bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of serum interleukin-6 (IL-6) levels and clinical outcome in hormone-independent (HI) prostate cancer (PC) patients (PTS) treated with docetaxel
Authors: Visa L. , Pineda E. , Farrus B. , Codony-Servat J. , Filella X. , Albiol S. , Martinez A. , Domingo-Domench J. M. , Gascon P. , Mellado B.
Published: August 2020

e16044

Background: IL-6 acts as an autocrine and paracrine growth factor in PC, linked to HI progression. We previously reported preliminary data on the correlation of serum IL-6 and D response in metastatic HI PC pts. We present here a larger group of pts tested to asses the clinical relevance of IL-6 in these pts. Methods: Pts with HIPC treated with D were prospectively tested for IL-6 levels by ELISA before D. Prostate-specific antigen (PSA) response, time to PSA progression, overall survival (OS) and PC specific survival (SpS) were analyzed. Evaluated variables were age, performance status, PSA, Gleason, number (n) of D cycles, time to HI progression, presence of visceral metastasis, n of bone metastasis, hemoglobin, lactate deshydrogenase and alkaline phosphatase. Results: Seventy-two pts were included. At the time of the analysis 5 pts had died from non-PC related causes, two from treatment toxicity and 29 (40%) from PC. Mean of age was 69 ± 7 years. Median baseline IL-6 level was 14 pg/ml (range 0.1–1100). Thirty-five pts (49 %) had IL-6 levels > 14 pg/ml. IL-6 > 14 pg/ml correlated with lower D response (13 % vs 40%, p= 0.039); lower time to PSA progression (4 months vs 6, p=0.023); lower OS (10 months vs 25, p= 0.001) and lower PC SpS (12 months vs 26, p= 0.001), in contrast to pts with IL-6 ≤ 14pg/ml. In the multivariate analysis, serum IL-6 (p=0.002), n of bone metastasis (p=0.008) and n of D cycles (p=0.002), were independent prognostic factor for OS and PC SpS. Conclusions: High serum IL-6 correlates with an adverse clinical outcome of pts with HIPC treated with D. IL-6 determination may be a potential tool to select patients for D-based or targeted therapies. FIS ( PI070388 )

No significant financial relationships to disclose.
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.
Phase I trial of anti-PSMA designer T-cell autografting in prostate cancer
Authors: Abedi M. , Ma Q. , Bais A. , Gomes E. , Beaudoin E. , Lu L. , Davol P. , Cohen S. I. , Junghans R.
Published: August 2020

e16132

Background: We created chimeric immunoglobulin-T cell receptors (IgTCR) specific for prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” specifically kill prostate cancer cells in vitro and in vivo in animal models, with 5/9 (55%) of xenografted mice experiencing complete remissions (Ma et al. Prostate 2004:61:12–25). A Phase I clinical trial was approved by the FDA in metastatic prostate cancers. Methods: Patient T cells are retrovirally transduced and expanded ex vivo to span dose levels of 10^9 to 10^11 T cells. Adapting methods of Dudley, Rosenberg and colleagues, patients undergo prior non-myeloablative (NMA) conditioning to create a “hematologic space” into which the infused designer T cells will stably engraft for prolonged in vivo efficacy. Patients are co-administered continuous infusion IL2. Outcomes will include Phase Ia goals of safety and toxicity and Phase Ib goals of establishing an optimal biologic dose in terms of designer T cell engraftment and tumor response. Results: For the first two patients, excellent T cell modifications of 50–60% were obtained. After NMA conditioning, T cells were infused and stable engraftments of 1–5% were observed post recovery, even at this lowest 10^9 T cell dose level, thus affirming one of the study end-points. The patients had PSA reductions of 50 and 70% in the two months following treatment. Patients experienced neutropenia and lymphopenia after conditioning, but no designer T cell-related toxicities. Results with additional patients will be described in terms of safety, engraftment efficiency and tumor responses. Conclusions: A new approach to adoptive immune therapy in metastatic prostate cancer has been devised. This clinical trial is funded by the US Army/DOD.

No significant financial relationships to disclose.
Concomitant radical non-platinum radiochemotherapy for elderly patients with invasive bladder cancer
Authors: Rodica Maricela A. , Minea L. N. , Bacinschi X. , Isacu I. , Tarlea A.
Published: August 2020

e16135

Background: Treatment of bladder cancer in elderly patients is a challenging problem because surgery is often not tolerable and the combination of extensive radiotherapy with chemotherapy is also difficult because of patients’ compliance and associated comorbidities. Our study evaluated concurrent radiochemotherapy in elderly patients with locally advanced bladder cancer (T2-T4) in terms of efficacy and tolerability. Methods: Between January 2005 and December 2007, we treated 34 patients with transitional carcinoma of the bladder, with or without nodal involvement, no distant metastases, and median age 79 years (range 66 - 89 years). Their performance status was 0–1-2 in 10–16–8 patients respectively. Cardiovascular comorbidities were the most common (15 patients). The treatment consisted in conformal radiotherapy (mean irradiation dose = 56.4 Gy) concomitant with biweekly Gemcitabine 200 mg/sqm starting on day 1 of radiotherapy. Results: Response was assessed at 4–6 weeks after the end of treatment by cystoscopy with biopsies and MRI. All the patients could end the intended radiation therapy but four of them could not tolerate all the chemotherapy. 13 patients achieved complete response, 12 patients - partial response and 9 patients stable disease. The most common toxicities were: diarrhea (grade 1–2 in 11 patients, grade 3–6 patients), cystitis (grade 1–2 in 5 patients), leucopenia (grade 1–2 in 12 patients, grade 3–4 in 2 patients), thrombocytopenia (grade 1–2 in 6 patients) and anemia (grade 1–2 in 4 patients). Three patient required hospitalization for dehydration and two for febrile neutropenia. After a median follow-up time of 17.4 months, there were 7 relapses and 5 distant metastases. One-year survival rate was 82.41% (28 patients). 6 patients died, 3 from their cancer and 3 from comorbidities. Conclusions: Chemoradiation is well enough tolerated even in elderly patients and also an efficient and organ sparing therapeutic alternative for patients over 65 years old. The treatment choice was based on patients’ preference considering better quality of life with bladder preservation. The use of age-specific therapy adjustments has shown that aggressive treatment for bladder cancer is associated with improved survival even in elderly patients.

No significant financial relationships to disclose.
Nude mice model of primary human nonseminoma germ cell tumors to study biology and resistance to cisplatin treatment
Authors: Piulats J. M. , Nadal M. , Martinez-Iniesta M. , Puertas S. , Gonzalez S. , Vidal A. , Condom E. , Germa-Lluch J. , Garcia Del Muro X. , Villanueva A.
Published: August 2020

e16143

Testicular germ cell tumors (TGCTs) are the most common malignancy in young men. Recently, our group has reported the development of a model of human nonseminoma (NSE) after orthotopic nude mice implantation (Piulats et al, Amer Assoc Cancer Res. 2006). Pure and mix NSE anatomies were represented and they reproduce the main histological, genetic and epigenetic characteristics of paired primary tumors. Xenografts mimic distal dissemination patterns and cisplatin (CDDP) tumor behavior responses. This model has been useful for the study of antiangiogenic therapies (Piulats et al, ASCO. 2007), furthermore we want to demonstrate it is an useful tool to study the genetic mechanisms related with CDDP adquired resitance. We have generated in vivo five tumors showing increased resistance to CDDP by exposition to repetitive cycles and increasing the dose applied through different passages (1 yolk-sac; 1 choriocarcinoma; 2 embrional carcinoma; 1 mix tumor). A shortness time elipse between pasajes was observed for each tumor through CDDP treatments. To confirm increasin resistance, a parallel assay of chemotherapy response was performed between nontreated and CDDP resistant tumors. Whole genome analysis of tour xenografted tumors and their paired CDDP resistant tumor (#3 and #5 passage) were analyzed by CGH NimbeGen arrays using 60 Kb average windows. Few differential genomic changes were identified some of them were consistent across resistant tumors including gain of 9q21.11–9q33.3, 15q23–15q24.1, and 15q26.3 regions and loss of Xp22.33. In one tumour showing strong CDDP resistance compared with its sensitive counterpart it occur in absence of new genomic changes. No changes in the MSI or mutational TP53 status were observed in resisant tumors. Our data suggest that acquisition of tumor resistance to CDDP in TGCTs may proably depend of a combination of different mechanisms, including cromosomal imbalances.

No significant financial relationships to disclose.
The effects of sorafenib and sunitinib on bone turnover markers in patients with bone metastases from renal cell carcinoma
Authors: Sahi C. , Knox J. J. , Hinder V. , Deva S. , Cole D. , Clemons M. , Broom R. J.
Published: August 2020

e16145

Background: Bone metastases (BM) from renal cell carcinoma (RCC) are common and associated with poor outcomes. While the multi-tyrosine kinase inhibitors (TKI's) sunitinib and sorafenib have advanced the treatment of metastatic RCC, their efficacy on BM is unknown. Urinary N-telopeptide (uNTX) is a marker of bone turnover measured in nmol/mmol creatinine. Elevated uNTX levels correlate with an increased risk of skeletal related events and mortality in patients receiving bisphosphonates for BM from a range of primaries. In this pilot biomarker study we sought to prospectively evaluate the effects on BM of these multi-TKI's in RCC patients. Methods: Eligible patients had advanced RCC, at least one BM evident on imaging and no bisphosphonate exposure within 4 weeks. UNTX levels (OsteoMark) were measured at; baseline and weeks-1, 4, 8 and 12 after commencing either sunitinib or sorafenib. The primary endpoint was the percentage change (Ch) in uNTX levels from baseline. Serum samples were also collected for KIT and VEGFR-2 (Quantikine). Patients also completed pain (including bone pain) and quality of life questionnaires. Results: The uNTX results on the first 9 patients are presented in the table below (7 received sunitinib and 2 sorafenib). In this group, sVEGFR-2 and sKIT levels fell by week-1 and 4 respectively and at week-12 the mean % changes (95% CI) were -34% (-0.53,-0.14) and -38% (-0.58,-0.18). Conclusions: In patients with BM from RCC and at least moderately elevated uNTX levels at baseline, these multi-TKI's show a significant trend to decrease uNTX levels, but perhaps not as effectively as bone-specific therapies (e.g. bisphosphonates) do in other malignancies. SVEGFR-2 and sKIT levels also fell across the patient group over the same period. This pilot data raises questions about the activity of the multi-TKI's in BM from RCC and further research is needed. [Table: see text]

[Table: see text]
Discharge in less than 30 hours after an open radical retropubic prostatectomy. A prospective study
Authors: Café E. , Tannus M. , Nepomuceno E. , Quintiliano F. , Boente P.
Published: August 2020

e16156

Background: Radical Retropubic Prostatectomy (RRP) is one of the most frequent surgery performed by urologists and it has been accompanied by an improvement in surgical results such as duration of hospitalization. In this study we prospectively analyzed the viability of an early discharge from hospital after an open RRP. Methods: There were 37 consecutive RRP performed by the same surgeon from March 1st to August 30th of 2007. All of the patients were informed about the possibility of discharge from hospital in less than 30 hours after the surgery. The procedures were performed using a modified Walsh technique under combined anesthesia (general anesthesia and epidural anesthesia p analgesia with morphine) through midline incision initiated approximately 5,0 centimeters below of umbilicus. Obturatory lymphadenectomy was performed in only three patients and Exclusion criteria included patients with an Body Mass Index above 30, patients who refused to participate in the study and those with prior indication to go to the intensive care unit postoperatively. Respiratory and motor physiotherapy were initiated soon after return from the surgical block. Criteria to discharge from hospital included: good acceptance of oral diet, no need for parenteral analgesics; urinary volume > 75 ml/hour; no Foley catheter obstruction; absence of gross hematuria; urine drainage < 150 ml/24 hours. Results: 32 patients (86%) had discharged from hospital in less than 30 hours after the surgery: there were 25 patients (68%) discharged in the first 24 hours after surgery and 07 patients discharged between 24 and 30 hours after surgery. There wasn't any readmission in a period of 15 days after discharge from hospital. There were only three complications (8%)on days 07, 10 and 13 and 01 patient need to wash an obstructed Foley catheter with blood clot at postoperative day four. Conclusions: By means of simple criteria it is possible to early discharge patients after an open RRP in selected patients and it may represent a significant reduction in costs.

No significant financial relationships to disclose.
A review of the patterns of docetaxel use for hormone refractory prostate cancer (HRPC) at the Princess Margaret Hospital
Authors: Chin S. N. , Wang L. , Lau A. , Moore M. , Sridhar S. S.
Published: August 2020

e16161

Background: Docetaxel is standard of care for the treatment of HRPC, based on two large randomized clinical trials. The aim of this study was to determine if docetaxel use and effectiveness in routine clinical practice was similar to that seen in the TAX 327 randomized phase III clinical trial. Methods: A retrospective chart review was undertaken to assess patterns of docetaxel use for HRPC at our institution for the 2-year period since its approval for the first-line treatment of HRPC in 2005. Results: Eighty-eight patients, median age 71 and baseline PSA 107, received docetaxel in the first line setting. Main reasons for initiating docetaxel were rising PSA (90%) and progressive symptoms (71%). Eighteen percent of patients received docetaxel for rising PSA alone. A median of 7 cycles was administered. PSA response rates were 61%, time to response 1.5 months, and response duration 6.8 months. Disease progression was the most common reason for treatment discontinuation (36%). Main toxicities were fatigue (32%) and neuropathy (22%). Kaplan Meier survival analysis showed median duration of survival was 15.9 months (95% CI 12.4–20.5) from first drug use. 1-year survival was 0.63 (95% CI 0.52–0.72). Post-docetaxel, 36 patients received second-line treatment, mostly with mitoxantrone (89%). Second-line response rates were 22%, and median duration of response was 4 months. Conclusions: In routine clinical practice, docetaxel is a well-tolerated regimen for the treatment of HRPC. Response rates and toxicity profiles were comparable to the randomized trials. However, compared with the TAX 327 clinical trial, survival was slightly shorter than expected (15.9 vs. 18.9 months), possibly due to inclusion of patients with poorer performance status and comorbidities, who may be excluded from clinical trials. Second-line response rates were also comparable with previous reports.

No significant financial relationships to disclose.
Demographics, response, and overall survival of patients with advanced renal cell cancer to sunitinib in a cohort of minority patient population
Authors: Shah M. , Sreenivasappa S. , Kouz R. , Ciobanu B. , Mullane M. , Yim B.
Published: August 2020

e16164

Background: Sunitinib is a tyrosine kinase inhibitor active in renal cell cancer (RCC). There is scanty literature of its efficacy in minority population. Methods: 21 patients (pts) with RCC who received sunitinib between February 2006-September 2007 were identified and studied as a retrospective cohort. Clinical and survival data were analyzed using fisher's test, chi square test, Kaplan Meier analyses. Results: Of the 21 patients, 11 (52%) were female and 10 (47%) male, 7 (33.3%) African American, 7 (33.3%) Hispanic, and 5 (23.8%) Caucasian. Median age at diagnosis was 59 years (32–74). 7 (33.3%) had clear cell and 3 (14.3%) sarcomatoid pathology. Mixed, poorly differentiated, papillary and unknown histology were 2 (9.5%) each. 12 (57%) pts had stage 4 disease at diagnosis, stage 3 in 3 (14.3%), stage 2 in 1 (4.8%) and 5 (23%) had missing data. 14(66.7%) pts underwent nephrectomy while 7 (33.3%) did not. 6 (28.6%) pts has good MSKCC risk score, 11 (52.4%) intermediate risk and 3 (14.3%) poor risk. Sunitinib was given at a dose of 50 mg daily for 4 wks followed by 2 wks off. Median duration of treatment was 2.5 months (0–9 mts) and median follow up was 13 mts (1–21 mts). Common grade 3–4 toxicities observed were hand foot syndrome (n = 2), hypertension (n = 2) and thrombocytopenia (n = 1). 4 pts discontinued therapy due to adverse events. 5 (23.8%) has stable disease and 13 (61.9%) had progressive disease. Response to sunitinib was not influenced by sex, race, performance status, MSKCC Score, serum calcium level, LDH and hemoglobin level. Median survival of the group was 4 mts with no difference based on gender (p = 0.8), ethnicity (p = 0.8) or histologic type (p = 0.7). Survival of pts with ECOG performance status (PS) 1 was 8 mts, PS 2 was 4 mts, PS 3 was 2 mts (p = 0.001), MSKCC good risk was 9.4 mts, intermediate score was 9.4 mts and poor risk was 2 mts (p = 0.18). Hemoglobin (p = 0.6), LDH (p = 0.6), calcium (p = 0.2) did not affect the survival. Conclusions: In this minority cohort of pts with RCC treated with sunitinib, response and median survival is much lower than the historical controls. Tolerability and side effect profile are similar to reported literature. Prospective studies are warranted in the treatment of RCC with sunitinib in ethnic minority population.

No significant financial relationships to disclose.
The efficacy of systemic lymphadenectomy for overall survival in epithelial ovarian cancer: A systematic review and meta-analysis by KOGYMAG
Authors: Kim H. , Ju W. , Jee B. , Kim J. , Song Y. , Lee H.
Published: August 2020

e16509

Background: The role of systemic lymphadenectomy remains unclear for improving overall survival in epithelial ovarian cancer (EOC) till now. To evaluate the efficacy of systemic lymphadenectomy for survival in EOC, Korean Gynecologic Meta-analysis Group (KOGYMAG) performed a meta-analysis of all studies which compared systemic lymphadenectomy versus non-systemic lymphadenectomy (not performed or lymph node sampling). Methods: Studies were retrieved by searching PubMed, Embase, and Cochrane Controlled Trials Register (CENTRAL) electronic database. The literature search was conducted between 1995 and 2008. The meta-analysis was carried out on 11 studies (2 randomized controlled and 9 retrospective studies) and a total of 30,534 patients with EOC who underwent staging laparotomy including systemic lymphadenectomy or nonsystemic lymphadenectomy. The study endpoint was overall survival, and we extracted adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival from all studies and obtained pooled estimates using an inverse-variance model. Results: In all studies, systemic lymphadenectomy was a favorable factor for overall survival as compared to non-systemic lymphadenectomy (HR, 0.76, 95% CI, 0.65 to 0.88; random-effects model). When we performed sub-analysis according to disease status, patients treated with systemic lymphadenectomy showed improved overall survival compared to those with non-systemic lymphadenectomy in 3 studies where only patients with early-stage EOC (FIGO stage I-II) were included (HR, 0.70; 95% CI, 0.63 to 0.77; fixed-effects model). Furthermore, systemic lymphadenectomy was also a significant factor for improved overall survival in 5 studies where only patients with advanced-stage EOC (FIGO stage III-IV) were enrolled (HR, 0.91; 95% CI, 0.85–0.96; fixed-effects model). Conclusions: These results support that systemic lymphadnectomy may improve overall survival in patients with EOC. However, there are some limitaions including few randomized controlled studies and the deviation of weight in this meta-analysis. Thus, large-scale randomized controlled trials are required to evaluate the efficacy of systemic lymphadenectomy in EOC.

No significant financial relationships to disclose.
Regulation of the EGFR-E2F3a axis by the interferon regulatory factor (IRFs) and by promoter methylation of miR-34a in ovarian cancer
Authors: Reimer D. , Hubalek M. , Riedle S. , Skvortsov S. , Erdel M. , Mueller-Holzner E. , Marth C. , Altevogt P. , Zeimet A. G.
Published: August 2020

e16522

Background: Although, EGFR targeting has reached “bedside” in various tumor entities, including ovarian cancer, the essential role of E2F3a in EGFR mediated proliferation remained uncovered. Recently, we outlined the clinical relevance of E2F3a in ovarian cancer. Now we were able to elucidate the pathway between EGFR activation and E2F3a induction. Methods: Promoter mapping of E2F family members was assessed using the JASPER software. E2F3a protein was assessed by immunoblot analyses in siRNA based IRF-1, IRF-2 knockdown HOC-7 cells. Cell growth was determined by MTT assays after siRNA based knockdown of E2F3a. Expression of E2F3a regulating miR-34a, miR-210 and miR-20a were assessed by RT-PCR in 130 ovarian cancer patients and methylation status of the E2F3a promoter and of miRNA promoters were estimated using Methyllight. 6p22 amplification status of patients was determined by FISH analyses. Results: Promoter mapping of E2F family members revealed that IRF-1 and IRF-2 are potential intermediate components of the herein described EGFR-E2F3a axis. As evidenced by knock-down of IRF-1, IRF-2 or both, the ratio between the two mutually antagonistic IRF-1 and IRF-2 was found to be substantial for EGF induced E2F3a up-regulation. E2F3a knock-down yielded a complete abolishment of EGF induced cancer cell proliferation. Although, activated EGFR status showed a highly significant correlation with E2F3a expression, a subgroup of patients presented high E2F3a mRNA levels without EGFR activation. Within this subgroup promoter methylation of miRNA-34a, that regulates E2F3a, was revealed to represent an alternative mechanism of E2F3a regulation in ovarian cancer, whereas promoter methylation of E2F3a itself was not relevant in E2F3a control. Unlike in prostate or bladder cancer 6p22 amplification was not found to be relevant for E2F3a up-regulation in ovarian cancer. Conclusions: Our present data point to the substantial role of the ratio between IRF-1 and IRF-2 in EGFR mediated E2F3a induction. Furthermore, in vivo regulation of E2F3a involves methylation and thereby silencing of miR-34a. Targeting of the herein described molecular pathway, downstream EGFR, could represent an appealing therapeutic approach in ovarian cancer.

No significant financial relationships to disclose.