bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic neuroendocrine tumors: Single institution review over 10 years.
Authors: Asija Aakanksha , Milan Stacey , Prestipino Anthony , Yeo Charles , Pillai Madhavan V. 
Published: March 2020

e15183 Background: Pancreatic neuroendocrine tumors(pNET) are rare tumors accounting for less than 5% of pancreatic cancer. They are functionally and biologically heterogeneous and have not been studied in great detail until recently. Methods: We conducted a retrospective review of 79 consecutive patients with pNET diagnosed and treated at Thomas Jefferson University Hospital between the years of 2000 and 2010. Results: Of the 79 patients whose records were reviewed, 32 were male and 47 were female. Median age at diagnosis was 61 years. Two cases were associated with MEN1 syndrome. Primary tumor arose in the head, body and tail of the pancreas in 15, 10 and 26 patients, resp. In 6 patients, the tumor was multifocal. The neuroendocrine tumor was accompanied by pancreatic adenocarcinoma in 1 patient and intraductal papillary mucinous neoplasm in 3. In 10 patients, distant metastasis was detected, involving liver only. Tumor was functional in 9 patients: 5 insulinoma, 2 gastrinoma,1 glucagonoma and 1 VIPoma. As per TNM staging, 28, 22 and 10 patients were Stage I, II and III, and IV at diagnosis. Treatment by surgical resection was undertaken in 54 patients. In 21 patients, the tumor was discovered incidentally; 21 patients presented with abdominal pain. Other symptoms were irregular bowel movements, weight loss and jaundice. 51 of the 79 (64.5%) patients were alive at last follow up. On univariate analysis, median survival for females was 137 months vs 114 months for male. Median survival for patients with functional tumors was similar to those with nonfunctioning tumors (118 and 115 months, resp). Median survival for patients with Stage I, II, and III and Stage IV patients were 234,112 and 40 months resp. Median survival for patients who underwent surgical resection was 130 months vs those who did not (30 months). Conclusions: Majority of pNET were located in the body and tail of pancreas; an area requiring thorough scrutiny with special imaging studies for diagnosis. Only a minority of patients presented with liver metastasis(12%) and a smaller number showed hormonal activity (11%). Prognosis improved markedly in patients who underwent surgical resection. Therefore, whenever appropriate, surgical resection should be the treatment of choice in patients with pNET.
Combination therapy with radiation and weekly paclitaxel/carboplatin as definitive treatment for locally advanced esophageal cancer.
Authors: Doherty Mark , Cowzer Darren , Kelly Ciara Marie , Battley Jodie Emma , Leonard Gregory D. , Power Derek Gerard 
Published: March 2020

e15196 Background: Definitive chemoradiotherapy (CRT) is an established treatment option in localised esophageal cancer. While most patients are treated with cisplatin and fluorouracil, alternative chemotherapy regimens have been used. The combination of carboplatin and paclitaxel (CP) has been validated in a neoadjuvant CRT trial by the CROSS study. There has also been a phase II study (v. Meerten, ASCO 2010, e14508) showing efficacy and tolerability of this regimen in the definitive setting with radiation doses of 50.4Gy/28#. We report our experience using this strategy in two Irish centres. Methods: Patients treated with weekly CP and definitive radiation between Jan 2010 and Oct 2012 were identified from our pharmacy database. Clinicopathologic details were obtained from electronic medical records. The group contains patients with locally advanced unresectable disease, or those medically unfit for esophagectomy. Results: Between Jan 2010 and Oct 2012, we identified 22 patients. Thirteen patients had squamous histology, while 9 had adenocarcinoma. Staging was performed with CT, EUS, and PET/CT – 1 patient had T2 disease, while the remainder had T3/T4, and 10 patients had positive nodes. Reasons for not pursuing surgical resection were extent of disease and poor performance score. In total, 86% of patients received full dose treatment, with reasons for dose delay/reduction being grade 3 sepsis, grade 3 gastrointestinal toxicity, and decline in performance status. Overall 5 (23%) patients needed hospital admission during treatment. At a median follow up of 14 months (range 9-23months), 19 patients are alive with no evidence of disease, 2 patients have died of disease, and 1 patient is alive with relapsed disease. Our 1-year recurrence free survival rate is 86%. Conclusions: Definitive CRT with CP is a tolerable regimen that can be administered on an outpatient basis, and provides a treatment option in those who are unsuitable for surgical resection or Herskovic type CRT. Our results compare favorably with previous studies in this population. Further investigation is warranted in a prospective study to validate the efficacy of this approach.
Effect of the combination therapy of sorafenib and radiofrequency ablation on the survival time of advanced HCC.
Authors: Wang Nanya , Li Wei , Zhao Hengjun , Cui Jiuwei 
Published: March 2020

e15198 Background: Hepatocellular carcinoma (HCC) is one of the most common cancers in the worldwide. In China, accounts for 70% patients are in the advanced stage at the first diagnosis. Sorafenib is the only systemic therapy in adavanced HCC. Radiofrequency ablation (RFA) therapy is an new and effective minimally invasive method recent years and there are rare reports of the combination of RFA and sorafenib for the advanced HCC. This study was designed to observe the effect and security of the combination therapy with RFA and sorafenib for advanced HCC. Methods: Twenty-four advanced HCC patients treated with sorafenib for more than 3 months were divided into two groups: sorafenib alone (13 cases) and RFA/sorafenib (11 cases). The tumor status of these patients was evaluated with computed tomography (CT) every 1~2 months. Progression-free survival (PFS), Overall survival(OS) and adverse effects were observed. Results: The median PFS in sorafenib group was 3.9 (2.3-5.8) months, while median PFS in RFA/sorafenib group was 6.8 (2.5-12.8) months. The combination therapy got longer PFS than treated sorafenib only (P<0.05). And the mOS in sorafenib group and RFA/sorafenib group were 16.3 vs. 22.7months (P<0.05). The side effect of radiofrequency ablation are mainly included fever and pain in puncture location. And only 2 patients got pleural effusion post-operation. All the side effects are disappeared in 2 weeks. The most common adverse reactions observed in patients treated with sorafenib were: fatigue, weight loss, rash or superficial skin desquamation, hand-foot skin reaction, hair loss, diarrhea, anorexia, nausea and abdominal pain, only 3 patients got severe hand-foot skin reaction and diarrhea, but all of them continued the sorafenib oraled after symptomatic treatment. Conclusions: RFA combined with sorafenib prolonged the PFS and OS in advanced HCC. This combination therapy is safe and effective for patients with advanced HCC. This approach could be a new choice for advanced HCC.
Expression of HIF1a and HIF2a in bone metastatic clear cell renal cell cancer and use as prognostic markers.
Authors: Timar Jozsef , Szasz Attila Marcell , Kardos Magdolna , Tokes Annamaria , Kulka Janina , Szendroi Miklos , Szendroi Attila 
Published: March 2020

e15523 Background: Bone metastasis is a frequent complication of ccRCC and predictors of this type of progression are scanty. The aim of this study was to analyse HIF and HIF regulated gene expressions in bone metastatic ccRCC. Methods: A pre-target therapy era cohort of 125 ccRCC patients with <100 month follow-up period have been collected with paraffin embedded primary tumors. 65 patients developed bone metastasis where 45 metastases were available for analysis. RNA was isolated from FFPE tissues and gene expression of HIF1A, HIF2A as well as HIF-regulated genes GLUT1, LDH5, GAPDH, CAIX, VEGF, VEGFR2 and EPOR were measured by RT-PCR using B2M as control. Protein product of these genes was measured on TMA arrays using standardized immunohistochemistry and an image analysis program (Mirax Viewer, 3DHistech). Results: Expression of HIF1A and HIF2A was significantly increased in bone metastatic primary ccRCC tumor tissues both at mRNA and protein levels. Significant upregulation of 3 out of 7 HIF-regulated genes (VEGFR2, EPOR and LDH5) in the primary tumor tissues of bone metastatic ccRCC was proved at mRNA levels and confirmed at protein level for VEGFR2 as well. In bone metastatic tissues a significant overexpression of HIF2A and VEGF mRNA was also detected compared to the primary site. Prognostic power of the protein expression in primary tumor was found for HIF1A (p= .001), HIF2A (p = .041), and VEGFR2 (p = .001) (confirmed at mRNA levels as well) for overall survival at time of surgical removal of primary renal tumor using Kaplan-Meier method and log-rank statistics. To further test the power of HIF1A and HIF2A as prognostic factors we have performed multivariate analysis considering available clinicopathological variables (gender, Fuhrman grade, stage) and found that HIF2A protein level outperformed all other factors in the model. Conclusions: These data indicate that HIF genes are overexpressed in bone metastatic ccRCC among which HIF2A expression at mRNA and protein levels can be used as a strong independent prognostic marker.
Correlation of stomatitis and cutaneous toxicity with clinical outcome in patients with metastatic renal cell carcinoma treated with everolimus.
Authors: Rossi Lorena , Santoni Matteo , Medri Matelda , Scarpi Emanuela , Burattini Luciano , Burgio Salvatore Luca , Savini Agnese , Berardi Rossana , Stanganelli Ignazio , Cascinu Stefano , Amadori Dino , De Giorgi Ugo 
Published: March 2020

e15529 Background: We assessed the incidence and clinical presentation of stomatitis and cutaneous toxicity associated with everolimus in patients (pts) with metastatic renal cell carcinoma (mRCC). Correlation between these toxicities and clinical outcome was also determined. Methods: We retrospectively reviewed the clinical data of pts with mRCC treated with everolimus in two Italian Centers. Clinical evidence of stomatitis and/or cutaneous toxicity inducing a treatment discontinuation or a dose reduction were considered stomatitis-cutaneous toxicity events (SCTE). SCTE were evaluated and corresponding clinical data were reviewed for response and clinical outcome. Response was evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Results: The study population consisted of 79 mRCC pts treated everolimus (57 male, 22 female; median age 69 years, range 44–88). Fifty-two pts (66%) received everolimus as second-line therapy, while 27 (34%) as third-line. SCTE were seen in 20/79 pts (25%) at a median of 30.5 days on everolimus treatment (range 10–270 days). Tumor response was evaluable in 77 of 79 patients (19 of 20 SCTE pts and 58 of 59 non-SCTE). Partial response or stable disease was achieved in 15 of 19 pts with SCTE (79%) compared to 28 of 58 (48%) with no SCTE (p = 0.03). After a median follow-up of 19 months (range, 1 to, 39), the median progression-free survival (PFS) was 5.5 months (95% CI 3.4-7.7) and the median overall survival (OS) was 17.2 months (95% CI 13.2-24.4). A significant difference was found in the median PFS equal to 7.5 months (95% CI 3.4-24.4) in SCTE pts vs 3.7 months (95% CI 2.7-7.5) in non-SCTE, p = 0.047, and in the median OS equal to 30.6 months (95% CI 14.8-not reached) in SCTE pts vs 14.0 months (95% CI 9.9-17.7) in non-SCTE, p = 0.004. Conclusions: These data suggest that SCTE may be a predictive marker of favorable outcome in mRCC treated with everolimus. A prospective observational study with a dermatologic/stomatologic monitoring has been planned in mRCC pts treated with everolimus.
Association of a 2-weeks-on and 1-week-off schedule of sunitinib with decreased toxicity in metastatic renal cell carcinoma.
Authors: Najjar Yana George , Elson Paul , Wood Laura S. , Garcia Jorge A. , Dreicer Robert , Rini Brian I. 
Published: March 2020

e15534 Background: Treatment of metastatic renal cell carcinoma (mRCC) with sunitinib can be associated with toxicity leading to dose reduction. Maintaining adequate sunitinib dosing and avoiding dose interruptions that lower drug levels are essential for optimizing clinical efficacy. Standard sunitinib schedule is 4 weeks of treatment and 2 weeks of rest (schedule 4/2). Empirically in clinical practice, several metastatic RCC patients at The Cleveland Clinic (CCF) have been changed from a 4/2 schedule to a 2 weeks on /1 week off (2/1) schedule after experiencing toxicity in an attempt to maintain daily dose but reduce toxicity. Methods: The medical records of mRCC patients who were changed to a 2/1 schedule of sunitinib at CCF were retrospectively reviewed. Patient toxicity on each schedule was recorded during routine clinic visits and graded according to the Common Toxicity Criteria, version 4.0. Results: 21 patients were identified: 71% male, 78% clear cell histology, and 29% prior systemic therapy. All but one had prior nephrectomy. 95% of patients on the 4/2 schedule had grade 3 or 4 toxicity which led to the schedule change to 2/1. No grade 4 toxicities were observed on the 2/1 schedule, and 33% of patients experienced grade 3 toxicity (p = 0.0001 for comparison of worst grade toxicity on 4/2 versus 2/1). Two of the most common toxicities, fatigue and hand-foot syndrome (HFS), were significantly less frequent on the 2/1 schedule than on the 4/2 schedule (fatigue 52% all grade/33% grade 3 on 4/2 versus 33%/14% on 2/1; HFS 33%/29% on 4/2 versus 14%/0% on 2/1; p =.04 for both). Median overall treatment duration on the 4/2 schedule was 13.5 months (range 1.1-60.6 months) and median overall treatment duration on the 2/1 schedule was 24.4 months (range 1.3 to 67.6+ months). Conclusions: Treatment with sunitinib on a 2/1 schedule is associated with significantly decreased toxicity in patients who initially experience grade 3 or greater toxicity on the 4/2 schedule and can extend treatment duration considerably. Prospective clinical trials are required to define the optimal schedule of sunitinib to balance efficacy and toxicity.
Antihypertensive therapy with ACE-inhibitors and clinical outcome in metastatic renal cell carcinoma (mRCC) patients.
Authors: Bianconi Maristella , Scartozzi Mario , Faloppi Luca , Giampieri Riccardo , Bittoni Alessandro , Del Prete Michela , Cecchini Luca , Burattini Luciano , Montironi Rodolfo , Cascinu Stefano 
Published: March 2020

e15536 Background: Preclinical and clinical reports in various solid tumours, such as HCC, showed a potential enhancement of anti-angiogenic effect of TKIs treatment by the concomitant use of ACE-inhibitors. On the other hand hypertension is a common side-effect with the use of such therapeutic approach with an improved efficacy profile suggested in these patients. However data in metastatic renal cell carcinoma patients are lacking. The aim of our analysis was to evaluate the correlation between incidental use of ACE-inhibitors and clinical outcome in mRCC patients receiving first-line TKIs. Methods: 102 patients were eligible for our analysis. All patients received a TKI as a first-line treatment. ACE-inhibitors therapy was initiated prior or during the TKI administration. Results: Median OS was 32.13 months. 21 (21%) patients received ACE-inhibitors, while 81 (79%) did not. The OS was 37.5 months for patients treated with concomitant ACE-inhibitors and 17.8 months for those without such a treatment (p=0,005). No significant differences were found with other antihypertensive treatments or for the clinical variables considered. Conclusions: In our analysis the incidental use of ACE-inhibitors represents a relevant factor for clinical outcome in mRCC patients. If confirmed in larger case series the use of antihypertensive treatment, particularly ACE-inhibitors, could be considered a stratification factor.
Morphoproteomics of mTORC2 pathway as resistance signature and activated ERK and STAT3 prosurvival/antiapoptotic pathways in metastatic renal cell carcinoma (mRCC) progressing on rapalogs.
Authors: Yadav Swetha Siddappa , Buryanek Jamie , Brown Robert E , Ouyang Fangqian , Amato Robert J. 
Published: March 2020

e15548 Background: Resistance to rapalog therapies (rapamycin, temsirolimus or everolimus) in mRCC may be due to adaptive switching from mammalian target of rapamycin complex (mTORC)1 to mTORC2. A preclinical study using an agent targeting both complexes demonstrated the combination is more effective than temsirolimus in vitro but not in xenograft models (Zhang 2013 PLos One). Methods: Morphoproteomic analysis of mRCC biopsies showed progression while the patients were treated with everolimus or temsirolimus at the time of biopsy. Constitutive activation evidenced by expression (≤3) of phosphorylated (p)-mTOR (Ser 2448) in the nuclear compartment coupled with concomitant expression of p-Akt (Ser 473) favors mTORC2 and constitutive activation by p-extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Tyr204) and p-signal transducer and activator of transcription (STAT)3 (Tyr705) in the nuclear compartments (≤3) indicates convergent signaling through prosurvival/antiapoptotic pathways. Results: Overexpression of mTORC2 with strong expression of p-ERK1/2 and p-STAT3 indicates adaptive switch from mTORC1 to mTORC2 pathway and constitutive activation of prosurvival/antiapoptotic pathways (Table). Overexpression of mTORC1 with strong expression of p-ERK 1/2 and p-STAT3 indicates adaptive resistance to everolimus. Equal expression of mTORC 1 and 2 with concomitant strong expression of p-ERK1/2 and p-STAT3 indicates resistance to everolimus and constitutive activation of the adaptive prosurvival/antiapoptotic pathways. Conclusions: Morphoproteomics confirms mTORC2 as resistance signature to rapalog therapy and uncovers constitutive activation of the prosurvial ERK and STAT3 pathways as additional adaptive mechanisms to such treatment, indicating the need for a combinatorial therapeutic approach in mRCC progressing on rapalogs. [Table: see text]
Renal cell cancer (RCC): Use of metformin in the setting of renal impairment.
Authors: Ochuwa Nwabugwu , Finkel Kevin , Ouyang Fangqian , Amato Robert J. 
Published: March 2020

e15551 Background: Metformin is a biguanide that is widely used to treat type-2 diabetes and prediabetic syndromes. It has been found to inhibit RCC cell proliferation through activation of AMP-activated protein kinase (AMPK) and downstream inhibition of mammalian target of rapamycin (mTOR). Metformin is associated with potentially life threatening lactic acidosis (LA), but a clear link has not been established. We evaluated the occurrence of lactic acidosis in metformin-treated RCC patients with renal impairment. Methods: A retrospective study of 65 RCC patients treated with 250 to 2000 mg of metformin daily was conducted. Demographic data including age, gender, and ethnic background were collected. Data were collected on median metformin dose, eGFR, dialysis status, lactic acid, BUN, Na, K, Cl, and CO2 values. Results: Median metformin dose was 1000 mg daily in each group. Fifteen patients (23%) had elevated lactic acid >4. The mean eGFR for patients with elevated lactic acid of >4 vs. <4is comparable (p=0.98). The two populations were significantly different at the BUN baseline level: patients with lactic acids >4 have statistically significant smaller median baseline BUN level (median of 19.0 vs. 19.5; Wilcoxon two-sample p=0.03). Moreover, there is a marginally significant difference in age between these 2 groups (Mean of 58 vs. 62.8, Student's t-test p=0.07). Conclusions: Regardlessof lactic acid elevation, patients did not experience lactic acidosis. Complete data will be presented. [Table: see text]
Phase I clinical trial of external hyperthermia and intravesical mitomycin C to treat BCG-refractory bladder cancer.
Authors: Abern Michael , Vujaskovic Zeljko , Dewhirst Mark W. , Lan Lan , Craciunescu Oana I. , Stauffer Paul , Inman Brant Allen 
Published: March 2020

e15560 Background: Patients with non-muscle-invasive bladder cancer (NMIBC) that fail intravesical bacillus Calmette-Guérin (BCG) are at high risk for progression. Radical cystectomy is an effective but morbid treatment option. We tested the safety and efficacy of combined intravesical mitomycin C (MMC) and external deep regional hyperthermia (HT) as a bladder-sparing approach for BCG-refractory NMIBC. Methods: Patients with BCG-refractory NMIBC were eligible for this phase I clinical trial. Treatment consisted of intravesical MMC (40 mg in 40 mL) with concurrent HT with target temperature of 42°C. MMC dwell time was 60-120 min and heating time was 40-60 min. HT was delivered using a BSD2000 device and temperatures monitored with skin, bladder and rectal probes. Treatment was given weekly for 6 weeks (induction) then monthly for 4 months (maintenance). The primary endpoint was toxicity which was assessed using CTCAE 3.0. Secondary endpoints included recurrence-free survival (RFS), progression-free survival (PFS), cystectomy, and overall survival (OS) which were assessed at 3 month intervals with cystoscopy and cytology for 2 years. Results: Fifteen patients were eligible and consented to the clinical trial. Median age was 66 years and 87% were male. Median follow-up was 2.85 years. One patient did not tolerate supine position, two completed induction but recurred prior to maintenance, one recurred after 3 maintenance treatments, and 11 patients received all 10 treatments. The 2 year RFS was 33% (median RFS = 15.4 mos). Six patients (40%) required cystectomy (median time = 20.1 mos). No patient had bladder progression but two patients developed ureteral tumors (not present on baseline imaging). Two patients died, one from ureteral cancer and one of cardiovascular disease, for a 3-year OS of 83% (median OS not reached). No grade III toxicities were observed. Common toxicities were abdominal pain (36%), cystitis (22%), pruritis and urinary tract infection (14%). Conclusions: The combination of MMC and HT for BCG refractory NMIBC was safe and associated with low grade toxicity. While recurrence was common, progression did not occur, and recurrent patients were safely salvaged with cystectomy. Clinical trial information: NCT00734994.