Germ cell tumours of childhood and adolescence (extracranial and CNS)
Germ cell tumours arise from the cells meant to become eggs or sperm and can appear in the gonads, lower back, chest or brain. They are among the most curable childhood cancers because they respond to cisplatin chemotherapy and release blood markers that make monitoring easy. The work now is to cure with less: surgery alone for low-risk tumours, gentler platinum drugs, and protecting hearing.
Overview
Paediatric and adolescent germ cell tumours (GCTs) are a heterogeneous family (mature and immature teratoma, yolk sac tumour, germinoma or seminoma or dysgerminoma, embryonal carcinoma, choriocarcinoma and mixed tumours) arising in gonadal and extragonadal midline sites: sacrococcygeal region, retroperitoneum, mediastinum and the pineal and suprasellar regions of the brain. Infant tumours are mostly yolk sac tumours and teratomas with a distinct genome; adolescent tumours resemble adult testicular cancer, with 12p gain. Serum AFP and beta-hCG are diagnostic, prognostic and used for surveillance.
Malignant extracranial GCTs are cured in most children with surgery and cisplatin-based chemotherapy (PEb: cisplatin, etoposide, bleomycin in North America; JEb with carboplatin in the United Kingdom). The Malignant Germ Cell International Consortium (MaGIC) pooled COG and CCLG data to build a shared risk classification, which underpins the current joint trial AGCT1531: low-risk tumours are managed with surgery and active surveillance, with chemotherapy only on relapse, and standard-risk patients are randomised between cisplatin and carboplatin to test whether hearing and kidney toxicity can be reduced without losing cure. Cisplatin ototoxicity, the main long-term harm, can be reduced with sodium thiosulfate given after each dose (ACCL0431 and SIOPEL 6, approved for children with localised solid tumours). Salvage for relapse uses high-dose chemotherapy with stem-cell rescue as in adults.
CNS germ cell tumours are treated differently: germinomas are exquisitely radiosensitive and are cured with chemotherapy followed by reduced-dose whole-ventricular radiotherapy (SIOP CNS GCT II and ACNS1123 approaches), while non-germinomatous tumours need chemotherapy, craniospinal or focal radiotherapy and second-look surgery. Ovarian GCTs in adolescents are managed with fertility-sparing surgery and, for malignant tumours beyond stage I, the same platinum regimens. Because the adult, adolescent and paediatric worlds treat the same disease with different protocols, harmonising them is itself a research programme.
State of the art today
- Most children and adolescents with malignant germ cell tumours are cured; the agenda is reducing toxicity, tested directly in the joint COG/CCLG AGCT1531 trial.
- Active surveillance replaces chemotherapy for low-risk resected tumours, sparing many children platinum exposure altogether.
- Sodium thiosulfate after cisplatin protects hearing without compromising cure in localised disease and is now approved for children.
- CNS germinoma is cured with chemotherapy plus reduced-dose ventricular radiotherapy, sparing cognition compared with historical craniospinal irradiation.
Where it starts and where it drains
Germ cell tumours drain along the spermatic cord to the para-aortic nodes high in the abdomen, not to the groin, which is why staging scans look at the retroperitoneum.
- Germinal epitheliumTeratoma (mature, immature; sacrococcygeal in infants) · Yolk sac tumour (infants; AFP-secreting) · Germinoma / seminoma / dysgerminoma (adolescents; CNS germinoma) · Embryonal carcinoma and choriocarcinoma (hCG-secreting) · Mixed malignant germ cell tumour
- Epididymis and cord
- para-aortic (retroperitoneal)
- left renal hilum (left testis)
- inguinal (only after scrotal surgery)
Same organ: Testicular germ cell tumours
A few percent of childhood cancers overall, with peaks in infancy (sacrococcygeal and testicular teratomas and yolk sac tumours) and adolescence (ovarian, testicular and mediastinal tumours) (NCI PDQ).
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Complete resection followed by active surveillance with serial tumour markers and imaging; chemotherapy only for relapse (AGCT1531 stratum).
Cisplatin, etoposide and bleomycin (PEb) or carboplatin-based JEb, with surgery of residual masses; sodium thiosulfate for otoprotection; high-dose chemotherapy with stem-cell rescue at relapse.
Platinum-based chemotherapy followed by reduced-dose whole-ventricular radiotherapy with tumour boost (SIOP CNS GCT II, ACNS1123).
Intensive platinum-based chemotherapy, second-look surgery for residual disease, then craniospinal or whole-ventricular radiotherapy depending on response and stage.
Subtypes & biomarkers
top- Teratoma (mature, immature; sacrococcygeal in infants)
- Yolk sac tumour (infants; AFP-secreting)
- Germinoma / seminoma / dysgerminoma (adolescents; CNS germinoma)
- Embryonal carcinoma and choriocarcinoma (hCG-secreting)
- Mixed malignant germ cell tumour
- CNS non-germinomatous germ cell tumour
- Ovarian germ cell tumour (adolescent)
- Serum and cerebrospinal-fluid AFP
- Serum and cerebrospinal-fluid beta-hCG
- Lactate dehydrogenase
- Isochromosome 12p (adolescent tumours)
- MaGIC risk group (site, stage, age, marker level)
- Audiometry before and after cisplatin
- Fertility assessment and preservation
Target prevalence in this cancer
- 1977Cisplatin combinations cure disseminated germ cell tumours
Einhorn's PVB regimen in testicular cancer, later adapted to children.
- 1990Carboplatin-based JEb adopted in the United Kingdom
UKCCSG shows carboplatin can replace cisplatin in children with less hearing and kidney toxicity.
- 2004Surveillance for stage I paediatric testicular tumours
POG/CCG intergroup studies show surgery alone is safe for low-stage disease.
- 2015MaGIC pooled risk classification
Frazier and colleagues (JCO) combine COG and CCLG data to define shared risk groups.
- 2018Sodium thiosulfate protects hearing
SIOPEL 6 (NEJM 2018) and ACCL0431 show reduced cisplatin ototoxicity; FDA approval 2022.
- 2017AGCT1531 opens
Joint COG/CCLG trial of active surveillance and carboplatin versus cisplatin.
Open problems, and what is being done about each
Whether carboplatin can fully replace cisplatin without losing cures in standard-risk disease; AGCT1531 is the answer trial.
Relapsed and platinum-refractory disease, especially mediastinal and CNS non-germinomatous tumours, where high-dose chemotherapy is the only option.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable now- Survivorship care and late-effects surveillanceEstablished
- Liquid biopsy (ctDNA)Standard of care
- MRD / molecular residual disease testingEstablished
- Multiparameter flow cytometry MRDStandard of care
- NGS-based MRD (clonoSEQ and molecular MRD)Standard of care
- SignateraEstablished
In trials- ADAURAPositive
- CAMBRIA-1 & CAMBRIA-2Recruiting
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
- ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)Emerging
- DYNAMICPositive
- IMvigor011Positive
Ideas and roadmaps- A blood test for the pre-metastatic niche
- A bone marrow niche on a chip to study human dormancy
- A dedicated clinic for people whose blood test says the cancer is back
- A drug screen that only rewards killing sleeping cancer cells
- A national platform trial that every ctDNA-positive patient can join
- A national residual-disease weather service: serial blood tests for every curatively treated patient, pooled
Background: Circulating tumour DNA (ctDNA), Disseminated tumour cells (DTCs), Late recurrence, Minimal / molecular residual disease (MRD), MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶). Also on OnCo: Treatment journeys · Survivorship planner.
Long-term hearing, kidney, fertility and cardiovascular effects; otoprotection, fertility preservation and survivorship clinics address them.
Harmonising paediatric, adolescent and adult protocols so that a 17-year-old and a 19-year-old receive the same evidence-based care.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- Aarhus University HospitalAarhus, DKvia Proton therapy, IMRT / IGRT (modern external beam)
- American Society for Radiation OncologyArlington, VA, USvia Proton therapy, IMRT / IGRT (modern external beam)
- Centre Antoine LacassagneNice, FRvia Proton therapy, IMRT / IGRT (modern external beam)
- European Society for Radiotherapy and OncologyBrussels, BEvia Proton therapy, IMRT / IGRT (modern external beam)
- Hokkaido University HospitalSapporo, JPvia Proton therapy, IMRT / IGRT (modern external beam)
- Institute of Oncology LjubljanaLjubljana, SIvia Carboplatin, IMRT / IGRT (modern external beam)
- via Proton therapy, IMRT / IGRT (modern external beam)
- via Proton therapy, IMRT / IGRT (modern external beam)
- Royal Adelaide HospitalAdelaide, AUvia Proton therapy, IMRT / IGRT (modern external beam)
- via Proton therapy, IMRT / IGRT (modern external beam)
- Zhejiang Cancer HospitalHangzhou, CNvia Proton therapy, IMRT / IGRT (modern external beam)
- via Proton therapy
- Alliance for Clinical Trials in OncologyChicago, IL, USvia Carboplatin
- Apollo Hospitals (Apollo Cancer Centres)Chennai, INvia Proton therapy
- via Proton therapy
- via Proton therapy
- Centre François BaclesseCaen, FRvia Proton therapy
- Centre Oscar LambretLille, FRvia IMRT / IGRT (modern external beam)
- Chang Gung Memorial HospitalTaoyuan, TWvia Proton therapy
- via IMRT / IGRT (modern external beam)
- Children's Cancer and Leukaemia GroupLeicester, GBvia this cancer
- via IMRT / IGRT (modern external beam)
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia Proton therapy
- Children's Oncology Group (COG)Monrovia, CA, USvia this cancer
- Cleveland Clinic Abu DhabiAbu Dhabi, AEvia Proton therapy
- Comprehensive Cancer Center Freiburg (CCCF)Freiburg im Breisgau, DEvia IMRT / IGRT (modern external beam)
- via Proton therapy
- Erasmus MC Cancer InstituteRotterdam, NLvia Proton therapy
- Geneva University Hospitals (HUG)Geneva, CHvia IMRT / IGRT (modern external beam)
- German Breast Group (GBG)Neu-Isenburg, DEvia Carboplatin
- Groote Schuur Hospital / University of Cape TownCape Town, ZAvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Hacettepe University Cancer InstituteAnkara, TRvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Ho Chi Minh City Oncology HospitalHo Chi Minh City, VNvia IMRT / IGRT (modern external beam)
- Hunan Cancer HospitalChangsha, CNvia IMRT / IGRT (modern external beam)
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensivevia Cisplatin
- Institut BergoniéBordeaux, FRvia IMRT / IGRT (modern external beam)
- Institut National d'Oncologie, RabatRabat, MAvia IMRT / IGRT (modern external beam)
- Institut Salah AzaïezTunis, TNvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- International Extranodal Lymphoma Study GroupBellinzona, CHvia IMRT / IGRT (modern external beam)
- IRCCS Humanitas Research HospitalRozzano (Milan), ITvia IMRT / IGRT (modern external beam)
- Istanbul University Institute of OncologyIstanbul, TRvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CAvia IMRT / IGRT (modern external beam)
- Kenyatta National HospitalNairobi, KEvia IMRT / IGRT (modern external beam)
- via Proton therapy
- Korle Bu Teaching HospitalAccra, GHvia IMRT / IGRT (modern external beam)
- Lagos University Teaching HospitalLagos, NGvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- Leiden University Medical CenterLeiden, NLvia Proton therapy
- Maastricht UMC+ Comprehensive Cancer CenterMaastricht, NLvia Proton therapy
- via IMRT / IGRT (modern external beam)
- via Proton therapy
- via Proton therapy
- via Proton therapy
- National Cancer Center Hospital EastKashiwa, Chiba, JPvia Proton therapy
- National Cancer Center KoreaGoyang, KRvia Proton therapy
- National Cancer Centre SingaporeSingapore, SGvia Proton therapy
- via IMRT / IGRT (modern external beam)
- National Institute of Oncology, HungaryBudapest, HUvia IMRT / IGRT (modern external beam)
- National Taiwan University HospitalTaipei, TWvia Proton therapy
- via Proton therapy
- Ocean Road Cancer InstituteDar es Salaam, TZvia IMRT / IGRT (modern external beam)
- via Proton therapy
- via IMRT / IGRT (modern external beam)
- via Proton therapy
- Rajiv Gandhi Cancer Institute and Research CentreNew Delhi, INvia IMRT / IGRT (modern external beam)
- Rambam Health Care CampusHaifa, ILvia IMRT / IGRT (modern external beam)
- Rigshospitalet – Copenhagen University HospitalCopenhagen, DKvia IMRT / IGRT (modern external beam)
- Ruijin Hospital, Shanghai Jiao Tong UniversityShanghai, CNvia Proton therapy
- Shizuoka Cancer CenterNagaizumi, Shizuoka, JPvia Proton therapy
- via this cancer
- Siriraj Hospital, Mahidol UniversityBangkok, THvia IMRT / IGRT (modern external beam)
- via Proton therapy
- via Proton therapy
- Tata Medical Center, KolkataKolkata, INvia IMRT / IGRT (modern external beam)
- Tawam HospitalAl Ain, AEvia IMRT / IGRT (modern external beam)
- Tel Aviv Sourasky Medical CenterTel Aviv, ILvia IMRT / IGRT (modern external beam)
- The Clatterbridge Cancer Centre NHS Foundation TrustLiverpool, GBvia Proton therapy
- via IMRT / IGRT (modern external beam)
- TROG Cancer ResearchNewcastle, NSW, AUvia IMRT / IGRT (modern external beam)
- UMC Utrecht Cancer CenterUtrecht, NLvia IMRT / IGRT (modern external beam)
- via Proton therapy
- via Proton therapy
- via Proton therapy
- via Proton therapy
- University of Malaya Medical CentreKuala Lumpur, MYvia IMRT / IGRT (modern external beam)
- University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensivevia Proton therapy
- via IMRT / IGRT (modern external beam)
- via Proton therapy
- UZ Leuven / Leuven Cancer InstituteLeuven, BEvia Proton therapy
- Velindre Cancer CentreCardiff, GBvia IMRT / IGRT (modern external beam)
- via IMRT / IGRT (modern external beam)
- via Proton therapy
Questions to ask
topQuestions to ask your oncologist about Germ cell tumours of childhood and adolescence
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Serum and cerebrospinal-fluid AFP, Serum and cerebrospinal-fluid beta-hCG, Lactate dehydrogenase, Isochromosome 12p, MaGIC risk group), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Teratoma, Yolk sac tumour, Germinoma / seminoma / dysgerminoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Low-risk malignant extracranial GCT (e.g. stage I testicular, stage I ovarian)
- For my situation (low-risk malignant extracranial gct (e.g. stage i testicular, stage i ovarian)), which of the standard options do you recommend and why?Why: Guideline options include: Complete resection followed by active surveillance with serial tumour markers and imaging; chemotherapy only for relapse (AGCT1531 stratum).
Standard- and high-risk malignant extracranial GCT
- For my situation (standard- and high-risk malignant extracranial gct), which of the standard options do you recommend and why?Why: Guideline options include: Cisplatin, etoposide and bleomycin (PEb) or carboplatin-based JEb, with surgery of residual masses; sodium thiosulfate for otoprotection; high-dose chemotherapy with stem-cell rescue at relapse.
- Am I a candidate for Cisplatin, Carboplatin, Etoposide or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
CNS germinoma
- For my situation (cns germinoma), which of the standard options do you recommend and why?Why: Guideline options include: Platinum-based chemotherapy followed by reduced-dose whole-ventricular radiotherapy with tumour boost (SIOP CNS GCT II, ACNS1123).
- Am I a candidate for Carboplatin, Etoposide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
CNS non-germinomatous GCT
- For my situation (cns non-germinomatous gct), which of the standard options do you recommend and why?Why: Guideline options include: Intensive platinum-based chemotherapy, second-look surgery for residual disease, then craniospinal or whole-ventricular radiotherapy depending on response and stage.
- Am I a candidate for Cisplatin, Ifosfamide, Etoposide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Sodium thiosulfate (otoprotectant), Active surveillance, Oncofertility and fertility preservation, Proton therapy?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Whether carboplatin can fully replace cisplatin without losing cures in standard-risk disease; AGCT1531 is the answer trial”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Relapsed and platinum-refractory disease, especially mediastinal and CNS non-germinomatous tumours, where high-dose chemotherapy is the only option”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
10targets
1drugs
6institutions
3terms
4pairings
1bottlenecks
2Latest papers
topQuery for this cancer: (TITLE:"Germ cell tumours of childhood and adolescence" OR ABSTRACT:"Germ cell tumours of childhood and adolescence" OR TITLE:"extracranial and CNS" OR ABSTRACT:"extracranial and CNS" OR TITLE:"Childhood extracranial germ cell tumour" OR ABSTRACT:"Childhood extracranial germ cell tumour" OR TITLE:"CNS germ cell tumour" OR ABSTRACT:"CNS germ cell tumour" OR TITLE:"Germinoma" OR ABSTRACT:"Germinoma" OR TITLE:"Ovarian germ cell tumour" OR ABSTRACT:"Ovarian germ cell tumour") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Germ cell tumours of childhood and adolescence (extracranial and CNS), not a curated reading list.
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