bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of hospital readmission following cystectomy with omission of postoperative chemotherapy in patients with urothelial carcinoma of the bladder.
Authors: Smaldone Marc C. , Uzzo Robert G. , Kutikov Alexander , Handorf Elizabeth , Wong Yu-Ning , Armstrong Katrina , Bekelman Justin E. 
Published: February 2017

254 Background: Hypothesizing that complications after radical cystectomy requiring hospital re-admission may preclude subsequent systemic treatment, our objective was to test the association between readmission within 30 days of surgery and receipt of post-operative chemotherapy in Medicare beneficiaries. Methods: Using 1995-2007 linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data, all patients undergoing cystectomy for pathologic stage III-IV urothelial carcinoma were identified. Univariate and multivariate logistic regression analyses were used to test the association between hospital readmission within 30 days and receipt of post-operative chemotherapy (defined ≤9 months from surgery) adjusting for demographic, clinical, hospital, and procedural characteristics. Results: We identified 4,034 patients undergoing radical cystectomy for urothelial carcinoma, of which 1,498 met final inclusion criteria (mean age 75.9±6.3 years, 62.7% male). 563 patients (37.6%) were readmitted within 30 days of surgery (7.5% with ≥2 readmissions). Postoperative chemotherapy was administered in 26.1% of candidates who were readmitted, compared to 35.4% who were not readmitted following surgery (p<0.001). Following adjustment, the odds of receiving chemotherapy were 30% less in patients readmitted to the hospital (OR 0.70 [CI 0.53-0.92]) when compared to patients who were not readmitted. Stratified by number of readmissions, the odds of receiving chemotherapy in patients with 1 and ≥2 readmissions were 26% (OR 0.74 [CI 0.56-0.99]) and 54% (OR 0.46 [CI 0.27-0.79]) less when compared to patients not readmitted. Use of a more restrictive 6 month post operative chemotherapy definition did not significantly impact our findings (OR 0.66 [CI 0.47-0.93]). Conclusions: In a cohort of Medicare beneficiaries undergoing cystectomy, hospital readmission within 30 days is associated with omission of post-operative chemotherapy in patients with Stage III-IV urothelial carcinoma. These data inform treatment planning decisions and strengthen the argument supporting chemotherapy utilization in the neoadjuvant setting.
Efficacy and safety of zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: Results of CALGB 90202 (Alliance).
Authors: Smith Matthew Raymond , Halabi Susan , Ryan Charles J. , Stadler Walter Michael , Hussain Arif , Vogelzang Nicholas J. , Hauke Ralph J. , Sanford Ben L. , Small Eric Jay ,   Alliance
Published: February 2017

27 Background: Zoledronic acid (ZA) decreases risk of skeletal-related events (SREs) in men with castration-resistant prostate cancer (CRPC) and bone metastases. This phase III study evaluated efficacy and safety of earlier treatment with ZA in men with castration-sensitive metastatic prostate cancer. Methods: CALGB 90202 was a randomized, double-blinded, placebo-controlled phase III trial in men with castration-sensitive prostate cancer and bone metastases who had initiated androgen deprivation therapy within six months of study entry. Subjects were randomized 1:1 in blinded manner to receive ZA (4 mg intravenously every 4 weeks) or placebo (P). After progression to CRPC, all patients crossed over to open-label ZA. The primary endpoint was time to first SRE. Target sample size was 680. Time to SRE was defined as interval between date of randomization and date of first SRE (radiation to bone, or clinical fracture, or surgery to bone, or death due to prostate cancer). With 470 SRE events, the log-rank test has 88% power to detect a 23% decrease in hazard rate of SRE event assuming a one-sided type I error rate of 0.05. The study was discontinued prematurely after the corporate supporter withdrew study drug supply. Primary analysis was based on the stratified log-rank statistic adjusting on the stratification factors following observation of 284 SREs (60% of total events). Results: Between June 2004 and April 2012, 645 patients were randomly assigned to ZA or P. Median time to first SRE was 32.5 months in the ZA group and 29.8 months in the P group (hazard ratio (HR) 0.96 [0.76-1.22]; stratified log-rank P=0.74). A total of 271 deaths were observed; median follow-up time for surviving patients was 24.4 months (20.6, 28.3). Overall survival was similar between groups (HR= 0.89 [0.70-1.14]; stratified P=0.34). Rates of grade 3 or higher adverse events were similar between groups (15% vs. 12% in ZA and P). Conclusions: In men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs or death. Early termination limited statistical power of the study. Clinical trial information: NCT00079001.
Effectiveness and safety of valrubicin in non–muscle-invasive bladder cancer following reintroduction: Results from a medical chart review study.
Authors: Cookson Michael S. , Lihou Christine Francis , Harper Samira Q. , Li Thomas , Chitra Surya , Tutrone Ronald 
Published: February 2017

296 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report secondary outcomes and concomitant medication use from a US multicenter, observational, retrospective study. Methods: Medical records of adult patients with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted (March–September 2011). Kaplan-Meier analyses were performed for disease-free survival (DFS), progression-free survival (PFS), worsening-free survival (WFS), cystectomy-free survival (CFS), and time to cystectomy. Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 instillations [range, 2–18]). 107 patients (94.7%) received >3 instillations; 97 (85.8%) completed the full course of therapy (≥6 instillations). DFS was 51.6% (95% CI, 40.9%–61.3%) at 3 months, 30.4% (95% CI, 20.4%–41.1%) at 6 months, and median DFS was 3.5 months (95% CI, 2.5–4.0). PFS was 97.6% (95% CI, 90.9%–99.4%) at 3 months, 87.2% (95% CI, 75.4%–93.5%) at 6 months, and median PFS was 18.2 months (95% CI, 17.2–19.0). WFS was 47.4% (95% CI, 37.2%–57.0%) at 3 months and 28.1% (95% CI, 18.8%–38.2%) at 6 months. CFS was 98.0% (95% CI, 92.2%–99.5%) at 3 months and 93.7% (95% CI, 85.2%–97.4%) at 6 months. Median CFS was not reached; only 13.3% of patients underwent radical cystectomy after starting valrubicin. 56 patients (49.6%) experienced ≥1 local adverse reaction; the most common were hematuria and pollakiuria (both 17.7%), micturition urgency (15.9%), and bladder spasm (14.2%). 55 patients (48.7%) used ≥1 concomitant medication for local adverse reactions; the most commonly used were urinary antispasmodics (21.2%), fluoroquinolones (14.2%), and other urologicals (14.2%). Conclusions: In patients with NMIBC treated with intravesical valrubicin, median DFS and PFS were 3.5 and 18.2 months, respectively, and median CFS was not reached as only 13% of patients underwent radical cystectomy. Valrubicin was well tolerated, and most patients received the full course of 6 instillations. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc.
A 10-year retrospective review of germ cell tumors not cured with cisplatin-based chemotherapy.
Authors: O'Donnell Elizabeth , Gray Kathryn P. , Hirsch Michelle S. , Ravi Praful , Beard Clair , Sweeney Christopher 
Published: February 2017

325 Background: In 2011, there were about 8260 cases of Germ Cell Tumor (GCT) diagnosed in the US, of those, 350 or 4% will die of their disease. We sought to review our experience with a 10-year cohort of 819 patients treated for GCT at Dana-Farber and synthesize the cumulative findings of those who died from their disease specifically looking for different sub-types of incurable GCTs. Methods: Retrospective review of 819 germ-cell tumors treated in our center between 2000 and 2010 to identify patients not cured with cisplatin-based chemotherapy. Inclusion criteria were men over the age of 18 treated for malignant germ cell tumor between 2000 and 2010 at the Dana-Farber Cancer Institute that died from their disease. The outcomes of interest were smoking history, extent of disease at diagnosis, primary site of disease, histology, presence of lymphovascular invasion, outcomes to first- and second-line therapies, treatment with high dose chemotherapy (HDC), late relapse, brain metastases, and presence or absence of transformed teratoma as cause of death. Results: 38 men were identified. Median age 35. More than half had a smoking history. 3 presented with clinical stage 1 disease, 8 good-risk metastatic disease, 4 intermediate-risk and 22 poor-risk at diagnosis. The majority (28) had testicular primaries, 7 mediastinal, one pituitary, one retroperitoneal and one unknown. 21 of 48 had complete responses to first-line therapy. 4 received HDC for relapsed disease. 10 relapsed after 2 years of disease-free survival. 7 died of transformed teratoma. 63% progressed directly through cisplatin-based chemotherapy and died as a result of non-teratomatous germ cell tumor burden. 18% died from unresectable or transformed teratoma and 26% died after suffering a late relapse of disease. Conclusions: Within the cohort of patient who died from their GCTs there are three distinct biological subtypes – the majority is platinum-refractory germ cell tumor while unresectable/transformed teratoma and late relapse make up the remainder. Understanding the unique biology of these disease states compared with curable disease may provide informative insights into chemotherapy resistance for cancer in general.
Inguinal lymph node dissection for penile carcinoma: Postoperative complications using a validated classification system.
Authors: Jayaratna Isuru Sampath , Mitra Anirban Pradip , Dedhia Raj , Asbaghi Steven , Teruya Kara K. , Tygenhof Eric , Schuckman Anne K. 
Published: February 2017

326 Background: Inguinal lymph node dissection (ILND) is the gold standard for evaluating for locoregional disease in penile squamous cell carcinoma (PSCC), however, it has been previously described to have a high morbidity rate. We describe our postoperative complications using a validated classification system and examine possible associations with clinicopathologic factors. Methods: We retrospectively identified patients with a diagnosis of PSCC that underwent ILND at our institution from 1995 to 2012. Postoperative complications were characterized by the highest grade complication achieved by patients using the Clavien-Dindo classification system during the first 90 days after their surgery. Clavien-Dindo scores of 2 or less were defined as low grade, and scores of 3 or greater were defined as high grade. Univariate Cox regression analysis was performed to examine associations between complications and clinicopathologic factors. Results: We identified 36 patients who underwent ILND during this period, with 29 that had complete clinical, pathological and complication data. For the 50 ILNDs performed in our cohort, we report a 46% total complication rate, with a 36% low grade and a 10% high grade complication rate. Of the low grade complications, 39% were wound dehiscences that required wound packing, and 28% were wound infections that required antibiotic treatment. The highest grade of complications achieved was 3A, all of which were lymphoceles that required percutaneous drainage for resolution. We were unable to demonstrate any association of complications with age, ethnicity, tumor stage, tumor grade, AJCC stage, presence of palpable lymphadenopathy or pathologic nodal stage. Conclusions: While ILND still remains an operation with high morbidity, our findings show that the most common low grade complications can be managed with medications and dressing changes, and the relatively modest high grade complication rate consists entirely of percutaneous drain placement. The inability to show associations with clinicopathologic variables is likely due to our low sample size. These findings support the continued use of ILND for staging in PSCC.
Antitumor activity of brentuximab vedotin in CD30 positive refractory germ cell tumors.
Authors: Albany Costantine , Feldman Darren Richard , Garbo Lawrence E. , Einhorn Lawrence H. 
Published: February 2017

327 Background: Brentuximab Vedotin (BV) is a novel antibody drug conjugate that combines the agent mono-methyl auristatin E (MMAE) to a CD-30 specific monoclonal antibody by a protease-cleavable linker. It is approved by the FDA for treatment of relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL). In addition to HL and ALCL, CD-30 expression has been reported on malignant tumors of non-lymphoid origin including testicular embryonal carcinoma (EC). Here we report our initial experience in three heavily pre-treated patients with CD30-positive EC who were treated as part of an ongoing phase 2 open-label multicenter study designed to evaluate the antitumor activity of BV in patients with CD30-positive non-lymphomatous malignancies. Methods: Three men with relapsed or refractory, histologically confirmed CD-30 positive testicular cancer received BV until progression or toxicity. CD-30 expression was assessed by immunohistochemistry. All 3 patients were dosed at 1.8 mg/kg IV every 21 days and followed for response at cycles 2, 4. Results: Three patients were enrolled at 2 sites in the US. Median age was 26 years (range 24-33). All 3 patients progressed after high dose chemotherapy with peripheral blood stem cell transplant. Two patients received BV as 4th line and 1 patient as 3rd line therapy. Tumor sites included lungs, liver, retroperitoneal, mediastinal and supraclavicular lymph nodes. The first patient baseline hCG was 5571. After 2 cycles of therapy, hCG nadir was 45 with a radiologic partial response (PR) by RESICT that lasted 2 months. He then had serologic and radiographic progression in the liver while on therapy. Patient 2 was serologic marker negative and had a radiographic PR by RECIST in lung and mediastinum after cycle 2 and continues on therapy. Patient 3 had a baseline hCG of 10400, with nadir at 110 after 2 doses and continues to have serologic response. By RECIST he currently has stable disease. The treatment was well tolerated in all 3 patients with no grade 3-4 toxicities. Conclusions: All 3 patients with heavily pretreated CD-30 positive EC had clinical benefit after treatment with brentuximab vedotin. The treatment was well tolerated. The enrollment is ongoing in this Phase 2 study. Clinical trial information: NCT01461538.
Surface applicator high-dose-rate fractionated brachytherapy for conservative definitive management of extramammilary Paget’s disease of the penis, scrotum, and mons pubis.
Authors: Devlin Phillip M. 
Published: February 2017

333 Background: This case is of a 70 yo Asian male who had suffered for many years from a painful eroding, oozing, bleeding lesion that started on the mons and over time had spread the full length of the penis and onto the anterior scrotum. A surface mold applicator fractionated computer-optimized high-dose rate (HDR) brachytherapy to 50Gy given in 2 Gy/day 5 days/week for 5 weeks. Methods: For the mons and the anterior scrotum a flat plate of aquaplast was molded with an aperture through which to pass the penis. For the penis a soft wrap, make of two layers of 5mm superflab was created with 15 truguide catheters embedded between. The wrapped penis was then supported with towels and tapes. Using radio-opaque dummy markers a CT was generated and an optimized treatment plan using Oncentra Brachytherapy. Because of the need for daily setups and the intrinsically elastic nature of the penis and scrotum, effort was made to keep the dwell times even so as to minimize any effect from day to day variation in set up. The prescription isodose line was manually adjusted so that where possible there was sparing of deep tissue of the urethra, bladder and testes. When QA was approved the patient began with daily treatments and successfully completed 25 without a treatment break. Results: Sustained local control was observed. Discussion: Surface mold applicator brachytherapy provides the most conformal of radiation therapy to complex superficial targets. For these targets it compares most favorably with all external beam approaches including electron, photon, IMRT and proton therapy. Conclusions: This modality optimally treated these lesions. The depth of the dose can be modulated. The treatment plan can be adapted to deal with swelling late in the course of therapy. The chance of a geographic miss of therapy is low because of the direct application to the affected area.
Long-term outcomes of cisplatin-based chemotherapy in patients with stage II-III germ cell tumors: Center 30-year experience of a single center.
Authors: De Velasco Guillermo , Castellano Daniel E. , Sepúlveda Juan Manuel , Villacampa Felipe , Pascual Tomas , Manneh Ray , Parrilla Lucia , Farfán Carlos A. , Cortes-Funes Hernan 
Published: February 2017

338 Background: We retrospectively assessed long-term outcomes of cisplatin-based chemotherapy for stage II/IIII germ cell tumors (GCTs) at Medical Oncology Department of 12 Octubre University Hospital, Madrid (Spain). Methods: Two hundred fourteen (214) consecutive males with advanced GCTs of the testis or extragonadal origin who received standard cisplatin-based chemotherapy regimens between 1982 and 2012 were analyzed. Results: Demographic features: Median age 26.4 years (range 14- 72 years). Right and left testicular tumor present in 71 (37%) and 78 (41%) patients respectively and cryptorchidism in 11 (5%). Histology: 12% of the patients had seminomatous and 88% non-seminomatous histology. Stage distribution (TNM): Stage II 105p (49%), Stage III 109 p (51%). Twenty-five primary (11%) were extragonadal. Risk assessment according to IGCCCG - good 115 p (54%) intermediate 34 p (16%) and poor 62 p (29%). All patients received chemotherapy with cisplatin (BEP-73%, EP-15%, BOPM-EPI 5%, PVB 6%, others 1%). Survival analysis: The median follow-up period was 117 months (0 - 329). Totally, 158 patients (74%) achieved complete remission (CR). CR was achieved in 128 p (60%) after induction therapy (first line chemotherapy). Salvage treatment: surgery +/-chemotherapy was given to 72 (33%) and 85 (39%) patients respectively. High-dose chemotherapy (with carboplatin based- schemes at dosage (AUC20) as salvage therapy was performed in 65 patients (30%). Of them 35 p (53.4%) had complete remission of disease without relapse and the median progression free survival was of 47.2 months. Severe AEs were < to 5%, and classically already described renal impairment, ototoxicity and neurophaty with non chemotherapy-related toxic deaths. Conclusions: Improvement of medical management and survival during platinum-based chemotherapy and the development of several regimens for salvage chemotherapy seemed to contribute to improving outcomes of patients with advanced GCTs even for patients with platinum-refractory disease. However, we continue to investigate in the search for genetic and molecular mechanisms that help us change it.
Treatment of metastatic penile cancer in the adjuvant setting with ifosfamide, paclitaxel, and cisplatin: A single institution experience.
Authors: O'Reilly Aine , O'Keeffe Margaret , Aherne Paul , Mayer Nicholas J. , Sweeney John P. , Power Derek G. 
Published: February 2017

340 Background: Surgery alone rarely results in long-term disease-free control in patients with N2 or N3 (stage III or IV) metastatic penile cancer. Five-year overall survival rarely exceeds 40% in this group of patients. Ifosfamide, paclitaxel, and cisplatin chemotherapy (ITP) has been reported in the neoadjuvant setting in a phase II trial. The evidence supporting adjuvant chemotherapy after inguinal lymph node dissection (LND) is poor. We report our experience of ITP chemotherapy given in the adjuvant setting after bilateral inguinal LND for stage III and IV penile cancer Methods: In our regional cancer center we performed a retrospective analysis of a prospectively maintained database of all patients between May 2008 and February 2012 who received adjuvant chemotherapy for regional metastatic penile cancer. Results: Four patients received chemotherapy in the adjuvant setting. One patient completed 4 cycles of cisplatin and 5-Fluorouracil after bilateral inguinal LND (pT1N2). There is no evidence of disease recurrence at 20 months post completion of chemotherapy. Three patients received adjuvant chemotherapy with paclitaxel 175 mg/m2 on day 1; ifosfamide 1,200 mg/m2 on days 1-3; and cisplatin 20 mg/m2on days 1-3 (ITP). All pts received 4 X 3 weekly cycles with no significant toxicity. The first two patients underwent inguinal LND for pT3N2 (stage IIIB) disease followed by 4 cycles of ITP. In both patients surveillance imaging showed no evidence of disease recurrence 28 and 50 months, respectively, post completion of chemotherapy. The third patient underwent inguinal LND for pT1bN3 (stage IV) disease followed by 4 cycles of ITP. Surveillance imaging at 6 months post completion of chemotherapy showed no evidence of local or distant recurrence. Conclusions: Multimodality treatment of regional metastatic penile cancer offers the best chance of long-term disease-free and overall survival. The ITP regimen is relatively nontoxic and well-tolerated. We propose that this regimen should be further investigated in the adjuvant or peri-operative settings.
Clinical activity and safety of antiprogrammed death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (pts) with previously treated, metastatic renal cell carcinoma (mRCC): An updated analysis.
Authors: McDermott David F. , Drake Charles G. , Sznol Mario , Choueiri Toni K. , Powderly John D. , Smith David C. , Wigginton Jon M. , Kollia Georgia , Gupta Ashok Kumar , Atkins Michael B. 
Published: February 2017

351 Background: BMS-936558 is a fully human monoclonal antibody that blocks the PD-1 coinhibitory receptor expressed by activated T cells. In the initial portion of a phase I study (CA209-003), BMS-936558 showed promising activity in pts with various solid tumors, including mRCC. Accrual was expanded to better characterize antitumor, safety, and dose effects. Methods: Pts with RCC were treated with BMS-936558 IV q2wk at 10 mg/kg initially, followed by additional pts at 1 mg/kg. Pts received up to 12 cycles (4 doses/cycle) of treatment or until unacceptable toxicity, confirmed progressive disease, or complete response (CR). Clinical activity was assessed by RECIST v1.0. Results: As of July 3, 2012, 34 mRCC pts had been treated at 1 mg/kg (n=18) or 10 mg/kg (n=16). ECOG performance status was 0 in 13 pts and 1 in 21 pts. More than 40% of study patients received ≥3 prior therapies, >70% received prior antiangiogenic therapy, and >50% received prior immunotherapy. Sites of metastatic disease included lung (n=30), lymph node (n=28), bone (n=10), and liver (n=9). The incidence of grade 3-4 related adverse events was 21% and included hypophosphatemia (6%) and respiratory disorders (6%); there were no drug-related deaths among mRCC pts. Ongoing durable clinical responses were observed at both 1 and 10 mg/kg doses (Table) with some continuing off treatment. Three pts demonstrated nonconventional response patterns and were not categorized as responders by conventional RECIST. Current median duration of response was 12.9 months for both 1 and 10 mg/kg doses. Conclusions: BMS-936558 is tolerable and exhibits ongoing durable clinical activity in pts with previously treated mRCC. Clinical trial information: NCT00730639. [Table: see text]