Induction Chemotherapy Followed by Low-Dose Involved-Field Radiotherapy for Intracranial Germ Cell Tumors

2002 ◽  
Vol 20 (3) ◽  
pp. 857-865 ◽  
Author(s):  
Hidefumi Aoyama ◽  
Hiroki Shirato ◽  
Jun Ikeda ◽  
Kenji Fujieda ◽  
Kazuo Miyasaka ◽  
...  

PURPOSE: To investigate the efficacy of chemotherapy followed by low-dose involved-field radiotherapy for the treatment of intracranial germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty-three patients with GCTs, including 16 pure germinomas, 11 human chorionic gonadotropin-beta (HCG-β)–secreting germinomas, three mixed GCTs composed of immature teratomas plus germinomas (IMT/G), and three highly malignant mixed GCTs, were treated. Etoposide and cisplatin (EP) were used for the treatment of solitary pure germinomas, and ifosfamide, cisplatin, and etoposide (ICE) were used for the treatment of other GCTs. The dose schedule was 24 Gy for germinomas and 40 to 54 Gy for other GCTs. An involved-field set-up was used except for highly malignant GCTs, in which craniospinal irradiation was used. The median follow-up was 58 months (range, 18 to 102 months). RESULTS: Disease-related, overall, and relapse-free survival rates at 5 years were 100%, 93%, and 69% for all patients, 100%, 100%, and 86% for patients with pure germinomas, and 100%, 75%, and 44% for patients with HCG-β-secreting germinomas, respectively. All six patients with nongerminomatous GCTs were alive at the last follow-up. All eight relapses (one pure germinoma, five HCG-β-secreting germinomas, and two IMT/G), except one in a course of salvage treatment, were salvaged and free of disease at the last follow-up. No decline was observed in the full-scale, verbal, or performance intelligence quotient at 12 to 51 months after the treatment in 11 patients. CONCLUSION: Our results support an excellent prognosis after EP and ICE regimens followed by radiotherapy. Dose and volume can be reduced to 24 Gy in 12 fractions and involve a field set-up after EP chemotherapy for the treatment of pure germinomas.

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii334-iii334
Author(s):  
Chengcheng Guo ◽  
Qunying Yang ◽  
Jian Wang ◽  
Yonggao Mou ◽  
Zhongping Chen

Abstract BACKGROUND AND OBJECTIVE Primary intracranial germ cell tumors (PIGCTs) are a group of heterogeneous tumors. It is very difficult to treat those patients without pathological diagnosis. This study retrospectively analyzed the clinical data and outcomes of patients with clinically diagnosed (without histologically confirmed) PIGCTs in SunYat-sen University Cancer Center. METHODS Patients who were clinically diagnosed as PIGCTs without histological diagnosis through surgical resection or biopsy were included in this study. Patients were analyzed for clinical characteristics, treatment patterns, outcomes and adverse effects. RESULTS From May 2002 to July 2014, 74 patients clinically diagnosed with PIGCTs received chemotherapy and/or radiotherapy at the Sun Yat-sen University Cancer Center. The median age was 16.5 years old (4–45 years old, majority was teenagers). The most of tumors were found in male, and located in the pineal and suprasellar regions. When the patients were grouped into diagnostic chemotherapy group (57 cases), diagnostic radiotherapy group (5 cases) and gamma knife radiosurgery group (12 cases) based on their initial anti-tumor therapy. The 5-year survival rates were 84.3%, 75.0% and 75.0%, respectively. There was a trend that the chemotherapy group got a better survival. Patients were allocated to secretory tumor group (49 cases) and non-secretory tumor group (25 cases) based on their levels of tumor makers (α-FP and β-hCG). The 5- year survival rates were 80% and 77.8% (P value = 0.966), respectively. CONCLUSION Clinical diagnosed PIGCT (without histological confirmation) patients may obtain good responses when receiving comprehensive treatments of chemotherapy combined with radiotherapy.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22526-e22526
Author(s):  
Diana Lone ◽  
Karim Thomas Sadak ◽  
Bradley S Miller ◽  
Michelle Roesler ◽  
Jenny N Poynter

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.


1989 ◽  
Vol 70 (5) ◽  
pp. 676-681 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Jun Yoshida ◽  
Junzo Ishiyama ◽  
Satoshi Noda ◽  
Akira Kito ◽  
...  

✓ 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.


2020 ◽  
Vol 26 (12) ◽  
pp. 1458-1468
Author(s):  
Boni Xiang ◽  
Xiaoming Zhu ◽  
Min He ◽  
Wei Wu ◽  
Haopeng Pang ◽  
...  

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


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi216-vi216
Author(s):  
Linbo Cai ◽  
Mingyao Lai ◽  
Juan Li ◽  
Cheng Zhou ◽  
Qingjun Hu ◽  
...  

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.


1999 ◽  
Vol 90 (2) ◽  
pp. 258-264 ◽  
Author(s):  
Keiji Sano

Object. To determine the pathogenesis of intracranial germ cell tumors (GCTs), the author studied 153 cases of these tumors encountered through 1994, 62.7% of which showed monotypic histological patterns and 37.3% of which were shown to be mixed tumors.Methods. Six patients died soon after admission and underwent autopsy; the other patients underwent surgery followed by radio- and/or chemotherapy. One hundred thirty-four cases were followed through the end of 1997. All patients with a choriocarcinoma died within 1 year. Patients with a yolk sac tumor (endodermal sinus tumor) or an embryonal carcinoma also had poor outcomes. Patients with a mature teratoma had 5- and 10-year survival rates of 93% each. Patients with an immature teratoma had 5- and 10-year survival rates of 86% each, whereas patients who had a teratoma with malignant transformation had a 3-year survival rate of 50%. Patients with a germinoma had a 5-year survival rate of 96% and a 10-year survival rate of 93%. These results may bring into question the validity of the germ cell theory because germinoma, which should be the most undifferentiated tumor according to the theory, was the most benign and choriocarcinoma and yolk sac tumor (endodermal sinus tumor), which should be the most differentiated tumors, were the most malignant according to results obtained during the follow-up study.Conclusions. Germ cell tumors other than germinomas may not originate from one single type of cell (primordial germ cells). The embryonic cells of various stages of embryogenesis may perhaps be misplaced in the bilaminar embryonic disc at the time of the primitive streak formation, becoming involved in the stream of lateral mesoderm and carried to the neural plate area to become incorrectly enfolded into the brain at the time of neural tube formation. The author propounds the following hypothesis: tumors composed of cells resembling the cells that appear in the earlier stages of embryogenesis (ontogenesis) are more malignant than those composed of cells resembling the cells that appear in the later stages of embryogenesis.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii330-iii330
Author(s):  
Kyeong-O Go ◽  
Soyoung Ji ◽  
Kihwan Hwang ◽  
Jung Ho Han ◽  
Hyoung Soo Choi ◽  
...  

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.


2002 ◽  
Vol 17 (2) ◽  
pp. 112-118 ◽  
Author(s):  
E. Seregni ◽  
M. Massimino ◽  
S. Nerini Molteni ◽  
F. Pallotti ◽  
B. van der Hiel ◽  
...  

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.


2008 ◽  
Vol 26 (3) ◽  
pp. 421-427 ◽  
Author(s):  
Stéphane Culine ◽  
Andrew Kramar ◽  
Christine Théodore ◽  
Lionel Geoffrois ◽  
Christine Chevreau ◽  
...  

Purpose Two chemotherapy regimens for intermediate- and poor-risk metastatic nonseminomatous germ cell tumors were compared for efficacy and toxicity. Patients and Methods From February 1994 to February 2000, 190 patients were randomly assigned between either four cycles of BEP (bleomycin 30 mg d1, d8, d15; etoposide 100 mg/m2 d1-5; cisplatin 20 mg/m2 d1-5) or four to six alternating cycles of CISCA/VB (cyclophosphamide 400 mg/m2 d1-2, doxorubicin 35 mg/m2 d1-2, cisplatin 100 mg/m2 d3/vinblastine 2.5 mg/m2 d1-5, bleomycin 25 mg/m2 d1-5). Risk was initially defined according to the Institut Gustave Roussy (Villejuif, France) prognostic model based on serum alpha-fetoprotein and human chorionic gonadotropin levels only. Patients were retrospectively assigned into the International Germ Cell Consensus Classification. Results Among 185 assessable patients, favorable responses did not differ statistically between the two arms: 49 in the CISCA/VB arm (56%; 95% CI, 45% to 66%), 57 in the BEP arm (65%; 95% CI, 55% to 75%). The CISCA/VB regimen induced more significant hematologic and mucous toxicities compared with the BEP arm. The 5-year event-free survival rates were 37% (95% CI, 27% to 47%) and 47% (95% CI, 37% to 57%) in CISCA/VB and BEP arms, respectively (hazard ratio [HR] = 0.76; 95% CI, 0.52 to 1.11; P = .15). With a median follow-up of 7.8 years, the 5-year overall survival rates were 59% (95% CI, 47% to 67%) and 69% (95% CI, 58% to 77%) in CISCA/VB and BEP arms, respectively (HR = 0.73; 95% CI, 0.46 to 1.18; P = .24). Conclusion Because of equivalent efficacy and lesser toxicity, the standard treatment for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors remains four cycles of BEP.


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