Browsing by Subject "germ cell tumor"
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Item Contemporary trends in postchemotherapy retroperitoneal lymph node dissection: Additional procedures and perioperative complications(Elsevier, 2015-09) Cary, Clint; Masterson, Timothy A.; Bihrle, Richard; Foster, Richard S.; Department of Urology, IU School of MedicineIntroduction Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) is a mainstay in the treatment of men with metastatic testicular cancer. We sought to determine whether trends in the need for additional intraoperative procedures and development of perioperative complications have changed over time. Methods Patients undergoing PC-RPLND from 2003 to 2011 were identified in the Indiana University Testis Cancer Database. Trends in the incidence of perioperative complications and additional procedures were assessed over time using regression tests of trend. Complications were classified according to the modified Clavien system. Univariable and multivariable logistic regression was used to determine factors associated with undergoing additional procedures. Results After exclusion criteria, 755 patients were included in the final study cohort. The incidence of additional procedures at PC-RPLND was 22.1% (167 of 755). The rate of additional procedures per year ranged from 17% to 30%, with no significant trend in any direction (Ptrend = 0.66). After adjusting for covariates, preoperative retroperitoneal (RP) mass size, elevated markers, and RP pathology remained significantly associated with the odds of an additional procedure. RP mass size of>10 cm was the strongest predictor (odds ratio = 7.2, 95% CI: 2.6–19.5). Overall, the incidence of perioperative complications was 3.7% (28 of 755). The rate of perioperative complications per year ranged from 0% to 7.3% with no significant trend in any direction (Ptrend = 0.06). Conclusion The incidence of perioperative complications is low with no significant trend over the last decade. A substantial number of patients require additional intraoperative procedures during PC-RPLND, which has remained stable at our institution over time.Item Evidence of a dual histogenetic pathway of sacrococcygeal teratomas(Wiley, 2017-01) Emerson, Robert E.; Kao, Chia-Sui; Eble, John N.; Grignon, David J.; Wang, Mingsheng; Zhang, Shaobo; Wang, Xiaoyan; Fan, Rong; Masterson, Timothy A.; Roth, Lawrence M.; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of MedicineAims Sacrococcygeal teratomas are rare tumours that occur most frequently in neonates, although adult cases also occur. The molecular pathogenesis of these tumours and their long-term prognosis is uncertain. We investigated the i(12p) status of a large number of primary sacrococcygeal teratomas in both children and adults, including cases with malignant germ cell tumour elements. Methods and results Fifty-four sacrococcygeal teratoma specimens from 52 patients were identified, and available follow-up information was obtained. Fluorescence in-situ hybridization analysis was performed to identify isochromosome 12p [i(12p)] abnormalities on paraffin blocks of the tumours. Among the 48 paediatric patients, there were 44 teratomas and four tumours with combined teratoma and yolk sac tumour (one of whom also had primitive neuroectodermal tumour). The teratomas included 37 mature teratomas and 11 immature teratomas (four grade 1, two grade 2, and five grade 3). The 44 teratomas lacking a yolk sac tumour component were all negative for i(12p). The four tumours with a yolk sac tumour component were all positive for i(12p). The four adult cases all lacked non-teratomatous germ cell tumour components, immature elements, and i(12p). Follow-up information was available for 32 patients. Two patients with teratoma had recurrence, but were alive with no evidence of disease after long-term follow-up. One patient with combined teratoma and yolk sac tumour had recurrence 7 months after resection. The other patients were alive with no evidence of disease at last follow-up. Conclusions Our data suggest that paediatric sacrococcygeal teratomas should be considered as two distinct groups with divergent histogenetic pathways. The prognosis of these tumours is excellent, despite rare recurrence.Item Literature review of management of brain metastases from germ cell tumors(AME, 2022-04-30) Le , Amy; Arbab , Mona; Adra , Nabil; Miller , James C.; Watson , Gordon A.; Shiue, Kevin; Radiation Oncology, School of MedicineObjective: In this review article, we discuss the role of chemotherapy, surgery, and radiation therapy in the treatment of brain metastases from germ cell tumors (GCT). Background: GCT rarely metastasize to the brain and there is limited data to guide management. Most instances of brain metastases occur in patients with non-seminomatous germ cell tumors (NSGCT). Methods: We searched PubMed using the terms 'central nervous system (CNS) metastases' or 'brain metastases' and 'germ cell' from 2011 through August 2021. Review articles and prospective trials related to the treatment of brain metastases in GCT were included in addition to articles obtained by hand search of the references and clinical practice guidelines. Conclusions: We highlight the importance of using chemotherapy as first-line therapy in most situations. We discuss the very minimal data regarding surgery and its primary role when there is significant mass effect or brain shift. We also compare whole brain radiation therapy (WBRT) with the use of radiosurgery. We then provide overall recommendations based on the reviewed data and our experience as a referral center for GCT.Item Low CD34+ Cell Doses Are Associated with Increased Cost and Worse Outcome after Tandem Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Germ Cell Tumors(Elsevier, 2018) Hyder, Mustafa A.; Goebel, W. Scott; Ervin, Kirsten D.; Schwartz, Jennifer E.; Robertson, Michael J.; Thakrar, Teresa C.; Albany, Costantine; Farag, Sherif S.; Medicine, School of MedicineTandem autologous stem cell transplantation (ASCT) improves long-term survival of platinum-refractory germ cell tumor (GCT) patients. Studies, predominantly in lymphoma, showed that CD34+ cell doses > 5.0 × 106/kg/single transplant led to decreased resource utilization. Because most GCT patients have received prior cisplatin-based treatment, collecting >10 × 106 CD34+ cells/kg is challenging. We analyzed the effect of CD34+ cell dose on resource utilization and outcome in 131 GCT patients, median age 29.5 years (range, 16 to 58), undergoing tandem ASCT. Of 262 individual transplants performed, 120 were performed as inpatient and 142 as planned outpatient. Overall, median CD34+ dose per transplant was 3.1 × 106/kg (range, .8 to 16.0), with no significant difference between inpatient and outpatient transplants. Patients were divided into quartiles based on the CD34 cell dose infused: Q1, .8 to 1.9 × 106/kg; Q2, 2.0 to 2.9 × 106/kg; Q3, 3.0 to 4.1 × 106/kg; and Q4, 4.2 to 16.0 × 106/kg. For all patients higher CD34+ cell doses were associated with significantly shorter times to neutrophil (P <.001) and platelet recovery (P <.001). For inpatient transplants higher CD34+ doses were significantly associated with shorter length of hospital stay (P <.001); fewer days of filgrastim (P <.001), i.v. antibiotic (P = .012), and antifungal (P = .03) usage; and fewer RBC (P = .001) and platelet units transfused (P <.001), resulting in overall lower cost of care (P < .001). Of the 142 planned outpatient transplants, 100 admissions were required for a median length of hospital stay of 7.0 days (range, 1 to 18). Although there was no significant difference in the rates of hospitalization between patients in different CD34+ cell dose quartiles, a significant trend was observed for shorter hospitalization (P = .01) and fewer RBC (P = .002) and platelet (P = .005) transfusions with higher CD34+ cell dose quartiles. Patients receiving CD34+ cell doses in the lowest dose quartile (Q1) had significantly worse progression-free survival and overall survival compared with patients receiving higher CD34+ cell doses. Overall, resource utilization, including cost of care, is significantly reduced when patients receive higher CD34+ cell doses, indicating greater efforts to improve peripheral blood stem cell collection in this population are needed.Item Multidisciplinary clinic approach improves overall survival outcomes of patients with metastatic germ-cell tumors(Oxford, 2018-02) Albany, Costantine; Adra, Nabil; Snavely, A. C.; Cary, C.; Masterson, T. A.; Foster, R. S.; Kesler, Kenneth; Ulbright, Thomas M.; Cheng, Liang; Chovanec, Michal; Taza, Fadi; Brames, Mary J.; Hanna, Nasser H.; Einhorn, Lawrence H.; Medicine, School of MedicineBackground To report our experience utilizing a multidisciplinary clinic (MDC) at Indiana University (IU) since the publication of the International Germ Cell Cancer Collaborative Group (IGCCCG), and to compare our overall survival (OS) to that of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program. Patients and methods We conducted a retrospective analysis of all patients with metastatic germ-cell tumor (GCT) seen at IU from 1998 to 2014. A total of 1611 consecutive patients were identified, of whom 704 patients received an initial evaluation by our MDC (including medical oncology, pathology, urology and thoracic surgery) and started first-line chemotherapy at IU. These 704 patients were eligible for analysis. All patients in this cohort were treated with cisplatin–etoposide-based combination chemotherapy. We compared the progression-free survival (PFS) and OS of patients treated at IU with that of the published IGCCCG cohort. OS of the IU testis cancer primary cohort (n = 622) was further compared with the SEER data of 1283 patients labeled with ‘distant’ disease. The Kaplan–Meier method was used to estimate PFS and OS. Results With a median follow-up of 4.4 years, patients with good, intermediate, and poor risk disease by IGCCCG criteria treated at IU had 5-year PFS of 90%, 84%, and 54% and 5-year OS of 97%, 92%, and 73%, respectively. The 5-year PFS for all patients in the IU cohort was 79% [95% confidence interval (CI) 76% to 82%]. The 5-year OS for the IU cohort was 90% (95% CI 87% to 92%). IU testis cohort had 5-year OS 94% (95% CI 91% to 96%) versus 75% (95% CI 73% to 78%) for the SEER ‘distant’ cohort between 2000 and 2014, P-value <0.0001. Conclusion The MDC approach to GCT at high-volume cancer center associated with improved OS outcomes in this contemporary dataset. OS is significantly higher in the IU cohort compared with the IGCCCG and SEER ‘distant’ cohort.Item Pathologic Risk Factors for Higher Clinical Stage in Testicular Seminomas(Wiley, 2018) Trevino, Karen; Esmaeili-Shandiz, Alaleh; Saeed, Omer; Xu, Huiping; Ulbright, Thomas M.; Idrees, Muhammed; Pathology and Laboratory Medicine, School of MedicineIntroduction Testicular seminomas require accurate staging for effective management. 20% are metastatic at presentation while 80% are clinical stage I, requiring only orchiectomy and surveillance. Tumor size, rete testis invasion, hilar soft tissue invasion, and lymphovascular invasion have been shown to incur a higher risk of metastasis and recurrence in clinical stage I seminomas, with little congruence between studies. Materials and Methods We reviewed 211 cases of testicular seminomas and recorded patient age, tumor size, lymphovascular invasion and rete testis, hilar soft tissue, epididymis, spermatic cord, tunica albuginea, and tunica vaginalis involvement. A univariate and multivariate analysis was performed comparing clinical stage I to advanced clinical stage patients (stages II and III) in reference to these factors. Results We found that tumor size (p=0.02), vascular invasion (p=0.02), and invasion of rete testis stroma (p=0.01), epididymis (p=0.02), spermatic cord (p=0.047), and hilar soft tissue (p=0.04) were predictors of higher clinical stage at the univariate level. However, multivariate analysis showed that only tumor size and vascular invasion remained significant (p=0.008 and 0.032, respectively). A tumor size of 4 cm was the size cutoff found to be significant. Discussion Tumor size and vascular invasion are the strongest predictors of higher clinical stage in testicular seminomas. Our univariate data suggests that rete testis and hilar soft tissue invasion relate to higher clinical stage. However, neither of these factors were found to be independent risk factors at multivariate analysis. Therefore, this study supports tumor upstaging based only upon size and vascular invasion.Item Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: A Hoosier Cancer Research Network Study(Springer, 2016-07) Adra, Nabil; Albany, Costantine; Brames, Mary J.; Case-Eads, Somer; Calley, Cynthia; Liu, Ziyue; Fausel, Christopher A.; Breen, Timothy; Hanna, Nasser H.; Hauke, Ralph J.; Picus, Joel; Einhorn, Lawrence H.; Department of Medicine, IU School of MedicinePurpose A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen. Methods GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1–5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate—no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR > 27 %. Results Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %). Conclusion The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin.Item Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network Study GU14-206(Oxford, 2018-01) Adra, Nabil; Einhorn, Lawrence H.; Althouse, Sandra K.; Ammakkanavar, Natraj R.; Musapatika, Dana; Albany, Costantine; Vaughn, David; Hanna, Nasser H.; Medicine, School of MedicineBackground Despite remarkable results with salvage standard-dose or high-dose chemotherapy ∼15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and methods Single arm phase II trial investigating pembrolizumab 200 mg i.v. Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age ≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at least one salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary end point was overall response rate using immune-related response criteria. Simon two-stage design with type I error 20% and power 80% was utilized. Results Twelve male patients were enrolled. Median age was 38 years. All patients had nonseminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range 1–32, 760) and hCG 4 (range 0.6–37, 096). Six patients had late relapse (>2 years). Median number of previous chemotherapy regimens was 3. Six patients received prior high-dose chemotherapy. Two patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range 1–8). There were six grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. Two patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining. Conclusion This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT.Item Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: IV: Current and Future Utilization of Molecular-Genetic Tests for Testicular Germ Cell Tumors(Wolters Kluwer, 2020-03-20) Looijenga, Leendert H. J.; Van der Kwast, Theodorus H.; Grignon, David; Egevad, Lars; Kristiansen, Glen; Kao, Chia-Sui; Idrees, Muhammad T.; Pathology and Laboratory Medicine, School of MedicineThe International Society of Urological Pathology (ISUP) organized a Consultation Conference in March 2019 dealing with applications of molecular pathology in Urogenital Pathology, including testicular tumors (with a focus on germ cell tumors [GCTs]), preceded by a survey among its members to get insight into current practices in testicular germ cell tumor (TGCT) diagnostics and adoption of the ISUP immunohistochemical guidelines published in 2014. On the basis of the premeeting survey, the most commonly used immunomarker panel includes OCT3/4, placental alkaline phosphate, D2-40, SALL4, CD117, and CD30 for GCTs and the documentation of germ cell neoplasia in situ (GCNIS). Molecular testing, specifically 12p copy gain, is informative to distinguish non-GCNIS versus GCNIS related GCTs, and establishing germ cell origin of tumors both in the context of primary and metastatic lesions. Other molecular methodologies currently available but not widely utilized for TGCTs include genome-wide and targeted approaches for specific genetic anomalies, P53 mutations, genomic MDM2 amplification, and detection of the p53 inactivating miR-371a-3p. The latter also holds promise as a serum marker for malignant TGCTs. This manuscript provides an update on the classification of TGCTs, and describes the current and future role of molecular-genetic testing. The following recommendations are made: (1) Presence of GCNIS should be documented in all cases along with extent of spermatogenesis; (2) Immunohistochemical staining is optional in the following scenarios: identification of GCNIS, distinguishing embryonal carcinoma from seminoma, confirming presence of yolk sac tumor and/or choriocarcinoma, and differentiating spermatocytic tumor from potential mimics; (3) Detection of gain of the short arm of chromosome 12 is diagnostic to differentiate between non-GCNIS versus GCNIS related GCTs and supportive to the germ cell origin of both primary and metastatic tumors.Item Salvage therapy for relapsed testicular cancer(Impact Journals, 2017-09-14) Adra, Nabil; Einhorn, Lawrence H.; Medicine, School of Medicine