bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body composition as a predictor of sunitinib toxicity in patients with renal cell carcinoma.
Authors: Cushen Samantha , Ryan Aoife M , Teo MinYuen , MacEneaney Peter , McLaughlin Patrick , Fitzpatrick Frances , Rozumna-Martynyuk Nataliya , McDermott Raymond S. , Power Derek Gerard 
Published: March 2020

e15566 Background: Sunitinib is a standard first-line option for metastatic renal cell cancer (mRCC). Identification of biomarkers associated with outcome or toxicity is a challenge. Body composition is a prognostic factor in cancer and sarcopenia is associated with treatment toxicity and survival. We investigated if body composition by CT scan predicted dose limiting toxicity (DLT) from sunitinib in mRCC. Methods: Patients (pts) with mRCC receiving sunitinib 50mg as 1stline therapy between 2007-2012 were included. Ethical approval was obtained and prospectively maintained databases analysed. Skeletal muscle cross-sectional area at L3 was measured by CT. Sarcopenia was defined using published cut offs. Toxicity was assessed after 4 cycles of drug (CTCAE, v4.0). Results: 55 pts (43 male), mean age 64yrs (±10.6) were included. 67% were overweight/obese (BMI>25kg/m2). Sarcopenia was present in 33% (56% of normal BMI, 44% overweight group). Overall 40 pts (73%) experienced DLT (51% M, 100% F, p<0.016). DLT occurred in <6 months in 53% (44% M vs 83% F, p<0.016) and these pts were older (mean 68 yrs vs 60 yrs, p<0.01), had lower skeletal muscle mass (51.8 cm2/m2 vs 59.4 cm2/m2, p<0.012), and fat free mass (FFM) (51.4kg vs 57.7kg, p<0.03), and received higher drug dose in mg/kg FFM (1.01 vs 0.89, p<0.02). Common toxicities were GI (65%) and fatigue (47%). Of pts <25th percentile skeletal muscle mass 92% experienced DLT, higher than pts >75th percentile (p<0.05). Pts <25th percentile had an average of 5 toxicities vs 2 in those >75th percentile (p<0.003). All toxicities were more common in muscle wasted patients (p<0.05). 77% (n=10) of pts receiving a drug dose >75th percentile (1.105mg/FFM) experienced DLT in <6 months vs 44% (n=17) receiving a dose <75thpercentile (<1.099mg/FFM; p<0.037). Conclusions: Sarcopenia is prevalent in patients with mRCC, is easily measured, is an occult condition in pts with normal/high BMI, and is a significant predictor of DLT in pts receiving 1st line sunitinib. Our results highlight the potential use of baseline body composition to predict toxicity. The role of sarcopenia in targeted therapy is evolving and its potential to predict toxicity should be further studied.
Reversible posterior leucoencephalopathy syndrome (RPLS) associated with pazopanib.
Authors: Foerster Robert , Welzel Thomas , Debus Juergen , Gruellich Carsten , Jaeger Dirk , Potthoff Karin 
Published: March 2020

e15574 Background: Tyrosine kinase inhibitors (TKI) are a relatively new modality for the therapy of metastatic renal cell carcinoma (MRCC). Although there are promising results, their use is often limited due to adverse reactions. We report on a case of malignant hypertension (HTN) and RPLS in a patient (PT) treated with pazopanib for MRCC. Methods: Case report. Results: A 62 year old woman with MRCC and since 8 weeks under 3rd-line therapy with pazopanib had suddenly developed headaches, grand-mal seizures, paresis of the left arm, gait instability and nausea during her vacation. The emergency physician measured blood pressure (BP) values >300 mmHG systolic and suspected a stroke. A CT without contrast agent in a local hospital only showed bone metastases. Suspecting cerebral metastases or meningeosis carcinomatosa (MC) the colleagues referred her to our radiooncologic department for diagnostics and treatment planning. At admission the PT was somnolent and unable to communicate because she had received larger quantities of diazepam as an anticonvulsive on the plane. The next day the PT was fully awake but showed significant anterograde amnesia from the onset of the headaches, psychomotoric deceleration and persistent gait instability. Brain metastases and MC were ruled out in an MRI which showed signs of RPLS in the form of band-like hyperintensities in the left parietal lob. HTN up to 220/120 mmHg persisted under 3x antihypertensive therapy and the PT reported that similar values were measured after the start of 1st-line sunitinib 1 year ago. We discontinued pazopanib. Within 1 week the neurologic findings vanished and we discharged her. An MRI 3 weeks later showed RPLS-typical cortical infarctions in the affected area. The PT remained without any neurologic symptoms but intermittent HTN persisted. Conclusions: Vascular endothelial growth factor (VEGF) inhibitors and TKI are associated with HTN. Currently the exact mechanism remains unknown. HTN is an indicator for improved outcome under TKI therapy. BP should be closely monitored under TKI therapy. RPLS clinically mimicking cerebral metastases should always be considered as the actual reason for neurologic findings in patients with known metastatic cancers under TKI therapy.
Testicular microlithiasis in Japanese male infertility patients: Clinical implications for predicting future testicular malignancy.
Authors: Arai Gaku , Okada Hiroshi , Sadaoka Yuko , Ohta Shigeyuki , Nishio Koujiro , Sato Ryo , Kawaguchi Makoto , Kobori Yoshitomo , Ashizawa Yshio , Yagi Hiroshi , Soh Shigehiro 
Published: March 2020

e15579 Background: Testicular microlithiasis (TM) is commonly diagnosed by scrotal ultrasonography (US) in which it appears as multiple, small, uniform, echogenic foci without shadowing, scattered randomly throughout the testicular parenchyma. It is also prevalent in several urologic diseases including subfertility and testicular germ cell tumor. TM has been reported to be associated with carcinoma in situ (CIS) and the development of second testicular germ cell tumor (TGCT) after contralateral orchiectomy treatment for primary TGCT; however, no prospective studies have investigated the relationship between the detection of TM in patients without TGCT and future development of TGCT. In the present study, therefore, we investigated the prevalence of TM in the testes of male infertility patients and unilateral TGCT patients to determine if TM could be a predictor of future germ cell tumor in such patients. Methods: A total of 1,139 subfertile patients (296 with nonobstructive azoospermia, 58 with obstructive azoospermia, and 785 with oligozoospermia) and 22 unilateral testicular germ cell tumor patients were enrolled in the study. Prevalence of testicular microlithiasis according to testicular ultrasonography was compared between patients, and development of testicular germ cell tumors was monitored for at least 3 years. All patients were fully informed about the study, and their prior consent was obtained according to the recommendation of the institutional ethics committee. Results: The prevalence of TM was significantly higher in unilateral TGCT patients (40.9%) than in subfertile men (8.6%). No infertile patients without TM developed TGCT but one infertile patient with TM developed TGCT (seminoma) during follow up. One seminoma patient with TM in his remaining testis went on to developed testicular seminoma 3years after primary surgery. Conclusions: Testicular microlithiasis is more common in testicular germ cell tumor patients than in subfertile men. Since TM could be a surrogate marker for future TGCT in both patient populations, TM patients are recommended to perform careful self-checking of the testes and periodical testicular ultrasonography.
Prognostic analysis of Chinese patients with metastasic renal cell cancer (mRCC) receiving sorafenib: A multicenter retrospective study.
Authors: Guo Fang , Xie Xiaodong , Liu Zhaozhe , Song Xishuang , Zhang Qifu , Kong Xiangbo , Li Changfu , Li Zhenhua , Li Chengge , Qu Shuxian , Liang Xuefeng , Zheng Zhendong , Piao Ying 
Published: March 2020

e15582 Background: This study was to investigate long-term efficacy of sorafenib and survival-related factors in Chinese patients with mRCC. Methods: 406 consecutive patients enrolled in this study between Oct. 2006 and Oct. 2009 from 6 comprehensive cancer centres in China. All cases were diagnosed as mRCC histopathologically without exception. 400mg sorafenib was orally taken twice daily until PD, death or intolerable toxic reaction. The primary endpoint was OS. The secondary endpoints were PFS and survival-related factors such as gender, age, ECOG PS, previous therapy and primary metastatic lesions. Data was analyzed using the SPSS statistical software. OS and PFS curves were output using the Kaplan-Meier method. Clinical parameters were included on univariate and multivariate analysis to evaluate associations with OS and PFS by the log-rank test and Cox proportional hazard models, P<0.05 (two-sided) was considered statistically significant. Results: 131 patients were available for survival analysis, including 96 males and 35 females. The median age was 60 years old. The median follow-up periods were 16.9 months. The median OS was 16.1 months. 1-year, 2-year and 3-year survival rates were 64.9%, 35.9% and 5.3%, respectively. The median PFS was 10.5 months. Univariate analysis demonstrated that OS was significantly associated with ECOG PS, metastatic lesions and previous therapy, whereas PFS was merely associated with ECOG PS and previous therapy. Multivariate analysis suggested that ECOG PS and previous therapy were independent prognostic factors for OS(P=0.004, P=0.019) and PFS (P=0.000, P=0.003), metastatic lesions was merely independent prognostic factor for OS (P=0.003). In the subgroup of patients with visceral metastasis, patients with lung metastasis alone had better prognosis than those with liver metastasis or dimerous metastasis. Conclusions: This long-term study demonstrated that sorafenib had good effects on Chinese patients with mRCC, especially for patients with lung metastasis alone. ECOG PS, metastatic lesions and previous therapy could be important parameters for survival and need attention in future.
A moncentric review of targeted therapy on overall survival in metastatic renal clear cell carcinoma.
Authors: Tadj Melanie , Arnoux Valentin , Mousseau Mireille , Descotes Jean Luc , Quesada Jean-Louis , Bensaadi Lamia , Laramas Mathieu 
Published: March 2020

e15593 Background: Anti-angiogenic treatment had radically modified therapeutic strategy in metastatic renal cell carcinoma (mRCC). This study is aimed to determine the overall survival (OS) improvement in clinical practice. Methods: Retrospective, monocentric and non-interventional study in mRCC diagnosed since 2000 with 2 cohorts of patients determined according to the first line treatment (targeted therapy or others treatment). Results: Between 1 January 2000 and 31 December 2010, 98 patients were included. The 2 cohorts were balanced with regard to baseline disease and demographic characteristics in particular for prognosis profiles distribution. As first line, 58 patients received targeted therapy whose 21% were treated by bevacizumab, 71% by sunitinib and 8% by temsirolimus. In non-targeted therapy cohort (n=40), 37.5% were treated by cytokines, 15% by cytotoxic chemotherapy or hormonal therapy. Patients treated with targeted therapy had a significantly longer median OS (30 months versus 13 months; p<.003, log-rank test). The Hazard Ratio (HR) of death at 3 years was 0.53 (95% Confidence Interval, 0.33-0.85; p=.008, log-rank test). When adjusted to the prognosis profile, the HR of death was 0.43 (95%CI, 0.27-0.71). Conclusions: This retrospective study demonstrated the improvement of OS due to targeted treatments, for all prognostic risk groups. This result supported the complete change of care of mRCC patients with extension of therapeutic indications and efficient therapeutic lines.
Long-term response in a patient with urothelial cancer (UC) treated with AEZS-108.
Authors: Fernandez Gustavo L. , Schally Andrew V. , Koru-Sengul Tulay , Jorda Merce , Merchan Jaime R. , Flores Aurea M. , Block Norman L. , Manoharan Murugesan , Engel Juergen 
Published: March 2020

e15596 Background: AEZS-108 (AN-152, zoptarelin doxorubicin) is an LHRH-cytotoxic hybrid drug consisting of a Luteinizing Hormone Releasing Hormone (LHRH) agonist coupled to the cytotoxic radical, doxorubicin. The binding permits AEZS-108 to accumulate on the surface of cells expressing LHRH receptors (LHRH-R) thus allowing drug uptake. This approach exploits LHRH-R to gain access to the targeted tumor cells. Once internalized, the cytotoxic properties of doxorubicin induce the anti-tumor response. Methods: This is a case report of a 66 year old male with a superficial bladder cancer history who was diagnosed in May 2009 with metastatic UC from the prostatic urethra. He presented with pelvic and retroperitoneal lymph nodes (LN). Patient had a partial response to cisplatin based chemotherapy and underwent radical cystoprostatectomy in Oct 2009. No residual UC in bladder or prostate was seen on pathology's examination. However he did have 11/24 removed LN positive for UC. The patient showed increased retroperitoneal LN by December 2009. He received 2 further lines of chemotherapy with no response and developed severe back pain, cervical LN, extensive liver metastases and a bulky retroperitoneal mass. The patient entered a Phase I clinical trial of AEZS-108, for “locally advanced unresectable or metastatic LHRH-R positive UC patients who failed platinum based chemotherapy“. He received AEZS-108 every 3 weeks for 9 cycles from May to October, 2011. Results: After 2 cycles of the investigational drug all pain and palpable lymph neck nodes disappeared; he stopped all narcotics and tolerated treatment very well. Mostly grade1-2 with few grade 3 toxicities were seen. CT scan pretreatment, and at 8, 22, 75 weeks post-treatment showed dramatic response at all disease sites. Twenty months after treatment start, the patient is symptom- free with no evidence of disease. Conclusions: This is the first case of a patient with LHRH-R positive Urothelial Carcinoma treated with AEZS-108 that is being reported. Considering the generally poor outcome of progressive UC and the short survival of these patients, the effect of this drug in this patient has been remarkable. The phase one study is ongoing.
An economic analysis of axitinib and sorafenib for second-line treatment of cytokine-refractory patients with advanced renal cell carcinoma in the United States (US).
Authors: Özer-Stillman Ipek , Ambavane Apoorva , Cislo Paul 
Published: March 2020

e15601 Background: Cytokines are a first-line treatment option for a subset of advanced RCC patients in the US. After progression on cytokines, NCCN guidelines recommend targeted agents, such as axitinib and sorafenib. Subgroup analysis of post-cytokine patients in the phase III AXIS trial found that axitinib increased median progression free survival (PFS) compared with sorafenib (12.0 vs. 6.6 months, p<0.0001), while overall survival (OS) showed no difference (29.4 vs. 27.8 months, p=0.144). An economic analysis for this subgroup was conducted from a US healthcare payer perspective. Methods: A cohort partition model with monthly cycles was constructed to estimate direct medical costs and health outcomes, discounted at 3.0% per annum, over cohort lifetime. Patients were apportioned into 3 health states (progression-free, progressed and dead) based on OS and PFS Kaplan-Meier curves for the post-cytokine subgroup in the AXIS trial. Active treatment was applied until progression, followed by best supportive care (BSC) alone thereafter. The wholesale acquisition costs were based from RedBook. Adverse event (AE) management costs were obtained from published studies. AE rates and utility values were informed by the AXIS trial. Administrative claims data from MarketScan Database were analyzed to estimate costs for BSC and routine care of second-line advanced RCC patients. Results: The total per-patient lifetime costs were estimated to be $242,750 for axitinib and $168,880 for sorafenib and most of the cost difference (84%) was due to the higher total medication cost of axitinib. The cost difference was sensitive to dose intensity and length of treatment. The difference in quality-adjusted life-years (QALY) for axitinib versus sorafenib was minor (1.3 versus 1.2) and the incremental cost-effectiveness ratio (ICER) for axitinib compared with sorafenib was $683,209/QALY. Conclusions: For cytokine-refractory advanced RCC patients, axitinib resulted in an ICER > $650,000/QALY versus sorafenib due to high drug costs and lack of OS benefit, indicating that axitinib may not present good value for money as 2nd line treatment when compared to sorafenib in the US.
Response to sunitinib in patients with metastatic renal cell carcinoma: Experience of one center.
Authors: Jazvic Marijana , Radic Jasna , Soldic Zeljko , Bolanca Ante , Kusic Zvonko 
Published: March 2020

e15603 Background: Five-years survival of patients with metastatic renal cell carcinoma (mRCC) is only 10%. A complete response (CR) to therapy is rare but has been achieved in minority of patients using high-dose interleukin-2. Sunitinib is an oral multitargeted receptor tyrosin kinase inhibitor and is currently considered the standard of care for first-line therapy of mRCC. CRs and long-term responders (LTR) to sunitinib have been documented in the literature. However, a detailed description and analysis of these patients is lacking. We report LTR, defined as patients achieving ongoing CR or remaining progression-free for ≥ 18 months on sunitinib. Methods: From 10/2008 till 12/2012, 48 patients were treated with sunitinib (50 mg/day, 4 weeks on/2 weeks off) as the first line therapy of clear cell mRCC. Tumor assessments were performed at baseline and every two cycles thereafter until the end of treatment, using RECIST criteria. Results: Nine patients were identified as LTR (18.8%). Retrospective data of these patients are reported in the Table. Conclusions: Sunitinib achieves LTR in a subset of patients with mRCC. Lung metastases and favourable MSKCC risk group may predict LTR. Maintaining full-dose sunitinib and management of therapy- related toxicity are crucial for treatment efficacy. [Table: see text]
Long-term outcome of sunitinib in metastatic renal cell carcinoma: Single center experience.
Authors: Maruzzo Marco , Basso Umberto , Zustovich Fable , Fiduccia Pasquale , Brunello Antonella , Roma Anna , Farina Patrizia , Bezzon Elisabetta , Banzato Alberto , Zattoni Filiberto , Zagonel Vittorina 
Published: March 2020

e15606 Background: The multi-target tyrosine-kinase inhibitor sunitinib has been widely used in first or subsequent lines of treatment for metastatic renal cell carcinoma (mRCC). Since results of registrative clinical trials may be overestimated due to patient selection, outcome data of sunitinib in the routine clinical practice are warranted. Methods: We retrospectively reviewed clinical data of all consecutive mRCC patients starting sunitinib from March 2006 to September 2012 at our Institution. Results: Eligible were 106 pts, median age 63 years (range 27-89), 70% males, 89% clear cell histology, 87% prior nephrectomy. Sunitinib was prescribed either as first (70%) or second or further line of treatment after cytokines or targeted therapies. Patients received a median of 8 sunitinib cycles (1-49). Median PFS and OS in the first line were 15.0 mo (95% CI= 9.8-20) and 35 mo. PFS and OS in the second or further line were 15 mo (11.7-18.2) and 25 mo. Motzer risk score retained its prognostic relevance both in the first and in the second of further line. Patients who received at least 4 cycles at standard dose (50 mg/d 4 wks on/2wks off) had a significantly better PFS and OS compared to patients who did not (PFS 23.0 vs 12.0 mo p=0.012, OS 49.0 vs 16.0 mo p=0.006). First line pts progressing within three months from starting sunitinib were 18.9% (primary refractory), while 25.7% pts were treated for more than 24 mo (long term responders). Grade 3 or 4 toxicities have been recorded in 35% of pts but only 7 pts (6.6%) discontinued the treatment due to unacceptable toxicities. Conclusions: Sunitinib is active and feasible in a broader population of mRCC pts, with apparently superior PFS and OS results compared to pivotal trials. Better management of drug toxicities, less strict criteria for radiological progression, and availability of further sequential treatments may explain such results. Pts receiving at least 4 full dose cycles achieved statistically significant better outcomes.
Pazopanib in metastatic renal carcinoma (mRC): Experience of 31 centers in Spain in first, second, third, or subsequent lines in daily clinical practice.
Authors: Rodriguez Sanchez Angel , García Domínguez Rocio , De Velasco Guillermo , Pinto Alvaro , Puente Javier , Rubio Gustavo , Vazquez-Estevez Sergio , Juan Marta , Constenla Manuel , Lopez Brea Marta , Sereno Maria , Puertas Javier L. , Garrido Maria , Marrupe David , Villalobos Maria L , Cantos Blanca , de Portugal Teresa , Vilchez Rocio , Gonzalez-Larriba Jose-Luis , Arranz Arija Jose Angel 
Published: March 2020

e15609 Background: In clinical trials pazopanib (P) was superior to placebo, noninferior to sunitinib, and very well tolerated as 1st-line for mRC, but there is limited information in daily clinical practice. Methods: We retrospectively reviewed 159 patients (p) who received P in in 31 centers in Spain during the first 18 month after P approval, to evaluate the timing of use and its efficacy. Results: Mean age was 66 y, 64.8% were males, 81.1% clear-cell, 12% non-clear cell, and 6.9% unspecified. At diagnosis of mRC 73.6% had nephrectomy, 78.6% and 71.7% of p were of good-intermediate risk (MSKCC and Heng criteria respectively). Metastatic sites were lung (59.7%), lymph nodes (26.4%), bone (22.6%), skin/soft-tissues (17.6%), liver (11.9%), CNS (2.5%), and 31.4% others (adrenal, pancreas, etc.). Median follow-up since diagnosis of mRC was 16 months (m). P was given as 1st systemic treatment in 81 p, (50.9%), as 2nd line in 32 p (20.1%, most after sunitinib, 17 due to intolerance), or as ≥3r line (46 p, 29%). Median follow-up after P was 7 m in 1st line, and 10 m in 2nd or ≥ 3rd line. Toxicity was as expected. No toxic deaths were registered. At the time of analysis, 85 p have discontinued P (progression: 73 p, toxicity: 10 p, other causes: 2 p), and 35 p have died. The table shows time to treatment failure due to progression or toxicity (TTF), and overall survival (OS) since the 1st dose of P. There were statistically significant differences in 1st line TTF and OS between MSKCC subgroups. Conclusions: In p with mRC and good-intermediate prognosis, P appears to be as effective in daily clinical practice as it was in 1st line trials. P also showed efficacy in p with poor risk, in 2nd-line (particularly progression or intolerance to sunitinib), and after 2 or more TKIs. Updated analysis will be available in June 2013. [Table: see text]