bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term survival and competing causes of death in men with stage I seminoma.
Authors: Beard C. , Chen M. , Arvold N. D. , Nguyen P. L. , Ng A. K. , Hoffman K. E. 
Published: February 2017

226 Background: To better understand the impact of RT on mortality, we analyzed long-term survival and patterns of excess mortality in men with stage I seminoma. Methods: 9,045 men with stage I seminoma were identified in the Surveillance Epidemiology and End Results database. Time to testicular-cancer mortality (TCM), death from second malignancy (SM), cardiovascular mortality (CVM) or suicide (SUIC) and all-cause mortality (ACM) were calculated. Survival estimates were calculated using the Kaplan-Meier method. Gender- and age-adjusted standardized mortality ratios (SMR) were calculated using U.S. population data. Cox and Fine and Gray multivariable analysis were used to evaluate the effect of RT on mortality outcomes. Results: 7,025 men (78%) received RT. After a median follow-up of 11.7 years, 869 men (9.6%) had died: sixty-five from TCM, 279 from SM, 169 from CVM and 37 from SUIC. 10-year rates of ACM and TCM were 4.24% and 0.52% among men who received RT and 7.14% and 1.22% among men who did not. Compared to the adjusted general population, men with seminoma had increased risk of ACM (SMR 1.12; 95% confidence interval [CI] 1.12-1.28), SM (SMR 1.78; 95% CI 1.58-2.00) and SUIC (SMR 1.40; 95% CI 1.02-1.94) and decreased risk of CVM (SMR 0.73; 95% CI 0.62-0.84). Rates of ACM, SM and SUIC (SMR, all p < 0.05) were increased whether RT was used or not. Men who received RT were less likely to die (adjusted hazard ratio [AHR] 0.76; 95% CI 0.65-0.89; p < 0.001) and had a lower risk of TCM (AHR 0.39; 95% CI 0.24-0.65; p < 0.001). There was no difference in CVM between men who did and did not receive RT (AHR 0.89; 95% CI 0.60-1.15; p = 0.230) and a numerical increase in SM in men who received RT as compared to others (AHR 1.25; 95% CI 0.90-1.72; p=0.180). Conclusions: Compared to the general population, men with a history of stage I seminoma had increased risks of all-cause mortality, death from second malignancies, and suicide. Our data suggest that 15 years after diagnosis, men who did receive RT may be more likely to die from a second malignancy than men who did not. Although not receiving RT was associated with higher testicular-cancer mortality, the results may reflect decreased access to care or follow-up as active surveillance protocols were not common during the study era. No significant financial relationships to disclose.
Adjuvant radiation therapy for early-stage seminoma: Proton-photon comparison and second cancer risk.
Authors: Efstathiou J. A. , Paly J. J. , Lu H. , Athar B. S. , Niemierko A. , Bekelman J. E. , Coen J. , Shipley W. U. , Zietman A. L. , Paganetti H. 
Published: February 2017

228 Background: Seminoma constitutes the majority of testicular cancers and 75% percent of patients present with localized disease. Given that seminoma remains the most curable solid tumor, concerns of toxicity including late sequelae such as excess malignancies have given pause to the use of conventional adjuvant radiation therapy (RT) following orchiectomy for early-stage seminoma. As a result of the unique physical dose deposition characteristics of protons to avoid normal tissue, we evaluated both photon and proton beam therapy (PBT) treatment plans for para-aortic irradiation to assess dose distributions to organs at-risk and model rates of second cancers. Methods: Ten patients with stage I seminoma treated with conventional adjuvant para-aortic AP-PA photon RT to 25.5 Gy between 2004-2009 at Massachusetts General Hospital had PBT plans generated (AP-PA and PA alone). The dose differences to critical organs, as modeled by Equivalent Uniform Dose (EUD), were examined. The risks of second primary malignancies were calculated using validated methods and compared both to each other and to baseline population risks. Results: PBT plans were superior to photons in limiting dose to organs at-risk. The volume of whole body normal tissue spared 0.1 Gy was 9.0L and 7.8L for PA and AP-PA protons, respectively, compared to photons. The volume spared 1Gy was 5.0L and 3.8L for PA and AP-PA protons, respectively; while the volume spared 10Gy was 1.3L and 0.85L, respectively. PBT decreased the EUD by 46% (8.2 Gy) and 64% (10.2 Gy) to the stomach and large bowel, respectively (p<0.01), presumably translating into lower levels of nausea and fatigue. Notably, PBT was found to avert 612 excess second cancers among a population of 10,000 men diagnosed at age 35 and surviving to age 75 (p<0.01). Conclusions: In this comparative dosimetric and modeling study, the use of protons provided a favorable dose distribution with an ability to limit unnecessary exposure to critical normal structures in the treatment of stage I seminoma patients. It is expected that this will translate into decreased acute toxicity and reduced risk of second cancers, for which prospective studies are warranted. No significant financial relationships to disclose.
Surveillance for stage I testicular seminoma at a single institution in Japan: Retrospective analysis of prognostic factors for relapse.
Authors: Kakimoto K. , Takeda K. , Yoshida T. , Nakayama M. , Arai Y. , Nishimura K. 
Published: February 2017

234 Background: Treatment options for clinical stage I seminoma include adjuvant radiotherapy (RT) as well as surveillance and adjuvant chemotherapy (CT). Data available from the surveillance, adjuvant RT and adjuvant CT series suggest that all treatment strategies achieve a complete cure in almost 100% of the patients with stage I testicular seminoma. The success of surveillance of patients with stage I nonseminomatous germ cell tumors and the establishment of curative CT for advanced disease have led to re-examination of the standard treatment approach. We report the results of a retrospective analysis of the prognostic factors for stage I testicular seminoma. Methods: We retrospectively reviewed the survey of 87 patients with stage I testicular seminoma who were admitted in an institution between January 1982 and January 2009. We examined if the following tumor characteristics could possibly predict the relapse: age at diagnosis, tumor size, pathological T (pT) stage, elevation of beta-hCG level and/or LDH level, invasion of the rete testis, vascular invasion and lymphatic invasion. The cause-specific survival rate was calculated using the Kaplan-Meier method. Results: During a median follow-up of 8.1 years (range, 1.2-25.7 years), 13 (14.9%) relapses were observed, with an actuarial 5-year relapse-free rate (RFR) of 87.9%. The univariate analysis showed that the following characteristics were not predictive of relapse: age at diagnosis (RFR: 89% [<36 years] vs. 88% [≥36 years]), tumor size (RFR: 90% [<5.6 cm(median)] vs. 85% [≥5.6 cm]), pT stage (RFR: 91% [pT = 1] vs. 84% [pT = 2 and pT = 3]), elevation of beta-hCG level (RFR: 89% [normal] vs. 87% [elevated]), invasion of the rete testis (RFR:90% [absent] vs. 80% [present]), vascular invasion (RFR:86% [absent] vs. 87% [present]), and lymphatic invasion (RFR: 88% [absent] vs. 87% [present]). The overall 5-year survival rate was 97%. Conclusions: Prognostic factors for relapse could not be identified in this retrospective analysis of the patients admitted in a single institution. To identify the prognostic factors for risk-adapted treatment for stage I testicular seminoma, we need to study a large sample population in Japan. No significant financial relationships to disclose.
Defining molecular determinants of sensitivity to EGFR inhibition in urothelial carinoma.
Authors: Kim W. Y. , Hadzic T. , Heathcote S. A. , Gammons D. T. , Rathmell K. , Whang Y. E. , Godley P. A. , Nielsen M. E. , Wallen E. , Pruthi R. 
Published: February 2017

268 Background: Activation of EGFR in cancer patients has been shown to correlate with tumor proliferation, angiogenesis, and metastasis. EGFR inhibition has been shown to be clinically beneficial in several solid tumors and appears to be a tractable therapeutic target. EGFR is over-expressed in bladder cancer and a phase II trial of neoadjuvant erlotinib in patients with muscle invasive bladder cancer suggests possible clinical activity. We therefore hypothesized that we could define molecular correlates to predict response to EGFR inhibition. Methods: Correlative tumor samples derived from a phase II trial of neoadjuvant erlotinib in muscle invasive urothelial carcinoma of the bladder were analyzed to define molecular determinants of response to EGFR inhibition. The effect of silencing a candidate molecular predictor of resistance to EGFR inhibition, HRAS, was assessed by changes in the IC50 of T24 cells (harbor mutant HRAS) expressing short hairpin RNAs to HRAS or a control shRNA. Results: Analysis of the gene expression profiles of TURB-T (pretreatment) samples show that tumors from non-pT0 patients had significantly elevated levels of HRAS relative to tumors from pT0 patients. Furthermore, knock-down of HRAS in T24 cells enhanced the sensitivity of these cells to erlotinib. Conclusions: Elevated HRAS expression is correlated with a lack of response to erlotinib in vivo and silencing of HRAS in T24 cells results in enhanced sensitivity to erlotinib in vitro. Further molecular analyses are ongoing. No significant financial relationships to disclose.
Perioperative morbidity and mortality in patients treated by radical cystectomy: A multi-institutional retrospective study.
Authors: Takada N. , Abe T. , Maruyama S. , Sazawa A. , Shinohara N. , Seki T. , Togashi M. , Nonomura K. ,   Hokkaido Urothelial Research Cancer Group
Published: February 2017

270 Background: It is well known that radical cystectomy is associated with comparatively high perioperative morbidity and mortality. In the present study, we collected data of perioperative outcomes from Hokkaido University Graduate School of Medicine and our teaching hospitals and assessed the complications and death rate within 90 days after radical cystectomy. Methods: We collected clinical data of 970 patients undergoing radical cystectomy for nonmetastatic bladder cancer in 21 institutions between 1999 and 2009. We then assessed 90-day complications and death after radical cystectomy. The complications were classified according to the modified Clavien classification. Over 40 variables were included in the analysis, including age, ASA score, BMI, comorbidity, neoadjuvant chemotherapy, clinical stage, type of urinary diversion, operative time, estimated blood loss, transfusion, and hospital stay. Statistical analysis was performed utilizing Student's t-tests, chi-square tests, and logistic regression analysis. Results: The median patient age was 70 (range, 25-91) years old. 62.5% of patients had an ASA score≥2. Regarding the urinary diversion, ileal conduit was performed in 523 (53.6%) patients, neobladder in 178 (18.4%), ureterocutaneostomy in 255 (26.3%). Median operative time was 399 (range, 100-927) minutes. Median hospital stay was 39 (0-364) days. Regarding the complications, 660 (68%) patients experienced at least one complication and death rate within 90 days after surgery was 1.34% (n=13), respectively. Of the complications, 34.1% was classified as grade 1, 41.5% as grade 2, 20.1% as grade 3, 1.1% as grade 4, 1.2% as grade 5. Multivariate analysis identified age≥70 (odds ratio 1.41), urinary diversion utilizing intestine (OR 1.58) and operative time ≥ 400 (OR 1.54) were independent risk factors. Conclusions: Death rate was 1.34%, which was compatible to reports form western high- volume centers. About two-thirds of the patients experienced at least one complication, although they were mostly classified as grade 2 or less. Age, urinary diversion, and operative time were significant risk factors for perioperative complications after radical cystectomy. No significant financial relationships to disclose.
Phase II study of a polyethoxylated castor oil–free, polymeric micelle formulation of paclitaxel for patients with advanced urothelial cancer previously treated with gemcitabine and platinum.
Authors: Lee J. , Park S. , Lim H. , Kwon J. , Kim G. , Song C. , Hong J. , Kim C. , Ahn H. , Ahn J. 
Published: February 2017

272 Background: Paclitaxel-loaded polymeric micelle (Genexol-PM; G-PM) is a novel polyethoxylated castor oil (Cremophor EL [CrEL])-free formulation of paclitaxel. This multicenter phase II study was designed to evaluate the efficacy and safety of the G-PM monotherapy for the treatment of gemcitabine- and cisplatin-refractory advanced urothelial cancer. Methods: Patients with advanced urothelial cancer received G-PM 240 mg/m2 intravenously over 3 hours every 3 weeks without premedication as salvage chemotherapy after failure to gemcitabine and cisplatin combination chemotherapy. Intrapatient dose escalation of G-PM to 300 mg/m2 was carried out from the second cycle if the prespecified toxicities were not observed after the first cycle. Results: Thirty-seven patients were enrolled in this study. Platinum-free interval was less than 6 months in 72% of patients and 64% of patients were categorized into intermediate or poor prognostic group. Overall response rate was 19% including one complete response. When response occurs it is long lasting with a median response duration of 7.8 months (range 1.5∼19.3+). The median progression-free survival was 2.7 months (95% CI, 09-4.6) with a median overall survival of 5.7 months (95% CI, 3.1-8.3). The most common major grade 3-4 non-hematologic toxicity was peripheral neuropathy (sensory type 5.6% and motor type 8.3%) followed by infection (5.6%). Grade 3 or worse hematologic toxicities were observed in only one patient. Conclusions: G-PM showed modest activity with favorable toxicity profiles when used as salvage therapy after gemcitabine-cisplatin failure in advanced urothelial cancer. No significant financial relationships to disclose.
Gemcitabine/cisplatin in patients with advanced bladder and impaired renal function: A retrospective analysis.
Authors: Morales R. , Serrano C. , Bellmunt J. , Mellado B. , Guix M. , Gallen M. , Font A. , Suarez C. , Valverde C. M. , Carles J. 
Published: February 2017

274 Background: A four-weekly regimen of gemcitabine and cisplatin (GEMCIS) has similar activity and is less toxic than MVAC in advanced bladder cancer. However, full-dose cisplatin in unfit patients with impaired renal function is contraindicated and other carboplatin-based schedules have been developed. We have previously reported the feasibility of GEMCIS in a biweekly schedule in unfit patients with renal impairment. Here we report a multicenter retrospective study of this biweekly regimen in patients with impaired renal function. Methods: Between January 2004 and October 2009, 40 patients with locally advanced nonsurgically resectable or metastatic bladder cancer and impaired renal function were included. Treatment consisted of gemcitabine 2500 mg/m2 on day 1 and cisplatin 35 mg/m2 on day 1, every 14 days. Results: Median age of the patients was 73 years (range: 51-82 years). Median IK was 80% (range: 60-100%). Mean creatinine clearance was 49 ml/min (range:37-59 ml/min). Eight patients had previously received chemotherapy with gemcitabine and/or platinum based therapy. Metastatic localizations were: 17 lymph nodes, 10 pulmonary, 10 bone, 7 liver, 12 pelvic and 1 central nervous system. The median number of cycles/patient was 6 (1-13). Out of 36 patients evaluable for response, there was one complete response, 14 partial responses (ORR: 42%; 95% CI 27-58%), 11 stabilizations and 10 progressive diseases. Hematologic toxicities were grade 1 anaemia in 15 patients, grade 2 in 8; grade 3 in 2; grade 3 neutropenia in 5 patients and grade 4 in 1 patient; grade 3 plaquetopenia in 3 patients. Nonhematologic toxicities were grade 1-2 vomiting in 2 patients. Two patients showed a grade 2 hepatic toxicity. Worsening of the renal function was observed in two patients. Alopecia grade 1-2 was seen in three patients. There was one toxic death related to metabolic acidosis.The median progression-free survival is 15 weeks. The median OS from first cycle of GEMCIS is 35 weeks and 1-year OS is 43% (St error 9%). Conclusions: A two-weekly schedule of gemcitabine plus cisplatin is feasible, active, and generally well tolerated in an outpatient setting in unfit patients with poor renal reserve. No significant financial relationships to disclose.
Effect of signet-ring cell carcinoma histology on bladder cancer outcome.
Authors: Wang J. , Wang F. , Enke C. A. 
Published: February 2017

275 Background: Signet-ring cell carcinoma (SRCC) of the urinary bladder is a rare entity. Recent case series of the condition showed inconsistent results. We used a population-based data set to compare the cancer specific survival of patients with signet-ring cell carcinoma vs. transitional cell carcinoma (TCC) of the urinary bladder. Methods: Signet-ring cell carcinoma of the urinary bladder and transitional carcinoma of the urinary bladder were identified in the Surveillance, Epidemiology and End Results program (2001 to 2004). Demographic and pathological characteristics at diagnosis were compared. Differences in cancer specific survival were compared with univariate and multivariate Cox regression analysis. Results: A total of 103 SRCC cases were present in the database from 2001 to 2004. In that time 14,648 cases TCC cases were diagnosed. SRCC was more common in younger than in older patients (p <0.001); more commonly presented with high grade histology (p <0.001) and advanced stage disease (p <0.001). The 3-year cancer specific survival rate was 67.0% and 33.2% for TCC and SRCC, respectively. On multivariate analysis there was an increased mortality risk in patients with SRCC vs TCC (HR 1.42, 95% CI 1.03–1.97, p <0.001). When only high grade cases of SRCC and TCC were compared, the risk was still worse in SRCC (HR 1.430, 95% CI 1.035–1.976, 0.03). When only local stage of SRCC and TCC were compared, the risk was worse in SRCC (HR 4.294, 95% CI 1.035–17.825, 0.045). Limited to patient who underwent cystectomy only, the difference in cancer specific survival disappeared (HR 1.289, 95% CI 0.771–2.155, 0.33). Conclusions: Even after adjusting for demographic, pathological and treatment factors, cancer specific survival is significantly worse in patients with SRCC than TCC. Further research into the biology of this rare tumor is required to explain these results. No significant financial relationships to disclose.
Gene expression profile of circulating tumor cells (CTCs) in clear cell metastatic renal cell carcinoma (mRCC).
Authors: Iacovelli R. , Nicolazzo C. , Petracca A. , Risi E. , Cortesi E. 
Published: February 2017

302 Background: The presence of circulating tumor cells (CTCs) is described in 50% of patients affected by mRCC. The detection of CTC seems to be correlated with advanced tumor stage and more aggressive tumor phenotype. In some other solid tumors, such as breast, colorectal and prostate cancer, a growing body of evidence is emerging about the molecular portrait of these cells, whose nature is still largely unknown. The lack of information about CTCs characterization in RCC strongly hampers their application into the clinical practice. Aim of the study was to trace a gene expression profile of CTCs in mRCC patients. Methods: 18 metastatic clear cell mRCC patients were enrolled in the study. All patients provided informed consent. CTCs were isolated from 10cc of peripheral blood by CELLection Dynabeads coated with the monoclonal antibody towards the human Epithelial Cell Adhesion Molecule (EpCam). CELLection Epithelial Enrich is designed to optimally enrich bead-free, viable epithelial tumor cells. Tumor cells were eluted, subjected to RNA extraction and cDNA synthesis. PCR was then performed to investigate the expression of cytokeratin 8 (CK8) and vimentin as markers of clear cell RCC, multidrug resistance (MDR1), multidrug resistance related proteins 1–5–7 (MRP 1, MRP5, MRP 7) as drug resistance markers. Results: According with standard CTCs definition (CK+/CD45-), we found their presence in 9/18 samples (50%). Out of them, vimentin was found in 2/9 (22%), MDR1 in 3/9 (33%), MRP1 in 1/9 (11%), MRP5 in 6/9 (66%) and MRP7 in 9/9 (100%). Conclusions: To our knowledge this is the first attempt to describe a gene expression portrait in CTCs from clear cell mRCC. Of note is that vimentin, classically used as diagnostic marker for clear cell RCC is often lost in CTCs. This seems to further confirm the discrepancy between CTCs and primary tumor phenotype, already demonstrated in breast cancer. The expression profile of genes involved in multidrug resistance in CTCs seems to reflect the well known drug resistance observed in RCC. How these biological information obtainable from a gene expression profile performed on CTCs in clear cell mRCC may be translated into the clinic is currently under investigation. No significant financial relationships to disclose.
TORAVA trial: Lessons from this trial in the two control arms, sunitinib and bevacizumab in combination with interferon.
Authors: Escudier B. J. , Perol D. , Ferlay C. , Gravis G. , Chevreau C. , Delva R. , Bay J. , Geoffrois L. , Blanc E. , Negrier S. 
Published: February 2017

315 Background: The TORAVA trial, reported at ASCO 2010, was a randomized phase II study aimed to determine the efficacy and safety of temsirolimus and bevacizumab combination. Both efficacy and safety were demonstrated as insufficient. Interestingly, 2 control arms were used in this study, sunitinib (arm B) or bevacizumab and a-interferon (arm C). Both PFS and RR were higher in arm C than arm B (16.8 mths and 39% vs. 8.6 mths and 23.8%). Post-hoc analysis were thus performed to determine the predictive factors for better efficacy. Methods: Overall, 171 pts were randomized in this study, 42 in arm B and 41 in arm C. The study was stratified on PS only, 0–1 vs 2. These 83 pts were analyzed regarding baseline characteristics, and dose reduction. Results: Some important differences were detected in the 2 arms, in favor of arm C: DFI>12mths (29 vs. 39%), good MSKCC risk (31 vs. 39%), Fuhrman grade 1–2 (32 vs. 38%), liver metastases (19 vs. 14.6%), high LDH (17.1 vs. 7.9%). Interestingly, pts who had dose reduction of interferon (27/41 pts) had a longer PFS than those who did not reduced the dose. Updated analyses will be presented. Conclusions: Small randomized trials such as randomized phase II trials are not guaranteed to balance predictive/ prognostic factors across treatment arms. Before interpreting RR and PFS in mRCC, careful analysis of pt characteristics should be performed. However, this study will probably help to determine a population more likely to benefit from bevacizumab-interferon combination. [Table: see text]