tbuckley/cabot-search huggingface dataset:
A phase II pilot of St. John’s wort for the treatment of hot flushes in women with a history of breast cancer.
Authors: M. J. Naughton, L. D. Case, R. Rosdahl, E. G. Shaw
Journal: Journal of Clinical Oncology (2011)

e19685 Background: Effective treatments for hot flush reduction among post-menopausal breast cancer survivors are sparse. We conducted a pilot study of the use of St. John’s Wort in reducing the frequency and severity of hot flushes over a 4 week period. Methods: Participants were recruited from the CCOP Research Base of the Comprehensive Cancer Center of Wake Forest University. Women were aged >/= 18 years, two or more years from active treatment for non-metastatic breast cancer, and with a minimum of 3 hot flushes per day or 21 per week. Women were ineligible if they were taking an aromatase inhibitor, receiving cytotoxic chemotherapy, or on medication for the management of hot flushes (e.g., estrogen, antidepressants). Participants completed a 1 week pill run-in to determine any drug intolerance and adherence concerns, and then took three 300 mg St. John’s Wort capsules daily for 4 weeks. Participants completed hot flush diaries during active treatment (weeks 1-4), and for two weeks post-treatment (weeks 5-6) to assess hot flush frequency and severity. In addition, women completed quality of life assessments (SF-12 and Profile of Mood States [POMS]) at baseline, 2, 4 and 6 weeks. Results: 9 women were recruited and all were 100% compliant in taking the study pills and completing forms. Recruitment was hampered by the FDA requirement that no participants could be on aromatase inhibitors while on study. All participants were Caucasian with a mean age of 53 years (range: 48-70). No adverse events were reported. Analyses indicated that St. John’s Wort was not effective in reducing either the frequency (p=0.98) or severity (p=0.29) of hot flushes among the study participants. Quality of life, as assessed by the SF-12 (i.e., PCS [p=0.80]; MCS [p=0.29]), and the POMS (p=0.08), was also not improved by the use of St. John’s Wort. Conclusions: St. John’s Wort was not effective in reducing the number and severity of hot flushes in this pilot, or in improving quality of life.
Clinical significance of microsatellite instability in sporadic epithelial ovarian tumor
Authors: J. Kim, S. Kim, Y. T. Kim, J. H. Kim, N. H. Cho
Journal: Journal of Clinical Oncology (2005)

5128 Background: The microsatellite instability (MSI), first identified in colorectal cancers in 1993, has been recognized in other malignancies. In HNPCC and associated malignancies demonstrating MSI have a unique histological appearance, improved prognosis and altered response to chemotherapy. Although the panel of markers for ovarian tumors is not known, we evaluated epithelial ovarian tumors for MSI based on the 14 markers including NCI recommendations. Moreover, MSI expression according to histologic subtype and stage were evaluated. Methods: Twenty-one cases of borderline ovarian carcinoma and 25 cases of ovarian carcinoma were analyzed for MSI using frozen specimens fluorescence technology and 14 selected markers (BAT25, BAT26, D5S346, D2S123, D17S250, NME1, D3S1611, D10S197, D11S904, D13S175, DXS981, DXS6800, DXS6807, AR). According to the histologic subtype, total 46 cases were consisted of 10 cases of serous, 26 cases of mucinous, and 10 cases of endometrioid tumor. Twenty-five ovarian carcinomas were divided to 9 cases of stage I, 3 cases of stage II, and 13 cases of stage III. The interpretation of MSI included MSI-H and MSI-L. Results: On the basis of the NCI markers, 2 (9.5%) borderline ovarian carcinomas demonstrated MSI and 2 (8%) ovarian carcinomas had MSI. When all of the 14 markers were considered, 3 (14.2%) borderline ovarian carcinomas and 4 (16%) ovarian carcinomas showed MSI. The MSI was demonstrated in 3 (30%) serous, 2 (12%) mucinous, and 1 (10%) endometrioid subtype, respectively. One (11%) case of stage I and 3 (23%) cases of stage III had MSI. Conclusions: In our study, the detection of MSI using 14 markers including NCI recommendations found to have little contribution to reveal the carcinogenesis of sporadic epithelial ovarian tumor. Further studies based on another MSI markers are necessary to correlate these markers with the carcinogenesis of epithelial ovarian tumor. No significant financial relationships to disclose.
Primary Thrombophilia in Mexico XII: Miscarriages Are More Frequent in Persons with the Sticky Platelet Syndrome (SPS)
Authors: Guillermo J Ruiz-Delgado, Yahveth Cantero-Fortiz, Mariana Méndez-Huerta, Mónica León-González, Andrés A. León-Peña, Ana Karen Nuñez-Cortés, Guillermo J. Ruiz-Arguelles
Journal: Blood (2016)
C6-ceramide's effect on KRAS-defined colorectal cancer cells treated with oxaliplatin, 5-fluoruracil with and without cetuximab.
Authors: Alvaro G. Menendez, Daniel J. Curzake, LuGuang Luo, Harold J. Wanebo
Journal: Journal of Clinical Oncology (2016)

619 Background: Cetuximab (Cet) is beneficial for patients with metastatic KRAS Wild type (WT) colorectal cancer (mCRC) only. C6-Ceramide (C6-Cer) can act synergistically with chemotherapy to induce cancer cell death. The aim of this study was to compare growth inhibition percentage (GIP) of cytostatics 5-fluoruracil (5-FU), oxaliplatin (Ox) and Cet with or without C6-Cer in KRAS WT and KRAS mutant (KRAS Mut) CRC cell lines (SW48 and SW480, respectively). Methods: Both cell lines were incubated with IC50 concentrations of test drugs. Drug concentrations included 0.8µM for 5-FU, 0.04µM for Ox, 25 µg/mL for Cet, and C6-Cer concentrations ranged from 5 to 10 µM. Cell survival was assessed 72h after using 0.4% Trypan Blue. Results: With above mentioned concentrations, C6-Cer’s GIP was 78.3% for SW-480 (vs. 33.33% for SW-48). It was also noted that the addition of C6-Cer to a combination of steady concentrations of Ox, Cet and 5-FU increased GIP with an especially significant effect on SW-480. Addition of 5 and 7.5µM resulted in doubling of GIP (75% and 86.25%, respectively, vs 32.5% of 5-FU + Ox + Cet). The greatest effect was seen when 10µM of C6-Cer was added to the IC50 concentrations of chemotherapeutic agents (using the 25µg/mL concentration of Cet), where GIP increased from 32.5% to 92.5% in SW-480. Same concentration of drugs increased GIP for SW-48 to a similar 93.5%. Conclusions: C6-Cer appears to have direct inhibitory properties, especially on KRAS Mut cells. Additionally when added to Ox, 5-FU and Cet, C6-Cer reversed the apparent insensitivity of KRAS Mut to Cet. Also, the study showed C6-Cer can provide additional synergism to their cytostatic properties in KRAS WT CRC cell lines. The true mechanism of these observations is still undergoing analysis, however the effect of isolated C6-Cer on KRAS Mut raises possibility of a different pathway that could bypass EFGR pathway. We believe the results of this study provide a starting point for clinical studies with C6-Ceramide in patients with relapsing or metastatic KRAS Mut CRC in combination with standard chemotherapy plus molecular target agents hoping they will translate into clinical benefit for this difficult to treat patient population.
Quantifying the effect of everolimus on both tumor growth and new metastases in metastatic renal cell carcinoma (RCC): A dynamic tumor model of the RECORD-1 phase III trial.
Authors: A. M. Stein, A. Carter, N. Hollaender, R. J. Motzer, C. Sarr
Journal: Journal of Clinical Oncology (2011)

4602^ Background: The randomized, placebo-controlled phase III trial RECORD-1 (NCT00410124) established mammalian target of rapamycin (mTOR) inhibitor everolimus as an effective therapy for prolonging progression-free survival (PFS) in patients with advanced RCC who had progressed after sunitinib or sorafenib. The 10-mg daily everolimus dose administered in RECORD-1 was based on phase I studies correlating this regimen with constant and near-complete inhibition of mTOR pathway signaling. Dose reduction to 5 mg daily was allowed for toxicity. We developed a mathematical model of tumor growth in RECORD-1 to evaluate the effect of these 2 everolimus doses on growth of target lesions, nontarget lesions, and new metastases. Methods: Tumor growth in all patients with a baseline tumor measurement (n = 407) was described using nonlinear mixed effects modeling. Local radiological data was collected over time on the sum of largest target lesion diameters (SLD), progression status of nontarget lesions, and appearance of new lesions. By fitting a mathematical model for tumor growth to each patient, the impact of everolimus dose on all 3 lesion types was investigated. Results: Everolimus slowed growth of all 3 lesion types versus placebo (P <.0001). For target lesions, a 10-mg dose had a larger effect than a 5-mg dose (P <.0001). No discernable difference between doses was seen for nontarget and new lesions. The model predicts that after 1 year of continuous dosing, the change in SLD of target lesions in the average patient would be 142.1% ± 98.3% on placebo, 22.4% ± 17.2% for a 5-mg dose, and −15.7% ± 11.5% for a 10-mg dose. Conclusions: We developed a dynamic tumor model linking everolimus dosing history with overall tumor time course for each patient from RECORD-1. These tumor growth biomarkers are closer to the primary clinical end point (PFS) than measures of mTOR pathway inhibition, and thus may provide better predictions of trial success. Our analysis demonstrates a significant drug effect on target, nontarget, and new lesions. Furthermore, an everolimus daily dose of 10 mg is more efficacious than 5 mg in reducing growth of target lesions in metastatic RCC.
The clinical impact of routine bladder biopsy after BCG treatment of high grade non muscle invasive bladder cancer.
Authors: Igle J. De Jong, Leonie Theresa Jonker, Maud Anne Sien Weerink, Erik Bastiaan Cornel, Daphne Luijendijk, Anna Maria Leliveld
Journal: Journal of Clinical Oncology (2016)

438 Background: The need for invasive and costly routine bladder biopsies after an induction course of intravesical Bacillus Calmette-Guérin (BCG) in patients with high-grade non-muscle invasive bladder cancer is being questioned. Previous studies focused on differences in tumor detection between cystoscopic, cytologic and histologic results, whereas the clinical impact was disregarded. The aim of this study is to determine the impact of routine bladder biopsies on treatment. Methods: This retrospective multicenter trial included 348 patients from four hospitals in the Netherlands, who had had their BCG therapy evaluated by routine bladder biopsies between 2005 and 2014. The results of urethrocystoscopy (UCS) and/or cytology were compared to pathology outcomes. The influence of malignancies missed by UCS and/or cytology on further treatment was analyzed in 348 patients and in subgroups of patients with and without carcinoma in situ (CIS). A number needed to test was calculated. Secondary outcomes were costs and complications. Results: In patients with a normal UCS, malignancies were detected in 27/228 (11,8%), 19/136 (14%) and 8/92 (8,7%) in respectively all patients, patients with CIS and patients without CIS. This resulted in a radical cystectomy in only six (2,6%) patients, of which five (3,7%) with and one (1,1%) without CIS. Thirty-eight patients with a normal UCS have to undergo routine biopsies to effect therapeutic treatment in one (Number needed to test, NNT = 38). Estimated costs of one change of treatment are $81.300 USD(€72.818). Twenty-three of 348 (6,6%) transurethral biopsies were complicated. Conclusions: Considering the small clinical impact and high costs, routine bladder biopsies to evaluate BCG-induction are not recommended. The decision to perform bladder biopsies should be based on cystoscopic and cytologic results.
Comparison of patient outcomes stratified by histology among pemetrexed (P)-treated patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC) in two phase II trials
Authors: G. Peng, R. G. Zinner, Y. Wang, J. Treat, M. Monberg, C. K. Obasaju, R. S. Herbst, S. Novello, G. V. Scagliotti
Journal: Journal of Clinical Oncology (2008)

8096 Background: Preclinical data indicated that overexpression of TS correlates with reduced sensitivity to P in antifolate- resistant cell lines. A planned subset analysis of a phase 3 trial (Scagliotti G, J Thorac Oncol 2007) among pts with stage IIIB/IV NSCLC showed that P plus cisplatin was more effective among pts with adenocarcinoma and large cell carcinoma compared with squamous histology (11.8 versus 10.4 months, P=0.03). This differential activity may be related to a differential expression of TS in different histotypes. Methods: This is a retrospective analysis of two phase 2 studies of P 500 mg/m2 plus carboplatin AUC 6 Q 21 days or P 500 mg/m2 plus oxaliplatin 120 mg/m2 Q 21 days in chemonaive patients with stage IIIB/IV NSCLC. More than three quarters of enrolled patients had a non-squamous histology. Only pts with ≥1 dose of P were included. A Cox model of overall survival (OS) and progression free survival (PFS) with main effects for squamous histology was used. Since a potential for imbalances between histologic groups with respect to prognostic factors existed, the models were cofactor-adjusted by including terms for ECOG performance status, disease stage, and gender. Unadjusted medians within histologic subgroups were calculated using the Kaplan-Meier method. Results: See table. Conclusions: The longer PFS associated with non-squamous histology compared with squamous histology among stage IIIB/IV NSCLC pts treated with P plus carboplatin or P plus oxaliplatin is consistent with previous results from a phase 3 trial. Characteristics/Results Non- squamous Squamous Age, mean (sd) 60 (9.4) 61 (10.5) Disease stage IIIB IV 20 79 10 19 Gender, n Male Female 65 35 26 3 ECOG Performance Status, n PS 0 PS 1 24 76 6 23 OS Median (mos) Adj HR (95% CI) (non-squamous/squamous) 10.5 0.95 (0.52, 1.74) 9.8 – PFS Median (mos) Adj HR (95% CI) (non-squamous/squamous) 5.6 0.72 (0.43, 1.19) 4.7 – Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company
Analysis of 45 patients treated with sipuleucel-T (SIP-T) in a community practice.
Authors: Tushar Shah, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2012)

94 Background: We reviewed our toxicity experience with Sip-T since its FDA approval in May 2010. 340 pts were screened and 100 satisfied the general eligibility criteria for Sip-T; metastatic castrate resistant prostate cancer (mCRPC), minimally or asymptomatic status, limited or no visceral mets and not on chemotherapy. Methods: 45 were and 55 were not treated with Sip-T. As expected the characteristics of the 2 groups differed in that the untreated pts tended to be older, have higher ECOG scores, higher PSA, lower Hgb, fewer radical prostatectomies, more local radiation and TURPs, and more co-morbidities (HTN/diabetes/DVTor PE/TIA or CVA/CAD/AF/obesity/lipids). Prior systemic Rx to the Sip T pts included anti-androgens 93%, estrogens 33%, chemotherapy 31% and abiraterone 20%. Results: Central lines were placed in 32 pts. 10 of the first 17 had tunneled lines (TLs). One pt had a 10 day hospitalization for MRSA infection, 2 pts were delayed due to TL technical issues and all 10 pts complained about the complexity of TL care ( ∼1000 hrs of carer for the line to be used for ∼ 9 hours) 22 subsequent pts with central lines had external jugular lines (EJs) placed by interventional radiology before leukapheresis and removed the same day. No line complications have subsequently occurred. One pt pre-treated with samarium and ERT had too few cells for Rx. Two pts underwent a 4 th pheresis for technical issues. One pt (no pre-meds) had marked rigors post-infusion #2. No other &gt;grade 1 adverse reactions were noted during or after Sip T. 18% could not be weaned off low dose steroids before Sip T. No vascular events occurred. Median follow up is ∼ 10 months. 6 SipT pts (13%) and 11 untreated pts (18%) died of progressive disease. 3 of the 6 Sip T pts died within 30 days, all of progressive disease. Conclusions: Sipuleucel T administration in a community setting is generally uncomplicated. For pts requiring central lines, EJs are preferred. Pts with rapidly progressive disease should not receive Sip T.
Normal tissue exposure during retroperitoneal radiotherapy for pure seminoma of the testis.
Authors: Leah Minnie Katz, Jason Alexander Efstathiou, Jonathan Opraseuth, Joseph Killoran, Jonathan J. Paly, Rita Weathers, Marilyn Stovall, Clair Beard
Journal: Journal of Clinical Oncology (2012)

334 Background: Emerging data suggest risk of cardiovascular disease following radiotherapy to the retroperitoneal nodes in stage I/II seminoma patients. This study quantifies radiation dose to organs contributing to cardiovascular disease. Methods: Organs at risk (OAR) were contoured using Eclipse. OARs consisted of the cardiac ventricles, kidneys, abdominal aorta, renal arteries, common iliac arteries, and external iliac arteries. Four dose-volume histograms corresponding to 4 treatment plans were generated for each patient. Each patient was planned as if being treated for a left primary seminoma. Plans 1/2 consisted of a standard PA strip field, while plans 3/4 consisted of a standard extended-field configuration. Field width for plans 1/3 spanned the transverse processes, while plans 2/4 included treatment of the left renal hilum. OAR doses were cumulatively reported for all 22. Results: Median doses to the left kidney for plans 1, 2, 3 and 4 were 1.2, 2.2, 1.3 and 2.7 Gy, respectively. The median dose in treatment plan 2 was 1.0 Gy higher than plan 1, and in plan 4 it was 1.4 Gy higher than plan 3; suggesting increased left kidney dose when the renal hilum was included. The maximum distance between the top of the treatment field and the inferior ventricle was 7.1 cm, while the maximum ventricular-field overlap measured 1.81 cm. There were 4 of 22 patients (18%) who had overlap with 16.7 to 46.44 cm 3 of contoured ventricle within the field. The dose received by the cardiac ventricles ranged from 0–26.5 Gy, with the maximum dose of 26.5 Gy received by the patient with the greatest amount of overlap (1.81 cm). Conclusions: Adjusting treatment fields to include the renal hilum results in a higher dose to the kidneys and a mild increase in dose to the heart. While most patients have good separation of the heart and treatment field with extremely low cardiac doses, those whose ventricles are in field experience potentially significant cardiac doses. Our data suggests that for those patients with less than 2 cm between the superior portion of the treatment field and the inferior ventricle, the dose to the ventricles is at or approaches prescription dose. Clinicians treating seminoma patients may wish to consider this when determining candidacy for RT.
Family caregiver grief and depression outcomes from the ENABLE III randomized controlled trial.
Authors: J Nicholas Dionne-Odom, Andres Azuero, Kathleen Lyons, Jay Hull, Tor Tosteson, Zhongze Li, Marie Bakitas
Journal: Journal of Clinical Oncology (2015)

48 Background: Little is known whether early palliative care (PC) support for family caregivers (FCGs) impacts grief and depression after care recipients die. We conducted a randomized controlled trial (RCT) of a nurse-led, phone-based concurrent PC intervention for FCGs delivered at the time of care recipients’ advanced cancer diagnosis (early group) or 12 weeks later (delayed group). We hypothesized that grief and depression scores would be lower for early compared to delayed group FCGs. Methods: Early vs. delayed RCT (10/2010-9/2013) of 123 FCGs of community dwelling persons with advanced cancer in a rural, New Hampshire NCI-designated comprehensive cancer center and affiliated outreach clinics and a Vermont VA medical center receiving a multicomponent intervention (ENABLE [Educate, Nurture, Advise, Before Life Ends]) consisting of 3 weekly sessions, monthly follow-up, and a bereavement call. FCGs of persons dying during the study period completed the Center for Epidemiological Study-Depression scale (CESD) and the Prigerson Inventory of Complicated Grief-Short Form (PG13) 8-12 weeks after care recipients’ deaths. Generalized estimating equations were used to compute group means, standard deviations, and between-group effect size differences. Results: For care recipients who died (n = 70), 44 FCGs (early: n = 19; delayed: n = 25) completed after-death questionnaires. Mean depression scores (CESD) for the early group was 14.6 (SD = 10.7) and for the delayed group was 17.6 (SD = 11.8). Mean grief scores (PG13) for the early group was 22.7 (SD = 4.9) and for the delayed group was 24.9 (SD = 6.9). Between-group effect size differences were not statistically significant (CESD: d = -.27, p = .38; PG13: d = -.36, p = .24). Conclusions: Though statistically insignificant, the magnitude of the observed between-group differences for depression was small and for grief was medium. Considering the small sample size and the delayed group’s mean depression score surpassing the clinical cutoff (CESD score &gt; 16), the clinical relevance of these findings cannot be ruled out. Future upstream FCG PC interventions initiated long before end of life should continue to examine intervention effects on FCG after-death outcomes. Clinical trial information: NCT01245621.
The efficacy of first-line IRIS with or without bevacizumab in patients with metastatic colorectal cancer: Including multivariate analysis of two phase II studies.
Authors: Satoshi Yuki, Yoshito Komatsu, Hiraku Fukushima, Takahide Sasaki, Yoshimitsu Kobayashi, Kazuaki Harada, Toraji Amano, Michio Nakamura, Mineo Kudo, Miki Tateyama, Kazuteru Hatanaka, Soh Saitoh, Takuto Miyagishima, Takashi Kato, Yasuyuki Kawamoto, Tomofumi Takagi, Ichiro Iwanaga, Kencho Miyashita, Manabu Onodera, Yuh Sakata
Journal: Journal of Clinical Oncology (2014)

603 Background: The safety and efficacy of first-line IRIS (S-1 in combination with irinotecan) and IRIS/Bev (IRIS in combination with bevacizumab [Bev]) have been evaluated in patients with metastatic colorectal cancer (mCRC). To date, no randomized studies comparing these regimens have been performed. This retrospective analysis compared efficacy data for the two regimens from separate phase II studies performed at Hokkaido Gastrointestinal Cancer Study Group (HGCSG). Methods: Patients with histologically confirmed unresectable metastatic or recurrent CRC and received no prior chemotherapy were enrolled. In the first trial, patients received irinotecan 100 mg/m 2 on day 1,15 and oral S-1 40 mg/m 2 twice daily on days 1-14 every 4 weeks (IRIS study: HGCSG0302). In the second trial, patients received the same regimen plus Bev 5 mg/kg on day 1,15 (IRIS/Bev study). Results: A total of 40 and 52 patients were enrolled the IRIS and IRIS/Bev studies, respectively. Patient characteristics were generally similar in both groups, whereas there were more cases of good performance status and less number of metastatic organ in IRIS/Bev group. The median overall survival was 39.6 months in IRIS/Bev, as compared with 23.4 months in IRIS, corresponding to a hazard ratio for death of 0.418 (p&lt;0.001). The median progression-free survival was 17.0 months in IRIS/Bev, as compared with 8.6 months in IRIS (hazard ratio for disease progression, 0.402; p &lt; 0.001); the corresponding response rate were 63.5 percent and 52.5 percent (p = 0.393). In a multivariate analysis of PFS and OS, IRIS/Bev was significantly associated with longer PFS and OS compared with IRIS alone. Conclusions: In this retrospective comparison of two studies, the addition of Bev to IRIS appeared to improve outcome compared with IRIS alone in the first-line treatment of patients with mCRC.