tbuckley/cabot-search huggingface dataset:
Improvement of initial management of sarcomas after diffusion of evidence-based guidelines, dependent on the primary location: A population-based study.
Authors: Karine Ligier, Carlos Maynou, Xavier Leroy, Yves Marie Robin, Philippe Martin, Christophe Szymanski, Stephanie Clisant, Florence Richard, Nicolas Penel
Journal: Journal of Clinical Oncology (2014)

e17623 Background: To improve initial management of adult sarcomas, a Northern France regional expert team carried out 2 actions: diffusion of evidence-based guidelines (EBG) for management of soft tissue/visceral sarcoma and yearly educational symposia. The aim of this study is to measure the impact of EBG on key-indicators of adult sarcoma management. Methods: We conducted a population-based before-after study (year 2005 versus 2008-2009; 63 versus 86 cases) in the Lille region (Northern France urban/suburban area comprising of 800,000 inhab.). Key-indicators were pre-therapeutic biopsy, appropriate tumour and chest imaging, expert interdisciplinary discussion, expert interdisciplinary discussion before the first treatment, and the rate of R0 resection for cases that had been operated on. Results: There was no statistical difference in patient and tumour characteristics between both periods (in terms of gender, prior cancer, primary location, histological subtype, grade, size, metastasis or lymph node involvement). There was no statistical improvement in primary tumour imaging (83 versus 87%), in chest imaging (67 vs 71%), pre-therapeutic biopsy (57 vs 58%), in expert multidisciplinary discussion (37 vs 45%) and discussion before the first treatment (26 vs 44%). However, when soft tissue and bone sarcoma were analyzed separately, we observed significant improvement in expert multidisciplinary discussion (50 vs 74%, p=0.02) and in R0 resection rate (58 vs 91%, p=0.002). On the contrary, for visceral sarcoma, there was no improvement in expert multidisciplinary discussion (10 vs 16%, p=0.3), nor in R0 resection (88 vs 81%, p=0.7). Conclusions: The diffusion of EBG is associated with a limited improvement of sarcoma management when measured in a before-after population-based study and this improvement depends on the primary location of the tumour. Efforts have to make to implement these guidelines in all surgical teams that may treat sarcoma, including visceral sarcoma.
Long term overall survival (OS) in patients with primary metastatic kidney cancer: An analysis of 1468 patients from the Austrian National Cancer Registry (ANCR).
Authors: Martin Marszalek, Henrike E Karim-Kos, Stephan Madersbacher, Michael Rauchenwald, Monika Hackl
Journal: Journal of Clinical Oncology (2017)

489 Background: The introduction of thyrosinkinase inhibitors (TKI) changed the treatment of metastatic kidney cancer fundamentally. To elaborate the potential impact of TKI therapies, we studied trends in OS for patients with primary metastatic kidney cancer between 1998 and 2014 in Austria. Methods: All patients with primary metastatic kidney cancer aged ≥18 years, diagnosed from 1998-2009 were derived from the ANCR (n=2134). Patients diagnosed from 2004-2006 (n=316) were excluded (transition period of systemic therapies). To evaluate differences in OS between patients treated in preTKI-era and TKI-era, two periods were defined: 1998-2003 (before the introduction of Sunitinib in Austria, P1; n=926) and 2006-2009 (P2; n=542). Follow-up was complete until December 31 st , 2014. OS rates were estimated by using the Kaplan-Meier method. The Cox proportional hazard model was used to calculate hazard ratios (HR). Results: A total 1468 patients was included in the analysis. The median age of the study population was 70 yrs (sd ±12) and did not differ between the two eras. The incidence of T1 tumors increased from 6.6% in P1 to 10% in P2 while T4 tumors decreased from 15% to 6.5% (p&lt;0.001). Surgery rate remained stable at 48% (p=0.14). Five-year OS for patients undergoing surgery slightly increased from 16% in P1 to 20% in P2, although not significant (p=0.11). For patients without surgery 5-year OS improved from 4.3% in P1 to 7.9% in P2 (p=0.02). Apart from surgery, survival gain was observed for younger patients (&lt;75 yrs) of 4% (p=0.04) and for T3/T4 tumors of 7% (p=0.008). The risk of death (HR) for patients treated in the TKI-era was reduced compared to the preTKI-era (HR 0.83, 95% CI 0.74-0.93) adjusted for sex, age, T-stage, and surgery. Survival advantage for patients undergoing surgery remained significant (HR: 0.50, 95% CI 0.45-0.57) after adjustment for TKI-era, sex, age, and T-stage. Conclusions: Patients with primary metastatic kidney cancer treated in the TKI era show improved OS compared to the cytokine era. Most benefit was observed in non-surgical patients, younger patients, and for T3/T4 disease. Surgery remains as an important therapy for additional survival benefit.
Previous history of bladder cancer as a prognostic factor for patients diagnosed with transitional cell carcinoma of the upper urinary tract
Authors: M. Mullerad, D. Golijanin, H. N. Chen, S. Donat, B. Bochner, H. W. Herr, P. C. Sogani, P. Russo, M. W. Kattan, G. Dalbagni
Journal: Journal of Clinical Oncology (2004)

4598 Background: Upper tract transitional cell carcinoma (UTTCC) is a relatively rare tumor. Tumor stage, grade, carcinoma in situ and multifocality have been previously described as adverse prognostic factors. This study evaluate whether prior history of bladder TCC (BTCC) is a prognostic factor for patients diagnosed with UTTCC. Methods: We report on 129 patients, median age 68 years, who underwent 129 nephroureterectomies for UTTCC from July 1989 to June 2002. Sixty seven patients had primary UTTCC and 62 had either previous (n=52) or synchronous (n=10) BTCC. Medical records were reviewed and analyzed for possible prognostic predictors (primary tumor stage, grade, multifocality, carcinoma in situ, symptoms and signs at presentation, gender, and history of smoking ). Disease specific survival and bladder recurrence free survival was analyzed by the Kaplan-Meier curves, and differences between the groups were compared by the log-rank test. The Cox Proportional Hazards regression model was used to assess the significance of each predictor. Results: Disease specific death was reported for 44 patients. In a multivariate analysis, using previous BTCC as a predictor (categorized to superficial, invasive or none), both primary disease stage and history of BTCC (invasive and superficial) were significantly associated with disease specific survival (P=0.0013, P=0.0124). Kaplan Meier curves demonstrate that history of BTCC grouped the patients into distinct populations in terms of disease specific survival and bladder free recurrence (P<0.05). Conclusions: This study demonstrates that prior history of BTCC (either invasive or superficial) has an adverse effect on the prognosis of patients diagnosed with UTTCC independent of primary tumor stage. No significant financial relationships to disclose.
A National Cancer Database analysis of treatment utilization and associated outcomes in elderly patients with locally advanced esophageal cancer.
Authors: Gregory Riccardo Vlacich, Pamela Parker Samson, Stephanie Mabry Perkins, Michael Charles Roach, Parag J. Parikh, Jeffrey D. Bradley, Albert C. Lockhart, Varun Puri, Bryan F Meyers, Benjamin D. Kozower, Cliff Grant Robinson
Journal: Journal of Clinical Oncology (2017)

138 Background: Elderly patients with locally advanced esophageal cancer pose a therapeutic challenge since definitive treatment involves aggressive combined-modality therapy. Whether these individuals are offered or benefit from these approaches in the modern, trimodality era has not been widely explored. Methods: Patients ≥ 70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment. Variables independently associated with treatment utilization were evaluated using logistic regression and mortality hazard evaluated using Cox-proportional hazards analysis. The primary aim was to compare overall survival by treatment group. The secondary aim was to identify variables associated with receiving each modality. Results: A total of 21,593 patients were identified. Median and maximum ages were 77 and 90 respectively. In 12.9%, no therapy was delivered, 24.3% received palliative therapy, 37.1% received definitive chemoradiation, 5.6% received esophagectomy alone, and 10.0% received trimodality therapy. On multivariate analysis, age ≥ 80 (OR 0.73, p &lt; 0.001), female gender (OR 0.81, p &lt; 0.001), and treatment at high-volume centers (OR 0.83, p = 0.008) were associated with a decreased likelihood of palliative therapy over no treatment. Age ≥ 80 (OR 0.15, p &lt; 0.001), female gender (OR 0.80, p = 0.03), and non-Caucasian race (OR 0.63, p &lt; 0.001) were associated with decreased trimodality use compared to definitive chemoradiation. Each treatment independently demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49), concurrent chemoradiation (HR 0.36), esophagectomy (HR 0.31), trimodality therapy (HR 0.25), all p &lt; 0.001. Conclusions: Any therapy, including palliative care, was associated with improved survival compared to no treatment in elderly patients with esophageal cancer. Subsets of patients are less likely to receive aggressive therapy based on social and institutional factors. Care should be taken to not unnecessarily deprive elderly patients of treatment that may improve survival.
Radium-223 Inhibits Osseous Prostate Cancer Growth by Dual Targeting of Cancer Cells and Bone Microenvironment in Mouse Models
Authors: Mari I. Suominen, Katja M. Fagerlund, Jukka P. Rissanen, Yvonne M. Konkol, Jukka P. Morko, ZhiQi Peng, Esa J. Alhoniemi, Salla K. Laine, Eva Corey, Dominik Mumberg, Karl Ziegelbauer, Sanna-Maria Käkönen, Jussi M. Halleen, Robert L. Vessella, Arne Scholz
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Radium-223 dichloride (radium-223, Xofigo), a targeted alpha therapy, is currently used for the treatment of patients with castration-resistant prostate cancer (CRPC) with bone metastases. This study examines the mode-of-action and antitumor efficacy of radium-223 in two prostate cancer xenograft models. Experimental Design: Mice bearing intratibial LNCaP or LuCaP 58 tumors were randomized into groups (n = 12–17) based on lesion grade and/or serum PSA level and administered radium-223 (300 kBq/kg) or vehicle, twice at 4-week intervals. X-rays and serum samples were obtained biweekly. Soft tissue tumors were observed macroscopically at sacrifice. Tibiae were analyzed by gamma counter, micro-CT, autoradiography and histology. Results: Radium-223 inhibited tumor-induced osteoblastic bone growth and protected normal bone architecture, leading to reduced bone volume in LNCaP and abiraterone-resistant LuCaP 58 models. Furthermore, radium-223 resulted in lower PSA values and reduced total tissue and tumor areas, indicating that treatment constrains prostate cancer growth in bone. In addition, radium-223 suppressed abnormal bone metabolic activity as evidenced by decreased number of osteoblasts and osteoclasts and reduced level of the bone formation marker PINP. Mode-of-action studies revealed that radium-223 was deposited in the intratumoral bone matrix. DNA double-strand breaks were induced in cancer cells within 24 hours after radium-223 treatment, and PSA levels were significantly lower 72 hours after treatment, providing further evidence of the antitumor effects. Conclusions: Taken together, radium-223 therapy exhibits a dual targeting mode-of-action that induces tumor cell death and suppresses tumor-induced pathologic bone formation in tumor microenvironment of osseous CRPC growth in mice. Clin Cancer Res; 23(15); 4335–46. ©2017 AACR.
Denosumab versus placebo as adjuvant treatment for women with early-stage breast cancer who are at high risk of disease recurrence (D-CARE): An international, randomized, double-blind, placebo-controlled phase III clinical trial.
Authors: Paul Edward Goss, Carlos H. Barrios, Richard Bell, Dianne M Finkelstein, Hiroji Iwata, Miguel Martin, Ada H. Braun, Chunlei Ke, Tapan Maniar, Robert Edward Coleman
Journal: Journal of Clinical Oncology (2012)

TPS670 Background: Bone is a common site of distant recurrence in women with early-stage breast cancer, and represents approximately 40% of all first recurrences. Tumor cells in bone release growth factors and cytokines that stimulate osteoclast-mediated bone resorption through the RANK ligand (RANKL) pathway. In preclinical studies, RANKL inhibition significantly delays skeletal tumor formation, reduces skeletal tumor burden, and prolongs survival of tumor-bearing mice. Denosumab is a fully human monoclonal antibody that binds to RANKL with high affinity and specificity. It is approved for the prevention of skeletal-related events in patients with established bone metastases from a variety of solid tumors. The purpose of the D-CARE trial is to evaluate the ability of denosumab to prolong bone metastasis-free survival (BMFS) and disease-free survival (DFS) in the adjuvant breast cancer setting. Methods: Approximately 4,500 women with stage II or III breast cancer, at high risk for recurrence and with known hormone and HER-2 receptor status, are eligible. Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination must be planned. Exclusion criteria include: a prior history of breast cancer (except DCIS or LCIS) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization or any intravenous BP use. Patients are randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 months, then every 3 months for a total of 5 years of treatment. All patients receive vitamin D (≥ 400 IU) and calcium (≥ 500 mg) supplements. Primary endpoint of this event-driven trial is BMFS. Secondary endpoints include DFS and overall survival. Safety, quality of life assessments, breast density, and biomarkers are additional endpoints. The trial, sponsored by Amgen Inc. and registered with the ClinicalTrials.gov identifier NCT01077154, began enrolling patients in June 2010 and is expected to complete in October 2016. Paul Goss and Dianne Finkelstein supported in part by the Avon Foundation New York.
The ability of physical performance test and Karnofsky performance status to identify elderly cancer patients requiring a comprehensive geriatric assessment: A comparative study.
Authors: Najib Antoine Nassani, Sassine Ghanem, Elie Kassouf, Lana El Osta, Fadi El Karak, Marwan Ghosn
Journal: Journal of Clinical Oncology (2013)

e20534 Background: The role of Physical Performance Test (PPT) as a screening tool for patients in geriatric oncology requiring a Comprehensive Geriatric Assessment (CGA) has not been studied so far. We undergo this study to assess PPT as a screening tool in comparison with Karnofsky Performance Status (KPS) and CGA. Methods: One hundred patients, aged ≥ 70 and diagnosed with cancer participated in our study. Inclusion criteria were knowledge of Arabic, French or English and absence of significant cognitive impairment. Exclusion criteria were: KPS&lt;60% or severe medical condition. ROC curves were used to compare PPT and KPS in identifying ≥ 2 impairments on CGA. Results: Median age was 76 years (70 – 89). Most frequent malignancies were: Lung (19%), colo-rectum (16%), and breast (15%). Stage IV was present in half of patients. Patients were at increased risk of malnutrition (46%) and malnourished (15%), had moderate to severe pain uncontrolled by medication (41%), were at risk of falls (42%), were suffering from frequent sleeping problems (43%), had vision (56%) and hearing (36%) impairment, have had urinary incontinence within one year (21%). All had social support in case of emergency. Cardiovascular (67%), diabetes mellitus (30%) and pulmonary (26%) were the most frequent comorbidities. A remarkable prevalence of geriatric problems was noted with 69% having ≥ 2 impairments on CGA. A good correlation existed between KPS and PPT r = 0.68 (p&lt;.0001). PPT (Se=65%, Sp=84%, PPV=90%, NPV=52%, cut-off ≤24) was equivalent to KPS (Se=65%, Sp=81%, PPV=88%, NPV=51%, cut-off ≤80%) in identifying ≥ 2 impairments on CGA. Conclusions: Patients aged ≥ 70, diagnosed with cancer and having a KPS ≤ 80% or a PPT ≤ 24 must be referred to specialists in geriatric oncology or to geriatricians for a thorough assessment.
Evaluation of meaningful change in bowel move frequency for patients with carcinoid syndrome.
Authors: Stacie Hudgens, Jonathon Gable, Matthew H. Kulke, Emily Bergsland, Lowell Brian Anthony, Martyn E. Caplin, Kjell E. Oberg, Marianne E. Pavel, Phillip Banks, Qi Melissa Yang, Pablo Lapuerta
Journal: Journal of Clinical Oncology (2017)

583 Background: Telotristat ethyl is a tryptophan hydroxylase inhibitor in development for the treatment of carcinoid syndrome (CS) in patients who receive somatostatin analog (SSA) therapy. In TELESTAR, a pivotal Phase 3 study, telotristat ethyl significantly reduced bowel movement (BM) frequency compared to placebo. Objective: The objective of this study was to psychometrically assess meaningful change in BM frequency using data collected within the TELESTAR study. Methods: An anchor-based approach consisted of mapping change from baseline in BM frequency to other patient reported assessments of change. These included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30) Diarrhea Symptom responders, the EORTC GI.NET21 GI Symptom responders, and patient reported adequate relief at Week 12 (responders had a ≥ 10-point decrease in scores from Day 1 to Week 12). Parameters included within group mean change from baseline to Week 12, t-tests of the change (Wilcoxon Rank Sum for adequate relief), effect size (ES: calculated as the difference between mean on-treatment and baseline BM frequency, divided by the standard deviation of the baseline), and related confidence intervals. Results: There were 135 patients with CS, with a mean age of 63.6 years and mean baseline BM frequency of 5.7 BM/day. Anchor-based analyses indicated significant differences in BM frequency between adequate relief groups at Week 12 (ES: -1.58 vs. -0.79; p = 0.014), responders and non-responders on the EORTC QLQ-C30 Diarrhea Symptoms domain (ES: -1.24 vs. -0.59; p &lt; 0.0001), and responders and non-responders on the EORTC GI.NET21 GI Symptoms Domain (ES: -1.49 vs. -0.75; p = 0.0053). These corresponded to BM frequency reductions of 1.7-1.9 BM/day, or ≥ 30%. Conclusions: Results of this study indicated that patients with CS experienced clinically meaningful reductions in BM frequency of ≥ 30% over the course of 12 weeks.
The Risk of Suicidality and Depression From 5-α Reductase Inhibitors
Authors: Stephen Thielke
Journal: JAMA Internal Medicine (2017)

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A phase III study of ibrutinib in combination with bendamustine and rituximab (BR) in elderly patients with newly diagnosed mantle cell lymphoma (MCL).
Authors: Michael Wang, Leo I. Gordon, Simon Rule, Andre Goy, Olivier Hermine, Aleksandra Rizo, Sen Hong Zhuang, Martin H. Dreyling
Journal: Journal of Clinical Oncology (2013)

TPS8613^ Background: MCL is a distinct subtype of B-cell non-Hodgkin lymphoma (NHL) accounting for approximately 6% of NHL diagnoses. Current immunochemotherapy followed by rituximab maintenance results in a prolonged duration of remission, but a constant relapse pattern is still observed. Ibrutinib, an oral Bruton's tyrosine kinase(BTK) inhibitor, demonstrated promising single-agent activity in 115 patients with relapsed or refractory MCL who were enrolled in the phase II study PCYC-1104. The overall response rate (ORR) was 68%, with 46% of patients achieving partial response (PR) and 22% achieving complete remission (CR) (Wang ASH 2012). Blum et al (ASH 2012) demonstrated that ibrutinib can be safely combined with BR in a phase I combination study in relapsed or refractory NHL and that it enhanced BR’s clinical activity with an ORR in 5 evaluable MCL patients of 100% (80% CR, 20% PR). These data suggest that combining ibrutinib with BR will improve the outcome of these patients. Methods: The SHINE study, PCI-32765MCL3002, is a phase III double-blind study of ibrutinib in combination with BR versus BR for the treatment of patients with newly diagnosed MCL. The study aims to enroll 520 patients (approximately 260 patients per arm). All patients will receive BR therapy for 6 cycles; those patients achieving a CR or PR will receive R maintenance for 2 years. In addition to BR and R, all patients will receive an oral daily dose of 560 mg ibrutinib or placebo concomitant with the chemotherapy and ongoing as a single agent until disease progression or unacceptable toxicity. The primary objective is to evaluate if the addition of ibrutinib to BR will result in prolongation of progression-free survival, with secondary objectives of ORR (CR+PR), CR rate, duration of response, safety, and overall survival. The study will enroll patients aged 65 years or older who are not suitable for high-dose chemotherapy. Key exclusion criteria include diagnosis or treatment for malignancy other than MCL, requirement for treatment with warfarin or equivalent vitamin K antagonists, and treatment with strong CYP3A4/5 inhibitors. Approximately 200 sites globally will enroll patients. Enrollment began in Q1 of 2013. Clinical trial information: NCT01776840.