bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chimeric antigen receptor (CAR+) modified T cells targeting prostate-specific membrane antigen (PSMA) in patients (pts) with castrate metastatic prostate cancer (CMPC).
Authors: Slovin Susan F. , Wang Xiuyan , Hullings Melanie , Arauz Gabrielle , Bartido Shirley , Lewis Jason Stuart , Schöder Heiko , Zanzonico Pat , Scher Howard I. , Sadelain Michel , Riviere Isabelle 
Published: February 2017

72 Background: A phase I dose-escalating study to assess safety, dose and targeting efficiency of genetically modified autologous human T cells targeted to PSMA was initiated. Preclinical models demonstrated anti-tumor activity and accumulation, migration, and persistence of these cells to tumor. The autologous PSMA-targeted T cells utilizes the P28z second generation chimeric antigen receptor following iv cyclophosphamide (Cy). For safety, the herpes simplex virus-1 thymidine kinase (hsvtk) gene is co-expressed with the P28z receptor, rendering T cells sensitive to ganciclovir for immediate T cell elimination. The expression of hsvtk enables PET imaging using radiolabeled FIAU to localize these T cells. Methods: Autologous T cells are activated from a leukapheresis product using anti-CD3/CD28 Dynabeads. Release criteria include mean vector copy number by Q-PCR and vector identity by Southern blot, absence of Replication Competent Retrovirus and residual Dynabeads. Pts were dosed from 107 to 3 x 107 CAR+ T cells/kg. All 7 pts received 300mg/m2 of Cy one day before infusion. Baseline and post treatment imaging included FDG, FDHT and 18F-FIAU PET scans. Results: Three pts in cohort 1 received 1 x 107 CAR+ T cells/kg safely. A fourth pt received the same dose with a modified vector with higher copy number. One pt had stable disease for > 6 months; a second pt has stable scans for > 16 months; the third and fourth patients progressed. Of 3 pts in cohort 2, one received 1.5 x 107 CAR+ T cells/kg and 2 received 3 x 107 CAR+ cell/kg. All 3 had intermittent fever spikes up to 39oC associated with increased levels of IL-4, IL-8, IP-10, sIL-2ra and IL-6 suggesting T cell activation. CAR+ cells persisted in the circulation for up to 2 weeks. Scans with 18F-FIAU labeling suggests that imaging may be cell dose dependent. Conclusions: We have shown that pts can be safetly treated with an ex vivo transduction, expansion and therapeutic protocol for the generation of PSMA targeted T cells. Cytokine production suggests activation of these T cells with their persistence in blood for up to 2 weeks. If imaging with FIAU is suboptimal, a second cohort of pts will be studied with 124I- FIAU. Clinical trial information: NCT01140373.
Importance of Gleason score on 18F-choline PET/CT findings in patients with biochemical relapse of prostate cancer disease (PSA<1.0 ng/ml).
Authors: Hodolic Marina , Cimitan Marino , Fettich Jure 
Published: February 2017

86 Background: Not all tumors show significant increase of metabolic activity on 18F-FDG PET/CT imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. As a component of cell membrane phospholipids, choline is an excellent biomarker for the malignant transformation and increased proliferation of cells. 18F-choline (18F-FCH) PET/CT is a nuclear medicine procedure that has greater sensitivity and accuracy than 18F-FDG PET/CT to detect prostate malignancy: sensitivity 73% vs. 31% and accuracy 67% vs. 53%, respectively. The efficiency of FCH to detect prostate cancer disease before and after treatment is related to the PSA levels. Evaluation of recurrent disease with 18F-FCH PET/CT imaging in patients with prostate cancer disease is becoming a routine procedure. Purpose: To investigate the role of Gleason score (GS), as a marker of proliferation, on 18F-FCH PET/CT findings in patients with biochemical relapse of prostate cancer disease defined as increased level of prostate specific antigen (PSA). Methods: 140 patients with biochemical relapse (PSA<1.0 ng/ml) underwent 18F-FCH PET/CT scan after treatment: radical prostatectomy, radiotherapy, hormonal therapy alone or combined treatment. Results: 18F-FCH PET/CT detected prostate cancer recurrence in 97% of patients with GS>7, 82% of patients with GS=7 and 63% of patients with GS<7. All patients had PSA between 0.2 and 1.0 ng/ml. Out of 140 patients 43% had recurrence in prostatic bed and 57% patients had local metastasis. Conclusions: Prostate cancer proliferation defined as Gleason score, influence 18F-FCH PET/CT findings in patients with biochemical relapse of prostate cancer disease at any PSA level.
Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial.
Authors: Sweeney Christopher , Chen Yu-Hui , Carducci Michael Anthony , Liu Glenn , Jarrard David Frasier , Eisenberger Mario A. , Wong Yu-Ning , Hahn Noah M. , Kohli Manish , Vogelzang Nicholas J. , Cooney Matthew M. , Dreicer Robert , Picus Joel , Shevrin Daniel H. , Hussain Maha , Garcia Jorge A. , DiPaola Robert S. 
Published: February 2017

LBA2 Background: Docetaxel (D) improves OS of men with mPrCa who have progressed on androgen deprivation therapy (ADT). We aimed to assess the benefit of upfront chemohormonal therapy for metastatic PrCa. Methods: 1:1 randomization to ADT alone or ADT + D dosed 75mg/m2 every 3 weeks for 6 cycles within 4 month (mos) of starting ADT. Stratification factors: high volume (HV) vs. low volume (LV) disease (HV: visceral metastases and/or 4 or more bone metastases); anti-androgen use beyond 30 days; Age ≥70 vs. < 70 years; ECOG PS 0-1 vs. 2; Prior adjuvant ADT > 12 vs. ≤ 12 mos; FDA approved drug for delaying skeletal related events. Key eligibility criteria: suitable organ and neurological function for D; adjuvant ADT ≤ 24 mos and no progression within 12 mos of adjuvant ADT. OS was the primary endpoint and the study was powered to assess for a 33.3% improvement in median OS (80% power and 1-sided alpha=2.5%). Projected median OS for ADT alone: HV-33 mos; LV-67 mos. Results: 790 men were accrued from 7/28/06 to 11/21/2012: ADT N=393; ADT + D: N=397; balanced for demographic, stratification and disease factors. Median age: 63 years (range: 36 to 91); 98% ECOG PS 0 or 1; 89% Caucasian; 24% prior radiotherapy, 24% prior prostatectomy; HV 64% on ADT and 67% on ADT + D. Data released after 4th interim analysis in Sept 2013 when O’Brien Fleming upper boundary was crossed with 53.1% information. This report reflects 1/16/2014 data with median follow-up of 29 mos with 137 deaths on ADT alone vs. 104 deaths on ADT+D. ADT+D: Grade (G) 3/4 Neutropenic fever: 4%/2%; G3 neuropathy: 1% sensory, 1% motor; 1 death due to treatment (no deaths due to treatment on ADT). Efficacy data is in the table below. After disease progression, 123 pts on ADT alone and 45 pts on ADT + D received docetaxel. Conclusions: ADT + D improves OS over ADT alone in men with HV mPrCa. Longer follow-up is needed for men with LV mPrCa. Clinical trial information: NCT00309985. [Table: see text]
Efficacy of subcutaneous testosterone on menopausal symptoms in breast cancer survivors.
Authors: Glaser Rebecca L. , York Anne E. , Dimitrakakis Constantine 
Published: February 2017

109 Background: Menopausal symptoms can be severe in breast cancer survivors in whom estrogen therapy is contraindicated. Our previous pilot trial demonstrated that testosterone (T) combined with anastrozole (A) in subcutaneous implants provided therapeutic T levels without elevating estradiol. Our current goal was to document the clinical effect of T+A combination implants (no estrogen) on menopausal symptoms. Methods: This IRB approved study was designed to prospectively follow breast cancer survivors (stage 0-4) treated with subcutaneous T+A, for breast cancer recurrence. The therapeutic effectiveness of T on the relief of psychological, somatic and urogenital symptoms was documented using the validated, self administered, 11 item Menopause Rating Scale. Patients completed the survey prior to and following therapy. Results: Over 950 T/T+A pellet insertions have been performed in breast cancer survivors since 2006. Since 4/2013, 72 patients have been enrolled in the study. T dosing is weight based. Implants are inserted at 3-month intervals on average. Therapeutic T levels were confirmed without elevation of estradiol in any postmenopausal survivor. There have been no cancer recurrences in up to 8 years of therapy. A single patient with active metastatic disease at enrollment developed ascites. There was statistically significant improvement (P < 0.0001) in psychological symptoms (depression, irritability/aggression, anxiety), somatic symptoms (hot flashes/sweating, heart discomfort, sleep problems/insomnia, physical exhaustion, impaired memory, joint/muscular pain) and urogenital symptoms (vaginal dryness, bladder problems/incontinence, sexual problems). Conclusions: Testosterone in combination with an aromatase inhibitor, delivered by subcutaneous implant, was extremely effective for the relief of hormone deficiency symptoms in breast cancer survivors. Furthermore, this supports testosterone’s therapeutic effect via the androgen receptor. [Table: see text]
Mortality among women diagnosed with stage II or III breast cancer based on SEER-Medicare data.
Authors: Hernandez Rohini Khorana , Liede Alexander , Li Shuling , Liu Jiannong , Hu Yan , Stryker Scott , Blaes Anne Hudson , Collins Allan J 
Published: February 2017

111 Background: Increasing emphasis on assessing the quality of treatment (tx) for cancer patients highlights the need for real-world data sets that can address critical policy questions about cancer care in the US. This study examined treatment and mortality in women with incident early-stage breast cancer (BC) 2007-2009 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. Methods: We identified women age ≥66 years at the diagnosis of AJCC stage II/III BC between 2007-2009, who received surgery and were enrolled with Medicare Parts A and B. Women were followed from definitive surgery until the end of 2010, death, or change in enrollment status. Risk (cumulative incidence proportion [CIP]) of all-cause death was calculated with 95% confidence intervals (CI) using the Kaplan-Meier method stratified by tumor characteristics and tx type. Results: The cohort included 10,048 women with stage II (78%) or III (22%); 58% were ≥75 years and 78% had hormone-receptor (HR) positive tumors (77% ER positive, 64% PR positive). After the definitive surgery, 1,271 deaths reflected a CIP of 5.7% (95% CI 5.3-6.2) at 1 year, 10.9% (10.2-11.5) at 2 years, and 16.9% (15.9-17.9) at 3 years. Unadjusted mortality (Table) was higher among those without chemotherapy (chemo), women with neo-adjuvant tx, and those identified as “triple negative” phenotype (HR negative, no trastuzumab). Conclusions: Linking SEER and Medicare allowed us to assess mortality according to tumor characteristics and cancer treatments, respectively, which are both related to prognosis. The use of administrative data from Medicare should be further enhanced with inclusion of test results from standard gene expression panels to ensure a better match of therapy for the patient and adequate assessment of resource utilization. [Table: see text]
Exercise training, inflammatory cytokines, and other markers of low-grade inflammation in breast cancer survivors: A systematic review and meta-analysis.
Authors: Meneses-Echavez Jose F , Ramirez-Velez Robinson , Gonzalez-Jimenez Emilio , Schmidt Rio-Valle Jacqueline , Sanchez Perez Maria Jose , Molina Montes Esther 
Published: February 2017

121 Background: Low-grade inﬂammation, characterized by high cytokine activity, plays a crucial role in tumorigenesis. Further, cytokines and other inflammatory biomarkers are closely implicated in tumor growth, angiogenesis, and metastasis. This metaanalysis of randomized controlled trials estimates the effects of exercise training in the control of the serum levels of cytokines and other inflammatory markers in breast cancer survivors. Methods: PRISMA statement and the Cochrane Handbook were followed. We searched MEDLINE, CENTRAL, EMBASE, Scopus and DARE database to retrieve randomized controlled trials published between 1980- March 2014 providing effect estimates of exercise interventions in the serum levels of cytokines, such as interleukin (IL) -2, IL-6, IL-8, tumoral necrosis factor alpha (TNF-α) and C-reactive protein (CRP) in breast cancer survivors. An Inverse of variance (IV) fixed-effects model was conducted in absence of heterogeneity (I2<50%); otherwise a random-effects model was selected. Mean Differences (MD) were calculated to estimate differences between groups (p<0.05 with 95% Confidence interval). Heterogeneity was measured with the Chi2 test (p<0.10) and I2 statistics. Results: A total of 15 studies were included (n=1,447; mean age= 51.6 years old). Exercise interventions resulted in positive effects for CRP (MD= 0.37, 95%CI, 0.04 to 0.71; p= 0.03; I2=15%), IL-2 (MD= -6.04, 85%CI, -11.41 to -0.67; p=0.03; I2=0%), IL-10 (-22.90, 95%CI, -41.27 to -4.53; p=0.001, I2=0%) and waist circumference as indicator of body composition (MD= -1.12, 95%CI, -2.06 to -0.18; p=0.02; I2=45%). Non-significant differences were observed for IL-6 and TNF-α. There was no evidence of publication bias. Conclusions: These findings suggest that exercise training improves the systemic pro-inflammatory profile in breast cancer survivors and consequently the immunological responses and the carcinogenic processes related to tumoral environment. The effects observed for IL-10 provide a novel focus of evidence for the role of exercise as an effective anti-inflammatory intervention in cancer survivors.
Value of routine staging imaging studies (RSIS) for patients with stage III breast cancer (BC).
Authors: Piatek Caroline Irene , Ji Lingyun , Kaur Chandanpreet , Church Terry , Spicer Darcy V. , Tripathy Debu , Russell Christy Ann , Lang Julie E. , Macdonald Heather R. , Sener Stephen Francis , Silberman Howard , Sposto Richard , Garcia Agustin A. 
Published: February 2017

122 Background: RSIS (CT, bone and PET scan) in pts with stage I or II BC is not recommended by NCCN and is considered optional in stage III BC. 10-15% of pts with stage III BC have occult metastases by RSIS, but it is unclear if this finding affects pt management or outcome. The addition of PET scans to conventional imaging (CT and bone scans) is of little added value (Niikura, et al. Oncologist 2011; 16: 772-82). We hypothesized that the use of RSIS in pts with stage III BC does not lead to changes in treatment or pt outcomes. Methods: After IRB approval, we retrospectively identified 875 women with stage III or stage IV BC from 2000-2010 through the Los Angeles County-University of Southern California and Norris Comprehensive Cancer Center cancer registries. Pts with clinically apparent stage IV disease, pregnancy at time of diagnosis, a history of prior malignancy, or incomplete medical records were excluded. Pts who underwent RSIS prior to planned treatment (before surgery, neoadjuvant or adjuvant therapy) were identified. RSIS results and the treatment plan in response to the results were recorded. Results: 424 pts were identified with clinical or pathologic stage III BC: 197 pts (46%) were < 50 years old, 224 (53%) had ER+ or PR+/HER2- tumors, 111 (26%) had ER-/PR-/HER2+ tumors, 74 (17%) had triple negative tumors, 15 (4%) had missing biomarker data, and 61 (14%) had inflammatory BC. 365 pts (86%) underwent RSIS. RSIS were negative for metastatic disease in 266 (73%), indeterminate in 75 (21%), and positive in 24 (7%). Treatment was altered in 21 pts (6%) based on RSIS (20 with metastatic disease, 1 with indeterminate disease). Median follow-up was 3.8 years (range: 0.1 to 13.3). When controlled for age, stage, or biomarker status, no differences in progression-free survival (PFS) were observed between the pts who underwent RSIS compared to those that did not. Conclusions: Most pts with stage III BC undergo RSIS. However, the results of RSIS infrequently affect treatment decisions. We did not observe a difference in PFS between pts who underwent RSIS and those who did not. Our findings suggest RSIS in stage III BC has limited value. A prospective study of this research question is warranted.
Primary analysis of the prospective, randomized, phase II trial of GP2+GM-CSF vaccine versus GM-CSF alone administered in the adjuvant setting to high-risk breast cancer patients.
Authors: Schneble Erika J , Perez Sonia A. , Murray James L. , Berry John S. , Trappey Alfred F. , Vreeland Timothy J. , Hale Diane F. , Greene Julia M. , Clifton Guy T. , Ardavanis Alexandros , Litton Jennifer Keating , Ponniah Sathibalan , Shumway Nathan M. , Papamichail Michael , Peoples George Earl , Mittendorf Elizabeth Ann 
Published: February 2017

134 Background: GP2 is a HER2 derived, HLA-A2+-restricted immunogenic peptide designed to stimulate CD8+T cells to recognize tumor cells with any level of HER2 expression (IHC 1-3+). Accrual to a prospective, randomized, multi-center, phase II trial of the GP2 vaccine for prevention of breast cancer recurrence has completed. Here, the planned primary analysis of disease-free survival (DFS) is presented. Methods: HLA-A2+ node positive or high-risk node negative breast cancer patients (pts) with any level of HER2 expression rendered disease-free by standard of care therapy (to include trastuzumab where appropriate) were randomized to receive GP2+GM-CSF (VG) or GM-CSF (CG) alone. Pts received 6 monthly inoculations (primary vaccine series = PVS) followed by 4 boosters administered every 6 months. The Kaplan Meier method was used for statistical analysis. The intention-to-treat (ITT) population is defined as the entire randomly assigned population. The per-treatment (PT) group excluded pts who recurred during the PVS or developed a second malignancy. A pre-specified subgroup analysis was performed based on HER2 expression level. HER2 overexpression (OE) is defined as IHC 3+or FISH >2.2. Results: With 89 VG and 91 CG pts enrolled and vaccinated, there are no differences between groups with respect to age, node positivity, tumor size, grade, ER/PR status, and HER2 expression (p>0.05). The vaccine has been well tolerated with toxicities comparable between the VG and CG. Only one grade 3 local and systemic toxicity reaction has been reported in the VG. At 34 (1-60) month median follow-up, DFS was compared in the ITT (85% VG v 81% CG, p = 0.57) and PT (94% VG v 85% CG, p = 0.17) populations. In OE patients (51 VG and 50 CG) DFS was 94% VG v 89% CG, p = 0.86 (ITT) and 100% VG v 89% CG, p = 0.08 (PT). Conclusions: GP2+GM-CSF is a novel vaccine that is safe and well tolerated. This phase II trial demonstrates potentially greater benefit in pts with HER2 OE tumors, in whom there have been no recurrences in the PT group. This may be due to synergism with trastuzumab therapy, thus justifying a phase III trial evaluating GP2 administered in the adjuvant setting to a HER2 OE population. Clinical trial information: NCT00524277.
Stomatitis incidence and its relationship with efficacy: A meta-analysis of everolimus clinical studies.
Authors: Rugo Hope S. , Yao James C. , Pavel Marianne , Ravaud Alain , Franz David Neal , Taran Tanya , Gallo Jorge , Rouyrre Nicolas , Anak Oezlem , Motzer Robert J. 
Published: February 2017

151 Background: The most common adverse event (AE) with everolimus (EVE) is stomatitis. This meta-analysis evaluated the incidence, severity, and possible impact of stomatitis on efficacy in patients (pts) with cancer or tuberous sclerosis complex (TSC) who received EVE. Methods: Stomatitis events from 7 randomized, double-blind, phase 3 EVE studies included: RECORD-1 (RCC), RADIANT-2 (NET), RADIANT-3 (pNET), BOLERO-2 (HR+/HER2- breast cancer [BC]), BOLERO-3 (HER2+BC), and EXIST-1 and -2 (TSC). Time to first stomatitis occurrence and recurrence were analyzed using Kaplan-Meier (KM) methods. Stratified Cox regression analysis adjusted for baseline prognostic factors and corrected for confounding effect of duration of exposure was used to analyze association between stomatitis occurrence (≤ 8 wks of EVE start) and PFS in pts with cancer and response rate in pts with TSC. Results: This evaluation included EVE-treated pts with cancer (n = 1,455) and TSC (n = 157). Pts with cancer had stomatitis incidence of 66.9%, which occurred early, median 0.82 mo (95% CI, 0.7-1.0; 2-mo KM estimate 60.8%). 8.6% were grade 3/4 events. 1.7% of pts discontinued due to stomatitis. Stomatitis recurred in 40% of pts and appeared gradually. In pts with TSC similar results were observed. In EVE-treated pts, development of stomatitis was associated with longer PFS (corrected HR [95% CI]) in BOLERO-2 (0.78 [0.62-1.00]) and RADIANT-3 (0.70 [0.48-1.01]), and similar trend was observed in RECORD-1 (0.90 [0.66-1.22]) and RADIANT-2 (0.87 [0.61-1.22]), but not in BOLERO-3. In TSC, probably due to few pts, relationship between stomatitis and response was not conclusive. In all trials, pts on EVE had longer PFS vs placebo irrespective of stomatitis incidence. Conclusions: Stomatitis is observed frequently in initial wks of EVE therapy. Most AEs were grade 1/2 and manageable, rarely led to pt discontinuation. Stomatitis recurred in < 50% of pts. EVE-treated pts with cancer who had stomatitis achieved stable benefit similar to overall population, suggesting that continuing EVE is helpful. The importance of prophylactic measures in reducing EVE-induced stomatitis incidence and improving its management is being determined by ongoing studies.
Refractory granulomas of breast: Benign or malignant disease.
Authors: Freeman Christopher Mark , Lewis Jaime D , Lower Elyse E. , Khan Shagufta , Shaughnessy Elizabeth 
Published: February 2017

21 Background: Idiopathic granulomatous mastitis (IGM) is an uncommon benign inflammatory breast disease of unknown etiology that may mimic malignancy, infectious diseases, or autoimmune conditions requiring a diagnosis of exclusion. Because the differential diagnosis includes benign as well as malignant disease, an organized approach to the diagnosis and its symptom management is needed. Treatment may include corticosteroids, immunosuppression, or in severe refractory cases, surgery. Methods: This IRB-approved single tertiary referral center study was performed to better characterize the presentation, risk factors, differential diagnosis, and treatment options for IGM. All patients identified in a pathology database with a biopsy consistent with IGM were studied. Data collected included demographics, duration and quality of symptoms, imaging results, microbiology, pathology, systemic and surgical therapies, and outcomes. Results: Between 2006 and 2014, 16 eligible patients were identified. Patients with a prior history of IGM, cancer, or other granulomatous diseases were excluded. Twelve patients were evaluable, and four patients were excluded due to insufficient records. The mean age was 31.9 years (23 to 54) with 50% of patients black and 25% Hispanic. Pregnancy occurred within 5 years of biopsy in 67% of patients. The most common presenting symptom was mass (83%) with focal pain (75%), and the mean duration of symptoms was 5.1 months (0.5 to 16). All microbial cultures were negative. Following diagnosis, systemic treatment included antibiotics (58%), corticosteroids (25%), and methotrexate (17%). Due to refractory symptoms and toxicity despite steroids and methotrexate, surgical intervention was necessary in 67%. Partial mastectomy was performed in 50% and total mastectomy in 17%, with one patient requesting mastectomy for palliation. Conclusions: Although rare, IGM is difficult to diagnose and manage, and an accurate diagnosis must exclude malignancy and other granulomatous processes. Despite the benign nature of the disease, surgical intervention may be required. Systemic treatment with corticosteroids and methotrexate may decrease the need for surgical intervention.