bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of maintenance of dose intensity (DI) during induction chemotherapy (iCT) for metastatic nonseminomatous germ cell tumors (NSGCT)
Authors: Fedyanin M. , Tryakin A. , Titov D. , Zakharova T. , Fainstein I. , Figurin K. , Polockii B. , Sergeev J. , Garin A. , Tjulandin S. 
Published: August 2020

e16063 Background: Cisplatin- and etoposide-based CT allows curing the majority of patients (pts) with metastatic germ cell tumor. There are limited data concerning the importance of maintenance of DI during iCT. In the retrospective study we analyzed the role of DI of iCT on metastatic NSGCT. Methods: 589 chemotherapy-naïve pts with advanced NSGCT received induction iCT from 1987 to 2006 in our center. We compared data of all pts who relapsed after iCT (147 pts) with data of 159 randomly sampled pts without relapses. During iCT all pts received classical E500P (24%) or BE500P (76%) regimens. Median follow-up time was 49 (range, 3–218) months. Eighty four (27.5%) of 306 pts, 107 (35%) and 115 (37.5%) were from good, intermediate and poor prognostic groups, respectively. DI was calculated for every drug and expressed in mg/m2 per week. Multivariate Cox stepwise regression analysis was performed to determine independent prognostic factors in each IGCCCG prognostic group. Progression free survival was used as endpoint of the analysis. Results: Multivariate analysis revealed the following negative prognostic factors as independent: in pts of the IGCCCG good prognostic group: retroperitoneal lymph nodes >5 cm (HR 3.53, 95% Cl 1.66–7.51). In pts with the intermediate prognosis: DI of etoposide <80% (HR 4.73; 95 % CI 4.85–25.04) and presence of pulmonary metastases (HR 0.45, 95% Cl 0.203–0.977). In IGCCCG poor prognostic group: DI of etoposide <80% (HR 1.82, 95% Cl 1.143–2.913). Conclusions: Maintaining a DI of greater then 80% of etoposide during iCT, for the treatment metastatic NSGCT, is one of the crucial factors for pts outcome, particularly in intermediate and poor IGCCCG prognostic groups. No significant financial relationships to disclose.
Prostate cancer clinical trials consortium: A multicenter mechanism for the rapid design, development, and implementation of early phase clinical trials
Authors: Vinson J. , Mathew P. , Beer T. M. , Carducci M. A. , Oh W. , Small E. , Wilding G. , Higano C. , Hussain M. , Scher H. I. 
Published: August 2020

e16065 Background: Leading investigators in prostate cancer have hypothesized that clinical trials (CT) are optimally conducted as multicenter studies. To test this, the Prostate Cancer Clinical Trials Consortium (PCCTC) was formed with support from the Prostate Cancer Foundation (PCF) and the Department of Defense Clinical Consortium Award (DOD). Since the PCCTC's inception in 2006, members have cooperatively designed, carried out, and evaluated phase 1 and 2 multicenter studies in prostate cancer. Methods: PCF and DOD awards support a consortium of 13 cancer research centers. Memorial Sloan-Kettering Cancer Center serves as the coordinating center and is charged with creating an infrastructure to conduct early phase, multicenter trials. Annually, each participating center is required to introduce at least one CT for consideration by the PCCTC and accrue at least 35 patients to PCCTC studies. Investigators meet face-to-face twice per year to discuss the PCCTC's progress, and hold monthly conference calls to discuss scientific objectives, trial design, and ongoing studies. Results: Since inception, the PCCTC has expanded from 8 to 13 leading research centers. Through September 2008, it has opened 47 trials and accrued 1,282 patients at member sites. Members utilize a CT management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review have been established. Each year, the number of trials presented and patients accrued increases, and three concepts have progressed to the next phase of clinical testing. Conclusions: The PCCTC fulfills a congressional directive to create a CT instrument dedicated to rapid accrual to early-phase, multicenter studies in prostate cancer. The member institutions have built a shared administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. As the PCCTC has expanded and taken an increasingly active role in designing and evaluating protocols, clinical trials continue to open and accrue in excess of federally mandated goals. No significant financial relationships to disclose.
Results of a phase II study of carboplatin and etoposide in patients with progressive metastatic castration refractory prostate cancer (mCRPC) and neuro-endocrine differentiation
Authors: Flechon A. , Pouessel D. , Ferlay C. , Perol D. , Beuzeboc P. , Gravis G. , Joly F. , Oudard S. , Deplanque G. , Droz J. , Culine S. 
Published: August 2020

e16073 Background: Neuro-endocrine differentiation is often observed in the evolution of mCRPC. We assessed the efficacy and toxicity of a platin-based chemotherapy regimen in patients with mCPRC and neuro-endocrine differentiation defined by: either increased circulating neuro-endocrine markers (chromogranin A: CgA, Neuron Specific Enolase: NSE) more than 1.5 X normal serum values and/or visceral metastases confirmed with immunihistochemical proof of neuro-endocrine differentiation on pathological sample. Methods: Sixty patients were included (Simon optimal two stages design with P0 = 20%, P1 = 40%, α = 5% and power 90% for a total of 54 evaluable patients) and were treated by the combination of carboplatin AUC 4 d1 IV and etoposide 100 mg/m2/d d1–3 IV every 3 weeks for a maximum of 6 cycles. Efficacy endpoints included PSA and neuro-endocrine marker response rate (defined as a decrease of 50% or greater of the baseline serum value), objective response rate (according to RECIST criteria), and toxicity. Results: Sixty patients were included between April 2005 to January 2008, median age was 67 (range: 45–80). Sixty-seven per cent patients received prior chemotherapy. Patients had bone metastases (78%), lymph nodes involvement (49%), lung metastases (35%), hepatic involvement (33%) and other localizations (17%). The objective response rate was 33% in the 48 assessable patients. A neuro-endocrine response was observed in 28% of 32 evaluable patients for neuro-endocrine marker level (CgA 6%, NSE 25% and both 3%). The PSA response rate was 9%. The most common grade 3–4 treatment-related toxicities were neutropenia (67%), thrombocytopenia (31%), anemia (27%), asthenia (14%) nausea and vomiting grade (12%). There were 6% febrile neutropenia, with one related toxic death. The median follow-up is 9 months. The median response duration was 1.8 months (range: 0.2–13.4 months). The median overall survival is 10 months. Conclusions: Despite an absolute response rate in accordance with the study assumptions, the benefit-risk ratio of this regimen seems unfavourable due to observed toxicities. Another trials must be conducted in order to define a group of patients which may benefit of this regimen. No significant financial relationships to disclose.
A phase II noncomparative study of neoadjuvant (NA) chemohormone therapy (CHT), radical prostatectomy (RP), and postoperative radiotherapy (RT) in locally advanced (LA) high-risk prostate cancer (HRPC): A monoinstitutional 6-year experience with two NA CHT regimens
Authors: Lo Re G. , Boccalon M. , Maruzzi D. , Bortolus R. , Lenardon O. , Marus V. , Rustici C. , Tumolo S. , Garbeglio A. , Sulfaro S. 
Published: August 2020

e16091 Background: HRPC criteria include stage T2b-T2c according to the AJCC classification, PSA ≥ 10 ng/ml, Gleason score (GS) 7–10 with 12, 6% 7-year cancer specific mortality rate (D'Amico AV, Cancer. 2006). Several small nonrandomized NA chemotherapy studies were performed in this setting (Kim N. Chi J Urol. 2008; Prayer-Galletti T. Br J Urol. 2007; Konety BR. J Urol. 2004) with DFS of 42%-70%. Aim of this study: to evaluate the feasibility, efficacy, and toxicity of NA-CHT followed by RP and postoperative RT. Methods: Histological diagnosis of LA HRPC (T2b-T4), GS > 8, PSA > 10 ng/ml, age < 65 years, PS 0–1. Treatment: group A) paclitaxel 80 mg/sqm/weekly and estramustine phosphate (EP) 10 mg/Kg/day for 5 days/week for 4 months. Group B) carboplatin (AUC 5) i.v day 1 q 21 plus docetaxel 30 mg/sqm i.v day 1,8 and EP day -1-+4 and 7–11 q 21 for 4 cycles. Thereafter, the responsive and stable patients (pts) were submitted to RP and adjuvant RT (60–70Gy/30–35 fr) or to radical (R) RT (78 Gy/39 fr) respectively. Primary endpoint: disease-free survival (DFS); secondary endpoint: PSA relapse-free survival (RFS), overall survival (OS). Results: Between 2002 and 2008, 29 pts entered onto the studies. The toxicity was mild. The down-staging was obtained on 2 group A pts and on 1 group B pt respectively. Conclusions: NA-CHT with both regimens was been shown feasible and nontoxic in LAHRPC. Although a clinical response was documented, the pathological response was anecdotal.The DFS and OS are encouraging considering the historical data but warrant a randomized study. [Table: see text] No significant financial relationships to disclose.
How many lymph nodes may serve as a guideline for a sufficient extended lymph node dissection during radical prostatectomy?
Authors: Pomara G. , Campo G. , Milesi C. , Casale P. , Francesca F. 
Published: August 2020

e16102 Background: Recent data suggest that extended lymph node (LN) dissection at radical prostatectomy (RP) may be necessary to detect occult positive lymph nodes, and that extended dissection may also have a positive impact on disease progression and long-term disease-free survival. However, evaluation of lymphadenectomy to be complete and sufficient as judged by the number of removed lymph nodes is sometimes difficult. Some authors reported that approximately 20 pelvic lymph nodes may serve as a guideline for a sufficient extended lymph node dissection during RP. The purposes of this study were 1) to assess the reproducibility of this number (20 LN) in experienced hands; 2) to evaluate the effect of the number of LNs removed on lymph node metastasis. Materials and Methods: Data from 293 consecutives patients undergone to RP with extended lymphadenectomy were prospectively analyzed [median age 66 (35–79), median PSA 7.98 ng/ml (2.5–35)]. The number of lymph nodes extracted and the number of patients with positive lymph nodes detected were analyzed and compared. Moreover we distinguished and analyzed RPs data of most experienced surgeon: 124 patients [median age 65aa (44–79), median PSA 6.7(2.5–19)]. Results: Analyzing all the population, the median number of removed lymph nodes was 15 (1–39). Analyzing only the most experienced surgeon results, the median number of removed lymph nodes was 20 (range 6–39). The effect of the number of LNs removed on lymph node metastasis is shown in the Table . Conclusions: Compared to limited lymph node dissection (< 10 removed LNs), extended pelvic lymphadenectomy appears to identify men with positive lymph nodes more frequently. Although very experienced surgeons remove approximately 20 pelvic lymph nodes (comparable to the literature), our results seem to underline that 15 removed LNs are sufficient as a guideline for an extended lymph node dissection during RP. [Table: see text] No significant financial relationships to disclose.
Prognostic outcome in Japanese men with prostate cancer treated with androgen-deprivation therapy (ADT) alone: Data from multi-institutional cooperative study in Kyoto Prostate Cancer Registry (KPCR)
Authors: Okihara K. , Takeuchi I. , Ukimura O. , Takaha N. , Kawauchi A. , Miki T. 
Published: August 2020

e16106 Background: There is scarce data of ADT alone concerning prognostic outcome in terms of clinical stage, and in comparison with radical treatments specifically in men without metastatic diseases. The aim of this study was to analyze prognostic outcome for ADT alone, and to assess the significant prognostic parameters in Japanese men. Methods: Database in the KPCR, which is a multi-institutional urologic cancer registry, was screened to identify prostate cancer patients who received ADT alone between 1988 and 2008. Clinical data including age, clinical stage, biopsy differentiation, initial prostate-specific antigen (PSA) level and type of ADT: luteinizing hormone-releasing hormone (LH-RH) monotherapy or combined androgen blockade (CAB), were analyzed. Time to prostate cancer relapse as well as cause specific survivals were also analyzed. Results: Of 1167 men with prostate cancer registered in KPCR, 373 patients (32%) received primary ADT and continued ADT alone during the observation period. Of those men, age and PSA level ranged from 52 to 95 y.o (median: 75) and from 2.17 to 8,650 ng/ml (median: 23.5), respectively. The numbers of clinical stage in A to B, C and D were 148 (40%), 127 (34%), and 98 (26%), respectively. The observation period ranged from 1 to 125 months (median: 55). Of the 373 men, 113 men (30%) recurred after the primary ADT. Of the 131men, 36 men (10%) changed from LH-RH monotherapy to CAB, and 46 (12%) and 52 men (14%) underwent anti-androgen alternative therapy and secondary hormonal therapy using estramustine phosphate and/or oral dexamethasone, respectively. There was a significant difference in 5-year cause specific survival between stage A-C (98%) and D (63%, p < 0.0001). Cox proportional hazards multivariate regression analyses revealed that localized cancer (stage A and B) was the most significant prognostic factor in the time to relapse (p < 0.0001) as well as the cause specific survival (p < 0.0001). Conclusions: There was substantial number of men with localized disease who were treated ADT alone. The use of ADT therapy alone appeared to have favor prognosis in the majority of patients without metastatic diseases, at least for an intermediate period. No significant financial relationships to disclose.
Skeletal related events in patients with metastatic renal cell carcinoma: A retrospective review
Authors: Secter M. , MacKenzie M. J. , O'Brien P. , Whiston F. 
Published: August 2020

e16118 Background: Approximately one third of patients with renal cell carcinoma (RCC) will develop bone metastases during the course of their disease. Previous studies suggest that the rate of skeletal related events (SREs) in patients with metastatic renal cell carcinoma is high, and that bisphosphonate therapy can lower the rate of SREs. We conducted a retrospective review of patients with metastatic renal cell carcinoma and bone metastases seen at our academic cancer centre. Methods: After approval by the Research Ethics Board, a retrospective review of all patients seen at the London Regional Cancer Centre with a diagnosis of RCC between January 2006 and December 2008 was performed. Data points collected included the number of patients with bone metastases, number of SREs, length of hospital stay, and treatments related to SREs. A SRE was defined as one of the following: pathologic fracture, spinal cord compression, radiotherapy or surgery to bone, or hypercalcemia in the presence of bone metastases. Results: 196 patients with metastatic RCC were identified. Of these, 63 (32%) had bone metastases. 75% of these patients with bone metastases received medical therapies including sunitinib, sorafenib or temsirolimus. 66% of patients received at least one dose of bisphosponate therapy. Common sites of metastases were vertebra (66%), pelvis (50%), and femur (42%). Of those with bone metastases, 61 (95%) experienced at least one SRE. 42% sustained a pathologic fracture; 28% suffered a spinal cord compression or cauda equina syndrome; 22% had surgery for bone metastases; 87.5% required radiotherapy and 27% had hypercalcemia. 40% of patients were hospitalized due to an SRE, and the mean length of hospital stay was 21 days (range 1–120 days). Conclusions: Despite significant recent improvements in the overall care of RCC, and expansion of the number of therapeutic options, bone metastases and consequent SREs continue to cause significant morbidity. These SREs come with frequent and prolonged hospitalizations. Our rate of SREs is actually higher than that documented in the placebo arm of a randomized trial of a bisphosphonate in RCC from the pre-tyrosine kinase era. Bone-related morbidity in mRCC remains a clinical problem with a significant unmet medical need. [Table: see text]
In vivo activity of R1530 (R) alone and in combination with docetaxel (D) and bevacizumab (B) in a prostate carcinoma (PCa) xenograft model
Authors: Kolinsky K. D. , Zhang Y. , Packman K. , Higgins B. 
Published: August 2020

e16124 Background: R is a multikinase inhibitor currently in phase I clinical testing. Its inhibitory profile includes several kinases that play critical roles in cancer cell growth and division leading to disruption at M-phase and antiangiogenic effects. Studies were conducted to evaluate the efficacy and tolerability of R alone and in combination with D and B in the 22rv1 androgen independent PCa model. Methods: Initially TGI of optimal dose (OD) R, D and B were evaluated. Then the TGI and increased life span (ILS) of the minimum efficacious dose (MED) and 2/3 OD R ± 2/3 OD D was tested. A final study compared doublets of 2/3 OD R + 2/3 OD D, 2/3 OD D + OD B, 2/3 OD R + OD B, and triplet of 2/3 OD D + 2/3 OD R+ 2/3 OD B. Results: All treatment groups were tolerated and there was no antagonism. TGI and ILS results are listed below ( Table ). Conclusions: The OD of R B and D showed monotherapy TGI in this model. MED R + 2/3 OD D gave ILS statistically better (sb) than singlets but TGI was sb than MED R but not the D singlet. 2/3 OD R + 2/3 OD D produced sb TGI and ILS than each singlet. TGI and ILS with 2/3 OD R is sb than 2/3 OD D. TGI and ILS of 2/3 OD R + 2/3 OD D was sb than the 2/3 OD D + OD B but not the 2/3 OD R + B doublet. TGI and ILS was sb for 2/3 OD R + OD B versus 2/3 OD D + OD B. The TGI of the triplet was equivalent to the 2/3 OD R + 2/3 OD D doublet, but ILS was sb in the triplet. Also, the TGI and ILS was sb for triplet versus 2/3 OD D + OD B. TGI and ILS of the triplet was equal to 2/3 OD R + OD B. In general, the results demonstrate that the shared mechanism of mitotic disruption by R and D do not render antagonism, but in fact, allow for potentiated TGI and ILS. Also of note is the equally superior TGI and ILS provided by R + B and R + B + D. In general, the preclinical results generated support clinical testing of these agents in PCa. * p value for all. [Table: see text] [Table: see text]
Evaluation of safety, tolerability, and activity: A registry for temsirolimus-treated patients with advanced or metastatic renal cell carcinoma (aRCC) in the usual health care setting
Authors: Pelz H. F. , Krekeler G. , Bergmann L. , Roigas J. , Steiner T. , Loeschmann P. A. , Kosch M. 
Published: August 2020

e16127 Background: In November 2007, temsirolimus (TEMS) was approved in the EU for the first-line treatment of patients with aRCC who have at least 3 of 6 prognostic risk factors. A pivotal study had demonstrated significantly increased overall survival with TEMS in poor risk aRCC compared to the former standard Interferon (10.9 mo vs 7.3 mo). A pre-registration compassionate use program (CUP) for patients with aRCC confirmed the known safety profile of TEMS. However, the low incidence of reported serious adverse events (SAE) even in the CUP (8 SAE during about 2,200 applications) reflects the low level of spontaneous SAE reporting in oncology. To better identify the true safety profile of newly approved drugs, collection of data on pharmacovigilance in the post-approval period is essential. Hence, a noninterventional trial appears to be adequate. Methods: To prospectively evaluate TEMS in the usual health care setting we started a registry for TEMS-treated patients with aRCC. Primary objective is the evaluation of TEMS´s safety profile. Secondary objectives include the tolerability and activity of TEMS as well as the profile, comorbidity and characteristics of patients and sequence of systemic therapies in aRCC. Inclusion criteria: histologically confirmed aRCC treated with TEMS, written informed consent by the patient. Results: With regulatory and ethic committee's notification the registry started in Germany in January 2008. The registry is set up and managed by Wyeth´s medical department in collaboration with a scientific advisory board. Up to the December 15, 2008, 124 centers have recruited 130 patients. Preliminary documentation is available for 68 patients (57 male, 11 female), median age 65.8 yrs (43.2 –86.7), median Karnofsky index 75%. 32 pts experienced 90 AE, including 15 pts with 40 SAE (16 of them considered related, 24 not related by the treating physician). Conclusions: To further evaluate the safety, tolerability and efficacy of TEMS in the post-approval period and also due to the low level of spontaneously reported SAE in oncology Wyeth started a registry for TEMS-treated patients in aRCC. Updated results will be presented. [Table: see text]
Circulating chromogranin A as a marker for poor-prognosis hormone refractory prostate cancer without neuroendocrine features: Prospective analyses of a cohort of patients
Authors: Maroto-Rey P. , Sala N. , Mora J. , Villavicencio H. , Esquena S. , Robert L. , Perez J. , Mazarico J. , Barnadas A. 
Published: August 2020

e16130 Background: Some patients may develop hormone refractory prostate (HRPC) cancer with neuroendocrine features, although they were not recognizable in the initial biopsy. Serum chromogranin is a marker for tumors with neuroendrocrine differentiation. Purpose: To analyze if serum levels of chromogranin A may identify poor prognosis HRPC patients in patients without neuroendocrine features in the initial biopsy. Methods: Circulating chromogranin A was prospectively analyzed in 34 patients when they were diagnosed under the standard criteria of HRPC. A patient was considered to have higher than normal levels of serum chromogranin if levels were above 100 ug/L. Patients were also assessed for serum PSA, enolase, serum alkaline phosphatase, albumin, and hemoglobin. Results were correlated with clinical prognostic factors as ECOG, PSA double time and Gleason score. We analyzed the time to hormone-refractory disease since diagnosis, and overall survival, as well as pattern of relapse (visceral vs. nonvisceral disease). Results: Median age was 63 (49–85). Median PSA was 33 (0.04–1455). At baseline, 16 patients were chromogranin-negative (46%), and 18 patients were chromogranin-positive (54). Chromogranin A did not correlate with either enolase or PSA. Patients with positive (>100 ug/L) had stadistically significant lower levels of hemoglobine (13.8 vs 12.3), and a trend to have more visceral disease vs locoregional diasease or bone metastases, a lower albumine level (39.85 vs 45.05), higher alkaline phosphatase (221 vs 111), and LDH (1,914.5 vs 415). In this group of patients, we did not find differences in PSA double time, time to hormone-refractory disease or Gleason score. Conclusions: The analysis of this cohort of patients suggests that serum chromogranine A correlates with other known adverse prognosis factors of survival in prostate cancer patients. No significant financial relationships to disclose.