bluuebunny/crossref_metadata_2025 huggingface dataset:
Intensity modulation of chemoimmunotherapy for late stages of liver carcinoma.
Authors: Yu Baofa , Ma ZhenLu , Guan Changjiang , Han Wei , Che Yebin , Fu Qiang ,   Shandong Baofa Cancer Therapeutic Groups
Published: March 2020

e14716

Background: Provenge (Dendreon Co.) is an autologous cellular vaccine and represents a significant milestone for cancer immunotherapy and generates renewed interest in the field. Chemoimmunotherapy as a highly attractive way for cancer treatment has been studied over years but this is not generated a specific powerful immunotherapy yet. Intensity Modulation of Chemoimmunotherapy (IMCIT) is similarly with Provenge function and plays in kill tumor cells and induces patient’s own immunological effect against micro size cancers more than just Introtumoral Chemotherapy(ITCT) alone. Methods: Introtumoral injection of IMCIT into late stages of liver Cancer (447 cases) which is a proprietary therapeutic regimen composed of three components for intensity modulation of chemoimmunotherapy, i.e., an oxidant, a cytotoxic drug and a hapten. Results: After intratumoral injection, coagulate tumor mass for sustained drug release and drug kills tumor cells, a small molecule hapten binds to these antigens and other large carriers for intensity modulation, then autologous tumor antigens released from the dead tumor cells and trigger immune response as a self-vaccination to further boost systemic humoral and cellular immunity for suppression and eradication of tumor recurrence. For single liver tumor, 6 months survival rate for IMCIT 63.03% and ITCT 36.17%(p<0.01), 12 months survival rate for IMCIT 32.77% and ITCT 21.28% (P.0.05);for mutable liver tumors, 6 months survival rate for IMCIT 54.44% and ITCT 20.93%(p<0.01),12 months survival rate for IMCIT 21.11% and ITCT 6.98%(p<0.05). Therefore, more importantly, IMCIT provides a new option for cancer treatment by integrating local chemotherapeutic effect with systemic anti-tumor immunity; cell death induced by chemotherapeutic drugs is a priming event and allows the injected tumor act as its own vaccine. Conclusions: Introtumoral injection of IMCIT is a safe, aggressive and cost-effective clinical treatment for solid tumors. IMCIT displays the following advantages: clinically effective for single and multiple masses liver cancer and minimal side effects and better quality of life; simple and cost-effective treatment and strong intellectual property position..
Totally laparoscopic pancreaticoduodenectomy: Learning curve.
Authors: Khatkov Igor , Tsvirkun Viktor , Izrailov Roman , Tiutiunnik Pavel
Published: March 2020

e14717

Background: Laparoscopic pancreaticoduodenectomy (LPDE) has become increasingly popular in the world and now is considered to be a technically feasible and safe procedure for patients with tumors of the head of the pancreas and the periampullare area. At the same time, according to the literature data, a lot of surgeons stop performing totally laparoscopic pancreaticoduodenectomy (TLPDE) after 5 – 15 procedures because of the difficulties of learning curve. Aim of thew study: to evaluate the learning curve of totally laparoscopic pancreaticoduodenectomy. Methods: The data of 43 patients who were planed for LPDE during 5 year were analyzed. All the procedures were performed by one surgical team. 35 patients underwent totally laparoscopic pancreaticoduodenectomy (TLPDE). For 8 patients the procedures were palliative or converted. Patients were divided in three groups. Group A, B and C – 12;12;11 patients respectively. Operative time, intraoperative blood loss and the level of postoperative morbidity were examined. Results: Among the 43 patients, 35 patients underwent TLPDE. The conversion rate was in the group A - 33% (4 patients), group B – 33%(4 patients) and group C – no conversions. Mean operative time of TLPDE for the group A was - 542min; group B – 542min and group C less than 360min, minimally - 280). Mean blood loss was for group A - 683ml, group B – 612ml and group C 250ml. Total level of all kinds of postoperative morbidity was: group A - 66,5%, group B – 65,5% and group C – 36,0%. Postoperative mortality was: group A - 8,3%(one of the patients died from insufficiency of the pancreatojejenostomy, another – because of acute heart failure without any surgical complications); group B – 0% and group C - 0%. Conclusions: The results of TLPDE become significantly better after 25 procedures. The most difficult and potentially dangerous for intra and postoperative complications were: dissection along superior mesenteric and portal vein and suturing of pancreaticojejuno anastomosis. Performing TLPDE by the same team, including nurses, is a very important factor for quick learning curve and safety.
I-131-lipiodol therapy in local disease control and survival in patients with advanced hepatocellular carcinoma: An observational study.
Authors: Kallur Kumar G. , Aditi Bhatt , Prashanth Gothlu Ramachandra , Sridhar Papaiah Susheela , Indushekar Subbanna , Govindarajan Mallarajapatna , Nagaraj Kanakapura Ramanna , Gopinath Kodaganur Srinivasachar , Diwakar Ravi B , Patil Shekhar , S Ramesh Bilimagga , Somorat Bhattacharjee , Ajaikumar Basavalinga S.
Published: March 2020

e14721

Background: In patients with Locally advanced/metastatic HCC, the median survival is 3 months. Most of these patients have altered liver functions which makes them unsuitable for any therapy. In this exploratory study we aim to test the effectiveness of I-131-lipiodol in prolonging survival in these patients. Methods: 15 patients with locally advanced HCC (unresectable) and metastatic HCC with altered liver functions (CHILDS B and C) were given I-131-lipiodol. Patients had received prior chemotherapy, prior TACE therapy, prior sorafenib and had treatment refractory progressive disease. We compared effects of I-131-Lipiodol in prolonging survival beyond three months in these patients. We performed a non parametric one sample kolmogorov Smirnov test comparing survival with I-131-lipiodol to an average 90 days survival reported in patients with advanced HCC. Results: Survival ranged from 46 to 417 days with a median survival of 144 days. However one sample test showed significant improvement in survival with I-131-lipiodol therapy compared to standard of care (z = 1.4, p = 0.04). Conclusions: I-131-lipiodol is a useful local therapy in management of patients with advanced HCC, randomized controlled trials are needed to validate its findings in adjuvant and palliative settings.
Comparison of efficacy between irinotecan and paclitaxel monotherapy as second- or third-line chemotherapy after S-1 containing regimen for advanced or recurrent gastric cancer.
Authors: Kusumoto Tetsuya , Oki Eiji , Hiroshige Shoji , Hashimoto Kenkichi , Suzuki Kousuke , Hirashita Teijiro , Matsumoto Toshifumi , Takeuchi Hideya , Matsuura Hiroshi , Muto Yoichi , Maehara Yoshihiko
Published: March 2020

e14722

Background: S-1 is effective and clinically important agent in the initial chemotherapy against advanced or recurrent gastric cancer (ARGC) in Asia. Although several prospective studies on the second-line chemotherapy for ARGC are currently in progress in Japan, the sufficient investigation on the proposition has not been made. We assessed here the clinical efficacy of irinotecan (CPT-11) and paclitaxel (PTX) as the second or thirdline chemotherapeutic agents following the S-1 based treatment, as those has been frequently used in practice. Methods: We conducted the retrospective review of the data of 30 patients with unresectable ARGC who received CPT-11 or PTX monotherapy after administration of S-1 as prior treatment. Each 15 patients were given chemotherapy including CPT-11 and PTX monotherapy treatments, after S-1 containing regimens, as second or third line treatments. The objective response, adverse events, progression-free survival (PFS), and overall survival (OS) were compared between CPT-11 and PTX monotherapy groups. Results: The similar data of the overall response rates (ORRs) were obtained between two groups. Survival data showed that the MST was 329 days and the median PFS was 220 days for the administration of CPT-11, compared with 297 days and 132 days in PTX group from the beginning of these drugs administration, were not significantly different. The OS was 707 days in CPT-11 group, compared with 751 days in PTX group, were not significantly different. Conclusions: There is no order of priority of regimens including CPT-11 or PTX after S-1 containing chemotherapy treatments. We believe that both awareness of the next line chemotherapy and the selection of drugs were important of survival prolongation for patients with ARGC.
Biliary tract cancer in a Moroccan medical oncology unit.
Authors: Bouyahia Nezar , Brahmi Sami Aziz , Chad Amine Mohammed , Daoudi Khaoula , Hijri Fatima Zahra , Ibrahimi Adil , EL Haoudi Khalid , Maazaz Khalid , Arifi Samia , Nawfel Mellas , El Mesbahi Omar
Published: March 2020

e14726

Background: Biliary tract cancers (BTC) are relatively rare (3% of digestive cancers), they mainly affect older women and are located in the gallbladder in about 70% of the cases. Methods: In this retrospective study, we reviewed 63 cases of BTC admitted in the medical oncology unit of HASSAN II university center between January 2007 and December 2011. The aim of this study is to define epidemiologic, diagnostic and therapeutic aspects of this disease in a Moroccan population. Results: In our study, BTC account for 4,9% of digestive cancers. The mean age of our patients was 58,2 years ranged from 32 to 81 years, female gender represent 69%. The tumors were located in the gallbladder (GB) in 70% of the cases divided into adenocarcinoma (79%) and squamous cell carcinoma (21%). The other locations were hilar cholangiocarcinoma (24%) and intrahepatic cholangiocarcinoma (6%). Magnetic resonance cholangiographic was performed (n=15) and suspected cancer in all cases. Incidental finding of GB cancer at surgery was recorded in 21 patients: intraoperatively in 8 cases or after pathological study in 13 cases. Staging of the disease was divided into localized stage (7%), locally advanced stage (13%) and metastatic stage (80%). A complete surgery in GB cancer was performed in 13 patients, a palliative surgery was done in 20 patients: cholecystectomy (n=7) and biliary drainage (n=13). For metastatic patients (n=44), a palliative chemotherapy was administred as following: combination of cisplatin and gemcitabin (n=18), gemcitabin (n=7), combination of cisplatin and 5 fluoro uracile (n=5), combination of oxaliplatin and gemcitabin (n=3), capecitabine (n=3), FUFOL Mayo clinic (n=2) and combination of capecitabine and oxaliplatin (n=2). While 9% of the patients received supportive care because of their comorbidities and the deterioration of the performans status and liver blood tests. Conclusions: Because of the silent evolution of BTC, the diagnosis is therefore delayed, the prognosis is poor and treatment is usually palliative. Our results are consistent with those of the literature concerning the epidemiological finding and diagnosis aspects.A multidisciplinary approach is recommended to improve the prognosis of patients with BTC.
Prognosis and patterns of failure after curative pancreaticoduodenectomy for early-stage ampullary adenocarcinomas.
Authors: Ribeiro Adriana Regina G. , Silva Milton Jose B , Costa Wilson Luiz , Maia Joyce Maria L. , Padua Fernando Vidigal , Diniz Alessandro Landskron , Ribeiro Heber Salvador de Castro , Coimbra Felipe José Fernandez , Mello Celso Lopes , Begnami Maria D. , Dettino Aldo A. , Formiga Maria Nirvana , Pereira Augusto Akikubo Rodrigues , Fanelli Marcello Ferretti
Published: March 2020

e14728

Background: Ampullary cancer (AC) is a rare malignancy. There is no consensus about the role of adjuvant radiotherapy and chemotherapy, mainly for early-stage tumors. Methods: Between 2007 and 2012 we performed a retrospective analysis of patients with AC that underwent a pancreaticoduodenectomy (PD) with curative intent in our institution. Results: Twenty-four patients underwent (PD), (M:F=13:11), median age was 63 (range35-83), 87% had R0 resection, median of resected lymph-nodes was 8.5 (range 2-30), 29% had positive lymph-nodes, 46% had perineural invasion, 21% had vascular invasion, 29% had lymphatic invasion, 50% had tumors > 2 cm, 54% had moderately differentiated tumors. AJCC stage pathologic grouping was: I=37,5%, II=29%, III=33%; Median follow-up was 27 months, median progression free survival was 29 months and median overall survival was 101 months. Only lymph-node status was independent prognostic factor for disease free survival on multivariate analysis (p=0,045, HR: 7,8). Among patients with early-stage tumors (n=13), only one received adjuvant therapy. The relapse rate was 23% and 50%, for stage I and IIa tumors, respectively. Among the recurrences, 80% of relapses were distant metastasis without local relapse. In patients with stage IIb and III tumors (n=11), 63,6% received adjuvant treatment (57% chemotherapy and 43% radiochemotherapy). The relapse rate was 100% and 75%, respectively, and 66% of these relapses were distant metastasis without local relapse. 75% of patients who had local recurrence had tumors in stage IIb or III. Conclusions: Our study shows a high disease relapse rate in well-operated patients, even in early-stage tumors, with no nodal involvement, mainly with distant disease. The majority of patients who had local relapses had a more advanced stage and systemic relapses associated. This information can help guide decisions on the choice of adjuvant therapy.
Serial application and development of a new treatment paradigm for pancreatic cancer.
Authors: Stega Jeanetta , Bruckner Howard , Schwartz Myron E. , Hirschfeld Azriel
Published: March 2020

e14729

Background: New "paradigm driven" treatments (rx) “doubled” phase II survival (S) for 250 pts (ASCO, Bruckner 01, 04, 05, 08, 11). Addition or repartnering of drugs which failed trials or individual use (all in cost saving doses) produced synergism and reversed drug resistance. New rxs and safer doses were rapidly discovered by application of game theory to models of rxs, testing human pancreatic ca (PC) in vitro. Some measures of response (R) and extreme drug resistance as selection criteria were downgraded. Priority went to disease specific in vitro “R” rate (RR), increased number of simultaneously impacted drugs, activity at low doses and avoiding both duplication of targeting and antagonism. Clinical objectives now included wider eligibility, safety and 50% cost saving. Methods: With prospective registration and IRB consent rxs evolved: GFLIP>GFLIO>GFLIO -/+ docetaxel (D) -/+Mitoymcin-C (M). GFLIO and on progression GFLIO-D-M was the rx for 107 new tests (biopsy high risk ductal PC, PS 0-2, no active obstruction). Pts: unresectable (U) or metastatic (IV), G1; failing prior rx with some rx drugs, G2 or resected PC +/- margin G3 (G1, G2 all with progressive disease). Serial findings were compared (ASCO 05, 08). Results: OS for U/IV (G1 and G2) adding D-MMC to GFLIO was: n=70, at 24 mos 22/38 (S) (61%) alive; at 36 mos 8/20 (40%) vs prior 32 and 21%. Adjuvant, G3: n=37 at 18 mos 15, (50%) PFS, 28/30 S; alive S at 24 mos 10, (43%) PFS 20/23 S; at 36 mos 6, 40% PFS 14/15 S. Cumulative RR depending on R criteria meet models for 40-60% R per treatment with benefit rx (61-84%). Rxs were safe, no induction hospital AEs. Conclusions: This 350 pt prospective Phase II further supports testing of low dose rx; use of D-MMC as additions and adjuvant GFLIO rx (see Reni, Fine, Isakoff). The pts large N and long OS have testworthy practice changing: consent, reimbursement and trial (algorithm) “design” implications. Cost of drugs per unit of survival (S) can often be saved, safely while possibly improving QL and OS. Palliative applications of dose intensity, drug efficacy, tumor resistance and one drug at a time testing as rx concepts are (sometimes) questionable. improving QL and OS.
Efficacy and tolerability of biweekly gemcitabine plus cisplatin (GEMCIS) or gemcitabine plus paclitaxel (GEMPAC) as neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder.
Authors: Karaoglu Aziz , Nieh Peter , Canter Daniel , Master Viraj A. , Carthon Bradley , Harris Wayne , Shelton Joseph , Rossi Peter John , Jani Ashesh B. , Khan Mohammad K. , Osunkoya Adeboya O. , Ogan Ken , Pattaras John , Ritenour Chad , Kucuk Omer
Published: March 2020

e15006

Background: Cisplatin, gemcitabine and paclitaxel are active chemotherapeutic agents for invasive urothelial carcinoma of the bladder (UCB). Biweekly administration of gemcitabine in combination with cisplatin (GEMCIS) or paclitaxel (GEMPAC) has been reported to have better tolerability than other schedules. Methods: Between 2009- 2011, we have treated 34 patients (median age 69 years, range 56-85) with muscle invasive UCB using gemcitabine (1500 mg/m2) in combination with cisplatin (50 mg/m2) or paclitaxel (150 mg/m2) given on days 1 and 15, every 4 weeks, for 3 cycles prior to radical cystectomy (RC) with bilateral pelvic lymph node dissection and urinary diversion. Patients deemed unsuitable for GEMCIS due to old age, frailty, multiple comorbidities or poor renal function received GEMPAC (n=9); all others received GEMCIS (n=25). Results: Clinical staging revealed T2, T3 and T4 disease in 20 (58.8 %), 8 (23.5 %) and 6 (17.6 %) patients, respectively. Patients were re-evaluated after 2 cycles with MRI or CT scans, which showed improvement in 21 (61.8 %) patients, no change in 12 (35.3 %) and progression in 1 patient (2.9%). Pathologic examination of the surgical specimens revealed T0, Tis, T2, T3 and T4 disease in 8 (23.5 %), 6 (17.6 %), 10 (29.4 %), 6 (17.6 %) and 4 (11.8 %) patients, respectively. Overall, pathologic downstaging was observed in 41.1% of patients. In the GEMCIS group, 12 patients (48%) had pT0 or pTis; in the GEMPAC group, 2 pts (22.2%) had pT0 disease. The most commonly observed toxicities are tabulated below. Conclusions: Biweekly GEMCIS or GEMPAC regimens were active and exceptionally well tolerated in the neoadjuvant setting in patients with muscle invasive UCB, producing favorable pathologic outcomes in an initial cohort of patients. To our knowledge, these data represent the first report detailing clinical results with these regimens in this setting. [Table: see text]
Biomarker profiling of bladder cancer patients undergoing radical cystectomy: Relevance of thrombotic and inflammatory processes.
Authors: Clark Melanie , Quek Marcus Lee , Kahn Daniel , Hoppensteadt Debra , Cunanan Josephine , Fareed Jawed
Published: March 2020

e15008

Background: Postsurgical thrombosis represents a serious comorbidity in bladder cancer. Inflammation and hemostatic activation mediators contribute to thrombotic pathogenesis. Our study profiles biomarkers antiphospholipid antibody, IgG subtype (APA), procoagulant microparticles (MP) and antiglycosaminoglycan antibody (AGA). Protein and peptide biomarkers were profiled using SELDI-TOF mass spectrometry. Methods: This study was done retrospectively using an IRB approved protocol with 134 baseline serum samples collected from patients undergoing radical cystectomy. The samples were banked at -70C and thawed prior to analysis. The APA were measured with an ELISA for IgG specific antibodies (American diagnostica, Stanford CT). The MP were measured using an anexin capture chromogenic substrate to quantify functional procoagulant activities (Hyphen Biomedical, Paris France). The AGA were measured with a commercially available method with a polysulfonate polymer capture probe for the antibodies (GTI Madison, WI). The proteomic profile was analyzed on a GoldChip in the range of 5-150 kDa. Results: Although a wide scatter in values was noted in the test samples, they exhibited a higher prevalence of elevated biomarkers compared to normal. The average MP value was 3.1 5.8 (range 0.1-34.6nM) with 26 of 134 samples above normal. The average APA value was 6.7 11 (range 4-65nM) with 32 above normal. The average AGA value was 0.22 0.09 (range .01-.8OD) with 10 above normal. The SELDI analysis showed unique biomarkers in the area of 11-12kDa, 15.1-15.4kDa, and 15.8-16.2kDa. Conclusions: The biomarker upregulation suggests that bladder cancer patients have subclinical activation of thrombotic and inflammatory processes. The MP may be generated in cellular damage whereas the APA and AGA suggest vascular endothelial damage and activation. The unique proteomic biomarkers in these patients suggest endogenous protease activation. A clinical correlation in the subset with higher markers may provide insight into the biomarker role in prognosis, risk stratification and treatment of bladder cancer.
Cell adhesion molecules in the progression of bladder cancer: The important role of cadherins and catenins.
Authors: Torres-Galea Patricia , Stoemmer Peter E.
Published: March 2020

e15013

Background: Cell-adhesion- molecules (CAMs) are important factors in the maintenance of normal tissue structure, morphology, aggressivity and invasivity of tumors. Few CAMs, such as E-cadherin and its substitution by N-cadherin in the progression of urothelial neoplasia are wellknown. CAMs, such as cadherin P, catenins alpha and beta are much less known..We analysed their distribution in tumors of different patients and in respect to its architecture. Methods: 100 FFPE blocks of superficial ( pTa/ pTis and pT1) and myoinvasive (>pT1) carcinomas G1-3 were analysed by semiquantitative IHC- . Antibodies: E-Cadherin, P-Cadherin and Catenin Beta: Thermo Scientific, Freemont CA,USA . N-Cadherin Lab Vision, UK, Ltd, Catenin Alpha and H-CAM (CD44) Novocastra Laboratories Ltd. Results: E-Cadherin: Normal and reactive, inflammatory urothelium and dysplasia express high membranous E-cadherin-concentrations. High grade (HG) in-situ-carcinomas:discontinously ,intensively reacting cellmembranes; myoinvasive HG carcinomas lose their E-cadherin membranous component but show low diffuse intracytoplasmic reaction. N-Cadherin: in basal cells but not in normal transitional cells and LG dysplasia. High expression in HG dysplasia and deep invasive carcinomas, HG. P-cadherin:normal urothelium, as well as papillary LG and HG and CIS show an extensive membranous expression. Catenin alpha: high expression in pTa/pT1 LG tumors; low expression in myoinvasive carcinomas. Catenin beta: high membranous expression in normal and dysplastic urothelium as well as in in pTa LG tumors; low membranous cytoplasmic and intranuclear expression in myoinvasive carcinomas and HG tumors. Transition of beta-catenin from cellmembrane to nucleus in neoplasms was not visible Conclusions: E-Cadherin to N-Cadherin shift in the EMT destabilize tumorcells for CAMs, enabling by this the connection to fibrous tissues and augmenting the invasive potential. Catenins alpha and beta: strong prognosticators of progression and recidives; as they are integral parts of E-cadherin, they disappear together with E-cadherin in invasive tumor cell complexes.
Prognostic implications of perineural invasion following radical cystectomy for urothelial carcinoma.
Authors: Rao Manoj , Vellos Ted , Barkan Guliz , Gupta Gopal Nand , Flanigan Robert Charles , Quek Marcus Lee
Published: March 2020

e15014

Background: Perineural invasion(PNI) with urothelial carcinoma may be identified in radical cystectomy specimens, and its prognostic significance is controversial. We sought to determine the incidence and prognostic implications of PNI in a cohort of patients undergoing radical cystectomy for primary bladder cancer. Methods: From January 1996 to June 2011, 440 patients underwent radical cystectomy for urothelial bladder cancer with curative intent. Presence of PNI was determined in the cystectomy specimens, in addition to other histopathologic variables (grade, stage, surgical margins, lymphovascular invasion, concomitant variant secondary histologic subtypes, and presence of carcinoma-in-situ). Recurrence and survival data were analyzed to determine the prognostic significance of PNI in this cohort. Results: PNI was identified in 101 patients (23%) in our series. Those with extravesical primary tumors (61/128, 48%) and node-positive disease (34/86, 40%) were more likely to have PNI than organ-confined tumors (<pT2; 10/183, 5%) (p<0.001). Median follow-up was 2 years (range: 0.1 to 12.5 years). Compared to those with no evidence of PNI, recurrence-free survival was worse in the PNI-positive extravesical (p=0.01) and node-positive (p=0.02) tumors. Overall survival was also worse for PNI-positive patients (p<0.001). On multivariate analysis, PNI was an independent risk factor for recurrence after radical cystectomy (p=0.01, RR=2.8: 95% CI 2.0-10.0). In the setting of PNI, adjuvant chemotherapy significantly improved overall survival(p=0.01). When analyzing PNI and lymphovascular invasion(LVI), there appears to be a worse recurrence-free survival for those who have both PNI and LVI than those with either alone(p<0.001). Conclusions: PNI with urothelial carcinoma may be associated with a worse prognosis, especially for extravesical and node-positive disease following radical cystectomy. Adjuvant chemotherapy may benefit those patients who have PNI. Patients who have both PNI and LVI may be at higher risk for disease recurrence.
Neoadjuvant cisplatin/gemcitabine chemotherapy for muscle invasive bladder carcinoma: A single institution experience.
Authors: Kalachand Roshni Deepa , McDonnell Felicity , McHugh Deaglan , McDermott Raymond
Published: March 2020

e15016

Background: Neoadjuvant chemotherapy (NAC) with MVAC has been shown to improve overall survival in patients with muscle invasive transitional cell carcinoma of the bladder (MIBC), with pathological complete response (pCR) correlating with a survival benefit. Despite the lack of randomized data for cisplatin/gemcitabine (GC) in the neoadjuvant setting, it is commonly used in clinical practice, given its favorable toxicity profile and comparable efficacy to MVAC in the context of metastatic disease. Methods: Data was retrospectively obtained on 93 patients with T2-T4, N0-2 M0 MIBC treated with curative intent in our institution between 2005-2011. Characteristics of patients treated with GC NAC, along with treatment tolerance and outcomes, were collected. Results: Of 93 patients, 27% (n=25) were treated with GC NAC. Median age was 66 (range 49-81). 88% (n=22) of patients were clinical stage T3/4 and/or N1/2. 68% of patients received 28-day cycles of GC, with 32% receiving 21-day cycles of GC. One patient had split cisplatin dosing. 91% and 82% of planned cisplatin and gemcitabine were delivered, respectively. There were no treatment-related deaths. On completion of NAC, 52% (n=13) of patients underwent radical cystectomy, of whom 38% (n=5) achieved a pCR, and 62% (n=8) were downstaged to non-muscle invasive bladder cancer (nMIBC). Definitive chemoradiotherapy was used in 20% (n=5) of patients, whilst 12% (n=3) had no radical treatment due to progressive disease (n=2), or to a decline in ECOG performance status (n=1). Amongst patients without radical cystectomy, 12% (n=3) of patients achieved a biopsy-proven clinical complete response (cCR). In the intent-to-treat population, median disease-free survival was 32 months, and median overall survival 38.8 months. All patients with a pCR, cCR, or downstaging to nMIBC (n=12), were alive at a median follow-up of 16 months (3.9 – 49.1 months), although 1 patient had relapsed. Conclusions: GC is a well-tolerated regimen in the neoadjuvant treatment of MIBC, with a pCR rate comparable to that reported with MVAC. Our findings support the use of GC in the neoadjuvant treatment of MIBC.
The effect of neoadjuvant chemotherapy on pathologic downstaging and survival for patients with muscle-invasive bladder cancer with mixed histological features.
Authors: Lin James , Holder Dara Denise , Whalen Michael , Hruby Gregory , DeCastro Guarionex , McKiernan James M.
Published: March 2020

e15019

Background: Urothelial carcinoma of the bladder (UCB) with mixed histological features (MH) is thought to portend a worse prognosis when compared to pure UC, based on reports of decreased survival for pure non-UC tumors. While patients with muscle-invasive UCB have been shown to derive a survival benefit from treatment with neoadjuvant chemotherapy (NC), the response of patients with MH is unclear. We sought to examine the pathologic and clinical outcomes of treatment with NC of patients with MH versus those with pure UC. Methods: Between 1990-2011, 318 patients were identified with clinical stage T2-T4a, N0-Nx, M0-Mx UCB who had either NC (+/- radical cystectomy) (n=67) or radical cystectomy (RC) alone (n=251). Among those given NC, 58% received methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and 24% received gemcitabine/cisplatin. 265 patients had pure UC and 53 patients had MH, defined as UC with concomitant squamous or glandular differentiation on final pathology (biopsy histology used if pT0 or RC not performed). Endpoints included downstaging to pT0 and overall survival. Multivariable Cox regression was used to estimate the effect of histological type (MH vs. pure UC) on all-cause mortality within each treatment arm (NC vs. RC only) and to test for treatment-by-histological type interaction. Results: The rate of downstaging to pT0 was significantly higher in NC treated patients (34.3%) compared to those with RC alone (4.4%, p<0.01). When stratified by histology, downstaging to pT0 was not significantly different for those treated with NC (37.0% for pure UC vs. 23.1% for MH, p=0.34). After adjusting for age, pathologic stage, and positive surgical margins on multivariate Cox regression, there was no difference in survival outcome for those with MH vs. pure UC (HR=1.5, p=0.5), nor for those treated with NC vs. RC only (HR=2.8, p=0.1). Conclusions: Prior evidence on the benefits of NC for patients with MH is mixed, but our data suggest that there is improvement in rate of pT0 on final pathology in those treated with NC, regardless of histology. As NC is not detrimental to the overall survival of MH patients, its administration should be continued.
Bilateral testicular germ cell tumors (TGCT) prevalence: The 24-year-long single-center experience.
Authors: Gamulin Marija , Grgic Mislav , Jajac Brucic Lana
Published: March 2020

e15031

Background: Theetiology andreliable biomarkers for the risk of bilateral TGCT are still under investigation. Long-term relapse risks of up to 20 years after the therapy in contralateral testes demand a specific model of surveillance. Due to the rarity of the tumor type, reports of national experiences of bilateral TGCT are of a crucial significance for a future global database. Methods: The study was conducted during the treatment of 1 823 patients with TGCT in a single center from 1987-2011. Their mean age was 24 years at the time of diagnosis. Results: Out of 1 823 patients diagnosed with TGCT, 33 developed the bilateral disease (1.81%), 11 of them had synchronous tumors (33%). In the rest of patients the second testicular tumor was diagnosed 1 to 17 years after the initial diagnosis. The mean age of patients with bilateral TGCT was 28. According to the histological type: 11 were seminoma, 14 non-seminoma and 8 mixed seminoma and non-seminoma. Seven patients with bilateral tumor had a seminoma component at initial diagnosis. Compared to 5 patients out of 11 with synchronous tumor, the yolk sac component was detected only in 2 out of 22 metachronous patients. Conclusions: The presented findings of bilateral TGCT prevalence (1.8%) are in concordance with similar previous studies. As this type of tumor may be effectively treated, the risk assessment of metachronous tumor development should in future be facilitated by new biomarkers based on omics techniques. Thus, the investigation of karyotyping, c-KIT and transcriptome specificities will contribute to elucidation which pathways contribute to germ cell neoplasms. The stem cell markers for pluripotency maintenance may in future become potential diagnostic markers used as predictors for metastatic germ cell tumors. The development of a global database on these rare tumors will be of a crucial importance.
Over 100 cases of zero-ischemia robotic/laparoscopic partial nephrectomy: Is global renal ischemia necessary?
Authors: Leslie Scott , Abreu Andre Luis de Castro , Lee Dennis J , Berger Andre K , Goh Alvin , Ahmadi Hamed , Bruins Harman Maxim , Ukimura Osamu , Aron Monish , Desai Mihir , Gill Inderbir S
Published: March 2020

e15060

Background: We report peri-operative and short-term outcomes of a novel technique of zero-ischemia robotic and laparoscopic partial nephrectomy (PN) for renal masses. Methods: From March 2010 to July 2011, 100 zero-ischemia robotic (n=40) and laparoscopic (n=60) PN were performed at our institution. The technique consists of performing micro-dissection of tertiary or higher-order renal arterial branches to super-selectively devascularize the tumor and surrounding parenchyma. Blood flow continues uninterrupted to the remainder of the kidney. As such, PN is performed without hilar cross-clamping. The procedure was offered to all-comers regardless of the tumor complexity or renovascular anatomy. Results: Median patient age was 59 years, tumor size was 3cm (0.9-13.6), baseline serum creatinine (SCr) was 1 mg/dl (0.5-2.6), and estimated glomerular filtration rate (eGFR) was 73 ml/min per 1.73m2 (24-149). 9 patients had a solitary kidney and 8 patients had multiple ipsilateral tumors. Overall, 70% of tumors were complex: central (43%), completely intra-renal (23%), cT1b >4cm (21%), and hilar (19%). Median (range) RENAL, PADUA and C-Index scores were 8 (4-11), 9 (6-13), 2.2 (0.5 c 13.2), respectively. Warm ischemia time was zero, median operative time was 275 min (126-534), estimated blood loss was 200cc, percent of kidney excised was 20 (5-70) and hospital stay was 4 days (2-20). There were 13 complications in 12 patients, with major complications, Clavien grade ≥3, in 4 patients. Histology confirmed malignancy in 80% of tumors. All surgical margins were negative for cancer. There were no significant difference for median percent change in SCr, 0 mg/dl (-31 to 215), and eGFR, -1 (-74 to 53), at discharge. In 65 patients with more than 2 months (median 219 days) follow up data available, median percent change in SCr and eGFR were 18 (-31 to 154), p<.001 and -18 (-66 t0 53), p<.001, respectively. 1 patient developed pulmonary metastases at 1 year follow up. Conclusions: Zero-ischemia robotic/laparoscopic PN without hilar clamping is feasible and safe. It could be performed even in the setting of complex tumors and various vascular anatomy scenarios. Eliminating global renal ischemia now appears achievable.
The effect of continuing therapy for more than one course and CRP level on PFS and OS in the general practice of sunitinib therapy in Japanese patients with metastatic renal cancer.
Authors: Takayama Hitoshi , Kawashima Atsunari , Arai Yasuyuki , Nin Mikio , Tanigawa Go , Yasunaga Yutaka , Nomura Hironori , Mukai Masatoshi , Yoshioka Toshiaki , Uemura Motohide , Nakai Yasutomo , Nishimura Kazuo , Tsujimura Akira , Nonomura Norio ,   Osaka Renal Cell Carcinoma Clinical Study
Published: March 2020

e15069

Background: Sunitinib is a multikinase inhibitor used as first- and second-line treatment of metastatic renal cell carcinoma (mRCC). However, there are few reports on the efficacy and adverse events (AE) profile of sunitinib in general practice with Japanese patients. We examined clinical outcomes of sunitinib therapy in a multi-institutional study. Methods: A study population of 98 mRCC patients was eligible for this investigation. Clinical outcomes were evaluated according to clinical features and duration of therapy. Results: he most frequent grade 3/4 laboratory AE were decreased platelet (30.6%) and white blood cell (20.4%) counts. Treatment was discontinued in 20 patients (32.8%) initially receiving a 50-mg/day dose within only one course, and only 2 patients (3.3%) who were initially medicated with 50 mg/day could continue this oral dose. Median PFS time was 2.3 months in patients treated for only one course and 10.8 months in patients treated for more than one course (P < 0.0001). Multivariate analysis showed that duration of treatment, regardless of initial sunitinib dose (50 mg/day or <50 mg/day) was significantly associated with both PFS (HR: 0.120, 95% CI: 0.049-0.294, P < 0.001) and OS (HR: 0.196, 95% CI: 0.082-0.472, P < 0.001). Moreover, C-reactive protein level was significantly associated with PFS and OS times. Conclusions: Sunitinib therapy of 50 mg/day might be an overdose in Japanese patients. Continuing therapy for more than one course and CRP level were very important in the prolongation of PFS and OS times.
External validation of a sunitinib prognostic nomogram in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Yu Changhong , Kattan Michael W. , Hutson Thomas E. , Hudes Gary R. , Yuan Jinyu , Valota Olga , Motzer Robert John
Published: March 2020

e15070

Background: A nomogram was previously developed from pretreatment clinical features to predict the probability of achieving 12-month progression-free survival (PFS) with sunitinib in treatment (Tx)-naïve mRCC pts from a randomized, phase 3 trial (Cancer 2008;113:1552). Here, validation and update of this nomogram using pts from a phase 2 sunitinib mRCC study (Renal EFFECT Trial) is reported, as is evaluation of its usefulness for clinical decision making. Methods: The Tx-naïve mRCC pts included in the current analysis were randomized 1:1 to sunitinib 50 mg/d on a 4-weeks-on-2-weeks-off schedule (Schedule 4/2; n=146) or 37.5 mg/d on a continuous daily dosing (CDD) schedule (n=146). The variables included in the prior nomogram and used here for validation purposes were corrected serum calcium, number of metastatic sites, hemoglobin, prior nephrectomy, presence of lung and liver metastases, ECOG performance status, thrombocytosis, time from diagnosis to treatment, alkaline phosphatase, and lactate dehydrogenase. The nomogram was updated by removing prior nephrectomy as a variable, including baseline neutrophils and presence of bone metastases, and replacing thrombocytosis with baseline platelets. Validation of the existing and updated nomograms consisted of quantification of the discrimination with the concordance index. A decision curve analysis was used to examine whether this prediction model is useful for medical decision making. Results: With comparable pt characteristics and no significant difference in PFS (8.5 vs. 7.0 months; P=0.070) between the Schedule 4/2 and CDD arms of the phase 2 trial, the combined pt population (N=292) was used to validate the existing nomogram. The overall concordance index was 0.615. Based on the decision curve analysis, the existing nomogram has clinical utility when the probability of 12-month PFS exceeds 60%. Using Schedule 4/2 pts only, the concordance index was 0.594 for the updated nomogram; however, its utility showed more variability. Conclusions: The sunitinib nomogram has been validated in a similar pt cohort; however, its clinical utility may be limited and more research is needed to refine the tool further.
Translocation renal cell carcinomas: An evolving entity.
Authors: Power Derek Gerard , Battley Jodie E , McCarthy Aoife , Brady Claire , Sweeney John P. , Fleming Stewart , Mayer Nicholas J. , Bambury Richard Martin
Published: March 2020

e15078

Background: Translocation renal cell carcinomas (tRCCs) are a novel, rare and distinct clinicopathological entity. The term refers to RCCs with overexpression of transcription factor E3 (TFE3) due to translocation involving the Xp11 locus or less commonly with overexpression of transcription factor EB (TFEB) due to a t(6:11) translocation. In children it is estimated that these tumours account for 40% of RCCs but in adults this proportion is estimated to be 1-4%. These neoplasms are only recently recognised and outcome data are premature. We report 2 cases of tRCC in an Irish regional cancer centre and describe clinicopathological characteristics and early outcome. Methods: : Approximately 70 new cases of RCC are referred to our centre annually. Recently, 2 renal cell carcinomas were suspected to be tRCCs on morphology and immunohistochemical(IHC) features (RCC+/CK7-/EMA-). Using IHC we tested for expression of TFE3 and TFEB. Results: : Both tumours were tRCCs. The first case was a 74 year old lady who presented with right upper quadrant pain and had a 9cm right renal mass with no metastatic disease on CT imaging. Radical nephrectomy was performed and histology revealed a pT3aN2, Fuhrman grade 4 RCC with mixed clear cell and papillary architecture. IHC for TFE3 showed focal nuclear positivity consistent with an Xp11 translocation RCC. She relapsed 9 months later with local recurrence, retroperitoneal adenopathy and lung metastases. She commenced sunitinib and response assessment is pending. The 2nd case was a 46 year old man with an incidental finding of a right renal mass on ultrasound abdomen. Staging CT revealed no metastatic disease and he underwent laparoscopic nephrectomy. Histology revealed a pT1aNx, Fuhrman grade 3 renal cell carcinoma with predominantly alveolar architecture and focal papillary and microcystic areas. IHC for TFEB was positive consistent with a t6:11 translocation RCC. He remains disease free 9 months post surgery. Conclusions: We report 2 new cases of this rare subset of RCC. The therapeutic implications for patients with these mutations are as yet unclear. We plan to update with ongoing follow-up and will also report 3 further cases suspected to be tRCCs based on morphology and IHC. Confirmatory TFE3/TFEB IHC is awaited.
Clinical analysis of introduction chemotherapy for advanced germ cell tumors at Japanese high-volume center.
Authors: Nakamura Terukazu , Mikami Kazuya , Kimura Yasunori , Hongo Fumiya , Takaha Natsuki , Miki Tsuneharu
Published: March 2020

e15099

Background: Recently, cure rate of advanced testicular cancer even with poor prognostic factors have much improved. Inadequate treatment, however, may lead the patients "difficult-to-treat" situation. The aim of this study is to assess the results of the induction therapy at the Japanese single high volume center. Methods: We assessed clinical outcomes about 82 cases of advanced germ cell tumors that had induction chemotherapy at our hospital from Jun, 1998 until Dec, 2010. Results: Median age was 58 year-old (range:17-34y.o.). Seminoma was found in 16 cases (19.5%) and non-seminoma in 66 cases (80.5%), regarding primary histology. Clinical stageII was 37 cases, stageIIIA, IIIB, IIIC was 8, 24, 13 cases, respectively. IGCCC showed good in 41 cases (50%), intermediate 25 (30.5%), poor 15 (19.5%). BEP therapy was done in 74 (90.3%), EP 5 (6.1%), VIP 2 (2.4%) and PVB 1 (1.2%). Median cycles of induction therapy was 4 (range 1~5). Complete response was observed in 14 cases (17.1%), partial response with marker normalization in 58.5%, partial response without marker normalization in 12.2%, progressive disease in 8.5% including 4 cases of growing teratoma. RPLND after induction therapy was performed in 55 patients. Necrosis was found in 56.4%, teratoma only in 27.3% and viable cancer in 16.3%. Patients with salvage chemotherapy were 22 (27.5%) cases. Five- and 10-year overall survival was 93.3% and 89.6%, respectively. Clinical outcomes at 63 months of median follow-up was as follows; no evidence of disease 73 cases (89.0%), alive with disease 1case (2.4%) and death 7 cases (8.6%). Stratified by IGCCC, 5-year overall survival was 97.6% in good prognosis, 96.0% in intermediate prognosis and 79.0% in poor prognosis. Causes of death were as follows; pancreatic juice leakage after RPLND in 1 case, cerebral infarction in 1 case, cerebral bleeding in 1 case, traffic accident in 1 case, and cancer death in 3 cases. Conclusions: Clinical outcomes at Japanese high volume center were good, especially in good and intermediate prognosis. It was very clear that improvement of poor prognosis, especially high tumor volume, was required.
Cost-effectiveness evaluation of abiraterone in the treatment of patients with castration-resistant prostate cancer who previously received docetaxel.
Authors: Chopra Akhil , Gluck Stefan , Montero Alberto J. , Avancha Kiran Kumar Venkata Raja , Lopes Gilberto
Published: March 2020

e15107

Background: Treatment with abiraterone improves overall survival (OS), time to prostate-specific antigen progression and radiologic progression-free survival when added to prednisone and best supportive care in patients with advanced castrate-resistant prostate cancer (CRPC) who previously received docetaxel. Little is known about its cost-effectiveness in the United States. Methods: In order to raise awareness of pharmacoeconomics concepts and inform policy-makers in the US, this study aimed to assess the cost-effectiveness of abiraterone in the treatment of advanced CRPC patients, from a payer perspective. We created a decision-analytical model using clinical data from the pivotal phase III trial: COU-AA-301. Health utilities were derived from the available literature. Costs for drug acquisition, physician visits and laboratory tests were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2011 US dollars. Life-years saved (LY), Quality-adjusted life years (QALY) and Incremental Cost Effectiveness Ratio (ICER) were calculated using updated survival data presented at the 2011 ASCO meeting. Other main scenarios used the original median survival data published in the New England Journal of Medicine article and adjusted median OS to represent an overall survival hazard ratio of .66. Sensitivity analyses were performed using the confidence intervals for median OS in the pivotal study as well as by halving or doubling all other model inputs. No discounting was used due to the short time-horizon. Results: Abiraterone added 0.38 LY and 0.30 QALY with an incremental cost of $39,320 and therefore a cost of $102,600/LY and an ICER of $129,000/QALY. The main drivers of the model were drug acquisition cost, median OS, and health utility values. The results of the model were robust in different scenarios and sensitivity analyses. Conclusions: Using commonly accepted willingness-to-pay thresholds, such as those suggested by the World Health Organization, treatment of patients with advanced CRPC patients with abiraterone is likely to be cost-effective in the US.