Treatment of Recurrent Malignant Sacrococcygeal Germ Cell Tumors: Analysis of 22 Patients Registered in the German Protocols MAKEI 83/86, 89, and 96

2001 ◽  
Vol 19 (7) ◽  
pp. 1951-1960 ◽  
Author(s):  
D. T. Schneider ◽  
R. Wessalowski ◽  
G. Calaminus ◽  
H. Pape ◽  
M. Bamberg ◽  
...  

PURPOSE: To evaluate therapeutic options for recurrent malignant sacrococcygeal germ cell tumors (GCT) following three-agent, cisplatinum-based, first-line chemotherapy and tumor resection. PATIENTS AND METHODS: Twenty-two patients were evaluated in 22 first-, 14 second-, five third-, and two fourth-relapse situations. One patient, who relapsed with pure teratoma, was excluded from the analysis of adjuvant treatment. RESULTS: Seventeen patients presented with an isolated local recurrence, two patients showed a distant relapse, and three patients suffered from a combined local and distant recurrence. Twelve patients achieved complete remission (CR) after surgery (n = 12) and adjuvant platinum chemotherapy (n = 10). Seven of these patients remain in continuous CR, and five patients relapsed. All patients who achieved only a partial remission developed a second relapse. Three of 14 patients could be cured after a second (or further) relapse. Altogether, 10 patients survived disease free, and 12 patients died as a result of tumor progression (n = 11) or therapy-related complications (n = 1). The completeness of salvage surgery and clinical remission status after first salvage treatment were the most important prognostic parameters. In addition, patients in first or second relapse with locally advanced or poorly responding tumors benefited from preoperative chemotherapy in combination with regional hyperthermia (RHT). In some patients after microscopically incomplete resection, irradiation at doses > 45 Gy contributed to a favorable outcome. CONCLUSION: The complete resection of the local recurrence represents the cornerstone of salvage treatment. Preoperative platinum-based chemotherapy, combined with RHT in some patients, facilitates complete tumor resection. Radiotherapy should be reserved for those patients with microscopically incomplete tumor resection. As the chance of cure decreases with further relapses, it is important to establish a stringent therapeutic strategy to avoid significant treatment delays and, most importantly, insufficient local therapy.

2000 ◽  
Vol 18 (6) ◽  
pp. 1181-1186 ◽  
Author(s):  
Pierluigi Porcu ◽  
Sumeet Bhatia ◽  
Matt Sharma ◽  
Lawrence H. Einhorn

PURPOSE: To identify therapy-related or patient-related characteristics that predict response and long-term survival after failure of high-dose chemotherapy (HDCT) for germ cell tumors (GCT). PATIENTS AND METHODS: Between 1986 and 1997, 101 GCT patients relapsed after high-dose carboplatin and etoposide (VP-16) at Indiana University (Indianapolis, IN). Median time to relapse was 10 months (range, 1 to 17 months). HDCT was the first salvage treatment in 29 patients and second or later salvage treatment in 72 patients. RESULTS: Fifty-four of 101 patients received post-HDCT treatment. Of these, 47 received chemotherapy, alone (n = 35) or in combination with surgery (n = 12). Seven patients underwent surgery alone. There were only 12 objective responses (three complete and nine partial responses) for 66 chemotherapy regimens given to 47 patients, for an overall response rate of 18.2%. Fifteen patients received platinum-based chemotherapy, with only one objective response. Chemotherapy was discontinued in 17% of cases because of toxicity. A longer interval between HDCT and post-HDCT treatment was the only variable that was associated with response. Five patients (4.9%) are disease-free at 30, 53, 57, 85, and 93 months after relapse. Of these, three responded to oral VP-16 and underwent resection of residual mediastinal, retroperitoneal, and inguinal cancer, respectively. One had resection of residual mediastinal yolk sac tumor, followed by oral VP-16. One relapsed with teratoma and received thoracoabdominal resection without chemotherapy. CONCLUSION: Patients who experience disease progression after HDCT often receive further chemotherapy and/or surgery. Chemotherapy resulted in a response rate of less than 20%, with only three complete responses. All of the long-term survivors (4.9%) had surgery as a component of their post-HDCT regimen.


2000 ◽  
Vol 18 (4) ◽  
pp. 832-832 ◽  
Author(s):  
Dominik T. Schneider ◽  
Gabriele Calaminus ◽  
Harald Reinhard ◽  
Peter Gutjahr ◽  
Bernhard Kremens ◽  
...  

PURPOSE: To evaluate children and adolescents with primary mediastinal teratoma and malignant germ cell tumors (GCTs).PATIENTS AND METHODS: Forty-seven patients from the German nontesticular GCT studies were analyzed (median age, 2.5 years; range, neonate to 17 years). Teratoma (n = 21) were resected, and no adjuvant treatment was given. Malignant GCTs (n = 26) were treated with cisplatin-based chemotherapy and resection. Three of 26 patients underwent radiotherapy.RESULTS: In all patients with teratoma, tumor markers were normal. Surgery of teratoma was complete in 17 of 21 patients and microscopically incomplete in four of 21 patients, and we observed no relapse after a median follow-up of 29 months. In 23 of 26 patients with malignant GCTs, alpha-fetoprotein and/or beta-human chorionic gonadotropin were elevated. Twelve of 26 patients received adjuvant chemotherapy after initial resection, which was complete in six of 12 patients, whereas delayed resection after preoperative chemotherapy was complete in 10 of 11 patients (P = .03). Four of six patients underwent second-look thoracotomy after incomplete primary surgery. Three of 26 patients did not undergo tumor resection. The final completeness of resection was the strongest prognostic indicator (event-free survival [EFS], 0.94 ± 0.06 v 0.42 ± 0.33; P < .002). Local stage and distant metastases were not prognostically significant at the .05 level. For all malignant GCTs, the 5-year survival rate was 0.87 ± 0.05 (median follow-up, 51 months), with an EFS of 0.83 ± 0.05.CONCLUSION: The prognosis of mediastinal teratoma is excellent after complete or microscopically incomplete resection. In children with malignant GCT, the prognosis is favorable with a therapeutic strategy of delayed resection after preoperative chemotherapy. In most children, the diagnosis can be based on elevated tumor markers and imaging. Biopsy is indicated in nonsecreting GCT.


2001 ◽  
Vol 19 (7) ◽  
pp. 1943-1950 ◽  
Author(s):  
U. Göbel ◽  
D. T. Schneider ◽  
G. Calaminus ◽  
H. Jürgens ◽  
H. J. Spaar ◽  
...  

PURPOSE: To evaluate a multimodal approach including surgery and cisplatinum chemotherapy for treatment of children with malignant sacrococcygeal germ cell tumors (GCT) and to compare adjuvant and neoadjuvant strategies in advanced tumors. PATIENTS AND METHODS: Between 1983 and 1995, 71 patients with malignant sacrococcygeal GCT were prospectively enrolled onto the German protocols for nontesticular GCT Maligne Keimzelltumoren 83/86 and 89. Five patients who received no chemotherapy (n = 2) or nonplatinum chemotherapy (n = 2) or who did not undergo tumor resection (n = 1) were excluded from this analysis. Among the 66 patients analyzed were 14 boys and 52 girls. The median age was 17.4 months (range, 7 months to 119 months). Median follow-up was 79 months (range, 4 months to 145 months). RESULTS: Fifty-two patients presented with locally advanced stage T2 tumors, and 30 patients had distant metastases at diagnosis. Patients received a median of eight cycles (range, four to nine cycles) of cisplatinum-based chemotherapy. Thirty-five patients underwent tumor resection at diagnosis and received adjuvant cisplatinum-based chemotherapy (group A). Thirty-one patients received up-front chemotherapy followed by delayed tumor resection (group B). Group B included more metastatic tumors than group A (group B, 19 of 31 patients; group A, 11 of 35 patients, P = .01). Preoperative chemotherapy facilitated complete tumor resections (group B, 20 of 31 patients; group A, five of 35 patients, P < .001) and avoided second-look surgery. Metastases at diagnosis and completeness of the first attempt of tumor resection were significant prognostic predictors; however, metastases were not predictive for patients treated with up-front chemotherapy. At 5 years follow-up, event-free survival was 0.76 ± 0.05 (50 of 66 patients), and overall survival was 0.81 ± 0.05 (54 of 66 patients). Four patients died as a result of therapy-related complications, and eight patients died of their tumors. Patients with locally advanced and metastatic tumors (T2b M1) fared better with neoadjuvant treatment [overall survival: 0.83 ± 0.09 (16 of 19 patients) versus 0.45 ± 0.15 (five of 11 patients), P = .01]. CONCLUSION: Even locally advanced and metastatic sacrococcygeal GCT can be successfully treated with up-front cisplatinum-based chemotherapy followed by delayed but complete tumor resection.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii329-iii329
Author(s):  
Hiroki Yamada ◽  
Tomohiro Abiko ◽  
Hirokazu Fujiwara ◽  
Kazunari Yoshida ◽  
Hikaru Sasaki

Abstract INTRODUCTION Germ cell tumors in the central nervous system (CNS) typically arise either at suprasellar and/or pineal region, and occasionally at basal ganglia. We report a case of diagnostically challenging, recurrent germ cell tumor presented with diffuse intraaxial abnormality in and across the lower brainstem, which was diagnosed by the elevated placental alkaline phosphatase (PLAP) level in cerebrospinal fluid (CSF). CASE DESCRIPTION: A 28-year-old man had been treated by chemoradiotherapy at the previous hospital for bifocal suprasellar and pineal lesions with the provisional diagnosis of germinoma without histological confirmation. Three years later, he presented with progressive weakness of bilateral extremities for weeks. Magnetic resonance imaging showed a diffuse, bilaterally symmetric high intensity lesion on T2-weighted image with slight contrast enhancement across the ventral side of the medulla oblongata to the upper cervical spinal cord. Serum and CSF hCG, hCG-β, and AFP were all negative. Since the image findings were atypical for recurrent germ cell tumor, some kind of myelitis was initially suspected. Therefore, steroid pulse therapy was administered. However, the patient’s symptom was still gradually progressing. Then, the CSF PLAP turned out to be positive, indicating the recurrence of germinoma. Accordingly, platinum-based chemotherapy was administered, and the imaging findings, patient’s symptoms, and CSF PLAP began to improve. The patient is to be treated with radiotherapy following chemotherapy. CONCLUSION We report a rare case of CNS germ cell tumor that presented with diffuse intraaxial lesion in the lower brainstem in which examination of CSF PLAP was extremely useful.


2001 ◽  
Vol 19 (1) ◽  
pp. 81-88 ◽  
Author(s):  
O. Rick ◽  
C. Bokemeyer ◽  
J. Beyer ◽  
J. T. Hartmann ◽  
N. Schwella ◽  
...  

PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m2, ifosfamide 5 × 1.2 g/m2, and cisplatin 5 × 20 mg/m2 (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m2 × 3, etoposide 600 mg/m2 × 4, and thiotepa 150 to 250 mg/m2 × 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m2 and ifosfamide 5 g/m2 (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects. CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.


2004 ◽  
Vol 22 (18) ◽  
pp. 3713-3719 ◽  
Author(s):  
O. Rick ◽  
C. Bokemeyer ◽  
S. Weinknecht ◽  
J. Schirren ◽  
T. Pottek ◽  
...  

Purpose To assess the role of residual tumor resection performed after high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ cell tumors (GCT). Patients and Methods Between July 1987 and October 1999, postchemotherapy resections of residual tumors were performed in 57 patients who had been treated with HDCT for relapsed or refractory GCT and who had achieved a partial remission to this treatment. Results Complete resections of residual masses were achieved in 52 (91%) of 57 patients who were rendered disease free; in five (9%) of 57 patients, the resections were incomplete. Resection of a single site was performed in 39 (68%) of 57 patients, and the remaining 18 (32%) of 57 patients required interventions at two or more residual tumor sites. Necrosis was found in 22 (38%) of 57 patients, mature teratoma with or without necrosis was found in nine (16%) of 57 patients, and viable cancer with or without additional necrosis or mature teratoma was found in 26 (46%) of 57 patients. Viable cancer consisted either of residual germ cell or undifferentiated cancer in 22 (85%) of 26 patients, with additional non-GCT histologies in the remaining four patients. Patients with viable cancer had a significantly inferior outcome after surgery compared with patients with necrosis and/or mature teratoma even if all cancer was completely resected. Pulmonary lesions with a diameter of more than 2 cm were the only predictive variable for viable cancer in univariate analysis. Conclusion Resections of all residual tumors should be attempted in patients with relapsed or refractory GCT and partial remissions after HDCT.


2019 ◽  
Vol 37 (26) ◽  
pp. 2329-2337 ◽  
Author(s):  
Samuel A. Funt ◽  
Sujata Patil ◽  
Darren R. Feldman ◽  
Robert J. Motzer ◽  
Dean F. Bajorin ◽  
...  

PURPOSE In men with metastatic germ cell tumors (GCTs), risk-directed treatment is determined, in part, by a distinction between seminoma and nonseminomatous GCT (NSGCT). The importance of NSGCT cell type is uncertain. We evaluated the long-term impact of teratoma on survival in patients with NSGCT. METHODS Prechemotherapy, primary tumors from patients who received platinum-based chemotherapy were studied, and the histology was confirmed by a genitourinary pathologist. The cumulative incidence of disease-related death (CIDD) was the primary end point, and a competing-risk analysis was performed. RESULTS Tumors were available from 232 patients, including 193 with NSGCT. An element of teratoma was present in 82 NSGCT primary tumors (42%). With a median follow-up of 17 years (range, 0.3 to 35 years), 58 patients with NSGCT died, 47 as a result of GCT and 11 as a result of other causes. Most GCT deaths occurred within the first 5 years and were associated with pretreatment risk status ( P < .001). Death as a result of other causes rose steadily after 15 years and was not associated with risk status ( P = .66). A higher CIDD was observed in patients who had NSGCT with teratoma than those with NSGCT without teratoma and seminoma (5-year CIDD rate, 27.4%, 17.4%, and 10.3%, respectively; P = .03). A higher CIDD was observed in patients who had NSGCT with mature teratoma compared with those with either NSGCT with immature teratoma or NSGCT without teratoma (5-year CIDD rate, 38.1%, 19.9%, and 17.4%, respectively; P = .01). CONCLUSION The presence of teratoma, particularly mature teratoma, in an NSGCT primary tumor is associated with a higher CIDD, consistent with the hypothesis that differentiation is associated with adverse outcomes. Death as a result of non-GCT causes is not associated with risk status and must be separated from GCT death when evaluating long-term survival.


2008 ◽  
Vol 2 (5) ◽  
pp. 331-338 ◽  
Author(s):  
Rémy Noudel ◽  
Mathieu Vinchon ◽  
Patrick Dhellemmes ◽  
Claude Fabien Litré ◽  
Pascal Rousseaux

Object In this study, the authors report their experience with the surgical treatment of intracranial teratomas with an emphasis on the indications for delayed resection after oncological treatment. Methods The authors retrospectively reviewed the cases of 14 children with intracranial teratomas. The mean age at diagnosis was 10.5 years (range 2 days–18 years), and 11 patients were male. The final histological analysis revealed pure mature teratoma in 5 cases, mixed teratoma with germinoma in 3 cases, and nongerminomatous malignant germ cell tumor in 6 cases. Thirteen patients underwent tumor resection, and these patients were divided into 2 subgroups according to the timing of surgery. In Group A, 10 patients underwent resection as the primary treatment because no tumor markers were detected in 4 patients, a teratomatous component was revealed on biopsy sampling in 3 patients, and a large tumor volume in 3 patients. In Group B, 3 patients underwent removal of residual pure mature teratoma after oncological treatment. Results Seven of the 8 patients (87.5%) with pure mature teratomas or with mixed teratoma and germinoma are currently alive (mean follow-up of 9 years); the eighth patient died of postoperative meningitis. Two of the 6 patients (33%) with mixed nongerminomatous malignant germ cell tumors died of tumor progression regardless of the timing of surgery. Conclusions The results of this study support the belief that microsurgical removal is the only effective treatment for intracranial teratomas. Surgery may be performed as the primary therapy when there is evidence of a noninvasive teratoma, and as a secondary therapy if there is only a partial response to neoadjuvant therapy or if progression is observed in mixed malignant germ cell tumors.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13027-e13027
Author(s):  
Dawn QQ Chong ◽  
Iain BeeHuat Tan ◽  
Daniel HY Tan ◽  
Eu Tiong Chua ◽  
Chee Kian Tham

e13027 Background: Intracranial germ cell tumors (GCTs) represent up to 11 percent of pediatric central nervous system (CNS) tumors in Asia. We compared the efficacy of radiotherapy alone (RT) with platinum-based chemotherapy (CT) in combination with dose-attenuated RT. Methods: We identified 61 patients treated at National Cancer Centre Singapore from 1995 to 2011. Patient’s demographics, histopathologic characteristics and survival data were collected. Median follow up was 39 months. Results: Forty-eight (79%) patients were male; mean age at diagnosis was 17 years. Most (87%) patients had pineal or suprasellar tumors. The distribution of pure germinomas, non-germinomatous tumors and mixed tumors was 54 (89%), 5 (8%) and 2 (3%) patients, respectively. Twenty patients had RT alone, 2 had CT alone, and 31 received a combination of CT and attenuated RT. There was no difference in overall survival (OS) between unifocal or multifocal disease (p = 0.81). Amongst the germinomas, there was no difference in OS between patients given RT alone and CT combined with attenuated RT (median OS not reached vs 145 months, respectively, p = 0.668). Conclusions: Treatment with CT followed by dose attenuated RT is an alternative to conventional craniospinal RT and did not compromise survival in patients with germinomas. This may represent a therapeutic modality with a more favorable long term toxicity profile in these patients who have excellent long term outcomes.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16048-e16048
Author(s):  
Anand Sharma ◽  
David Palmer ◽  
Hannah Brown ◽  
Sophie Merrick ◽  
Andrew Gogbashian ◽  
...  

e16048 Background: Germ cell tumours (GCT) are predominantly a disease of the young, with < 10% of cases being diagnosed at ≥45 years. Platinum based chemotherapy is the gold standard in treating these patients. Data regarding outcomes and treatment toxicities in elderly patients is lacking. We studied the efficacy, toxicities and survival rates in a cohort of men diagnosed with GCT aged ≥45 years receiving chemotherapy in a metastatic setting. Methods: Data was collected retrospectively from 48 patient’s ≥45 years with GCT’s identified at Mount Vernon Cancer Centre, London. The histology, stage and international germ cell consensus (IGCC) risk classification was identified in all patients. Data was collected regarding chemotherapy regimens, number of cycles completed, toxicities and complications that led to treatment modifications or early cessation. Treatment toxicities were evaluated using the common terminology criteria for adverse events (ctCAE) grading. We then assessed progression free survival, relapse rates and overall survival (OS). Results: We identified 48 patients diagnosed with GCTs aged ≥45 years. The median age at diagnosis was 52 (range 45-70) and 75% of patients were aged ≥50. Classic seminoma and nonseminomatous GCTs were seen in 65% and 35% of patients, respectively. 75% of patients were ≥stage II at diagnosis. In total 29 patients received BEP, 4 EP, 7 Carboplatin AUC10, 2 Carboplatin AUC7 and 5 received POMBACE. 73 % (35/48) of patients experienced one or more complication/s from chemotherapy (15/48 ctCAE grade ≥3), of which the most common were neuropathies (27%), thromboembolism (10%) and tinnitus (10%). In 8 cases omissions or dose reductions had to be made and treatment delays occurred in 3 cases. Only 2 patients did not complete all intended cycles. Over 70% (35/48) of patients had an OS of > 5 years. One patient died during chemotherapy due to gastro-intestinal bleed. Conclusions: Survival rates in patients with GCTs aged ≥45 treated with chemotherapy are good with the majority achieving a > 5 year OS. Although age is not a prognostic factor, these patients are more prone to toxicities and have underlying comorbidities. This data will be of value to oncologists weighing up the risks versus benefits of treatment in this older cohort of patients in combination with similar studies.


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