bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcome and molecular characterization of patients receiving systemic therapy for metastatic sarcomatoid renal cell carcinoma.
Authors: Hsu Joann , Pal Sumanta Kumar , Twardowski Przemyslaw , Carmichael Courtney , Saikia Junmi , Liu Xueli , Wilson Timothy G. , Figlin Robert A. , Jones Jeremy 
Published: March 2020

e15084 Background: Sarcomatoid metastatic renal cell carcinoma (mRCC) represents an aggressive subset of disease, and a definitive therapeutic strategy is lacking. Methods: From an institutional database including 270 patients with mRCC, we identified 34 patients with documented sarcomatoid features. Within this cohort, we assessed 21 patients who received systemic therapy. Survival was assessed in the overall cohort and in subgroups divided by clinicopathologic characteristics, including the extent of sarcomatoid features, MSKCC risk criteria, and the nature of systemic therapy given. Available tissue from 11 of these patients has been identified for correlative studies to assess markers of epithelial to mesenchymal transition (EMT). Tissue will be obtained from a cohort of patients matched for age and MSKCC risk status (but lacking a sarcomatoid component) for comparison. Results: Of the 21 patients assessed, 2 patients received chemotherapy, 7 patients received immunotherapy, and 12 patients received targeted agents as their first line treatment. Median overall survival (OS) in the overall cohort was 18.0 months (95%CI 6.9-22.0). By MSKCC status, patients with poor-risk disease had a median OS of 4.7 months, as compared to 20.1 months for patients with intermediate-risk disease (HR 0.02, 95%CI 0.003-0.15; P=0.0001). Survival in subgroups stratified by the Heng criteria will be presented at the meeting. There was no significant difference in survival in patients with sarcomatoid predominant disease (>20%) vs non-predominant disease (HR 0.62, 95%CI 0.23-1.65; P=0.34), nor was there a difference amongst patients who received targeted therapies vs non-targeted therapies (HR 1.0, 95%CI 0.61-1.40; P=0.36). Correlative analyses are ongoing, and will be presented at the meeting. Conclusions: As compared to previous retrospective series (Golshayan et al JCO 2009) and prospective trials (Haas et al Med Oncol 2011) assessing patients with sarcomatoid mRCC, the survival in our cohort was substantially prolonged. Further clinical and translational studies are needed to refine current prognostic schema for this disease, and to define the optimal therapeutic strategy.
Does RECIST-defined progression correlate with lack of further sunitinib (SU) benefit in advanced renal cell carcinoma (aRCC)?
Authors: Teo MinYuen , McDermott Raymond S. 
Published: March 2020

e15093 Background: RECIST defined radiographic progression on SU may be confounded by the intermittent dosing schedule and scan timing. Response rates to second line agents are typically lower and of shorter duration We analysed the potential for continued clinical benefit from continuation on Sunitinib following RECIST-defined progression in selected pts . Methods: Our institutional database was reviewed to identify aRCC pts who: 1) received SU, 2) achieved response or stable disease, and 3) had continuation of SU after documentation of RECIST-defined progression. Treatment history was obtained from medical chart review. CT scans were retrospectively assessed by RECIST criteria, pattern of progression was documented. SU cessation reasons were identified. Progression-free survival (PFS), post-progression treatment duration (PPD) and overall survival (OS) estimated by Kaplan Meier method. Results: Of 39 patients (pts) treated with SU between 2006 and 2009, 13 met entry criteria. Median age was 62 years (range: 33 – 66) with 11(85%) males. Eleven (85%) had prior nephrectomy and 4 (31%) had prior immunotherapy. Number of pts with MSKCC good/intermediate/poor risk groups were 5/7/1. Best radiographic response achieved was complete response/partial response/stable disease in two, five and six pts. Median PFS was 16.4 mos (11.8 – 23.8). Seven (54%) had progression of existing lesions while the six developed new lesions. Pts continued on SU as progression was relatively minor and clinical status was maintained. Median PPD was 4.2 months (0.6 – 40.5). Most common reasons for SU cessation were on-going radiographic progression (71%) and toxicity (18%). Only 2 pts stopped SU secondary to clinical deterioration. 62% of pts received subsequent lines of treatment, with half receiving 3rd line therapy. Median OS for the cohort was 31.7 mos. Conclusions: Continuation of treatment with SU following RECIST progression appears feasible and safe with prolonged disease control in selected pts . This approach should be further validated prospectively in a larger patient cohort. In this group, current standards for disease response assessment may underestimate the duration of clinical benefit conferred.
Treatment of carcinoma in situ of the glans penis with topical chemotherapy agents.
Authors: Alnajjar Hussain M , Lam Wayne , Bolgeri Marco , Rees Rowland , Perry Matthew , Watkin Nicholas 
Published: March 2020

e15100 Background: To establish the response rate of 5-flurouracil (5-FU) and imiquimod (IQ) in the treatment of penile CIS in a large contemporary series in a supra-network center. The use of topical agents in the treatment of CIS of the penis has been well described in the literature. Previous studies have been limited by small sample size and imprecise end-points. Methods: Retrospective review of all primary and recurrent cases of penile CIS treated with 5-FU and IQ identified from a prospective database over a 10- year period. Therapy was standardised in all cases with application to the lesion for 12 hours every 48 hours for 28 days. 5-FU was the first line therapy and IQ used as second line topical agent. The primary end-point was defined as complete response (CR = resolution of lesion), partial response (PR = lesion reduced in size and or visibility) or no response (NR = no improvement in lesion size and or visibility). The secondary end-points included local toxicity and adverse events. Results: A total of 86 patients were diagnosed with CIS of the penis over the 10-year period. 44/86 (51%) received topical chemotherapy. Mean follow-up was 34 months. The response rates, local toxicity and adverse events were analysed. The overall complete response rate for topical agents was 57% (Table). Conclusions: Topical chemotherapy agents are moderately effective first line therapy in the treatment of penile CIS. Toxicity and adverse events were low with our treatment protocol. The issue of long-term surveillance and assessment of partial responders remains a challenge. Topical chemotherapy should remain a first line treatment option for penile CIS. [Table: see text]
Second-line chemotherapy with cabzitaxel and prednisolone (CP) in castratation-resistant prostate cancer (CRPC): Tolerability and efficacy—A U.K. institution experience.
Authors: Montazeri Amir H , Eswarvee Chinnamani , Wong Helen , Malik Zafar I 
Published: March 2020

e15128 Background: There are limited options for CRPC patients post docetaxel treatment. The majority of these patients have advanced disease with bone metastasis and often have reduced marrow reserve. Cabazitaxel is a novel taxane with activity in docetaxel-resistant/ sensitive cancers with proven clinical benefit in a phase 3 trial. Concerns have been expressed about efficacy and toxicity of this agent in a non trial population. Methods: In this retrospective case study, patients with CRPC treated with CP between Jan-Dec 2011 were included. Response rates (PSA, ALP, radiological) and toxicities (CTCAE) were recorded. All statistical analysis was performed using SPSS v18. Results: 22 men received CP with pegfilgrastim. 41% completed at least 6 cycles of CP and 23% completed 10 cycles. 27% had radiological partial response (RECIST). 36% of patients had ≥50% reduction in PSA level and 61% of patients with elevated ALP had ≥50% reduction. Median follow up was 7.9 months. Progression was defined as clinical, PSA or radiological. 3 patients discontinued treatment because of abnormal LFTs and a further 5 patients for toxicities summarised below. Conclusions: Response rates (RR) in our series (RECIST 27% & PSA 36%) compared favourably with those in the TROPIC trial (14% & 39% respectively) and support CP as an effective and well tolerated option in CRPC. An intriguing finding was the significant RR in ALP level with CP. This may reflect bone penetration of this agent and may correlate with symptom relief and improved clinical outcome. Further prospective studies are needed to investigate this marker with clinical outcome. Data for time to progression, progression free survival and overall survival is immature at this stage and will be updated for the meeting. To our knowledge this is the first case series of patients treated with CP presented outside a clinical trial. [Table: see text]
Combination of a polyamine-free oral nutritional supplement (ONS) with docetaxel in castrate-resistant prostate cancer (CRPC) patients (pts): A phase II trial.
Authors: Cipolla Bernard G , Artignan Xavier , Miglianico Laurent , Bligny Dominique , Abraham Christine , Moulinoux Jacques Philippe 
Published: March 2020

e15131 Background: Polyamines (PA) are essential for cancer cell growth. Reducing exogenous PA (foods + gut flora) and blocking PA synthesis, reduces tumour growth and potentializes chemotherapy in rodent tumour models. We have developed a PA “free” ONS, which inhibits tumour growth by 40% in pre-clinical models and assessed its tolerance with docetaxel in CRPC pts. Methods: 30 pts, 71 ± 7 years, with metastatic CRPC, median PSA: 95 ng/ml, were assessed for tolerance, quality of life (QOL) (QLQ C-30 questionnaire), W.H.O. performance status (P.S.), pain scores and prostate specific antigen (PSA) response. 90% pts were painful. 75% pts had opiate or morphinic analgesics at day 0 (D0). Median pain score is 5 (0 to 10 scale). The PA free ONS was given as sole diet (6 cans a day) for 14 days then progressively reduced and given with low PA containing foods. Docetaxel administration started on day 21 for 6, 75 mg/m2 injections, every three weeks with prednisone. Nutrialys Medical Nutrition, France, provided the PA free ONS. Results: 27 pts were evaluated for the PA ONS free phase. 18 pts completed the trial at scheduled dates and docetaxel doses. 9 pts did not complete the trial: disease progression (n=4), initial thrombocytemia (n=2), 2 deaths and 1 GI intolerance PA free ONS stage: No specific toxicity. QOL (p=0,04), pain (p=0,03) and anorexia (p=0,01) are improved at day 14. 1 pt had a > 50 % PSA decrease. PA free ONS + docetaxel stage: grade 1 or 2 nausea, vomiting or diarrhoea in < 35 % pts, 12% grade 1 neuropathy, no onycholysis or skin toxicity. Body weight and biological parameters are preserved except for two grade 4 neutropenias. P.S., Q.O.L. and pain scores and anorexia are improved. 55% pts cut their analgesics by ≥ 30% WITH stable or improved pain score. 13 pts (70% pts who completed the trial) had an > 50% PSA decrease with an 8 weeks median response time. Conclusions: A PA free ONS exclusive diet is well tolerated with significant QOL and pain improvements. The docetaxel PA free ONS combination tolerance is excellent with improved P.S., pain score and analgesic reduction. AE during chemotherapy are minimal. PSA responses are observed in a significant proportion of treated patients.
Vitamin D status and skeletal health in black men starting androgen deprivation therapy for prostate cancer.
Authors: Gunnarsson Orvar , Basaria Shehzad , Gignac Gretchen 
Published: March 2020

e15139 Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with increased incidence of osteoporosis and fractures. However, much of this information is in Caucasian men. Our aim was to evaluate the prevalence low 25-hydroxyvitamin-D levels and low bone mass in black men starting ADT. Methods: A chart-based retrospective review was conducted on all patients diagnosed with PCa and were deemed appropriate to start ADT in a tertiary care center between September 2007 and July 2010. Baseline data were collected on vitamin-D status and bone mineral density (BMD). Vitamin-D sufficiency was defined as levels ≥30 ng/ml, insufficiency as <30ng/ml and deficiency as ≤20ng/ml. Osteopenia was defined when T scores were between -1 to -2.5 and osteoporosis when T scores ≤ -2.5. Results: A total of 113 black men had evaluable data (mean age 68.9±9.0; range 45-92). At baseline, mean vitamin-D levels were 20.8±9.0 ng/ml (range 4.0-43.0), lumbar Spine T-score was -0.37±1.46 (range -4.20-3.34;) and femoral neck T-score was -0.94±1.04 (range -3.00-1.50). A total of 49.4% of our patients were vitamin-D deficient (13.5±4.6), 33.7% had insufficiency (24.5±3.1) and 16.9% had sufficient vitamin-D levels ( 34.7±4.3). 59.3% of patients had normal BMD, 31.5% had osteopenia and 9.3% had osteoporosis. Conclusions: A significant proportion of black men starting ADT have low Vitamin-D levels and low bone mass. These observations should be taken into account when starting ADT in black men.
Safety data of cabazitaxel in patients treated for metastatic castration-resistant prostate cancer after docetaxel treatment: Results of a cohort of patients during the temporary authorization for use in France (ATU).
Authors: Houede Nadine , Eymard Jean-Christophe , Tahar Zoubir 
Published: March 2020

e15142 Background: The TROPIC (Johann Sebastien de Bono et al ; Lancet 2010) study demonstrated that cabazitaxel (a novel tubulin-binding taxane drug) improves overall survival of patients (pts) with mCRPC who progressed during or after docetaxel-based chemotherapy, with a median survival of 15.1 months. Based on this result, a compassionate-use program has been established to provide pts with mCRPC the opportunity to receive the treatment, before licensing of the drug. Methods: ATU of cabazitaxel in France has been granted before its marketing authorization; all safety data from pts treated during this period were collected following a specific therapeutic use protocol. All participating physicians were instructed about the molecule by a company physician and contacted before the first treatment, on day 15 and at the end of treatment of each patient to make sure that all G3/4 and serious adverse events were collected. Results: We report baseline characteristics and safety data from the 184 pts treated in 92 French centers. Median age was 67.2 years (46 - 92), ECOG performance status was 0-1 for 85% of pts, 88% had bone metastases and 21% had visceral metastases. All the pts had received prior docetaxel, 55% had discontinued for disease progression; 85% of the pts received previously 1-2 lines of chemotherapy. Pts received a median of 3 cycles of cabazitaxel (1-6). Rates of grade 3-4 hematological toxicities were: neutropenia grade≥ 3 (4%), febrile neutropenia (3%), all resolved. All grade other toxicities were: nausea (0.5%), diarrhea (2.7%) and fatigue (0.5%). No treatment-related death was reported. Conclusions: The ATU program provides additional safety information on cabazitaxel in the real-life setting; they are consistent with the TROPIC study safety results. The incidence of neutropenia grade≥ 3 (4%) and febrile neutropenia (3%) appears to be lower than expected. Therapeutic use protocols such as these can be helpful for physicians when new therapies become available. Proactive education of healthcare givers on AEs management could be considered when new treatments are introduced.
Bone metastasis (BM) based on SEER registry versus Medicare claims among metastatic prostate cancer (PCa) patients (pts) in SEER-Medicare.
Authors: Onukwugha Ebere , Mullins C. Daniel , Yong Candice , McNally Diane L. , Seal Brian S. , Hussain Arif 
Published: March 2020

e15148 Background: There is questionable reliability of administrative claims data to identify BM, yet historically such claims were the only source for identifying BM in SEER-Medicare (SM). Starting in 2004, SEER provided tumor registry information on incident BM. We compared frequencies of BM using registry and claims data among men diagnosed with PCa. Methods: We analyzed pts aged 66 and older from the linked SM database. Pts with stage IV (M1) PCa diagnosed between 2004 and 2007 were followed until death or censoring. Identifying pts with BM using claims required at least one inpatient or outpatient claim with a diagnosis code of 198.5 within (i.e., +/-) 1 month of the SEER diagnosis month (designated BMclaims-90) or at any time during follow up (designated BMclaims-ever). BM identified using SEER was based on an indicator for bone metastasis at diagnosis using the AJCC M1b classification (designated BMseer). We calculated the sensitivity and specificity of BM at diagnosis in claims (BMclaims-90) with respect to the incident BM data in SEER, assuming BMseer to be the gold standard. Results: Application of inclusion/exclusion criteria resulted in 3,664 stage IV (M1) PCa pts. Average age was 79 years, 13% were African American, and 61% had poorly/un-differentiated tumors. BMseer (n=2,301; 63%) was higher than BMclaims-90 (n=1,979; 54%) and lower than BMclaims-ever (n=2,878; 79%). Assuming BMseer as the standard measure of BM at diagnosis, BMclaims-90 had 58.8% sensitivity (n=1,353), 54.1% specificity (n=737), and 68.4% positive predictive value for identifying BM at diagnosis. Among men with BM identified using BMseer, 84% (1,931) had BMclaims-ever and the median (min; max; average) time to the first BM claim was 0.9 (-2.6; 57.1; 3.9) months. Among men with BM identified using BMclaims-90, the median (min; max; average) time to the first BM claim was 0.6 (-1.0; 2.0; 0.7) months. Conclusions: The incidence of BM in PCa pts differs between a commonly-used algorithm to identify BM in claims data and the AJCC staging information in tumor registry data. There was moderate concordance between the claims-based measure and the SEER-based measure of BM at diagnosis.
Evaluation of the response to cabazitaxel of a docetaxel-responsive hormone-refractory prostate tumor xenograft model (HID28).
Authors: Bourre Ludovic , Nicolle Delphine , Legrier Marie-Emmanuelle , Yvonnet Vanessa , Charpentier Julie , Poupon Marie-France , Vrignaud Patricia , Geffriaud-Ricouard Christine , Oudard Stephane , Judde Jean-Gabriel 
Published: March 2020

e15161 Background: Docetaxel was the first cytotoxic treatment demonstrating a survival benefit in metastatic castration-resistant prostate cancer (mCRPC) patients. Recently, cabazitaxel (a novel taxane) and abiraterone acetate (specific inhibitor of CYP17) have demonstrated a significant survival benefit in mCRPC patients progressing after receiving a docetaxel – containing regimen. Here we compare the antitumor efficacy of docetaxel, cabazitaxel and abiraterone acetate in the HID28 hormone-refractory human prostate carcinoma xenograft. Methods: HID28 tumor bearing nude mice received 20 mg/kg of docetaxel (IP, q3wk x 2), cabazitaxel at 15 and 20 mg/kg (IP, q3wk x 2) and abiraterone acetate at 50 mg/kg (PO, qdx21). Median tumor growth inhibition (T/C%) was evaluated as well as time course androgen receptor expression (4, 8 and 24h post dosing) by western blot analysis. Results: Docetaxel (20 mg/kg) inhibited tumor growth with a T/C%= 16.7% at D35, 2 partial (PR) and 1 complete (CR) tumor regressions, and with relapse of all tumors (6/6) observed at D42. Cabazitaxel demonstrated dose-dependent efficacy at D35 with T/C%= 10.8% and 1.4% for 15 and 20 mg/kg doses respectively. At a cabazitaxel dose of 15 mg/kg, 4/10 PR and 3/10 CR were observed, whereas 4/10 PR and 6/10 CR were observed at 20 mg/kg. At D42, 6/6 tumor relapses were observed at 15 mg/kg; whereas, only 3/6 relapses were observed at 20 mg/kg. No anti-tumor activity was demonstrated with abiraterone acetate as well as no significant decreases in testosterone levels compared to the vehicle group. Tolerability was good for all treatment groups, with a transitory maximum mean body weight loss of 12%, 6 days after treatments. Androgen receptor western blot expression analysis after 4, 8 and 24h post dosing demonstrated no significant difference between groups and over time. Conclusions: Cabazitaxel and docetaxel showed similar tolerability at equivalent dose levels. Cabazitaxel demonstrated superior antitumor efficacy over docetaxel at equivalent dosing in the HID28 hormone-refractory tumor model. These results support the clinical development of cabazitaxel in first line treatment of mCRPC patients.
Elevated serum activin A and survival in CRPC.
Authors: Ali Suhail M. , Zubritsky Lindsey , Jacobus Susanna J. , Leitzel Kim , Regan Meredith M. , Nakabayashi Mari , Knight Robert D. , Laadem Abderrahmane , Sherman Matthew L. , Lipton Allan , Kantoff Philip 
Published: March 2020

e15170 Background: The prognosis of castration-resistant prostate cancer (CRPC) varies widely. Activin A is a ligand in the TGF-B superfamily that regulates cell proliferation, apoptosis, differentiation, and immune responses. In patients with multiple myeloma, elevated activin A is associated with advanced disease and poorer overall survival (OS). Methods: 60 Metastatic CRPC patients whose serum samples were stored at the Dana-Farber Cancer Institute were used for this study. Plasma activin A levels were measured using ELISA (R&D Systems, Minneapolis, MN). Levels of activin A within key patient and disease characteristics were analyzed using the Wilcoxon rank sum test. OS distributions by activin A tertile status were estimated with Kaplan-Meier (KM) and compared with the logrank test. Cox regression was used to produce hazard ratios (HR). Results: In this cohort of 60 patients with metastatic CRPC, median age at diagnosis was 62y, median PSA was 15.3 ng/mL and 37% had a biopsy Gleason score (GS) >8. The index blood draw was a median of 32.9 mo from androgen-deprivation therapy. Median age and PSA at blood draw were 71y and 23.5 ng/mL. At the time of blood draw, 57% of patients had bone only metastasis, 30% were receiving primary or 38% secondary hormonal therapy, and 30% were receiving chemotherapy. Median survival follow-up was 17 months after blood collection (27 deaths). Activin A levels were 621.9 pg/mL (median) and 1382.7 pg/mL (mean). Activin A levels were elevated among older patients (> 65y) and only within patients with higher PSA (>20 ng/mL) at blood draw. KM estimates of median OS (months) for the low, mid and high serum activin A tertile groups were 19.7, 13.8 and 5.4, respectively (p<0.001). The HR (referent low) was 1.4 (95% CI: 0.5-4.5) for the mid and 5.6 (95% CI: 2.1-14.9) for the high tertile. OS was significantly different within age and GS groups, but not within PSA groups. In multivariable analysis, tertile activin A remained significant (p<0.02) when adjusted separately for age at diagnosis, biopsy Gleason score, and serum TIMP-1 (reported previously). Conclusions: Elevated serum activin A predicted for shortened OS in metastatic CRPC, and deserves further study as a biomarker of aggressive disease.