bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase IB trial redesign to test role of IL2 with anti-PSMA designer T cells to yield responses in advanced prostate cancer.
Authors: Junghans Richard P. 
Published: February 2017

70 Background: We created a chimeric antigen receptor (CAR) for prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” specifically kill prostate cancer cells in vitro and in vivo in animal models (Ma et al. Prostate 2004:61:12-25). FDA approved a Phase I clinical trial. Methods: Patient T cells are retrovirally transduced and expanded. Patients undergo non-myeloablative (NMA) conditioning to create “hematologic space” into which designer T cells are infused for engraftment and improved in vivo efficacy. Patients are co-administered continuous infusion IL2. Patients are monitored for safety and response. Results: Five patients were treated, three at 10^9 and two at 10^10 cell dose levels with safety. Partial responses (PR) were seen in 2/5 patients (40%), with PSA suppressions of 50 and 70% over 1-2 months and PSA progression delay of 70 and 150 days. Yet these responses were observed only at the lowest T cell dose (10^9 cells) and not the higher tested dose (10^10 cells). Response correlated with plasma IL2 that was as much as 10-fold lower in non-responders vs responders. This low IL2 correlated in turn with high engrafted fractions of infused activated T cells. This prompted a hypothesis that infused activated T cells at high engrafted cell numbers absorbed out IL2 to a level too low to sustain dTc activation for effective tumor killing. A study redesign will test high dose IL2 (HDI) versus moderate dose IL2 (MDI) in Phase Ib/Pilot at 10^10 cell dose, then advancing to the maximum practical dose (MPD, 10^11 cells) of dTc under the optimal IL2 plan. Conclusions: A new approach to adoptive immune therapy in metastatic prostate cancer has been devised with encouraging early results. We postulate that adequate higher IL2 in vivo will allow the greater potency of higher dTc doses to be revealed, thereby potentially inducing PSA reductions of 100%, with durable remissions of metastatic prostate cancer that is refractory to all other treatments. Patients are being recruited. This clinical trial received funding from US Army/DOD and from Prostate Cancer Foundation for preclinical work.
Rye bread consumption in early life and reduced risk of advanced prostate cancer.
Authors: Torfadottir Johanna Eyrun , Valdimarsdottir Unnur Anna , Mucci Lorelei , Stampfer Meir J. , Kasperzyk Julie , Fall Katja , Tryggvadottir Laufey , Aspelund Thor , Olafsson Orn , Harris Tamara B. , Jonsson Eirikur , Tulinus Hrafn , Adami Hans-Olov , Gudnason Vilmundur , Steingrimsdottir Laufey 
Published: February 2017

79 Background: Prior evidence suggests that rye consumption may reduce risk of prostate cancer (PCa). Our aim is to study whether consumption of rye bread and oatmeal (sources of lignans and fiber), both in early- and midlife, is associated with risk of PCa. Methods: In 2002 to 2006, 2,268 men, aged 67-96 years, reported their dietary habits in the AGES-Reykjavik cohort study. Dietary habits were assessed retrospectively, for early and midlife using a validated food frequency questionnaire (FFQ). Through linkage to cancer- and mortality registers, we retrieved information on PCa diagnosis and mortality through 2009. We used logistic regression to estimate odds ratios (ORs) for PCa according to rye- and oatmeal consumption, adjusted for possible confounding factors including fish-, fish liver oil-, meat-, and milk intake. Results: Of the 2268 men, 347 had or were diagnosed with PCa during follow-up, 63 with advanced disease (stage 3+ or died of PCa). Daily rye bread consumption in adolescence (vs. less than daily) was associated with a decreased risk of PCa diagnosis (OR 0.78; 95% CI: 0.60, 1.00), and of advanced PCa (OR 0.53; 95% CI: 0.32, 0.93). High intake of oatmeal in adolescence (≥5 vs. ≤4 times/ week) was not significantly associated with risk of PCa diagnosis (OR 1.00; 95% CI: 0.78, 1.29) nor advanced PCa (OR 0.73; 95% CI: 0.41, 1.31). Midlife consumption of rye or oatmeal was not associated with PCa risk. Conclusions: Our data suggest that frequent rye bread consumption in adolescence may be associated with reduced risk of PCa, particularly advanced disease.
Significance of a case-management-led, multidisciplinary team approach in the treatment of prostate cancer.
Authors: Helbert Matthew , Brand Timothy 
Published: February 2017

81 Background: Prostate cancer is the most commonly diagnosed non-skin malignancy within the Madigan Health System. Madigan recognized the burden of prostate cancer and began a process improvement initiative on June 1, 2009 to provide patient-focused multi-disciplinary counseling and consultative service to patients newly and previously diagnosed with prostate cancer. Methods: The multi-disciplinary team and Prostate Cancer Pathway are led by a RN Case Manager in collaboration with the Departments of Urology, Radiation Oncology and Hematology Oncology. Patients enrolled in the pathway are case managed in accordance with NCCN evidenced based guidelines and have access to all specialty services contained within Madigan, the U.S. Army Western Region Medical Command, and the Tricare referral network. Major program goals of the Prostate Cancer Pathway are to bolster patient surveillance to levels congruent with national evidenced based guidelines, and to promote efficient use of clinic time by selectively scheduling patients based on acuity. The aims of the pathway are primarily accomplished through case management. Results: Prior to the implementation of case management, prostate cancer patients averaged 3.3 appointments per annum. Per NCCN guidelines, the average number of annual visits is 2.8 during the initial 5 year post treatment phase. Upon completion of 18 consecutive months of case management, program metrics indicate that the average number prostate cancer visits decreased to 2.9 appointments per year. Concurrently, case management screening impacted scheduled visits; resulting in 485 avoided appointments for reasons of clinical stability and favorable patient reported quality of life indicators. As a result of enhanced access, the total number of post program deployment prostate cancer patients increased by approximately 15%. Conclusions: Initial identified metrics indicate that prostate cancer case management can considerably impact surveillance rates and clinic efficiency and may be disseminated to additional populations. The case management led model has recently been utilized to create a similar pathway to address testicular cancer within the Madigan Health System.
Single or two instillations of pirarubicin as prophylaxis for recurrence after transurethral resection of Ta and T1 transitional cell bladder cancer: A prospective, randomized controlled study.
Authors: Saika Takashi , Tsushima Tomoyasu , Nasu Yasutomo , Kumon Hiromi ,   Okayama Urological Research Group
Published: February 2017

LBA266 Background: Although single intravesical instillation chemotherapy immediately after transurethral resection (TUR) is the standard treatment for non-muscle-invasive bladder tumors, 40% to 80% of tumors show intravesical recurrence. In this prospective randomized controlled study, we try to evaluate the prophylactic efficacy and safety of twice intravesical instillation using pirarubicin (THP) administered immediately after TUR and on the next day following TUR by comparison with single instillation immediately after TUR. Methods: Between 2005 and 2009, 250 patients with Ta and T1 solitary bladder carcinoma were enrolled in this study. Patients were randomized into two groups. Group A patients were treated with two intravesical instillations of THP 30 mg/50 ml saline immediately after TUR and within 24 hours. Group B patients were treated with single instillation of the same dose immediately after TUR as a control group. The primary endpoint was duration to the first recurrence, and the secondary endpoint was safety. Results: The enrollment was closed on 2009, and the follow-up phase is in process. Of the 250 patients, 125 in Group A and 125 in Group B could be evaluated as full analysis set. One hundred eight male and 17 female were in Group A, on the other hands, one hundred five male and 20 female were in Group B. Eighty-six cases (69%) in group A, and 88 cases (70%) in group B were primary tumor. Fifty-seven cases (46%) in group A, and 56 cases (45%) in group B were small tumor (less than 10mm). There was no difference between backgrounds of both groups. The randomization worked well. In this ad interim report, median follow up was 48 months. Two-year recurrence-free rates were 76.8% in group A and 67.5% in group B. Adverse reactions related to instillation were observed in about 20% of the patients. These toxicities were mild and transient. Only the incidence of frequency in group A was higher than that in group B (20% vs. 8%, p=0.0106). Conclusions: Intravesical instillation of THP 30 mg twice within 24 hours after TUR was effective as prophylactic therapy for non-muscle-invasive cancer with tolerable toxicity problems.
Inflammatory Cytokines and Comorbidity Development in Breast Cancer Survivors Versus Noncancer Controls: Evidence for Accelerated Aging?
Authors: Alfano Catherine M. , Peng Juan , Andridge Rebecca R. , Lindgren Monica E. , Povoski Stephen P. , Lipari Adele M. , Agnese Doreen M. , Farrar William B. , Yee Lisa D. , Carson William E. , Kiecolt-Glaser Janice K. 
Published: February 2017

Purpose The sequelae of cancer treatment may increase systemic inflammation and create a phenotype at increased risk of functional decline and comorbidities, leading to premature mortality. Little is known about how this trajectory compares with natural aging among peers of the same age without cancer. This longitudinal study investigated proinflammatory cytokines and comorbidity development over time among breast cancer survivors and a noncancer control group. Methods Women (N = 315; 209 with breast cancer and 106 in the control group) were recruited at the time of their work-up for breast cancer; they completed the baseline questionnaire, interview, and blood draw (lipopolysaccharide-stimulated production of interleukin [IL] -6, tumor necrosis factor-α, and IL-1β). Measures were repeated 6 and 18 months after primary cancer treatment (cancer survivors) or within a comparable time frame (control group). Results There were no baseline differences in comorbidities or cytokines between survivors and the control group. Over time, breast cancer survivors had significantly higher tumor necrosis factor-α and IL-6 compared with the control group. Survivors treated with surgery, radiation, and chemotherapy accumulated a significantly greater burden of comorbid conditions and suffered greater pain associated with inflammation over time after cancer treatment than did the control group. Conclusion Survivors who had multimodal treatment had higher cytokines and comorbidities, suggestive of accelerated aging. Comorbidities were related to inflammation in this sample, which could increase the likelihood of premature mortality. Given that many comorbidities take years to develop, future research with extended follow-up beyond 18 months is necessary to examine the evidence of accelerated aging in cancer survivors and to determine the responsible mechanisms.
Randomized Phase II Trial of Seribantumab in Combination With Paclitaxel in Patients With Advanced Platinum-Resistant or -Refractory Ovarian Cancer
Authors: Liu Joyce F. , Ray-Coquard Isabelle , Selle Frederic , Poveda Andrés M. , Cibula David , Hirte Hal , Hilpert Felix , Raspagliesi Francesco , Gladieff Laurence , Harter Philipp , Siena Salvatore , del Campo Josep Maria , Tabah-Fisch Isabelle , Pearlberg Joseph , Moyo Victor , Riahi Kaveh , Nering Rachel , Kubasek William , Adiwijaya Bambang , Czibere Akos , Naumann R. Wendel , Coleman Robert L. , Vergote Ignace , MacBeath Gavin , Pujade-Lauraine Eric 
Published: February 2017

Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) –mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab. Patients and Methods Patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned at a ratio of two to one to receive seribantumab plus paclitaxel or paclitaxel alone. Patients underwent pretreatment core needle biopsy; archival tumor samples were also obtained to support biomarker analyses. Results A total of 223 patients were randomly assigned (seribantumab plus paclitaxel, n = 140; paclitaxel alone, n = 83). Median PFS in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741 to 1.425; P = .864). Among patients whose tumors had detectable HRG mRNA and low HER2 (n = 57 [38%] of 151 with available biomarker data), increased treatment benefit was observed in those receiving seribantumab plus paclitaxel compared with paclitaxel alone (PFS HR, 0.37; 95% CI, 0.18 to 0.76; P = .007). The HR in patients not meeting these criteria was 1.80 (95% CI, 1.08 to 2.98; P = .023). Conclusion The addition of seribantumab to paclitaxel did not result in improved PFS in unselected patients. Exploratory analyses suggest that detectable HRG and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for HRG expression and focus on cancers with low HER2 levels.
Cetuximab Plus Chemoradiotherapy for HIV-Associated Anal Carcinoma: A Phase II AIDS Malignancy Consortium Trial
Authors: Sparano Joseph A. , Lee Jeannette Y. , Palefsky Joel , Henry David H. , Wachsman William , Rajdev Lakshmi , Aboulafia David , Ratner Lee , Fitzgerald Thomas J. , Kachnic Lisa , Mitsuyasu Ronald 
Published: February 2017

Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after definitive chemoradiation (CRT), associated with anogenital human papilloma virus, and often appears in HIV infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus–associated oropharyngeal SCC, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Forty-five patients with stage I to III SCCAC and HIV infection received CRT: 45 to 54 Gy radiation therapy to the primary tumor and regional lymph nodes plus eight once-weekly doses of concurrent cetuximab and two cycles of cisplatin and fluorouracil. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power, 90%), assuming a 35% LRF rate from historical data. Results The 3-year LRF rate was 42% (95% CI, 28% to 56%; one-sided P = .9) by binomial proportional estimate using the prespecified end point (LRF or alive without LRF and followed < 3 years), and 20% (95% CI, 10% to 37%) by Kaplan-Meier estimate in post hoc analysis using definitions and methods consistent with historical data. Three-year rates by Kaplan-Meier estimate were 72% (95% CI, 56% to 84%) for progression-free survival and 79% (95% CI, 63% to 89%) for overall survival. Grade 4 toxicity occurred in 26%, and 4% had treatment-associated deaths. Conclusion HIV-associated SCCAC is potentially curable with definitive CRT. Although addition of cetuximab may result in less LRF, the 20% recurrence and 26% grade 4 toxicity rates indicate the continued need for more-effective and less-toxic therapies.
How to Manage the Obese Patient With Cancer
Authors: Renehan Andrew G. , Harvie Michelle , Cutress Ramsey I. , Leitzmann Michael , Pischon Tobias , Howell Sacha , Howell Anthony 
Published: February 2017

Purpose Obesity (body mass index [BMI] ≥ 30 kg/m2) is common among patients with cancer. We reviewed management issues in the obese patient with cancer, focusing on how obesity influences treatment selection (including chemotherapy dosing), affects chemotherapy toxicity and surgical complications, and might be a treatment effect modifier. Methods The majority of evidence is drawn from observational studies and secondary analyses of trial data, typically analyzed in N × 3 BMI categories (normal weight, overweight, and obese) matrix structures. We propose a methodological framework for interpretation focusing on sample size and composition, nonlinearity, and unmeasured confounding. Results There is a common perception that obesity is associated with increased treatment-related toxicity. Accordingly, cytotoxic chemotherapy dose reduction is common in patients with elevated BMI. Contrary to this, there is some evidence that full dosing in obese patients does not result in increased toxicity. However, these data are from a limited number of regimens, and fail to fully capture cytotoxic drug pharmacodynamics and pharmacokinetic variability in obese patients. Among patients undergoing surgery, there is evidence that elevated BMI is associated with increased perioperative mortality and increased rates of infectious complications. A novel finding is that these relationships hold after surgery for malignancy, but not for benign indications. There are biologic plausibilities that obesity might be an effect modifier of treatment, but supporting evidence from clinical studies is inconsistent. Conclusion In line with the ASCO 2012 guidelines, chemotherapy dosing is probably best performed using actual body weight in obese patients. However, specific regimens known to be associated with increased toxicity in this group should be used with caution. There is no guidance on dose for obese patients treated with biologic agents. Currently, there are no specific recommendations for the surgical management of the obese patient with cancer.
Performance of Four Frailty Classifications in Older Patients With Cancer: Prospective Elderly Cancer Patients Cohort Study
Authors: Ferrat Emilie , Paillaud Elena , Caillet Philippe , Laurent Marie , Tournigand Christophe , Lagrange Jean-Léon , Droz Jean-Pierre , Balducci Lodovico , Audureau Etienne , Canouï-Poitrine Florence , Bastuji-Garin Sylvie 
Published: February 2017

Purpose Frailty classifications of older patients with cancer have been developed to assist physicians in selecting cancer treatments and geriatric interventions. They have not been compared, and their performance in predicting outcomes has not been assessed. Our objectives were to assess agreement among four classifications and to compare their predictive performance in a large cohort of in- and outpatients with various cancers. Patients and Methods We prospectively included 1,021 patients age 70 years or older who had solid or hematologic malignancies and underwent a geriatric assessment in one of two French teaching hospitals between 2007 and 2012. Among them, 763 were assessed using four classifications: Balducci, International Society of Geriatric Oncology (SIOG) 1, SIOG2, and a latent class typology. Agreement was assessed using the κ statistic. Outcomes were 1-year mortality and 6-month unscheduled admissions. Results All four classifications had good discrimination for 1-year mortality (C-index ≥ 0.70); discrimination was best with SIOG1. For 6-month unscheduled admissions, discrimination was good with all four classifications (C-index ≥ 0.70). For classification into three (fit, vulnerable, or frail) or two categories (fit v vulnerable or frail and fit or vulnerable v frail), agreement among the four classifications ranged from very poor (κ ≤ 0.20) to good (0.60 < κ ≤ 0.80). Agreement was best between SIOG1 and the latent class typology and between SIOG1 and Balducci. Conclusion These four frailty classifications have good prognostic performance among older in- and outpatients with various cancers. They may prove useful in decision making about cancer treatments and geriatric interventions and/or in stratifying older patients with cancer in clinical trials.
Pulmonary Infiltrates in a Patient With Advanced Melanoma
Authors: Powell Charles A. 
Published: February 2017

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 60-year-old former smoker with metastatic melanoma presented with the chief complaint of pulmonary infiltrates. Five years ago, he was diagnosed with a left chest wall melanoma. He underwent surgery but received no additional therapy for an American Joint Committee on Cancer stage T3a N0 M0 tumor that was 2.7 mm in depth with no ulceration of the epidermal surface. Resection margins were free of tumor. Four years later, he underwent excision of a raised pigmented skin lesion on his left calf that proved to be melanoma with positive margins. He underwent re-excision of melanoma but 2 months later developed a new left hip soft tissue nodule. Positron emission tomography (PET) –computed tomography showed multiple hypermetabolic lesions involving subcutaneous tissue, muscle osseous structures, and bone marrow, consistent with advanced melanoma. He began systemic therapy with ipilimumab and nivolumab. After four cycles of immunotherapy, he developed a nonproductive cough and mild dyspnea on exertion (Modified Medical Research Council dyspnea scale score of 2 [ie, he had to stop for breath when walking at his own pace on level ground]). A chest x-ray showed bilateral hilar enlargement, thickening of the right paratracheal stripe, and scattered patchy increased interstitial markings bilaterally. PET and chest computed tomography images showed enlarged mediastinal adenopathy with increased [18F]fluorodeoxyglucose uptake on PET and scattered diffuse 1- to 2-mm pulmonary nodules with ground-glass opacities ( Fig 1 ). The patient was referred for pulmonary input. The patient had smoked one pack of cigarettes per day for 35 years; he quit 6 years ago. He had no history of pneumonia, childhood asthma, or tuberculosis. His mother had asthma, but there was no other family history of asthma or other lung disease.