cancersCancer

Central nervous system germ cell tumours (germinoma and non-germinomatous)

aka Intracranial germ cell tumour, CNS germinoma, Pineal germinoma, Suprasellar germinoma, Non-germinomatous germ cell tumour (NGGCT), Intracranial teratoma

Germ cell tumours of the brain grow near the pineal gland or above the pituitary in teenagers. The commonest kind, germinoma, is so sensitive to radiation and chemotherapy that most patients are cured; the other kinds need stronger chemotherapy and radiotherapy, and doctors measure two proteins in the blood and spinal fluid to tell them apart and to follow treatment.

Part ofBrain and spinal cord tumours (all types)

Central nervous system germ cell tumours arise in the midline, in the pineal region (more often in boys) and suprasellar region (with diabetes insipidus and hormone deficits), sometimes at both sites (bifocal). WHO 2021 lists germinoma, embryonal carcinoma, yolk sac tumour, choriocarcinoma, mature and immature teratoma, teratoma with somatic-type malignancy and mixed germ cell tumour; clinically they divide into germinoma and non-germinomatous germ cell tumours (NGGCT). Alpha-fetoprotein and beta-hCG in serum and cerebrospinal fluid are diagnostic and prognostic: marked elevation indicates NGGCT and can spare biopsy, while normal or mildly raised hCG with typical imaging leads to biopsy to confirm germinoma. Staging requires spinal MRI and cerebrospinal fluid cytology. Klinefelter and Down syndromes raise risk, and KIT and RAS pathway mutations are frequent.

Germinoma is exquisitely radiosensitive. Craniospinal irradiation alone cured more than nine in ten patients with localised disease in SIOP CNS GCT 96 (five-year event-free survival above 90 percent), and the same trial showed that carboplatin, etoposide and ifosfamide followed by focal radiotherapy gave similar survival but more relapses in the ventricles; SIOP CNS GCT II and the Children's Oncology Group's ACNS1123 therefore adopted chemotherapy followed by reduced-dose whole-ventricular irradiation with a tumour boost, the current standard for localised germinoma, with craniospinal irradiation kept for disseminated disease. NGGCT is treated with intensive platinum-based chemotherapy (cisplatin or carboplatin with etoposide and ifosfamide), second-look surgery for residual masses, which often prove to be teratoma, and then radiotherapy; ACNS0122 used craniospinal irradiation after chemotherapy with good results, and attempts to reduce to whole-ventricular fields in ACNS1123 were tempered by spinal relapses. High-dose chemotherapy with stem cell rescue is used at relapse.

The agenda is reducing late effects without losing cure: lowering radiation dose and volume, proton therapy, and defining which NGGCT patients can safely avoid craniospinal irradiation. Long-term survivors need endocrine replacement, neurocognitive support and fertility counselling. International harmonisation of the SIOP and COG approaches, which historically differed on the role of chemotherapy for germinoma, is progressing through joint trials.

State of the art

Germinoma is cured in the great majority with chemotherapy and reduced-field radiotherapy, and each trial generation has lowered the radiation dose and volume.
Tumour markers in blood and spinal fluid allow diagnosis and risk assignment with less surgery than any other brain tumour.
Proton therapy is reducing the endocrine and cognitive cost of ventricular and craniospinal irradiation in children.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Carboplatin Cisplatin Etoposide Ifosfamide Thiotepa source
Check before combining
Kidneys: Carboplatin
Dose by Calvert formula using GFR (see the calculators).
Carboplatin source
Check before combining
Kidneys: Cisplatin
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
Cisplatin source
Check before combining
Kidneys: Etoposide
Reduce to 75% for CrCl 15-50.
Etoposide source
Good to know
Infusion reactions, hypersensitivity and extravasation
Reactions around the moment a drug is given: chills, fever or breathlessness from antibodies (infusion reactions), true allergy (hypersensitivity, rarely anaphylaxis), and leakage of a damaging drug into tissue around the vein (extravasation).
Carboplatin source

See all on the product pages:Carboplatin Cisplatin Etoposide Ifosfamide Thiotepa·Printable cards in the navigator

Anatomy and lymph node drainage

Brain: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

Gliomas infiltrate along white matter and can cross the corpus callosum, medulloblastoma sits in the cerebellum, and CNS lymphoma favours deep periventricular tissue; none spread through lymph nodes.

Subsites

Frontal lobe (glioblastoma commonest)
Temporal lobe
Corpus callosum (butterfly glioma)
Lower-grade IDH-mutant glioma
Cerebellum (medulloblastoma)
Brainstem and spinal cord (diffuse midline glioma, cord tumours)Metastatic or disseminated CNS germ cell tumour (cerebrospinal fluid spread)
Ventricles and ependymal lining (ependymoma)
Sella and pituitary (pituitary tumours, craniopharyngioma)
Deep periventricular tissue (CNS lymphoma)
Meninges and convexity (meningioma)
Grey-white junction (brain metastases)
Cerebellopontine angle and eighth nerve (vestibular schwannoma)
Pineal and suprasellar midline (germ cell tumours)Germinoma of the pineal or suprasellar region (bifocal when both) · Non-germinomatous germ cell tumour: embryonal carcinoma, yolk sac tumour, choriocarcinoma, mixed · Mature and immature teratoma (surgical disease; growing teratoma after chemotherapy) · Teratoma with somatic-type malignancy · Metastatic or disseminated CNS germ cell tumour (cerebrospinal fluid spread)

Regional lymph nodes

No conventional lymphatics: gliomas spread along white matter tracts and, rarely, through cerebrospinal fluid; medulloblastoma can seed the spine.

Same organ: Glioma & glioblastoma, Primary CNS lymphoma, Medulloblastoma, Paediatric low-grade glioma, Diffuse midline glioma, H3 K27-altered (including DIPG), Atypical teratoid/rhabdoid tumour (ATRT), Ependymoma, Craniopharyngioma, Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma, Brain and spinal cord tumours (all types), Astrocytoma, IDH-mutant (grades 2 to 4), Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, Paediatric high-grade glioma (excluding diffuse midline glioma), Meningioma, Brain metastases (secondary brain tumours), Vestibular schwannoma (acoustic neuroma), Spinal cord tumours (intramedullary and intradural)

Who gets it and what has changed

A few percent of childhood and adolescent brain tumours in Western countries and several times commoner in East Asia; peak age is the second decade with a male excess, and germinoma is one of the most curable brain tumours.

Group

central nervous system

What is being done about this

Finding cancer earlier

and how the field plans to fix it →

Available now

MRIStandard of care

In trials

Nothing recorded yet.

Ideas and roadmaps

Nothing recorded yet.

Background: Alpha-fetoprotein (AFP). Also on OnCo: Symptoms and red flags · Early detection roadmap.

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

4 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

Localised germinoma5 Disseminated germinoma2 Non-germinomatous germ cell tumour6 Teratoma Relapse2

Localised germinoma

Platinum-based chemotherapy (carboplatin and etoposide, with ifosfamide in the SIOP schedule) followed by reduced-dose whole-ventricular irradiation with a tumour boost (SIOP CNS GCT II, ACNS1123); craniospinal irradiation alone remains an alternative in adults.

NCI PDQ: childhood CNS germ cell tumours

CarboplatinEtoposideIfosfamideIMRT / IGRT (modern external beam)Proton therapy

Disseminated germinoma

Craniospinal irradiation with boosts, with or without chemotherapy.

NCI PDQ: childhood CNS germ cell tumours

IMRT / IGRT (modern external beam)Proton therapy

Non-germinomatous germ cell tumour

Intensive cisplatin or carboplatin, etoposide and ifosfamide chemotherapy, second-look surgery for residual disease, then craniospinal or whole-ventricular irradiation depending on stage and response (ACNS0122, ACNS1123, SIOP CNS GCT II).

NCI PDQ: childhood CNS germ cell tumours

CisplatinCarboplatinEtoposideIfosfamideIMRT / IGRT (modern external beam)Proton therapy

Teratoma

Complete surgical resection; growing teratoma after chemotherapy is also managed surgically.

MRI

Relapse

High-dose chemotherapy (thiotepa-based) with autologous stem cell rescue, with re-irradiation where possible.

ThiotepaAutologous stem cell transplant (high-dose therapy)Re-irradiation

Subtypes & biomarkers

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Subtypes

Germinoma of the pineal or suprasellar region (bifocal when both)
Non-germinomatous germ cell tumour : embryonal carcinoma, yolk sac tumour, choriocarcinoma, mixed
Mature and immature teratoma (surgical disease; growing teratoma after chemotherapy)
Teratoma with somatic-type malignancy
Metastatic or disseminated CNS germ cell tumour (cerebrospinal fluid spread)

Biomarkers clinicians test

Alpha-fetoprotein in serum and cerebrospinal fluid
Beta-hCG in serum and cerebrospinal fluid
Placental alkaline phosphatase and c-KIT on germinoma cells
Cerebrospinal fluid cytology and spinal MRI for staging
Pituitary hormone panel for suprasellar tumours

How often this target appears

History

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1985Jennings reviews intracranial germ cell tumours and their site and age patterns
1997Matsutani proposes the Japanese good, intermediate and poor prognosis grouping
Basis for risk-adapted therapy in Japan and later international trials.
2013SIOP CNS GCT 96: craniospinal irradiation alone or chemotherapy plus focal radiotherapy for germinoma
Calaminus and colleagues (Neuro-Oncology): equivalent survival, more ventricular relapses with focal fields; whole-ventricular irradiation adopted.
CarboplatinEtoposideIfosfamide
2015ACNS0122: chemotherapy then craniospinal irradiation for non-germinomatous tumours
Goldman and colleagues (JCO).
CarboplatinEtoposideIfosfamide
2021WHO 2021 lists CNS germ cell tumour types alongside their gonadal counterparts

What changed

6top

Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 6 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for Central nervous system germ cell tumours (germinoma and non-germinomatous), drawn from the whole corpus: 0 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Nothing recorded in development for this cancer yet.

Open problems and what is being done

Which non-germinomatous patients can safely avoid craniospinal irradiation.
Late endocrine, cognitive and vascular effects of radiotherapy in survivors treated as teenagers.
Relapsed non-germinomatous tumours have poor salvage rates.
What is being done about this
Recurrence and residual disease
and how the field plans to fix it →
Available now
Autologous stem cell transplant (high-dose therapy)Standard of care
In trials
Nothing recorded yet.
Ideas and roadmaps
Nothing recorded yet.
Also on OnCo: Treatment journeys · Survivorship planner.
Why incidence is several times higher in East Asia.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Central nervous system germ cell tumours (germinoma and non-germinomatous)

condition: Central nervous system germ cell tumor

Open on ClinicalTrials.gov →

within

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Expert centres

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Where the expertise is

Expert centres

119 centres in 42 countries · 0 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

119 centres


MD Anderson Cancer Center Houston · cancer center	United States	NCI comprehensive	6,724	95,007	CAR-NK & CAR-macrophage Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +2	#2
Samsung Medical Center Seoul · hospital	South Korea	none recorded	1,312	17,172	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#3
Mayo Clinic Rochester, MN · hospital	United States	NCI comprehensive	4,511	44,748	Carbon-ion therapy Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#5
Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center Baltimore · cancer center	United States	NCI comprehensive	2,955	41,449	Multi-cancer early detection (MCED)Liquid biopsy (ctDNA)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems +2	#10
Charité Universitätsmedizin Berlin Berlin · university	Germany	none recorded	1,563	17,749	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems CyberKnife robotic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#12
Massachusetts General Hospital Cancer Center Boston · hospital	United States	NCI comprehensive	3,582	54,857	Proton therapy Small-molecule kinase inhibitors Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#16
Heidelberg University Hospital / NCT / DKFZ Heidelberg · cancer center	Germany	none recorded	3,456	45,745	FAPI PET Targeted alpha therapy Carbon-ion therapy DNA methylation profiling +5	#18
Cleveland Clinic Taussig Cancer Institute Cleveland · hospital	United States	NCI comprehensive	2,264	29,412	Off-the-shelf cancer vaccines Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#20
Institut Curie Paris · cancer center	France	none recorded	1,065	15,111	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	#21
The Christie NHS Foundation Trust Manchester · cancer center	United Kingdom	none recorded	104	2,145	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems MR-guided adaptive radiotherapy TomoTherapy and Radixact (helical radiotherapy)	#23
Fudan University Shanghai Cancer Center Shanghai · cancer center	China	none recorded	1,678	18,354	TROP2 PET Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Carbon-ion therapy +1	#55
Abramson Cancer Center, University of Pennsylvania Philadelphia · cancer center	United States	NCI comprehensive	3,148	54,267	CAR-T cell therapy In vivo CAR-T PARP PET Personalised neoantigen (mRNA) vaccines +2	-
University of Michigan Rogel Cancer Center Ann Arbor, MI · cancer center	United States	NCI comprehensive	2,991	29,686	PROTACs & molecular glues (targeted protein degradation)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	-
University College London Hospitals / UCL Cancer Institute London · hospital	United Kingdom	none recorded	2,376	28,940	Proton therapy CAR-T cell therapy Liquid biopsy (ctDNA)Whole-exome & whole-genome sequencing +5	-
Fred Hutchinson Cancer Center Seattle · cancer center	United States	NCI comprehensive	2,123	29,954	CAR-T cell therapy Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	-

(showing the first 15)

These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Central nervous system germ cell tumours but is thinly recorded here will look small.

Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Central nervous system germ cell tumours

Generated from this cancer's standard of care, biomarkers, and pipeline · 17 questions

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 Alpha-fetoprotein in serum and cerebrospinal fluid, Beta-hCG in serum and cerebrospinal fluid, Placental alkaline phosphatase and c-KIT on germinoma cells, Cerebrospinal fluid cytology and spinal MRI for staging, Pituitary hormone panel for suprasellar tumours), 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 Germinoma of the pineal or suprasellar region, Non-germinomatous germ cell tumour: embryonal carcinoma, yolk sac tumour, choriocarcinoma, mixed, Mature and immature teratoma.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Localised germinoma

For my situation (localised germinoma), which of the standard options do you recommend and why?
Why: Guideline options include: Platinum-based chemotherapy (carboplatin and etoposide, with ifosfamide in the SIOP schedule) followed by reduced-dose whole-ventricular irradiation with a tumour boost (SIOP CNS GCT II, ACNS1123); craniospinal irradiation alone remains an alternative in adults.
Am I a candidate for Carboplatin, Etoposide, Ifosfamide, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Disseminated germinoma

For my situation (disseminated germinoma), which of the standard options do you recommend and why?
Why: Guideline options include: Craniospinal irradiation with boosts, with or without chemotherapy.

Non-germinomatous germ cell tumour

For my situation (non-germinomatous germ cell tumour), which of the standard options do you recommend and why?
Why: Guideline options include: Intensive cisplatin or carboplatin, etoposide and ifosfamide chemotherapy, second-look surgery for residual disease, then craniospinal or whole-ventricular irradiation depending on stage and response (ACNS0122, ACNS1123, SIOP CNS GCT II).
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.

Teratoma

For my situation (teratoma), which of the standard options do you recommend and why?
Why: Guideline options include: Complete surgical resection; growing teratoma after chemotherapy is also managed surgically.

Relapse

For my situation (relapse), which of the standard options do you recommend and why?
Why: Guideline options include: High-dose chemotherapy (thiotepa-based) with autologous stem cell rescue, with re-irradiation where possible.
Am I a candidate for Thiotepa, 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 Proton therapy, Autologous stem cell transplant (high-dose 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 “Which non-germinomatous patients can safely avoid craniospinal irradiation”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “Late endocrine, cognitive and vascular effects of radiotherapy in survivors treated as teenagers”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.