bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective and less toxic trimodality approach in muscle invasive urinary bladder cancer.
Authors: Abdel-Wahab Reham , Eltaher Ahmed M. , Essa Hoda H. , Eid Samir-Shehata M. 
Published: March 2020

e15505 Background: Bladder cancer represents a global health problem. Radical cystectomy considered the standard of care for invasive bladder cancer. Because of the potential morbidity with surgery, organ preservation via trimodality approach has been the subject of investigation. The concurrent use of cisplatin with 5-FU or gemcitabin with local radiotherapy has been studied and the results were better than radical cystectomy. However, this was associated with grade 3-4 (G3-4) toxicity. Recently, similarly effective but less toxic regimen by the use of paclitaxel and cisplatin is under investigation. Methods: We proposed a single-center, single arm, phase II prospective cohort study. 30 patients (22 male and 8 female) with T2-T3 bladder cancer according to the AJCC 2010 were included. All patients were >18y with exclusion of those with bladder capacity < 350cc, hydronephrosis, with previous intravesical therapy, systemic chemotherapy or pelvic radiation, those currently receiving nephrotoxic or ototoxic drugs, and those with other malignancies. All patients treated with maximum transurethral resection (TUR) followed by local radiotherapy 64Gy concurrently with weekly 60mg/m2 Paclitaxel and 20mg/m2 Cisplatin. Results: Cystoscopic re-evaluation 6-8 weeks after the end of treatment revealed that 90% of patients achieve complete response (CR), 6.7% achieve partial response (PR) and 3.3% had stable disease (SD). Mild toxicity was infrequent and easily controlled without interruption of treatment except in one patient. Toxicity was in the form of cystitis G1 in 46.7% and G2 in 3.3%. Diarrhea G1 in 33.3% and G2 in 3.3%. Only one patient who has past history of piles, developed G2 proctitis that leads to irregularity of treatment. Other mild toxicities were: G1 dermatitis (80%), G1 bleeding per rectum (3.3%), G1 anemia (13.3%), G1 and G2 nausea and vomiting (50% and 33.3% respectively), while neutropenia and thrompocytopenia were not seen. Conclusions: Our preliminary results revealed that weekly low dose paclitaxel and cisplatin concurrently with local radiotherapy was effective, tolerable and has acceptable toxicity in the treatment of muscle invasive urinary bladder cancer.
Effect of race on survival of metastatic renal cell carcinoma treated with VEGFR-TKI therapy.
Authors: Kuykendal Adam Rea , Snavely Anna C , Nielsen Matthew Edward , Kim William Y. 
Published: March 2020

e15507 Background: African Americans (AAs) with renal cell carcinoma (RCC) have a higher incidence of disease, younger age of onset, and at least in the cytokine era AA have had a shorter progression free survival (PFS) and overall survival (OS) relative to Caucasians (Cs). Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors (VEGFR-TKIs) were approved for advanced RCC based on trials with minimal AA participation. This study was undertaken to examine if VEGFR-TKIs are similarly effective in AA patients. Methods: This was a single institution retrospective cohort study. We examined the medical records from 2004 to 2012 of all C and AA patients with metastatic RCC started on first line VEGFR-TKI therapy with at least one follow up visit. This resulted in 34 C patients and 12 AA patients. We abstracted self- reported race, treatment type, MSKCC prognosis, date of progression as defined by the treating physician, and other demographic and clinical variables. The Social Security Death Index was used to establish date of death. OS and PFS were analyzed using Kaplan-Meier and Cox proportional hazards models. Gene expression data from TCGA was analyzed for biological differences between RCC occurring in AAs and Cs. Results: 54.6% of AAs were classified into the MSKCC poor prognosis group compared with 10.7% of Cs. AAs compared to Cs had a non-significant trend toward worse OS (HR 1.49, p = 0.36) and PFS (HR 1.59, p = 0.27). After adjustment for risk group we found no significant difference between AAs and Cs for OS (HR 1.00, p = 0.99) and PFS (HR 1.26, p = 0.66). Comparison of the RCC gene expression profiles demonstrated significant differences in gene expression with AA tumors showing enrichment for genes involved in ion transport and cell-cell junctions. Conclusions: This is a preliminary study that suggests first line VEGFR-TKI therapy is an effective choice for AA patients as metastatic RCC in AAs responds similarly as Cs to VEGFR-TKI treatment. In addition, there are distinct gene expression differences that distinguish AA and C tumors.
The role of prognostic factors in metastatic renal cell carcinoma (mRCC) treated with targeted therapies (TT): Data from an Italian retrospective multicentric study.
Authors: Barile Carmen , Fraccon Anna Paola , Zustovich Fable , Gaion Fernando , Salvagno Luigi , Massari Francesco , Martellucci Ignazio , Modenesi Caterina , Giusto Mauro , Segati Romana , Bearz Alessandra , Ogliosi Chiara , Macrini Sveva , Maruzzo Marco , Larussa Francesca , Nicolardi Linda , Bonciarelli Giorgio , Menon Daniela , Inno Alessandro , Pasini Felice 
Published: March 2020

e15512 Background: Several prognostic factors in mRCC have been largely described in the literature. This study was aimed to verify whether some of these factors maintain their prognostic role in a cohort of pts treated in the community setting outside clinical trials. Methods: 902 pts with mRCC treated with TT from 2007 to December 2012 in 28 Italian centres were included in the analysis. Various potential prognostic factors were correlated with overall survival (OS). Results: Median age was 60 (range 25-89), 75% of pts were males; median OS (mOS) was 24 mo. Histology was clear cell (CC), CC with sarcomatoid component, papillary, NOS, not available in 82%, 6%, 4%, 4% and 4 %, respectively. mOS in the CC subgroup was 28 vs 12.5 mo of the non CC subset (p<0.001). Nephrectomy was performed in 88% of the cases. mOS of these pts was 28 mo vs 6.5 in those without surgery (p<0.001). The number of metastatic sites was >2 in 43% of the pts. mOS of this group was 18 mo vs 31 mo of pts with ≤2 metastatic sites (p=0.0001). MSKCC risk was good in 32%, intermediate in 53% and poor in 15% of the pts. According to MSKCC risk score, mOS was 6.4, 24 and 49 mo in poor, intermediate and good subsets, respectively (p<0.001). The small subset of pts (2%) with both thrombophilia and neutrophilia had a dismal mOS of 3 mo. PS (ECOG) was 0-1 in 90% of the pts; mOS of pts with PS ≥2 was 6 mo (p=0.0001). The findings of multivariate analysis are showed in the Table. Conclusions: The results of our survey confirm that clear cell histology, prior nephrectomy, number of metastatic sites, PS, MSKCC risk, platelets, and neutrophils count maintain their prognostic value also in mRCC pts treated with TT in the everyday clinical practice. [Table: see text]
Targeted therapy for renal cell carcinoma (RCC) with brain metastasis: Overall survival (OS) and safety.
Authors: Bastos Diogo Assed , Molina Ana M. , Jia Xiaoyu , Velasco Susanne , Patil Sujata , Voss Martin Henner , Feldman Darren Richard , Motzer Robert John 
Published: March 2020

e15517 Background: Brain metastases (b-met) in RCC are associated with poor prognosis and median OS of about 7 months in the pre-targeted therapy (TT) era (Culine, Cancer 1998). The role of TT in this setting is not well established since patients (pts) with b-met were excluded from most clinical trials. The primary objective was to assess OS and central nervous system (CNS) safety of pts with b-met treated with TT. Methods: Pts with mRCC treated with ≥ 28 days of TT after b-met diagnoses were retrospectively identified. Kaplan-Meier method and Cox proportional hazards model were used to analyze the association between clinical features and OS. Results: 65 pts were identified, 52 (80%) treated with anti-angiogenic agents and 13 (20%) treated with mTOR inhibitors. Most pts had extracranial metastasis (98%) and 54% had ≥ 2 brain lesions. Fifty seven pts (88%) had local therapy for b-met before TT including surgery in 3 (5%), radiation therapy (RT) in 36 (55%) and both surgery and RT in 18 (28%). Median follow-up was 12.3 months (1.1 – 58.8) and median time from RCC diagnosis to b-met was 17.8 months (0 – 192.2). Median TT duration was 3.4 months (0.3 – 31.9) for 1st line and 1.9 months (0.2 – 23.6) for 2nd line. Median OS was 12.2 months (95% CI 8.0 to 15.5). On univariate analysis using various clinical and treatment variables, MSKCC risk group (P= 0.001), histology subtype (clear vs other) (P< 0.0001), and number of b-met at diagnosis (P= 0.004) correlated with OS and retained statistical significance on multivariate analysis (Table). CNS complications were identified in 5 pts (8%), including 2 with radiation necrosis and 3 with b-met hemorrhage. Conclusions: The use of TT in the multimodality treatment of pts with RCC and b-met appears safe with OS that compares favorably to historical results in the pre-TT era. Clear cell RCC, favorable MSKCC risk status, and solitary b-met are associated with better outcome. [Table: see text]
Patience is a virtue: Wait and see strategy for metastatic or recurrent renal cell carcinoma.
Authors: Park Inkeun , Lee Jae-Lyun , Ahn Jin-Hee , Jeong In Gab , Song Cheryn , Hong Bum-Sik , Hong Jun Hyuk , Kim Choung-Soo , Ahn Hanjong 
Published: March 2020

e15519 Background: Metastatic renal cell carcinoma (MRCC) often presents with very indolent course without any symptom, and treatment (Tx) for MRCC is mostly palliative rather than curative in a molecular target agents era. There exist several Tx options for MRCC, but all available agents have considerable toxicities, cause economic burden to patients (pts), and impair quality of life. For some cancers like indolent lymphoma, “wait and see” strategy (W&S) is adopted for asymptomatic pts. We retrospectively evaluate clinical outcomes of W&S for asymptomatic MRCC pts. Methods: we enrolled MRCC pts who was followed-up with deferred treatment for the purpose of W&S in our institution between 2000 and 2012. Clinical characteristics, response to W&S, predictive factor for time-to-progression (TTP), and response to succeeding first line Tx were analyzed. Results: Of 44 pts found, 30 pts had recurrent disease and 13 pts initially metastatic disease. Most pts had good Karnofsty PS (KPS), 100% for 26 pts and 90% for 13 pts. Lung (38 pts), lymph nodes (16 pts), kidney (6 pts) were most common site of metastasis. During W&S, stable disease (SD) and progressive disease (PD) were the best overall response for 36 (82%) and 8 (18%) pts, respectively, and 37 pts had PD finally. With a median F/U period of 24.7 months, median TTP and OS were 12.5 months (95% CI, 6.7-18.4) and 91.1 months (95% CI, 41.3-141.0). After univariate and multivariate analysis for TTP, KPS<100%, liver metastasis, time from diagnosis to W&S< 1year, and neutrophilia were found to be predictive factors for TTP during W&S. After PD, 27 pts proceeded to systemic treatment (13 sunitinib, 10 pazopanib, 3 immunotherapy, and 1 temsirolimus). Objective response rate were 54% for sunitinib, and 50% for pazopanib. Conclusions: This study suggests that W&S could be a viable treatment option for the first-line approach in asymptomatic MRCC pts, especially for those who have good performance status without neurtrphilia or liver metastases.
Extent of neutrophil (NTP) infiltration in benign lymph nodes (LNs) to predict survival in patients with muscle-invasive bladder cancer (MIBC).
Authors: Liang Wei , Jove Richard , Yuh Bertram E. , Chan Kevin , Wilson Timothy G. , McConkey David James , Lerner Seth P. , Pal Sumanta Kumar 
Published: March 2020

e15522 Background: In preclinical models, NTPs appear to establish a pre-metastatic niche that fosters the invasion of metastases (Kowanetz et al. PNAS 2010). This observation still requires clinical validation in MIBC. Methods: Benign LN tissue was obtained from patients (pts) who had undergone cystectomy and LN dissection for documented MIBC. Immunohistochemical (IHC) staining for CD15 (a NTP marker) was performed. Interleukin-17 (IL-17) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3), putative mediators of NTP recruitment, were assessed through the same method (Laan et al. J Immunol 1999; Fielding et al. J Immunol 2008). Positively staining cells were counted and averaged over 8 high power fields. Pts were stratified by the median cell count for each biomarker. Analyses of overall survival (OS) were performed using the Kaplan-Meier method and log-rank test. Results: Of 55 pts with MIBC, 19 pts received no neoadjuvant chemotherapy (NAC), while 36 pts had received NAC with either GC (n=17) or MVAC (n=19). CD15 and IL-17 expression was significantly lower in pts with prior NAC (P<0.001 for both), while expression of pSTAT3 was similar in both groups. Furthermore, across the whole cohort, a strong association was seen between expression of CD15 and IL-17 (r=0.73, P<0.001). Amongst patients with no prior NAC, median OS was higher in those pts with low CD15 v high CD15 (158.7 mos v 36.9 mos, P=0.02), and low pSTAT3 v high pSTAT3 (NR v 106.4 mos, P=0.04). Median OS was numerically higher in pts with low IL-17 v high IL-17 (114.5 v 36.9 mos; P=0.14). Patients with both low CD15/IL-17 had a particularly favorable outcome. Amongst pts with prior exposure to NAC, no difference in survival was noted based on CD15, pSTAT3 or IL-17. Conclusions: NTP recruitment to benign LNs (potentially mediated by IL-17) may be prognostic of OS in pts with MIBC who have not received NAC. Bolstered by these findings, the prognostic value of NTP recruitment will be examined prospectively in SWOG 1011, a trial comparing limited v extended LN dissection in pts with MIBC.
Sequential salvage chemotherapy for CDDP-refractory advanced testicular cancer: Japanese high-volume center experience.
Authors: Nakamura Terukazu , Kimura Yasunori , Ueda Takashi , Naya Yoshio , Hongo Fumiya , Miki Tsuneharu 
Published: March 2020

e15526 Background: Chemotherapy- refractory or resistant GCTs, so called ‘difficult-to-treat’ GCTs would remain continuously disease-free with salvage chemotherapy or surgery. The optimal salvage chemotherapy remains unclear. The aim of this study was to assess the efficacy of ‘sequential’ chemotherapy for advanced testicular cancer. Methods: Salvage chemotherapy was required in 129 patients out of 233 advanced GCTs treated at Kyoto Prefectural University of Medicine from June, 1998 to December, 2011. Clinical outcomes were retrospectively assessed. Results: Median age was 31 year-old (range:17-65y.o.). Non-seminoma was in 111 cases (86.0%). IGCCC showed good in 37 cases (28.9%), intermediate 33 (25.6%), poor 47 (36.4%), and unknown 12 (9.1%). As the 2nd line therapy, VIP/VeIP and TIP/N therapy were done in 43 (33.3%) and 49 cases (38.0%), respectively. With regard to the patients requiring 3rd line or more chemotherapy, 95, 67, 40, 26 cases had 3rd, 4th, 5th and 6th line or more chemotherapy, respectively. TIN therapy was performed in 48 patients as 3rd line and in 24 patients as 4th line. Irinotecan-containing chemotherapy was done in 24 and 36 cased as 2nd +3rd line therapy and 4th line or more, respectively. Gemcitabine-containing therapy was done in 33 cases with 3rdline or more chemotherapy. Overall survival rate at median follow-up period was 71.0%at median follow-up of 48m. Overall survival stratified by IGCCC was shown in the figure. There was no significant difference between any two groups. Clinical outcomes showed no evidence of disease (NED) was obtained in 86.1% with second line therapy. Noteworthy mentioned, about 40% patients had NED even in the 4thline or more chemotherapy group. Conclusions: Relatively good prognosis was obtained in the patients with salvage chemotherapy at Japanese high volume center. Sequential continuous chemotherapy would be very important to manage ‘difficult-to-treat’ advanced germ cell tumors.
Searching for predictors markers in renal cell carcinoma: A regression model.
Authors: Quindós Varela Maria , Medina Villaamil Vanessa , Santamarina Cainzos Isabel , Aparicio Guadalupe , Valladares Ayerbes Manuel , Antón Aparicio Luis M. 
Published: March 2020

e15542 Background: Renal cell carcinoma (RCC) is known to be resistant to chemotherapy. The need for the identification of biomarkers capable of determining RCC prognosis factors and metastatic potential that are obtainable from non-invasive or minimally invasive techniques are desirable. The purpose from this analysis was to derive predictive models which could predict more accurately than any one factor alone. Methods: By tissue micro-array (TMA) technology we assessed 29 markers involved in the cascade of events leading to the formation and progression of this disease. The ability of multivariate logistic regression to improve the diagnostic accuracy for RCC by combining determinations of proteins markers and pathological variables was evaluated. Univariate analysis was used to select factors (p<0.05) for entry into a multivariate stepwise logistic regression model using the forward method. Odds ratios with 95% CI were calculated. A p-value of < 0.05 was significant. Results: The regression equations obtained were the next: for lymphatic vessels invasion, Y(x)=6.815- 0.442 (EGFR value); for node status Y(x)=2.07+ 0.494(NOTCH1 value) - 0.269(GLUT5 value); for veins invasion Y(x)=57.61+ 6.01 (NOTCH2 value)- 9.3 (GLUT1 value)+ 1.73 (C-KIT value); for breaking capsule Y(x)=2.713- 0.261(EGFR value)+ 0.407 (NOTCH1 value)- 0.305(NOTCH2 value)+ 0.463 (GLUT1 value); for pelvis invasion Y(x)=8.624-0.198 (EGFR value)- 0.514 (DLL3 value). Receiver-operator characteristic (ROC) curve analyses were made to analyse the accuracy of the best candidate proteins. Should be noted from this analysis NOTCH1 and GLUT5 for node status prediction (AUC=0.833, 95% CI, 0.744-0.922; p<0.001) and EGFR and DLL3 for pelvis invasion (AUC=0.777, 95% CI, 0.631-0.922; p=0.007). Conclusions: In the age of individual therapy, the approach to percutaneous image-guided RCC biopsy procedures plays an expanded role. Applying a 2 mm punch needle for constructing a TMA, thereby mimicking the percutaneous biopsy technique we could describe for the first time how are combined 29 protein markers in regression equations to predict in the most optimal way a number of pathological variables associated with RCC that may help in the diagnosis and prognosis of this disease.
Clinical efficacy of sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma.
Authors: Zhang Xu , Yuan Jianlin , Wang Liang , Chen Lijun , Pan Jinhong , Ye Linyang , Xiao Xuren , Qiu Jianhong , Zhang Keqin , Ye Gang 
Published: March 2020

e15547 Background: To evaluate the efficacy and safety of Sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma (RCC). Methods: A total of 60 patients with resected, histologically confirmed clear cell RCC were enrolled in this study. Patients received orally Sunitinib either at a dose of 50mg on treatment schedule 4/2 (once daily for 4 weeks followed by 2 weeks off) or at a dose of 37.5mg once daily for three 6-week cycles from 1 month after surgery. Results: All 60 patients tolerated Sunitinib treatment well and no patient discontinued treatment due to adverse events. Most adverse events were grade 1 to 2. The most frequently reported adverse events were neutropenia (56.7%), thrombocytopenia (53.3%), leucopenia (48.3%), hand-foot syndrome (46.7%) and hypertension (36.7%). The most frequently reported grade 3 or 4 toxicities were thrombocytopenia (25%), neutropenia (15%), hand-foot syndrome (11.7%) and leucopenia (8.3%). The majority of adverse events occurred within the first 1-2 cycles of Sunitinib treatment, and was ameliorated 1 month after 3 cycles finished. No irreversible adverse event was observed. As of January 31, 2013, recurrence occurred in 3 of 60 (5%) patients except one death due to cerebrovascular accident unrelated to treatment, with 12-month disease-free survival (DFS) rate of 96.6% (RCC recurred 7 months after surgery in 2 patients and recurred 14 months after surgery in 1 patient). Conclusions: Myelosuppression occurred less frequently in high-risk RCC patients treated with Sunitinib as operative adjuvant therapy than in advanced RCC patients, with a better benefit trend. Long-term follow-up data are needed to further confirm the efficacy of Sunitinib in the adjuvant setting.
Phase I study of TH-302, investigational hypoxia-targeted drug, in combination with sunitinib.
Authors: Starodub Alexander , Milhem Mohammed M. , Pennington Kenneth Lee , Kio Ebenezer A. , Bruetman Daniel , Thorne Tracy , Hickingbottom Barbara , Kroll Stew 
Published: March 2020

e15557 Background: Tumors often consist of highly hypoxic subregions known to be resistant to chemotherapy and radiotherapy. TH-302 is an investigational hypoxia-targeted drug with a 2-nitroimidazole trigger designed to release the DNA alkylator bromo-isophosphoramide mustard (Br-IPM) when reduced in severe hypoxia. Preclinical models demonstrate that treatment with sunitinib increased the tumor hypoxic fraction, the therapeutic target of TH-302. Initiating TH-302 following sunitinib significantly increased the efficacy of sunitinib in these models. In this phase 1 dose escalation study, TH-302 was combined with standard dose sunitinib. Methods: Eligible patients (pts) for the study (NCT01381822) had advanced RCC, GIST or PNET tumors, evaluable disease by RECIST, ECOG ≤2 and acceptable hematologic, hepatic and renal function. Pts received TH-302 in combination with standard full doses of 50 mg PO sunitinib daily from Day 1 to Day 28 of a 6 week cycle. TH-302 was administered IV on Days 8, 15 and 22. TH-302 starting dose was 240 mg/m2. The study objectives were to determine the MTD, DLTs and RP2D and to evaluate the safety and preliminary efficacy of TH-302 when used in combination with sunitinib. Results: Ten pts were enrolled. Median age: 63 (range 27-72); Female (5)/ Male (5); ECOG 0 (5); ECOG 1 (5); Primary tumor: RCC (6), GIST (4). Median prior chemotherapies: 3 (range: 0-3) including prior sunitinib in 7 pts. No DLTs were observed in the 3 pts at the 240 mg/m2 cohort and 1 pt of 5 DLT evaluable in the 340 mg/m2 cohort had a DLT of stomatitis. Eight pts discontinued (progressive disease (6), pursued other treatment options, adverse event unrelated to study drugs). Three pts had a study drug related SAE (neutropenic sepsis, anemia, hyperthyroidism). Common TH-302 related AEs were nausea and mucosal toxicity and were mostly grade 1 or 2. Grade 3/4 thrombocytopenia and neutropenia were reported in 4 pts and 3 pts, respectively. One of 4 (25%) pts with GIST had a confirmed PR and 3 of 4 (75%) pts with RCC had PRs including 2 with confirmed PRs. Conclusions: TH-302 can be administered in combination with full dose sunitinib. Mucositis was dose limiting. There is preliminary evidence of activity of TH-302 in combination with sunitinib in RCC. Clinical trial information: NCT01381822.