bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causes and patterns of mortality in patients with lethal germ cell tumor (GCT).
Authors: Hamid Anis , Funt Samuel Aaron , Markt Sarah C. , Bromberg Maria , O'Donnell Devon , Adra Nabil , Taza Fadi , Albany Costantine , Krailo Mark D. , Frazier A. Lindsay , Einhorn Lawrence H. , Feldman Darren R. , Sweeney Christopher 
Published: February 2020

421 Background: Most metastatic GCTs are cured with cisplatin-based chemotherapy. Clinical factors of adverse GCT-specific survival have been identified, however patterns of death are not well-defined and would inform clinical care and biological investigation. Methods: This multi-institutional study pooled data of male pts with death related to GCT from high-volume adult GCT academic centers (Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Indiana University) over 20 years (1997-2017). Pts were annotated for site, stage, IGCCC risk, histology, primary therapy and relapse variables (including relapse histology, metastatic (met) burden, salvage and palliative therapies), and detailed cause of GCT death. Cox regression assessed associations with survival. Results: The pooled cohort of 620 pts comprised 90% non-seminoma, 21% mediastinal primary and at diagnosis, 59% were stage III, 64% poor risk; 48% received high-dose chemotherapy plus transplantation. Median survival (OS) from first relapse after metastasis was 12.0 mos. Leading causes of death were chemorefractory GCT (83.1%), secondary somatic malignancy (SSM) arising from teratoma (9.4%), acute toxicity (4.5%), late toxicity (2.3%) and progressive untransformed pure teratoma (0.8%). Late relapse (relapse >2 years after 1st-line therapy) occurred in 11.3% at a median of 5.9 yrs. Of these pts, 1/3 were stage I at initial diagnosis and 75% were good or intermediate risk at met diagnosis, and were more likely to have SSM histology/death vs early relapse. Late relapsing disease (HR 0.48, p<0.0001) and presence of SSM (HR 0.74, p=0.017) were associated with longer OS from first relapse after metastasis. Brain metastasis at any time occurred in 29.8%, associated with poorer OS. Conclusions: Comprehensive characterization of GCT-related death reveals a predominant pattern of mortality marked by de novo metastatic, poor-risk disease with subsequent early relapse and death due to chemorefractory non-teratomatous GCT. By contrast, a subset of pts with late-relapsing disease are more likely to have SSM-teratoma and a protracted clinical course. Lethal late relapses frequently occurred beyond 5 years, emphasizing the importance of long-term follow-up.
Safety and efficacy of intravesical nadofaragene firadenovec for patients with high-grade, BCG unresponsive nonmuscle invasive bladder cancer (NMIBC): Results from a phase III trial.
Authors: Boorjian Stephen A. , Dinney Colin P.N. ,   SUO Clinical Trials Consortium
Published: February 2020

442 Background: Patients (pts) with BCG-unresponsive NMIBC are at significant risk for disease recurrence and progression. While cystectomy can be curative, many such pts are unwilling or unable given the attendant morbidity of surgery. To date, effective salvage intravesical therapies in this setting remain lacking. Nadofaragene firadenovec is a novel intravesical gene-mediated therapy that delivers the human IFNα2b gene resulting in IFNα2b expression that provided durable responses in a previous Phase 2 trial. Herein, we report the results from a follow-up Phase III trial of this agent for pts with BCG unresponsive NMIBC. Methods: This multicenter, open-label Phase 3 study investigated nadofaragene for high-grade NMIBC (CIS ± Ta/T1, or Ta/T1 alone) unresponsive to BCG. Nadofaragene (3X1011 vp/mL [75 mL]) was administered once every 3 months for up 4 doses in the initial 12 months, with additional dosing at the investigator’s discretion. The primary endpoint was complete response (CR) at any time in pts with carcinoma in situ (CIS). Results: A total of 157 pts (safety population, n=157; efficacy population, n=151) were enrolled. Among pts with CIS (n=103), 55 (53.4%) (95% CI, 43.3-63.3) achieved CR, all by month 3 after treatment. Of these 55 CIS CR pts, 25 (45.5%) remained free of high-grade recurrence at month 12, confirmed on protocol-mandated biopsy. For pts with HG Ta/T1 alone, 35 (72.9%) and 21 (43.8%) were free from recurrence at 3 and 12mos, respectively. Most treatment-emergent adverse events (TEAEs) were transient in nature: instillation site discharge 33.1%; fatigue 23.6%; bladder spasm 19.7%; micturition urgency 17.8%; hematuria 16.6%. There were 2 Gr4 TEAEs (sepsis and anaphylactic reaction, neither related to study drug) and no Gr5 TEAEs. Conclusions: Nadofaragene achieved CR in 53.4% of pts with BCG-unresponsive CIS, and was well tolerated. Responses were noted early and remained durable to one year. These data represent a potentially significant management advancement for a historically difficult to treat disease state. Clinical trial information: NCT02773849.
Bladder cancer caregiver quality of life and patient cancer severity.
Authors: Gessner Kathryn , McCabe Sean , Filippou Pauline , McCloskey Hannah , Hamad Judy , Deal Allison Mary , Gore John L. , Smith Angela 
Published: February 2020

456 Background: Bladder cancer patients’ care is often managed by caregivers, yet caregiving can create a physiologic and emotional burden that compromises the caregivers’ own quality of life (QOL). Our objective was to determine the impact of disease stage on caregiver QOL among a large national cohort of bladder cancer patients. Methods: We performed a cross-sectional survey of bladder cancer caregivers using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine caregiver QOL using the CareGiver QOL questionnaire (CarGOQoL). Caregivers were also queried regarding demographic, socioeconomic and clinical characteristics of their loved one. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 132 respondents self-identified as caregivers of patients with bladder cancer. Among respondents, 85% were a spouse, 86% were female, and 97% were white. The mean age was 63 years (range 34 to 72 years) and 73% of respondents completed college. The highest cancer stage for patients was non-invasive in 42%, muscle-invasive in 33%, and metastatic in 24%. On bivariable analysis, stage was associated with leisure and social support but was not associated with global QOL, psychologic or physical well-being, burden, relationship with healthcare, administration and finances, coping, self-esteem or private life. However, on multivariable analysis controlling for age, race, years since diagnosis, and comorbidity, stage was significantly associated with Caregiver QOL (p=0.04). Conclusions: Disease stage significantly impacts QOL among bladder cancer caregivers. As the caregiver is increasingly considered as a stakeholder in survivorship efforts, future interventions should consider targeting social support among caregivers of patients with advanced bladder cancer.
The impact of physician specialty on general and bladder cancer-specific quality of life among patients with muscle invasive bladder cancer.
Authors: McCloskey Hannah , McCabe Sean , Gessner Kathryn , Filippou Pauline , Hamad Judy , Deal Allison Mary , Gore John L. , Smith Angela 
Published: February 2020

462 Background: Treatment delivery for muscle invasive bladder cancer (MIBC) may involve general urologists, urologic oncologists or a multidisciplinary team that includes medical oncology and radiation oncology. Our objective was to evaluate differences in general and bladder cancer-specific quality of life (QOL) based on treating physician among MIBC patients. Methods: We performed a cross-sectional survey of bladder cancer patients using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine general and bladder cancer-specific QOL using the EORTC QLQ-C30 and Bladder Cancer Index, respectively. Patients were also queried regarding demographic, socioeconomic and clinical characteristics. Patients were asked whether they sought care from a general urologist, urologic oncologist, medical oncologist and/or radiation oncologist. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 270 respondents identified as MIBC patients. Among MIBC respondents, 38% were female and 97% were white. The mean age was 67.4 years (range 30 to 93 years). Respondents were highly educated (67% completed college). Among MIBC patients, 17% sought care from a general urologist only, 33% from a urologic oncologist only, and 50% from a multidisciplinary team that included either a medical or radiation oncologist. Physician specialty was not associated with generic, sexual, or bowel QOL. Patients seeing a general urologist had—on average—better urinary function compared with those seeing a urologic oncologist or multidisciplinary team. On multivariable analysis, physician specialty remained a significant predictor of urinary function (p = 0.02), controlling for age, sex, race, recurrence, and comorbidity. Conclusions: Among MIBC patients, physician specialty does not substantially impact general QOL but may be associated with urinary function. This may relate to cancer severity or other unmeasured patient characteristics.
The impact of age on general and bladder cancer-specific quality of life among bladder cancer survivors.
Authors: Filippou Pauline , McCabe Sean , McCloskey Hannah , Gessner Kathryn , Hamad Judy , Deal Allison Mary , Smith Angela , Gore John L. 
Published: February 2020

463 Background: Quality of life among cancer survivors has been shown to vary by age. Our objective was to evaluate differences in general and bladder cancer-specific quality of life based on age among a large cross-sectional bladder cancer cohort. Methods: We performed a cross-sectional survey of bladder cancer patients using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine general and bladder cancer-specific quality of life (QOL) using the EORTC QLQ-C30 and Bladder Cancer Index. Patients were also queried regarding demographic, socioeconomic and clinical characteristics. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 972 respondents self-identified as patients with bladder cancer, of whom 41% were female and 97 % were white. The mean age was 67.6 years (range 29 to 93 years). Respondents were highly educated (67% completed college). 63% of patients identified as having non-invasive (NMIBC) cancer (n=578), 30% had MIBC (n=270), and 7% had metastatic bladder cancer (n=63). On multivariable analysis, older age was significantly associated with better generic QOL and urinary function ( Table), but not sexual function (p=0.19) or bowel function (p=0.73), controlling for sex, race, stage, comorbidity and years since diagnosis. Conclusions: Higher general and domain-specific QOL scores are more common among older bladder cancer patients. Differential impact by age may be important for the development of tailored interventions to improve QOL for bladder cancer patients. [Table: see text]
Gender and quality of life in bladder cancer.
Authors: Gessner Kathryn , McCabe Sean , Filippou Pauline , McCloskey Hannah , Hamad Judy , Deal Allison Mary , Gore John L. , Smith Angela 
Published: February 2020

464 Background: Quality of life among cancer survivors has been shown to vary by gender. Our objective was to evaluate differences in generic and bladder cancer-specific quality of life (QOL) based on gender among a large bladder cancer cohort. Methods: We performed a cross-sectional survey of bladder cancer patients using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine generic and bladder cancer-specific QOL using the EORTC QLQ-C30 and Bladder Cancer Index. Patients were also queried regarding demographic, socioeconomic and clinical characteristics. The survey was advertised. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 972 respondents self-identified as patients with bladder cancer. Among respondents, 41% were female and 97% were white. The mean age was 67.6 years (range 29 to 93 years). Respondents were highly educated (67% completed college). 63% of patients identified as having non-invasive (NMIBC) cancer (n=578), 30% had MIBC (n=270), and 7% had metastatic bladder cancer (n=63). On multivariable analysis ( Table), female gender was significantly associated with worse generic QOL (p<0.001), bowel function (p=0.001), and sexual function (p=0.02), and women trended toward worse urinary function (p=0.06), controlling for age, race, stage, comorbidity and years since diagnosis. Conclusions: Lower generic and domain-specific QOL scores are more common among female bladder cancer patients. Differential impact by gender may be important for the development of tailored interventions to improve QOL for bladder cancer patients. [Table: see text]
Feasibility of neobladder reconstruction after pelvic irradiation.
Authors: Vassantachart April , Miranda Gus , Daneshmand Siamak , Schuckman Anne K. , Djaladat Hooman , Ballas Leslie 
Published: February 2020

479 Background: To assess the effects of pelvic radiotherapy (RT) on orthotopic neobladder reconstruction (ONR), this review presents retrospective data of surgical outcomes following prior RT. Methods: Our institutional IRB approved bladder cancer database was queried for all patients who underwent radical cystectomy and ONR between 1980 and 2018. Radiation data was abstracted from the electronic medical record (EMR) with inclusion of patients receiving >40 Gy to the pelvis prior to surgery. Surgical outcomes including estimated blood loss (EBL), operative time, margin status, overall survival (OS), and need for subsequent surgeries were evaluated. Results: Of 2117 ONRs performed, 96 patients received prior RT. Of those, RT details could be obtained on 24 patients. Fifteen patients underwent definitive bladder RT with a median dose of 6480 cGy (range, 4500 - 8640 cGy); 7 of these patients received concurrent chemoradiotherapy, 2 received chemotherapy and RT with timing uncertain, and 6 received RT alone. Eight patients had prior prostate RT (median 7200 cGy) and one patient underwent prior cervical RT (7910 cGy). The median time interval between bladder RT and ONR was 7 months (range, 2 – 116 months) verses a median of 29 months between other pelvic RT and ONR (range, 6 – 163 months). Median EBL was 875 cc (range, 200-3000 cc) in patients with prior pelvic RT. Median operative time was 355 minutes (range, 231-600) in those who had prior RT compared with 354 minutes (range, 111-778) in those who underwent ONR without prior RT. Twenty-three patients had negative margins on surgical resection and one had a positive ureteral or urethral margin. The median OS following surgery was 50 months. Two patients died within 1 year due to disease progression. Seven patients (29%) required a surgical intervention after ONR: two patients developed fistulas (both with pouch to cutaneous fistulas), four patients had artificial urinary sphincters placed, and one developed small bowel obstruction due to adhesions. One patient required urethrectomy for recurrent disease. Conclusions: Orthotopic ileal neobladder reconstruction after pelvic irradiation is feasible with acceptable functional results.
A phase II trial of regorafenib for advanced urothelial cancer (aUC) following prior chemotherapy.
Authors: Naik Gurudatta , Vaishampayan Ulka N. , Nabell Lisle , De Shazo Mollie R. , Nandagopal Lakshminarayanan , Grivas Petros , Morgan Charity , Hardwick Pamela , Sonpavde Guru 
Published: February 2020

498 Background: Salvage therapy options for aUC following platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) have modest activity. Regorafenib is a multitargeted TKI that targets VEGF and Tie2 receptors among others, which is approved for multiple malignancies. Both VEGF and Tie2 inhibitors have preliminarily exhibited activity in aUC. Hence, a rationale was made to evaluate regorafenib in aUC progressing following chemotherapy. Methods: We conducted a single arm, non-randomized Phase II study (NCT02459119) of regorafenib for aUC following chemotherapy. All patients (pts) started at 120 mg po qd for one cycle (28 days) before escalating to 160 mg po qd in the absence of intolerable regorafenib related toxicities. Pts who had progressed after 1-3 prior chemotherapy regimens and exhibited measurable disease by RECIST 1.1 were selected. The primary objectives was progression free survival at 6 months (PFS-6) and the secondary objectives were objective response rates (ORR), overall survival (OS) and toxicities. PFS6 of ≥20% was considered of interest and the target accrual was 32 evaluable pts. The treatment was continued until progression or intolerable adverse events. Results: We enrolled 17 pts across 3 institutions (UAB, Wayne State and Cleveland Clinic) between May 2015 and May 2019. Of these, 14 patients were male (82%) and the median age was 67 years. Pts received a median of 2 prior therapies including chemotherapy. 9 pts had received a prior ICI. 13 pts (76.5%) experienced treatment related adverse events (AE), and 7 pts (41.2%) had grade 3 toxicities including–anemia, thrombocytopenia, myalgia, hypophosphatemia, abdominal pain and fatigue. Treatment was discontinued for patients who suffered grade 3 myalgia and abdominal pain. There were no treatment related deaths. 3 patients attained PFS6 (18%) who also displayed minor regressions and 1 of them had received a prior ICI. Conclusions: Although the trial was halted for slow accrual, regorafenib appeared to demonstrate activity in heavily pretreated pts with aUC who had received chemotherapy or ICI. Further evaluation may be warranted in less heavily pretreated pts and in combination with rational agents with non-overlapping toxicities. Clinical trial information: NCT02459119.
Concurrent or layered treatment (Tx) with radium-223 (Ra-223) and enzalutamide (Enza) or abiraterone plus prednisone/prednisolone (Abi/pred): A retrospective study of real-world clinical outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Shore Neal D. , Sartor Oliver A. , Sternberg Cora N. , Saad Fred , TOMBAL Bertrand F. , Miller Kurt , Kalinovsky Jan , Jiao Xiaolong , Tangirala Krishna , Higano Celestia S. 
Published: February 2020

50 Background: In clinical practice, Ra-223 is often combined with Enza or Abi/pred. ERA 223 (NCT02043678) showed increased fracture risk with concurrent Ra-223+Abi/pred. We assessed real-world symptomatic skeletal events (SSEs) and overall survival (OS) of pts with mCRPC who received concurrent or layered Ra-223+Enza or Abi/pred. Methods: Patients with mCRPC treated with Ra-223 in US cancer clinics from 1/01/2013 to 6/30/2017 were identified from a Flatiron prostate cancer registry of electronic health records. Tx initiation defined subgroups: concurrent (both started within 30 days) or layered (1 started ≥30 days after the other). Baseline (BL) was the first dose of Ra-223. Descriptive analysis was performed for BL characteristics, SSEs, and OS (Kaplan–Meier). Results: Of 625 pts treated with Ra-223, 48% received Ra-223+Enza or Abi/pred. Layered Tx was more common (73%) than concurrent (27%). BL characteristics and clinical outcomes were summarized [Table]. Conclusions: Ra-223+Enza or Abi/pred Tx was mainly layered. SSE rates with layered vs concurrent Ra-223+Abi/pred varied between subgroups; results must be treated cautiously given small pt numbers and a non-randomized study. The ongoing PEACE III trial is investigating concurrent Ra-223+Enza; a Phase III study (ESCALATE) exploring layered Ra-223+Enza is planned. Clinical trial information: NCT02043678. [Table: see text]
Patterns of use of chemotherapy with radiotherapy in the treatment of muscle-invasive bladder cancer: Data from the RAIDER randomized trial of adaptive radiotherapy.
Authors: Huddart Robert A. , Lewis Rebecca , Griffin Clare , Alonzi Roberto , Birtle Alison Jane , Choudhury Ananya , Cresswell Joanne , Foroudi Farshad , Hafeez Shaista , Henry Ann , Hindson Ben , McLaren Duncan , Mitra Anita , Nikapota Ashok , Parikh Omi , Rimmer Yvonne L. , Syndikus Isabel , Varughese Mohini Anna , Hall Emma ,   on behalf of Raider Trial Management Group
Published: February 2020

503 Background: Level 1 evidence exists for the use of both neoadjuvant chemotherapy (NAC) and concomitant radiosensitization (CRS) to improve outcomes in patients receiving radical radiotherapy (RT) for muscle invasive bladder cancer, but uptake has been patchy. We report here the current patterns of usage in an ongoing trial of adaptive radiotherapy. Methods: RAIDER is an international randomized phase II trial recruiting patients with unifocal T2-T4a urothelial carcinoma of the bladder suitable for RT (ISCRTN:26779187). Patients are randomized in a 1:1:2 ratio to one of 3 arms: Standard whole bladder RT (control); Standard dose adaptive tumour focused RT; Dose escalated (DE) adaptive tumour boost RT. Standard dose patients are treated to either 64Gy/32f or 55Gy/20f and DE patients to 70Gy in 32f or 60Gy in 20f. Patients are encouraged to receive NAC and CRS. The primary endpoint is the rate of late toxicity 6-18 months post treatment in arm 3, with secondary endpoints of patient reported and disease related outcomes. Results: To August 2019, 285 patients had been recruited. Median age is 72 years (IQR 67-79). Stage of disease is T2 79%, T3 19%, T4 2%; 19% have hydronephrosis. Patients receiving NAC were more likely to be PS 0 at trial entry (70% v 45%). Variation in frequency of CRS use is seen across sites, with some offering to >90% of participants and some <50%. Data on NAC and CRS use is available for 249 patients recruited to date is shown in table. Conclusions: In this ongoing clinical trial the majority of patients are receiving NAC and/or CRS. However, uptake is not universal with ~30% of patients not receiving low dose CRS, including some who have received NAC. Clinical trial information: 26779187. [Table: see text]