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Biomedical subjects

A Gerl

Publications and source records attributed to A Gerl.

At least 37 records · Page 2Linked to original sources
PubMed1999

Treatment of patients with cisplatin-refractory testicular germ-cell cancer. German Testicular Cancer Study Group (GTCSG).

With the use of cisplatin-based combination chemotherapy, metastatic testicular germ-cell tumors can be cured in 70% to 80% of patients. The combination of cisplatin, etoposide and bleomycine (PEB) is considered standard therapy. Patients refractory to cisplatin-based chemotherapy have a markedly poor prognosis. Several chemotherapeutic agents have been evaluated in intensively pre-treated or cisplatin-refractory patients. Neither the anthracyclines nor vinorelbine, topotecan or biological agents such as suramin and retinoic acid have demonstrated clinical activity. Paclitaxel has been evaluated at different doses and schedules and yielded a response rate of 21% (range 11-30%), with single patients achieving complete remissions. This has led to the inclusion of paclitaxel in salvage regimens in combination with cisplatin and/or ifosfamide. Two studies have evaluated gemcitabine in refractory germ-cell tumors and demonstrated a response rate of 17% (95% CI 7-28%) in 52 intensively pre-treated patients, two-thirds of whom had relapsed after previous high-dose chemotherapy plus autologous stem-cell transplantation. The non-hematological toxicity of weekly gemcitabine at doses of 1,000 to 1,250 mg/m2 was tolerable, and hematological side effects included thrombocytopenia in approximately 20% of patients. Ongoing studies in refractory germ-cell tumors performed by the German Testicular Cancer Study Group are evaluating bendamustine, an alkylating agent with activity in breast and small-cell lung cancer, and oxaliplatin, a platinum derivative with incomplete cross-resistance to cisplatin. Future trials combining new active agents may examine alternating treatment strategies in patients with poor-prognostic disease or as salvage treatment.

Antimetabolites, Antineoplastic↗
PubMed1999

Treatment outcome of patients with brain metastases from malignant germ cell tumors.

BACKGROUND: Multiinstitutional experience with the management of cerebral metastases from malignant germ cell tumors (MGCT) is presented. METHODS: Clinical data regarding brain metastases from MGCT at diagnosis (Group 1 [56 patients]) or after cisplatin-based chemotherapy (Group 2 [83 patients]) were collected retrospectively. All patients in Group 1 received "conventional" cisplatin-based chemotherapy supplemented by cerebral radiotherapy (36 patients) and/or neurosurgery (10 patients). In the patients in Group 2 cerebral metastases were detected a median of 9 months after the initiation of chemotherapy. Thirty-five patients received chemotherapy, 59 patients received radiotherapy, and 25 patients underwent neurosurgery. RESULTS: The 5-year cause specific survival rate in Group 1 was 45% (95% confidence interval [CI], 31-59%). Neurosurgery and the absence of extracerebral, nonpulmonary visceral disease, but not cerebral radiotherapy, were independent predictors of good prognosis. The 5-year cause specific survival rate in Group 2 was 12% (95% CI, 4-20%), but was 39% among patients with an isolated brain recurrence (24 patients). Radiotherapy, but not chemotherapy, represented an independent predictor of good prognosis together with brain metastases at first recurrence and the absence of extracerebral recurrence. CONCLUSIONS: Among patients with brain metastases at the time of diagnosis of an MGCT, cisplatin-based chemotherapy resulted in a 5-year cause specific survival rate of 45%, with cerebral radiotherapy having limited impact. The 5-year cause specific survival rate for all patients with brain metastases after cisplatin-based chemotherapy was 12%, but increased to 39% in patients with an isolated brain recurrence. Cerebral radiotherapy (and neurosurgery) represent essential treatment modalities for patients in whom brain metastases are diagnosed after induction chemotherapy.

Adolescent↗
PubMed1999

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.

Adolescent↗
PubMed1999

Gemcitabine in patients with relapsed or cisplatin-refractory testicular cancer.

PURPOSE: Despite generally high cure rates in patients with metastatic testicular germ cell tumors, patients with incomplete response to cisplatin-based first-line therapy or with relapsed disease after high-dose salvage chemotherapy have a very poor prognosis. This phase II study evaluates the use of gemcitabine in patients with intensively pretreated or cisplatin-refractory testicular germ cell cancers. PATIENTS AND METHODS: Thirty-five patients (median age, 33 years) were enrolled; 31 patients were fully assessable. All patients had metastatic nonseminomatous germ cell tumors; eight patients had extragonadal primary tumors. Twenty patients (63%) had lung metastases, and 12 patients (39%) had liver metastases. The median number of prior cisplatin-based chemotherapy cycles was seven; 22 patients (71%) had received high-dose chemotherapy with autologous stem-cell transplantation, and 19 patients (61%) had received treatment with paclitaxel. Seventeen patients (54%) were considered refractory or absolutely refractory to chemotherapy. RESULTS: Six of 31 assessable patients (19%) responded favorably to gemcitabine, 11 patients (35%) displayed no change, and 14 patients (45%) had disease progression. The median time to treatment failure was 4 months (range, 2 to 9+ months), and the median survival was 6 months (range, 2 to 23 months). Patients received a median of six gemcitabine applications. Ten patients (32%) required dose reductions, mainly owing to hematologic toxicity. Grade 3/4 granulocytopenia occurred in four patients (13%) and grade 3/4 thrombocytopenia in seven patients (22%). One case of severe sepsis was observed. CONCLUSION: Gemcitabine displays antitumor activity in intensively pretreated and refractory germ cell tumors. Responses were observed in approximately 20% of patients, including three of 22 patients after previous high-dose chemotherapy and one of four patients with mediastinal tumors. Gemcitabine may be a reasonable palliative option for intensively pretreated patients and should be further investigated to define its role in the risk-adapted treatment strategies for germ cell tumors.

Adolescent↗
PubMed1998

Validity of predictions of residual retroperitoneal mass histology in nonseminomatous testicular cancer.

PURPOSE: To validate predictions of the histology (necrosis, mature teratoma, or cancer) of residual retroperitoneal masses in patients treated with chemotherapy for metastatic nonseminomatous testicular germ cell tumor. PATIENTS AND METHODS: We studied 172 testicular cancer patients who underwent resection while tumor markers were normal. Predictive characteristics for the residual histology were registered, including the presence of teratoma elements in the primary tumor, the prechemotherapy level of tumor markers (alpha-fetaprotein [AFP], human chorionic gonadotropin [HCG], lactate dehydrogenase [LDH]), the size of the residual mass, and the percentage of shrinkage in mass diameter. We calculated the predicted probability of necrosis and the ratio of cancer and mature teratoma with previously published logistic regression formulas. RESULTS: The distribution of the residual histology was necrosis in 77 (45%), mature teratoma in 72 (42%), and cancer in 23 (13%). Necrosis could be well distinguished from other tissue, with an area under the receiver operating characteristic (ROC) curve of 82%. No tumor was found in 15 patients with a predicted probability of necrosis over 90%. The predicted probabilities corresponded reliably with the observed probabilities (goodness-of-fit tests, P > .20), although a somewhat higher probability of necrosis was observed in patients treated with chemotherapy containing etoposide. Conversely, cancer could not reliably be predicted or adequately discriminated from mature teratoma. CONCLUSION: The predicted probabilities of necrosis have adequate reliability and discriminative power. These predictions may validly support the decision-making process regarding the need and extent of retroperitoneal lymph node dissection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Residual pulmonary masses after chemotherapy for metastatic nonseminomatous germ cell tumor. Prediction of histology. ReHiT Study Group.

BACKGROUND: After chemotherapy for a metastatic nonseminomatous germ cell tumor, pulmonary masses may be seen on a computed tomography scan. These residual masses may contain one of three histologic elements: necrosis, mature teratoma, or cancer. Because surgical resection of masses containing only necrosis is unnecessary, the authors aimed to predict the histology of these residual masses. METHODS: Six study groups contributed patient data on a total of 215 patients undergoing thoracotomy after cisplatin-based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumors. Logistic regression analysis was used to estimate the probability of necrosis, mature teratoma, and cancer in relation to predictors known before thoracotomy. RESULTS: The pulmonary mass histology was necrosis in 116 patients (54%), mature teratoma in 70 (33%), and cancer in 29 (13%). Necrosis was found at thoracotomy in 89% of those patients with necrosis at retroperitoneal lymph node dissection (RPLND). Other predictors included the primary tumor histology, prechemotherapy tumor marker levels, change in mass size during chemotherapy, and the presence of a single, unilateral mass. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P > 0.20), which discriminated necrosis well from other histologies, especially if RPLND histology was available (area under the receiver operating characteristic curve, 0.86). CONCLUSIONS: This analysis indicated subgroups of patients with a high probability of necrosis and a low risk of cancer for whom close follow-up of the residual pulmonary mass might be considered. In most patients, a RPLND should be performed before a thoracotomy is considered, because the probability of necrosis is generally higher at thoracotomy than at RPLND and the histology at RPLND is a strong predictor of the histology at thoracotomy.

Analysis of Variance↗
PubMed1997

Residual masses after chemotherapy for metastatic testicular cancer: the clinical implications of the association between retroperitoneal and pulmonary histology. Re-analysis of Histology in Testicular Cancer (ReHiT) Study Group.

PURPOSE: We determined the need and sequence of retroperitoneal lymph node dissection and thoracotomy in patients with nonseminomatous testicular cancer, and with residual retroperitoneal and pulmonary masses after chemotherapy. MATERIALS AND METHODS: We studied 159 patients undergoing retroperitoneal lymph node dissection and a thoracotomy following cisplatin based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumor. Several well-known predictors for residual histology (necrosis, mature teratoma and cancer) were evaluated. RESULTS: As expected, necrosis was found more often at retroperitoneal lymph node dissection if the primary tumor was negative for teratoma, the residual mass was small or the decrease in size was great. Contrary, neither residual mass size nor the decrease in size was predictive of the histological status of the residual lung lesion. Histological findings in the retroperitoneum and lung were strongly correlated, such that necrosis at retroperitoneal lymph node dissection was associated with an 89% probability of necrosis in the lung. CONCLUSIONS: Retroperitoneal lymph node dissection should be performed before thoracotomy is considered, since the histological status at dissection is a strong predictor of that at thoracotomy.

Germinoma↗
PubMed1997

Late relapse of germ cell tumors after cisplatin-based chemotherapy.

BACKGROUND: Sparse data are available with regard to the incidence, clinical characteristics, therapeutic management and prognosis of male patients with germ cell tumors, who relapse more than two years after completion of cisplatin-based chemotherapy. PATIENTS AND METHODS: A review of 530 patients treated at two institutions from 1978 to April 1994 was conducted. Twenty-five cases of late relapse were identified. Cumulative risk of late relapse was calculated according to the Kaplan-Meier method. RESULTS: 418 of 523 patients (80%) who received their first-line treatment at our institutions were relapse-free at two years. Among these 418 patients 18 cases (4.3%) developed a late relapse. The cumulative risk of late relapse was 1.1% at five years and 4.0% at ten years excluding patients with prior early relapses who carried risks of 9.4% and 29%, respectively (P < 0.0001). No case of late relapse was observed among patients receiving adjuvant chemotherapy. The risk of late relapse was lower in patients with good-risk non-seminomatous germ cell tumors than in poor-risk patients according to Medical Research Council criteria (P < 0.01). Seven further patients were referred from other institutions for treatment of late relapse. At a median follow-up of 38 months (range, 3 to 121) after treatment of late relapse 9 of 25 patients (36%) are continuously disease-free. Six of these nine patients had surgical resection of carcinoma or teratoma as a component of their therapy. CONCLUSION: The incidence of late relapse after cisplatin-based chemotherapy of germ cell tumors is related to initial tumor burden and is somewhat higher than previously expected. Chemotherapy seems to have only minor curative potential, but localized resectable disease can be cured by surgery. Annual follow-up evaluations allow to detect the majority of late relapses at an asymptomatic stage and should be extended throughout the patient's life.

Adult↗
PubMed1996

Cisplatin-based chemotherapy of primary extragonadal germ cell tumors. A single institution experience.

BACKGROUND: Extragonadal germ cell tumors account for only 2-5% of all germ cell neoplasms in adult males. Because these tumors are rare and, in part, biologically distinct from their testicular counterparts, their optimal management continues to be defined. METHODS: The medical records of 51 patients with extragonadal germ cell tumors were reviewed. All patients were treated with cisplatin-based chemotherapy at a single institution between 1981 and 1994. RESULTS: Thirty-five patients had nonseminomatous germ cell tumors and 16 had pure seminomas. Sixteen tumors arose in the mediastinum (12 nonseminomas, 4 seminomas), and 35 in the retroperitoneum (23 nonseminomas, 12 seminomas). Six of 12 patients (50%) with mediastinal nonseminomas survived with no evidence of disease (NED) at 33-137 months (median, 96 months); all had undergone surgery as part of their treatment. Fifteen of 23 patients (65%) with retroperitoneal nonseminomas are alive with NED at 2-145 months (median, 39 months). Fifteen of 16 patients (94%) with extragonadal seminomas survived with NED at 2-141 months (median, 66 months), and 1 patient died from late irradiation-related toxicity. Three patients with retroperitoneal nonseminomas developed a testicular seminoma at 35, 42, and 77 months, respectively; all are currently disease free. CONCLUSIONS: Mediastinal and retroperitoneal nonseminomas have distinct clinical features. As in other series, clinical outcome is somewhat inferior for mediastinal nonseminomas compared with retroperitoneal nonseminomas. Regardless of the site of presentation, the vast majority of patients with extragonadal seminomas can expect cure. It remains controversial, however, whether retroperitoneal germ cell tumors are metastatic from a primary testicular germ cell tumor.

Adolescent↗
PubMed1996

Advances in the management of metastatic non-seminomatous germ cell tumours during the cisplatin era: a single-institution experience.

Long-term outcome was reviewed in 266 consecutive patients with metastatic non-seminomatous germ cell tumours treated at a single institution. The overall 3 year survival was 77%, and 3 year progression-free survival was 71%. Multivariate analysis identified the following clinical features as independent prognostic factors: the presence of liver, bone or brain metastasis, serum human chorionic gonadotropin > or = 10000 U l-1 and/or alpha-fetoprotein > or = 1000 ng ml-1, a mediastinal mass > 5 cm and the presence of 20 or more lung metastases. Age was not of prognostic significance. Patients without any of the above poor-risk factors had a 3 year survival of 91% regardless of etoposide- or vinblastine-containing chemotherapy compared with 61% for the remaining patients. However, etoposide-containing protocols led to significantly improved survival in patients with at least one poor risk factor. After 612 patient-years of observation no case of secondary leukaemia was observed among 119 surviving patients who had received etoposide as part of their treatment. With a median follow-up of 93 months, five patients developed a second germ cell tumour, two patients nongerm cell malignancies. Fourteen patients relapsed after a disease-free interval of more than 2 years, and nine patients died more than 5 years after commencement of treatment underscoring the need to report long-term results. There is some evidence that cumulative experience translates into improved survival and cure rates for patients with poor-risk metastatic disease.

Adolescent↗
PubMed1996

Antitumor activity of paclitaxel after failure of high-dose chemotherapy in a patient with late relapse of a non-seminomatous germ cell tumor.

Although cisplatin-based chemotherapy considerably improved the clinical outcome of patients with metastatic germ cell tumors, approximately 20% of patients fail to achieve a durable remission to first-line treatment and require effective salvage treatment. As only 20-30% of patients can expect disease-free long-term survival after conventional salvage treatment, an increasing proportion of patients has been referred to high-dose chemotherapy with autologous stem cell rescue during recent years. However, high-dose chemotherapy still fails to cure a considerable number of patients, emphasizing the need to continue the search for new active drugs. We report here the case of a patient with late relapse of a non-seminomatous germ cell tumor who failed to respond to high-dose chemotherapy after heavy pretreatment with 11 cycles of cisplatin-based chemotherapy. The patient received paciltaxel for symptomatic disease with hepatic and pulmonary metastases, and attained a partial remission. Despite the heavy pretreatment, hematologic toxicity of paciltaxel was tolerable. As recent reports described responses to single-agent paciltaxel in a quarter of pretreated patients with germ cell tumors, further clinical trials seem justified to study the role of paciltaxel in combination regimens against this cancer type.

Adult↗
PubMed1996

Does serum tumor marker half-life complement pretreatment risk stratification in metastatic nonseminomatous germ cell tumors?

The goal of this study was to determine whether the serum tumor marker half-life (MHL) of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) during initial chemotherapy can complement pretreatment risk stratification in metastatic nonseminomatous germ cell tumors. One hundred forty-seven patients were assessable for MHL during the first two cycles of platinum-based chemotherapy. MHL calculation was based on two consecutive values using Kohn's apparent half-life formula (MHL =ln 1/2/G, where G was the gradient of the marker slope) or on three (or more) values using simple linear regression. MHL was regarded as prolonged if it was more than 3.5 days for HCG or more than 7 days for AFP. The median MHL for HCG was 2.8 days (range, 0.7-16.7) and for AFP was 6.2 days (range, 2. 6-65.4). Thirty-five of 108 patients (32%) had a prolonged MHL for HCG, 41 of 114 (36%) had a prolonged MHL for AFP, and in 59 of 147 patients (40%), either or both MHLs were prolonged. If patients with both MHLs normal were compared against patients with either or both MHLs prolonged, highly significant differences in progression-free survival (P < 0.0001) and overall survival (P = 0.0005) were demonstrated. The test accuracy was 70% for both progression-free and overall survival, and it was slightly greater than the overall predictive value of the Medical Research Council prognostic classification. A combination of Medical Research Council criteria and MHL analysis allowed us to refine prognostic assessment. Because MHL analysis is able to complement pretreatment risk stratification and can support selection of patients for early-dose intensified chemotherapy, it should be included in prospective clinical trials for patients with poor-prognosis disease.

Adolescent↗
PubMed1995

Prognosis after salvage treatment for unselected male patients with germ cell tumours.

Long-term outcome of salvage treatment was reviewed in 67 unselected male patients relapsing during or after their primary cisplatin-based chemotherapy for metastatic germ cell tumours. Seven patients underwent only surgery and/or radiotherapy as curatively intended salvage treatment. Thirty-five patients (52%) had a complete or partial response to salvage treatment, 20 (57%) of whom relapsed again. With a median follow-up of 90 months (range 3-143 months) 20 patients (30%) are alive with no evidence of disease, 15 continuously disease-free and five currently disease-free. The 5 year survival from start of salvage treatment is 37% for the group as a whole. Multivariate analysis identified age < or = 35 years, complete response to primary treatment and a relapse-free interval > 3 months as independent predictors of favourable outcome of salvage treatment. A group of patients with these good-risk factors (42%) had a 5 year survival of 72% compared with the remaining patients (58%) with a 5 year survival of only 11%. Whereas patients with good-risk features may be adequately managed by conventional salvage treatment, the remaining patients carry a very poor prognosis and require innovative and more aggressive approaches.

Adolescent↗
PubMed1995

Outcome analysis after post-chemotherapy surgery in patients with non-seminomatous germ cell tumours.

BACKGROUND: The goal of the study was to analyse long-term outcome after post-chemotherapy surgery in male patients with non-seminomatous germ cell tumours (NSGCT). PATIENTS AND METHODS: We reviewed the charts of 111 patients with metastatic NSGCT treated at a single institution from 1979 to 1993 who underwent post-chemotherapy resection of residual masses after normalisation of tumour markers. The prognostic relevance of the extent of tumour residuals, the comprehensiveness of surgery and the histology at resection was analysed. RESULTS: Thirteen patients (12%) harboured viable cancer, and 46 patients (41%) mature teratoma at post-chemotherapy surgery. Only seven (54%) of the 13 patients with viable cancer remained continuously disease-free. Incomplete surgery predicted an impaired outcome (62% vs. 86% survival), although only one recurrence was observed at a site of an incompletely resected mass. Moreover, a progression-free interval < or = 3 months after post-chemotherapy surgery was correlated with worse subsequent survival (p = 0.0001). CONCLUSIONS: Post-chemotherapy surgery remains an essential part of the treatment for metastatic NSGCT. Resection of viable cancer and mature teratoma is of therapeutic benefit. Viable cancer at surgery defines the need for further chemotherapy.

Adolescent↗
PubMed1994

[Primary extragonadal germ cell tumors. Clinical manifestations, differential diagnosis and therapy].

BACKGROUND: Primary extragonadal germ cell tumors are a rare malignant disease in young males. They account for only 1 to 4% of all germ cell tumors. PATIENTS AND METHODS: In this paper we describe three selected cases of primary extragonadal germ cell tumors. The literature is reviewed with regard to clinical features, differential diagnosis and treatment. RESULTS: Tumor markers alpha-fetoprotein and human chorionic gonadotropin are of considerable diagnostic value if disease distribution is considered. With cisplatin-based combination chemotherapy similar disease-free survival rates are achieved as for testicular tumors with poor-prognosis metastatic disease. Surgical procedures play a role as adjunctive modality. CONCLUSIONS: If young males present with a mass in the retroperitoneum or in the anterosuperior mediastinum, a primary extragonadal germ cell tumor, should be taken into consideration. Tumors of both localisations have distinct clinical features but carry a similar prognosis. Patients benefit from the cumulative experience of a specialist unit.

Adolescent↗