bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial trends of second-line chemotherapy in advanced pancreatic cancer.
Authors: Silva Milton Jose B. , Maia Joyce Maria L. , Ribeiro Adriana Regina G. , Chinen Ludmilla T. D. , Paiva Jr Tadeu Ferreira , Padua Fernando Vidigal , Pinto Flavio Augusto Ismael , Santos Elizabeth Santana , Mello Celso Lopes , Campanha Daniel , Pereira Augusto Akikubo Rodrigues , Fanelli Marcello Ferretti
Published: March 2020

e14680

Background: Despite the lack of high-quality clinical trial data suggesting that second-line chemotherapy (SLC) may affect survival on metastatic pancreatic cancer (mPC), most of centers utilizes them after the failure of initial treatment in patients who maintain a good performance status. The aim of the present study was to review our institutional experience with SLC and estimate its role in overall survival (OS). Methods: We performed a retrospective matched case-control analysis based on search of medical records in 106 consecutive patients with mPC at our institution. Patients received first line chemotherapy (FLC) and SLC (n = 49) or FLC only (n =57) from September 2005 to December 2010. Case matching was performed with respect to age (< 60y versus ≥ 60y), topography (head of the pancreas versus body or tail), sites of metastasis. Overall survival was analyzed by Kaplan-Meier method. Results: Median age was 63 (32-86) and 60 (38-85) for SLC group and FLC group respectively. There was no significant difference between the two groups regarding topography, TNM stage at diagnosis, and sites of metastasis. The main site of metastasis was the liver (24,4%), followed by peritoneum (2,8%).Median follow-up of both groups was 8.4 months (0.23m-54.93m). First line treatment consisted of Gemcitabine (55.1% x 49.1%) and gemcitabine + cisplatin (18.4%x14%) in SLC and FLC group respectively. The most used second line treatment was Capecitabine (32.7%), followed by Folfox (16.3%), and Fluoracil (10.2%). The Kaplan-Meier estimate of the overall median survival, 1-year and 2-years survival rate was 15.72 months versus 7.2 months (p:0.021), and 60% vs. 32%, and 30% vs. 19% in SLC and FLC group, respectively. Conclusions: Our result suggests that second-line chemotherapy may be beneficial to improve overall survival in patients with advanced pancreatic cancer. It’s important that new and ongoing clinical trials clarify which is the best chemotherapy scheme in this setting.
Effects of metformin on pancreatic cancer survival among Medicare beneficiaries.
Authors: Witkowski Elan R. , Ragulin-Coyne Elizaveta , Chau Zeling , McDade Theodore P. , Ng Sing Chau , Tseng Jennifer F.
Published: March 2020

e14691

Background: Evidence from preclinical models suggests that metformin may have antitumor activity against pancreatic adenocarcinoma. The effect in humans has not been well-described. A recent single-institution retrospective analysis suggested improved survival in diabetic patients who had been exposed to metformin. The current study was designed to determine whether metformin was independently associated with improved pancreatic cancer (PC) survival when compared to non-metformin controls using newly available national pharmacy data from Medicare Part D. Methods: Patients with diagnosed with AJCC Stage II-IV PC during 2007 were identified in the SEER-Medicare linked database. Part D events for oral diabetic medications were identified from the date of diagnosis until death or 12/31/2008, and divided into metformin-containing or non-metformin. Patients who did not receive an oral medication for diabetes, lacked continuous Part D prescription drug coverage, underwent surgical resection, or survived less than 30 days were excluded. Patient characteristics were compared by chi-square and Wilcoxon. Overall survival was compared by Kaplan-Meier log rank. Results: From an initial cohort of 899 patients, 100 met inclusion criteria and received oral diabetic medication. Of these, 31 received metformin and 69 non-metformin. Patient characteristics were similar among the groups, including median age (76.6 vs. 76.2, p=0.75), race distribution, Charlson comorbidity score and disease stage (p>0.05 for each). There was no statistically significant difference in median survival between the two groups: 5.6 months for metformin vs. 6.1 for non-metformin, p=0.93. Conclusions: This study using national Medicare Part D prescription drug claims revealed no detectable survival benefit for unresectable pancreatic cancer patients who received metformin when compared to non-metformin oral hypoglycemics. Sufficient power to detect modest benefits, however, will require additional subjects, which we anticipate in the near future. Additional studies are warranted and ongoing to determine the effect of metformin on pancreatic cancer survival.
Neuroendocrine tumors (NET) of the gastrointestinal tract: Experience at Winship Cancer Institute of Emory University.
Authors: Zafar Syed Farhan , Patil Dattatraya Hari , Kauh John S. , Adsay Volkan , Kooby David A. , Brutcher Edith , Maithel Shishir Kumar , El-Rayes Bassel F.
Published: March 2020

e14692

Background: NET are relatively uncommon malignancies with variable natural history and often indolent clinical behavior. Pancreatic neuroendocrine tumors (PNET) have been reported to have worse outcomes as compared to neuroendocrine tumors of the gastrointestinal tract other than pancreatic (GNET). The objective of our study was to compare the clinicopathologic characteristics, presentation, treatment and survival outcomes in PNET and GNET. Methods: After IRB approval, we identified 125 patients (pts) with NET of the gastrointestinal tract from 2006-2011 in the Winship Institute cancer registry. A retrospective chart review was performed. Patients were categorized in mutually exclusive groups of PNET and GNET. Results: Demographic information and comparison of basic characteristics are listed in the table. Treatment modalities employed for PNET included surgery (72%), chemotherapy (30%), biological therapy (13%) and somatostatin analogues (11%). Liver-directed therapies were employed for hepatic metastases in 9 pts with PNET. Most common modality was radiofrequency ablation (4 pts) followed by Yttrium-90 embolization (3 pts), chemoembolization (1 pt) and bland embolization (1 pt). Majority of GNET were of midgut origin (47%) followed by foregut (35%) and hidgut (13%). Treatment for GNET included surgery (64%), chemotherapy (11%) and somatostatin analogues (17%). 90% of pts in PNET and 89% in GNET were alive at median follow up of 82 months. Conclusions: Overall, pts with NET have good prognosis. In our series, patients with PNET and GNET, had comparable survival outcomes even in advanced stage. These patients should be evaluated by a multidisciplinary team as new therapies become available. [Table: see text]
Role of chemoradiotherapy in advanced biliary cancers.
Authors: Nayak Asha , Arora Sameer , Kruse Edward J.
Published: March 2020

e14694

Background: Patients with metastatic biliary tract cancers have a poor outcome and radiotherapy is administered largely to patients with an intent of palliation. We analyzed our institutional biliary tract cancer database to compare the outcome between chemotherapy alone vs. chemoradiotherapy. Methods: From January 2005 to December 2010, 126 metastatic and inoperable biliary cancer patients were retrospectively analyzed. 59(46.8%) patients received chemoradiotherapy(CRT) and 67(53.1%) patients received chemotherapy alone. Chemotherapy regimens consisted of 5-fluorouracil, gemcitabine, or cisplatin. CRT patients received 3D-CRT with a median dose of 30 Gy (range, 25-35Gy ) at 1.8-2 Gy per fraction per day.Patients were categorized into Gall bladder, extrahepatic or intrahepatic bileduct cancers .The follow-up time was calculated from the time of diagnosis to the date of death or the last contact. Kaplan-Meier analysis was used to calculate the overall survival (OS). Results: Median OS was 6.6 months for all patients. Median OS was 6.9 months (0.8-26.0) for patients treated with chemotherapy alone and 10.2 months (0.8-46.9) for those treated with chemoradiotherapy (p = 0.002). Univariate survival analysis of categorical variables for patients treated with chemoradiotherapy revealed that age, race, gender, location of metastatic site, site of primary tumor ,T stage (T3 v. T4) or nodal stage were not significant. However, ECOG performance status (1 v. 2/3) and the dose of radiation (<30 v. >30 Gy) received were associated with improved survival (p = 0.002, p=0.032). Median OS was 13.2 months for ECOG 1 vs. 4.3 months for ECOG 2/3. Median OS was 12.3 months for patients treated with radiotherapy dose more than 30 Gy vs. 6.4 months for those who received less than 30 Gy. 12/59(20.3%) patients who received chemoradiotherapy lived approximately 2 years longer. Conclusions: Metastatic biliary tract cancer patients with good performance score may benefit from chemoradiotherapy, and this modality did not increase the mortality. Long-term survival was observed in this selected group.
Impacts of epidermal growth factor receptor, HER2, and mTOR status on outcomes of patients with gastric cancer.
Authors: Aydin Kubra , Okutur Kerem , Bozkurt Mustafa , Namal Esat , Ozturk Akin , Planci Kezban Nur , Akcali Zafer , Tecimer Coskun , Demir Gokhan
Published: March 2020

e14698

Background: Expression of EGFR, Her-2 and mTOR have been linked to clinical outcomes in several solid tumors. However clinical significance of these biomarkers in gastric cancer remain unclear. This study was designed to detect the clinical implications of these three biomarkers in Turkish population. Methods: Paraffin-embedded tissue microarray blocks containing gastric cancer tissue obtained from 30 patients were constructed. Expression of mTOR, EGFR were detected by immunohistochemistry. Her-2 gene ampflication was detected by FISH. The correlation of these biomarkers to clinicopathologic features and survival of patients with gastric cancer was studied. Results: The overall rates of positive mTOR, EGFR and Her-2 status were 36.7%, 63.3% and 23.3% respectively. The EGFR expression(any grade) was significantly correlated with better OS(Overall Survival)(p=0.01). Median survival time is 34.7 months in EGFR +patients and 10.6 months in EGFR - patients. There was no significant correlation with Her-2 status and survival. But 5 of these 7 Her-2 positive patients have already took trastuzumab treatment. Also we find that her-2 pozitive tumors significantly metastasized much more frequently to liver than her-2 negative tumors.(p= 0.043) In Contrast, her-2 positive tumors significantly metastasized less commonly to periton, over, omentum as seeding than her-2 negative tumors.(p=0.009). There was no association was noted between the expression of mTOR and survival time. Conclusions: EGFR is good prognostic marker in gastric cancer patients.
What is the clinical impact of PET/CT in evaluating patients for recurrent pancreatic cancer, and is it a useful tool in suspicious pancreatic lesions?
Authors: Alkaied Homam , Asaad Razan , Popalzai Muhammad Jawad , Brenner Arnold
Published: March 2020

e14704

Background: Recurrence of pancreatic cancer after surgery is difficult to detect with conventional computed scan (CT) which has limited ability to distinguish local recurrence from postoperative changes. FDG – (18-fluorine deoxyglucose) positron emission tomography/computed tomography (PET/CT) evaluates biologic tumor activity related to glucose metabolism. Hence, it may improve the diagnostic accuracy postoperatively for pancreatic carcinoma. PET/CT can also evaluate suspicious pancreatic lesions to predict their malignant potential. Methods: 31 PET/CT scans were reviewed retrospectively for 18 patients with pancreatic lesions found on abdominal CT. Results: 14 of 18 patients had documented pancreatic cancer. 9 patients underwent resection; 7 had Whipple procedure; 2 had distal pancreatectomy with splenectomy. All 9 patients who underwent resection had recurrent disease; 4 (44%) of them had recurrence detected by PET/CT that was not detected on CT performed within 4 weeks of the PET/CT, potentially altering their management and prognosis. 1 patient had a recurrent lesion resected and 3 patients were started on chemotherapy or chemo-radiation therapy. In 2 cases with recurrence, PET/CT was able to distinguish pancreatic bed recurrence from postsurgical changes in comparison with CT. 4 of 18 patients had suspicious pancreatic findings on CT. PET/CT in these patients showed no FDG avid pancreatic lesion. Among these 4 patients, 1 had no pancreatic biopsy performed due to comorbidity and is still alive 3.5 years later. 1 had benign finding on pancreatic biopsy. 2 had a non diagnostic pancreatic biopsy. 1 expired 2 years later due to sepsis, and the other patient was 86 years old and expired a year later of unknown cause. Conclusions: FDG PET/CT is valuable in evaluating patients with suspected recurrent pancreatic carcinoma. PET/CT is helpful in managing patients with a suspicious CT pancreatic lesion who lack histologic confirmation. If the lesion is not metabolically active, this may allow follow up with observation and reduction in unnecessary intervention in selected patients.
Identification of two HCC phenotypes based on thrombocytopenia.
Authors: Carr Brian I.
Published: March 2020

e14720

Background: Clinical phenotypes of small and larger HCCs are not well characterized. Aims. To characterize small HCC phenotypes. Methods: A cohort of 430 small HCCs that were diagnosed through screening, were dichotomized by size of < 3cm or > 3cm maximum tumor diameter and compared for radiologic and blood test parameters and analyzed by Chi-square test for categorical variables and Mann-Whitney test for continuous variables. Results: Significant differences between the tumor size groups included AFP values and platelet counts, with thrombocytopenia and elevated bilirubin levels being associated with smaller tumors. In comparing PVT+ and PVT- patients, AFP levels and platelet counts were also significantly different between the 2 groups. Conclusions: Larger tumors were associated with normal platelets and bilirubin levels, compared to smaller tumors that were more typically found in the presence of thrombocytopenia, suggesting that smaller and larger HCCs might have different developmental pathways.
Neoadjuvant chemoradiation for potentially resectable gastric cancer.
Authors: Barfield Michael E. , Untch Brian R. , Arcury Justin T. , Czito Brian G. , Willett Christopher , Pappas Theodore N. , White Rebekah Ruth , Tyler Douglas S. , Blazer Dan G.
Published: March 2020

e14724

Background: Outcomes are poor in patients with gastric cancer, and recurrence is common. Perioperative chemotherapy and adjuvant chemoradiation therapy (CRT) improve survival in patients with resectable disease. Experience with neoadjuvant CRT for potentially resectable disease is limited, and its role remains undefined. We report our experience using neoadjuvant CRT for potentially resectable gastric cancer. Methods: An IRB-approved, retrospective review from 1994 to 2007 identified 23 patients with biopsy-proven, potentially resectable gastric cancer. Patients had T2/T3 and/or N1 disease and no evidence of metastatic disease by endoscopic ultrasound and cross-sectional imaging. All underwent neoadjuvant external beam radiation with concurrent 5-FU or platinum-based chemotherapy followed by restaging and surgery if appropriate. Results: Of the 23 patients, 20 completed neoadjuvant CRT and surgical exploration. Two patients (n=2) had radiographic disease progression during neoadjuvant CRT and did not undergo resection. One patient (n=1) developed a perforated gastric ulcer during CRT and underwent emergent resection. The median time from diagnosis to surgery and completion of neoadjuvant CRT to surgery was 104 days and 37.5 days, respectively. Gastrectomy was performed in 17 (85%) patients who completed neoadjuvant CRT. Metastatic disease was identified in the remaining 3 (15%) patients. Following gastrectomy, a complete pathologic response was observed in 4 (23.5%) patients, a partial response in 11 (64.7%) patients, and no response was identified in 2 (11.8%) patients. One (6%) patient had microscopic positive margins, and 9 (53%) had positive lymph nodes. There was no perioperative mortality. Two (11.8%) patients had anastomotic leaks, which were managed non-operatively. The median length of stay was 10 days. The median disease-free survival was 10.5 months, and median overall survival was 19.6 months. Conclusions: Gastric cancer carries a poor prognosis. Surgical resection after neoadjuvant CRT has low treatment-associated morbidity and mortality. Survival and complete response rates are comparable to published series. Further evaluation of this treatment strategy is warranted to assess its efficacy.
CF102 for the treatment of hepatocellular carcinoma: A phase I/II, open-label, dose-escalation study.
Authors: Stemmer Salomon M. , Benjaminov Ofer , Medalia Gal , Ciuraru Noa , Silverman Michael H. , Bar Yehuda Sara , Fishman Sari , Harpaz Zivit , Farbstein Motti , Cohen Shira , Petoka Renana , Singer Barak , Kerns William D , Fishman Pnina
Published: March 2020

e14731

Background: The A3 adenosine receptor (A3AR) is over-expressed in hepatocellular carcinoma (HCC) cells as well as in the peripheral blood mononuclear cells (PBMCs) of patients with HCC. The orally active drug candidate CF102, an A3AR agonist, induces in vivo apoptosis of HCC cells via de-regulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC. Methods: The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally twice daily in continuous cycles of 28 days each. Evaluation of anti-tumor effects and the utilization of A3AR as a biological predictive marker of response to CF102 were the secondary objectives. Results: 18 patients received CF102, six at each dose level (1 mg, 5 mg and 25 mg BID). No serious drug-related adverse events or dose-limiting toxicity were observed. Most adverse events were of grade 1-2 severity. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom were sorafenib failures, was 7.8 months (range, 3·5-27·3 months) and for Child-Pugh B patients (28%) was 8.1 months. Stable disease (SD) by RECIST was observed in four patients for at least 4 months. CF102 had no adverse effect on routine measures of liver function over a 6 months period in 12 patients. A direct correlation between A3AR expression levels at baseline and patients’ response to CF102 was found. Conclusions: CF102 is safe and well-tolerated and shows favorable PK characteristics and hepatoprotective effects in patients with HCC. CF102 has shown preliminary evidence of clinical activity in Child-Pugh A and B HCC patients, justifying further clinical development.
Comparison of planning target volume for esophageal cancer target delineation with different ways.
Authors: Shao Qian
Published: March 2020

e14735

Background: To compare the planning target volume (PTV) of esophageal cancer target delineation with different ways. Methods: There were 15 patients with middle chest esophageal cancer, involving 12 males and 3 females and aged 45-72 years. The median age was 59 years. Positioning in the CT slice thickness of 3mm on the outline of esophageal lesions as GTV.The CTV0 was created by manually contouring the esophagus for 30mm superiorly and inferior to GTV then adding 5mm circumferentially to the created volume to account for microscopic spread. For the PTV0, a 10mm margin in all direction was added to CTV0. The CTV6 was created by manually contouring the esophagus for 24mm superiorly and inferior to GTV then adding 5mm For circumferentially. The PTV6, a 16mm margin in superiorly and inferiorall direction and a 10mm margin in other direction was added to CTV6. The CTV15 was created by manually contouring the esophagus for 15mm superiorly and inferior to GTV then adding 5mm For circumferentially. The PTV15, a 25mm margin in superiorly and inferiorall direction and a 10mm margin in other direction was added to CTV15.The CTV30 was created by manually contouring the esophagus for 0mm superiorly and inferior to GTV then adding 5mm For circumferentially. The PTV30, a 40mm margin in superiorly and inferiorall direction and a 10mm margin in other direction was added to CTV15. Paired t-test using SPSS17.0 to p <0.05 was considered significant difference, compared PTV30, PTV15, PTV6, PTV0 volume. Results: The volumes of PTV30, PTV15, PTV6 and PTV0 showing with the mean ± standard deviation, were 392.51 ± 123.32cm3, 366.07 ± 112.78cm3, 346.55 ± 103.70cm3 and 342.36 ± 108.65cm3, respectively. The results were significant differences (p ≤ 0.001) except PTV6 vs PTV0. Conclusions: Different ways of esophageal cancer target delineation make significant effects on the PTVs. Choosing the delineation ways of CTV6 or CTV0 are better. It may benefit patients.
Analysis of tolerability of intravesical bacillus Calmette-Guérin (BCG) therapy in non-muscle-invasive bladder cancer.
Authors: Miyazaki Jun , Ishizuka Naoki , Hinotsu Shiro , Akaza Hideyuki , Nishiyama Hiroyuki
Published: March 2020

e15004

Background: Although the effectiveness of BCG intravesical instillation with maintenance therapy (MT) has been shown (Hinotsu S. BJUI 2010), the treatment was not well tolerated. We aimed to characterize adverse events (AEs) affecting tolerability and to study the possible prediction of MT tolerability during the induction therapy (IT) by using data from the previous phase III trial. Methods: Forty-two patients received 81 mg intravesical BCG once weekly for 6 weeks as IT followed by thrice weekly instillations at 3, 6, 12 and 18 months as MT. AEs after each instillation were analyzed. The hazard ratio (HR) and 95% confidence intervals (CI) between the risk of each AE during IT and MT were analyzed by Cox regression. To assess the time between the randomization and the onset of each AE, HR and CI for patients without an AE were measured against those who developed the AE once, using the Wei-Lin-Weissfeld (WLW) Model. The WLW Model allows the analysis of recurrent AEs by controlling within-patient correlations in a marginal Cox model. Results: Fourteen of the 42 patients completed MT, of whom 11 completed as scheduled, and 3 completed with some modifications. For 28 who did not complete, 6 were withdrawn during IT and 22 during MT (of whom 15 had some MT modifications). Among 17 patients who experienced Grade (Gr) 3 AEs, 4 completed the treatment. In total there were 65 Gr3 events. Urinary frequency was most frequent event causing treatment cessation (7/38 events) and hematuria was the most common cause of treatment modification (7/13). The risk of an AE that occurred during IT recurring during MT was high for malaise (HR:3.49), pyrexia (3.33), and difficulty in urination (2.90). The WLW analysis revealed that malaise was relapsed in 18/21 patients (HR:5.81, CI:2.94-11.50, p<0.0001), difficulty in urination in 13/21 (4.56, 1.92-10.84, 0.0006), pyrexia in 14/18 (4.27, 2.18-8.37, <0.0001), hematuria in 36/39 (2.69, 1.79-4.04, <0.0001) and urinary frequency in 35/39 (2.30, 1.38-3.84, 0.0014). Conclusions: Gr3 urinary frequency was the most common cause of treatment cessation. The risk of the recurrent AE during MT will increase in those who develop AEs such as malaise, pyrexia, and difficulty in urination at IT.
Brain metastases in patients with urothelial carcinoma.
Authors: Boyle Helen Jane , Lavergne Emile , Droz Jean Pierre , Bonnin Nathalie , Flechon Aude
Published: March 2020

e15009

Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.
Role of MCM as an adjuvant to urine cytology in the diagnosis of bladder cancer.
Authors: Narine Nadira , Thottakam Bensita M.V , Donnini Alessia , Dhanvijay Sushant , Saeb-Parsy Kasra , Wilson Alex , Rana Durgesh N
Published: March 2020

e15011

Background: Urine cytology, a cheap non invasive first line test (PAP) has traditionally been used for the diagnosis of urothelial carcinoma (UC) as it has excellent sensitivity for the detection of high grade and in situ lesions. However, sensitivity for low grade carcinoma is rather varied as this is a problematic area with various mimics leading to both over and under diagnoses. To overcome this dilemma, a number of biomarkers and molecular tests have been employed with mixed results and varied financial implications. We report on a relatively cheap and easily adopted in vitro diagnostic test, Minichromosome maintenance (MCM) proteins, as an adjuvant to cytology in the diagnosis of both low and high grade bladder cancer (BC). MCM proteins play an important regulatory role in eukaryotic DNA replication and is expressed only as normal cells progress from G0 into G1/S phase of the cell cycle. However, over expression has been demonstrated in neoplasia in a range of sites including urothelium. Methods: 106 patients from gross haematuria (GH, 39) and cystoscopic surveillance (CS, 67) clinics were investigated for newly diagnosed and recurrent BC respectively by MCM and cytology with histological outcome being used as the gold standard. Results: Using biopsy positive outcome, MCM and cytology had a sensitivity of 91.7%, specificity of 86.6%, PPV of 66.7% and NPV of 97.3%. There was noticeably improved correlation of MCM and cytology with increasing grade of BC (Table). Conclusions: We showed the combination of MCM and cytology to be highly sensitive and specific for the determination of CIS, G2, and G3 BC with improved detection of G1 bladder cancer. The combination of MCM and cytology suggests that this offers promise as a novel diagnostic biomarker in GH and CS patients. [Table: see text]
Multidisciplinary management and use of neoadjuvant cisplatin combination chemotherapy in patients with muscle-invasive urothelial bladder cancer.
Authors: Hoffman-Censits Jean H. , Lin Jianqing , Lallas Costas D. , Showalter Timothy Norman , Den Robert Benjamin , Doubet Ellen , Brown Jillian , Singh Jaspreet , Dicker Adam , Gomella Leonard G. , Kelly William Kevin , Trabulsi Edouard John
Published: March 2020

e15012

Background: Although randomized data support neoadjuvant cisplatin-based chemotherapy prior to cystectomy for muscle invasive bladder cancer (MIBC), a recent retrospective study of 14 academic centers demonstrated only 12% of patients eligible for cystectomy received neoadjuvant chemotherapy. We reviewed utilization of neoadjuvant chemotherapy in a cohort of patients with MIBC seen at the Genitourinary Multidisciplinary Cancer Clinic (GUMDCC) of the Kimmel Cancer Center at Thomas Jefferson University (TJU). Methods: With IRB approval, records were reviewed for patients seen in the GUMDCC by urologists, radiation and medical oncologists with MIBC expertise from August 2009 to August 2011. Results: Of the201 patients with bladder or urothelial carcinoma, 46 (23%) with T2-T4 MIBC were identified and evaluated for neoadjuvant chemotherapy prior to radical cystectomy. 14 of 46 (30%) had renal, cardiac or other comorbidities rendering them unfit for cisplatin or cystectomy, and 2 were never referred to medical oncology. Of the 30 patients eligible for cisplatin and cystectomy, 2 were treated at outside institutions, 4 were recommended for treatment but were lost to follow up, and 4 who had refused neoadjuvant chemotherapy had adverse pathology at cystectomy and received adjuvant chemotherapy. Twenty eligible patients (66%) initiated neoadjuvant chemotherapy at TJU, 8 of those (40%) on clinical trial. 100% of patients treated with neoadjuvant chemotherapy at TJU received cisplatin based regimens, and 17 of 20 patients received at least 3 cycles. Chemotherapy was initiated in an average of 29.8 days of multidisciplinary evaluation. Conclusions: Multidisciplinary evaluation and management of patients with MIBC leads to improved compliance with evidence based guidelines and higher rates of cisplatin based neoadjuvant chemotherapy administration compared with historic data.
Decision making in clinical stage I (CSI) testicular cancer (TC).
Authors: Palmieri Giovannella , Nappi Lucia , Condello Caterina , Formisano Luigi , Federico Piera , Rescigno Pasquale , Di Lorenzo Giuseppe , Matano Elide , De Placido Sabino , Damiano Vincenzo
Published: March 2020

e15034

Background: Optimal management of CSI seminomatous (S) and nonseminomatous (NS) TC is an open question. Quality of life and patient preferences are the principal end-points for the best treatment choice. Multidisciplinary approach is required for CSI TC patients to allow an individualized treatment with a patient-centered approach and an active participation in decisions. The “shared decision making” (SDM) is the prevailing approach because patients together with clinicians arrive at a mutually agreed-on choice. We have a project concerning the involvement of patients with CSI TC in the SDM. Methods: We used some key points of SDM: define the problem; treatment options; discuss pros/cons; clarify patient preferences; clarify the patient’s understanding. Educational material are offered to patients. From 2005 to 2012, 32 patients with CSI TC were evaluated. For each patient some clinical and socio-demographic features, type of treatment chosen and some sequel related to treatment were analyzed. Results: Patients characteristics are reported in the table. 4 S patients chose surveillance, 10 chemotherapy and 6 radiotherapy. 2 NS patients chose surveillance, 9 chemotherapy. 4 relapsed: 1 S patient after 13 months from chemotherapy and 1 during the surveillance after 24 months. 2 NS patients relapsed after 12 and 18 months both during the surveillance. All relapsed patients received chemotherapy. Metabolic alterations were analyzed. 1 S patient treated with chemotherapy had a cardiovascular accident. Conclusions: We observed an high gap between surveillance and the active treatments: there is no best choice for every one so we should improve decision-making process and decision aids into the management of CSI patients with TC. [Table: see text]
Significance of zoledronic acid on survival in patients with bone metastases from renal cell carcinoma.
Authors: Fujii Yasuhisa , Yasuda Yosuke , Yuasa Takeshi , Sukegawa Gen , Kitsukawa Shinichi , Urakami Shinji , Yamamoto Shinya , Yonese Junji , Takahashi Shunji , Fukui Iwao
Published: March 2020

e15038

Background: It remains unclear whether zoledronic acid (ZOL) improves overall survival (OS) for renal cell carcinoma (RCC) patients with bone metastases. We retrospectively investigated the clinical benefit of ZOL for OS in RCC patients with bone metastases. Methods: Between 1978 and 2010, 77 patients who had RCC metastatic to bone were treated in our hospital. Of them, 36 were treated with ZOL and their OS was significantly better than that of the other 41 patients (1- and 3-year survival, 84% and 73% versus 49% and 27%, respectively, p<0.001). OS rates were clearly discriminated according to MSKCC model stratification: 3-year survival rates in the favorable, intermediate and poor risk groups were 83% (n=12), 49% (n=45), and 19% (n=20), respectively (p=0.0033). To match characteristics in our retrospective study, we selected 45 patients conforming to MSKCC intermediate risk group criterion. In this cohort, 23 patients received ZOL (ZOL-treated group) whereas the other 22 did not (non-ZOL-treated group). The primary endpoint was OS and the secondary endpoint was the skeletal-related event (SRE) rate defined as the total number of SREs divided by the total years on study. Results: For the cohort of 45 patients, the median OS from diagnosis of bone metastases was 27.2 months. Multivariate analysis showed that low serum calcium (hazard ratio [HR]: 2.58, 95% confidence interval [CI]: 1.31 to 4.69; p=0.0083) and ZOL treatment (HR: 1.89, 95% CI: 1.27 to 2.96; p=0.0013) were independent factors predicting longer survival. The ZOL-treated group had significantly longer OS (1-year survival: 80.8%) than the non-ZOL-treated group (1-year survival: 59.1%, p=0.0034). A difference in OS between the two groups still was present (p=0.012) when the duration of molecular-targeted therapy was excluded from the OS period. Patients in the ZOL-treated group experienced a lower SRE rate (0.87/year) than patients in the non-ZOL-treated group (1.82/year, p=0.0453). In particular, none of the patients in the ZOL-treated group developed spinal compression whereas 6 (28%) in the non-ZOL-treated group did (p=0.0479). Conclusions: The current study indicates that ZOL not only reduces SREs but possibly improves OS in these patients.
Evaluation of parameters for treatment duration of sunitinib in metastatic renal cell carcinoma.
Authors: Kossoff Ellen , Batty Nicolas , Ceacareanu Alice C. , Attwood Kristopher , Miller Dustyn , Rabey Jonathan , Lee Charlene , Ahmad Ahmad , Ebos John M. , Schwaab Thomas , George Saby , Pili Roberto
Published: March 2020

e15042

Background: In metastatic renal cell carcinoma (mRCC), there is a need for predictive indicators for treatment duration (TD) of sunitinib. Our study evaluates parameters that may be associated with TD of sunitinib. Methods: From 01/2007-12/2011, consecutive mRCC patients (pts) were reviewed. Responders (R) were defined as having either complete response (CR) or partial response (PR) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, while non-responders (NR) were defined as having either stable disease (SD) or progressive disease (PD). Long term duration (LTD) was defined as therapy with sunitinib ≥ 18 months (mos). Hazard ratios (HR) and 95% confidence interval (95CI) representing the association between TD and specific parameters were computed with Cox proportional hazard model. Results: After a median follow-up of 9.8 mos (<1 - 63.8) of 128 mRCC pts, 57 (45%) received sunitinib. Responses were CR, PR, SD, PD of 3, 13, 8 and 33 pts, respectively. LTD was observed in 9 pts (21%). Hemoglobin < 12.5 g/dL (p = 0.048), prior nephrectomy (PN) (p = 0.001), prior therapies (p = 0.016), dose reduction (DR) (p = 0.001), an increased skin toxicity (p = 0.025) and low/intermediate (LI) Memorial Sloan-Kettering Cancer Center (MSKCC) risk-groups (p = 0.003) were associated with longer TD and a higher ANC (p < 0.0001) with shorter TD. In the multivariate analysis, PN was the only significant prognostic factor [HR 0.3 (95CI 0.12 -0.72) p = 0.007] that was associated with prolonged TD. Pts with LTD had a lower baseline ANC (p= 0.037), a LI MSKCC (p = 0.026), higher frequency of DR (p = 0.007), increased skin (p = 0.017) and endocrine (p = 0.015) toxicities and an increase of body mass index (BMI) from baseline (p = 0.008). When adjusted for BMI and performance status, results were maintained. Progression free survival (PFS) and overall survival (OS) of pts with LTD were not reached. However, both PFS and OS of R with TD < 18 mos, were 19.5 mos 95CI (3.4 - 27.9). Conclusions: PN, lower baseline ANC, DR, an increase of BMI from baseline, skin and endocrine toxicities were associated with prolonged TD of sunitinib in mRCC. There is a need for prospective studies to develop a predictive TD model in this setting.
Comparative effectiveness of front-line agents in the treatment of metastatic clear cell renal cell carcinoma.
Authors: Haaland Benjamin , Chopra Akhil , Lopes Gilberto de Lima
Published: March 2020

e15045

Background: Based on improved clinical outcomes in randomized controlled clinical trials (RCT) the FDA has approved 4 drugs in the front line treatment of good to intermediate risk metastatic clear cell renal cell carcinoma (RCC). However, there is little if any comparative data to help choose the most effective drug among these agents. Methods: We performed an indirect comparative effectiveness analysis of the pivotal RCTs (Escudier JCO 2009 and 2010, Rini JCO 2010, Motzer JCO 2009, Sternberg JCO 2010, MRCRCC Lancet 1999, Steineck Acta Oncologica 1990, Pyrhonen JCO 1999, Kriegmair Urology 1995) evaluating outcomes with sunitinib (SU), sorafenib (SO), bevacizumab plus interferon alpha (B+I), pazopanib (P), interferon alone (I) and other controls. Progression-free-survival (PFS) was the main endpoint. Other endpoints included response rate (RR) and overall survival (OS). Estimates, confidence intervals, and p-values from analyses that are stratified by risk factors were used throughout if available. A linear mixed effects model with a random effect for each study and known error variances was fit by restricted maximum likelihood and used to obtain indirect estimates. Results: The indirect estimate of the hazard ratio (95% confidence interval; p-value) for PFS for SU vs. B+I is 0.813 (0.624-1.059; p=0.125); for B+I vs. SO is 0.753 (0.497-1.141; p=0.181); for P vs. B+I is 0.963 (0.612-1.518; p=0.874); for SU vs. SO is 0.613 (0.392-0.956; p=0.0311); for SU vs. P is 0.844 (0.521-1.366; p=0.49; for P vs. SO is 0.726 (0.407-1.295; p=0.278)(Figure 1). SU, P, B+I had better PFS than I alone and than other controls, while SO did not. SU had statistically significantly better RR when compared to P, SO and B+I with HR of 0.254, 0.215 and 0.419 (all p<0.05). OS data was not available to compare all agents and may be confounded by cross-over in the trials. Conclusions: Based on PFS, SU, B+I and P are adequate front line options in the treatment of advanced clear cell RCC. As SU had better RR it may be a preferred option for patients with symptoms or large disease burden. SO should not be considered an optimal front line treatment.
CD98hc (SLC3A2), a novel biomarker correlating with grade of malignancy in renal cell cancer.
Authors: Pöttler Marina , Aaitel Andrea , Schmidinger Manuela , Zielinski Christoph , Prager Gerald
Published: March 2020

e15083

Background: In a variety of malignant diseases certain malignant markers either predict treatment response towards systemic therapies or have a prognostic impact for cancer patients. While a variety of such actionable as well as treatable targets have been characterized, although only in certain cancers, in renal cell cancer (RCC) no prognostic markers have so far been identified. Thus, grading according to the S.A. Fuhrman grading system from 1982 is the only prognostic feature and currently widely considered for treatment assessment. Methods: Paraffin-embedded tumor tissue sections derived from clear cell RCCs were immuno-histochemically analyzed for expression of embryonic transmembrane antigen CD98hc (SLC3A2). Expression levels were semi-quantitative analyzed and results were correlated with grade of differentiation, using the widely accepted Fuhrman classification. Results: We found that grade of malignancy of ccRCCs were directly correlated with high CD98hc expression levels. Semi-quantivative analyses revealed that 0 % (0/2) of grade 1 ccRCC, 70.0 % of grade 2 ccRCC (14/20), 86.6 % of grade 3 (26/30) and 100 % of grade 4 (10/10) were CD98hc positive. (p < 0.01, Qui-Quadrat Pearson test, n = 62). In contrast, tumor stage as determined by the WHO TNM system did not correlate with CD98hc levels (p > 0.05). Conclusions: From these data, we conclude that CD98hc is expressed in RCCs, whereby the extent of expression is likely to correlate directly with grade of malignancy. In ccRCCs, CD98hc might represent a novel and reliable marker for more aggressive and less differentiated subtypes.
Clinical outcome and molecular characterization of patients receiving systemic therapy for metastatic sarcomatoid renal cell carcinoma.
Authors: Hsu Joann , Pal Sumanta Kumar , Twardowski Przemyslaw , Carmichael Courtney , Saikia Junmi , Liu Xueli , Wilson Timothy G. , Figlin Robert A. , Jones Jeremy
Published: March 2020

e15084

Background: Sarcomatoid metastatic renal cell carcinoma (mRCC) represents an aggressive subset of disease, and a definitive therapeutic strategy is lacking. Methods: From an institutional database including 270 patients with mRCC, we identified 34 patients with documented sarcomatoid features. Within this cohort, we assessed 21 patients who received systemic therapy. Survival was assessed in the overall cohort and in subgroups divided by clinicopathologic characteristics, including the extent of sarcomatoid features, MSKCC risk criteria, and the nature of systemic therapy given. Available tissue from 11 of these patients has been identified for correlative studies to assess markers of epithelial to mesenchymal transition (EMT). Tissue will be obtained from a cohort of patients matched for age and MSKCC risk status (but lacking a sarcomatoid component) for comparison. Results: Of the 21 patients assessed, 2 patients received chemotherapy, 7 patients received immunotherapy, and 12 patients received targeted agents as their first line treatment. Median overall survival (OS) in the overall cohort was 18.0 months (95%CI 6.9-22.0). By MSKCC status, patients with poor-risk disease had a median OS of 4.7 months, as compared to 20.1 months for patients with intermediate-risk disease (HR 0.02, 95%CI 0.003-0.15; P=0.0001). Survival in subgroups stratified by the Heng criteria will be presented at the meeting. There was no significant difference in survival in patients with sarcomatoid predominant disease (>20%) vs non-predominant disease (HR 0.62, 95%CI 0.23-1.65; P=0.34), nor was there a difference amongst patients who received targeted therapies vs non-targeted therapies (HR 1.0, 95%CI 0.61-1.40; P=0.36). Correlative analyses are ongoing, and will be presented at the meeting. Conclusions: As compared to previous retrospective series (Golshayan et al JCO 2009) and prospective trials (Haas et al Med Oncol 2011) assessing patients with sarcomatoid mRCC, the survival in our cohort was substantially prolonged. Further clinical and translational studies are needed to refine current prognostic schema for this disease, and to define the optimal therapeutic strategy.
Does RECIST-defined progression correlate with lack of further sunitinib (SU) benefit in advanced renal cell carcinoma (aRCC)?
Authors: Teo MinYuen , McDermott Raymond S.
Published: March 2020

e15093

Background: RECIST defined radiographic progression on SU may be confounded by the intermittent dosing schedule and scan timing. Response rates to second line agents are typically lower and of shorter duration We analysed the potential for continued clinical benefit from continuation on Sunitinib following RECIST-defined progression in selected pts . Methods: Our institutional database was reviewed to identify aRCC pts who: 1) received SU, 2) achieved response or stable disease, and 3) had continuation of SU after documentation of RECIST-defined progression. Treatment history was obtained from medical chart review. CT scans were retrospectively assessed by RECIST criteria, pattern of progression was documented. SU cessation reasons were identified. Progression-free survival (PFS), post-progression treatment duration (PPD) and overall survival (OS) estimated by Kaplan Meier method. Results: Of 39 patients (pts) treated with SU between 2006 and 2009, 13 met entry criteria. Median age was 62 years (range: 33 – 66) with 11(85%) males. Eleven (85%) had prior nephrectomy and 4 (31%) had prior immunotherapy. Number of pts with MSKCC good/intermediate/poor risk groups were 5/7/1. Best radiographic response achieved was complete response/partial response/stable disease in two, five and six pts. Median PFS was 16.4 mos (11.8 – 23.8). Seven (54%) had progression of existing lesions while the six developed new lesions. Pts continued on SU as progression was relatively minor and clinical status was maintained. Median PPD was 4.2 months (0.6 – 40.5). Most common reasons for SU cessation were on-going radiographic progression (71%) and toxicity (18%). Only 2 pts stopped SU secondary to clinical deterioration. 62% of pts received subsequent lines of treatment, with half receiving 3rd line therapy. Median OS for the cohort was 31.7 mos. Conclusions: Continuation of treatment with SU following RECIST progression appears feasible and safe with prolonged disease control in selected pts . This approach should be further validated prospectively in a larger patient cohort. In this group, current standards for disease response assessment may underestimate the duration of clinical benefit conferred.
Treatment of carcinoma in situ of the glans penis with topical chemotherapy agents.
Authors: Alnajjar Hussain M , Lam Wayne , Bolgeri Marco , Rees Rowland , Perry Matthew , Watkin Nicholas
Published: March 2020

e15100

Background: To establish the response rate of 5-flurouracil (5-FU) and imiquimod (IQ) in the treatment of penile CIS in a large contemporary series in a supra-network center. The use of topical agents in the treatment of CIS of the penis has been well described in the literature. Previous studies have been limited by small sample size and imprecise end-points. Methods: Retrospective review of all primary and recurrent cases of penile CIS treated with 5-FU and IQ identified from a prospective database over a 10- year period. Therapy was standardised in all cases with application to the lesion for 12 hours every 48 hours for 28 days. 5-FU was the first line therapy and IQ used as second line topical agent. The primary end-point was defined as complete response (CR = resolution of lesion), partial response (PR = lesion reduced in size and or visibility) or no response (NR = no improvement in lesion size and or visibility). The secondary end-points included local toxicity and adverse events. Results: A total of 86 patients were diagnosed with CIS of the penis over the 10-year period. 44/86 (51%) received topical chemotherapy. Mean follow-up was 34 months. The response rates, local toxicity and adverse events were analysed. The overall complete response rate for topical agents was 57% (Table). Conclusions: Topical chemotherapy agents are moderately effective first line therapy in the treatment of penile CIS. Toxicity and adverse events were low with our treatment protocol. The issue of long-term surveillance and assessment of partial responders remains a challenge. Topical chemotherapy should remain a first line treatment option for penile CIS. [Table: see text]