bluuebunny/crossref_metadata_2025_split huggingface dataset:
A longitudinal assessment of treatment-related differences in quality of life among prostate cancer patients
Authors: Giedzinska-Simons A. , Christie K. M. , Meyerowitz B. E. , Gross M. , Agus D. B. 
Published: March 2020

15605 Background: Physicians increasingly are asked about changes in quality of life (QOL) following treatment. This is especially relevant for prostate cancer (PC), a disease for which different primary treatments expose patients to differing risks of adverse effect with similar expected benefits in terms of survival. Few studies have compared QOL for the major treatment approaches in a prospective, longitudinal design. Methods: 53 PC patients completed mailed questionnaires assessing general, emotional, social, functional, physical, and prostate-specific QOL with the FACT; stress with the Impact of Events Scale-R (IES-R); and mood with the Positive and Negative Affect Schedule. Data were collected prior to treatment and at 1 month and 6 months post-primary disease treatment. Patients’ primary treatments were radical prostatectomy (RP; N=22), radiation (N=16), or conservative therapy (androgen deprivation treatment only (ADT); N=15). Responses were compared in a mixed-factorial ANCOVA design, controlling for disease severity (Gleason score) and age. Results: Although there were no main effect differences by treatment group, treatment by time interactions emerged for physical QOL (p=.002), stress (p=.04), and negative affect (p=.01). Examination of patterns of response indicated that physical difficulties remained fairly consistent for RP and radiation patients over time, whereas ADT patients showed a gradual decline in physical QOL. For stress and negative affect, RP patients reported highest levels of distress prior to treatment and experienced a gradual recovery over time. Radiation patients followed a similar, although less dramatic, trajectory for stress but showed little change in negative affect. ADT patients had relatively low levels of stress at each time point. Their levels of negative affect were similar to those of radiation patients. Conclusions: Even after controlling for age and disease severity, this examination of patient QOL over time suggests the pre-treatment period is especially stressful for RP patients, and that ADT patients exhibit a gradual decline in physical QOL over time. These results may help physicians anticipate and discuss treatment-specific trends in QOL with their patients, thus enhancing patient care. No significant financial relationships to disclose.
Low-dose docetaxel, estramustine and thalidomide followed by maintenance thalidomide in androgen-independent prostate cancer (AIPC): Final results of a phase II community based study in elderly men
Authors: Frank R. C. , Versea L. , Cohen N. , Long J. , Nair K. 
Published: March 2020

15609 Background: The TET regimen was developed to test the potential synergy and tolerability of low dose, metronomic chemotherapy plus an anti-angiogenesis agent in the treatment of AIPC in elderly men. Preliminary results were presented in 2004 (ASCO Proceedings #4681); we now present the final results 5 years from protocol initiation. Methods: Eligible patients had progressive AIPC, an adequate PS (0–2) and were chemotherapy naïve. All patients received the TET regimen: Docetaxel (Taxotere [T]) 25 mg/m2 weekly for three weeks per month, Estramustine 140 mg po tid x 3 days per week (with T) and Thalidomide (Thal) 100–200 mg as tolerated. After six monthly cycles of TET, patients with responding or stable disease received maintenance Thal until progression. Coumadin 2 mg daily was given for thromboprophylaxis. A total of 19 patients out of an intended 25 were accrued from 6/01 to 9/05. Results: The median age was 79 (59–86); 70% of patients were ≥ 75 years of age. The median PSA was 83 (20–2266), median Gleason score 7, bone metastases were present in 14/19 patients and measurable disease in 12/19 patients. 17 patients completed at least one cycle of TET and were eligible for analysis. The PSA declined >50% in 10/17 (59%); there was 1 PR and 7 SD by RECIST criteria. Of six patients that received maintenance Thal, only one had PSA stabilization for more than three months. The median survival was 17 months. The major grade ¾ toxicities included non-life threatening DVT (3 patients), asthenia (6 patients), edema and dyspnea (one patient each). Thal 200 mg was especially poorly tolerated, requiring dose reductions in over half of the patients. Conclusions: In this trial of elderly men with AIPC, low-dose TET did not seem to improve upon the results previously reported for docetaxel or docetaxel/estramustine. The observed toxicities make it doubtful that a higher dose TET regimen could be tolerated by this population. Thalidomide maintenance was ineffective in maintaining responses. No significant financial relationships to disclose.
Clinical trial accrual rates in prostate cancer: Prospective experience from a single institution
Authors: Vogelzang N. J. , Wong B. , Pomerantz D. , Power K. L. , Adams C. W. , McBeath R. B. , Dincer A. , Symanowski J. T. , Sharma S. 
Published: March 2020

15611 Background: Clinical trial (CT) participation is a key to better cancer therapy. The Nevada Cancer Institute (NVCI), the official cancer center of NV, is committed to CT participation. We hypothesized that CT accrual at the NVCI should exceed the national average of 3–5%. Methods: Patient (pt) visits began in 3/05 and by 12/31/07 1363 pts had been seen. Prostate cancer (PC) was the largest group (N=270; 50 with 1 visit only). All records are electronic and entered into a cancer registry. A relatively robust portfolio of PC CTs has been available, thus the cancer registry data base was compared to the CT data base for the 16 PC CTs (8 phase III, 1 phase II, 7 phase I) that accrued pts. The data base records all accruals, screen failures, consent withdrawals, and subsequent treatments (on or off CT). Results: 101 consents were signed by 68 PC pts (25 consented to 2 or more CTs). 31 consents lead to screen failures/consent withdrawal (5 pts were screen failures for 2 CTs while 1 pt was a screen failure for 3 CTs). Screen failure was less common in phase II/III CTs (18/74 =24%) than in phase I CTs (10/27=37%). Most of the phase I screen failures were due to rapid decreases in performance status or organ function dysfunction. Among the 68 unique pts who consented, 35 pts were treated on 1 CT and 16 pts were treated on 2 or more CTs resulting in a total of 51 PC pts being treated on at least 1 CT. Conclusions: CT accrual at the NVCI of PC pts (51/270=19%) exceeds the national average. Reports of CT activity should specify the denominator and include both consent and accrual rates. Screen failure/consent withdrawal was common in this older male population with advanced disease. This analysis has limitations; Phase I CTs were activated only after 10/05, only 1 phase II CT was open during this period and CTs for radiation and surgery alone for PC pts were not open. Thus, the percent of pts on CT should rise as more CTs are activated. No significant financial relationships to disclose.
Ex vivo isolation of RCC-reactive CD8+ CTL clones from HLA-identical allogeneic donor T cell lines stimulated by CD80-transfected tumor cells
Authors: Tykodi S. S. , Thompson J. A. , Sandmaier B. M. , Maris M. B. , Storb R. , Manley T. J. , Riddell S. R. , Warren E. H. 
Published: March 2020

15625 Background: Regression of metastatic renal cell carcinoma (mRCC) is observed in a minority of patients treated by immunotherapies such as interleukin-2 (IL-2), interferon-a (IFN-a), or reduced-intensity allogeneic hematopoietic cell transplantation. However, the development of specific cellular immunotherapies for mRCC has been hindered by the lack of molecularly characterized T cell antigens with preferential expression on RCC cells. We have developed an ex vivo strategy for the isolation of RCC-reactive CD8+ CTL clones that may facilitate the identification of novel RCC-associated T cell antigens. Methods: RCC tumor lines were established from two patients with mRCC presenting to our institution for allogeneic HCT received from either an HLA-matched sibling or volunteer unrelated donor. Irradiated RCC tumor lines that were unmodified or transfected with a cDNA for human CD80 were used to stimulate responder CD8+ T cells isolated from pretransplant patient (autologous) or donor-derived (allogeneic) blood samples in mixed lymphocyte/tumor cell (MLTC) cultures supplemented with recombinant human IL-7 and IL-12 (stimulation #1) or IL-2 (2nd and subsequent stimulations). T cell lines with anti-tumor activity measured by IFN-γ ELISA were then cloned by limiting dilution. Results: After two or more in vitro stimulations, allogeneic CD8+ T cell lines stimulated by CD80- transfected RCC tumor cells, but not the other MLTC culture combinations tested demonstrated tumor-specific IFN-γ release. CD3+/CD8+/TCRaβ+ CTL clones with potent in vitro anti-tumor activity for unmodified RCC tumor were isolated from both sibling- and unrelated- donor derived T cell lines. Three such clones with unique specificities for allogeneic targets recognized the unmodified RCC tumor but not LCL or fibroblast target cells isolated from the same patient suggesting tumor-restricted expression of the target antigens. Conclusions: Ex vivo MLTC culture utilizing CD80-transfected RCC tumor and HLA- matched allogeneic responder CD8+ T cells warrants further study as a strategy to isolate CTL clones that may be used to identify novel RCC-associated T cell antigens. No significant financial relationships to disclose.
Erectile function following unilateral cavernosal nerve graft
Authors: Corman J. M. , Borden L. S. , Hanson G. R. 
Published: March 2020

15642 Background: Over the past 20 years, radical prostatectomy has been a mainstay in the treatment of localized prostate cancer. With the adoption of nerve-sparing procedures, select patients may avoid the consequence of erectile dysfunction.Certain patients who are not candidates for nerve-sparing procedures may be eligible for nerve interposition grafts. While bilateral cavernosal nerve grafting after radical prostatectomy has shown efficacy, the effect of unilateral nerve grafting remains unclear. To further ascertain this outcome, we evaluated a large group of patients who underwent a unilateral cavernosal nerve replacement. Methods: Forty patients underwent unilateral nerve sparing surgery with concomitant contralateral cavernosal nerve replacement by a single surgeon from 2002 to 2006. Patient were selected based upon pre-op nomogram risk assessment, endorectal MRI evidence of extra capsular disease or intraop histology demonstrating margin positivity. Age, demographic data, Gleason score, clinical and pathologic stage and pre and post op IIEF data was collected and prospectively analyzed. An additional phone interview was conducted to assess outcomes and morbidity. Results: Full demographic and interview data was available for 28 of 40 patients (70%). Median follow-up was 19 months. The median age at RRP was 53 with a median pre-operative PSA of 6.5. Median pre- and post-op IIEF scores were 25 and 15 respectively. Median change in IIEF scores was 7.5. 22 of 28 patients (79%) men report being able to penetrate after surgery. 17 of those 22 (77%) continue to require PDE-5 inhibitors to facilitate penetration. 3 of the 6 patients (50%) who were unable to have intercourse following nerve replacement received adjuvant hormonal or radiation therapy. 27 patients (96%) reported numbness at the graft harvest site with three (10.7%) describing this as bothersome. One patient experienced a graft site infection and two of 28 (7.1%) patients reported pain at the harvest site. Conclusion: Unilateral sural nerve grafting is a feasible and well-tolerated approach for patients who must undergo wide resection of a neurovascular bundle. While men do show a sizable decrease in their IIEF score, 79% were able to achieve penetration following surgery. The majority of men require PDE-5 inhibitors to facilitate intercourse. No significant financial relationships to disclose.
A randomized prospective study of low-dose interleukin-2 (IL-2) in combination with interferon-alpha (IFN) and 5-fluorouracil (5-FU) for metastatic renal cell carcinoma: Final results
Authors: Demidov L. , Kharkevich G. , Tsimafeyeu I. 
Published: March 2020

15643 Background: High and intermediate IL-2 regimens are difficult to recommend because of great toxicity. Based on previous activity of combination low-dose cytokines (including 1 MIU IL-2) in metastatic renal cell carcinoma (MRCC) patients (pts) (J Europ Urol, Supp. 2006;5 (2):286), we performed this randomized study. The primary endpoint was response rate. The secondary endpoints were median overall survival (OS) and toxicity in groups. Methods: Eligibility criteria included histopathologically confirmed MRCC, ECOG PS 0- 2, no autoimmune diseases, no brain metastases, and normal organ function. All pts are randomized to IL-2 alone, 1 MIU, iv, t.i.w., weeks 1–3 or IL-2, 1 MIU, iv, t.i.w., weeks 1–3 plus IFN 5 MIU, sc, t.i.w, weeks 1–3 or biochemotherapy group 5-FU, 500 mg/m2, iv, once a week, weeks 1–3 plus IL-2 and IFN. Cycles were repeated every three weeks. Response evaluation was performed according to RECIST every 2 cycles. Results: From Jan 2003 to Jun 2006, 66 pts with any type of MRCC histology were randomized. Median age of the pts was 55.4 years (range 16–74). 43.9% of the patients had been previously treated by chemo- or immunotherapy. 54.5 percent of the pts had poor prognosis by MSKCC criteria. Bone metastases were present in 52.4% pts. Baseline characteristics were well balanced in groups. Pts treated with IL-2+IFN or 5-FU+IL-2+IFN had a statistically longer survival than those treated with IL-2 alone ( Table ). OS and TTP of pts in combined arms were not statistically different. There were no toxicity grade 3 and 4. Conclusions: Low-dose IL-2 alone is not effective. 5- FU does not improve efficacy of the cytokine combination. Low dose IL-2 and IFN demonstrate reasonable efficacy and could be recommend for MRCC pts outside clinical trials and available target therapy. All regiments are well tolerated. [Table: see text] No significant financial relationships to disclose.
Long-term outcome of penile cancer: Single North American institutional study
Authors: Radhakrishnan N. , Roy R. , Thomas A. , Mehrotra B. , Iqbal U. 
Published: March 2020

15645 Background: Penile cancer is a rare malignancy in the Western world with limited published data. We conducted a review of patient (pt.) records diagnosed with penile cancer at our instituition to evaluate the patterns of treatment, responses, recurrences and long term outcomes. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry data was analysed for all adult patients diagnosed with penile cancers between 1995 and 2005. Patient characteristics including age, disease stage, histology, grade, ethnicity, treatment modalities and outcomes were recorded. Results: 24 pts were identified. Median age: 68 years (range: 38 - 86), Stage distribution: Stage 0 (n=7, 29%), Stage I: n =8 (33.%) ; Stage II: n= 4 (17%); Stage III: n = 1 (4%), Stage IV: n=4 (16.7%); ethnicity: Caucasian:17, African-American: n=3; Hispanic: n=1;and South Asian: n=6; Histology: squamous (sq.): n = 21(88%), sq. with sarcomatoid features: n=1(4%), small cell ca: n = 1, (4%); poorly diff. ca: n = 1 (4%). Grades 1,2,3 in each stage respectively : stage I: ( n= 4, 2, 1), stage II: (n = 0,1,2), stage III: (1,0,0), stage IV: (n = 1,2,1). Treatment and Outcome: All pts with stage 0 disease were treated with excision biopsy. 3 of 7 (40%) recurred but are disease free after re-excision. All pts with Stage I disease were treated with partial penectomy. Two of 8 (25%) recurred, of which one pt died of his disease. All pts with stage II were treated with surgery (penectomy) and CT. One pt was additionally treated with RT to the groin. Except for this pt all stage II pts recurred and died due to recurrent disease. The pt with stage III disease was treated with a partial penectomy and CT and remains disease free without recurrence. All pts with stage IV disease were treated with CT, 3 were also treated with RT , but all died of metastatic disease. Median OS: Stage 0: 70+ mo, (20–150 ); Stage I: 69 mo (11–133); Stage II: 25 mo(12–84); Stage III: 25 mo; Stage IV: 7 mo ( 7- 23); Conclusions: Pts with early stage 0 and I disease have a high local recurrence rate (33%) but are curable with surgical salvage. Stages II, III and IV pts have high recurrence rates and poor prognoses despite treatment with penectomy and CT. Future trials should address the benefit of adjuvant chemo/RT in patients with intermediate stage (II & III) disease. No significant financial relationships to disclose.
Phase I clinical study on docetaxel/zoledronic acid combination administered in two different sequences in hormone refractory prostate cancer patients
Authors: Iaffaioli R. V. , Facchini G. , Caraglia M. , Bruni G. S. , Maiolino P. , Nasti G. , Marra M. , Addeo S. R. , Gallo L. , Budillon A. 
Published: March 2020

15646 Background: Docetaxel (DTX) has been proposed in the treatment of hormone-refractory prostate carcinoma (HRPC) as single agent and the combination between DTX and prednisone and that one between DTX and estramustine has been reported to give a higher survival as compared with the combination between mitoxanthrone and estramustine. Zoledronic acid (ZOL) is an important therapeutic weapon in the treatment of the patients affected by advanced hormone refractory prostate cancer (HRPC). Our preliminary data on prostate cancer cells in vitro suggest that ZOL and DTX are synergistic on the growth inhibition of these cells and the synergism is sequence-dependent. Prostate cancer is, therefore, a suitable target for a pharmacological combination between DTX and ZOL. On the basis of these considerations, a phase I trial on the combination between ZOL and DTX was designed in the treatment of HRPC. Methods: Phase I study with a dose-escalation DTX in combination with a defined and fixed dose of ZOL (2 mg), both administered every 14 days. The following two different sequences of administration were, moreover, explored: Sequence A: DTX at the day 1 followed by ZOL at the day 2. Sequence B: ZOL at the day 1 followed by DTX at the day 2. The first dose level of DTX was 30 mg/m2 with a programmed dose escalation of 10 mg/m2 for each level until 50 mg/m2. Sear and PBMC were also collected prior and after the different treatments at each cycle. Results: Up to date the MTD was not achieved. We have reached the second level (40 mg/m2) without recording any treatment related toxicities. Interestingly one of the 2 sequences induced a less number of haematological side effects and absence of gastrointestinal effects. A different pattern of modulation of circulating angiogenic factors (interleukin 8 and 12, VEGF, PDGF), cytokines (TNF alpha, IFN gamma, interleukin-6 and 4) and gamma/delta T lymphocyte subpopulation is recording in the 2 sequences of administration. Conclusions: The study is still ongoing and further results will be presented at ASCO meeting. No significant financial relationships to disclose.
Hypoxia-inducible protein 2 (HIG2) as a new biomarker of ovarian clear cell adenocarcinoma
Authors: Nishimura S. , Tsuda H. , Ito K. , Kita T. , Terai Y. , Sudo T. , Jobo T. , Kigawa J. , Sugiyama T. , Yaegashi N. 
Published: March 2020

16001 Background: Epithelial ovarian cancer (EOC) can be subclassified into five major histologic types (Serous(SC), Mucinous(MC), Endometrioid(EC), Clear cell(CC), Undifferentiated (UC)). Among them, CC generally has a poor response to combination chemotherapy and its overall prognosis is poorer, as compared with other histologic types. In previous reports, we compared gene expression profiles in CC and SC using cDNA microarrays and suggested that HIG2 gene might be a new biomarker for CC (Clin Cancer Res, 2005). In this study, we generated a polyclonal antibody for HIG2 and further validated the expression of HIG2 in EOC. In addition, HIG2 expression was evaluated in CC derived from endometrium(EMCC) and kidney(KDCC). Methods: Formalin-fixed surgical samples from 254 EOC, 17 EMCC and 29 KDCC patients were included in this study. HIG2 expression was investigated by immunohistochemistry. HIG2 cytoplasmic staining were divided into positive or negative. Results: Histologic types and stages of EOC were as followed: (SC: 51; MC: 25; EC: 31; CC: 130; UC: 17) and (I: 96; II: 37; III: 100; IV: 21). In EOC, 175 of 254(69%) cases had HIG2 expression. The relationship between HIG2 expression and histologic types was shown in table . The positive rate of HIG2 in CC was significantly higher than other histologic types in EOC. However, there is no significant correlation between HIG2 expression and stages or grades. In addition, both CC of the ovary and endometrium showed significantly higher levels of HIG2 expression compared to those of CC of the kidney. Conclusions: HIG2 expression is a new biomarker for CC. [Table: see text] No significant financial relationships to disclose.
Profiles of ovarian cancer patients that benefit from taxane-platinum and platinum-based chemotherapy
Authors: Markowska J. , Bidziáski M. , Stelmachów J. , Kraszewska E. , Ziółkowska-Seta I. , Madry R. , Timorek A. , Rembiszewska A. , Kupryjaáczyk J. 
Published: March 2020

16005 Background: Taxane-platinum therapy (TP; regarded as more efficient than platinum-based therapy, PC) is a standard postoperative treatment of ovarian cancer patients; however, in 20 to 30% of patients the treatment is uneffective. Normal TP53 protein is a prerequisite of cancer cell response to PC, while TP53 inefficiency may enhance tumor sensitivity to taxanes. We compared the effectiveness of PC (n=253) and TP (n=199) with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease. Methods: Immunohistochemical analysis with PAb1801 antibody was performed on 452 archival tumors; multivariate analysis by the Cox and logistic regression models was performed in all patients and in subgroups with [TP53(+)] and without TP53 accumulation [TP53(-)]. The therapeutic regimens were evaluated in comparison with each other and also with interactions with clinicopathological parameters. Results: TP enhanced probability of complete remission (CR, p=.05), platinum sensitivity (PS, p=.02) and longer survival (OS, p=.008) in the TP53(+) group. In the TP53(-) group TP did not show an advantage over PC in regard to CR and PS and it diminished a chance of platinum highly sensitive response (p=.04). However, in the TP53(-) group TP appeared to diminish risk of death of patients >53 yrs (p=.063). Analysis of interactions revealed that TP therapy might be more efficient in patients with: endometrioid and clear cell carcinomas, stage III disease, G2 tumors or residual tumor > 2cm. Nevertheless, in the TP53(-) group TP did not diminish risk of death of patients =53 yrs with these characteristics. Conclusions: Our results suggest that taxane-platinum therapy should be given to patients older than 53 years and to all with TP53 accumulation in their tumors. In the group of patients =53 yrs and with TP53(-) tumors (20% of patients in our study) treatment with PC may be equally or possibly more efficient than TP. No significant financial relationships to disclose.