bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboplatin-based sequential chemotherapy for aged patients with advanced bladder cancer.
Authors: Yoneyama Takahiro , Tobisawa Yuki , Yoneyama Tohru , Yamamoto Hayato , Imai Atsushi , Mori Kazuyuki , Hatakeyama Shingo , Hashimoto Yasuhiro , Koie Takuya , Ohyama Chikara 
Published: February 2017

342 Background: We retrospectively evaluated the feasibility and effectiveness of carboplatin based chemotherapy for the patients 65 years or older with advanced bladder cancer. Methods: We treated 86 patients with advanced bladder cancer at our clinic between August 2004 and June 2014. 56 patients (40 men and 16 women) with the age of 65 years or older were enrolled. Their average age was 75.8 years old (65–86), average Ccr was 54.4 ml/min (14.5–113.0), and an average follow-up period was 21.7 months (2–81). There were 18 recurrent cases after radical surgery and 38 inoperable cases. The therapeutic regimen consisted of 2 lines: gemcitabine/carboplatin (GCarbo) therapy as the first line, with two courses as a set; GCarbo/docetaxel (GCarboD) therapy as the second line if the response in the first line was insufficient. GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to GCarboD, which consisted of 800mg/m2 gemcitabine on days 1 and 8, 70mg/m2 docetaxel on day 1, and carboplatin(AUC 3) on day 2. Treatment efficacy was checked every 2 course. Results: Of the 56 subjects who had undergone the GCarbo therapy, the response rate was 37.5% (CR+PR) with 4 and 17 subjects exhibiting CR and a PR, respectively; the average response duration was 10.0 months (2–78). The response rates of 12 instances of GCardoD was25.0 %; the overall median survival was 14.0 months throughout the carboplatin-based sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 33 of those who had undergone the GCarbo therapy (58.9%). In GCarboD regimen, there were 11 (91.7 %) of G3/4 AEs. Conclusions: Although the present study is small and preliminary, the present carboplatin-based sequential chemotherapy is safe and active for advanced bladder cancer of the patients 65 years or older. GCarbo regimen achieved acceptable response rate (37.5%) in advanced bladder cancer. The median overall survival of 14.0 months is acceptable when average age of 75.8 year for the subjects is took into consideration. However, GCardoD had limited effectiveness for non-responder of GCarbo.
Validating a local failure risk stratification for use in a prospective study of adjuvant radiation in bladder cancer.
Authors: Baumann Brian C. , He Jiwei , Hwang Wei-Ting , Tucker Kai , Bekelman Justin E. , Herr Harry W. , Lerner Seth P. , Tangen Catherine M. , Guzzo Thomas J. , Malkowicz S. Bruce , Christodouleas John Paul 
Published: February 2017

347 Background: To inform the design of trials of adjuvant radiation (RT) for bladder cancer, a local failure (LF) risk grouping has been proposed and externally validated that stratifies radical cystectomy (RC) pts into 3 groups based on pathologic factors. This stratification was developed using historical surgical databases and may not reflect outcomes in the observation arm of a modern trial. The purpose of the study is to assess whether trial accrual bias or improving surgical techniques over time impact the validity of the stratification or reduce the LF risk estimates for each subgroup. Methods: The LF stratification was developed using 2 cohorts treated with RC +/- chemo: a single-institution cohort of 442 pts (1990-2008) and the multi-center SWOG 8710 cohort of 264 pts (1987-1998). To assess the impact of trial accrual bias, we excluded pts who developed LF, DM, died, or were lost to follow up <90 days from surgery or completing post-op chemo as these pts are very unlikely to be enrolled in an adjuvant RT trial. 3-yr LF rates were estimated using Gray’s test. The stratification was considered valid if all 3 risk groups had significantly different LF rates. To assess the impact of improving surgical techniques over time, a Fine-Gray regression estimated the association of LF and year of RC while controlling for risk group. Results: Using the stricter criteria, 10% of SWOG pts and 14% from the other cohort were excluded. Analysis of the remaining pts confirmed 3 subgroups with significantly different LF risk: low risk (stage ≤pT2), intermediate risk (≥pT3 with negative margins and ≥10 nodes identified at surgery), and high risk (≥pT3 with positive margins OR <10 nodes identified) with 3-yr LF rates of 7%, 17%, and 36%, respectively (p<0.01), nearly identical to the rates when not accounting for accrual bias. Year of RC was not associated with LF risk on univariate analysis or after controlling for risk group in the SWOG, single-institution, or combined cohorts. Conclusions: These results suggest that neither trial accrual bias nor improvements in surgical techniques over time invalidate the LF risk stratification or substantially affect LF estimates. The proposed stratification is promising for use in adjuvant RT trials.
Measuring success after radical cystectomy: Feasibility of a novel composite endpoint ("poor recovery") to quantify outcomes after surgery.
Authors: Wood Erika L. , Baack Kukreja Janet E. , Porten Sima P. , Ezeagu Raphael , Qiao Wei , Navai Neema , Kamat Ashish M. , Dinney Colin P. N. , Shah Jay Bakul 
Published: February 2017

357 Background: Given the predilection of invasive bladder cancer toward older sicker patients and the complexity of radical cystectomy (RC), it is not surprising many patients experience prolonged, difficult recoveries. There is growing interest in identifying ways to improve recovery after RC. To date, studies have focused on inpatient length of stay (LOS) as the primary measure of recovery improvement efforts. Given that many patients suffer complications after discharge and require hospital readmission, inpatient LOS may not be the most useful measure. We propose a novel endpoint – “Poor Recovery” – as a more encompassing measure of outcomes after RC. Methods: A comprehensive perioperative multidisciplinary algorithm known as the Optimized Surgical Journey (OSJ) has been in development at our institution over the last 18 months. We selected 50 patients who underwent RC with the OSJ algorithm and 50 patients who underwent RC with usual care during the same time period. Poor Recovery was defined by inpatient LOS > 7 days or hospital readmission within 30 days. Statistical analyses included Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables. Results: Patients in the OSJ group had significantly shorter times to first flatus, bowel movement, ambulation, and resumption of regular diet (Table). There were no differences between the groups in operative time, blood loss, opioid use, or rate of ICU admission. Mean LOS was significantly shorter in the OSJ group (5.6 and 8.5 days, p<0.01). Poor Recovery was experienced by 18% of the patients in the OSJ group and 70% of the patients in the non-OSJ group (p<0.01). Conclusions: We define a novel composite endpoint, Poor Recovery, that can help measure outcomes after RC. For future prospective studies of accelerated recovery pathways, the poor recovery endpoint may be a useful metric by which to determine the efficacy of various interventions. [Table: see text]
Institutional retrospective review of presurgical cisplatin-based chemotherapy (chemo) in patients with urothelial carcinoma (UC): Gemcitabine+cisplatin (GC) versus dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC).
Authors: Harshman Lauren Christine , Jacobus Susanna J. , Mullane Stephanie A. , Feldman Hope , Hirsch Michelle S. , Kantoff Philip W. , Choueiri Toni K. , Bellmunt Joaquim 
Published: February 2017

365 Background: Neoadjuvant cisplatin-based chemo is the standard of care for muscle invasive UC. ddMVAC and GC are frequently used regimens but have not been directly compared. The choice is often based on physician preference and toxicity profile. We interrogated a pre-existing database of UC patients (pts) for differences in efficacy and toxicity among them. Methods: From 2007-2013, consecutive pts who had received presurgical chemo prior to primary tumor resection for muscle invasive, non-metastatic UC were identified. Tolerability, toxicity and efficacy were evaluated. Rates were calculated by regimen and compared using Fisher’s exact test. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by regimen using logrank test. Cox regression estimated hazard ratios (HR) in univariate and adjusted models. Results: Of the96 patients eligible for analysis (GC: 40, ddMVAC: 56), 42% of GC pts had ≥cT3 and 23% had cN+ compared to 62% and 39% with ddMVAC. pCR rate was 18% for GC and 27% for ddMVAC (p=0.33). With a median follow-up of 28 mo., 2-yr OS probabilities were 59% [95% CI:(39-74)] on GC and 77%[95%CI:(60-87%)] on ddMVAC (p=0.1). Conclusions: Despite having more clinical ≥T3 and node positive disease at baseline, ddMVAC is at least as active as GC and achieved a numerically higher rate of pCRs/≤pT1 than GC in our cohort. No unexpected toxicities surfaced. Dose delays, discontinuations, and most selected toxicities appeared higher with GC. Neither DFS or OS significantly differed between the two regimens, however, there was a trend to greater benefit with ddMVAC. [Table: see text]
Outcomes of progression on surveillance for clinical stage I nonseminomatous germ cell tumours (NSGCT).
Authors: Hamilton Robert James , Nayan Madhur , Anson-Cartwright Lynn , Bedard Philippe L. , Moore Malcolm , Chung Peter W. M. , Warde Padraig Richard , Sweet Joan , O'Malley Martin , Atenafu Eshetu G. , Jewett Michael A. S. 
Published: February 2017

377 Background: Active surveillance (AS) is universally accepted for clinical stage (CS) IA and favoured by most centers for CSIB. Patients progressing on AS are typically treated with chemotherapy, but there is no consensus. We describe patterns and mode of detection of progression and treatment of progression in our NSGCT AS cohort. Methods: From Dec 1980 to Aug 2011, 466 CSI NSGCT patients were managed with AS and 133 (28%) had disease progression while on AS. Treatment upon progression was physician choice but based on site of progression (e.g. retroperitoneum vs. extra-retroperitoneal), size or multifocality, and markers (S0 or stable, low level S1 vs. ≥ S1). Mode of detection of progression, characteristics at progression and primary treatment of progression (chemotherapy vs. retroperitoneal lymphadenectomy (RPLND)) were explored. Multivariate logistic regression was used to explore factors associated with receipt of more than one therapy in treatment of progression after surveillance. Results: Median time to progression was 7.3 months and detected by routine imaging (47%), routine serum tumour markers (37%), or both (12%). Progression most frequently occurred in the retroperitoneum (67%). Following progression, first-line treatment was chemotherapy for 71 (53%), RPLND for 51 (38%) and 11 (8.3%) underwent other therapy. In 59%, only one modality of treatment was required: chemotherapy only in 42/71 (59%); RPLND only in 36/51 (71%). For those treated with chemotherapy, pure embryonal carcinoma in the orchiectomy pathology (OR 0.11; p=0.05) was inversely associated with requiring further therapy. For those treated with RPLND, elevated markers pre-RPLND (OR 7.31; p=0.01) was associated with requiring further therapy. Overall, a second relapse occurred in 25/133 (19%) patients. With a median follow-up of 8.2 years, there were 5 deaths from testis cancer (3.8% of AS progressors; only 1.1% of overall AS cohort). Conclusions: The majority of patients progressing on surveillance do so in the retroperitoneum and within the first year. Of those that progress, most will achieve complete response with single modality treatment. In particular, RPLND can be utilized as monotherapy in select cases.
The use of radiation for stage I seminoma: Analysis of the National Cancer Database.
Authors: Waingankar Nikhil , Handorf Elizabeth , Smaldone Marc C. , Plimack Elizabeth R. , Wong Yu-Ning , Haseebuddin Mohammed , Horwitz Eric M. , Uzzo Robert G. , Kutikov Alexander 
Published: February 2017

385 Background: Primary radiotherapy has historically been the preferred treatment for stage I seminoma. However, there is emerging consensus that observation or primary chemotherapy may be preferred in order to reduce overtreatment and risk of secondary malignancy. Hypothesizing that the use of radiotherapy has decreased in the modern era, our objective was to assess temporal practice patterns in stage I seminoma using a large national cancer registry. Methods: The National Cancer Database (NCDB) was queried for all patients diagnosed with stage I seminoma from 1998 to 2011. Temporal trends for receipt of systemic chemotherapy, radiation, and observation (defined as no treatment) were assessed. Following adjustment for patient, demographic, and clinicopathologic characteristics, generalized estimating equations were used to assess for associations between covariates and receipt of primary radiotherapy. Results: Of the 34,251 patients identified with stage I seminoma in the NCDB, 20,627 were treated with radiation (60.2%), 2,278 were treated with chemotherapy (6.7%), and 11,346 were managed with observation (33.1%). Radiation use significantly declined from 73.5% in 1998 to 29.6% in 2011 (p<0.0001), while utilization of chemotherapy (1.9% to 16.5%, p<0.0001) and observation (24.6% to 53.9%, p<0.0001) increased. Following adjustment, age categories 30−39 years (OR 1.06 [CI 1.01−1.13]) and 40−49 years (OR 1.10 [CI 1.03−1.17]), and stage T2 (OR 1.25 [CI 1.17−1.32]) and T3 (OR 1.21 [CI 1.04−1.41]) were associated with increased utilization of radiotherapy. Uninsured patients (OR 0.78 [CI 0.71−0.86]) and those with Medicaid (OR 0.82 [CI 0.73−0.92]) or Medicare (OR 0.62 [CI 0.55−0.69]) were less likely to undergo primary radiotherapy, while those with non-Medicare/Medicaid government insurance were more likely to receive radiation (OR 1.40 [CI 1.13-1.75]). Conclusions: In the largest known cohort of patients with Stage I seminoma reported to date, these data demonstrate that utilization of radiation therapy for stage I seminoma is on the decline. Coinciding with shifts in evidence−based guidelines, observation is now the most commonly employed management strategy for patients with Stage I seminoma.
Initial results from ASSURE (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma, an ECOG-ACRIN-led, NCTN phase III trial.
Authors: Haas Naomi B. , Manola Judith , Uzzo Robert G. , Atkins Michael B. , Wilding George , Pins Michael , Jewett Michael A. S. , Kane Christopher J. , Cella David , Wagner Lynne I. , Coomes Bob , Wood Christopher G. , Dutcher Janice P. , Flaherty Keith , DiPaola Robert S. 
Published: February 2017

403 Background: Patients (pts) with locally advanced renal cell carcinoma (RCC) are not uniformly cured by resection. The pursuit of tolerable and effective adjuvant therapies led to this investigation of two oral agents that are widely effective in the metastatic setting. Methods: 1,943 pts with completely resected RCC (pT1b high grade to pT4 any grade N any) were stratified on risk (intermediate-high or very high), clear/non-clear histology, ECOG PS, and resection approach, and randomized equally to sunitinib daily for 4 of 6 wk cycle, sorafenib daily, or placebo, then treated for up to 1 year. The primary endpoint was disease-free survival (DFS). The study was designed to detect a 25% reduction in the hazard rate, corresponding to an improvement from 5.8 to 7.7 years median DFS. After accrual of 1322 pts, the starting dose was reduced and then individually titrated to mitigate the effect of pt discontinuation from treatment intolerance. Results: At an interim analysis conducted with 62% information, although no efficacy or futility boundaries were crossed, the Data Safety Monitoring Committee recommended release of results. Using a stratified log-rank test, there were no significant differences in DFS or overall survival between either of the experimental arms and placebo. The redesign reduced the discontinuation rate on the experimental arms from about 26% in pts starting at full dose to about 14% in pts starting at reduced dose. Most common grade ≥3 adverse events were hypertension (16%/16%/4%), hand-foot reaction (15%/33%/1%), Rash (2%/15%/<1%), and fatigue (17%/7%/3%) on sunitinib, sorafenib and placebo, respectively. (See Table.) Conclusions: In pts with locally advanced, resected RCC, adjuvant treatment with sorafenib or sunitinib should not be pursued. Dose titration reduced the treatment discontinuation rate; this finding may have relevance in other settings. Clinical trial information: NCT00326898. [Table: see text]
A phase II trial of sunitinib and gemcitabine in sarcomatoid and/or poor-risk patients with metastatic renal cell carcinoma.
Authors: McKay Rana R. , Choueiri Toni K. , Werner Lillian , Atkins Michael B. , Olivier Kara M. , Song Jiaxi , Signoretti Sabina , McDermott David F. , Michaelson M Dror 
Published: February 2017

408 Background: Sarcomatoid renal cell carcinoma (sRCC) is associated with aggressive biology and poor prognosis. Poor-risk RCC, as defined by established risk factors, demonstrates similar aggressive behavior. Though vascular endothelial growth factor (VEGF) therapy is the standard initial therapy for RCC, insufficient data exist in sRCC and efficacy is limited in poor-risk disease. The objective of this study was to investigate the efficacy of anti-angiogenic therapy and cytotoxic chemotherapy in clinically aggressive RCC. Methods: We conducted a phase II single arm trial at 3 institutions of sunitinib (37.5 mg PO daily, 2-weeks on, 1-week off) and gemcitabine (1,000 mg/m2 IV day 1 and 8 of every 21-day cycle) in patients (pts) with sarcomatoid or poor-risk RCC (NCT00556049). The primary endpoint was objective response rate (ORR) defined by RECIST. Secondary endpoints included overall survival (OS), safety, and biomarker correlatives. Results: Overall, 39 pts had sRCC and 33 had poor-risk RCC. Of the 32 sRCC pts with evaluable disease, the ORR was 26% (n=10) and stable disease rate (SDR) was 38% (n=15). Of the 31 evaluable poor-risk RCC pts, ORR was 24% (n=8) and SDR was 39% (n=13). OS for pts with sRCC was 10 months (95% CI 6, 24) and 15 months (95% CI 9, 29) for pts with poor-risk RCC. The most common ≥ grade 3 treatment-related adverse events included neutropenia (n=20), anemia (n=10), and fatigue (n=7). Of the 27 sRCC pts with tissue for central review, increased sarcomatoid histology (>10%) correlated with an improved clinical benefit rate (CBR, ORR + SDR) compared to pts with ≤10% sarcomatoid histology (CBR 100% for >10% versus 55% for ≤10% sarcomatoid, p=0.04), suggesting that sRCC was sensitive to combination therapy. Pts with clear-cell histology were more likely to experience an OR compared to those without clear-cell histology (32% versus 16%, p=0.23). Of 11 pts with tumor DNA sequencing data, no actionable gene mutations were identified. Conclusions: Our results suggest that VEGF targeted therapy and cytotoxic chemotherapy are an active combination in pts with rapidly progressive RCC. The combination may be more efficacious than either therapy alone and this is under further investigation (NCT01164228). Clinical trial information: NCT00556049.
Patients' preferences for adjuvant sorafenib after resection of intermediate or high-risk renal cell carcinoma in the SORCE trial: What makes it worthwhile?
Authors: Blinman Prunella Louise , Davis Ian D. , Martin Andrew , Troon Simon , Sengupta Shomik , Hovey Elizabeth J. , Coskinas Xanthi , Kaplan Richard S. , Ritchie Alastair W. S. , Meade Angela M. , Eisen Tim , Stockler Martin R. 
Published: February 2017

415 Background: SORCE is an international, double-blind, placebo-controlled, phase 3 trial comparing adjuvant sorafenib for 1 year, for 3 years, or observation after resection of intermediate or high risk (as per the Leibovich score), localised renal cell carcinoma (RCC). We determined the survival benefits that SORCE participants judged necessary to make adjuvant sorafenib worthwhile 3 months after starting study treatment. Methods: Participants recruited to SORCE from Australia and selected UK sites completed a validated, self-administered questionnaire 3 months after starting study treatment to determine the minimum survival benefits they judged necessary to make adjuvant sorafenib worthwhile. Scenarios used baseline survival times (without adjuvant sorafenib) of 5 and 15 years; and baseline survival rates (without adjuvant sorafenib) of 65% and 85% at 5 years. Preferences were determined for 1 year of adjuvant sorafenib (versus none) and for 3 years of adjuvant sorafenib (versus 1 year). All tests were 2-sided and non-parametric. This substudy of SORCE was conducted by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Results: The 179 participants were mostly male (72%) with a median age of 57 years (range 29 to 78). Participants allocated sorafenib judged larger benefits necessary to make 1 year of adjuvant sorafenib worthwhile than those allocated placebo: median benefit of an extra 1 year versus an extra 1 month for baselines of 5 years (p=0.004) and 15 years (p=0.02); median benefit of an extra 5% versus an extra 1% for baseline of 65% (p=0.03), and an extra 3% versus an extra 1% for a baseline of 85% (p=0.07). Larger survival benefits were judged necessary to make 3 years of adjuvant sorafenib worthwhile (versus 1 year) regardless of treatment allocation: median benefit of an extra 2 months to 1 year for baselines of 5 years (p=0.02) and 15 years (0.02). Conclusions: Experienced toxicity and duration of treatment are important determinants of patients’ preferences for adjuvant sorafenib in RCC.