|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2001 American Society for Clinical Oncology Treatment of Recurrent Malignant Sacrococcygeal Germ Cell Tumors: Analysis of 22 Patients Registered in the German Protocols MAKEI 83/86, 89, and 96From the Department of Pediatric Hematology and Oncology, Children’s Hospital, and the Department of Radiotherapy, Heinrich-Heine-University, Medical Center, Düsseldorf; the Department of Radiotherapy, University of Tübingen; the Department of Pediatric Surgery, Ruhr University Bochum, Marienhospital, Herne; the Department of Pediatric Surgery, University Hospital Mannheim, Germany; and the Department of Pediatric Hematology and Oncology, St. Anna Children’s Hospital, Vienna, Austria. Address reprint requests to D.T. Schneider, MD, Department of Pediatric Hematology and Oncology, Children’s Hospital, Heinrich-Heine-University, Medical Center, Moorenstr. 5, D-40225 Düsseldorf, Germany; email: makei{at}med.uni-duesseldorf.de
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.
THE LAST 20 YEARS have been characterized by a dramatic improvement in the prognosis of malignant germ cell tumors (GCT) in children.1 This has been attributed mainly to the introduction of platinum-containing chemotherapy.1-4 In addition, the use of neoadjuvant strategies in patients with locally advanced or metastatic tumors has resulted in a significantly better outcome for advanced tumor stages with less mutilating surgery.5,6 However, despite overall cure rates of well above 80%, those children that suffer a recurrence after three-agent cisplatinum-based combination chemotherapy and tumor resection have an unfavorable prognosis. Because no reports are available from the literature that evaluate different therapeutic approaches in relapsing pediatric GCT, most patients are treated on an individual basis. Furthermore, to our knowledge, none of the cooperative pediatric GCT study groups (Pediatric Oncology Group, Children’s Cancer Group, United Kingdom Children’s Cancer Study Group [UKCCSG], French Society of Pediatric Oncology, and Maligne Keimzelltumoren [MAKEI]) has developed specific protocols for salvage treatment of extracranial GCT. One may speculate that strategies used in adult recurrent GCT may be applied in children. But in children, the majority of GCT occur at nongonadal sites, whereas more than 90% of GCT in adults develop in the gonads.4 Therefore, the treatment strategies, surgical recommendations, and success rates are different. While even large gonadal (testicular or ovarian) GCT can be completely removed in most patients, the surgical en bloc resection of extragonadal pediatric GCT is often problematic. This is particularly true for sacrococcygeal tumors, which often show local bone involvement, infiltration into the spinal canal or the nerve sheaths of the sacral plexus (G. Calaminus, manuscript submitted for publication).7 As a result, children with relapsing GCT present with a specific clinical picture different from adults. In adult patients, most relapses occur at distant sites such as the retroperitoneal lymph nodes or the lungs, and efforts have been taken to intensify chemotherapy to control systemic disease8,9(for review see Nichols10). In contrast with adult patients, most recurrences of pediatric extragonadal GCT, such as sacrococcygeal tumors, occur at the primary site of the tumor. Incomplete tumor resection represents an important risk factor for relapse of malignant GCT, despite effective cisplatinum-based chemotherapy3,11. This observation suggests that the treatment of recurrent sacrococcygeal GCT must follow a strategy different from treatment strategies in adult patients. We evaluated 22 children with malignant sacrococcygeal GCT and recurrent disease after resection and adjuvant chemotherapy. We analyzed clinical presentation, relapse treatment, and the relative contributions of local and systemic therapy to the success of salvage treatment. Because the cumulative doses of chemotherapy were reduced by 50% during the subsequent MAKEI trials, we also evaluated the influence of the primary treatment on outcome after relapse. The aim of this study is to reveal future strategies for the optimization of primary treatment and follow-up of high-risk patients as well as the improvement of relapse treatment.
The 22 relapse patients analyzed in this study belong to a cohort of 104 patients with malignant sacrococcygeal GCT who have been prospectively enrolled onto the German protocols for children with nontesticular GCT (MAKEI 83/86, 89, 96) of the German Society of Pediatric Oncology and Hematology. Among these 104 patients, five patients had a history of a neonatal sacrococcygeal teratoma and were retrospectively recorded to the MAKEI study after occurrence of malignant histology at relapse. Three patients were not treated according to the guidelines of the protocols and were considered follow-up patients [(no tumor resection: n = 1 ( Table 1: no. 19), no platinum-containing chemotherapy: n = 2)]. The median follow-up period at the time of this report was 49 months (4 months to 149 months).
Informed consent in central data registration and statistical evaluation was obtained. The MAKEI protocols had been approved by the Ethics Committee of the Heinrich-Heine-University, Düsseldorf, Germany.
Clinical Investigations In case of relapse, a complete clinical and radiographic restaging was performed. Local restaging was performed clinically with CT or magnetic nuclear resonance tomography including sagittal images (if available). Abdominal lymph nodes and the parenchymatous organs were assessed with CT and abdominal ultrasound. A chest x-ray was performed to monitor for pulmonary metastasis. If the patient had lung metastasis at initial diagnosis, a chest CT was recommended. Skeletal scintigraphy was performed only in patients with clinical symptoms that indicated possible bone metastasis. Lastly, the tumor markers AFP and human chorionic gonadotropin were evaluated. If the AFP was normal with regard to the age-related normal range, histologic specimens were obtained. In patients with significantly elevated AFP levels, histologic confirmation of relapse was not necessary if radiography was unequivocal.
Histopathology and Staging System The surgical records were evaluated centrally. For initial surgery, tumor resection was considered complete if the tumor, including its pseudocapsule and the coccyx, were resected in toto and without evidence of rupture. Microscopically, the resection margins had to be free of tumor cells (microscopically complete resection). The resection was regarded as microscopically incomplete if there were malignant cells at the resection margins, if the tumor had been removed in more than one piece, or if a tumor cyst had been punctuated or ruptured during surgery. In case of visible tumor residues after surgery, the resection was considered macroscopically incomplete. The extent of relapse surgery was evaluated according to the same standards, and special attention was given to the histologic examination of the resection margins. If the coccyx had not been excised completely during initial surgery, the resection of the remaining coccyx at the sacrococcygeal joint was recommended.
Treatment The MAKEI protocols did not provide a standardized therapeutic approach for patients with recurrent sacrococcygeal GCT. Therapeutic decisions were made with regard to the response to the previous treatment and treatment-related toxicity. Therefore, the therapy given to each individual patient was heterogeneous, particularly during the MAKEI 83/86 protocol. When possible, cisplatinum-based regimen were applied. If cisplatinum administration was impossible because of pretreatment-related toxicity, cisplatinum was replaced with carboplatinum at 600 mg/m2. From the MAKEI 89 protocol on, the combination of cisplatinum, etoposide, and ifosfamide has been applied more often. In some patients who showed poor response to chemotherapy alone, concomitant locoregional hyperthermia was administered. Radiotherapy was administered as external-beam irradiation. One patient received intraoperative brachytherapy.
Statistical Analysis The overall survival (OS) and event-free survival (EFS) were estimated according to the Kaplan and Meier method, the influences of suspected prognostic factors were analyzed with the log-rank test. EFS was calculated as the time from diagnosis to the first relapse or death (death of disease or death of therapy-related complication) or from the first relapse to the next relapse. The other patients were censored at the time of the last reported follow-up examination. P values less than .05 were considered significant.
Primary Treatment and Relapse Pattern At 5 years follow-up, EFS after primary treatment of malignant sacrococcygeal GCT was 0.72 ± 0.05 (78 of 104 patients) and OS was 0.82 ± 0.04 (88 of 104 patients). Four patients died as a result of primary treatment-related complications. Therefore, 22 patients with relapse were analyzed in this study. Among these, three patients showed partial responses to first-line treatment or had progressive disease (Table 1). Only one of these patients (no. 7) finally achieved a long-lasting complete clinical remission (104+ months) after high-dose chemotherapy, salvage surgery, and local irradiation at 50 Gy. Nineteen patients developed a tumor recurrence after a first complete clinical remission. Most relapses occurred within the first year after diagnosis (median, 11 months; range, 5 months to 25 months), and within a median of 5.5 months (range, 0 months to 21 months) after the end of the primary treatment. Seventeen patients had an isolated local recurrence, two patients had isolated distant metastases, and three patients showed a combined relapse with both local recurrence and metastases ( Table 2). The predominant histology of the recurrent tumor was yolk sac tumor (YST, n = 12). Three patients showed a mixed histology with teratoma and YST components. In six patients, the diagnosis was based on radiographic findings and a significant increase of the serum AFP levels, and no histology was obtained before relapse therapy. One patient who developed a relapse as a pure mature teratoma was excluded from the analysis of adjuvant relapse treatment (Tables 1 and 2, no. 15). Only this patient showed age-related normal AFP serum levels at relapse. In all other patients, the relapse was associated with elevated AFP-levels (< 1,000µg/L, n = 10; 1,000µg/L to 10,000µg/L, n = 8; > 10,000 µg/L, n = 3).
The data of the initial tumor staging, the primary therapy, and the achieved clinical status of the 22 patients after first-line treatment are summarized in Table 1. Strikingly, five patients (no. 2, 13, 15, 18, and 22) had a history of neonatal teratoma before the diagnosis of malignant GCT. Three of these patients (no. 13, 15, 18) did not undergo resection of their teratoma until evidence of malignant transformation occurred. Two patients (no. 2, 22) underwent an incomplete resection of their teratoma, did not receive adjuvant chemotherapy, and relapsed with YST histology. For these patients, their first presentation with malignant histology are analyzed (Table 1). Altogether, 17 of 22 patients had a local T2 stage at primary diagnosis, and 10 patients suffered distant metastases (Table 1).
Outcome After Relapse
Seven of nine patients who achieved PR eventually died of tumor progression. One patient achieved a CR, which at the time of this report has continued to 55 months. Another patient finally achieved a CR from her GCT but unfortunately developed a secondary leukemia and died as a result of therapy-related complications following allogeneic bone marrow transplantation. Among the 12 patients who achieved CR after first relapse, seven have remained in continuous CR for a median of 42+ months (range, 22 months to 184+ months) months. Five patients developed a second relapse (or more), but two of these patients were cured (no. 7, 9). Among the three patients who did not achieve CR after primary treatment (no. 7, 8, 12), only one patient with an isolated distant relapse (no. 7) achieved CR with second-line treatment including high-dose chemotherapy. Eventually, this patient developed a second, local relapse and was cured with surgery and local irradiation. The remaining two patients died of tumor progression. At 5 years follow-up, the EFS for all 22 relapse patients was 0.3 ± 0.1 (seven of 22 patients), and the OS was 0.42 ± 0.11 (10 of 22 patients, Fig 2).
Prognostic Parameters for Outcome After Relapse Those patients who achieved a complete clinical remission after the first relapse therapy had a significantly better prognosis than those patients who did not (5-year OS, 0.74 ± 0.13 [nine of 12 patients] v 0.1 ± 0.1 [one of 10 patients], P < .01, log-rank test, Fig 3). The chance of achieving a stable and continuous remission decreased with higher numbers of relapses, but nevertheless, one patient survived after four relapses.
Most of the second or further relapses occurred within the first 6 months after the end of treatment of their first relapse (Table 2). No second (or further) relapse occurred later than 12 months after the diagnosis of the previous relapse. The time of relapse (early, < 1 year after diagnosis, versus late, > 1 year after diagnosis) did not impose a statistically significant influence on outcome. Furthermore, histology of the recurrent tumor, AFP serum levels, and tumor size were not associated with outcome. Only one of five patients (no. 2) with distant metastases at the time of first relapse achieved a continuous CR. The remaining four patients suffered a second relapse, either with distant metastases or as combined local and distant recurrence, and only one of these patients (no. 7) survived after a second, local relapse. Interestingly, all patients with metastases at first relapse received primary treatment according to the MAKEI 83/86 protocol. Otherwise, we found no significant influence of the chemotherapeutic pretreatment on prognosis at first relapse.
Salvage Treatment
Tumor Resection In 16 relapse situations, a primary resection was performed. Among these, six complete resections were reported. In nine relapses, the tumor was excised after preoperative chemotherapy, and resection was complete in four cases. In 13 relapses, no resection was performed. In four relapse situations, no data concerning the timely order of chemotherapy and surgery were available.
Chemotherapy Fifteen relapse situations were available for the analysis of primary chemotherapy. In five relapses, the tumor progressed despite chemotherapy. In 10 relapse situations, chemotherapy resulted in partial remission of the tumor, thus facilitating delayed complete resection, which was followed by a continuous clinical remission in four patients. Two patients (no. 7 and 9) underwent autologous bone marrow transplantation as salvage treatment of their first recurrence, but both patients developed a local second relapse (Table 2). Alternative drugs such as paclitaxel have not been studied.
Locoregional Thermochemotherapy
Radiotherapy
The current literature provides only very limited data concerning therapeutic options and prognosis in recurrent malignant GCT in children. A recent evaluation of the French Society of Pediatric Oncology protocols reported 12 relapses among 21 children with localized, nonmetastatic malignant sacrococcygeal GCT, resulting in a 3-year failure-free survival of 43%.16 This was attributed to the use of carboplatinum (at a single dose of 400 mg/m2 per cycle and a cumulative dose of 1,200 mg/m2) instead of cisplatin, as most of the patients with incomplete response to primary therapy could be cured with cisplatinum chemotherapy. Nevertheless, five of 21 patients died (resulting in a 3-year survival of 86%16), and in multivariate analysis, the sacrococcygeal site was considered prognostically unfavorable. The evaluation of 37 patients with malignant sacrococcygeal GCT treated according to the Children’s Cancer Group protocol also demonstrated an unfavorable prognosis of these tumors compared with their gonadal counterparts. In this subgroup, 23 of 37 patients developed a relapse despite cisplatinum chemotherapy. This article did not provide the survival data of this specific subgroup, but for all 63 nongonadal GCT, the 4-year survival was 42%, thus reflecting the limited impact of salvage therapy on overall survival. Interestingly, this report clearly demonstrated the significant influence of complete tumor resection on prognosis. Recent reports of the British GCI and GCII studies reveal that carboplatinum-based regimens (at a single dose of 600 mg/m2, and a cumulative dose of 3,600 mg/m2) may result in an excellent outcome after sacrococcygeal GCT (5-year EFS, 93% [range, 77% to 98%]).17 In the updated report of the GCII protocol, 37 children with malignant sacrococcygeal GCT were included. All patients received carboplatinum, etoposide, and bleomycin until remission was achieved followed by two additional consolidation courses. Five-year EFS was 86.5% (range, 72% to 94.1%) with a favorable toxicity profile.18 However, survival for sacrococcygeal GCT was only slightly better (87.6%, range, 72.1% to 95.1%).18 This indicates the limited impact of salvage therapy when patients relapsed. Three of five relapse patients received regimens with vincristine, actinomycin, and cyclophosphamide (± doxorubicin) or ifosfamide, vincristine, and doxorubicin. Three of five patients who received platinum-based regimens are alive, and three patients who received other nonplatinum regimens died.18 Summarizing these data, it seems that patients with recurrent malignant sacrococcygeal GCT who have been treated with less-intensive regimens (such as carboplatinum at 400 mg/m2) can be successfully treated with intensification of chemotherapy (eg, by administration of cisplatinum).16 However, treatment of patients with an intensive pretreatment may be problematic.18 The study presented here contributes important additional information as, for the first time, the specific relapse pattern and different therapeutic options in recurrent sacrococcygeal GCT are evaluated. Our data show that the vast majority of patients with recurrent sacrococcygeal GCT present with locoregional recurrence. Interestingly, all patients suffering from distant metastasis at first relapse (no. 2, 3, 4, 6, 7) received primary treatment according to the MAKEI 83/86 protocol. In this protocol, etoposide was not included in the first four cycles of chemotherapy. All of these patients had major residues after resection at diagnosis or did not undergo primary tumor resection, and all had either lymph node (no. 2, 4) or distant metastasis (no. 2, 3, 6, 7) at diagnosis. Conversely, none of the 67 patients registered until this analysis on the MAKEI 89 and 96 protocols showed distant metastasis at first relapse. This cohort includes 12 patients with lymph node metastases and 18 patients with distant metastases. Therefore, the exclusion of etoposide from the initial chemotherapy may have resulted in an inferior systemic tumor control. In addition to these patients, our recent analysis of primary mediastinal GCT included one patient who developed an isolated distant relapse (brain metastasis).6 This patient was also treated according to the MAKEI 83/86 protocol and was cured with etoposide-containing chemotherapy (second CR > 12 years). In conclusion, the analysis of these relapse patients underlines the importance of a platinum- and etoposide-based first-line chemotherapy. A recent analysis of sacrococcygeal GCT reveals that insufficient local therapy represents one important risk factor of recurrence.11 However, 19 of 22 patients with locally infiltrating and metastatic stage T2 M1 tumors were cured with preoperative chemotherapy followed by a delayed tumor resection (5-year EFS: 83%). This also indicates that cisplatinum and etoposide chemotherapy results in sufficient control of metastases.11 In addition, our data suggest that compared with GCT in adults, resistance to cisplatinum seems to play only a minor role in the development of recurrent disease. Only three of 104 registered patients did not achieve CR after primary treatment. Furthermore, the analysis of relapse situations in which primary chemotherapy was administered showed a favorable response to chemotherapy in 10 of 15 relapses. Lastly, the French and British data also support that cisplatinum-based or carboplatinum regimens (at 600 mg/m2) are effective.16,18 In the perspective of these data, it can be concluded that children with recurrent GCT may benefit from intensification of local treatment rather than systemic treatment. This can be achieved by third-look surgery, locoregional hyperthermia, or irradiation. Therefore, we analyzed for the first time the relative contributions of the different therapeutic modalities to the prognosis in recurrent malignant sacrococcygeal GCT. Our data demonstrate that the complete resection of the recurrent tumor represents the cornerstone of salvage treatment. Therefore, the diagnostic work-up at relapse must include an accurate evaluation of the surgical options, because in rare patients with a small circumscribed recurrence detected at a very early stage, surgery alone may be sufficient. One girl with a small relapsing YST (no. 22) achieved a continuous CR after complete resection with wide resection margins. However, patient no. 9 impressively demonstrates that even high-dose chemotherapy does not overcome insufficient local tumor control. This patient finally achieved a continuous CR after five surgical procedures and 95 Gy of local irradiation. Patient no. 7, who suffered a progressive lung metastasis under first-line treatment, illustrates that high-dose chemotherapy may substantially contribute to systemic tumor control. But when this patient developed a second, local relapse, a long-term remission was achieved with surgery and local irradiation (50 Gy) without additional systemic chemotherapy. Nevertheless, most patients present with locally advanced tumors. In these patients, preoperative chemotherapy helps to reduce the tumor size and allows for complete surgical resection. Studies in adult patients with recurrent GCT and the data of first-line treatment in pediatric GCT suggest that cisplatinum-containing regimens or carboplatinum regimens at doses of 600 mg/m2 (UKCCSG study) represent the best regimens currently available for the treatment of recurrent GCT. The therapeutic decision must be based on an individual basis, considering the patient’s specific toxicity of the previous chemotherapy. In some patients, it may be necessary to replace cisplatinum with carboplatinum because of significant preexisting renal damage or hearing loss. However, myelotoxicity of carboplatinum may be significant.18 As etoposide and ifosfamide have been shown to have significant single agent efficacy in recurrent GCT, a combination of cisplatinum with the two drugs appears advisable.10,19 For instance, most RHT patients received this combination. In our analysis, high-dose chemotherapy has not proven useful unless a local cure is achieved. Nevertheless, it may be helpful to harvest hematopoietic stem cells early in relapse treatment, which can be used for stem-cell support in patients suffering from prolonged myelosuppression after conventional chemotherapy. This strategy may help to ensure sufficient treatment intensity and to avoid significant delays of the cytostatic treatment. Patients who respond poorly to salvage therapy may benefit from RHT. This observation is supported by two previously published reports of our study group.20,21 One study evaluated 10 patients with abdominal and pelvic GCT enrolled on a phase I/II study of RHT as adjuvant treatment of recurrent GCT. In this study, response to RHT was achieved in seven of 10 patients (CR: five patients, PR: two patients).20 Another study evaluated nine RHT patients and 23 matched non-RHT patients. The EFS for RHT patients was 0.41 ± 0.33 (five of nine patients) compared with 0.16 ± 0.25 (five of 23 patients) for the non-RHT patients.21 An important observation of these studies was that some patients with local recurrence could be cured with RHT despite insufficient response to previous cisplatinum chemotherapy. Again, both studies show that children with recurrent malignant GCT face an unfavorable prognosis unless sufficient local tumor control is achieved. In addition, the data presented in this article reveal that the success rate of RHT is better when RHT is applied in early relapse situations. This may be because the intensive pretreatment results in prolonged myelosuppression that causes significant delays in chemotherapy. Even in low-risk patients, a significant delay of chemotherapy of more than 7 days adversely influences outcome.22 This observation has led to the inclusion of RHT for advanced and poorly responding GCT into the primary treatment regimens of the current MAKEI 96 protocol.
All patients must receive a complete resection of residual tumor and adjacent structures after preoperative chemotherapy. Those patients in whom the coccyx has not been removed during primary treatment should undergo an in toto resection of the coccyx at the sacrococcygeal joint, because intraosseous spread may have occurred (G. Calaminus, manuscript submitted for publication). Because the completeness of salvage surgery is an important prognostic parameter and because the resection is often complicated by growth within the nerve sheaths of the sacral plexus, a referral to pediatric surgical centers specialized in this specific procedure is strongly encouraged. In patients in whom a complete salvage resection is not obtained, a high dose of postoperative local irradiation of As the study presented here represents no standardized or even randomized therapeutic trial for relapse treatment, our data cannot answer the question whether RHT or radiotherapy will be more beneficial. However, both therapeutic modalities have mostly been used in different clinical situations. RHT was often administered concomitant to preoperative chemotherapy, whereas radiotherapy was given postoperatively after incomplete resec-tions. Therefore, both modalities may show additional efficacy when administered in a combined or sequential approach. Fig 4 presents a proposed rational for the therapeutic strategies in relapsing sacrococcygeal GCT that is based on the reported observations. It is important to bear in mind that the chance of cure decreases with further relapses. Therefore, it is crucial to promote a stringent therapeutic concept to avoid significant treatment delays, and most important, to achieve local tumor control. Future studies will show if the incorporation of salvage strategies into cooperative protocols will substantially contribute to a further improvement of the prognosis of children with malignant GCT.
This work was supported by the Deutsche Krebshilfe e.V., Bonn, Germany. We thank Susanne Dippert and Carmen Teske for expert data management, Carmen Grüttner for secretarial assistance, and Dr Michael Fritsch for his valuable contributions to this manuscript.
1. Mann JR, Stiller CA: Changing pattern of incidence and survival in children with germ cell tumours (GCTs), in Jones WG, Harnden P, Appleyard I (eds.): Germ Cell Tumours III. Oxford, England, Elsevier Science Ltd, 1994, pp 152-158 2. Marina N, Fontanesi J, Kun L et al: Treatment of childhood germ cell tumors: Review of the St. Jude experience from 1979 to 1988. Cancer 70:2568-2575, 1992 3. Ablin AR, Krailo MD, Ramsay NK et al: Results of treatment of malignant germ cell tumors in 93 children: A report from the Children’s Cancer Study Group. J Clin Oncol 9: 1782-1792, 1991[Abstract]
4.
Göbel U, Schneider DT, Calaminus G, et al: Germ-cell tumors in childhood and adolescence. Ann Oncol 11: 263-271, 2000 5. Mauz-Körholz C, Harms D, Calaminus G, et al: Primary chemotherapy and conservative surgery for vaginal yolk-sac tumour: Maligne Keimzelltumoren Study Group. Lancet 355: 625, 2000 (letter)[Medline]
6.
Schneider DT, Calaminus G, Reinhard H et al: Primary Mediastinal Germ Cell Tumors in Children and Adolescents: Results of the German Cooperative Protocols MAKEI 83/86, 89, and 96. J Clin Oncol 18: 832-839, 2000 7. Kaste SC, Bridges JO, Marina NM: Sacrococcygeal yolk sac carcinoma: Imaging findings during treatment. Pediatr Radiol 26: 212-219, 1996[Medline] 8. Bokemeyer C, Kollmannsberger C, Harstrick A, et al: Treatment of patients with cisplatin-refractory testicular germ cell cancer: German Testicular Cancer Study Group (GTCSG). Int J Cancer 83: 848-851, 1999[Medline] 9. Siegert W, Rick O, Beyer J: High-dose chemotherapy with autologous stem cell support in poor-risk germ cell tumors. Ann Hematol 76: 183-188, 1998[Medline] 10. Nichols CR: Treatment of recurrent germ cell tumors. Semin Surg Oncol 17: 268-274, 1999[Medline] 11. Göbel U, Schneider DT, Calaminus G, et al: Multimodal treatment of malignant sacrococcygeal germ cell tumors: A prospective analysis of 95 patients of the German cooperative protocols MAKEI 83/86, 89 and 96. Proc Am Soc Clin Oncol 19: 587a, 2000 (abstr 2309) 12. Mostofi FK, Sobin LH: Histopathological typing of testis tumors. Geneva, Switzerland, World Health Organization, 1993 13. UICC Tumor-Node-Metastasis Atlas: Illustrated Guide to the Tumor-Node-Metastasis/pTNM Classification of Malignant Tumours (ed 3). New York, NY, Springer, 1992 14. Russell WO, Cohen J, Enzinger F, et al: A clinical and pathological staging system for soft tissue sarcomas. Cancer 40: 1562-1570, 1977[Medline] 15. Göbel U, Calaminus G, Teske C et al: BEP/VIP in children and adolescents with malignant non testicular germ cell tumors: A comparison of the results of treatment of therapy studies MAKEI 83/86 and 89P/89. Klin Pädiatr 205: 231-240, 1993[Medline]
16.
Baranzelli MC, Kramar A, Bouffet E, et al: Prognostic factors in children with localized malignant nonseminomatous germ cell tumors. J Clin Oncol 17: 1212-1219, 1999 17. Mann JR, Raafat F, Robinson K et al: UKCCSG’s germ cell tumour (GCT) studies: Improving outcome for children with malignant extracranial nongonadal tumours—Carboplatin, etoposide, and bleomycin are effective and less toxic than previous regimens. United Kingdom Children’s Cancer Study Group. Med Pediatr Oncol 30: 217-227, 1998[Medline] 18. Mann JR, Raafat F, Robinson K et al: The United Kingdom Children’s Cancer Study Group’s Second Germ Cell Tumor Study: Carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity. J Clin Oncol. 18: 3809-3818, 2000
19.
McCaffrey JA, Mazumdar M, Bajorin DF et al: Ifosfamide- and cisplatin-containing chemotherapy as first-line salvage therapy in germ cell tumors: Response and survival. J Clin Oncol 15: 2559-2563, 1997 20. Wessalowski R, Kruck H, Pape H, et al: Hyperthermia for the treatment of patients with malignant germ cell tumors: A phase I/II study in ten children and adolescents with recurrent or refractory tumors. Cancer 82: 793-800, 1998[Medline] 21. Wessalowski R, Blohm M, Calaminus G et al: Treatment results in children and adolescents with loco-regional recurrences of abdominal germ cell tumors (GCTs): A pilot-study with PEI chemotherapy and regional deep hyperthermia (RHT) in comparison to a matched cohort. Klin Pädiatr 209: 250-256, 1997[Medline] 22. Motzer RJ, Geller NL, Bosl GJ: The effect of a 7-day delay in chemotherapy cycles on complete response and event-free survival in good-risk disseminated germ cell tumor patients. Cancer 66: 857-861, 1990[Medline] 23. Calaminus G, Bamberg M, Baranzelli MC, et al: Intracranial germ cell tumors: A comprehensive update of the European data. Neuropediatrics. 25: 26-32, 1994 Submitted September 26, 2000; accepted December 27, 2000.
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
2 test was applied. Numerical data were calculated with the Mann-Whitney U rank test. Complete remission was defined as normalization of the AFP tumor marker (< 10 µg/L or below the age-related reference value) and absence of suspicious structures in CT or magnetic nuclear resonance imaging. Partial remission was defined as AFP decline and reduction of tumor size by at least 50%. Tumors showing less response to chemotherapy or a regrowth of tumor within 4 weeks after the last cisplatinum chemotherapy were considered progressive disease. 
45 Gy (three of six irradiations) achieved a CR. Another patient (no. 9) received an additional 50 Gy brachytherapy and achieved a stable CR after final surgery and adjuvant chemotherapy. Taken together, four of six patients with high dose irradiation have remained disease free for 46+ months to 104+ months. 
