Germ Cell Tumor Survivors Research Articles

CN68 From surviving cancer to getting on with life: Adult testicular germ cell tumor survivors’ perspectives on transition from follow-up care to long-term survivorship

CN68 From surviving cancer to getting on with life: Adult testicular germ cell tumor survivors’ perspectives on transition from follow-up care to long-term survivorship

Remote Field Application of Digital Technology for Hearing Assessments in a Cohort of Pediatric Germ Cell Tumor Survivors.

Childhood cancer survivors treated with platinum-based chemotherapy are at risk of treatment-induced hearing loss. Accurate evaluation of hearing thresholds has historically been limited to clinical audiometry, which is logistically challenging and expensive to include in epidemiologic studies. We evaluated the feasibility of using a remote, tablet-based hearing assessment in a cohort of pediatric germ cell tumor survivors treated with platinum-based chemotherapy. Survivors from the GCT Outcomes and Late effects Data (GOLD) study were recruited to the pilot study (n = 100). Study personnel conducted remote hearing assessments of standard and extended high frequency thresholds using validated tablet-based audiometry (SHOEBOX, Inc.). T tests and Wilcoxon rank-sum tests evaluated differences in assessment characteristics between children and adults. Agreement between self-reported and measured hearing loss was calculated using Cohen κ. We were able to reach 136/168 (81%) eligible participants, of which 100 (74%) agreed to participate. Successful completion of the remote hearing assessment was high [97%; 20 children (ages 7-17), 77 adults (ages 18-31)]. The mean assessment length was 37.6 minutes, and the mean turnaround time was 8.3 days. We observed hearing loss at standard frequencies in 21% of participants. Agreement between self-reported and measured hearing loss was significant (P value = 1.41 × 10-7), with 83.5% concordance. Hearing loss measured using the remote assessment aligns with self-reporting and rates of hearing loss reported in the literature for this population. Remote application of tablet-based audiometry is a feasible and efficacious method for measuring hearing in epidemiologic studies with participants spread across large geographic areas.

Testicular cancer survivorship program at National Cancer Institute in Slovakia.

e13792 Background: Testicular germ cell tumors (GCTs) are highly curable malignancies. Survivors of GCTs represent a growing population with a long life expectancy after curative cancer treatment. GCT survivors may experience a variety of late adverse effects of treatment and reduced quality of life. Therefore, National Cancer Institute in Slovakia has developed a testicular cancer survivorship program with a long-term follow-up of GCT survivors aiming to evaluate late toxicities and their underlying molecular mechanisms. Methods: The long-term annual follow-up of GCT survivors is established per our institutional guidelines for testicular cancer survivorship program. GCT survivors are referred to our testicular survivorship outpatient clinic at least 5 years after completion of curative treatment, and are followed annually throughout their lives. During each visit, patient’s history is updated, physical examination is performed, blood and urine samples are collected, and survivors complete validated questionnaires for evaluation of late toxicities (peripheral neuropathy, sexual dysfunction, cognitive impairment) and quality of life. Complete blood count, metabolic panel, lipid panel, levels of serum tumor markers, testosterone, luteinizing hormone and follicle stimulating hormone are measured at each visit. Plasma aliquots and urine samples from every visit are prospectively collected and stored in the biobank of our Translational Research Unit. Data including age, medical history, histological type, stage, prognostic group, type of treatment, laboratory values, and questionnaire scores are collected and recorded in our electronic survivorship database. In addition, information on important survivorship topics is provided and healthy lifestyle changes are suggested to all survivors. Results: From August 2015 to January 2024 our testicular survivorship outpatient clinic performed 1733 follow-up visits in 407 GCT survivors treated at our institution from 1984 to 2019. Median age at the first follow-up visit at the survivorship clinic was 41 years (range 21 - 77). Median time from the curative treatment to the first follow-up visit at the survivorship clinic was 7 years (range 4 - 32). To date, 104 patients have had at least 7 follow-ups. Eighty-six (21.13 %) patients were treated with surgery only, 278 (68.3 %) with chemotherapy, 28 (6.88 %) with radiotherapy, and 15 (3.69 %) patients with both chemotherapy and radiotherapy. To date, 18 publications (including papers and abstracts) have been published using the data from our testicular survivorship database. Conclusions: Testicular cancer survivorship program with the long-term annual follow-up of GCT survivors has been established at National Cancer Institute in Slovakia. The ongoing prospective study for evaluation of late toxicities and their underlying mechanisms is part of the program. Our large database offers valuable data for the future research.

Cardiometabolic assessment through erythrocyte fatty acid profile, cardiometabolic index (CMI), and lipid accumulation product (LAP) in testicular germ-cell tumor survivors

Cardiometabolic assessment through erythrocyte fatty acid profile, cardiometabolic index (CMI), and lipid accumulation product (LAP) in testicular germ-cell tumor survivors

Chemotherapy-Induced Peripheral Neuropathy (CIPN) as a Predictor of Decreased Quality of Life in Testicular Germ Cell Tumor Survivors

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) after curative treatment for testicular germ cell tumors (GCTs) has been previously reported. It has been shown that CIPN can contribute to impaired quality of life (QOL) in cancer survivors. Herein, we aimed to evaluate CIPN in association with QOL in GCT survivors. Patients and methodsEuropean Organization for Research and Treatment of Cancer (EORTC) Quality of Life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20) and Quality of Life Questionnaire (QLQ-C30) were prospectively completed by GCT survivors (N = 151) at National Cancer Institute in Slovakia during their annual follow-up. The median follow-up was 10 years (range 4-30). Upon obtaining the scores from each questionnaire, each score from QLQ-C30 was correlated with CIPN defined as high or low (above and below median) as obtained from CIPN20. ResultsGCT survivors with high overall CIPN score reported impaired QOL in QLQ-C30. The global health status was lower in survivors with high CIPN versus low CIPN (mean score ± SEM: 67.17 ± 2.00 vs. 86.18 ± 1.76, P < .00001). Survivors with high CIPN reported worse physical, role, emotional, cognitive, and social functioning compared to survivors with low CIPN (all P < .00001). CIPN high survivors perceived more fatigue, nausea, pain, dyspnea, sleeping disorders, and appetite loss compared to CIPN low survivors (all P < .004). Higher burden of CIPN was associated with more financial problems vs CIPN low (mean score ± SEM: 19.70 ± 2.64 vs. 6.67 ± 2.32, P = .00025). Spearman analysis has confirmed negative correlation of overall CIPN20 score with QLQ-C30 global health status (R = −0.53, P < .0001). ConclusionCIPN is a strong predictor of impairment in QOL among GCT survivors. Molecular mechanisms of neurotoxicity should be intensively studied to find preventive and therapeutic strategies.

Longitudinal assessment of cognitive functioning in testicular germ cell tumor survivors.

514 Background: Survivors of testicular germ cell tumors (GCT) may experience late toxicities derived from cancer treatment. Long-term cognitive impairment has been previously described in GCT survivors. This study aimed to prospectively perform a longitudinal assessment of cognitive functioning in GCT survivors. Methods: GCT survivors (N = 151) from National Cancer Institute in Slovakia completed the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) questionnaires during their annual follow-up visits. The study group consisted of survivors who completed at least four consecutive follow-up visits. The median of the 1st follow-up visit was 8 years (range 4-24). Survivors were treated with orchiectomy and active surveillance only (AS) (N = 21), cisplatin-based chemotherapy (CT) (N = 109), radiotherapy to the retroperitoneum (RT) (N = 11) or both chemotherapy and radiotherapy (CTRT) (N = 10). According to the received treatment, we longitudinally assessed cognitive scores in four cognitive domains: perceived cognitive impairment (CogPCI), quality of life affected by cognitive impairment (CogQoL), cognitive impairment perceived by others (CogOth) and perceived cognitive abilities (CogPCA), and overall cognitive function score. We also performed a subgroup analysis of survivors receiving cumulative doses &lt; 400 mg/m2 (N = 48) and ≥ 400 mg/m2 (N = 70) of cisplatin. Results: Survivors treated with CTRT had persistently lower scores in CogPCA domain annually between the 1st and the 5th follow-up compared to AS group (all p &lt; 0.05). CTRT group also had lower overall cognitive function scores compared to AS (all p &lt; 0.03) in all follow-ups between the 2nd and the 5th follow-up visit. Survivors who received ≥ 400 mg/m2 of cisplatin had lower scores in CogPCA domain at the 1st and the 2nd follow-up visit compared to AS (mean score ± SEM: 21.56 ± 0.66 vs. 24.10 ± 0.63, p = 0.05, and 21.14 ± 0.59 vs. 23.76 ± 0.98, p = 0.014), lower overall cognitive function score at the 2nd follow-up compared to AS (110.66 ± 2.06 vs. 118.75 ± 2.66, p = 0.048), followed by a nonsignificant numerical trend of decline in CogPCA domain and overall cognitive score annually from the 3rd to the 5th follow-up. There was a nonsignificant numerical decline in all survivors annually between the 1st and the 4th follow-up in all cognitive domains and overall cognitive score. We observed a similar trend in all treatment groups separately. Conclusions: GCT survivors experience a long-term cognitive impairment that changes moderately over time. Survivors who received both chemotherapy and radiotherapy had the worst cognitive performance persisting at all follow-up visits. In addition, we observed a cognitive decline in survivors who received higher doses of cisplatin-based chemotherapy. To date, this is the first study that prospectively performed a longitudinal assessment of long-term cognitive functioning in GCT survivors.

Fertility outcomes following surgery and multiagent chemotherapy in malignant ovarian germ cell tumor survivors: a survey study

ObjectiveTo assess fertility outcomes in long-term survivors of malignant ovarian germ cell tumors treated with fertility-sparing surgery with or without additional chemotherapy.MethodsWomen diagnosed and treated for malignant ovarian germ cell...

Quality of life assessment in testicular non-seminomatous germ cell tumour survivors.

Patients with Germ cell tumours (GCT) are at risk of long-term toxicities due to multimodality therapy. It is debatable whether there is an impact on the quality of life(QoL) of GCT survivors. A case-control study was conducted at a tertiary care centre in India, using the EORTC QLQ C30 questionnaire, to compare the QoL between GCT survivors(disease free > 2years) and healthy matched controls. A multivariate regression model was used to identify factors affecting QoL. A total of 55 cases and 100 controls were recruited. Cases had a median age of 32years (interquartile range, IQR 28-40years), ECOG PS of 0-1(75%), advanced stage III (58%), chemotherapy (94%) and 66% were > 5years from diagnosis. The median age of controls: 35years (IQR 28-43years). A statistically significant difference was seen for emotional (85.8 ± 14.2 vs 91.7 ± 10.4, p 0.005), social(83.0 ± 22.0 vs 95.2 ± 9.6, p < 0.001) and global scales (80.4 ± 21.1 vs 91.3 ± 9.7, p < 0.001). Cases had more nausea and vomiting(3.3 ± 7.4 vs 1.0 ± 3.9, p 0.015), pain(13.9 ± 13.9 vs 4.8 ± 9.8, p < 0.001), dyspnea(7.9 + 14.3 vs 2.7 ± 9.1, p 0.007), and appetite loss(6.7 ± 14.9 vs 1.9 ± 7.9, p 0.016) and greater financial toxicity(31.5 ± 32.3 vs 9.0 ± 16.3, p < 0.001). Adjusting for age, performance status, BMI, stage, chemotherapy, RPLND, recurrent disease, and time since diagnosis, no predictive variables were significant. There is a detrimental impact of history of GCT in long term survivors of GCT.

From Surviving Cancer to Getting on With Life: Adult Testicular Germ Cell Tumor Survivors' Perspectives on Transition From Follow-Up Care to Long-Term Survivorship.

With an increasing incidence and a high cure rate, a growing number of testicular germ cell tumor (TGCT) survivors require specialized follow-up care. However, knowledge of these patients' needs is lacking, leaving TGCT survivors with unmet care needs at risk of symptom burden when transitioning to long-term survivorship. This grounded theory study aimed to understand the perspectives of TGCT survivors' transition from follow-up care to long-term survivorship. A total of 12 adult TGCT survivors in follow-up care or completion less than a year were in-depth semi-structured interviewed. Interviews were audiotaped and transcribed verbatim. Transcripts were analyzed by constant comparison, and the core category "Dealing with back-and-forth forces" emerged in the integrated concepts. Two comparative processes in dealing with those forces were identified: the process of Living beyond the sword of Damocles involved the transition from feeling threatened by cancer to overcoming those threats; the process of Getting on with one's life can be described as transitioning from a period where cancer overruled their lives to carrying on with everyday life. The processes toward long-term survivorship follow general characteristics; the transition itself is an individual journey that depends on (life) experiences. The constructed model can guide healthcare professionals and researchers involved in TGCT survivorship to understand TGCT survivors' individual and ensuing needs. When TGCT survivors receive individualized and tailored follow-up care, it can assist in preventing and reducing long-term and late effects on long-term survivorship.

Chemotherapy induced peripheral neuropathy (CIPN) and biomarkers of gut microbial translocation in long-term survivors of testicular germ cell tumors.

e17032 Background: Survivors of testicular germ cell tumors (GCT) may suffer from long-term treatment induced peripheral neuropathy. We hypothesized markers of gut microbial translocation after chemotherapy and/or radiotherapy may be contributing factors of peripheral neuropathy. Methods: GCT survivors (N = 194) from National Cancer Institute of Slovakia completed the EORTC QLQ Chemotherapy-Induced Peripheral Neuropathy (CIPN20) questionnaires during their annual follow-up visit at 10-year median (range 2-25). Biomarkers of gut microbial translocaion and dysbiosis (GMT) lipopolysaccharide (LPS), high mobility group box-1 (HMGB-1), d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Upon obtaining the scores from questionnaires per recommended guidelines, each score was correlated with biomarkers of GMT scored as as high or low (above and below median). Survivors were treated with orchiectomy only (N = 30), cisplatin-based chemotherapy (N = 135), radiotherapy to the retroperitoneum (N = 14) or both chemotherapy and radiotherapy (N = 10). Results: GCT survivors with higher vs lower plasma levels of HMGB-1 had worse overall CIPN20 score (median ± SD = 18 229.0 ± 13 644.2 vs 17 387.0 ± 5106.6 p = 0.048). Patients with higher vs lower plasma HMGB-1 also had worse motor function (9.0 ± 1.8 vs 8.0 ± 2.3, p = 0.036). Sensory and autonomy subscales of CIPN20 qestionaire did not show significant association with HMGB-1 (both P &gt; 0.05). There was no significant difference in CIPN20 symptom burden associated with LPS, d-lactate and sCD14 (all P &gt; 0.05). Conclusions: HMGB-1 may serve as a promising biomarker of CIPN20 in long-term cancer survivors. Proinflammatory pathways are suggested as underlying mechanism of CIPN. Furhter research and larger patient cohorts are needed to explore the pathogenesis of CIPN in GCT survivors.

Cognitive impairment and biomarkers of gut microbial translocation in testicular germ cell tumor survivors.

Survivors of testicular germ cell tumors (GCT) may suffer from late cognitive impairment. We hypothesized that disruption of intestinal barrier during chemotherapy and/or radiotherapy may be a contributing factor of cognitive dysfunction within the gut-blood-brain axis. GCT survivors (N = 142) from National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function questionnaires during their annual follow-up visit at 9-year median (range 4-32). Biomarkers of gut microbial translocation and dysbiosis high mobility group box-1 (HMGB-1), lipopolysaccharide, d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Each questionnaire score was correlated with biomarkers. Survivors were treated with orchiectomy only (N = 17), cisplatin-based chemotherapy (N = 108), radiotherapy to the retroperitoneum (N = 11) or both (N = 6). GCT survivors with higher sCD14 (above median) had worse cognitive function perceived by others (CogOth domain) (mean ± SEM; 14.6 ± 0.25 vs 15.4 ± 0.25, p = 0.019), lower perceived cognitive abilities (CogPCA domain) (20.0 ± 0.74 vs 23.4 ± 0.73, p = 0.025) and lower overall cognitive function score (109.2 ± 0.74 vs 116.7 ± 1.90, p = 0.021). There were no significant cognitive declines associated with HMGB-1, d-lactate and lipopolysaccharide. Survivors treated with ≥ 400mg/m2 vs < 400mg/m2 of cisplatin-based chemotherapy had a higher lipopolysaccharide (567.8 μg/L ± 42.7 vs 462.9 μg/L ± 51.9, (p = 0.03). sCD14 is a marker of monocytic activation by lipopolysaccharide and may also serve as a promising biomarker of cognitive impairment in long-term cancer survivors. While chemotherapy and radiotherapy-induced intestinal injury may be the underlying mechanism, further research using animal models and larger patient cohorts are needed to explore the pathogenesis of cognitive impairment in GCT survivors within the gut-brain axis.

Psychological distress and its influencing factors in survivors of malignant ovarian germ cell and sex-cord stromal tumors—an analysis of the AGO-CORSETT database

Zusammenfassung Hintergrund Keimstrangstroma(SCST)- und Keimzelltumoren (MOGCT) sind seltene ovarielle Neoplasien, die häufig bei Jugendlichen oder prämenopausalen Patientinnen auftreten. Die Prognose ist in allen Stadien gut, weshalb psychisches Wohlbefinden, Lebensqualität, Fertilitätserhalt und Kinderwunsch zu relevanten Themen der Langzeitüberlebenden werden. Ziel der Arbeit Untersuchung der Prävalenz der fertilitätserhaltenden Therapie bei Patientinnen mit ovariellen Keimstrangstromatumoren und Keimzelltumoren und die Erfassung von Zusammenhängen mit Angst, Depression, Lebensqualität und Sexualität nach Therapie. Material und Methoden Die Current-Ovarian-geRM-cell-and-Sex-Cord-stromal-Tumour-Treatment-strategies(CORSETT)-Studie ist eine multizentrische, retro- und prospektiv beobachtende Kohortenstudie der Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) der Deutschen Krebsgesellschaft. Patientinnen nach Keimstrangstroma- oder Keimzelltumorbehandlung wurden gebeten, Fragebögen zu beantworten (Hospital Anxiety and Depression Scale [HADS], Sexual Activity Questionnaire [SAQ], European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC QLQ-C30]). Im Fokus dieser Analyse standen der Stellenwert der fertilitätserhaltenden Operation sowie die Ausprägung und potenziellen Zusammenhänge mit Sexualität, Lebensqualität, Schmerz, Angst und Depressivität. Ergebnisse Von 355 eingeschlossenen Patientinnen hatten 152 Patientinnen die Fragebögen ausgefüllt und wurden in die Analysen eingeschlossen. 85 Patientinnen hiervon (56 %) wurden fertilitätserhaltend operiert. 34 % der Patientinnen hatten klinisch relevante Angst und Depressivität. Patientinnen nach fertilitätserhaltender Operation waren signifikant häufiger sexuell aktiv, hatten mehr sexuelles Verlangen und litten seltener unter Angst und Depressivität als Patientinnen ohne fertilitätserhaltende operative Therapie. Das Ausmaß von Angst und Depressivität korrelierte mit dem Schmerzniveau, unabhängig vom zeitlichen Abstand zur Krebsdiagnose. Diskussion Die fertilitätserhaltende operative Therapie sollte, wann immer onkologisch vertretbar, den Patientinnen mit SCST und MOGCT angeboten werden, um den Krebsüberlebenden bestmögliche Lebensqualität zu ermöglichen. Ein wiederholtes Screening auf Angst, Depressivität, Schmerzen und Probleme in der Sexualität sollte anhand von standardisierten Fragebögen bei allen Patientinnen durchgeführt werden.

Peripheral blood immune cell profiling in survivors of testicular germ cell tumors.

417 Background: Testicular germ cell tumors (GCT) achieve exceptional cure rate with cisplatin-based chemotherapy. Survivors of GCTs represent a unique population to study post-cancer treatment physiology and late toxicities. The impact of cancer treatment on the immune-cell profile in long-term GCT survivors is unknown. In this study, we performed an immune-phenotyping in survivors of GCTs. Methods: Whole peripheral blood was obtained from GCT survivors (N = 202) at National Cancer Institute of Slovakia within the protocol of the ongoing survivorship study on a day of their annual follow-up visit. The median follow-up was 11 years (2-25). GCT survivors were distributed into treatment groups: RT – radiotherapy to the retroperitoneum (N = 18), CT - chemotherapy (N = 143), CTRT - chemotherapy + radiotherapy (N=9); and a control group: AS - active surveillance/orchiectomy only (N=32). Immuno-phenotyping of peripheral blood leukocyte populations was performed with flow-cytometry. Immune cell subpopulations were statistically assessed for associations with received treatment. Results: Survivors treated with RT vs AS had higher no of classical dendritic cells (DCs) (mean ± SEM = 82.0 ± 1.9 vs 76.5 ±1.5, p = 0.03) and non-significantly lower no of plasmacytoid DCs and CD16+ DCs (0.11 ± 0.01 vs 0.15 ± 0.01, p = 0.06 and 54.4 ± 4.1 vs 64.8 ± 3.2, p = 0.07, respectively). Survivors treated with CT vs AS had higher no of CD19+ B cells (11.9 ± 0.3 vs 10.4 ± 0.7, p = 0.04)and lower no of CD8+ T cells (26.0 ± 1.3 vs 23.7 ± 0.6, p = 0.04). Similarly, survivors treated with CTRT vs AS had higher no of CD19+ B cells (13.6 ± 1.4 vs 10.4 ± 0.7, p = 0.04) and lower no of CD8+ T cells (20.7 ± 2.4 vs 26.0 ± 1.3, p = 0.04). Survivors treated with ≥ 400mg/m2 of cisplatin-based chemotherapy vs AS had no of CD19+ B cells (12.2 ± 0.5 vs 10.4 ± 0.7, p = 0.04) and lower no of CD8+ T cells (23.4 ± 0.9 vs 26.3 ±1.3, p = 0.04). The immunoregulatory index CD4/CD8 was higher in CTRT vs AS (2.5 ± 0.3 vs 1.8 ± 0.1, p = 0.04). Conclusions: Certain subpopulations of leukocytes differ according to received treatment in survivors of GCTs. Our results may suggest that chemotherapy and/or radiotherapy may produce long-term immunomodulatory effects. Interplay between B and T cells may be a contributing mechanism of late toxicities. Further research is needed to uncover the causal relationship to the long-term health of GCT survivors.

Looking Beyond Toxicities: Other Health-related Morbidities Noted in Childhood Solid Tumor Survivors.

In addition to the well-known toxicities of treatment, survivors of pediatric solid tumors can also develop other health-related conditions. They may either be an indirect consequence of therapy or could be unrelated to their prior history of malignancy. We aim to evaluate the nontoxicity related health conditions in survivors of pediatric solid tumors. The study included a cohort of hepatoblastoma (HB), Wilm's tumor (WT), and malignant germ cell tumors (MGCT) survivors registered at pediatric surgical-oncology clinic from 1994 to 2016. Follow-up was done according to standard protocols and children were evaluated at each visit for any health-related conditions. Of the survivors, 318 survivors, comprising of 48, 81, and 189 survivors of HB, MGCT, and WT, respectively, were included in the analysis. We found 20.8% of patients with HB, 11.1% of patients with MGCT, and 16.4% of patients with WT to report nontoxicity-related health issues. A high prevalence of surgical conditions (3.4%), secondary malignancies (1.2%), gynecological conditions in girls (16.9%), tuberculosis (1.2%), gallstone disease (0.9%), pelvi-ureteral junction obstruction (0.9%), and neurological issues (0.9%) was noted. Two presumed survivors had died, one due to a late recurrence and the other due to a secondary malignancy. A high prevalence of medically or surgically manageable conditions makes it imperative to keep these children under follow-up to address any health-related conditions they may subsequently develop.

Cardiovascular diseases in testicular germ cell tumors survivors

Cardiovascular diseases in testicular germ cell tumors survivors

Late mortality reduction among survivors of germ cell tumors in childhood and adolescence in Europe: A report from the PanCareSurFup cohort.

Data on late mortality from pediatric germ cell tumors (GCTs) are limited to small case series. Our population-based study aimed to investigate excess risk of death in survivors of GCT in childhood and adolescence, whether long-term mortality changed over time and by period of diagnosis. The PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) cohort includes 2773 five-year survivors diagnosed under 21years of age with gonadal and extragonadal GCT (from 1940 to 2008). We calculated standardized mortality ratios (SMRs) and absolute excess risks (AERs). We fitted a Cox's model to assess the impact of treatment period. We estimated 10-year survival and calculated average percentage changes between periods of diagnosis (1970-1979, 1980-1989, 1990-1999) to assess whether late mortality decreased. GCT survivors had an almost four-fold excess risk of dying compared to general population. The risk of death for patients treated after 1980 was nearly halved compared to patients treated before 1980. Survivors diagnosed in 1990-1999 had a 10-year survival rate of 99%, which was 2.4% and 1.1% higher than for patients treated in 1970-1979 and 1980-1989, respectively. This is the largest population-based study in Europe and showed a decrease in long-term mortality for survivors of GCTs in childhood and adolescence over the last decades. After the introduction of platinum compound in 1980, which is a paradigm of success compared to the previous treatments, no major changes in drug therapies have been made to treat GCTs in the last 40years. However, GCT survivors maintain an excessive risk of death that requires long-term care.

Depression and anxiety in women with malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST): an analysis of the AGO-CORSETT database

IntroductionThe intention of this study was to evaluate the level of anxiety and depression of malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) survivors and to identify possible alterable cofactors.MethodsCORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO Studygroup. Women who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Hospital Anxiety and Depression Scale (HADS) to evaluate distress. Predictors of distress (type of surgery, chemotherapy, time since diagnosis, recurrence, second tumor, pain) were investigated using multivariate linear regression analysis.Results150 MOGCT and SCST patients with confirmed histological diagnosis completed the questionnaire median seven years after diagnosis. They had a HADS total score ≥ 13 indicating severe mental distress in 34% of cases. Patients after fertility-conserving surgery had lower probability of severe mental distress than those without fertility-conserving treatment (β = − 3.1, p = 0.04). Pain was associated with the level of distress in uni- and multivariate analysis (coef 0.1, p < 0.01, coef. Beta 0.5).DiscussionSevere mental distress was frequent in patients with MOGCT and SCST and the level of pain was associated with the level of distress. Fertility conserving therapy, however, was associated with less mental distress. Screening and treatment of pain and depression is required to improve mental well-being in survivors of MOGCT and SCST.

Risk of osteoporosis in testicular germ cell tumour survivors: A systematic review of the literature.

Testicular germ cell tumour (TGCT) survivors are potentially at risk of developing osteoporosis, because of increased risk for disturbed bone remodelling associated with hypogonadism and anti-cancer treatment. A number of studies show bone loss and increased fracture risk in TGCT survivors, but data are scarce. There are no clinical guidelines or recommendations issued to address skeletal health in this group of patients potentially at high risk for osteoporosis. To conduct a systematic review of available literature addressing bone health in TGCT patients. Subgroup analysis was performed to identify risk factors for bone loss and increased fracture risk. Relevant databases, including MEDLINE, Embase and the Cochrane Library, including all English written comparative studies addressing bone health in TGCT patients, were searched up to December 2021 and a narrative synthesis was undertaken. Risk of bias (RoB) was assessed using Cochrane ROBINS-I tool. Ten studies (eight cross-sectional and two longitudinal), recruiting a total of 1997 unique TGCT patients, were identified and included in the analysis. Bone health was reported in various ways in different studies, and subgroups were defined heterogeneously, resulting in a widely varying prevalence of osteoporosis of up to 73.2% of patients. Six studies reported low BMD associated with higher luteinizing hormone levels and one study showed a correlation between follow up duration and bone loss. TGCT survivors are at risk of developing osteoporosis and sustaining fragility fractures. Chemotherapy, pituitary-gonadal axis dysfunction and ageing are key risk factors, although available data are scarce. With increasing survival of TGCT patients, a clear unmet need has been identified to systematically evaluate and monitor skeletal health in larger numbers of survivors in order to develop best clinical practice guidelines to manage the insidious but potentially preventable and treatable skeletal complications of TGCT.

Growth Hormone Deficiency in Childhood Intracranial Germ Cell Tumor Survivors.

Intracranial germ cell tumor (iGCT) survivors have multiple risk factors for growth hormone (GH) deficiency, a commonly reported late effect in childhood cancer survivors. The objective of this study is to examine the prevalence of GH deficiency among childhood iGCT survivors. Participants were previously enrolled in the Germ Cell Tumor Epidemiology Study (GaMETES), a case parent triad study conducted using the Children's Oncology Group registry protocols, including 216 cases with iGCTs. Data on late effects and outcomes are available for 129 iGCT cases who consented for a follow-up study including a self-administered questionnaire and medical record retrieval. GH deficiency was identified via self-report and validated through medical record review. Chi-squared and Fisher's exact tests were used to examine cases with GH deficiency predating iGCT detection. Logistic regression was used to identify predictors of GH deficiency as a late effect. Of 129 iGCT cases who participated in the late effects study, 45% had GH deficiency; 18% had GH deficiency predating the iGCT and 27% developed GH deficiency within a median of 19 months after diagnosis. Younger age at diagnosis, suprasellar location, and higher radiation doses were associated with GH deficiency as a late effect. GH deficiency is highly prevalent as an early clinical sign for iGCT and frequently arises as an early late effect after treatment. Additional investigation is needed to address earlier detection and treatment for this highly prevalent late effect in iGCT survivors.

Improvement of erectile dysfunction in germ cell tumor survivors

ABSTRACT Introduction Germ cell tumors (GCTs) are the most common malignant neoplasms in adolescents and young adults, and most patients with these tumors can be completely cured. Therefore, maintaining quality of life (QOL) is important. Erectile dysfunction (ED) is one factor that reduces the QOL of GCT survivors. Objective We aimed to clarify the relationship between ED and age, follow-up period, serum levels of hormones, and treatment methods for GCT survivors. Methods We evaluated ED using the Sexual Health Inventory for Men questionnaire (SHIM) and measured serum levels of hormones in survivors after GCT treatment. The relationships between the SHIM score responses and age, serum levels of hormones, follow-up period, and treatment methods were assessed using a logistic analysis. Results Fifty-two GCT survivors were enrolled and 46 survivors completed the SHIM. The median age, follow-up period, and SHIM score were 38 years, 35 months, and 18, respectively. Regarding the SHIM scores, 85% had scores &amp;lt;22 and 46% had scores &amp;lt;17. The percentage of SHIM scores &amp;lt;17 was 69% in patients with under 2 years of follow-up. It significantly improved to 33% in patients with over 2 years of follow-up. The multivariate analysis identified the follow-up period as an independent factor for SHIM scores &amp;lt;17. Age, serum levels of hormone, and treatment method were not significant factors for SHIM scores &amp;lt;17. Conclusions Improvement of SHIM score can be expected after GCT treatment regardless of age, serum levels of hormone, and treatment method. Disclosure Work supported by industry: no.