Prolonged survival in patients with persistently elevated tumor markers after chemotherapy for nonseminomatous germ cell cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5051-5051
Author(s):  
Z. He ◽  
Z. Sun ◽  
G. Liu ◽  
J. Manola ◽  
P. Loehrer
Keyword(s):  
Germ Cell ◽  
Tumor Marker ◽  
Tumor Markers ◽  
Univariate Analysis ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Retrospective Data Analysis ◽  
Significant Difference ◽  
The Impact ◽  
To Receive

5051 Background: Persistently elevated levels of either AFP or HCG or both after chemotherapy are thought to represent residual viable disease while the normalization of tumor markers predicts favorable outcomes. This study was to evaluate the clinical implication of tumor marker normalization for disseminated nonseminomatous germ cell tumors (GCTs). Methods: This was a retrospective data analysis from two prospective randomized trials (ECOG E4887 and E3887). In E4887, 178 patients with minimal- or moderate-stage disease (Indiana stage) were randomized to receive three cycles of cisplatin plus etoposide with/without bleomycin. In E3887, 304 patients with advanced disseminated GCTs were randomized to receive four cycles of bleomycin, etoposide and cisplatin versus the combination of etoposide, ifosfamide and cisplatin. AFP and HCG were assessed at baseline and after each cycle of chemotherapy. Tumor marker normalization was defined as AFP or HCG normalized after completing chemotherapy. OS and PFS curves were estimated by the Kaplan-Meier method. Multivariate and univariate models, stratified on International Germ Cell Consensus Classification (IGCCCG), were used to assess the impact of marker normalization for patients with abnormal markers at study entry. Results: Median follow-up is 14.8 years. About 40% to 60% of Patients with persistently elevated AFP or HCG after chemotherapy have prolonged PFS and/or OS. In IGCCCG poor risk patients, 35% to 55% of them with persistently elevated AFP or HCG after chemotherapy have prolonged PFS and/or OS. There is a statistically significant difference in OS associated with AFP normalization in both multivariate (p=0.008, HR=0.51 with 95% CI=0.31–0.84) and univariate analysis (p=0.0008, HR=0.43 with 95% CI=0.26–0.71). However, there was no statistically significant difference in OS associated with normalization of HCG in both multivariate analysis (p=0.52, HR=0.84 with 95% CI=0.50–1.41) and univariate analysis (p=0.29, HR=0.76 with 95% CI=0.46–1.26). Conclusions: Patients with persistently elevated AFP or HCG after chemotherapy may still have prolonged PFS and/or OS. Normalization of AFP but not HCG is associated with better OS in patients with disseminated nonseminomatous GCTs. No significant financial relationships to disclose.

The effect of pulmonary function testing on bleomycin dosing in germ cell tumors.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 227-227 ◽  
Author(s):  
B. B. Houghton ◽  
P. S. Grimison ◽  
G. C. Toner ◽  
M. Chatfield ◽  
D. B. Thomson ◽  
...  
Keyword(s):  
Germ Cell ◽  
Pulmonary Toxicity ◽  
Lung Metastases ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Consensus Classification ◽  
The Impact ◽  
To Receive ◽  
Function Testing ◽  
Good Risk

227 Background: Lung function testing (LFT) during chemotherapy with bleomycin is controversial. We describe the impact of LFT on bleomycin dosing in a phase II trial of accelerated BEP for advanced germ cell tumors. Methods: Patients had measurable disease and were stratified with the International Germ Cell Cancer Consensus Classification (IGCCC). The planned number of weekly bleomycin doses was 12 for intermediate risk (IR) and poor risk (PR) disease, and 9 for good risk (GR) disease. Clinical assessments, CXR, DLCO corrected for haemoglobin, and FVC were done 2-weekly. Bleomycin was to be stopped for: predefined clinical or CXR evidence of pulmonary toxicity; or a >25% reduction in DLCO or FVC; or GFR <35mL/min. We determined bleomycin doses planned, received, and omitted; and, patients receiving all, ≥2/3, or <2/3 of their planned bleomycin doses. Results: The first 30 patients had a median age of 28 (range 19-39) and 10 with lung metastases. 80% (259/324) of planned bleomycin doses were received; 75 doses (20%) were omitted in 15 pts, all for >25% reduction in DLCO. 16 patients had a 10 to 24% reduction in DLCO but none had >35%. In all patients the decline in FVC was < 10%. No patient developed other evidence of pulmonary toxicity. Patients with lung metastases were 2.5 times as likely to have a >25% reduction in DLCO (50% vs 20%, p=0.15), and 4 times as likely to receive <2/3 of their planned doses (40% v 10%, p=0.14). Conclusions: Asymptomatic reductions in DLCO caused 20% of bleomycin doses to be omitted and 20% of patients to receive < 2/3 of their planned doses. A 25% reduction in DLCO may be too cautious a threshold, particularly in those with lung metastases. [Table: see text] No significant financial relationships to disclose.

scholarly journals Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.

1997 ◽  
Vol 15 (5) ◽  
pp. 1844-1852 ◽  
Author(s):  
A Horwich ◽  
D T Sleijfer ◽  
S D Fosså ◽  
S B Kaye ◽  
R T Oliver ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Survival Rates ◽  
Germ Cell Tumors ◽  
Good Prognosis ◽  
Cancer Trial ◽  
European Organization ◽  
To Receive ◽  
Nonseminomatous Germ Cell Tumors ◽  
Good Risk

PURPOSE This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with good-risk nonseminomatous germ cell tumors. PATIENTS AND METHODS Between September 1989 and May 1993, a total of 598 patients with good-risk nonseminomatous germ cell tumors were randomized to receive four cycles of either BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3, and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20 mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the carboplatin dose was calculated from the glomerular filtration rate to achieve a serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21-day intervals to a total of four cycles. RESULTS Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P = .009). There were 30 treatment failures in the 300 patients allocated to BEP and 79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P < .001), which led to failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%) and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P = .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90% (95% CI, 86% to 94%), respectively. CONCLUSION With these drug doses and schedules, combination chemotherapy based on carboplatin was inferior to that based on cisplatin. This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.

Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indian University experience.

1998 ◽  
Vol 16 (2) ◽  
pp. 702-706 ◽  
Author(s):  
S B Saxman ◽  
D Finch ◽  
R Gonin ◽  
L H Einhorn
Keyword(s):  
Germ Cell ◽  
Univariate Analysis ◽  
Germ Cell Tumors ◽  
Phase Iii ◽  
Term Survival ◽  
Favorable Prognosis ◽  
Significant Difference ◽  
Long Term Follow Up

PURPOSE In a previously reported randomized Southeastern Cancer Study Group (SECSG) trial, three cycles of chemotherapy were found to be equivalent to four cycles in patients with favorable-prognosis germ-cell cancer. We have conducted a follow-up analysis of patients treated at Indiana University (Indianapolis, IN) to compare long-term survival between the two groups and to examine factors associated with survival. PATIENTS AND METHODS Sixty-nine patients with minimal-stage and 49 patients with moderate-stage disseminated germ-cell tumors were randomized to either three or four courses of bleomycin, etoposide, and cisplatin (BEP) administered every 3 weeks. Median follow-up time is 10.1 years (range, 7 months to 12.6 years). Ninety-two percent of patients have an actual follow-up time of > 5 years, and 97.5% of patients have an actual follow-up time of > 3 years. RESULTS Survival analysis shows no significant difference between the two treatment groups in terms of overall (P = .80) or disease-free (P = .93) survival. Several clinical variables were examined by univariate analysis; only serum human chorionic gonadotropin (HCG) had an impact on survival. There were two disease-related deaths in 104 patients with HCG < or = 1,000 mIU/mL and five disease-related deaths in 14 patients with HCG greater than 1,000 mIU/mL (P < .001). Ninety-eight percent (95% CI, 95.2 to 100) of patients with favorable prognosis germ-cell tumor with an initial HCG of < or = 1,000 mIU/mL are alive without evidence of disease at 5+ years. CONCLUSION With long-term follow-up, there is no statistically significant difference in survival between three or four cycles of BEP chemotherapy in patients with favorable prognosis germ-cell carcinoma. Serum HCG elevation of greater than 1,000 mIU/mL is a significant predictor of poor outcome in patients with otherwise good-risk disease.

scholarly journals Placental alkaline phosphatase levels in cerebrospinal fluid can have a decisive role in the differential diagnosis of intracranial germ cell tumors

2019 ◽  
Vol 131 (3) ◽  
pp. 687-694 ◽  
Author(s):  
Yasuo Aihara ◽  
Sinichiro Watanabe ◽  
Kosaku Amano ◽  
Kana Komatsu ◽  
Kentaro Chiba ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Germ Cell ◽  
Tumor Marker ◽  
Tumor Markers ◽  
Germ Cell Tumors ◽  
Diagnostic Value ◽  
Placental Alkaline Phosphatase ◽  
Intracranial Germinoma ◽  
Intracranial Germ Cell Tumors ◽  
Very High

OBJECTIVEPlacental alkaline phosphatase (PLAP) in CSF can provide a very high diagnostic value in cases of intracranial germ cell tumors (GCTs), especially in pure germinomas, to the level of not requiring histological confirmation. Unlike other tumor markers, reliable data analysis with respect to the diagnostic value of PLAP serum or CSF levels has not been available until now. This is the first systematic and comprehensive study examining the diagnostic value of CSF PLAP in patients with intracranial GCTs.METHODSFrom 2004 to 2014, 74 patients (average age 19.6 ± 10.6 years) with intracranial GCTs were evaluated using PLAP from their CSF and histological samples. Chemiluminescent enzyme immunoassay was utilized to measure CSF PLAP in the following tumor sites: pineal (n = 32), pituitary stalk, suprasellar (n = 16), basal ganglia (n = 15), intraventricular (n = 9), and cerebellar (n = 5) regions. In addition to classifying GCT cases, all patients underwent tumor biopsy for correlation with tumor marker data.RESULTSPLAP in combination with other tumor markers resulted in extremely high sensitivity and specificity of the diagnostic value of intracranial GCTs. Intracranial GCT cases were classified into 1) germinomas, both “pure” and syncytiotrophoblastic giant cell types (n = 38); 2) nongerminomatous GCTs, choriocarcinomas (n = 9) and teratomas (n = 4); and 3) nongerminomas, other kinds of tumors (n = 23). Consequently, all patients received chemoradiation therapy based on elevation of PLAP and the histopathological results. It was also speculated that the level of PLAP could show the amount of intracranial germ cell components of a GCT. PLAP was 100% upregulated in all intracranial germinoma cases. The absence of CSF PLAP proved that the tumor was not a germinoma.CONCLUSIONSThe current study is the first systematic and comprehensive examination of the diagnostic value of the tumor marker PLAP in pediatric patients with intracranial GCT. Using the level of PLAP in CSF, we were able to detect the instances of intracranial germinoma with very high reliability, equivalent to a pathological diagnosis.

RBIO-05. THE IMPACT OF STEREOTATIC RADIOSURGERY (SRS) FOR THE RESIDUAL LESIONS OF PINEAL NON-GERMINOMATOUS GERM CELL TUMORS (NGGCTS) FOLLOWING CONVENTIONAL RADIOTHERAPY: A RETROSPECTIVE STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi192-vi192
Author(s):  
Mingyao Lai ◽  
Juan Li ◽  
Qingjun Hu ◽  
Shaoqun Li ◽  
Linbo Cai
Keyword(s):  
Survival Rate ◽  
Germ Cell ◽  
Local Control ◽  
Univariate Analysis ◽  
Germ Cell Tumors ◽  
Maximum Diameter ◽  
Conventional Radiotherapy ◽  
Free Survival ◽  
The Impact ◽  
Residual Lesions

Abstract OBJECTIVE To evaluate the safety and efficacy of stereotatic radiosurgery (SRS) in treating residual lesions of pineal non-germinomatous germ cell tumors (NGGCTs) after conventional radiotherapy. METHODS The patients admitted to Guangdong Sanjiu Brain Hospital from 1 January 2008 to 31 December 2018 who diagnosed with pineal NGGCTs pathologically or clinically were retrospectively analyzed. Among those, the patients received conventional radiotherapy with or without SRS were included. The residual lesions after radiotherapy were defined with a maximum diameter &gt; 10mm. Prognosis related parameters such as local control rate, progress-free survival, overall survival and treatment-related toxicity were determined. RESULTS The median follow-up time was 34 months (range 8-142 months). The objective response rate and disease control rate were 71.4% and 95.2%, respectively. Three-year progression-free survival rate was 85.2% and 3-year total survival rate was 88.0%. The univariate analysis revealed that both age and concurrent chemotherapy were not correlated with the prognosis (P=0.286, 0.824). Partial tumor resection before radiotherapy and chemotherapy, AFP &gt;500ng/ml, and no more than 4 cycles of adjuvant chemotherapy were poor prognostic factors (P=0.037, 0.010, 0.006). Moreover, no acute radiation response was observed after treatment with SRS. Only 1 out of 27 patients (3.7%) had brain neurotoxicity related to a prolonged course of radiochemotherapy. CONCLUSION SRS for residual lesions of NGGCTs following conventional radiotherapy appears to be well tolerant and improved local control. However, the therapeutic efficacy of conventional radiotherapy combined with SRS warrants further investigations in a large-scale randomized controlled clinical trials.

scholarly journals Detection of Relapse by Tumor Markers Versus Imaging in Children and Adolescents With Nongerminomatous Malignant Germ Cell Tumors: A Report From the Children’s Oncology Group

2019 ◽  
Vol 37 (5) ◽  
pp. 396-402 ◽  
Author(s):  
Adriana Fonseca ◽  
Caihong Xia ◽  
Armando J. Lorenzo ◽  
Mark Krailo ◽  
Thomas A. Olson ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Marker ◽  
Children And Adolescents ◽  
Tumor Markers ◽  
Germ Cell Tumors ◽  
Initial Diagnosis ◽  
Phase Iii ◽  
Detection Methods ◽  
Pathology Reports ◽  
Malignant Germ Cell Tumors

PURPOSE To investigate relapse detection methods among children and adolescents with nongerminomatous malignant germ cell tumors (MGCTs) and to determine whether tumor markers alone might be sufficient for surveillance. METHODS We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs. The method used to detect relapse was assessed based on case report forms, tumor markers, imaging, and pathology reports. Relapses were classified into one of two categories on the basis of whether they were (1) detectable by tumor marker elevation or (2) not detectable by tumor markers. RESULTS A total of 302 patients were enrolled, and 284 patients had complete data for review. Seven patients had normal tumor markers at initial diagnosis, and none experienced a relapse. At a median follow-up of 5.3 years, 48 patients (16.9%) had experienced a relapse. After central review, 47 of 48 relapses (98%) were detected by tumor marker elevation. Of the 47 patients, 16 (33.3%) had abnormal tumor markers with normal/unknown imaging, 31 patients (64.6%) had abnormal tumor markers with abnormal imaging, and one patient (2.1%) had abnormal imaging with unknown marker levels at relapse. CONCLUSION Tumor marker elevation is a highly sensitive method of relapse surveillance, at least among children and adolescents with tumor marker elevation at initial diagnosis. Eliminating exposure to imaging with ionizing radiation may enhance the safety of relapse surveillance in patients treated for MGCT.

Early Predicted Time to Normalization of Tumor Markers Predicts Outcome in Poor-Prognosis Nonseminomatous Germ Cell Tumors

2004 ◽  
Vol 22 (19) ◽  
pp. 3868-3876 ◽  
Author(s):  
Karim Fizazi ◽  
Stéphane Culine ◽  
Andrew Kramar ◽  
Robert J. Amato ◽  
Jeannine Bouzy ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Marker ◽  
Tumor Markers ◽  
Poor Prognosis ◽  
Germ Cell Tumors ◽  
Hazard Ratio ◽  
Primary Tumor Site ◽  
Decline Rate ◽  
Prognosis Group ◽  
Nonseminomatous Germ Cell Tumors

Purpose The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Patients and Methods Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. Results The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P < .0001) and overall survival (OS; P < .0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P = .01) and OS (hazard ratio = 4.6; P = .002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. Conclusion Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.

scholarly journals A Survey of Marine Coastal Litters around Zhoushan Island, China and Their Impacts

2021 ◽  
Vol 9 (2) ◽  
pp. 183
Author(s):  
Xuehua Ma ◽  
Yi Zhou ◽  
Luyi Yang ◽  
Jianfeng Tong
Keyword(s):  
Rapid Development ◽  
Univariate Analysis ◽  
Local Environment ◽  
Marine Litter ◽  
Social Ecological ◽  
The Social ◽  
Significant Difference ◽  
Valuable Method ◽  
Beach Litter ◽  
The Impact

Rapid development of the economy increased marine litter around Zhoushan Island. Social-ecological scenario studies can help to develop strategies to adapt to such change. To investigate the present situation of marine litter pollution, a stratified random sampling (StRS) method was applied to survey the distribution of marine coastal litters around Zhoushan Island. A univariate analysis of variance was conducted to access the amount of litter in different landforms that include mudflats, artificial and rocky beaches. In addition, two questionnaires were designed for local fishermen and tourists to provide social scenarios. The results showed that the distribution of litter in different landforms was significantly different, while the distribution of litter in different sampling points had no significant difference. The StRS survey showed to be a valuable method for giving a relative overview of beach litter around Zhoushan Island with less effort in a future survey. The questionnaire feedbacks helped to understand the source of marine litter and showed the impact on the local environment and economy. Based on the social-ecological scenarios, governance recommendations were provided in this paper.

scholarly journals Teratomatous Elements in Orchiectomy Specimens Are Associated with a Reduced Relapse-Free Survival in Metastasized Testicular Germ Cell Tumors

2021 ◽  
pp. 1-7
Author(s):  
Pia Paffenholz ◽  
Tim Nestler ◽  
Yasmine Maatoug ◽  
Melanie von Brandenstein ◽  
Barbara Köditz ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Retroperitoneal Lymph Node Dissection ◽  
Advanced Tumor Stage ◽  
Testicular Germ Cell Tumors ◽  
Relapse Free Survival ◽  
Testicular Germ Cell ◽  
Free Survival ◽  
Advanced Tumor ◽  
The Impact

<b><i>Introduction:</i></b> The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear. <b><i>Methods:</i></b> We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics. <b><i>Results:</i></b> Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, <i>p</i> = 0.031), visceral metastases (58 vs. 32%, <i>p</i> = 0.015), and poor prognosis (<i>p</i> = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, <i>p</i> = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, <i>p</i> = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (<i>p</i> = 0.049) during a median follow-up of 36 months (10–115.5). <b><i>Conclusions:</i></b> The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

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