tbuckley/cabot-search huggingface dataset:
Phase I/II study of neoadjuvant docetaxel plus intensity-modulated radiotherapy (IMRT) prior to surgery for high-risk prostate cancer.
Authors: M. Garzotto, A. Hung, T. M. Beer, J. J. Alumkal, J. N. Graff, P. E. Farris, J. F. Flamiatos, S. Mongoue-Tchokote, S. N. Carter
Journal: Journal of Clinical Oncology (2011)

4662 Background: High-risk localized prostate cancer remains a considerable therapeutic challenge in part due to an inability to attain local control with either surgical or radiation monotherapy. Neoadjuvant chemoradiation improves local relapse rates of several tumor types but has not been evaluated in prostate cancer. The primary objectives were to assess the safety and pathologic complete response rate of pre-operative docetaxel and IMRT. Secondary aims included biochemical recurrence-free survival (PSA >0.4ng/ml) and PSA response to chemo-IMRT. Methods: Eligible patients had: 1) T2b or resectable T3a disease, 2) PSA ≥15 ng/ml or 3) or primary Gleason grade ≥4. Pts received 45 Gy over 25 fractions to the prostate and seminal vesicles with 7-field IMR. In phase I, cohorts of 3 pts were accrued at weekly doses of 0 mg/m2, 10 mg/m2, 20 mg/m2 and 30 mg/m2. Docetaxel and standard oral dexamethasone were given weekly until reaching max planned dose or confirmed DLT. No DLTs were observed at the max planned dose of 30 mg/m2 which was chosen for phase II testing. Results: 25 patients enrolled between April 2006 and November 2009. All pts received all planned therapy. Non-hematologic toxicities from chemo-IMRT included Grade 3 reports in 6 pts and Grade 4 hyperglycemia in one pt. Pre- and post-treatment PSA values were available in 22 of 25 pts. Chemo-IMRT resulted in a 49% (95% CI: -60.3% to -36.7%) mean decrease in PSA with no significant change in testosterone (p = .46). Surgical morbidity was acceptable; there were no DVT’s, wound complications, rectal or ureteral injuries. Pathological staging was: T0 – 0 pts, T2 – 16 pts, T3 – 9 pts and N+ – 6 pts. Surgical margins were negative in 88% of cases. Initial post-op PSA was undetectable (<0.1 ng/ml) in 24 of 25 pts. With a median follow-up of 20.8 mo., estimated 2-year recurrence free survival was 84% (95% CI: 83.86 to 84.14). Conclusions: Neoadjuvant chemoradiation is feasible with acceptable toxicity for high-risk localized prostate cancer. Improved rates of negative surgical margins and early post-op PSA levels likely represent markers of improved local control. Based on these results, further investigation of neoadjuvant chemoradiation is warranted.
Risk of anxiety/depression events in patients newly diagnosed with neuroendocrine tumors.
Authors: C. Chen, G. P. Hess, Z. Liu, J. C. Yao, A. T. Phan, J. W. Hill
Journal: Journal of Clinical Oncology (2011)

e16591 Background: Neuroendocrine tumors (NET) are malignant neoplasms capable of systemic hormone production. This retrospective study analyzed patient’s risk of having anxiety/depression conditions in the three years’ post 1st NET diagnosis. Methods: Qualifying patients were adults newly diagnosed with NET having greater than or equal to one claim with one or more of the following ICD-9-CM codes: 157.4 (islet cell,), 209.xx (carcinoid), 258.01 (MEN1), or 259.2 (carcinoid syndrome) during 10/1/01 – 5/31/07, and with ≥ 3 years follow-up in SDI’s medical claims. Non-cancer patients were matched 2:1 to NET patients on age, gender, region, and hospital data availability. Risk of anxiety/depression related diagnosis or procedures were capture during the 3 years post index period, and were analyzed using logistic regressions adjusting for baseline anxiety/depression, comorbidity index, age, gender, region, payer, and physician specialty/academic affiliation. Results: The study sample consisted of 1,762 newly diagnosed NET (median age=61 years, 59.3% female, 70.4% commercially insured and 28.8% Medicare patients) and 3,524 matched control patients. During the 3-year follow-up, 8.1% of NET and 7.4% of control patients experienced anxiety/depression events (p=0.34). Anxiety/depression event rates were significantly higher in NET patients (10.4%) than controls (8.1%, p=0.03) in the patients aged less than 65 years (n=3,048, 1,016 NET and 2,032 control patients). NET patients had a higher adjusted risk of anxiety/depression events than controls in the under 65 age group (odds ratio=1.48, 95% CI: 1.06-2.07, p=0.02). Conclusions: NET patients less than 65 years had a significantly higher frequency of anxiety/depression post-diagnosis compared to matched controls. Results are important for highlighting the impact of anxiety/depression in younger NET patients.
Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy
Authors: Takafumi Nakayama, Yasuo Sugano, Tetsuro Yokokawa, Toshiyuki Nagai, Taka‐aki Matsuyama, Keiko Ohta‐Ogo, Yoshihiko Ikeda, Hatsue Ishibashi‐Ueda, Takeshi Nakatani, Nobuyuki Ohte, Satoshi Yasuda, Toshihisa Anzai
Journal: European Journal of Heart Failure (2017)
Oral health in patients with head and neck cancer: A review of current management
Authors: M. E. Brosky, C. Lee
Journal: Journal of Clinical Oncology (2005)

5561 Background: Radiation therapy (RT) for head and neck cancer (HNC) is associated with a high incidence of long-term adverse events, including xerostomia, mucositis, and dental caries. The importance of a comprehensive dental evaluation and rigorous oral care before, during, and after RT is widely recognized. However, relatively few data are available on the extent of oral health interventions or compliance in patients with HNC. Methods: A Medline literature search was performed using HNC, oral complications (eg, xerostomia, mucositis, stomatitis, caries, gingivitis), and oral healthcare (eg, oral care, oral health, dental care, dental health) search terms. The search was limited to 1984–2004, adults ≥18 y and English language publications. Results: Of 331 publications identified, 19 were clinical trials, surveys, or case reports that described oral/dental interventions in irradiated patients with HNC and/or patient compliance with oral care regimens. There is considerable variation in the approach to management of oral/dental complications, and a lack of established and well-accepted clinical guidelines. The rate of pre-irradiation dental consultation in patients with HNC is low (12.1% to 44%). Between 50% and 76% of patients are noncompliant even when routine dental care is available, and about half (51%) of patients are lost to dental follow-up. Conclusions: Dental care and oral hygiene are crucial to the prevention and management of long-term adverse events following RT for HNC. These findings indicate that many patients do not receive adequate care or instruction in oral hygiene, and highlight the importance of integrating good dental care education and practices into the management of patients with HNC. No significant financial relationships to disclose.
TAS-102 versus placebo (PBO) in patients (pts) ≥65 years (y) with metastatic colorectal cancer (mCRC): An age-based analysis of the recourse trial.
Authors: Eric Van Cutsem, Fabio M. Benedetti, Hirokazu Mizuguchi, Robert J. Mayer, Alfredo Falcone, Rocio Garcia-Carbonero, Josep Tabernero, Alberto F. Sobrero, Marc Peeters, Alberto Zaniboni, Takayuki Yoshino, Yasuhiro Shimada, Kentaro Yamazaki, Yoshito Komatsu, Howard S. Hochster, Heinz-Josef Lenz, Ben Tran, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2016)

638 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil hydrochloride, at a molar ratio of 1:0.5 (weight ratio, 1:0.471). Efficacy and safety of TAS-102 in pts with mCRC refractory to standard therapies were evaluated in the RECOURSE trial; enrollment criteria included ≥2 prior lines of standard chemotherapy. Primary results of RECOURSE demonstrated a significant improvement in overall survival (OS) (TAS-102 7.1 mo vs PBO 5.3 mo; HR=0.68; P&lt;0.0001) and progression-free survival (PFS) (HR=0.48; P&lt;0.0001). Methods: This prespecified analysis compared the efficacy and safety of TAS-102 vs PBO in pts ≥65 y and &lt;65 y with mCRC. A retrospective analysis of pts ≥75 y was also performed. Results: Of 800 randomized pts, 352 (44.0%) were ≥65 y and 60 (7.5%) were ≥75 y. Median OS in pts ≥65 y was 7.0 mo with TAS-102 vs 4.6 mo with PBO (HR=0.62, 95% CI: 0.48-0.80, P=0.0002). PFS HR was 0.41 (95% CI: 0.32-0.52, P&lt;0.0001) for pts ≥65 y, also favoring TAS-102. In pts ≥65 y, disease control rate (complete or partial response or stable disease) was 48.7% with TAS-102 vs 15.5% with PBO. An age-related difference in overall incidence of adverse events (AEs) was not observed in either treatment arm. Treatment-related AEs, ≥ Grade 3 AEs, and severe AEs were generally more common in pts ≥65 y than in pts &lt;65 y (Table). Mean drug exposure was similar among pts ≥65 y and ≥75 y, as was overall safety profile. Conclusions: Significant improvements in OS and PFS were observed in pts ≥65 y who received TAS-102 vs PBO, with a mild increase in toxicity. Pts ≥65 y and &lt;65 y showed a generally favorable safety profile. A significant increase in toxicity in pts ≥75 y was not apparent vs the overall ≥65 y population. Clinical trial information: NCT01607957. [Table: see text]
Everolimus as first-line therapy in nonrapidly progressive metastatic castration-resistant prostate cancer (mCRPC): A multicenter phase II trial (SAKK 08/08).
Authors: A. Templeton, C. Rothermundt, R. Cathomas, D. Baertschi, C. Droege, O. Gautschi, M. M. Borner, E. Fechter, F. Stenner, R. C. Winterhalder, B. Mueller, V. Dutoit, P. Dietrich, R. Schiess, P. Wild, G. N. Thalmann, D. Klingbiel, S. Gillessen
Journal: Journal of Clinical Oncology (2011)

4588 Background: Everolimus is a potent, orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) pathway and has shown activity in preclinical cancer models. This phase II study investigated the activity of single agent everolimus as first-line treatment in patients (pts) with mCRPC. Methods: Pts with rising PSA while castrate (testosterone < 50ng/dl) and a PSA-doubling time (PSA-DT) of ≥ 55 days, no prior chemotherapy, and adequate organ function were eligible. Continuation of androgen deprivation therapy was required. Everolimus was administered continuously at a dose of 10mg daily. The primary endpoint was progression free survival (PFS) at 12 weeks defined as absence of PSA increase ≥ 25% over baseline, and no progression of metastases on imaging or clinically. Secondary endpoints included adverse events (AE), PFS, response (PSA, measureable disease), and overall survival. 32 evaluable pts were needed in a Simon's two stage minimax design with a power of 90% and a significance level of 10% to test a PFS rate at 12 weeks of ≤ 15% (H0) vs. ≥ 35% (H1). Accordingly, ≥ 8 pts without progression at 12 weeks were needed to reject H0. New predictive serum biomarkers are evaluated by proteomics and PTEN status / PI3-kinase-dependent pathway activation is monitored in tumor tissue. Results: 37 pts were enrolled at 10 Swiss centers between 9/09 and 8/10. Median age was 69 (range 47–85) years, performance status was 0 in 78%, and 1 in 22%; median PSA was 50µg/l (range 7–2039µg/l), 16% of pts had visceral metastases. 12 pts (32%; 95% CI 18–50%) remained free of progression at 12 weeks. PSA decline ≥ 30% and ≥ 50% was seen in 4 (11%) and 1 (3%) pts, respectively. Treatment related AE’s were as expected and included mucositis/stomatitis, fatigue, diarrhea (in > 20%, all grades). Alveolitis/pneumonitis occurred at ≤ G2. G3 events occurring in more than 1 pt were anemia and lymphopenia. In depth analysis of lymphocyte subpopulation and function will be presented. Conclusions: To our knowledge this is the first trial testing everolimus as first line monotherapy in patients with mCRPC which shows encouraging activity and manageable toxicity. Further studies are warranted.
Biliary tract cancer (BTC) in the older adult: Complex decisions for complex patients.
Authors: A. M. Horgan, E. McKeever, J. J. Knox
Journal: Journal of Clinical Oncology (2011)

295 Background: BTC is an uncommon malignancy. Complex patient (pt) factors potentially determine treatment choices in older pts and may independently impact outcomes. Methods: Between 2000 and 2010, 133 pts aged ≥ 75 years with BTC were evaluated at Princess Margaret Hospital. Clinical and histopathological characteristics, geriatric-specific factors, and survival outcomes were studied in a retrospective analysis. Results: Median age was 79 years (range 75-93). Predominant histology was adenocarcinoma (95%). 31 pts (23%) had curative surgery, 4 (13%) had additional (neo)adjuvant chemotherapy (CT) ± radiation therapy (RT). Pathological staging included: I/II: 20 (65%); III: 6 (19%); IV: 5 (16%). 25 pts (19%) received CT ± RT alone, 4 (15%) had stage I/II and 21(84%) stage III/IV disease. 77 pts (58%) received best supportive care (BSC) alone. Radiological complete or partial response was noted for 33% of pts treated with CT [gemcitabine (gem) alone 48%; gem doublet 52%]. 24% pts discontinued CT with toxicity. Untreated pts had greater degrees of functional dependence and poorer social supports. Of those untreated, the risk of treatment was felt to outweigh potential benefit given age ± comorbidities in 17%. In 22%, the pt opted not to receive treatment. Median overall survival was 19.7 months for the surgical group, 12.3 mths for the CT ± RT group and 4.37 mths for the BSC group. Conclusions: Untreated BTC has a poor prognosis. Factors other than clinicopathological features may impact treatment decisions. Integrating geriatric assessements into the evaluation of this vulnerable patient group may help better guide treatment choices. [Table: see text] No significant financial relationships to disclose.
Exposure-response (E-R) analysis to facilitate phase III (P3) dose selection for ganitumab (GAN, AMG 479) in combination with gemcitabine (G) to treat metastatic pancreatic cancer (mPC).
Authors: J. Lu, H. Deng, R. Tang, C. Hsu, H. L. Kindler, C. S. Fuchs, J. L. Gansert, S. Bray, S. S. Suzuki, E. Loh, M. Zhu
Journal: Journal of Clinical Oncology (2011)

4049 Background: GAN is an investigational, fully human monoclonal antibody against IGF1R. In a phase II study, 125 patients (pts) with mPC were randomized 1:1:1 to GAN +G, placebo (P) +G, or conatumumab + G. Addition of GAN (12 mg/kg IV, Q2W) to G (1,000 mg/m2) showed evidence of improved OS and PFS (Kindler, JCO 2010:28 abstr 4035). An E-R analysis was done to inform P3 dose selection for GAN. Methods: GAN PK was estimated via a population PK model. An E-R analysis was performed with pts from the GAN+G and P+G arms (~40 pts/arm). The effect of estimated steady-state area under the curve (AUCss) on OS and PFS was evaluated with a Cox proportional hazard model. Effects of potential confounding factors on OS-AUCss and PFS-AUCss associations were assessed by multivariate analysis. Exposure-safety data were analyzed with descriptive statistics and linear regression. P3 doses for GAN were explored with Monte Carlo simulations using population PK and parametric survival models. Results: There was a positive association between OS or PFS and higher AUCss in the GAN+G arm (P<0.001, <0.001) that remained even when data from the GAN+G median (19.2 mg·h/µL) had longer median OS and PFS (16.0, 7.6 months) than pts with AUCss < median (4.7, 1.9 months). OS-AUCss and PFS-AUCss associations were significant after adjusting for potential confounding factors. The incidence of most adverse events was similar between the AUCss < and ≥ median groups, although grade ≥3 hyperglycemia and thrombocytopenia trended higher in pts with AUCss ≥ median. Hepatic toxicity was more frequent in pts with AUCss < median. Faster clearance of GAN was observed in mPC vs. non-mPC pts. No G-GAN PK interactions were identified. PK simulations showed similar AUCss of GAN in mPC pts at 20 mg/kg and in non-mPC pts at 12 mg/kg. Clinical trial simulations projected improved OS and PFS with 20 vs 12 mg/kg GAN. Conclusions: In this study, increased exposure to GAN was associated with improved PFS and OS in mPC. These data were used to inform dose selection for an ongoing randomized P-controlled P3 study in which 12 and 20 mg/kg GAN + G will be evaluated.
Single Center Analysis of Risk Factors for Puberty Disorders in Children after Allogeneic Haematopoietic Stem Cell Transplantation (HSCT).
Authors: Dorota M. Wojcik, Ewa Barg, Ewa Niedzielska, Krzysztof Kalwak, Marek Ussowicz, Adrian Doroszko, Alicja Chybicka
Journal: Blood (2006)
Effect of omega-3 fatty acids alone and in combination with raloxifene on biomarkers of breast cancer risk in postmenopausal healthy women at high risk.
Authors: C. Signori, J. P. Richie, B. Prokopczyk, A. Calcagnotto, C. Hamilton, N. Trushin, C. Dubrock, L. M. Demers, J. Liao, K. El-Bayoumy, A. Manni
Journal: Journal of Clinical Oncology (2011)

e11036 Background: Prevention represents the most effective approach to reducing mortality from breast cancer. To translate our preclinical findings in this regard we are conducting a 2-year randomized clinical trial in healthy postmenopausal women with increased breast cancer risk based on breast density (>25%). Methods: We are studying the effects of omega-3 fatty acids (FA) alone and in combination with raloxifene on several biomarkers including those of inflammation (CRP, IL-6), estrogen metabolism (2-hydroxyestrone, 16-α-hydroxyestrone), oxidative status (glutathione [GSH]), IGF-1 signaling (IGF-1, IGFBP-3) and plasma FA. Our study consists of 5 groups: (1) no intervention; (2) raloxifene 60mg; (3) raloxifene 30mg; (4) omega-3-acid ethyl esters (Lovaza) 4g; (5) raloxifene 30mg + Lovaza 4g. We report here preliminary findings from the first 46 women after 1 year. Results: Raloxifene reduced serum IGF-1 (12% in Group 3 and 20% in Group 2) compared to control (Group 1) in a dose-dependent fashion (p=0.005) while Lovaza alone had no effect (Group 4). The effect of Lovaza in combination with raloxifene (Group 5) was comparable to raloxifene alone (Group 3). Serum CRP, IL-6, IGFBP-3, 2-hydroxyestrone and 16-α-hydroxyestrone were unchanged in all groups. Blood GSH showed an increasing trend with Lovaza, but was not significant (p=0.07). Plasma FA changes by Lovaza included 2.5-fold increases in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), an increase in the omega-3/omega-6 ratio (0.12 + 0.01 at baseline to 0.30 + 0.06 at 1 year) and decreased arachidonic acid (AA) (0.54 + 0.05 μmol/mL at baseline to 0.35 + 0.02 at 1 year) (p<0.05). Conclusions: Our results support the role of decreased IGF-1 levels as a potential mechanism of breast cancer risk reduction by raloxifene which may not be driven by effects on IGFBP-3. The Lovaza-induced increase in omega-3 FA levels and decrease in AA are consistent with our preclinical findings. An increased trend of blood GSH by Lovaza may indicate enhanced antioxidant activity. Collectively, these results suggest that the combination of omega-3 FA and raloxifene may be a promising approach for impacting critical targets for breast cancer prevention.
First-in-man study of E-3810, a novel VEGFR and FGFR inhibitor, in patients with advanced solid tumors.
Authors: J. Soria, F. G. De Braud, R. Cereda, R. Bahleda, A. Delmonte, E. Angevin, A. Varga, C. Noberasco, E. Dall'O', N. Lassau, C. Dromain, M. Bellomi, F. Farace, F. Bertolini, M. Zucchetti, S. Marsoni, M. G. Camboni
Journal: Journal of Clinical Oncology (2011)

TPS149 Background: Co-selective inhibition of VEGFRs and FGFR has the potential benefit of blocking the two most relevant players in tumor angiogenesis and simultaneously targeting proliferation in FGF-driven tumors. E-3810 (Cancer Res. 2011 in press) is a novel dual-targeted small molecule inhibitor of VEGFR1, 2, 3 and FGFR1 showing strong anti-angiogenic and anti-tumor activity in preclinical models at well-tolerated oral doses, with a favorable pharmacokinetic profile and potential for use in combination. Methods: A first-in-man, phase I dose escalation study is ongoing in patients with advanced solid tumors and no established therapeutic options to evaluate the safety, pharmacokinetics (PK) and pharmacodinamics of E-3810 given orally, once daily for a 4-week course. Treatment can continue without interval until progression based on overall clinical benefit. We use a standard 3+3 MTD design, starting from 5 mg (1/12 of monkey MTD) and up to the MTD based on DLTs in the initial cycle. Dose is doubled till the first instance of G2 drug-related toxicity or G2 uncontrolled hypertension, with smaller increments thereafter. The MTD is the level where ≥ 2/6 patients suffer a DLT, the next lower level being the recommended dose (RD). An expansion basket phase is planned at the RD, in patients who could benefit from E-3810, i.e. with tumors sensitive to anti-angiogenic therapy and failing a prior anti-angiogenic regimen, or breast cancer with FGFR1 amplification, to identify indications for further development. PK after single and repeated administration is evaluated by a validated LC-MS/MS method. Correlative studies (baseline, days 7 and 28) include: (i) quantitative assessment of the effects of E-3810 on tumor vasculature by DCE-MRI and DCE-US imaging; (ii) assay of angiogenesis biomarkers i.e. soluble VEGFR2, VEGFR1, VEGF, bFGF, Collagen IV (by ELISA) and circulating endothelial and progenitors cells (CEC and CEP, by flow cytometry). Tumor response is based on imaging according to RECIST; circulating tumor cells (CTC) are measured by the immunomagnetic CellSearch method. Recruitment started in July 2010; the dose escalation phase is ongoing with 10 patients enrolled as of January 2011. No DLT has been observed up to 20 mg.
Factors affecting nodal involvement in mucinous breast cancer.
Authors: Tracy Nguyen, Bryce Stash, Portia Siwawa, Subhasis Misra
Journal: Journal of Clinical Oncology (2015)

124 Background: Mucinous carcinoma of the breast is a rare type of invasive ductal breast cancer that accounts for 2-5% of all primary breast cancers. Axillary lymph node involvement for mucinous breast carcinoma is rare and correlated with a poor prognosis. However, the relation of lymph node involvement to certain factors is unknown, hence the purpose of our study. Methods: Retrospective chart review of patients diagnosed with mucinous breast carcinoma from 2004 to 2014 from the local tumor registry. Variables include age, tumor size, lymph node metastasis, diagnosis type (pure/mixed), and hormone status of patients. Chi square and T-test was performed. Results: 45 female patients were included in the study with the age range of 35 to 97 years old. 39 patients were diagnosed with mixed mucinous carcinoma and 6 had pure mucinous carcinoma. 9 patients had positive axillary lymph node involvement. 78% of patients with positive lymph node had mixed mucinous carcinoma and 22% had pure mucinous carcinoma. There is no statistical significance (p &gt; 0.05) between lymph node involvement and diagnosis type. Tumor size ranged from 4 to 120 mm, with a mean of 28 mm. 78% of patients with positive lymph node had a tumor size smaller than 60 mm. The other two had a tumor size of 65 mm. and 120 mm. There is no statistical significance (p &gt; 0.05) in the proportion of people who are lymph node positive to tumor size less than 60 mm. Out of the 45 patients, 42 patients expressed ER receptors, 36 expressed PR receptors, and 12 expressed HER2 receptors. 89% of positive lymph node patients express ER hormone receptors, 78% expressed PR receptors, and 56% expressed HER2 receptors. No correlation between ER/PR status and lymph node involvement (p &gt; 0.05) was found but there was a positive correlation between HER2 receptor status and lymph node involvement (p &lt; 0.05). Conclusions: No significant difference between diagnosis type/tumor size in relation to lymph node involvement. Although there is a trend between small tumor size to positive lymph node, it is not significant enough. There is a significant relationship between HER2 positive receptors and lymph node involvement. This is suggestive that the biological nature of the tumor has a larger influence on lymph node involvement than the physical nature.