Fertility and prognosis assessment between bleomycin/etoposide/cisplatin and paclitaxel/carboplatin chemotherapy regimens in the conservative treatment of malignant ovarian germ cell tumors: a multicenter and retrospective study.

OBJECTIVE: To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (PC) chemotherapy regimens on the fertility and prognostic outcomes in malignant ovarian germ cell tumor (MOGCT) patients who underwent fertility-sparing surgery (FSS). METHODS: A propensity score matching algorithm was performed between the BEP and PC groups. The χ² test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS) and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factor of DFS. RESULTS: We included 213 patients, 185 (86.9%) underwent BEP chemotherapy, and 28 (13.1%) underwent PC chemotherapy. The median age was 22 years (range, 8-44 years), and the median follow-up period was 63 months (range, 2-191 months). Fifty-one (29.3%) patients had a pregnancy plan, and 35 (85.4%) delivered successfully. In the before and after propensity score matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during-pregnancy status, and live birth between the BEP and PC groups (p>0.05). Fourteen (6.6%) patients experienced recurrence, including 11 (5.9%) in the BEP group and 3 (10.7%) in the PC group. Four (1.9%) patients in the BEP group died. Kaplan-Meier analysis revealed no significant differences in DFS (p=0.328) and OS (p=0.446) between the BEP and PC groups, and the same survival results were observed in the after matching cohort. CONCLUSION: The PC regimen is as safe as the BEP regimen for MOGCT patients with fertility preservation treatment, and no differences were observed in fertility and clinical prognosis.

Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases.

BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.

Cisplatin for testicular germ cell tumors: a rapid review.

OBJECTIVE: Cisplatin is one of efficacious medicines for TGCT, but is not in 18th WHO EML now. The Union for International Cancer Control recommended cisplatin to the 19th WHO EML for TGCT. To evaluate the effectiveness, safety and cost of cisplatin for TGCT according to the requirements of WHO EML Expert Committee, and to provide the evidence whether cisplatin should be included in WHO EML. METHOD: We searched The Cochrane Library, PubMed, EMbase, NHS EED, US National Guideline Clearinghouse (NGC) and WHO guidelines. Guidelines and systematic reviews (SRs) on cisplatin for TGCT were included. Two reviewers selected studies and extracted relevant information independently. Quality of SRs was appraised through AMSTAR. RESULTS: Seven guidelines and four SRs were included in this rapid review. Quality of SRs was moderate according to AMSTAR. The results showed that: (a) effectiveness: cisplatin-based chemotherapy significantly improved in response rates and overall survival for more advanced disease (stage II and stage III). Bleomycin, etoposide, and cisplatin (BEP)-one of the most widely used of cisplatin-based chemotherapy regimens should be considered as the standard treatment of good-prognosis patients with survival rates of 90% and as the best option for intermediate- or poor-prognosis patients with survival rates of 75% and 50%, respectively. (b) Safety: nephrotoxicity, ototoxicity and peripheral neuropathy are common adverse effects of cisplatin. (c) Cost: there was no relevant study about cost of cisplatin for TGCT. But the affordability of cispaltin is good for Chinese patients, due to it is in health insurance directory of China. CONCLUSIONS: We recommend cisplatin to be listed in 19th WHO EML for TGCT, due to adequate evidence of effectiveness and good affordability.

[Incidence and Risk Assessment of Tumor Lysis Syndrome in Patients with Advanced Germ Cell Cancer].

Tumor lysis syndrome (TLS) is a major oncological emergency. TLS is common in patients with hematological malignancies, but it can occur across a spectrum of cancer types. Germ cell tumors (GCT) have rapid cancer cell turnover and often present with bulky metastasis. The international TLS expert consensus panel has recommended guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. GCT is classified as intermediate risk for TLS, and the patients who have other TLS risks factors are classified to be at high risk for TLS. In this study, we retrospectively analyzed 67 patients with metastatic GCT who were treated with induction chemotherapy at Tsukuba University Hospital between 2000 and 2013. Thirty-one, 15 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Twelve patients (18%) were classified to be at high risk for TLS, and two patients were treated with allopurinol or rasburicase as prophylaxes for TLS. They did not show progression to laboratory TLS (L-TLS). In the remaining 10 TLS high-risk patients, three (30%) patients developed L-TLS after chemotherapy and started receiving oral allopurinol. As a result, no patients developed clinical TLS (C-TLS). In this study, 30% of TLS-high risk patients developed L-TLS without prophylactic treatment. Therefore, it is important to conduct TLS-risk stratification and consider prophylaxis such as rasburicase for advanced GCT patients at induction chemotherapy.

Reproductive function assessment after surgery plus chemotherapy for germ cell ovarian tumors (MOGCT): novel clues deriving from the field of fertility preservation.

Germ cell ovarian tumors (malignant ovarian germ cell tumors - MOGCT) affect young women and are treated by surgery plus chemotherapy. It is well known that cytotoxic treatment may accelerate depletion of the primordial follicle pool leading to impaired fertility and premature menopause. Aim of this study is to identify patient candidates for fertility preservation strategies. We report our experience in preservation of fertility for four patients affected by MOGCT, referred to San Raffaele Hospital Oncofertility Unit. All patients received fertility sparing surgery plus platinum-based chemotherapy. Two patients were affected by mixed germ cell tumors and two by disgerminomas. After 24 months from the end of treatment, serum AMH levels have been measured. We report lower serum anti-Mullerian hormone (AMH) levels in our patients than in healthy general population as serum AMH levels were under the 25th age-specific percentiles. Fertility preservation, in terms of oocytes cryopreservation, was offered to those two patients with serum AMH levels predictive of significantly poor ovarian reserve (1st and 2nd patients). Using the gonadotropin releasing hormone (GnRH) antagonist protocol for ovarian stimulation, we obtained two and six oocytes, respectively. Therefore, serum AMH, as a marker of ovarian function, can improve the identification of patients that need to be referred to fertility preservation strategies.

Clinical implementation of germ line cancer pharmacogenetic variants during the next-generation sequencing era.

More than 100 medications approved by the US Food and Drug Administration include pharmacogenetic biomarkers in the drug label, many with cancer indications referencing germ line DNA variations. With the advent of next-generation sequencing (NGS) and its rapidly increasing uptake into cancer research and clinical practice, an enormous amount of data to inform documented gene-drug associations will be collected that must be exploited to optimize patient benefit. This review focuses on the implementation of germ line cancer pharmacogenetics in clinical practice. Specifically, it discusses the importance of germ line variation in cancer and the role of NGS in pharmacogenetic discovery and implementation. In the context of a scenario in which massive amounts of NGS-based genetic information will be increasingly available to health stakeholders, this review explores the ongoing debate regarding the threshold of evidence necessary for implementation, provides an overview of recommendations in cancer by professional organizations and regulatory bodies, and discusses limitations of current guidelines and strategies to improve third-party coverage.

Brain metastases during follow-up of children and adolescents with extracranial malignant germ cell tumors: risk adapted management decision tree analysis based on data of the MAHO/MAKEI-registry.

BACKGROUND: The overall risk for brain metastases among children and adolescents with extracranial malignant germ cell tumors (mGCT) is low but may vary between subgroups. Early identification of subgroups with an increased risk for brain metastasis is therefore important. PROCEDURE: We analyzed 900/2,160 patients from the German MAHO/MAKEI registry on children and adolescents with malignant extracranial GCT (pure teratomas (grade 0-3) were not included). For follow-up evaluation, patients with brain metastases at diagnosis and those with a follow-up shorter than 32 months after diagnosis (longest interval to brain metastases in our cohort) were excluded. Patients were censored at detection of brain metastases or death due to other causes. A decision tree analysis considering age, gender, site of primary tumor, and presence of other metastases at diagnosis as risk factors for brain metastases was performed. RESULTS: Among 838 eligible patients, 9 acquired brain metastases during follow-up, accounting for death in 5. There were no brain metastases in absence of extracranial metastases at diagnosis. If extracranial metastases were detected in absence of mediastinal mGCT the risk for brain metastases was 1.2% (95% CI: 0.2-3.5.%). In contrast, risk was increased to 37.5 (95% CI 15.2-64.6%) in patients with mediastinal GCTs and extracranial metastases. CONCLUSION: A high-risk subgroup is detected with a decision tree analysis approach. These patients may benefit from an intensified chemotherapy. Close surveillance for CNS-metastases is warranted in this high-risk group while less close monitoring in low-risk patients is justified. Pediatr Blood Cancer 2013;60:217-223. © 2012 Wiley Periodicals, Inc.

Predictive value of marker half-life in relapsed and nonrelapsed nonseminomatous germ cell testicular tumor patients undergoing chemotherapy.

BACKGROUND: The aim of this study was to investigate the influence of a marker half-life (MHL) on relapse in nonseminomatous germ cell testicular tumor patients. METHODS: MHL was retrospectively analyzed in relapsed (n = 37) and nonrelapsed patients (n = 28) undergoing first-line chemotherapy (CT). Before CT and after the second cycle of CT, serum α-fetoprotein (AFP) and ß-human chorionic gonadotropin levels were measured for MHL analysis. The International Germ Cell Cancer Collaborative Group risk classification system was used to assess the correlation between MHL and relapse. MHL was calculated according to a logarithmic formula. RESULTS: Median follow-up was 25 months (range, 6 to 96 mo). A statistically significant difference was not observed between initial AFP (P = 0.266) and ß-human chorionic gonadotropin (P=0.092) in both patient groups. MHL was statistically different between the relapsed and nonrelapsed patients with a good, intermediate, and poor prognosis, except for the half-life of AFP in patients with a poor prognosis. CONCLUSIONS: MHL is an indicator that predicted recurrence. Patients with an MHL longer than expected should be investigated to improve the effectiveness of treatment and should be treated with a recovery regimen.

Delayed orchiectomy at postchemotherapy retroperitoneal lymph node dissection due to laterality of retroperitoneal metastatic pattern consistent with testicular primary: assessment of pathologic findings.

OBJECTIVES: It has been estimated that extragonadal germ cell tumors (EGCTs) constitute 3% to 5% of germ cell neoplasms. An interesting clinical scenario occurs when a patient with a presumed EGCT and normal testicular examination and ultrasound findings has a retroperitoneal metastatic pattern consistent with either a right or left-sided testicular primary. We reviewed the pathologic data of patients presenting with these clinical findings after delayed orchiectomy at postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). METHODS: We identified 14 patients with apparent EGCT who had undergone simultaneous orchiectomy at PC-RPLND at our institution from July 1979 to July 2002 because of a lateralizing pattern of retroperitoneal metastases concerning for a testicular primary. Of the 14 patients, 3 had completely normal testicular ultrasound findings after chemotherapy and 11 had minimal ultrasound findings not consistent with a testicular tumor. RESULTS: Two (14%) of the PC orchiectomy specimens contained mature teratoma and eight (57%) contained necrosis and/or focal fibrosis. Thus, 10 (71%) of 14 patients undergoing PC orchiectomy at PC-RPLND because of metastatic disease laterality had evidence of a testicular primary. CONCLUSIONS: Most (71%) patients with a presumed EGCT who underwent PC orchiectomy because of lateralizing retroperitoneal metastases had histologic evidence of a testicular primary (20% teratoma, 80% focal necrosis or fibrosis). If the retroperitoneal pattern of metastatic tumor spread is consistent with a primary testicular tumor, we offer PC orchiectomy to patients with apparent EGCT at PC-RPLND, even if the PC testicular examination and ultrasound findings are normal.

A decision-analytic approach to define poor prognosis patients: a case study for non-seminomatous germ cell cancer patients.

BACKGROUND: Classification systems may be useful to direct more aggressive treatment to cancer patients with a relatively poor prognosis. The definition of 'poor prognosis' often lacks a formal basis. We propose a decision analytic approach to weigh benefits and harms explicitly to define the treatment threshold for more aggressive treatment. This approach is illustrated by a case study in advanced testicular cancer, where patients with a high risk of mortality under standard treatment may be eligible for high-dose chemotherapy with stem cell support, which is currently defined by the IGCC classification. METHODS: We used published literature to estimate the benefit and harm of high-dose chemotherapy (HD-CT) versus standard-dose chemotherapy (SD-CT) for patients with advanced non-seminomatous germ cell cancer. Benefit and harm were defined as the reduction and increase in absolute risk of mortality due to HD-CT respectively. Harm included early and late treatment related death, and treatment related morbidity (weighted by 'utility'). RESULTS: We considered a conservative and an optimistic benefit of 30 and 40% risk reduction respectively. We estimated the excess treatment related mortality at 2%. When treatment related morbidity was taken into account, the harm of HD-CT increased to 5%. With a relative benefit of 30% and harm of 2 or 5%, HD-CT might be beneficial for patients with over 7 or 17% risk of cancer specific mortality with SD chemotherapy, while with a relative benefit of 40% HD-CT was beneficial over 5 and 12.5% risk respectively. Compared to the IGCC classification 14% of the patients would receive more aggressive treatment, and 2% less intensive treatment. CONCLUSION: Benefit and harm can be used to define 'poor prognosis' explicitly for non-seminomatous germ cell cancer patients who are considered for high-dose chemotherapy. This approach can readily be adapted to new results and extended to other cancers to define candidates for more aggressive treatments.

Treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs. VIP) for poor-prognosis metastatic germ cell tumors.

BACKGROUND: In patients with small-volume disseminated disease of germ cell tumors, cure can be achieved with four cycles of bleomycin, etoposide, and cisplatin (BEP). However, around 20% of these cases are not curable. Strategies to improve cure rates have shown that none of the currently available modalities were superior to the others. Among the most used ones, BEP and VIP (etoposide, cisplatin, and ifosfamide) have been the most studied. However, there are no reports comparing the two, except for a few in abstract forms from southern India. Therefore, we did a treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs VIP) that are used in poor-prognosis metastatic germ cell tumors. MATERIALS AND METHODS: All male patients with germ cell tumors, diagnosed as having poor risk by IGCCCG, between January 2002 and December 2004 were included in the study. Clinical, laboratory, and other data were recorded. The patients were stratified into two categories on the basis of the type of chemotherapeutic regimen they received. RESULTS: In all, 46 patients were analyzed, with a median follow up of 26.6 months. The baseline characteristics (age, stage, PS, histology, and serum markers) were not different in the two treatment arms. There is no significant difference in the outcome with either of the chemotherapeutic modalities. VIP is less cost effective and more toxic compared to BEP. CONCLUSION: In view of the greater toxicity and cost of therapy, as well as lack of either overall or disease free survival advantage, VIP is not a preferred option for patients with high-risk germ cell tumors in the Indian setting and it is still advisable to treat patients with BEP.

Ejaculatory function in stage T1 nonseminomatous germ cell tumors: retroperitoneal lymph node dissection versus surveillance--a decision analysis.

PURPOSE: Ejaculatory function remains a major concern for patients with low stage nonseminomatous germ cell tumors of the testis. Whereas, it has been extensively studied in patients undergoing retroperitoneal lymph node dissection, preservation of ejaculatory function on surveillance protocols has not been studied. To compare ejaculatory function for surveillance protocols to primary retroperitoneal lymph node dissection appropriately, we constructed a decision analysis model mimicking the standard treatment algorithm for stage 1 nonseminomatous germ cell tumor of the testis. MATERIALS AND METHODS: The primary clinical payoff for this study is ejaculatory function. Based on this model, we established that a primary nerve sparing retroperitoneal dissection must be performed with a 96.8% ejaculatory function rate to be recommended as the appropriate therapy. However, if a highly skilled surgeon routinely performs post-chemotherapy dissection with an ejaculatory function rate of 69.2% or greater, surveillance should be offered as the primary treatment modality. This result simply demonstrates a high skill level to allow the surgeon to salvage ejaculatory function in post-chemotherapy retroperitoneal lymph node dissection settings. If this level cannot be achieved, primary retroperitoneal lymph node dissection is the best choice. If we account for a 10% loss of ejaculatory function from primary chemotherapy, the minimum ejaculatory function rate for primary retroperitoneal dissection decreases to 95.7%. RESULTS: In the post-chemotherapy setting an 85.7% ejaculatory function rate must be achieved for surveillance to be considered the optimal choice. Clearly, less surgical rigor is needed with a primary retroperitoneal lymph node dissection when correcting for the effects of chemotherapy on ejaculatory function. Despite this fact, 1-way sensitivity analysis revealed that our model is insensitive to the ejaculatory function effects of chemotherapy. Furthermore, if the likelihood of recurrence on surveillance is greater than 16%, primary nerve sparing retroperitoneal lymph node dissection should again be recommended. CONCLUSIONS: Thus, to maximize ejaculatory function for patients with stage 1 nonseminomatous germ cell tumor a nerve sparing primary retroperitoneal lymph node dissection should always be performed, unless the likelihood of recurrence on surveillance is low or the surgical skill level allows for a highly successful post chemotherapy nerve sparing dissection.

Assessment of amifostine as protection from chemotherapy-induced toxicities after conventional-dose and high-dose chemotherapy in patients with germ cell tumor.

BACKGROUND: We assessed the efficacy of amifostine for protection from chemotherapy-induced toxicities in patients treated with conventional-dose paclitaxel, ifosfamide, cisplatin (TIP) and high-dose carboplatin, etoposide and thiotepa (CET) followed by peripheral blood progenitor cell (PBPC) rescue. PATIENTS AND METHODS: In a prospective single-center study 40 patients with relapsed or refractory germ-cell tumors (GCT) were treated with 3 cycles of conventional-dose TIP followed by one cycle of high-dose CET. Patients were randomized either to receive one fixed dose of 500 mg amifostine per day of conventional-dose TIP and two fixed doses of 500 mg per day amifostine during high-dose CET (group A, n = 20) or no amifostine (group B, n = 20). Prior to the first cycle of TIP, one course of 175 mg/m2 paclitaxel and 5 g/m2 ifosfamide (TI) followed by granulocyte-colony stimulating factor (G-CSF) at 10 microg/kg/day were given for PBPC mobilization. RESULTS: Toxicities and response to conventional-dose TIP and high-dose CET could be evaluated in 40 patients (100%) and 32 of 40 patients (80%), respectively. Peripheral neurotoxicity (i.e. paresthesia or sensorymotor impairment), hearing impairment, hematologic toxicity, nephrotoxicity, nausea, myalgia, skin- and liver-toxicity did not differ siginificantly between the two patient groups. Likewise, the response rates to TIP and high-dose CET were comparable in patients with or without amifostine. After a median follow-up of 18 months, 8 of 20 (40%) patients of group A and 6 of 20 (30%) patients of group B are without relapse. CONCLUSION: Repeated low doses of 500 mg amifostine additional to conventional-dose TIP or high-dose CET showed no unequivocal advantage in protection from treatment-related toxicities. Furthermore, no significant differences in response rates or survival could be observed in this small number of patients.

Current concepts in risk factor assessment for advanced germ cell cancer.

Disseminated germ cell tumors (GCT) have come to represent the model for a curable malignancy, as cure rates with cisplatin-based chemotherapy coupled with appropriate surgery are 70% to 80%. For patients with favorable prognostic factors who achieve and maintain a complete response, the outlook is good. However, despite advances in the treatment of this disease, a significant number of patients with metastatic GCT fail to respond either primarily or secondarily. Being able to identify poor-risk patients up front would allow for appropriate selection of candidates for high-risk trials. Several different classification systems were previously developed at several treatment centers in the United States and Europe. These models recognized different clinical variables as prognosticators and had unique functional properties. However, these served as precursors to the International Germ Cell Consensus Classification that was developed to establish a universally accepted standard. The development of this system has allowed for valid comparisons of ongoing and future trials. Furthermore, this system will serve to encourage international collaboration for the study of high-risk GCT.

Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

Decision analysis for avoiding postchemotherapy surgery in patients with disseminated nonseminomatous germ cell tumors.

PURPOSE: This retrospective study was undertaken to assess the outcome of patients with disseminated nonseminomatous germ cell tumor (NSGCT) managed under a postchemotherapy strategy developed at Indiana University. PATIENTS AND METHODS: This is a retrospective analysis of 295 consecutive patients with disseminated NSGCT treated with primary chemotherapy at Indiana University from 1987 to 1994. The patients were placed into five groups based on response to primary chemotherapy and the presence or absence of teratoma in the primary tumor. The 295 patients were divided as follows: group A (complete remission [CR]) n = 78; group B (unresectable), n = 50; group C (serologic CR, teratoma-positive primary tumor, resectable partial remission [PR]), n = 90; group D [serologic CR, teratoma-negative primary tumor, < 90% radiographic PR], n = 50; and group E (serologic CR, teratoma-negative primary tumor, > or = 90% radiographic PR), n = 27. Groups A, B, and E patients were routinely observed after chemotherapy, whereas groups C and D patients were routinely taken to postchemotherapy surgery. RESULTS: The percent of patients who continuously had no evidence of disease (NED) were as follows: group A, 92%; group B, 40%; group C, 87%; group D, 86%; and group E, 74%. In assessing group A patients, the bulk of retroperitoneal disease at presentation had no influence on ultimate outcome. CONCLUSION: Patients with NSGCT who achieve a serologic and radiographic CR with primary chemotherapy (group A) can be safely observed without surgical intervention, regardless of initial tumor bulk. Patients with a teratoma-negative primary tumor who achieve a serologic CR and a > or = 90% radiographic remission and are followed-up without surgical resection (group E) are at an increased risk of relapsed NSGCT. Decisions about postchemotherapy resection in this group remain complicated and controversial. Options include observation with serial radiologic evaluation or surgical resection of persistent mass or masses.

Assessment of risk in metastatic testis carcinoma: impact on treatment.

The majority of patients have 'good risk' nonseminomatous germ cell tumors, that is, they are likely to obtain an initial complete response to chemotherapy. Trials in these patients attempt to reduce the toxicity of chemotherapy. The minority of patients have refractory disease ('poor risk' nonseminomatous germ cell tumors) and the primary objective in this population is to improve the proportion of complete response. Chemotherapy trials for the poor risk group are generally associated with greater toxicity. Clinical factors reported to impact on the prognosis of nonseminomatous germ cell tumor patients include the pretreatment level of serum tumor markers (AFP, HCG, LDH), extern or bulk of disease, the pathology and the site of the primary lesion. No consensus currently exists on which factors are most important in determining prognosis and how they should be used to allocate patients to good and poor risk nonseminomatous germ cell tumors trials. The data support the concept that biologic markers and extent or bulk of disease together are more predictive of response and survival than either one alone and their combined use results in a smaller percent of the germ cell tumor population allocated to poor risk trials. This minimizes exposure of good risk patients to toxic regimens and still maintains a high response rate in the good risk population. The current eligibility criteria for good and poor risk trials in use directly affects the reported response proportion and survival. In view of these differences, good and poor risk trials should be randomized against a comparative control population and nonrandomized trials comparing treatment results with those of other studies or historical controls should be viewed with extreme caution.

[Feasibility and relevance of tumor volumetry for stage classification and assessment of remission of germ cell tumors]. / Praktikabilität und Relevanz der Tumorvolumetrie zur Stadienklassifikation und Remissionsbeurteilung bei Keimzelltumoren.

Although tumor load has proven to be the most relevant prognostic factor in disseminated germ cell tumors (GCT), methods to determine tumor volume for staging have not been studied so far. In a prospective study, we therefore measured the volume of metastases before and during chemotherapy in 27 patients with disseminated GCT. Abdominal tumor volume was calculated using a General Electric CT scan 8800. Total volume was determined by cumulation of 1 cm slices measured by a cursor. Pulmonary volume was calculated by taking each metastasis as a sphere using V = 0.523 x d3, where V = volume and d = diameter. We used linear regression analysis to determine the dependence of tumor markers on volume. Before chemotherapy, the median tumor volume of all patients was 237 (range 4-2690) cm3. The tumor volume was 1-100 cm3 in 30%, 101-500 cm3 in 41%, and over 500 cm3 in 29% of the patients. NED (no evidence of disease) was achieved in 8/8 patients presenting with a small (1-100 cm3) and 9/10 with a moderate (101-500 cm3) tumor volume. In contrast, only 1/8 with advanced tumor load (greater than 500 cm3) achieved NED. While there was a significant correlation between the initial and the residual tumor volume (P = 0.0024, r = 0.72), there was none between the tumor volume and alpha fetoprotein, beta human chorionic gonadotropin, and lactate dehydrogenase. These results suggest that radiological determination of tumor volume is a reproducible and accurate staging method.

Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol.

Four courses of PVP16B (cisplatin plus etoposide [VP-16] plus bleomycin) has been standard chemotherapy for disseminated germ cell tumors at Indiana University and the Southeastern Cancer Study Group (SECSG) since 1984. We began a random prospective phase III study in patients with favorable-prognosis (minimal and moderate extent) disseminated germ cell tumors comparing four courses of PVP16B over 12 weeks to the identical dose PVP16B administered in three courses over 9 weeks. The categories of minimal and moderate disease constitute approximately two thirds of all disseminated germ cell tumors that require chemotherapy. One hundred eighty-four patients entered this trial, and all patients have a minimal follow-up of 1 year. Overall, 106 of 107 (99%) minimal extent and 73 of 77 moderate patients (95%) achieved an initial disease-free status (NED), confirming the favorable prognostic categories. Eighty-six of 88 patients (98%) randomized to three courses and 93 of 96 randomized to four courses (97%) of PVP16B achieved disease-free status. There have been ten relapses (5%), with five on each arm. Currently, 81 of 88 (92%) and 88 of 96 (92%) patients randomized to three v four courses of PVP16B are continuously disease-free. This study confirms the high cure rate with PVP16B in favorable-prognosis germ cell tumors. The deletion of the fourth course of PVP16B significantly reduces the toxicity, cost, and inconvenience of this curative regimen. We conclude that three courses of PVP16B is the preferred regimen for favorable-prognosis germ cell tumors.