bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal prophylactic method of venous thromboembolism for gastrectomy in Korean patients: A prospective randomized trial.
Authors: Song Kyo Young
Published: February 2017

TPS229

Background: Whereas routine prophylaxis for venous thromboembolism (VTE) is frequently utilized in the West, Asian physicians employ it much less often, based on its recorded rarity amongst their patients. This trial is to examine the incidence of VTE and to determine the optimal method of thromboembolic prophylaxis following gastrectomy for cancer. Methods: In this prospective randomized trial, patients will be assigned to either an intermittent pneumatic compression (IPC) only or an IPC plus enoxaparin. The primary end point of this study is to determine the VTE incidence rate within 30 days of surgery. A history with physical examinations for VTE and a serum d-dimer test is scheduled on postoperative days (POD) 0, 1, 4, and 7. Duplex ultrasonography (DUS) was performed as an objective test for deep vein thrombosis at POD 4. The number of patients to be randomized was calculated to be 682. Clinical trial information: NCT01448746.
A phase IIb, randomized, controlled, multicenter, open-label study of the efficacy and immune response of GVAX pancreas vaccine and CRS-207 compared to chemotherapy or to CRS-207 alone in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE Study).
Authors: Le Dung T. , Wang-Gillam Andrea , Picozzi Vincent J. , Crocenzi Todd S. , Morse Michael , Zeh Herbert , Fine Robert Lance , Murphy Aimee , Skoble Justin , Lemmens Ed , Ferber Sandy , Rosen Allan , Grous John J. , Dubensky Thomas , Brockstedt Dirk G. , Lutz Eric , Jaffee Elizabeth M.
Published: February 2017

TPS489

Background: A prime-boost vaccination strategy using GVAX pancreas vaccine and CRS-207 is showing activity in patients with metastatic pancreatic adenocarcinoma (PDA). GVAX is composed of lethally-irradiated, allogeneic pancreatic cancer cells modified to express GM-CSF. GVAX induces a response against multiple tumor antigens and is given after low-dose cyclophosphamide (CY) to inhibit regulatory T cells. CRS-207 is live-attenuated Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin. CRS-207 boosts responses against mesothelin and stimulates both innate and adaptive immunity by activating T cells and NK cells. Results from a phase 2 study demonstrated CY/GVAX plus CRS-207 improved overall survival (OS) compared to CY/GVAX alone (p-value<0.05; Le, GI ASCO 2014). Methods: This is a phase 2b study comparing CY/GVAX and CRS-207 to chemotherapy or to CRS-207 alone in patients with previously-treated metastatic PDA. Patients will be enrolled in two cohorts: 150 patients into a primary cohort of patients with at least two prior chemotherapy regimens for metastatic disease (third + line) and 90 patients into an exploratory cohort of patients with only one prior chemotherapy regimen for metastatic disease (second line). Patients will be randomized in a 1:1:1 ratio to receive 2 doses of CY/GVAX and 4 doses of CRS-207 (Arm A), six doses of CRS-207 (Arm B) or physician’s choice of single-agent chemotherapy (Arm C). The primary objective is to compare OS between Arms A and C in the primary cohort. Secondary/exploratory objectives include: comparison of OS in both primary and exploratory cohorts between all treatment arms, assessment of safety and clinical responses (tumor assessments and CA19-9 levels) and correlation of Lm- and mesothelin-specific T cell and other immunological responses with clinical responses. Updated enrollment will be reported. (Sponsor: Aduro BioTech, Inc.; NCT02004262). Clinical trial information: NCT02004262.
Treatment and underlying mechanisms of pancreatic cancer cachexia (PANCAX study).
Authors: Khanuja Jasleen , Gresham Gillian , Osipov Arsen , Tuli Richard , Hendifar Andrew Eugene
Published: February 2017

TPS491

Background: Advanced pancreatic adenocarcinoma is characterized by progressive weight loss and nutritional deterioration, resulting in a cachexia-anorexia syndrome. This wasting has been linked to poorer survival, alterations in host defenses, and decreased functional ability and quality of life. Gut microbiota alterations affect muscle composition and have been demonstrated in mouse models of cancer cachexia. The relationship between pancreatic cancer cachexia and the composition of the fecal microbiome will be investigated. We propose the first prospective study of peptide-based enteral nutritional support in cachectic advanced pancreatic adenocarcinoma patients undergoing chemotherapy. We aim to establish the feasibility and efficacy of enteral nutrition as measured by changes in weight, lean body mass, and hand-grip strength. We will also explore the relationship between anorexia-cachexia with gut hormone changes and alterations in the fecal micro-biome, which may account for resultant malnutrition and muscle loss. Methods: Eligible patients will have a diagnosis of both pancreatic adenocarcinoma and cachexia, defined as greater than 5% unintentional weight loss within the previous 6 months. Peptamen 1.5 will be administered via a jejunal tube for 12 weeks. Lean body mass, evaluated by DEXA, and weight will be assessed at predefined intervals. Oral food intake will measured by 24 hour food recall and a taste and smells alteration survey. Secondary outcomes including, response to chemotherapy, survival, and quality of life will be studied. Fecal microbiome, serum inflammatory markers, and gut hormone levels will be assessed at pre-defined intervals. We have received funding from NIH/NCATS Grant # UL1TR000124 and opened enrollment in September 2014.
A randomized, open-label, phase I/II trial of gemcitabine plus nab-paclitaxel with or without FG-3019 as neoadjuvant chemotherapy in locally advanced, unresectable pancreatic cancer.
Authors: Rocha Flavio G. , Helton Scott , Picozzi Vincent J.
Published: February 2017

TPS500

Background: Only 15% of patients with pancreatic ductal adenocarcinoma (PDAC) are eligible for resection. Patients with locally advanced PDAC may become candidates for surgery following donwstaging with neoadjuvant therapy. PDAC often exhibits a high degree of desmoplasia, characterized by extensive connective tissue stroma. FG-3019 is a recombinant human monoclonal antibody that binds to connective tissue growth factor and significantly reduces tumor growth, neovascularization, and metastases in mouse models of PDAC. Therefore, FG-3019 may change the fibrotic character of PDAC to one more amenable to resection. In a phase I trial of stage III/IV patients, FG-3019 did not add toxicity when combined with gemcitabine and erlotinib. Methods: Phase 1/2, randomized, open-label trial to evaluate safety and tolerability of gemcitabine plus Nab-paclitaxel with FG-3019 or gemcitabine plus Nab-paclitaxel in subjects with locally advanced, unresectable PDAC (clinicaltrials.gov #NCT02210559). Primary endpoint is treatment-related adverse events. Secondary endpoints include R0 resection rate, surgical complications, tumor response, and survival. Patients with biopsy-proven PDAC are included following radiographic and laparoscopic confirmation of irresectability and no metastases. Sample size of 40 is based on clinical judgment for initial exploration of safety, tolerability, and treatment effect. Each cycle is 28 days and subjects receive up to six cycles of treatment. Those who complete treatment undergo resection based on the following criteria: reduction in CA 19-9 level by more than 50%, FDG-PET SUVmax decrease by >30%, or radiological tumor response per RECIST to meet the definition of resectable or borderline resectable. Safety will be assessed through adverse event monitoring, clinical laboratory testing, ECG, ECOG performance status, vital signs, and physical exam until 28 days after the last FG-3019 infusion. All resected subjects will be followed for 30 days after discharge and undergo safety assessment per standard of care. Since the trial opened in 8/2014, we have enrolled 1/40 patients. Clinical trial information: NCT02210559.
Treatment of neuroendocrine tumors (NETs) with combination of everolimus and lu-177 radiolabeled somatostatin analogue.
Authors: Aljubran Ali Husain , Tuli Mahmoud , Raef Hussein
Published: February 2017

TPS502

Background: Treatment of Grade 1 and 2 NET is complex and involves surgical, Locoregional and systemic modalities depending on the manifestations as well as extent of disease. Of the emerging new systemic modalities are everolimus and radiolabelled somatostatin analogue. everolimus is FDA approved for advanced pancreatic NET whereas radiolabelled somatostatin analogue is still not standard therapy in the USA. However, it is gaining popularity especially in Europe as effective systemic therapy for somatostatin receptor positive tumors. Subclinical animal model research showed synergistic effect of the combination of everolimus and the Lu-177 radiolabeled somatostatin analogue. The goal of this study is to assess the safety and efficacy of the combination of Everolimus and the intravenous radiolabeled Lu-177 DOTATOC Therapy in the treatment of unresectable G1-2 neuroendocrine tumors of all gastrointestinal, lung and pancreatic origins. Methods: This is a phase 1 – 2 study. The phase 1 part involves finding the maximum tolerating dose (DLT) of everolimus and accordingly to recommend dose for the phase II part. The second part is a standard phase II trial assessing the efficacy and toxicity of the regimen at the recommended dose. A total of 30 patients will be enrolled, based on the expected response of the combination to be 20% with power of 80 and type 1 of.05, compared to the known everolimus alone overall all response of 5%. In phase 1, three patients will be treated with 5mg daily with expansion to six patients if one of the three patients experienced DLT. If DLT occurred in none of three or no more than one of six patients, everolimus dose will be escalated to 10 mg and will be considered the recommended dose for phase 2 part. Otherwise, everolimus dose will be kept at 5 mg daily and will be considered the recommended dose for phase II part. DLT in more than two of six patients will be considered unacceptable, and the trial will be closed because of high toxicity.
A phase 3 open-label, randomized, multicenter study of Imprime PGG in combination with cetuximab in patients with KRAS wild type metastatic colorectal cancer.
Authors: Huhn Richard Dale , Lowe Jamie , Grady Michele , Taitt Corina Candiani , Gargano Michele Anne , Braun Ada H.
Published: February 2017

TPS787

Background: Imprime PGG (Imprime) is a novel immune modulator (complex carbohydrate biologic), which harnesses innate immune cells to enhance killing of antibody-targeted tumor cells. In a phase 2 single-arm clinical trial in mCRC, the combination of Imprime with cetuximab resulted in 24% ORR, 62% disease control rate (DCR), and median time to progression (TTP) of 12 wks (Tamayo ME, Ann Onc 2010), representing approximate 100% increases vs historical control (Cunningham, NEJM 2004). ORR was 45%, DCR, 82% and TTP, 24 wks in pts with KRAS WT tumors (post hoc analysis). Single-agent cetuximab has been shown to improve objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients (pts) with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type (WT) metastatic colorectal cancer (mCRC) who failed oxaliplatin- and irinotecan-based therapy or are intolerant to irinotecan. The mechanism of action of cetuximab is thought to rely on competitive blockade of endogenous ligand binding and downstream signaling, internalization and down regulation of EGFR, as well as antibody-dependent cellular cytotoxicity (ADCC) (Erbitux SmPC). The current trial, sponsored by Biothera (registered with ClinicalTrials.gov NCT01309126) is to confirm these findings in phase 3. Methods: Eligible pts will have had prior oxaliplatin- and irinotecan-based therapy or be intolerant to irinotecan, and will meet key inclusion criteria including measurable disease and ECOG performance status of 0 or 1. In a 2:1 randomization, stratified by geographic region, prior chemotherapy and site, approximately 795 pts will receive weekly open-label Imprime plus cetuximab or cetuximab alone. The primary endpoint of the study is OS and primary analysis will occur when ~709 deaths have occurred. Secondary endpoints include PFS, ORR (based on RECIST 1.1), quality of life, safety and pharmacokinetics. Exploratory endpoints include biomarker analyses. Pt screening and enrollment is underway in the United States and Europe. Clinical trial information: NCT01309126.
E7208: A randomized phase II trial of irinotecan and cetuximab (IC) versus IC plus ramucirumab (ICR) in second line therapy of KRAS wild type colorectal cancer (CRC).
Authors: Hochster Howard S. , Catalano Paul J. , Mitchell Edith P. , Cohen Deirdre Jill , O'Dwyer Peter J. , Benson Al Bowen
Published: February 2017

TPS793

Background: Anti-angiogenic therapy for CRC has been accepted as standard therapy with approval of bevacizumab (bev) in both first-line and second-line settings. At the time this study was started, the benefit of continuing an anti-angiogenic in second line therapy was unproven. Ramucirumab (RAM, IMC 1121b) is a humanized antibody directed against the VEGF-R2 receptor, which may prove to have different activity compared to anti-VEGF antibody (bev). Additionally, while combining the anti-EGFR antibody, cetuximab (CMAB), with bev in first-line unselected patients was not effective, it is unknown whether the same may be true with RAM plus CMAB in a second-line setting for KRAS-selected patients. Methods: The study was designed as a randomized phase II trial with 147 patients assigned to IC = irinotecan (I) 180 mg/m2 IV plus CMAB 500 mg/m2 IV q2w versus ICR = IC plus RAM 8 mg/kg IV q2w. Eligibility included prior treatment on one prior oxaliplatin and bev-containing regimen and progression within 42 days of last bev, PS 0-1, KRAS codon 12,13 wild-type and standard other chemo and bev criteria. Doses were modified for neutropenia, diarrhea, mucositis, rash and grade 3 other toxicities. The study was activated 10/8/10. The first 35 patients were enrolled and accrual was held 6/24/12 for toxicity analysis per protocol. More grade 3 events of mucositis, diarrhea, neutropenia and perforation events (including peri-rectal abscesses) were seen in the ICR arm. The study has been modified reflect the actual doses received, and now uses modified ICR (mICR) = I 150 mg/m2, CMAB 400 mg/m2 and RAM 6 mg/kg IV q2w. The study was re-activataed in May 2014. An additional 100 pts will be accrued to the revised study, giving 85% power to detect improved median PFS from 4.5 to 7.65 months. New eligibility criteria include any progression from first-line chemo (on or off), normal albumin, no bowel perforation or obstruction in last 6 months. This study is now open to accrual in ECOG-ACRIN and in SWOG with endorsement, and via CTSU. Clinical trial information: NCT01079780.
Preemptive therapy of cetuximab-induced skin rash using doxycycline, sunscreen, hydrocortisone, and moisturizer in colorectal and head and neck cancer patients.
Authors: Redman Rebecca Ann , Perez Cesar Augusto , Sledjeski Lauren , Kessans Knable Mika , Sharma Vivek R.
Published: February 2017

TPS796

Background: Toxicities associated with the use of cetuximab include infusion reactions, dermatologic toxicity and electrolyte disturbances. Of these, skin toxicity including acneiform rash, dry skin and fissuring, paronychial inflammation, infectious sequelae and hypertrichosis occur most commonly, with acneiform rash developing in 76-88% of patients. These skin toxicities are rarely life-threatening, but they impact the quality of life of patients receiving therapy and directly affect adherence. The purpose of this study is to determine if preemptive therapy with doxycycline, sunscreen, hydrocortisone 1% cream, and moisturizer will reduce the incidence and severity of > grade 2 acneiform rash according to CTCAE v.4 in patients with colorectal and head and neck cancer receiving therapy with cetuximab. Methods: This is a single-institution, prospective, open-label, randomized study of 100 patients with colorectal and head and neck cancer receiving cetuximab in the locally advanced or metastatic setting. Those randomized to preemptive therapy will receive doxycycline 100 mg twice daily, sunscreen SPF 30, hydrocortisone 1% cream, and moisturizer beginning three days prior to the first dose of cetuximab for a duration of 8 weeks. Those randomized to standard of care will receive treatment of skin toxicity per national guidelines and treating physician discretion. Objectives are to evaluate the incidence of cetuximab-induced rash, compare the severity of cetuximab-induced rash between the preemptive treatment group and the standard care group, and monitor the toxicity of the preemptive therapy. Secondary objectives include quality of life, adherence rates, disease-specific outcomes, and survival. Patients will be evaluated at enrollment, 3 weeks into treatment and at the end of treatment for adherence, side effects and quality of life. They will be followed for up to two years for treatment outcomes and survival. With alpha of 0.05 and a power of 80%, we will be able to detect if the incidence of skin rash differs by 24% between the two groups using a two-sample one-sided binomial test. As of September 2014, 15 of 100 patients have been enrolled. Clinical trial information: NCT01874860.
A phase I study of investigational agent SGI-110 combined with irinotecan in previously treated metastatic colorectal cancer patients.
Authors: Wang Judy Sing-Zan , Gootjes Elske C. , Uram Jennifer N. , Zahurak Marianna , El-Khoueiry Anthony B. , Verheul Henk M.W. , Ahuja Nita , Azad Nilofer Saba
Published: February 2017

TPS797

Background: Studies have suggested that epigenetic modifications may play a role in oncogenesis and acquired chemoresistance in certain cancers including colorectal cancer (CRC). Our preclinical data has shown that DNA hypermethylation may confer acquired chemoresistance, and that combining a hypomethylating agent can re-induce tumor sensitivity to irinotecan in CRC cell lines. We propose a phase I study to assess the safety and tolerability of SGI-110 with irinotecan therapy in metastatic colon cancer previously treated with irinotecan. This will be followed by a randomized phase II study to evaluate efficacy of the combination. Methods: We will enroll 12-22 patients at two institutions with metastatic colon adenocarcinoma previously treated with irinotecan to our phase I study. Dose escalation will be performed in a traditional 3+3 design, where patients receive SGI-110 30-45mg/m2 SQ days 1-5 in combination with irinotecan 125mg/m2 days 1, 8, and 15 (depending on the dose level) every 28 days, with or without G-CSF. Patients will be monitored for safety and tolerance with laboratory studies, clinical exam, and periodic CT scans to assess response to therapy. In addition, pharmacokinetic studies on peripheral blood and paired tumor biopsies will be obtained to assess for global demethylation and evaluation of biomarkers. Major eligibility criteria include measureable disease with accessibility for paired tumor biopsies, and prior treatment with irinotecan without limit on number of total therapies. Current Enrollment: Dose level 1 enrolled 6 patients and encountered 1 DLT following expansion for safety assessment. Dose level -1 enrolled 3 patients and encountered 2 DLTs, which has since prompted amendments for additional dose levels with modifications to scheduled growth factor support. Dose level -1G enrollment began in September 2014. Clinical trial information: NCT01896856.
Prostate biopsies using both gray scale and 3D color flow power doppler ultrasound (3DCFPDU).
Authors: Dattoli Michael J. , Sorace Richard A , Bravo Stephen M , Bostwick David G.
Published: February 2017

103

Background: Historically, prostate cancer (CAP) is identified through random biopsies. Experts usually recommend 10-12 core transrectal ultrasound guided biopsies (TRUS). This often leads to sampling errors with missed diagnosis, delayed and repeated biopsies, understaging and finding indolent CAP leading to over treatment. Advances in 3DCFPD imaging suggest that selective biopsies may be superior to standard TRUS biopsies. Methods: 192 consecutive patients were biopsied (Feb. 2012 – July 2014) in the dorso-lithotomy position with local anesthesia. Median number of biopsies per patient = 8; total number of cores = 1,520. Only 3 patients had not been previously biopsied (median previous biopsies = 2). We studied tumor detection rate using combined gray scale and 3DCFPD with direct sampling of specific regions using the transperineal brachytherapy template guided method as a simple outpatient procedure. Inclusion criteria were abnormal DRE, PSA kinetics 0.75ng/mg/yr, PSA >10 and % free PSA <17. PSA density 0.27. Cores were stratified into 4 risk groups: 1) hypoechoic lesion (72 patients, 648 cores); 2) hypervascular lesion (26 patients, 182 cores); 3) hypoechogenic with hypervascular pulsatile vessels synchronous and coinciding with normal cardiac pulse (32 patients, 256 cores); and 4) hypoechogenic with hypervascular non-pulsatile vessels suggesting independent vascular flow consistent with neoplasm (62 patients, 434 cores). Isoechoic regions were not biopsied. Subgroups were analyzed using chi-square, student t-test, and logistic regression. Results: The diagnostic yield associated with Group 4 was statistically significantly higher compared to: 1.) 20% biopsy positive (p <0.5); 2.) 19% biopsy positive (p <0.3); 3.) 55% biopsy positive (p <0.1); 4.) 97% biopsy positive (p <0.1). Only Group 4 revealed a greater number of Gleason 7-10 CAP (p <0.1). Conclusions: Transperineal template guided biopsies with gray scale and 3DCFPD are highly effective and cost effective. This may lead to reducing the number of prostate biopsies performed, better staging and allowing for enhanced detection of serious CAP by targeting the most suspicious lesions. Additional research should study the diagnostic gain with 3DCFPD.
Is the apical margin real? An analysis of postprostatectomy PSA failure by site of involved margin.
Authors: Watkins John Morgan , Laszewski Michael , Rodacker Mark , Watkins Patricia L. , Russo James Kyle
Published: February 2017

105

Background: Though an involved margin at prostatectomy has been associated with elevated rates of PSA relapse, there has been an absence of consensus regarding the risk of relapse specific to the site(s) of margin involvement. Specifically, the apical margin has been sometimes considered "lower risk," based upon historical series. The present study seeks to determine the rate of PSA relapse in patients who had undergone prostatectomy with involved surgical margin, without immediate post-operative (adjuvant) therapy, with comparison of relapse rates by site of involved margin. Methods: A retrospective database review was performed, including patients with clinically localized prostate cancer and pre-operative PSA <30, who had undergone prostatectomy, with site(s) of involved margin characterized. Slides were re-reviewed by a pathologist for verification of site of margin involvement. Patients were excluded if seminal vesicle invasion or lymph node involvement was noted in the surgical specimen, if any adjuvant therapy was delivered prior to relapse, or if post-operative follow-up with PSA was <12 months. Relapse was defined as >0.2 and rising after prostatectomy. Log-rank analysis was employed for comparison of disease control between groups; the Kaplan-Meier method was employed to construct survival curves and estimate 5-year disease control. Results: Between 2002 and 2010, 155 patients were identified for inclusion in the present analysis. Of these, 105, 37, and 7 patients had 1, 2, and >2 sites of margin involvement, respectively. The apex was the sole site of margin involvement for 70 patients. At a median follow-up of 68 months (range 22-145), 62 patients (40%) had experienced PSA relapse. There was no statistically significant difference in risk of PSA relapse by site of margin involvement or number of foci of margin involvement. The 5-year estimates for PSA relapse for margin involvement of the apex only, other site only, or both were 40.5%, 33%, and 49.1%, respectively. Conclusions: Involvement of the apical margin is associated with a high rate of early PSA relapse, similar to rates noted when other site(s) of margin involvement are noted.
Reducing decisional conflict in men making treatment decisions on newly diagnosed localized prostate cancer.
Authors: Johnson David C. , Wallen Eric , Smith Angela , Woods Michael , Pruthi Raj , Mueller Dana , Nielsen Matthew Edward
Published: February 2017

106

Background: Men with newly diagnosed localized prostate cancer (LPC) face a complex, preference-sensitive treatment decision. Low “decisional conflict” (DC), defined as uncertainty over treatment choice, is a key component of decision quality. Lower scores on the Decisional Conflict Scale (DCS) are associated with lower likelihood of delaying a decision and assessing blame to a physician for bad outcomes. We hypothesized that using a novel software application to measure and report patients’ preferences for LPC treatment outcomes as part of a pre-consultation intervention would improve decisional quality in men with LPC by reducing DC. Methods: Men with newly diagnosed LPC completed the online WiserCare (WiserCare, Inc) prostate cancer module prior to their initial consultation at the University of North Carolina, Chapel Hill Multi-disciplinary Urologic Oncology Clinic. WiserCare is a software application that provides education, preference assessment, and personalized decision analysis for patients. Preferences are measured using conjoint analysis. WiserCare then generates an individualized report ranking treatment options based on their “fit”(expected value) based on clinical prognostic factors and personal preferences. This report is used with their physician during counseling. We measured DCS scores before and after completion of the WiserCare module. Paired 2-tailed T-tests were to evaluate the changes in DCS scores. Results: 48 men completed the WiserCare module and DCS prior to their initial consultation for newly diagnosed LPC. Overall DCS score decreased by 38% (p<0.00001) after completion of the WiserCare module. Analysis of DCS subscales revealed improvements in all five, including feeling informed by 56% (p<0.00001), value clarity by 49% (p=0.001), feeling effective in decision making by 36% (p=0.0001), feeling supported by 31% (p=0.0037), and reduced uncertainty by 24% (p=0.0023). Conclusions: A pre-consultation web-based module integrating evidence-based information, individualized clinical data and personal preference data is a feasible and effective strategy to reduce decisional conflict in men making treatment choices for localized prostate cancer.
Outcome of hypofractionated biological optimized dose-painting radiotherapy for high-risk prostate cancer.
Authors: Syndikus Isabel , Onjukka Eva , Uzan Julien , Nahum Alan
Published: February 2017

107

Background: Prostate dose-painting radiotherapy and hypo-fractionation both can improve biochemical contol in localised disease. We report toxicity and outcome for a cohort of high risk patients. Methods: We selected 28 patients with high-risk localised prostate cancer and 2 or 3 risk factors. Functional MRI’s were used to define boost volumes with a margin of 5 mm PTV. Neo-adjuvant hormone therapy was given for 3 months. Dose volume constraints, TCP and NTCP parameters were used for optimization of rotational IMRT treatment plans. We used fiducial markers, bowel and bladder preparation and daily IGRT. Results: Mean age was 66 years, mean PSA was 17.4 ng/ml (range 4.6-59.1), 20 patients had T3a and 10 had Gleason score ≥ 8. The mean dose to the prostate excluding the boost volume was 61.4 Gy (range 60.6-62.3) and the boost PTV 66.1 Gy (range 60.9-72.5). Mean NTCP for rectal bleeding was 4.7% (range 3.4-5.8), for faecal incontinence 3.5% (range 2.3-5) and mean TCP 75% (range 71-79) assuming a 71% biochemical control at 5 years for a standard plan. All patients completed radiotherapy, 16/28 patients had acute bladder toxicity grade 2 (RTOG score), but no grade 3 toxicity was observed. Worst acute bowel toxicity was grade 1 (4/28). Mean follow up was 15 months (range 8-25). For the 20 patients who had neo-adjuvant hormone therapy beyond 6months, the mean PSA was 0.33 ng/ml (range 0.2-0.8), 2 patients had relapsed at 12 month, 6 patients are still on hormone therapy. 4 patients had Grade 2 urinary late toxicities (CTCv4). Two patients developed grade 1 diarrhoea. Patient reported outcomes >6 month after completion of radiotherapy (EPIC QOL questionnaire) demonstrated similar scores to controls without prostate cancer for the bowel domains; reduction in the urinary domains was similar to other cohorts treated with external beam radiotherapy and hormone therapy. Conclusions: In this high risk group, dose escalation with hypo-fractionated dose painting radiotherapy achieved good biochemical control and urinary and bowel toxicity similar to standard dose radiotherapy during follow up.
External beam radiation therapy or high intensity-focused ultrasound for localized prostate cancer: A matched pair analysis in the prostate-specific antigen era.
Authors: Pasticier Gilles , Crouzet Sebastien , Pommier Pascal , Carrie Christian , Rouviere Olivier , Chapelon Jean-Yves , Rabilloud Muriel , Roche Laurent , Mege-Lechevallier Florence , Tonoli-Catez Helene , Martin Xavier , Gelet Albert
Published: February 2017

109

Background: In the absence of randomised study data institutional series have shown High Intensity Focused Ultrasound (HIFU) to produce excellent overall and cancer specific survival rates in patients with localized prostate cancer (LPCa) compared with alternative curative treatments. The aim of this study was to evaluate the oncologic outcome of patients treated with HIFU versus conformal external beam radiation therapy (C-EBRT) without previous or associated androgen deprivation(AD).This study was designed to overcome limitations of case series studies by using a matched pair design in patients treated contemporaneously with HIFU and C- EBRT in two institutions in the same town. Methods: 256 eligible patients with intermediate risk prostate cancer (d’Amico classification) treated between 2000 and 2005 were prospectively followed and matched to a 1:1 basis following know prognostic variables: prostate-specific antigen (PSA) level and Gleason score.190 perfect matches of patients (95 in each group) were further analysed. Progression free survival rate were the primary endpoint. Other endpoints were secondary used of salvage therapy, and survival rate without salvage palliative androgen deprivation therapy (S-ADT).The progression free survival rates were calculated with Kaplan-Meier estimate. For progression free calculation, failure was defined using the Phoenix definition (nadir + 2ng/ml) or at the time of a salvage treatment for local relapse evidenced by control biopsy. Results: The seven years progression free survival rate was not significantly different after HIFU than after C-EBRT (47% versus 52%, p: 0.311) . The palliative androgen deprivation free rate at seven years was significantly different after HIFU than after C-EBRT (85% versus 58%, p: 0.002). Conclusions: The progression free survival rate was not significantly different after HIFU use than after C-EBRT but the rate of patients who need palliative S-ADT was significantly different after HIFU or C-EBRT: Higher rate of S-ADT was associated with C-EBRT use than with HIFU use.
Contemporary trends in receipt of local therapy for men with clinically localized high-risk prostate cancer.
Authors: Wang Lora S , Handorf Elizabeth , Murphy Colin T. , Haseebuddin Mohammed , Waingankar Nikhil , Uzzo Robert G. , Kutikov Alexander , Bekelman Justin E. , Horwitz Eric M. , Smaldone Marc C.
Published: February 2017

111

Background: Level I evidence suggests local treatment results in improved survival as compared to androgen deprivation therapy (ADT) alone or watchful waiting for high risk prostate cancer (CaP), but contemporary trends in primary treatment for high risk CaP are poorly understood. Our aim is to examine local therapy utilization for patients with high risk CaP using a large national cancer registry. Methods: Using the National Cancer Database (NCDB), patients with clinically localized CaP meeting National Comprehensive Cancer Network high risk criteria were identified from 2004-2009. Men with node positive or metastatic disease were excluded. Adjusting for diagnosis year and demographic we examined the association between patient characteristics and local therapy, defined as radical prostatectomy (RP) or radiation (RT), in men with high risk CaP using logistic regression models. Results: A total of 132,369 men met inclusion criteria with 80% receiving local therapy and 12% receiving no treatment. There was a small but significant increase in local therapy utilization from 2004-2009 (79 to 81%, p<0.001) with the largest changes seen in increased use of RP alone (24 to 31%, p<0.001) and decreased use of RT+ADT (33 to 29%, p<0.001). In comparison, minor changes were noted in the rates of RT alone (14 to 13%, p=0.02), RP+RT (2.2 to 2.9%, p<0.001), RP+RT+ADT (1.6 to 1.9%, p=0.01), and ADT alone (8.9 to 7.0%, p<0.001). Following adjustment, patients with age >70 years (OR 0.27, CI 0.23-0.30) or Charlson morbidity count > 2 (OR 0.43, CI 0.39-0.46) were less likely to receive local therapy. Further, men of African American race (OR 0.7, CI 0.67-0.74) and Medicare (OR 0.82, CI 0.77-0.87) or Medicaid (OR 0.6, 0.53-0.68) insurance were less likely to receive primary treatment than Caucasian patients or those with private insurance. Conclusions: In the NCDB, 80% of men presenting with clinically localized high risk CaP undergo local therapy as part of multimodality treatment or as monotherapy, with RP overtaking RT+ADT as the primary local treatment of choice. Furthermore, racial and insurance disparities in the receipt of primary treatment are still evident, providing targets for emerging CaP quality of care initiatives.
Focal treatment of prostate cancer using Focal One device: Pilot study results.
Authors: Pasticier Gilles , Crouzet Sebastien , Rouviere Olivier , Chapelon Jean-Yves , Mege-Lechevallier Florence , Martin Xavier , Gelet Albert
Published: February 2017

112

Background: To evaluate the efficacy of Focal One device for focal treatment of localized prostate cancer. Methods: Focal One is a device designed for the focal therapy of Prostate Cancer integrating the ability to visualize, target, treat and validate the focal treatment. Magnetic Resonnance Imaging (MRI) volumes are imported through the hospital’s network into the device so that an elastic fusion can be done between the real time ultrasonography and the MRI where the regions to treat have been previousy drawn, thus allowing to apply limited and targeted HIFU lesions. During the HIFU energy delivery process, the operator sees a live ultrasound image of what is being treated and, if necessary, can readjust the treatment planning. At the end of the treatment process, a Contrast-enhanced Ultrasound volume is acquired showing the de-vascularized areas. Ten patients with mono focal prostate cancer were treated between march 2013 and January 2014.HIFU treatment process was realized with the Focal One device using a 6 mm safety margin around the tumor. Contrast enhanced MRI is performed at day 2 after HIFU and Control biopsies guided with contrast-enhanced Ultrasound imaging were achieved one month after HIFU inside and in the rime of the treated area. Results: The mean age of patients was 65.8±5.5 years. The Clinical stage was T1for 9 patients and T2afor 1patient.The Gleason sum was 6 for 7 patients and 7(3+4) for 3 patients. The PSA value was 4.47± 3.7 ng/ml and the mean Prostate Volume was 50±23 cc .The mean treated volume was 14 cc (7.3-20.4) 28% of prostate gland. The mean nadir PSA value was 3.46±2 ng/ml. In all patients, targeted biopsies inside the treated area performed day 30 after the HIFU session demonstrated a complete destruction of the targeted tumor. No Incontinence was observed .A partial loss of potency (IIEF <17) occurred in 2 patients. Conclusions: Focal One device is able to achieve a complete destruction of small prostate cancer using an elastic magnetic resonance-ultrasound (MR-US) registration system for tumor location and HIFU treatment planning. Multicenter trial is in progress (30 patients).
Prostate cancer radiation therapy with reduced planning target volume (PTV) margins.
Authors: Sun Kelly , Brand Timothy , Tinnel Brent , Kathpal Madeera , Ninneman Stephanie , Hughs Grant , Halligan John B. , Brown Michael , Brooks Joseph P. , Macdonald Dusten
Published: February 2017

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Background: Electromagnetic tracking of the prostate during radiation therapy for prostate cancer allows decreased PTV margins which may reduce dose to nearby tissues. Sandler, et al. reported a reduction in patient-reported acute morbidity with this strategy (Sandler HM, et al. Urology, 2010 May;75 (5):1004-8). We conducted a similar prospective study and compare our results with Sandler’s Assessing Impact of Margin Reduction (AIM) study and with a group treated with radiation therapy without reduced PTV margins from the Sanda, et al. PROST-QA cohort (Sanda MG, et al. NEJM, 2008 Mar 20;358 (12):1250-61). Methods: 25 patients with low-to-intermediate risk prostate cancer were treated on a prospective study with definitive intensity-modulated radiation therapy with 3 mm circumferential PTV margins and daily electromagnetic localization. An EPIC quality of life questionnaire was completed prior to treatment and at the last treatment. Using data from the referenced publications, we performed a two-tailed t-test to compare EPIC scores from our cohort with the AIM and PROST-QA cohorts treated with external beam radiation therapy alone. Results: Table lists mean pre- and post-treatment EPIC scores and the differences between them. Conclusions: Our patients fared similarly to the PROST-QA cohort, but had a significantly greater mean decrement in the urinary irritation and sexual domains in comparison to the AIM cohort. Clinical trial information: NCT01589939. [Table: see text]
A retrospective case series looking at the effectiveness of hyperbaric oxygen in treating radiation cystitis.
Authors: Gorenstein Scott , Katz Aaron , Regan Kimberly , Hangan Donna
Published: February 2017

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Background: A side effect of radiation therapy to treat genitourinary cancers is radiation-induced cystitis, which in its most severe form can be hemorrhagic cystitis (HC). Some studies have found the incidence of HC in radiation patients to range from 3% to 6.5% after radiation therapy and can develop anywhere from 6 months after radiation therapy to 10 years or more after the last treatment. The severity of symptoms, which includes hematuria, may drastically reduce quality of life. Recent studies have shown that hyperbaric oxygen therapy has improved symptoms of radiation cystitis in around 80% of patients. Methods: Sixty patients who received hyperbaric oxygen therapy (HBOT) for radiation-induced cystitis since 2010 at Winthrop University Hospital were identified. IRB approval was obtained for contacting these patients to gather outcome data. Patient reported outcomes were evaluated using a questionnaire that assessed the type and duration of radiation treatment, treatment other than HBOT for HC symptoms, surgical intervention, and patient perceived outcomes of HBOT. Results: 36 patients were consented. The average age of the patient was 71 with a range from 29-91. The majority of the patients 78% had prostate cancer with the Colon, Uterinem, Bladder and Testicular cancer also included The average time from completion of radiation to onset of symptoms was 3 years. The mean number of treatments was 35 with a range of 18-120 treatments. All treatments were for 90 minutes at 2.4 ATA. The majority of the patients (24) had external beam radiaiation and 12 patients had a urological procedure after completion of their therapy. 78 % of the patients reports either moderate improvement or complete resolution of symptoms. Conclusions: This case series seems to demonstrate that Hyperbaric Oxygen Therapy appears to be an effective treatment for radiation cystitis, however additional studies are necessary.
The impact of spatial distribution patterns of tumor foci on biochemical recurrence in prostate cancer.
Authors: Eminaga Okyaz , Hinkelammert Reemt , Semjonow Axel
Published: February 2017

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Background: The influence of spatial distribution patterns of organ-confined Prostate Cancer (PCa) on the biochemical recurrence (BCR) remains unclear. Therefore, we conducted a study investigating the association between distribution patterns and BCR-free rate in organ-confined PCa. Methods: The anatomical distribution of PCa in 743 men with pT1-pT3N0 and without neoadjuvant therapy was analyzed to determine 20 groups with similar distribution patterns of PCa. Then, 245 men with pT2N0R0 were considered for prognostic evaluation. Spatial distribution patterns of PCa were evaluated using a cMDX-based map model of the prostate. A comparison analysis including 552,049 compare operations was performed to assist the similarity levels of the distribution patterns. K-mean cluster analysis was applied to determine 20 groups with similar distribution patterns. A decision tree-Analysis was performed to divide these groups according to BCR. BCR-free survival was compared. Predictors of progression were investigated using a Cox proportional hazards model. Results: BCR was occurred in 8.2% men with pT2N0R0 PCa. In decision tree analysis, certain PCa distribution patterns revealed no BCR at a median follow-up of 60 mo. (IQR: 42.3-77.0) In univariate and multivariate analysis, the prostate volume, the distribution patterns were an independent predictor for BCR in univariate and multivariate, whereas tumor stage, Gleason score, PSA, relative tumor volume were not. When patients with pT2R0 were stratified according to PCa distribution patterns, the presence of BCR-negative PCa distribution patterns was significantly associated with no risk of BCR by comparison to BCR-associated PCa distribution patterns (P=0.001). Conclusions: PCa distribution patterns provide a prognostic value for BCR. Distribution patterns of PCa can be applied to create more meaningfully predictive pathological T2 sub-divisions than current pT2 prostate cancer sub-stages.
Do margin details matter? The prognostic significance of capsule invasion at the site of involved margin in prostatectomy specimens.
Authors: Watkins John Morgan , Russo James Kyle , Laszewski Michael , Rodacker Mark , Watkins Patricia L. , Dufan Tarek A. , Koleilat Nadim
Published: February 2017

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Background: An involved surgical margin at prostatectomy has long been associated with elevated risk of prostate cancer recurrence; however, not all patients with an involved margin will relapse, and thus details of the involved margin may provide an opportunity for risk subset stratification. The present investigation seeks to determine whether a difference exists in recurrence rates when the margin involvement is at a site of prostate capsule invasion versus within the prostate parenchyma proper. Methods: Patients were retrospectively identified for inclusion by clinically localized disease and PSA <30 at diagnosis, managed with prostatectomy alone and identified to have involvement of surgical margin(s). Exclusion criteria were: pT3b or pN1 disease, immediate/non-salvage post-operative radiation or hormone therapy, or insufficient follow-up (<12 months). Pathology slides were reviewed by a pathologist blinded to outcome, for determination of capsule invasion at a site of margin involvement. Disease recurrence was defined as PSA >0.2 and rising, per contemporary guidelines. Kaplan-Meier method was employed for disease control estimates. Results: Between 2003 and 2010, 155 patients were identified for inclusion in the present study. The median age was 61 years, and all had cT1-2 disease (75% T1c). At diagnosis, the Gleason score was 6, 7, and 8-9 for 103 (66%), 42 (27%), and 10 (6%) patients, respectively, with median PSA 5.6 (85% <10). For 149 patients with reviewable margin site data, 51 (34%) demonstrated involvement within or beyond the capsule. At a median follow-up of 68 months (range 13-137), 62 patients had experienced PSA relapse. The estimated 5-year PSA relapse rates for patients with an involved margin at the site of capsule invasion versus prostate parenchyma were 49% versus 34%, respectively (p=0.015). Conclusions: Early PSA relapse rates for all patients with involved surgical margin(s) but negative seminal vesicles and nodes at prostatectomy are high; however, for patients who are followed without immediate adjuvant therapy, presence of tumor cells at the margin in a site of capsule invasion or penetration confers a higher risk of recurrence.
The association between statin use and outcomes in patients initiating androgen deprivation therapy.
Authors: Hamilton Robert James , Ding Keyue , Crook Juanita M. , O'Callaghan Christopher J. , Higano Celestia S. , Dearnaley David , Horwitz Eric , Goldenberg Larry , Gospodarowicz Mary K. , Klotz Laurence
Published: February 2017

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Background: Studies are conflicting regarding the association between statin use and biochemical recurrence after surgery or radiotherapy for localized prostate cancer. A handful of studies have observed favorable associations between statins and prostate cancer-specific (PCSM) and overall mortality (OS), however, this has not been studied in an advanced disease cohort nor has the combination of statins and androgen deprivation therapy (ADT) been specifically studied. Methods: Patients with PSA >3 ng/mL after >1 year following primary or salvage radiotherapy (RT) were enrolled in a randomized trial of intermittent (IAD) vs. continuous (CAD) ADT (NCT00003653). Statin use at baseline and during the study was captured and modeled as a time-dependent covariate. The primary end-point was OS. Models were adjusted for age, time from RT to ADT and PSA at baseline. As results were nearly identical between the IAD and CAD arms they are reported as aggregates unless otherwise indicated. Results: Of 1,364 patients enrolled, 585 (43%) reported statin use during the study. Statin users were younger (72.7 vs. 73.8, p=0.001) and less likely to have PSA >15 (20 vs. 25%, p=0.04). Median follow-up was 6.9 years and 524 deaths occurred. Statin use was associated with a reduced risk of overall death (HR: 0.64; 95% C.I. 0.53 – 0.78, p<0.001) and PCSM (HR: 0.64, 95% C.I. 0.48 – 0.86, p=0.003). Statin users had 14% longer time to castration resistance but this did not reach statistical significance (p=0.15). In the IAD arm, statin users had more off-treatment intervals (p=0.04) and longer time off-treatment (median: 0.85 vs. 0.64 years, p=0.06). Across 6 functional domains, statin users reported better quality of life scores. Conclusions: In men treated with ADT following primary or salvage RT, statin use was associated with improved overall and prostate cancer-specific survival and improved quality of life. In patients treated with IAD, statin use was associated with more off-treatment intervals and longer time off-treatment. A prospective trial of statins in men commencing ADT is warranted to confirm this observation.