tbuckley/cabot-search huggingface dataset:
Patient-reported outcomes using a validated LENT-SOMA questionnaire for post-prostatectomy radiotherapy.
Authors: Ananya Choudhury, Arjun Agarwal, Ric Swindell, Anna Tran, Nooreen Sarah Alam, Catherine Coyle, Jacqueline E. Livsey, James Wylie, John P. Logue, Tony Elliot
Journal: Journal of Clinical Oncology (2014)

118 Background: Although local post-operative radiotherapy (RT) improves biochemical progression free survival, there is no evidence of overall survival benefit. With a trend for radical prostatectomy (RP) and radiotherapy for more advanced disease, the debate continues about the merits of multimodality treatment in these patients and the importance of survivorship. We assessed prospectively the effect of combination surgery and radiotherapy on the long term outcomes of patients. Methods: A validated LENT-SOMA (LS) questionnaire was posted to 238 UK patients treated from 2004 to 2009 with post-RP RT to assess patient-reported outcomes after prostate cancer treatment. Patients were treated with hypofractionated 3D conformal RT using image guidance delivering 52.5Gy in 20 fractions over 28 days to the prostate bed, but not to whole pelvis. LS responses were compared with patient perception of their bowel, bladder and sexual function post-RP. Results: Median follow up from RT was 6.26 years. Fifty five percent (130 out of 238) of patients returned questionnaires. Median maximum LS scores for bladder and bowel were three with over 75% of patients reporting at least one occasion of bowel or bladder difficulty in the past month. There was no difference in mean LS scores when compared pre and post RT. No patients had grade 3/4 RTOG toxicities. The median maximum LS score for sexual function was four. There was a significant difference in mean LS scores for sexual function (p=0.001) when compared pre and post radiotherapy. LS scores were not affected by post-RT hormones (26 out of 130 patients) or the time between RP and RT (median 1.76 years). Conclusions: The validated LS questionnaires revealed changes in sexual function post-RT compared with pre-RT were greater than bowel or bladder function. It remains difficult to determine the relative contributions of RP and RT to the late toxicity of multimodality treatment. Ongoing large multi-centre randomised control trials such as the UK-led RADICALS trial will answer questions about timing of RT and need for additional hormones. With the increasing importance of survivorship, it should be noted that prostate-specific antigen control at the expense of toxicity without an overall survival advantage should be treated with caution.
Exploration of alternative digit ratios as a predictor of prostate cancer aggressiveness.
Authors: Michael Stolten, Elisa Ledet, Aryeneesh Dotiwala, Eric Luk, A. Oliver Sartor, Byron Wood
Journal: Journal of Clinical Oncology (2014)

231 Background: During gestation, development of the prostate is dependent on a functional androgen receptor and the presence of dihydrotestosterone. Prenatal androgen exposure has been correlated with a range of diseases including prostate cancer (PCa). Historically, the ratio of the second to the fourth digit (2D:4D) has been linked to prenatal androgen levels; however, the use of alternate finger ratios have been shown to be a greater indicator of prenatal androgen exposure compared to the traditional 2D:4D ratio. Studies have shown that the distal fingertip extent of the second digit (2T:2D) was also associated with prenatal androgens. This study aims to use alternative digit ratio measurements to determine aggressiveness of PCa. Our hypothesis is that alternative digit ratios are more sensitive to prenatal androgen levels, and a better predictor of disease than the traditional 2D:4D ratio. Methods: Digital measurements were made from hand scans of PCa patients. All fingers on the right hand were measured from the basal crease to the fingertip as well as the distal fingertip extent of the second digit. Race, family history (FH) (first degree relatives with PCa), and age at diagnosis were recorded. These clinical covariates were then compared to the finger length ratios which were dichotomized based on the median values and analyzed for possible correlations. Results: Hand measurements were taken on 350 Caucasian (CA) and 100 African American (AA) PCa patients. AA men were more likely to have a smaller 2D:3D (P &lt; 0.0001) and 2D:4D digit ratio (P &lt; 0.0001), and larger 3D:5D (P = 0.0002) and 4D:5D (P = 0.0125) when compared to CA men. AA men with a smaller 2T:2D ratio were younger at the time of diagnosis (P = 0.0446). Additionally, AA men with a larger 2D:5D ratio were more likely to have a FH of PCa (P= 0.0238). Conclusions: Alternative finger length ratios show strong differences between AA and CA men. In AA men, alternative digit ratios are associated with age of PCa diagnosis and FH of PCa. These hypothesis generating results require validation in a larger cohort, but may provide insight to the underlying racial disparity observed in PCa. Finger length may represent a unique, non-invasive predictor of PCa, specifically age of onset and FH in AA men.
In vitro and in vivo effects of the mTOR inhibitors everolimus (EVE) and temsirolimus (TEM).
Authors: David Chen, Michael Terence O'Reilly, Paul M.J. McSheehy
Journal: Journal of Clinical Oncology (2014)

466 Background: Two mTOR inhibitors are approved for treating mRCC: EVE following the failure of VEGF-targeted therapy and TEM as first-line therapy in poor-risk patients. Both agents exert their clinical effect by binding to FKBP-12, which then interacts with mTOR to inhibit its kinase activity. We compared the activity of EVE and TEM in in vitro and in vivo models. Methods: EVE and TEM binding to mTOR was assessed using time-resolved fluorescence resonance energy transfer. Inhibition of cell proliferation in A549, NCI-H460, and MCF7 human tumor cell lines was assessed by methylene blue protein staining. Phosphorylation of the downstream mTOR target pS6 was assessed via immunohistochemistry in A549 cells. Antitumor activity of EVE (oral) and TEM (intraperitoneal) at doses between 0.1 and 2.5 mg/kg once daily was assessed in vivo in A549, KB-31, KB-8511, and HCT-116 human tumor xenograft models. Results: The binding efficiency of TEM for mTOR was reduced 10-fold compared with that of EVE (EC 50 , 56 nM vs 6 nM; p &lt; 0.01). EVE demonstrated 6- to 7-fold greater inhibition of cell proliferation than TEM (IC 50 , 1.0 nM vs 6.5 nM in A549 [p &lt; 0.001], 0.7 nM vs 4.7 nM in NCI-H460 [p &lt; 0.01], and 19.4 nM vs 150 nM in MCF7 [p &lt; 0.001]). Complete inhibition of pS6 phosphorylation in A549 cells at 24 hours was achieved with 6.7 nM EVE, but required 20 nM TEM. In all xenograft models, EVE and TEM showed a dose-response relationship over the range of 0.1-2.5 mg/kg/day. EVE was significantly more potent than TEM in the A549 model (EC 50 , 0.11 mg/kg vs 0.51 mg/kg; p = 0.002); no appreciable differences between EVE and TEM were observed in the KB-31, KB-8511, and HCT-116 xenograft models. However, correcting for drug exposure suggests increased potency of EVE over TEM. Conclusions: Compared with TEM, EVE had a higher affinity for the molecular target of FKBP-12. This was consistent with more potent antitumor activity in vitro and in vivo. Whether these data would translate into a better therapeutic index for EVE is unknown. However, the results suggest that these mTOR inhibitors may not be clinically interchangeable.
Physical activity communication between oncology providers and patients with early stage breast, colon or prostate cancer.
Authors: Kirsten A Nyrop, Allison Mary Deal, Grant Richard Williams, Emily Jean Guerard, Mackenzi Pergolotti, Hyman B. Muss
Journal: Journal of Clinical Oncology (2016)

171 Background: National guidelines recommend that patients with a cancer diagnosis engage in regular physical activity (PA) to reduce cancer-related fatigue, maintain quality of life and physical function, and improve overall prognosis and survival. This study investigates oncology provider communications about PA during routine clinic visits with early stage breast, colon or prostate cancer patients. Methods: Retrospective chart review for documentation of communications (inquiries or recommendations) pertaining to PA in clinician notes and after visit patient summaries. Mixed methods analysis. Results: In a 1-month period, 55 oncology providers had 361 encounters (clinic visits) with early stage cancer patients. Of these encounters, 35% included a provider communication about “physical activity”, “exercise” or “activity”. Encounters with a medical oncologist resulted in a PA communication 55% of the time as compared to 20% of encounters with other clinician specialties (p &lt; 0.0001). Older patients were more likely than younger patients to have a PA communication (p &lt; 0.001). When the encounter was with a patient who was being seen for surveillance, chemotherapy or endocrine treatment, the rate of PA communications was significantly higher (46%, 37%, 58% respectively) as compared to when the visit was during radiation treatment or surgery (6%, 19% respectively) (p &lt; 0.0001). Four PA themes emerged from our analysis of provider communications: (1) level and types of engagement in PA, (2) restrictions on PA either by the provider or perceived by patients, (3) encouragement or recommendations, or (4) relationships between PA and weight, nutrition, pain, and fatigue. There were no significant differences in PA communication rates by clinician gender, clinician training, patient gender, patient race, or disease site. Conclusions: This study shows it is feasible for oncology providers to have PA communications during routine clinic visits; however, the frequency of PA communications varies among providers. Interventions are needed to remind all oncology providers to encourage of their patients with early stage cancer to be physically active.
Phase I feasibility study of intraperitoneal cisplatin and intravenous paclitaxel followed by intraperitoneal paclitaxel in untreated ovarian, fallopian tube, and primary peritoneal carcinoma: Gynecologic Oncology Group study 9921.
Authors: D. S. Dizon, M. Sill, N. S. Gould, S. C. Rubin, S. D. Yamada, R. DeBernardo, R. S. Mannel, E. L. Eisenhauer, L. R. Duska, P. M. Fracasso
Journal: Journal of Clinical Oncology (2011)

5066 Background: Intraperitoneal-containing chemotherapy has shown a survival advantage over intravenous chemotherapy for women with newly diagnosed optimally debulked epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. However, significant toxicity has limited its acceptance. In an effort to reduce toxicity, the Gynecologic Oncology Group conducted a Phase I study to evaluate the feasibility of day 1 intravenous (IV) paclitaxel and intraperitoneal (IP) cisplatin followed by day 8 IP paclitaxel on an every 21-day cycle. Methods: Patients with Stage IIB-IV epithelial ovarian, fallopian tube, primary peritoneal carcinomas or carcinosarcoma received paclitaxel 135 mg/m2 IV over 3 hours followed by cisplatin 75 mg/m2 IP on day 1 and paclitaxel 60 mg/m2 IP on day 8 of a 21 day cycle with 6 cycles planned. Dose-limiting toxicity (DLT) was defined as febrile neutropenia or dose-delay of greater than 2 weeks due to failure to recover counts, or grade 3-5 non-hematologic toxicity occurring within the first 4 cycles of treatment. Results: Twenty of 23 patients enrolled were evaluable and nineteen (95%) completed all six cycles of therapy. Three patients experienced a DLT consisting of infection with normal absolute neutrophil count, grade 3 hyperglycemia, and grade 4 abdominal pain. Response was noted in one of nine (11%) patients with measurable disease, with stable disease in an additional four. Using GCIG criteria for CA-125 analysis, eighteen patients were evaluable and of these, 12 (67%) had a full response and 2 (11%) had a partial response for an overall response rate of 78%. Conclusions: This modified IP regimen which administers both IV paclitaxel and IP cisplatin on day one, followed by IP paclitaxel on day eight, of a twenty-one day cycle appears feasible and is an attractive alternative to the intraperitoneal treatment regimen administered in GOG-0172.
Assessing patient values first: Creating a platform for advance care planning (ACP) in the adult oncology population.
Authors: Sabrina Q. Mikan, Cynthia Taniguchi, J. Russell Hoverman, Susan Ash-Lee, Deb Harrison, Kevin Donald Olson, Aimee Arlen
Journal: Journal of Clinical Oncology (2013)

99 Background: Patients, families and healthcare providers can be apprehensive about having end-of-life (EOL) conversations. However, asking patients about personal values regarding their healthcare goals may create a platform for more in depth conversations. A quantitative instrument to assess patient values and ACP readiness was developed and validated to complement a process for identifying patients appropriate for ACP. Methods: Recruitment was conducted at seven cancer center sites in The US Oncology Network over a 90-day pilot study period. Of 871 identified patients, 301 Texas Oncology patients engaged in ACP. A cross-sectional descriptive design was used in 301 metastatic cancer patients. Sixty-three participants completed the questionnaire. The 13-item instrument was created after an extensive literature review regarding EOL choices and interventions using a 5-point Likert scale. Descriptive statistics were examined, in addition to analysis of the relationships between items using Pearson’s r correlations. Results: Participants were primarily female (59%) and Caucasian (95%); with a mean age of 66 years. Sixty-eight percent reported it "Very Important" to be told they were dying. There was a significant association between willingness to discuss feelings about dying and being told by their physician when dying, (r= 0.373, p&lt;0.01). Sixty-two percent reported it "Very Important" to be able to choose their EOL care location. EOL care location and level of burden for caregivers were significantly associated (r= 0.315, p&lt;0.05). Also, 76% reported being able to select the person who makes EOL decisions for them as "Very Important." Conclusions: Recent studies have shown the importance of assessment of patient healthcare values in the metastatic oncology population. The values and readiness instrument allows healthcare providers to understand the patient’s wishes early in the course of care. ACP can be guided through review of the validated instrument in the adult metastatic population. This provides appropriate weight to both sides of the care equation and is a major step toward creating patient-centered care. Further development of the instrument is needed in this population.
Using micro-RNA expression to predict response to neoadjuvant chemotherapy in urothelial carcinoma of the bladder.
Authors: Raya Leibowitz-Amit, Eduard Fridman, Noa Bossel, Liron Zehavi, Damien Urban, Yehudit Cohen, Zohar A. Dotan, Eytan Domany, Raanan Berger
Journal: Journal of Clinical Oncology (2013)

299 Background: Urothelial carcinoma of the bladder is among the 5 most common cancers in the US. Despite several clinical trials attempting to determine the best approach to muscle-invasive disease, the optimal treatment modalities and their sequence have not been established. Specifically, the decision to administer neo-adjuvant chemotherapy is currently based solely on clinical parameters, with no validated biomarkers. Micro-RNAs (miRNAs) are short RNA molecules that have roles in post-transcriptional gene expression regulation by binding to mRNAs. They were shown to have cardinal roles in many cancers, and their potential to serve as biomarkers is extensively studied. Our goal was to study whether miRNAs can serve as predictive biomarkers for response to neo-adjuvant chemotherapy in urothelial carcinoma. Methods: miRNAs were extracted from paraffin-embedded pre-operative muscle-invasive tumor biopsies of patients diagnosed with urothelial carcinoma, whose pathological surgical specimen was later found to either show complete or no-response to neo-adjuvant chemotherapy (termed 'responders' and 'non-responders', respectively). The expression pattern of approximately 900 miRNAs was compared using a commercial miRNA array, and the levels of candidate miRNAs was further assessed by quantitative real-time PCR (qRT-PCR). Results: The vast majority of miRNAs exhibited a similar expression pattern in the two patient groups, but two miRNAs were significantly lower in the responders (p &lt;0.001 and q&lt;0.1 using the false detection rate (FDR) method). Interestingly, both miRNAs can potentially target the mRNA of PTCH1 and SP5, two genes with known tumor-suppressor functions. qRT-PCR showed that high levels of one of the miRNAs correlated with lack of response to chemotherapy. Conclusions: This retrospective analysis identified two miRNAs that are differentially expressed between chemotherapy responders and non-responders. One of these miRNAs was confirmed to correlate with lack of response to neo-adjuvant chemotherapy. A prospective trial assessing the predictive values of these miRNAs is currently underway. Future research directions and potential implications will be discussed.
低悪性度神経膠腫患者において放射線療法に化学療法を追加することの認知機能に関する影響: RTOG98-02の二次分析
Authors: S Prabhu Roshan, Won Minhee, G Shaw Edward, Hu Chen, G Brachman David, C Buckner Jan, J Stelzer Keith, R Barger Geoffrey, D Brown Paul, R Gilbert Mark, P Mehta Minesh
Journal: Journal of Clinical Oncology (2014)
Minimal Residual Disease in Acute Myeloid Leukemia (AML) and Hematopoietic Stem Cell Transplantation (HSCT) - A Retrospective Study
Authors: Maura Valerio Ikoma, Vergílio Antônio Rensi Colturato, Camila Marques, Marcimara Penitenti, Anderson João Simione, Clarisse Martins Machado, Lenira Queiroz Mauad, Mair Pedro de Souza, Wellington Morais de Azevedo, Marcos Augusto Mauad
Journal: Blood (2011)
The role of SKP2 in docetaxel response and resistance in prostate cancer.
Authors: M. Khushman, O. Hwang, E. Barrack, P. Reddy, C. Hwang
Journal: Journal of Clinical Oncology (2011)

e15058 Background: Docetaxel, a microtubule-targeting agent, is the current standard of care for symptomatic metastatic castrate-resistant prostate cancer. Understanding the mechanisms underlying docetaxel resistance may help clinicians tailor patient treatment and develop strategies to overcome resistance. Our analysis identified the underexpression of S-phase kinase associated protein 2 (SKP2) as a potential novel docetaxel resistance marker. SKP2 ubiquitinates and degrades p27Kip1, a tumor suppressor which inhibits kinases that control progression to the S-phase of the cell cycle. Elevated SKP2 degrades p27Kip1, which in turn leads to uncontrolled proliferation. In this study, we investigated the effect of modulating SKP2 expression on docetaxel-response in a human prostate cancer cell line, DU145. Methods: Publicly available datasets were analyzed to identify transcripts whose expression correlated with docetaxel-resistance. The impact on docetaxel-response from changing the expression levels of one of the candidate biomarkers, SKP2, was evaluated using an siRNA approach. Loss of expression was confirmed with quantitative RTPCR and Western blot. Cytotoxicity was measured using a modified MTT assay. Results: SKP2 was found to be underexpressed in taxane-resistant lines with a median p-value of 7.31E-4. Loss of SKP2 expression decreased proliferation in DU145 cells. However, SKP2 knockdown did not have a statistically significant effect on docetaxel-sensitivity. Conclusions: Our analysis identified SKP2 as a potential novel docetaxel resistance marker. Knockdown experiments confirmed its role in proliferation but did not have a statistically significant effect on docetaxel-sensitivity. The clinical and biologic significance of SKP2 in determining docetaxel-sensitivity is yet to be determined.
Chemo-Transcriptomic Analysis of Complex Karyotype AML Reveals Increased Expression of Cell Cycle Components and Exquisite Dependency on Polo-like Kinase 1
Authors: Vincent-Philippe Lavallée, Clarisse Thiollier, Céline Moison, Marie-Ève Bordeleau, Isabel Boivin, Geneviève Boucher, Patrick Gendron, Sébastien Lemieux, Anne Marinier, Josée Hébert, Guy Sauvageau
Journal: Blood (2016)
Phase I study of abiraterone acetate (AA) in patients (pts) with estrogen receptor– (ER) or androgen receptor (AR) –positive advanced breast carcinoma resistant to standard endocrine therapies.
Authors: B. Basu, J. E. Ang, D. Crawley, E. Folkerd, D. Sarker, M. Blanco-Codesido, K. Moran, S. Wan, N. Dobbs, F. Raynaud, S. R. D. Johnston, M. Dowsett, A. N. J. Tutt, J. F. Spicer, C. Swanton, J. S. De Bono
Journal: Journal of Clinical Oncology (2011)

2525 Background: Many advanced ER+ breast cancer pts show intrinsic resistance to endocrine treatment with the remainder acquiring resistance. Androgenic steroids upstream of aromatase can drive steroid receptor signaling critical to tumour growth. Evidence also exists for an ERα-/AR+ subset of breast cancers transcriptionally similar to ERα+ disease. We hypothesized that AA, a cytochrome (CYP) 17 inhibitor that irreversibly inhibits androgen and estrogen synthesis, would have anti-tumour activity in ER+ or ER-/AR+ pts. Methods: Post-menopausal women with ER+ or ER-/AR+ advanced breast cancer resistant to >2 lines of hormone therapies were treated in 6-pt cohorts with AA at doses between 250 and 2000mg daily. Results: A total of 25 pts were treated in the phase I trial with 2 pts ongoing on study. Median time on treatment was 1.8 mths (range 0.7 – 11.6 mths). There were no dose limiting toxicities. The majority of adverse events (AEs) were Common Toxicity Criteria grade 1 or 2: fatigue, nausea, anorexia, dyspnoea, palpitations, dizziness and flushes. Hypokalemia was frequent, due to secondary mineralocorticoid syndrome: grade 3/4 hypokalemia occurred in 4 pts. This was effectively managed with potassium supplementation, hydrocortisone (20 mg mane, 10 mg nocte) and eplerenone (50-200 mg) with no clinical consequences. Other grade 3 AEs were neutropenia and reduced left ventricular ejection fraction (1 pt) and exercise-induced hypotension with dizziness (1 pt). At the 2000mg dose 5/5 subjects had suppression of estradiol, testosterone, DHEA and DHEAS to below the lower limit of detection of the assay. Two pts (both ER+/AR+) continued on study beyond 11 mths, one of whom achieved a radiological partial response and 80% reduction in serum CA15.3 from baseline. Pharmacokinetic data will be presented. Conclusions: AA is well tolerated in advanced breast cancer pts with preliminary evidence of antitumour activity. The predominant AEs are mechanism-based (hypokalemia) and can be managed expectantly, although careful monitoring of potassium levels is recommended.