bluuebunny/crossref_metadata_2025 huggingface dataset:
Audit of excisional breast biopsies in a Nigeria teaching hospital
Authors: Adisa C. A.
Published: March 2020

1553

Background: Excision biopsy is an accurate method for diagnosis of breast tumors especially where facilities for needle biopsies like tru cut needle biopsy or aspiration cytology method are not readily available. We report a 10-year prospective study of the clinical and pathological characteristics of excised breast masses in our centre. Methods: Clinical records and pathological results of all excised breast masses of consecutive patients referred to the Breast Clinic of the Abia State University Teaching Hospital, Aba, Nigeria were studied from January 1994 to December 2003. We present the outcome of the histology reports from breast biopsy for a period of 10 years (1994–2003) in Abia State University Teaching Hospital. Results: A total of 421 patients had breast masses excised. The age ranged from 12 years to 80 years. 79% of the patients with cancer of the breast were 50 years old or younger and the youngest patient was 14 years. Malignancies were discovered in 24% of the cases and the predominant histological type was infiltrating ductal carcinoma (NOS). 79% of the breast cancers occur in pre menopausal women and the majorities (85%) were late stages. Conclusions: Majority of breast masses in Nigerian women are benign. The preponderance of late staged tumors and pre menopausal patients call for early detection, public awareness and improved screening methods.

No significant financial relationships to disclose.
Factors predicting the development of and survival from brain metastasis in transitional cell carcinoma of the bladder
Authors: Tran C. T. , George J. , Miranda G. , Hamid O. , Stein J. P. , Quinn D. I.
Published: March 2020

15541

Background: To date there are no substantial series reported evaluating brain mets in TCC of the bladder. This makes therapeutic evidence-based decision making in this setting extremely difficult. Methods: We followed 1898 pts with TCC of the bladder treated with cystectomy from 1972–2004. Cohort analysis was undertaken for factors predisposing to and of factors that predict survival after brain mets. Results: With median follow-up of 3.6 yrs for this cohort, 545/1898 (28.7%) recurred, 30 (1.6%) with brain mets. Median time to brain mets development was 1.14 yrs, range 0.0710.92 yrs. Median time to first TCC recurrence in brain met pts was 0.86 yrs vs. 1.03 yrs for whole cohort (p=0.25). Median OS from cystectomy 1.36 yrs vs. 3.49 yrs for whole cohort (p<0.0001). Median time from brain mets to death, 3.3 mths range 0–143 mths, skewed by 2 outliers surviving 18 and 143 mths. The following factors were associated with risk of brain mets: younger age (60.2 vs. 66.3 yrs, p=0.01) and LN status at cystectomy (p=0.02) while gender, smoking status, T stage, margin status were not; tumor grade showed a nonsignificant trend to association with brain mets (p=0.14). Pathological parameters did not correlate with duration to development of brain mets. In predicting OS after brain mets, diagnosis age, duration to first recurrence, duration to brain met, original T and N stage and development of multiple vs. brain alone recurrence did not impact overall survival. Patients having any therapy (19/30): surgery (6), radiation (11) or chemotherapy (10) or combination had a better survival that those not treated (p=0.0002). Each modality was associated with at least a trend to better OS: surgery (p=0.03), RT (p=0.09), CT (p=0.08). Conclusions: These results need to be interpreted in the context of selection bias for active treatment, however, selected patients with brain mets from TCC bladder do appear to benefit from active therapy. More work in this area will hopefully lead to more rational therapy and better outcomes.

No significant financial relationships to disclose.
Radical retropubic prostatectomy in patients with high risk prostate cancer
Authors: Özgür E. , Ohlmann C. , Pfister D. , Engelmann U. , Heidenreich A.
Published: March 2020

15549

Background: Patients with high risk prostate cancer (Gleason score 8 to 10, cT3 disease or PSA > 20 ng/ml) are at high for cancer recurrence after local therapy such as radical retropubic prostatectomy (RPE) or radiation therapy. We examined the long-term oncological and functional outcome of patients with high risk prostate cancer (PCA) on biopsy. We further investigated prognostic risk factors associated with good prognosis. Methods: We retrospectively analysed the outcome of 304 patients with high risk PCA. All patients received a questionnaire to obtain information with regard to continence, potency, PSA recurrence, PSA mortality and quality of life (EORTC QLQ-30). 237 (78%) patients returned the questionnaires. Results: The mean follow-up is 94 (15–146) months, mean age of all patients is 62.6 (32–78) years. 231 (76%) patients had PSA serum levels of 20–50ng/ml, 62 (23.4%) and 39 (12.8%) had PSA serum levels of 50–100 ng/ml and > 100 ng/ml, resp., a pT3 PCA was identified in 192 (63.1%) patients, pTxpN1 disease was found in 84 (27.6%) patients. Overall survival rate is 81.9%, 86.2% and 85.3% in patients with PSA > 20ng/ml, pT3 or pTxpN1 PCA, resp.; cancer specific survival was 85%, 89.5% and 88.7% in PSA > 20ng/ml, pT3 and pTxpN1 PCA, resp. PSA recurrence rate is 28%; the most significant parameters associated with survival are biopsy Gleason score (p = 0.02), pN1 status (p = 0.001), perineural invasion (p = 0.001), seminal vesicle invasion (p < 0.0005). There was no significant difference with regard to pre- and postoperative quality of life. Continence was good with no pads in 85%, 1- 2 pads/day and = 3 pads/day in 10.6% and 4.4%, resp. Conclusions: RPE can be safely performed in patients with high risk PCA resulting in a high cancer specific survival rate. Most suitable candidates are patients with biopsy Gleason score < 8, pN0 and = pT3a; even in cT3 PCA RPE is a valuable therapeutic option with long-term PCA-free survival and might be considered in men with a long life expectancy.

No significant financial relationships to disclose.
Prostate specific antigen doubling time (PSADT) in patients with hormone refractory prostate cancer (HRPC) undergoing docetaxel chemotherapy as a predictor of overall survival
Authors: Pachynski R. K. , King C. , Srinivas S.
Published: March 2020

15556

Background: Few data correlating PSADT and overall survival(OS) in patients with HRPC undergoing chemotherapy exist. Docetaxel has recently been shown to significantly improve OS in patients with HRPC, but with significant toxicities. The decision of when to initiate chemotherapy is not well defined, but the presence of symptoms or narcotic use has widely been used to indicate this. The current retrospective study aims to identify a specific PSADT that independently correlates with OS in HRPC patients receiving docetaxel. Methods: A retrospective review of all patients with HRPC receiving docetaxel from 2001 to 2006 was performed. Androgen independent prostate cancer (AIPC) was defined as the time of a rising PSA despite castrate levels of testosterone. Variables evaluated from time of AIPC to initiation of chemotherapy included PSA, PSADT, hemoglobin, alkaline phosphatase, Gleason score. Time to AIPC was also evaluated. Patients who had pain or were on narcotics at the time of chemotherapy initiation were considered symptomatic. OS was calculated for both time from AIPC to death or last follow-up, and for time from chemotherapy to death or last follow-up. Results: 50 patients treated with docetaxel for HRPC were evaluated. Median OS was 32 months, and median survival from start of docetaxel was 14 months. There was no difference in OS between symptomatic or asymptomatic patients. A PSADT of >2 mos was significantly correlated with improved median OS (p= 0.005). Univariate analyses of all other factors were not significant. Furthermore, in patients with a favorable outcome ( >14 mos) from start of docetaxel, a PSADT of >2 mos was a significant predictor of improved survival (p=0.02). Conclusions: This is the first study to evaluate PSADT in HRPC patients receiving docetaxel exclusively. Our data shows that a shorter PSADT (<2 mos) significantly predicts shorter OS. Symptoms or narcotic use did not correlate with OS. Taken together, these data suggest that a PSADT of <2 mos may be a better predictor of when to initiate chemotherapy than symptoms or narcotic use. The lack of significant correlation between the other variables and OS may further suggest the robustness of PSADT as a predictive variable.

No significant financial relationships to disclose.
Cost of illness of renal cell carcinoma in Canada
Authors: Abugaber A. , Lang K. , Danchenko N. , Thompson D. , Bhardwaj T. , Bjarnason G. , Finelli A. , Kapoor A. , Jaszewski B.
Published: March 2020

15560

Background: Renal cell carcinoma (RCC) is the most common form of kidney cancer. RCC patients have limited treatment options and low survival rates, particularly for advanced-staged patients. Despite its importance, data on the economic burden of RCC are limited. Methods: A prevalence-based approach was used to estimate the aggregate annual societal cost burden of RCC in Canada. Key relationships represented in the model include the annual number of patients treated for RCC by age group and cancer stage; utilization of cancer treatments; unit costs; work-days missed, and wage rates. Results: The annual prevalence of RCC in Canada in 2005 was estimated to be 17,845 cases. The associated annual burden of RCC (Canadian $2005) was approximately $357 million ($19,981 per patient). Health-care costs and lost productivity accounted for 65.6% ($234 million) and 34.4% ($123 million) of the total, respectively. Reflecting its higher prevalence, the total cost associated with Stage II RCC accounted for the greatest share (67%) followed by Stage I, Stage III, and Stage IV RCC, at 19.8%, 11.6% and 1.6%, respectively. Conclusions: The economic burden of RCC in Canada is substantial at a cost of $357M which represents 2% of the total cost of illness of cancer in Canada ($16.64B, inflated to $2005). Interventions to reduce the prevalence of RCC have the potential to yield considerable economic benefits.

[Table: see text]
Relapse patterns and outcomes in a population-based study of Nova Scotia patients with germ cell tumors (GCT)
Authors: Murphy E. , Douglas J. , Qi Q. , Wood L.
Published: March 2020

15564

Objectives: To examine the frequency and pattern of relapse in a population-based cohort of Nova Scotia patients with germ cell tumors (GCT). Presentation and outcome of these patients will be described with an emphasis on late relapsers. Methods: A retrospective chart review of all patients diagnosed with GCT in Nova Scotia between 1984 and 2004 was completed. Data regarding initial diagnosis and treatment as well as data at time of relapse was collected. Relapse was defined as any recurrence of tumor after initial definitive therapy. Late relapse (LR) was defined as a relapse >2 years from initial definitive therapy or previous relapse. Results: Of the 383 patients diagnosed with GCT during the 20 year period, 135 received chemotherapy. 15/135 (3.7%) patients initially treated with chemotherapy relapsed; 10 early and 5 late. 1/10 early relapsers was alive and NED at 2 years from relapse compared to 4/ 5 late relapsers at 4 years. 3 of the 245 patients whose treatment did not include chemotherapy experienced a LR for a total of 8/383 (2.1%) of all patients. Median time to all LR was 6.6 years. Pathology for 6/8 (75%) patients with LR was nonseminomatous GCT. 50% of patients with LR died. Common to all LR survivors was complete surgical resection ± chemotherapy. All patients with LR who died had either no surgical resection or incomplete surgical resection of disease. Conclusions: The incidence of all GCT patients with LR was 2.1% and the incidence of LR post chemotherapy was 3.7% in this population. The only other population based report of incidence of LR in all GCT patients was 1.3%. A mixture of stages, pathology, and sites of metastases was observed with no obvious baseline or treatment differences between early and late relapsers. Interestingly, in this population, patients with LR had better outcomes than early relapsers. The success to curing patients with LR appears to be complete surgical resection of disease.

No significant financial relationships to disclose.
Trastuzumab (T) combined with standard chemotherapy in HER+ metastatic bladder cancer (BC) patients: Interim safety results of a prospective randomized phase II study
Authors: Beuzeboc P. , Banu E. , Voog E. , Bousquet G. , Priou F. , Deplanque G. , Bozec L. , Machiels J. P. , Vannetzel J. M. , Oudard S.
Published: March 2020

15565

Background: Almost 25% of BC patients overexpressed HER2 and 50 to 60% of them are responding to the combination of T with standard chemotherapy (gemcitabine and platinum salt). A prospective, randomized, European phase II study comparing this association with conventional chemotherapy alone is ongoing. Methods: Eligible HER+ BC pts were required to have an advanced and chemonaive bladder cancer and ECOG performance status (PS) 0–2. The aim is to demonstrate a progression-free survival benefit for investigational arm. Sample size was estimated at 126 patients, with a two-sided alpha and beta levels at 5 and 80%, respectively. Treatment-related toxicities were evaluated using CTC-NCI version 2. Fisher exact test was the main statistical method testing differences in percentage of toxicities. Results: Thirty-seven patients were included in 11 centres between February 2004 and December 2006. The planned safety interim analysis was performed after inclusion of 30 patients (15 in each arm). Median age was 59 years (range 46- 80), 93% of patients are men. Seven percent have an advanced disease, 33% have more than one single metastatic site and 83% were PS ECOG 0–1. There were no significant differences between arms concerning hematological and non-hematological all grade toxicities. Severe (grade III-IV) leucopenia, granulocytopenia, anemia and thrombocytopenia were registered in 53, 53, 33 and 60% for combined arm. Grade I-II of diarrhea was slightly more frequent for T arm. There were no differences for alopecia, constipation, nausea and edema. An asymptomatic reduction of the left ventricular ejection fraction was found in one patient in each arm. Conclusions: Combination of T with standard chemotherapy for BC patients was safe. No serious adverse events significant differences were registered, especially concerning T-related cardiac toxicities. The planned interim efficacy analysis is expected after inclusion of 60 patients.

No significant financial relationships to disclose.
Upper genitourinary tract transitional cell carcinoma (TCC): Long-term outcome data from a large single institutional series
Authors: Roy R. , Radhakrishnan N. , Kaufman M. , Thomas A. , Weiss G. , Iqbal U. , Mehrotra B.
Published: March 2020

15582

Background: TCC of the upper urinary tract (renal pelvis and ureters) is a relatively rare entity and carries a poor prognosis. Literature regarding long term outcomes are lacking. We embarked on a review of pt records to evaluate patterns of practice: ie adjuvant therapies and survival outcomes of pts treated at our tertiary care institution. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry data were analysed for all adult pts with TCC of the renal pelvis and ureter diagnosed from 1995 to 2005. Only patients with locoregionally confined disease were included in this study. Pt characteristics recorded: age, sex, site of disease, stage, grade, treatment modalities and survival outcome. Results: 175 patients were identified. Med. age: 75 yrs (range 40–90). Gender: M:F:107:68; Sites: Renal Pelvis: n=128; Ureters: n=47; Stages: Stg 0: n=46 (26.28%), Stg I: n=68 (38.85%), Stg II: n=19 (10.85%), Stg III: n=29 (16.57%), Stg IV (excl. M1):n=13 (7.4%). Gr 1: n=13 (7%), Gr 2: n=49 (28%), Gr 3: n=78 (45%), Gr 4: n=20 (11%); Unknown n=14 (8%). Gr 3/4 distribution for Stages 0, I, II, III, and IV were 17 (37%), 32 (47%), 15 (72%), 23 (79%) and 11 (84%) respectively. Treatment Modalities: All pts were treated with surgical resection; adjuvant chemotherapy was utilized in Stg I: 5/68; Stg II: 3/19; Stg III: 5/29; Stg IV: 1/13 pts. Adjuvant RT was administered in Stg III: 1/29; Stg IV: 3/13 pts. Med. survival and OS at 1, 2, 5 and 10 yrs are shown in Table 1 for all pts treated with surgical resection alone as standard therapy. Med. Survival of all patients who received any adjuvant therapy was 24 mos. Conclusions: Increasing frequency of higher grade disease was present in higher stage patients. Long term survival of early stage disease despite surgical resection is poor with 5 year OS of 45–62% in Stages 0-II and worse with higher stages III and IV with 5 yr OS of 17- 21%. Clearly, better adjuvant or neo-adjuvant strategies are needed to improve this dismal prognosis.

[Table: see text]

No significant financial relationships to disclose.
Coagulation markers D-dimer and prothrombin fragment 1.2 compared to disease and treatment status in prostate cancer patients
Authors: Wong B. Y. , Fink L. , Symanowski J. , Dincer A. , Adcock D. , Vogelzang N.
Published: March 2020

15587

Background: Activation of the coagulation cascade is a hallmark of advanced prostate cancer (PC). In patients (pts) with advanced PC, the D-dimer and prostate specific antigen (PSA) are frequently elevated; neither is an established predictive marker for response to treatment. We hypothesized that chemotherapy refractory (CRefrac) PC is associated with active thrombin generation, and that D- dimer and prothrombin fragment 1.2 (PF1.2) as activation markers of coagulation could be markers of CRefrac PC. Methods: We analyzed PSA, D-dimer and PF1.2 from a cross section of 29 PC pts. PSA values were measured by the Bayer/Centaur method (Bayer Healthcare, Tarrytown, NY). D-dimer assay was performed using quantitative latex-agglutination (Diagnostica Stago, Asnieres, France), and PF 1.2 levels were determined by enzyme-immunoassay (Dade Behring, Marburg, Germany). Values were analyzed with respect to disease and treatment status. Results: The median age was 66. Twenty pts had metastatic PC, while 9 pts had stable or rising PSA but no evidence of metastatic disease. Among the 20 metastatic pts, 10 were CRefrac, 3 were hormone refractory and 7 were responding to or stable on hormone therapy. Median PSA was 36 ng/ml (range 0.1–1170). Median D-dimer was 372 ng/ml [range 110–13,300; normal (<256 ng/ml)]. Median PF 1.2 was 402 ng/ml (range 100–853; normal 87–325 ng/ml). Only 19 pts had sufficient sample for PF1.2 values. Stratification by disease and treatment status showed significantly higher D-dimer values in CRefrac pts compared to all other pts (median 1144 vs 317, p=0.014, rank-transformed analysis). Eight of 11 CRefrac specimens had elevated D-dimer values; 2 of the 3 exceptions were pts receiving warfarin therapy. Only 3 of 20 non-CRefrac specimens had elevated D-dimer values. Five of 8 CRefrac pts and 8 of 12 non-CRefrac pts had elevated PF1.2 values. Conclusions: D-dimer values are substantially elevated in CRefrac PC. However, the clinical significance of these findings and of the apparent suppression of D-dimer by warfarin therapy is unknown. Longitudinal studies of D-dimer and PF1.2 in PC pts undergoing chemotherapy are needed.

No significant financial relationships to disclose.
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.
Intraoperative intraperitoneal (IP) chemotherapy with cisplatin and escalated dose of epinephrine in patient with recurrent peritoneal carcinomatosis of ovarian cancer: A phase I study
Authors: Guardiola E. , Chauffert B. , Delroeux D. , Benoit L. , Causeret S. , Combe M. , Royer B. , Plaza J. , Heyd B. , Pivot X.
Published: March 2020

16019

Background: IP epinephrine (E) has been shown to enhance the accumulation and antitumor activity of IP cisplatin in rats with peritoneal carcinomatosis (Duvillard et al. Int J Cancer, 1999). E induces a vasoconstriction of peritoneal vascular bed which limits platin peritoneal leakage and enhances drug penetration into tumor nodules. Results of a phase I study with the association of IP E and IP cisplatin in patient with refractory peritoneal carcinomatosis has been reported (Molucon-Chabrot et al, Anticancer Drugs, 2006). We conducted a phase I study to evaluate intraoperative IP chemotherapy with the association of cisplatin and escalated dose of E. Methods: 18 patients (pts) with recurrent ovarian cancer were enrolled. The median age was 56 years old (range 42–66). After an optimal cytoreductive surgery, IP chemotherapy was performed during surgery by filling twice the peritoneal cavity with 3 liters of an isotonic saline pre heated at 37°C and 90 mg of cisplatin associated with increasing concentrations of E during 1 hour. Results: E was escalated according to the following dosage: 0, 1, 2, 3 mg/L (3 pts by step). No toxicity was observed during and after intraoperative IP chemotherapy in the first 10 patients. The 2nd patient included in the 3 mg/L level of E experienced a tachycardia ≥ 120/min, ventricular extrasystoles (VES) ≥ 2/min, increase of troponine plasmatic concentration without significant electric sign of cardiac ischemia. The 3rd patient at this level experienced a tachycardia ≥ 120/min with ventricular VES ≥ 2/min and no increase of troponine concentration or electric sign of cardiac ischemia. According to the protocol design, 6 additional patients were included in the lower dose of 2 mg/L of E and no toxicity occurred. One can consider that the recommended dose of E was established. Conclusion: The combination of IP E with IP cisplatin in intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The limiting toxicity was the cardiovascular effect which occurred with 3 mg/L dose of E. A phase II-III study is planned to investigate if IP chemotherapy adds to a second look surgery for the initial treatment of stage III ovarian carcinoma.

No significant financial relationships to disclose.
Oxaliplatin and 5-fluorouracil in heavily pretreated patients with ovarian carcinoma: A well tolerated and efficient treatment
Authors: Rosa D. D. , Awada A. , Cardoso F. , Gil T. , Lebrun F. , Mano M. S. , Selleslags J. , Piccart M. J. , D'Hondt V.
Published: March 2020

16028

Background: Recurrent ovarian cancer is an incurable disease. The prognosis of patients with platinum refractory disease is dismal. We present data from heavily pretreated patients with recurrent ovarian cancer to whom the Folfox regimen was administered. Methods: Patients with recurrent, resistant or refractory, pretreated ovarian carcinoma were eligible for this compassionate use program of oxaliplatin (85 mg/m2 in 2 hours) and leucovorin (200 mg/m2 in 1 hour) on day 1, followed by a continuous infusion of 5FU (2,600 mg/m2 in 48 hours), every 2 weeks. The objectives of the study were primarily to assess response rate and secondarily to evaluate the safety profile. Results: Fourteen patients were treated. Median age: 56 years (49–70). Performance status: 0 (n=4) and 1 (n=10). Median number of previous chemotherapy regimens: 5 (3–10) and previous platinum-based regimens: 2 (1–3). Median chemotherapy-free interval: 9.5 weeks (1–39). Median administered cycles of Folfox/patient: 8 (2–11 cycles). Responses according to RECIST criteria: 2 CR (14.5%), 2 PR (14.5%), 4 SD (29%) and 6 PD (43%). Responses according to CA125 Rustin's criteria: 4 CR (29%), 2 PR (14.5%), 5 SD (35.5%) and 3 PD (21%). Grade 1/2 and 3 peripheral neuropathy: 10 (71%) and 2 (14.5%), respectively. There were no grade 4 adverse events or deaths due to the treatment. Conclusions: Folfox is a valuable option for heavily pre-treated patients with ovarian cancer, with an overall response rate of 29% (95% CI 15.2% to 41.8%), disease stabilization in an additional 29%, and a manageable toxicity profile. These results support the use of Folfox as salvage treatment for patients with ovarian carcinoma.

No significant financial relationships to disclose.