bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant gemcitabine-cisplatin (GC) for muscle-invasive bladder cancer (MIBC): Does midway CT staging predict for pathologic complete response (pCR)?
Authors: Seah Jo-An , Leibowitz-Amit Raya , Atenafu Eshetu G. , Alimohamed Nimira , Joshua Anthony Michael , Knox Jennifer J. , Tannock Ian , Sridhar Srikala S. 
Published: February 2017

306 Background: Neoadjuvant cisplatin-based chemotherapy (NC) improves overall survival in MIBC, with pCR post radical cystectomy (RC) linked to better outcomes. NC is underutilized in part due to concerns over disease progression during NC. Midway radiological CT (post 2 NC cycles) may identify patients (pts) progressing on NC who should proceed to definitive therapy (DT). Methods: We reviewed 39 MIBC pts planned to receive 4 cycles of NC (GC) between Jan2005-April2013. Most pts (70%) had midway CT staging. A radiological response was defined as clear improvement in tumour +/- nodal status on CT compared to baseline, taking into account prior trans-urethral resection of bladder tumour; any other result was considered no response. DT consisted of RC, concurrent chemoradiation (CCR), or radiation alone (R). Descriptive statistics and Fisher’s exact test examined associations between disease characteristics and outcomes. Results: Overall, 28 pts (72%) completed planned NC; 7 pts (18%) stopped early due to no response on midway CT; 4 (10%) discontinued due to death (1), sepsis (2), and fatigue (1). Twenty-six pts (67%) had RC, 3 (8%) had CCR, 6 (15 %) had R and 4 (10%) did not receive DT. Of the 26 RC pts – 6 (23%) had a pCR. There were no pCRs among pts who had no radiological response at midway CT. At time of last follow up, 8 pts (21%) had died, 13 (33%) had recurrence/ metastases, and the remainder are being actively followed. Of pts with pCR, there were no recurrences (median follow up 12.2 mo (range 6.3-20.9 mos). The rate of venothromboembolism (VTE) was 26%, and nearly half occurred during NC, but did not affect treatment. Conclusions: Lack of response on midway CT was associated with a lack of pCR at RC, suggesting midway staging may be of value in MIBC receiving NC. The rates of pCR were consistent with reported literature, but rates of VTE appear higher than expected and requires further investigation. [Table: see text]
Targeted sequencing of upper tract urothelial carcinoma.
Authors: Sfakianos John P. , Kim Philip H. , Iyer Gopa , Cha Eugene K. , Zabor Emily C. , Hakimi A. Ari , Scott Sasinya N. , Ramirez Ricardo , Hanrahan Aphrothiti , Rosenberg Jonathan E. , Al-Ahmadie Hikmat , Dalbagni Guido , Bajorin Dean F. , Berger Michael F. , Bochner Bernard H. , Solit David B. , Coleman Jonathan A. 
Published: February 2017

309 Background: Regardless of the anatomic location (renal pelvis or ureter (upper tract), bladder or urethra) urothelial carcinoma is considered a single entity. Outcomes differ depending on site of initial diagnosis. Moreover, little is known about the comparative biology across primary sites. To define the genomic profile of urothelial carcinoma arising from the upper tract, we used a next generation sequencing technology to analyze 26 sporadic high-grade urothelial tumors of the renal pelvis. Methods: Frozen tumor samples and matched germline blood or normal kidney DNA from 26 nephroureterectomy specimens were obtained under an IRB-approved protocol. DNA was analyzed using a next generation, targeted sequencing assay. We compared these tumors to a set of 108 bladder tumors. Fisher’s exact test analyzed associations with pathological stage and Cox regression with log-rank p-values examined associations with bladder recurrence and disease-free survival. Fisher’s exact test was used to compare mutation frequencies between upper tract and bladder tumors. P-values were adjusted for multiple comparisons using the Benjamini-Hochberg method. Results: Surgical pathology was Ta, T1, T2 and T3 in 7 (26.9%), 5 (19.2%), 4 (15.4%) and 10 (38.5%) patients, respectively. High-grade disease was found in 24 (92.3%) patients with 6 (27.3%) patients having node positive disease. The most frequently altered genes included FGFR3 (42.3%), KDM6A (38.5%), MLL2 (26.9%), TSC1 (26.9%), CREBBP (23.1%), CDKN2A (19.2%) and HRAS (19.2%). No significant differences in tumor and patient characteristics were found between the bladder and upper tract cohorts. A significant difference in the frequency of alterations between the upper tract and bladder cohorts was found in HRAS (19.2% vs 2.8%, p=0.032), TP53 (7.7% vs 57.4%, p<0.001) and TSC1(26.9% vs 5.6%, p=0.024). Conclusions: We identified unique patterns of genomic alterations within upper tract urothelial carcinoma compared to bladder cancers. Upper tract tumors are characterized by a higher frequency of activating FGFR3 and HRAS mutations, TSC1 nonsense mutations, and a lower frequency of TP53 alterations. These findings may have future implications on the utility of targeted therapies in this disease subtype.
Changes in health-related quality of life (HRQL) after bladder cancer (BC) diagnosis (DX): A longitudinal population-based study.
Authors: Fung Chunkit , Pandya Chintan , Guancial Elizabeth A. , Noel Shri , Noyes Katia , Sahasrabudhe Deepak M. , Messing Edward M. , Scosyrev Emelian , Mohile Supriya Gupta 
Published: February 2017

317 Background: Few studies have examined longitudinal changes in HRQL among BC patients. To our knowledge, this is the largest prospective population-based study to quantify HRQL changes from before to after BC DX and to compare their HRQL with a non-cancer cohort. Methods: Our sample included 179 BC patients (≥ age 65) and 376,986 non-cancer subjects within the SEER-Medicare Health Outcomes Survey database (1998-2007). We assessed HRQL as measured by physical (PCS) and mental (MCS) component summary scores of the veterans RAND 12-item health survey. An analysis of covariance model was used to estimate changes in HRQL scores for patients after BC DX relative to control subjects with adjustment for baseline HRQL scores and covariates. Results: 84.4% (N=151) of BC patients had non-muscle invasive BC (NMIBC) and 15.6% (N=28) had muscle invasive BC (MIBC). 49.2% and 39.1% of BC patients had ≥2 comorbid conditions and ≥1 activities of daily living (ADL) deficit, respectively. Compared to the control subjects, more BC patients were men (67.0% vs 38.5%; P<0.01), current or former smokers (58.7% vs 37.3%; P<0.01), and had income ≥ $50,000(15.1% vs 8.8%; P=0.02). Other baseline demographic and socioeconomic characteristics were similar (P>0.05). After DX, BC patients reported a significant decline in PCS (1.9; 95% CI 0.1, 3.7) score compared to non-cancer controls whereas the decrease in MCS score (1.4; 95% CI -0.1, 3.0) was not statistically significant. For those with NMIBC, HRQL was not significantly different than that of the non-cancer cohort (P>0.05) after DX. However, the PCS and MCS scores of MIBC patients decreased by 5.3 (95% CI 0.9, 9.8) and 3.8 points (95% CI -0.1, 7.7) after DX, respectively. Older age at BC DX, lower educational and income levels, smoking history, and higher numbers of comorbid conditions and ADL deficits were significantly associated with inferior PCS and MCS scores after BC DX (P<0.01). Conclusions: Treatment-related side effects and/or symptoms due to BC adversely affect HRQL of BC patients, especially in those with MIBC, and should be consistently assessed by health care providers. Future research that examines interventions to improve HRQL is critical to improve BC care.
Outcome of patients with clinically node-positive bladder cancer who undergo consolidative surgery after preoperative chemotherapy: MD Anderson Cancer Center experience.
Authors: Ho Philip Levy , Willis Daniel Levi , Patil Jeevitha , Tart Karen , Parikh Sahil , Shah Jay Bakul , Delacroix Scott Edward , Siefker-Radtke Arlene O. , Dinney Colin P. N. , Pisters Louis L. , Kamat Ashish M. 
Published: February 2017

318 Background: We previously reported results of our phase II study in patients with retroperitoneal lymph node (RPLN) metastasis from bladder cancer (BC) undergoing consolidative surgery after preoperative chemotherapy. Here we present an expanded cohort of patients who underwent consolidative surgery after chemotherapy for clinically node-positive BC. Methods: We reviewed results of patients from our IRB approved protocol including those with clinical evidence of nodal metastasis in the pelvis or retroperitoneum (M1), without visceral metastasis, from 1995-2010. Endpoint of the study was cancer-specific survival (CSS) calculated from time of surgery. Results: 55 patients with either clinical pelvic lymph node (PLN) metastasis (n=29) or PLN and RPLN metastasis (n=26) were identified. Median CSS was 19 months for all patients; 21 for PLN alone and 16 for PLN and RPLN disease. Kaplan-Meier estimate of 5-year CSS was 31% with no difference between PLN alone and PLN with RPLN disease. Clinical nodal stage was N1: 16, N2: 5, N3: 8, and M1 (RPLN): 26. Majority (94%) of patients received cisplatinum-based chemotherapy. At cystectomy, all patients underwent a PLN dissection with 12 patients (all clinical M1 RPLN) undergoing concurrent RPLN dissection (RPLND). In all, 30 of 55 (55%) patients were pN0 at the time of surgical extirpation while 26% (5 of 19) were pN+ despite radiologic complete response after chemotherapy. 5-year CSS was 57% for pN0 and 9% for pN+ disease (p<0.0001). Median survival in patients with residual tumor in PLN (n=17) was 10.5 months vs. 7 months for RPLN (n=8) (median survival not reached in pN0 patients, p< 0.001). 17 patients developed recurrences outside the surgical field after a median of 8 months. While no recurrences occurred within the lymphadenectomy template, 14% of patients with clinical M1 RPLN disease who did not undergo RPLND had recurrences in RPLN basin. Conclusions: Post-chemotherapy consolidative surgical resection may result in 5-year disease-free survival in patients with clinical evidence of node-positive disease, including those with RPLN positive disease, who have major response to chemotherapy.
Post-prostatectomy persisting PSA: Correlation with disease progression and survival in pT3 prostate cancer patients of the ARO 96-02 randomized phase III clinical trial—10 years' follow-up.
Authors: Wiegel Thomas , Bartkowiak Detlef , Bottke Dirk , Hinke Axel , Stöckle Michael , Wirth Manfred , Semjonow Axel , Miller Kurt 
Published: February 2017

32 Background: In the ARO 96-02 trial, patients with pT3 prostate cancer were randomly assigned before achieving an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP) to receive a wait and see policy (arm A) or adjuvant radiotherapy (RT) (arm B). If the undetectable PSA level was not achieved, patients were excluded by protocol and received RT with 66 Gy (arm C). Methods: Three hundred eighty eight patients with pT3-4 pN0 prostate cancer with positive or negative surgical margins were recruited; 78 retained a detectable PSA (median 0.6 ng/mL, range 0.05-5.6 ng/mL) after RP; 74 of them were irradiated with 66 Gy to the prostatic fossa. Radiotherapy was applied in median 86 days post-RP. Results: Compared to patients in arm A and B, the patients with persisting PSA after RP had higher preoperative PSA values (p<0.0001), higher tumor stages (p=0.0057), higher grades (more G3 tumors), higher Gleason scores (p=0.0013) and more positive surgical margins (p=0.033). For the 74 patients, the 10 years clinical relapse-free survival rate was 63%. Forty three men had hormonal therapy, 12 developed distant metastases; 23 patients died. Compared to patients who did achieve an undetectable PSA (arms A+B), arm-C patients fared significantly worse with a 10 year overall survival of 68% versus 84% (p=0.0019). The rate of developing distant metastases within 10 year post-RP was 2.5 fold higher (14.6 vs. 5.8%) for men with a persisting PSA compared with the patients in arm A (p=0.0079). Metastasis-free survival after 10 years was 67% in arm C versus 81% in arm B (p=0.01). Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors which should then prompt aggressive treatment. It correlates with a higher rate of distant metastases and with worse overall survival. The results underline the significance of achieving an undetectable PSA after radical prostatectomy.
Concurrent cisplatin and radiotherapy: Decision making, tolerability, and outcomes for patients treated in a multidisciplinary bladder clinic.
Authors: Lalani Nafisha , Richter Sue , Chung Peter W. M. , Fleshner Neil Eric , Jewett Michael A. , Zlotta Alexandre , Bristow Robert Glen , Milosevic Michael , Sridhar Srikala S. 
Published: February 2017

320 Background: For select muscle invasive bladder cancer (MIBC) patients, a multimodal approach using transurethral resection of the bladder tumor (TURBT) followed by concurrent cisplatin and external beam radiotherapy (EBRT) provides a curative bladder-sparing alternative to cystectomy. Our aim was to review decision making, tolerability and outcomes for patients treated in a multidisciplinary bladder clinic. Methods: Between June 1998-June 2011, MIBC patients treated with TURBT and concurrent cisplatin (40mg/m2 weekly) with EBRT (60-66Gy in 30-33 fractions to the bladder and pelvis) were identified. Post-treatment cystoscopy was performed every 3 months with regular imaging. Results: A total of 64 patients were assessed; mean age 73 (43-89), 83% were male. The decision to attempt bladder-sparing was based on patient preference (58%), nonsurgical candidate (25%), or unknown (17%). Patients received a mean 5/6 weeks of cisplatin with the most common toxicity being a 14% overall risk of grade 0-1 renal toxicity by NCIC CTC criteria. All patients completed the prescribed EBRT. No patients experienced acute toxicity requiring cystectomy or causing death. At a median follow-up of 3.5 years, 50/64 (78%) patients were alive and had their own bladders, 7/64 (11%) were alive after cystectomy for recurrence, 7/64 (11%) died. Of the 24/64 (38%) recurrences: 3/64 (5%) had positive cytology/carcinoma in-situ and received intravesicle therapy; 1/64 (2%) had local superficial recurrence and underwent TURBT; 7/64 (11%) had local invasive recurrence requiring cystectomy; 13/64 (20%) had distant recurrence, 6 received chemotherapy and 7 were observed. Estimated disease free survival was 51%, and overall survival was 90% at 3.5 years. Conclusions: Bladder-sparing therapy with concurrent cisplatin and EBRT is a well-tolerated and effective approach with outcomes comparable to cystectomy in carefully selected patients. Prospective trials are required to delineate clinical and molecular factors to further triage patients into sub-groups who may benefit from bladder sparing with neoadjuvant/adjuvant chemotherapy or molecularly-targeted agents to improve survival.
Phase Ib/II trial of gemcitabine, cisplatin, plus lenalidomide as first-line therapy for patients with metastatic urothelial carcinoma.
Authors: Tsao Che-Kai , Agarwal Neeraj , Apolo Andrea Borghese , Lee Karen M , Godbold James H. , Oh William K. , Galsky Matt D. 
Published: February 2017

321 Background: Cisplatin-based chemotherapy is standard in patients (pts) with metastatic urothelial carcinoma (MUC), though outcomes remain poor and novel approaches are needed. Lenalidomide, a potent thalidomide analog with antiangiogenic and immunomodulatory properties, has been shown to enhance the antiproliferative properties of standard chemotherapy in nonclinical studies of urothelial cancer (Apolo, ASCO 2011). In this phase Ib/II clinical trial we aimed to determine the safety and efficacy of gemcitabine, cisplatin, plus lenalidomide (GCL) in pts with MUC. Methods: Pts with chemotherapy-naïve MUC received gemcitabine 1000mg/m2 days 1 and 8 and cisplatin 70mg/m2 day 1, of a 21-day cycle. In the phase Ib portion, the dose of lenalidomide was to be dose escalated in successive cohorts starting at 10 mg PO daily, on days 1-14, using standard “3+3” dose escalation rules. The primary objective of the phase II portion was to determine the progression-free survival at one year. Results: A total of 7 pts received GCL (lenalidomide 10 mg dose level) in the phase 1b portion. A single pt experienced a dose limiting toxicity (DLT), grade 4 neutropenia. A decision was made to not dose escalate lenalidomide further due to the frequent need for dose delays and reductions of GC due to cytopenias. An additional 2 pts were enrolled in the phase II portion but the study was terminated due to frequent dose delays/reductions and slow accrual. Among the 9 pts enrolled, 5 required dose reductions of G (4 requiring >1), 4 required dose reductions of C (1 requiring >1), and 6 required at least one dose delay. The most frequent grade ≥ 3 adverse events were: neutropenia (n=7), anemia (n=3), thrombocytopenia (n=3), and diarrhea (n=2). Tumor responses included: partial response (n=3), stable disease (n=3), progressive disease (n=2), and unevaluable (n=1). Conclusions: Chronic administration of the combination of GCL was compromised by overlapping myelosuppression and the need for frequent dose reductions/delays of GC due to cytopenias. Despite promising nonclinical data, combining cytotoxic chemotherapy with “targeted” small molecules faces practical challenges. Clinical trial information: NCT01342172.
Efficacy of single-agent pemetrexed in platinum refractory metastatic urothelial cancer (mUC).
Authors: Benjamin David J. , Bambury Richard M. , Chaim Joshua , Zabor Emily C. , Ostrovnaya Irina , Garcia-Grossman Ilana Rebecca , Iyer Gopa , Bajorin Dean F. , Rosenberg Jonathan E. 
Published: February 2017

322 Background: No standard therapy exists for platinum refractory mUC. Single agent pemetrexed (Pmt) had objective response rates (ORR) of 8% and 28% in two phase II studies (enrolling 13 and 47 patients) and is commonly used in this setting. To address the difference in reported ORRs, we performed a retrospective analysis of Pmt use at MSKCC to evaluate objective response in a larger cohort of patients. A secondary aim was to explore whether neutrophil-lymphocyte ratio (NLR) added prognostic value beyond known factors (time from prior chemotherapy (TFPC), ECOG performance status (PS), liver metastases, and hemoglobin) in the UC salvage setting. Methods: Patients who received Pmt for platinum refractory mUC between 2008 and 2013 were identified. Baseline demographics, clinical characteristics, prior therapies, Pmt dose, and number of cycles were recorded. ORR was determined according to RECIST 1.1. Kaplan-Meier method and Cox regression were used to analyze associations with overall survival (OS). Results: 135 patients were identified with median age 66 (range 45-88), male 76%, ECOG 0 in 14% / 1 in 54% / ≥2 in 32%. Pmt was administered as 2nd-line chemotherapy in 56% / 3rd line in 30% / ≥4th line in 14%. ORR was 7% with median duration of response 10.2 months. There was no significant difference in ORR by line of therapy or PS. Median progression free survival was 2.4 months and median OS was 6.6 months. In this dataset, TFPC was not prognostic, while liver metastases, PS, and hemoglobin were prognostic. Higher NLR was significantly associated with worse OS independent of other known factors. Conclusions: In the largest reported series to date, Pmt had an ORR of 7% in metastatic UC regardless of line of therapy or ECOG performance status. This limited activity highlights the urgent need to develop novel therapeutic strategies. NLR was identified as an independent prognostic factor in this setting. [Table: see text]
Neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) in patients with high-grade upper-tract urothelial carcinoma.
Authors: Hoffman-Censits Jean H. , Trabulsi Edouard John , Chen David Y. T. , Kutikov Alexander , Lin Jianqing , Viterbo Rosalia , Hudes Gary R. , Healy Kelly A. , Hubosky Scott , Wong Yu-Ning , Kilpatrick Deborah , Adair Beth , Cione Charlotte , Plimack Elizabeth R. 
Published: February 2017

326 Background: Improved safety and response rates of AMVAC over standard MVAC in patients (pts) with metastatic bladder cancer support study of neoadjuvant AMVAC for pts with muscle invasive bladder cancer (MIBC) and prenephroureterectomy (NU) for pts with high-grade upper-tract urothelial cancer (UTUC). We performed a phase II study of neoadjuvant AMVAC in MIBC and UTUC, and herein report the results of the UTUC exploratory subgroup. Methods: Pts with UTUC (ureter or renal pelvis) with high-grade UC on biopsy, or positive urine cytology and mass on cross sectional imaging, N0-N1, CrCl >=50, adequate hepatic and marrow function were eligible. Pts received 3 cycles of AMVAC (methotrexate 30 mg/m2, vinblastine 3 mg/m2, doxorubicin 30 mg/m2, cisplatin 70mg/m2) day 1, pegfilgrastim 6 mg day 2 or 3, every 2 weeks. NU, with lymph node dissection at surgeon discretion, was performed 4-8 weeks after last cycle. Exploratory endpoint was pathologic complete response (pCR) rate. Results: Accrual is complete with 10 evaluable UTUC pts enrolled at 2 institutions (FCCC, TJU) over 46.5 months. Median age 67 (range 49-83). Of 10 pts, 6 completed all 3 cycles of AMVAC. Four pts received < 3 cycles due to grade 3 acute kidney injury (1), pyelonephritis and grade 3 diverticulitis (1), flare of underlying hepatitis (1), grade 3 fatigue (1). Additional related grade 3 adverse events (AE) were anemia (1) and nausea/vomiting (1), no grade 4 or 5 AE. All pts underwent NU within 8 weeks of last chemotherapy, median 5.5 weeks. Median time from day 1 AMVAC to NU was 9 wks. 1/10 pts had a pCR, 4/10 patients were staged <pT1, 2/10 pT2, and 3/10 >pT3 or N+. An additional 21.5 months of enrollment were needed in this expansion cohort to accrue 10 pts with UTUC, compared to 44 MIBC pts in 25 mos. All pts completed study treatment as of July 2013. Conclusions: In this small sample, neoadjuvant AMVAC prior to NU was clinically active with manageable toxicity. With short duration from start of chemotherapy to NU, 3 neoadjuvant AMVAC cycles should be considered for further study for high-grade UTUC prior to NU in the cooperative group setting. Clinical trial information: NCT01031420.