GCT-13. THE TREATMENT OUTCOMES OF INTRACRANIAL GERM CELL TUMORS WITH KSPNO PROTOCOL: SINGLE CENTER RETROSPECTIVE ANALYSIS

Abstract Dho et al. (BTRT, 2017) reported that 1.1% (127/11,827) of primary brain tumors are intracranial germ cell tumors (iGCT) in Korea. We analyzed the epidemiology and treatment results of germ cell tumors in our institution. From 2004 to 2019, among 6494 patients with intracranial neoplasms the 61 (0.9%) patients with iGCTs were enrolled: histologically diagnosed in 50 patients and clinically in 11 respectively. Pediatric patients underwent treatment according to the KSPNO protocol, and adult patients were treated with bleomycin, etoposide, and cisplatin regimens. The median age was 20 years (range: 1–42) and the follow-up period was 7.7 months (range: 10.0–203.4 months), respectively. The tumors arise most frequently in the pineal area (n=30, 49.2%). There were no significant differences in outcomes between protocols, but in KSPNO protocol group showed lower tumor recurrence rate (11.5% vs. 20%, p=0.494) and mortality (0% vs. 5.2%, p=0.503). According to the pathological subtype, the outcomes showed statistically significant differences between germinoma and non-germinomatous germ cell tumor (NGGCT) groups. The 10-year progression-free survival was 93.2% and 67.1% in the germinoma and the NGGCT group, respectively (p=0.009). The NGGCT pathological type (p=0.021) was a significant recurrence associated factor in multivariate analysis. Significant adverse events (CTCAE version 5.0 grade≥3) were showed in 14 patients (7 patients in both KSPNO and other treatment protocol groups). Pure germinoma has a higher survival rate and a lower recurrence rate than NGGCT. And KSPNO protocol might be safe and effective. For appropriate treatment for iGTCs, a multidisciplinary approach might be needed.

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RTHP-31. EMERGENCY RADIOTHERAPY IN INTRACRANIAL GERM CELL TUMORS (GCTS) PATIENTS WITH KPS≤ 40: ARETROSPECTIVE ANALYSIS OF 27 CASES

Neuro-Oncology ◽

10.1093/neuonc/noz175.902 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi216-vi216

Author(s):

Linbo Cai ◽

Mingyao Lai ◽

Juan Li ◽

Cheng Zhou ◽

Qingjun Hu ◽

...

Keyword(s):

Overall Survival ◽

Survival Rate ◽

Germ Cell ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Intracranial Germ Cell Tumors ◽

Direct Cell ◽

Emergency Radiotherapy

Abstract OBJECTIVES To evaluate the potential role of emergency radiotherapy in intracranial germ cell tumors GCTs) patients with KPS ≤ 40. METHODS A total of 27 primary intracranial germ cell tumors (GCTs) patients with KPS ≤ 40 between Jan 2007 and Dec 2018 were retrospectively evaluated. The median age at initial diagnosis was 15 years (range, 528 years). Among those, 11 patients were germinoma and 16 patients were nonseminomatous germ-cell tumors (NGGCTs). There were 9 solitary pineal, 5 suprasellar, 3 basal ganglia and 10 multifocal and disseminated tumors. All patients received emergency radiotherapy (2 Gy/fx/d). Prior to radiotherapy, 11 patients were manifested with hydrocephalus, 10 with hypopituitarism and 5 with intracranial tumo apoplexy. RESULTS The average follow up time was 44.4 months. The 5 year progression free survival rate and overall survival rate were 29.6% and 33.3%. The median overall survival time was 38 months. In particular, the median intracranial hypertension symptoms relief time was 2 days. The median KPS following radiotherapy was 80 comparing to 30 prior to radiotherapy (P < 0.05). A significant improvement on KPS of 46.7±27.3 was observed in this study. CONCLUSION Emergency radiotherapy is implicated as a promising intervention for GCTs patients with elevated intracranial pressure (ICP). These advantages can be interpreted as direct cell killing effect and fast tumor shrinkage by ionizing radiation. However, to substantiate our findings, further investigations were highly warranted.

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CTNI-63. PROGNOSTIC FACTORS IN PATIENTS WITH BASAL GANGLIA GERM-CELL TUMORS: A RETROSPECTIVE ANALYSIS OF THE SINGLE CHINESE INSTITUTE EXPERIENCE FROM 2009 TO 2019

Neuro-Oncology ◽

10.1093/neuonc/noaa215.229 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii57-ii57

Author(s):

Qingjun Hu ◽

Juan Li ◽

Mingyao Lai ◽

Cheng Zhou ◽

Zhaoming Zhou ◽

...

Keyword(s):

Survival Rate ◽

Basal Ganglia ◽

Germ Cell ◽

Retrospective Analysis ◽

Surgical Resection ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Course Of Disease ◽

Free Survival

Abstract OBJECTIVE To evaluate the clinical factors related to the prognosis of basal ganglia germ cell tumors. METHODS A retrospective analysis of 52 cases of the basal ganglia germ cell tumors treated from January 2009 to January 2019 in the department of oncology of Guangdong Sanjiu Brain Hospital. The median age: 12 years (range: 5–32), The median course of disease: 11.7 months (range: 1–54). Thirteen cases were diagnosed by biopsy and 39 cases were diagnosed by elevated tumor markers. There were 31 patients (59.6%) diagnosed with germinomas and 21 patients (40.4%) with non-germ germ cell tumors. Univariate and multivariate survival analysis was performed. RESULTS To October 15, 2019, the median follow-up time was 30.4 months (range 2–124 months). The 5-year survival rate was 85%, and the 5-year progression-free survival rate was 84%. Multivariate analysis found whether serum AFP was greater than 100mIU / ml, (with HR: 11.441,95% CI: 2.09–47.66, P = 0.005),the degree of surgical resection(with HR 5.323 (1.19–23.812), P = 0.029), PD as the effect of radiotherapy (HR: 16.53, (1.19–23.81), P = 0.001) were independent prognostic factor affecting survival. CONCLUSION The pathological type, degree of surgical resection, and response to initial treatment can all affect survival.

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Prevalence of childhood growth hormone deficiency in survivors of pediatric intracranial germ cell tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e22526 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e22526-e22526

Author(s):

Diana Lone ◽

Karim Thomas Sadak ◽

Bradley S Miller ◽

Michelle Roesler ◽

Jenny N Poynter

Keyword(s):

Growth Hormone ◽

Germ Cell ◽

Growth Hormone Deficiency ◽

Late Effects ◽

Germ Cell Tumors ◽

Hormone Deficiency ◽

Endocrine Disorders ◽

Intracranial Germ Cell Tumors

e22526 Background: Survival rates for childhood cancer continue to rise, and there are now greater than 420,000 survivors in the United States. However, high cure rates come at the cost of short and long-term treatment-related toxicities. Endocrine disorders are among the most common late effects and are associated with poor health outcomes and lower quality of life. Survivors of pediatric intracranial germ cell tumors (iGCTs) are at high risk for endocrine disorders, particularly for growth hormone deficiency (GHD), due to their exposures to cranial radiation, chemotherapy, and brain surgery. To date, no long-term follow-up studies have explored the late effects experienced by survivors of iGCTs. Methods: Study participants were enrolled in the Germ Cell Tumor Epidemiology Study, which is a case-parent triad study conducted using the resources of the Children’s Oncology Group’s Childhood Cancer Research Network. Eligibility criteria included diagnosis with a germ cell tumor in any location at age 0-19 years in the years 2008-2015. The study population included 233 cases with a diagnosis of iGCT. We are currently following the cohort to evaluate outcomes and late effects of treatment, including medical record review to extract data on treatment characteristics and hormone deficiencies. This interim analysis includes chart review for 57 iGCT cases. Results: Of the 57 cases reviewed, there was a male predominance (73.7%) with the highest prevalence in non-Hispanic whites (80.4%). Cases of iGCTs can be subdivided into two main histologic subtypes, germinomas (36 cases) and non-germinomatous GCTs (NGGCT, 21 cases). The median age at diagnosis was 14.6 years for the germinomas and 10.5 years for NGGCTs. Data on growth hormone deficiency (GHD) was available for 42 of the 57 cases with a median follow-up of 7.4 years. Twenty-eight of the 42 cases (66.7%) had GHD; 19 in the germinoma group and 9 in the NGGCT group (p = 0.47). 17 of those with GHD were males (p = 0.10). There was no significant difference in prevalence of GHD by age of tumor diagnosis (p = 0.20). Conclusions: Survivors of iGCTs are at high risk for growth hormone deficiency. Identifying specific risk factors for developing GHD amongst these survivors can enhance the current guidelines for screening and management.

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Combination chemotherapy with cisplatin and etoposide for malignant intracranial germ-cell tumors

Journal of Neurosurgery ◽

10.3171/jns.1989.70.5.0676 ◽

1989 ◽

Vol 70 (5) ◽

pp. 676-681 ◽

Cited By ~ 71

Author(s):

Tatsuya Kobayashi ◽

Jun Yoshida ◽

Junzo Ishiyama ◽

Satoshi Noda ◽

Akira Kito ◽

...

Keyword(s):

Germ Cell ◽

Combination Chemotherapy ◽

Germ Cell Tumors ◽

Intracranial Germ Cell Tumor ◽

Content Type ◽

Total Response Rate ◽

Intracranial Germ Cell Tumors ◽

Dna Histograms

✓ Antitumor activity against intracranial malignant teratoma by combination chemotherapy with cisplatin and etoposide was evaluated in experimental and clinical studies. A human teratoma cell line (Tera 2) was exposed in vitro to cisplatin and/or etoposide, after which cell growth inhibition and alterations of deoxyribonucleic acid (DNA) histograms were observed. The results indicated that a synergistic cytotoxic effect was achieved by use of both agents in combination. Four cases of recurrent intracranial germ-cell tumor (three malignant teratomas and one germinoma) were treated with cisplatin and etoposide. With this combinationtherapy, regression of the tumor was observed in all four cases (three complete and one partial), for a total response rate of 100%. During a follow-up period of 9 to 22 months, no recurrence or progression has been noted in three of these cases.

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A pragmatic diagnostic approach to primary intracranial germ cell tumors and their treatment outcomes

CNS Oncology ◽

10.2217/cns-2021-0012 ◽

2021 ◽

Vol 10 (4) ◽

Author(s):

Jeyaanth Venkatasai ◽

Rajesh Balakrishnan ◽

Balakrishnan Rajkrishna ◽

Patricia Sebastain ◽

Rikki Rorima John ◽

...

Keyword(s):

Overall Survival ◽

Germ Cell ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Cell Tumor ◽

Distinct Entity ◽

Intracranial Germ Cell Tumor ◽

Free Survival ◽

Intracranial Germ Cell Tumors ◽

Significant Difference

Background: Primary intracranial germ cell tumors (ICGCT) are often diagnosed with tumor markers and imaging, which may avoid the need for a biopsy. An intracranial germ cell tumor with mild elevation of markers is seldom stratified as a distinct entity. Methods: Fifty-nine patients were stratified into three groups: pure germinoma (PG), secreting germinoma (SG) and non-germinomatous germ cell tumors (NGGCTs). Results: At 5 years, progression-free survival and overall survival of the three groups (PG vs SG vs NGGCT) were 91% versus 81% versus 59%, and 100% versus 82% versus 68%, respectively. There was no statistically significant difference in outcome among histologically and clinically diagnosed germinomas. Conclusion: A criterion for clinical diagnosis when a biopsy is not feasible is elucidated, and comparable outcomes were demonstrated with histologically diagnosed germinomas.

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Extragonadal Germ Cell Tumors in the Mexican Population

10.52916/jmrs204029 ◽

2020 ◽

pp. 1-5

Author(s):

Guzmán-Casta Jordi

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Initial Response ◽

Tumor Stage ◽

Response To Therapy ◽

And Behavior ◽

Histopathological Type ◽

Extragonadal Germ Cell Tumors

Aim: Extragonadal Germ Cell Tumors (EGGCT) are rare malignancies which represent a unique entity because their biology and behavior is substantially different from the tumors whose source is the gonads. Methods: All cases of Extragonadal Germ Cell Tumors diagnosed and treated at the Department of Oncology of the General Hospital in Mexico City between 2015 and 2020 were retrospectively evaluated to determine the clinical and pathological characteristics of the tumors as well as the different treatments utilized and follow-up. Results: Among a total of 50 patients, the mediastinum was the most frequent location, being found in 46 patients followed by 2 in the retroperitoneal space, 1 in the ethmoidal air cells, and 1 in the pineal gland. The predominant histopathology was a mixed germinal tumor in 82% of the cases with the rest being pure seminomas. All patients received first-line systemic treatment followed by surgery or second-line treatment according to their initial response to therapy. Conclusions: Extragonadal Germ Cell Tumors require a multidisciplinary approach to achieve an adequate diagnosis and treatment. The clinical and pathological differences like tumor site, histopathological type, and tumor stage influence the progression-free survival and the global overall survival.

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Importance of maintenance of dose intensity (DI) during induction chemotherapy (iCT) for metastatic nonseminomatous germ cell tumors (NSGCT)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16063 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16063-e16063

Author(s):

M. Fedyanin ◽

A. Tryakin ◽

D. Titov ◽

T. Zakharova ◽

I. Fainstein ◽

...

Keyword(s):

Prognostic Factors ◽

Germ Cell ◽

Germ Cell Tumors ◽

Dose Intensity ◽

Progression Free Survival ◽

Limited Data ◽

Prognostic Groups ◽

Prognostic Group

e16063 Background: Cisplatin- and etoposide-based CT allows curing the majority of patients (pts) with metastatic germ cell tumor. There are limited data concerning the importance of maintenance of DI during iCT. In the retrospective study we analyzed the role of DI of iCT on metastatic NSGCT. Methods: 589 chemotherapy-naïve pts with advanced NSGCT received induction iCT from 1987 to 2006 in our center. We compared data of all pts who relapsed after iCT (147 pts) with data of 159 randomly sampled pts without relapses. During iCT all pts received classical E500P (24%) or BE500P (76%) regimens. Median follow-up time was 49 (range, 3–218) months. Eighty four (27.5%) of 306 pts, 107 (35%) and 115 (37.5%) were from good, intermediate and poor prognostic groups, respectively. DI was calculated for every drug and expressed in mg/m2 per week. Multivariate Cox stepwise regression analysis was performed to determine independent prognostic factors in each IGCCCG prognostic group. Progression free survival was used as endpoint of the analysis. Results: Multivariate analysis revealed the following negative prognostic factors as independent: in pts of the IGCCCG good prognostic group: retroperitoneal lymph nodes >5 cm (HR 3.53, 95% Cl 1.66–7.51). In pts with the intermediate prognosis: DI of etoposide <80% (HR 4.73; 95 % CI 4.85–25.04) and presence of pulmonary metastases (HR 0.45, 95% Cl 0.203–0.977). In IGCCCG poor prognostic group: DI of etoposide <80% (HR 1.82, 95% Cl 1.143–2.913). Conclusions: Maintaining a DI of greater then 80% of etoposide during iCT, for the treatment metastatic NSGCT, is one of the crucial factors for pts outcome, particularly in intermediate and poor IGCCCG prognostic groups. No significant financial relationships to disclose.

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PITUITARY DYSFUNCTION IN PATIENTS WITH INTRACRANIAL GERM CELL TUMORS TREATED WITH RADIOTHERAPY

Endocrine Practice ◽

10.4158/ep-2020-0192 ◽

2020 ◽

Vol 26 (12) ◽

pp. 1458-1468

Author(s):

Boni Xiang ◽

Xiaoming Zhu ◽

Min He ◽

Wei Wu ◽

Haopeng Pang ◽

...

Keyword(s):

Germ Cell ◽

Diabetes Insipidus ◽

Adrenal Insufficiency ◽

Germ Cell Tumors ◽

Central Diabetes Insipidus ◽

Central Hypothyroidism ◽

Free Survival ◽

Sellar Lesions ◽

Intracranial Germ Cell Tumors

Objective: To evaluate the endocrine abnormalities in intracranial germ cell tumors (iGCTs) treated with radio-therapy (RT), and to discuss the effects of RT on pituitary functions. Methods: Seventy-seven patients diagnosed with iGCTs who had received RT and endocrine follow-up in Huashan Hospital between January 2010 and July 2017 were retrospectively analyzed, consisting of 49 germinomas and 28 NGGCTs. The median follow-up period was 50.0 months. Fifty-one patients had radiologically proved suprasellar/sellar lesions. Results: The male to female ratio was 62/15. The median endocrine follow-up period was 19 (4, 42) months. The median age at the last endocrine visit was 18 (16, 20) years old. The 5-year overall and recurrence-free survival were both 98.7%. The overall prevalence of central adrenal insufficiency (CAI), central hypothyroidism (CHT), central hypogonadism (CHG), hyperprolactinemia, and central diabetes insipidus (CDI) was 57.3%, 56%, 56.6%, 35.3%, and 52.1%, respectively, after RT. Patients having suprasellar/sellar lesions showed significantly higher post-therapeutic prevalence of hypopituitarism than those who didn’t. Compared to that before RT, CAI, CHT, and CHG weren’t significantly improved while the levels of prolactin and the prevalence of CDI declined significantly ( P = .03 and .001). The radiation doses to pituitary and hypothalamus between those with and without CAI, CHT, and CHG weren’t significantly different. Conclusion: The prevalence of hypopituitarism was high in iGCTs, especially in those with suprasellar/sellar involvement. The levels of prolactin and the prevalence of CDI declined significantly after RT. The hypopituitarism in iGCTs was mainly induced by tumor effects, and RT showed no additional damage to pituitary functions in our study. Abbreviations: AFP = alpha-fetoprotein; CAI = central adrenal insufficiency; CDI = central diabetes insipidus; CHG = central hypogonadism; CHT = central hypothyroidism; CT = computed tomography; DA = dopamine; GH = growth hormone; βHCG = beta-human chorionic gonadotropin; HPA = hypothalamus-pituitary-adrenal; HPG = hypothalamus-pituitary-gonadal; HPL = hyperprolactinemia; HPT = hypothalamus-pituitary-thyroid; iGCT = intracranial germ cell tumor; IGF-1 = insulin-like growth factor 1; NGGCT = nongerminomatous germ cell tumors; OS = overall survival; PFS = progression-free survival; PRL = hypothalamus-pituitary-prolactin; RT = radiotherapy

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Secreting Germ Cell Tumors of the Central Nervous System: A Long-Term Follow-up Experience

Cancers ◽

10.3390/cancers12092688 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2688

Author(s):

Veronica Biassoni ◽

Elisabetta Schiavello ◽

Lorenza Gandola ◽

Emilia Pecori ◽

Geraldina Poggi ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Chemotherapy Response ◽

Disease Extent ◽

Tumor Bed ◽

System A ◽

Long Term Follow Up ◽

The Central Nervous System

Introduction: Due to the rarity of nongerminomatous germ cell tumors (NGGCT) with non-standard treatment as yet, we report retrospectively our 30 year experience with chemotherapy followed by craniospinal irradiation (CSI), plus a boost of whole ventricular irradiation (WVI)/tumor bed (TB), tailored to pre-radiation chemotherapy response. Methods: Between 1988 and 2016, 28 patients received four cycles of PEB (cisplatin/etoposide/bleomycin), then CSI, and two further PEB cycles. Between 1988 and1994, CSI was 25.5 Gy for patients in complete remission (CR), 30 Gy if in partial remission (PR) or metastatic, with a boost to TB up to 45–54 Gy. In the period of 1995–2010, the boost included WVI and any extra-ventricular tumor sites up to 45 Gy. After 2010, CSI was reduced to 25.5 Gy for all non-metastatic patients, and a boost was given only to TB up to 40.5/45.5 Gy, depending on patients’ CR/PR status. After 2003, patients with alfafetoprotein (αFP) > 1000 ng/mL received intensified treatment, also including autologous stem cell transplantation. Results: Among 28 patients (23 males; median age 12 years, 6 metastatic), 25 responded to PEB, and three progressed (PD) after one to four cycles; 26 received radiotherapy obtaining 13 CR, 7 PR and 5 stable disease (SD), 1 PD; 6 (21%) died (5 for disease, 1 for pneumonia while in CR). Five-year overall survival (OS) and progression-free survival (PFS) were both 81%; 10 year OS and PFS 81% and 76%, respectively (median follow-up 11 years). Conclusions: Survival for children with NGGCT, independently from disease extent, was encouraging. Further studies should elucidate which patients could benefit from reduced volume and dose irradiation.

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Serum and Cerebrospinal Fluid Human Chorionic Gonadotropin (hCG) and alpha-fetoprotein (AFP) in Intracranial Germ Cell Tumors

The International Journal of Biological Markers ◽

10.1177/172460080201700206 ◽

2002 ◽

Vol 17 (2) ◽

pp. 112-118 ◽

Cited By ~ 15

Author(s):

E. Seregni ◽

M. Massimino ◽

S. Nerini Molteni ◽

F. Pallotti ◽

B. van der Hiel ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Germ Cell ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Germ Cell Tumors ◽

High Serum ◽

Response To Therapy ◽

Alpha Fetoprotein ◽

Intracranial Germ Cell Tumors

We report a retrospective study on serum and cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) and β-human chorionic gonadotropin (βhCG) determination in a series of 30 patients bearing intracranial germ cell tumors. At diagnosis five patients had high serum and CSF AFP levels. No patient had positive serum AFP and negative CSF AFP or vice versa. Twelve of 30 patients had serum βhCG levels above 5 mIU/mL, eight had high βhCG only in CSF, and ten were completely negative. During treatment and follow-up both markers were accurate indicators of the response to therapy, decreasing rapidly and often becoming normal already after the first phase of treatment. We conclude that these two markers, and mostly βhCG, may be useful in the diagnosis and monitoring of the response to therapy of patients with intracranial germ cell tumors.

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