2022, in India. Newly diagnosed 90 patients with AYA (13-40 years) ALL were recruited. A B-ALL diagnosis was made based on morphology with cytochemical stains and immunophenotype by flow cytometry (FCM). Cytogenetic analysis was also performed using karyotyping and fluorescent in situ hybridization to identify chromosomal aberrations. The cytogenetics results were correlated with immunophenotyping and clinicopathological characteristics. Variables were analyzed using the Mann-Whitney U test and Chi-square test using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, NY, USA). Results The mean age was 22.68 ± 8.06 years. It was observed that the most common structural chromosomal abnormality for AYA was t(9;22) in 14 (15%) cases, followed by 6q deletions in seven (8%) cases, t(1;19) in four (4%) cases, and t(12;17) and t(6;14) in two (2%) cases each. In addition, t(3;12), t(2;11), t(12;21), t(1;9), t(2;12), and t(X;10) were found in one (1%) case each. The most common numerical abnormality was hyperdiploidy (15; 17%), followed by hypodiploidy (10; 11%). Further, myeloid antigen expression of CD33 was the most common aberrantly expressed marker found in 20 (28%) cases, followed by CD15 in three cases (5%), CD13 in three (4%) cases, and CD11b in two (3%) cases. It was also observed that in Ph+ve cases, CD33 and CD13 were most commonly expressed in three (33%) and two (17%) cases, respectively. In contrast, in Ph-ve patients, their expressions were lesser at 17 (27%) and one (2%) cases, respectively. In addition, leukemia-associated immunophenotype pattern (LAIP) markers CD44 6 (86%) and CD123 5 (55%) were also found to be significantly associated with Ph+ve, whereas their values in the Ph-ve group were lesser at 25 (42%) and 9 (17%), respectively. Our data also showed that older age wassignificantly associated with Ph+ve with a median age of 30 years (p = 0.012). In comparison, the median age of Ph-ve was only 21 years. Conclusion Our study established that the incidence of cytogenetic abnormalities for AYA was consistent with previously reported data. This study reaffirms that Ph+ve cases have significant associations with MyAg (CD13), LAIP (CD123 and CD44), and older age for the South Indian population.

Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.W.I.N.G.99 and Ewing-2008 trials.

We included patients with a localized high-risk disease, or pulmonary or pleural metastasis. We analysed the risk of severe toxicity according to randomised treatment group (VAI versus BuMel) and age group (<12 years, 12-17 years, 18-24 years, ≥25 years). We evaluated the heterogeneity of treatment effects by age group using interaction terms in logistic multivariable models.

The analysis included 243 patients treated with VAI and 205 with BuMel. Overall, BuMel was associated with a higher risk of severe acute toxicity than VAI particularly haematological, gastrointestinal, liver, sinusoidal occlusive syndrome, and infections. Severe haematological toxicity and lower general condition were significantly more frequent in younger patients, whatever treatment. We did not observe any significant heterogeneity in terms of the excess risk of severe toxicities associated with BuMel compared to VAI according to age group.

The excess of acute toxicity associated with BuMel compared to VAI does not vary significantly with age, suggesting the feasibility of BuMel across all age groups.

The assessment of chemotherapy response in osteosarcoma (OS) based on the average percentage of viable cells is limited, as it overlooks the spatial heterogeneity of tumor cell response (foci of resistant cells), immune microenvironment, and bone microarchitecture. Despite the resulting positive classification for response to chemotherapy, some patients experience early metastatic recurrence, demonstrating that our conventional tools for evaluating treatment response are insufficient. We studied the interactions between tumor cells, immune cells (lymphocytes, histiocytes, and osteoclasts), and bone extracellular matrix (ECM) in 18 surgical resection samples of OS using multiplex and conventional immunohistochemistry (IHC: CD8, CD163, CD68, and SATB2), combined with multiscale characterization approaches in territories of good and poor response (GRT/PRT) to treatment. GRT and PRT were defined as subregions with <10% and ≥10% of viable tumor cells, respectively. Local correlations between bone ECM porosity and density of immune cells were assessed in these territories. Immune cell density was then correlated to overall patient survival. Two patterns were identified for histiocytes and osteoclasts. In poor responder patients, CD68 osteoclast density exceeded that of CD163 histiocytes but was not related to bone ECM load. Conversely, in good responder patients, CD163 histiocytes were more numerous than CD68 osteoclasts. For both of them, a significant negative local correlation with bone ECM porosity was found (P < .01). Moreover, in PRT, multinucleated osteoclasts were rounded and intermingled with tumor cells, whereas in GRT, they were elongated and found in close contact with bone trabeculae. CD8 levels were always low in metastatic patients, and those initially considered good responders rapidly died from their disease. The specific recruitment of histiocytes and osteoclasts within the bone ECM, and the level of CD8 represent new features of OS response to treatment. The associated prognostic signatures should be integrated into the therapeutic stratification algorithm of patients after surgery.

Adolescents and young adults (AYAs) with Ewing sarcoma have a worse prognosis than children. Population-based survival evaluations stratifying findings by important clinical factors are, however, limited. This Dutch population study comprehensively compared survival of children and AYAs with Ewing sarcoma over three decades considering diagnostic period, tissue of origin, tumor site, and disease stage.

Data on all children (0-17 years, N = 463) and AYAs (18-39 years, N = 379) diagnosed with Ewing sarcoma in the Netherlands between 1990-2018 were collected from the Netherlands Cancer Registry with follow-up until February 2023. Five-year relative survival was calculated using the cohort method. Multivariable analyses were conducted through Poisson regression.

Children with Ewing sarcoma had a significantly higher 5-year relative survival than AYAs (65 % vs. 44 %). An increasing trend in survival was noted reaching 70 % in children and 53 % in AYAs in 2010-2018. Results were similar for Ewing bone sarcoma and extraosseous Ewing sarcoma. AYAs had a poorer prognosis than children for most tumor sites and regardless of disease stage. Survival probabilities were 60 % vs. 78 % for localized disease and 20 % vs. 33 % for metastatic disease. Multivariable-regression analysis, adjusted for follow-up time, diagnostic period, sex, disease stage, and tumor site, confirmed increased excess mortality among AYAs compared with children (excess HR: 1.7, 95 % CI: 1.3-2.1).

Despite survival improvements since the 1990s, AYAs with Ewing sarcoma in the Netherlands continue to fare considerably worse than children. This survival disparity was present irrespective of tissue of origin, tumor site, and disease stage.

Currently, there is limited knowledge on the clinical profile of drug-induced liver injury (DILI) in Chinese children. We aimed to assess the clinical characteristics, suspected drugs, and outcomes associated with pediatric DILI in China.

This nationwide, multicenter, retrospective study, conducted between 2012 and 2014, analyzed 25,927 cases of suspected DILI at 308 medical centers using the inpatient medical register system. Utilizing the Roussel Uclaf causality assessment method score, only patients with scores ≥6 or diagnosed with DILI by three experts after scoring <6 were included in the analysis. Among them, 460 cases met the EASL biochemical criteria. The study categorized children into three age groups: toddlers (≥30 days to <6 years old), school-age children (6 to <12 years old), and adolescents (12 to <18 years old).

Hepatocellular injury was the predominant clinical classification, accounting for 63% of cases, with 34% of these cases meeting Hy's law criteria. Adolescents comprised the majority of children with moderate/severe DILI (65%). Similarly, adolescents faced a significantly higher risk of severe liver injury compared to younger children (adjusted odd ratios 4.75, p = 0.002). The top three most frequently prescribed drug classes across all age groups were antineoplastic agents (25.9%), antimicrobials (21.5%), and traditional Chinese medicine (13.7%). For adolescents, the most commonly suspected drugs were antitubercular drugs (22%) and traditional Chinese medicine (23%).

Adolescents are at a greater risk of severe and potentially fatal liver injury compared to younger children. Recognizing the risk of pediatric DILI is crucial for ensuring safe medical practices.

Drug-induced liver injury, a poorly understood yet serious cause of pediatric liver disease, encompasses a spectrum of clinical presentations, ranging from asymptomatic liver enzyme elevation to acute liver failure. This retrospective study, utilizing a large Chinese cohort of pediatric liver injury cases from 308 centers nationwide, characterized the major clinical patterns and suspected drugs in detail, revealing that adolescents are at a greater risk of severe liver injury compared to younger children. Vigilant care and careful surveillance of at-risk pediatric patients are crucial for physicians, researchers, patients, caregivers, and policymakers. Additional multicenter prospective studies are needed to evaluate the risk of hepatotoxicity in outpatients and hospitalized pediatric patients.

There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer.

The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population.

Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater.

Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer.

Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.

Stomach adenocarcinoma (STAD) is one of the main reasons for cancer-related deaths worldwide. This investigation aimed to define the connection between STAD and Cuproptosis-related genes (CRGs). Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper.

To explore the identification of potential biomarkers for STAD disease based on cuproptosis.

A predictive model using Gene Ontology (GO), Least Absolute Shrinkage and Selection Operator (LASSO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis analyzed gene interconnections, focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD. Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed. The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic, Kaplan-Meier curves, and COX regression analysis. Validation was conducted with datasets GSE26942, GSE54129, and GSE66229. Expression of copper-related differentially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas.

Three significant genes (FDX1, LIAS, MTF1) were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups. These genes were down-regulated in both risk categories. GO and KEGG analyses highlighted their involvement mainly in the electron transport chain. After validating their differential expression, FDX1 emerged as the most accurate diagnostic marker for gastric cancer. Additionally, the RCircos package localized FDX1 on chromosome 11.

Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy, providing new ideas for further scientific research.

With the increasing survival rates of childhood cancer, nurses' familiarity with published evidence has become crucial to care for this population and their families throughout the survival process.

To systematically identify and conduct a bibliometric analysis of nursing-related evidence concerning extended and long-term survival of childhood survivors.

A scoping review was conducted using bibliometric analysis with searches performed in the PubMed, CINAHL, SCOPUS, and Web of Science databases. A total of 300 studies on childhood cancer survival within the nursing field were included.

The first study on this topic was published in 1975. American and Chinese researchers lead study publications, primarily publishing in nursing journals such as Cancer Nursing. Quantitative designs were prevalent, and the majority of the studies focused on physical late effects, overall quality of life, and survivor follow-up care.

This study has allowed us to map and synthesize the bibliometric evidence pertaining to the extended and long-term survivorship of childhood cancer survivors in the nursing field. Consequently, it identifies gaps in knowledge, research trends, and areas necessitating further exploration.

The evidence presented in this review can facilitate academic and clinical discussions, offering a comprehensive synthesis of the published knowledge. More research needs to be developed on the topic, particularly in Central and Latin America, Africa, Southern and Eastern Europe, and in some regions of Asia. Furthermore, the scope of studies should extend beyond late effects and quality of life, encompassing the experience of surviving childhood cancer, including psychosocial and spiritual dimensions.

Bruceantinol (BOL) is a quassinoid compound found in the fruits of Brucea javanica. Previous research has highlighted the manifold physiological and pharmacological activities of BOL. Notably, BOL has demonstrated antitumor cytotoxic and antibacterial effects, lending support to its potential as a promising therapeutic agent for various diseases. Despite being recognized as a potent antitumor inhibitor in multiple cancer types, its efficacy against osteosarcoma (OS) has not been elucidated. In this work, we investigated the antitumor properties of BOL against OS. Our findings showed that BOL significantly decreased the proliferation and migration of OS cells, induced apoptosis, and caused cell death without affecting the cell cycle. We further confirmed that BOL potently suppressed tumor growth in vivo. Mechanismly, we discovered that BOL directly bound to STAT3, and prevent the activation of STAT3 signaling at low nanomolar concentrations. Overall, our study demonstrated that BOL potently inhibited the growth and metastasis of OS, and efficiently suppressed STAT3 signaling pathway. These results suggest that BOL could be a promising therapeutic candidate for OS.

Background: Survival rates of cancer patients have increased globally and across age groups. Challenges arising from craniofacial growth-development disturbances and dental abnormalities might warrant modifications to standard orthodontic pathways of care. Objective: The aim of this study was to systematically summarize and critically assess the available literature regarding the characteristics of orthodontic treatment in cancer survivors. Materials and Methods: A systematic search was conducted in seven databases for studies on malignant tumor survivors having undergone orthodontic intervention with fixed appliances following cancer treatment up to August 2023. The outcomes of interest included quantitative data regarding various characteristics of orthodontic treatment and the post-treatment period. The risk of bias was assessed individually with the Newcastle-Ottawa scale. Results: Out of 347 records, 4 cohort studies were eventually included in the qualitative synthesis. Leukemia was the most common malignancy type, with treatment involving mainly chemotherapy and/or radiotherapy. The duration of orthodontic treatment in cancer survivors varied. Occlusal results, quality of life, and satisfaction were comparable to healthy peers. However, in some survivors' groups, treatment was shorter and the final results were compromised. Root resorption and oral mucositis were reported among the treated cancer survivors. Reduced occlusal outcome stability during the retention period was also reported. Conclusions: Overall, the duration of orthodontic treatment varied among cancer survivors. The occlusal results achieved were similar to those of their healthy peers, though potentially less stable. Patient-reported outcomes did not differ significantly between cancer survivors and healthy individuals treated orthodontically.

We used the comprehensive definition of AYA (age 15 to 39 years) to update 5-year relative survival (RS) estimates for AYAs in Europe and across countries and to evaluate improvements in survival over time.

We used data from EUROCARE-6. We analysed 700,000 AYAs with cancer diagnosed in 2000-2013 (follow-up to 2014). We focused the analyses on the 12 most common cancers in AYA. We used period analysis to estimate 5-year RS in Europe and 5-year RS differences in 29 countries (2010-2014 period estimate) and over time (2004-06 vs. 2010-14 period estimates).

5-year RS for all AYA tumours was 84%, ranging from 70% to 90% for most of the 12 tumours analysed. The exceptions were acute lymphoblastic leukaemia, acute myeloid leukaemia, and central nervous system tumours, presenting survival of 59%, 61%, and 62%, respectively. Differences in survival were observed among European countries for all cancers, except thyroid cancers and ovarian germ-cell tumours. Survival improved over time for most cancers in the 15- to 39-year-old age group, but for fewer cancers in adolescents and 20- to 29-year-olds.

This is the most comprehensive study to report the survival of 12 cancers in AYAs in 29 European countries. We showed variability in survival among countries most likely due to differences in stage at diagnosis, access to treatment, and lack of referral to expert centres. Survival has improved especially for haematological cancers. Further efforts are needed to improve survival for other cancers as well, especially in adolescents.

My contribution to honoring Professor Kinam Park celebrates and resonates with his scholarly career in drug delivery, his commitment to encouraging the next generation(s), and his efforts to keep us focused on clinically effective formulations. To do this I take as my example, niclosamide, a small molecule protonophore that, uniquely, can "target" all cell membranes, both plasma and organelle. As such, it acts upstream of many cell pathways and so has the potential to affect many of the essential events that a cell, and particularly a diseased cell or other entities like a virus, use to stay alive and prosper. Literature shows that it has so far been discovered to positively influence (at least): cancer, bacterial and viral infection, metabolic diseases such as Type II diabetes, NASH and NAFLD, artery constriction, endometriosis, neuropathic pain, rheumatoid arthritis, sclerodermatous graft-versus-host disease, systemic sclerosis, Parkinson's, and COPD. With such a fundamental action and broad-spectrum activity, I believe that studying niclosamide in all its manifestations, discovering if and to what extent it can contribute positively to disease control (and also where it can't), formulating it as effective therapeutics, and testing them in preclinical and clinical trials is a career builder for our next generation(s). The article is divided into two parts: Part I introduces niclosamide and other proton shunts mainly in cancer and viral infections and reviews an exponentially growing literature with some concepts and physicochemical properties that lead to its proton shunt mechanism. Part II focuses on repurposing by reformulation of niclosamide. I give two examples of "carrier-free formulations", - one for cancer (as a prodrug therapeutic of niclosamide stearate for i.v. and other administration routes, exemplified by our recent work on Osteosarcoma in mice and canine patients), and the other as a niclosamide solution formulation (that could provide the basis for a preventative nasal spray and early treatment option for COVID19 and other respiratory virus infections). My goal is to excite and enthuse, encourage, and motivate all involved in the drug development and testing process in academia, institutes, and industry, to learn more about this interesting molecule and others like it. To enable such endeavors, I give many proposed ideas throughout the document, that have been stimulated and inspired by gaps in the literature, urgent needs in disease, and new studies arising from our own work. The hope is that, by reading through this document and studying the suggested topics and references, the drug delivery and development community will continue our lineage and benefit from our legacy to achieve niclosamide's potential as an effective contributor to the treatment and control of many diseases and conditions.

The advancement of anti-cancer therapies has markedly improved the survival rate of children with cancer, making them long-term childhood cancer survivors (CCS). Nevertheless, these treatments cause a low-grade inflammatory state, determining inflamm-aging and, thus, favoring the early onset of chronic diseases normally associated with old age. Identification of novel and safer therapeutic strategies is needed to counteract and prevent inflamm-aging. Macrophages are cells involved in immune and inflammatory responses, with a pivotal role in iron metabolism, which is related to inflammation. We obtained macrophages from CCS patients and evaluated their phenotype markers, inflammatory states, and iron metabolism by Western blotting, ELISA, and iron assays. We observed a strong increase in classically activated phenotype markers (M1) and iron metabolism alteration in CCS, with an increase in intracellular iron concentration and inflammatory markers. These results suggest that the prevalence of M1 macrophages and alteration of iron metabolism could be involved in the worsening of inflammation in CCS. Therefore, we propose macrophages and iron metabolism as novel therapeutic targets to counteract inflamm-aging. To avoid toxic regimens, we tested some nutraceuticals (resveratrol, curcumin, and oil-enriched lycopene), which are already known to exert anti-inflammatory properties. After their administration, we observed a macrophage switch towards the anti-inflammatory phenotype M2, as well as reductions in pro-inflammatory cytokines and the intracellular iron concentration. Therefore, we suggest-for the first time-that nutraceuticals reduce inflammation in CCS macrophages through a novel anti-inflammatory mechanism of action, modulating iron metabolism.

Childhood cancer survivors (CCS) are at risk of deficits in their social outcomes, a key aspect of overall health and quality of life. Social outcomes of import are ill-defined leading to potential gaps in research and service provision. In this study, we undertook a preliminary consensus seeking exercise to support the development of a framework of the important social outcomes for CCS.

A modified e-Delphi study was conducted with four groups: CCS, health professionals, social workers and teachers. Round 1, developed from a literature review, included 34 questions rated for importance on a 7-point Likert scale. Rounds 2 and 3 presented items not achieving consensus, additionally proposed items and in round 3, a ranking question.

Survey 1 was completed by 38 participants, 31 (82%) completed survey 2 and 28 (76%) completed survey 3. A total of 36 items were prioritised across 6 domains (education, independence, work, relationships, community, lifestyle), together forming the final list of social outcomes. Of these, 22 items met consensus for importance. Items rated most important were "having autonomy" and "avoiding social isolation". Quantitative and qualitative results reflected that social outcomes for survivors and general public should be the same.

We have generated initial consensus on important social outcomes for CCS, highlighting the need for these to be matched to those of the general population. It suggests strategies are required to ensure autonomy and appropriate support for independence and relationships are provided through long-term aftercare and beyond. Further work is needed to validate and develop these findings into a framework to support appropriate social aftercare for CCS.

Advances in multimodality cancer treatments have increased long-term survival rates for early onset cancer patients, with 5-year survival rates reaching 80% in Northern Europe. According to recent recommendations, clinicians should, as early as possible, inform cancer patients about the impact that cancer treatment may have on their fertility. Still, there is limited published data on fertility counselling (FC) and fertility preservation (FP) for cancer patients.

This register-based study used hospital records to identify female cancer patients in the hospital district (n = 192) who received FC at the age of 16-42 years between 2011 and 2019.

Altogether, 97 (50.5%) cancer patients were eligible for FP. Of these, 55 (56.7%) underwent FP, whereas 42 (43.3%) declined. Women undergoing FP were recommended cancer treatments with a higher risk of infertility (p = 0.01), and women with breast cancer were more prone to undergo FP than women with lymphoma (p = 0.043). In FP treatment cycles, the mean number of oocytes retrieved (13.9 ± 7.7 vs. 12.0 ± 6.5, p = 0.04) and transferrable embryos (4.7 ± 2.9 vs. 3.7 ± 2.8, p = 0.002) was higher among cancer patients compared to age-matched comparisons with male or tubal factor infertility. The total mean gonadotropin dose used was higher among cancer patients (2243 ± 963 IU vs. 1679 ± 765 IU, p < 0.001).

We conclude that a good ovarian response during FP can be achieved in female cancer patients.