tbuckley/cabot-search huggingface dataset:
Patient reported outcomes in NRG Oncology/RTOG 0938, evaluating two ultrahypofractionated regimens (UHR) for prostate cancer (CaP).
Authors: Himanshu Lukka, Stephanie L. Pugh, Deborah Bruner, Jean-Paul Bahary, Colleen Anne Lawton, Jason A. Efstathiou, Rajat Kudchadker, Lee Evan Ponsky, Samantha A. Seaward, Ian S. Dayes, Darindra Gopaul, Jeff M. Michalski, Guila Delouya, Irving D. Kaplan, Eric M. Horwitz, Mack Roach, Wayne Pinover, David Beyer, Howard M. Sandler, Lisa A. Kachnic
Journal: Journal of Clinical Oncology (2016)

27 Background: The considerable interest in short UHR 5-12 fractions(fr) in management of CaP is based on potential radiobiological advantages, patient convenience &amp; resource allocation benefits. Prior to comparison with standard RT regimens (SRTR), a study was undertaken whose primary objective was to demonstrate that 1-year health-related quality of life (HRQOL) for at least one UHR arm was not significantly lower than baseline as measured by the Bowel &amp; Urinary domains EPIC instrument(EPIC B&amp;U). Secondary objectives included acute &amp; late GI &amp; GU toxicity. Methods: RTOG 0938 is a randomized phase II study of CaP patients(pts), (Gleason score 2-6, stage T1-2a &amp; PSA &lt; 10 ng/mL) receiving 36.25 Gy (5 fr of 7.25 Gy in 2 wks), or 51.6 Gy (12 fr of 4.3 Gy in 2.5 wks). Pts were stratified according to RT technique – Cyberknife vs IMRT/VMAT or protons. A change in EPIC bowel domain score (baseline to 1-year) &gt; 5 points &amp; in EPIC urinary domain score &gt; 2 points were felt to be clinically significant. The frequency for &gt; 5 point change in bowel score (FREQE-B) in ≤ 35% of pts was considered acceptable, with the frequency ≥ 55% unacceptable. Similarly, the frequency for &gt; 2 point change in urinary score (FREQE-U) in ≤ 40% was considered acceptable, with the frequency ≥ 60% unacceptable. A sample size of 156 pts was needed for 95% power with one-sided significance level of 0.025 to preserve an overall level of 0.05. Results: 240 pts were enrolled to ensure adequacy of data for analysis. The compliance for HRQOL completion was good ( &gt; 80%). The 1 year FREQE-B for 5 fr was 23.5% (p &lt; 0.001) &amp; 12 fr was 23.1% (p &lt; 0.001). The 1 year FREQE-U for 5 fr was 35.3% (p &lt; 0.001) &amp; 12 fr was 34.7% (p &lt; 0.001). Conclusions: This study confirms that based on changes in EPIC B&amp;U (baseline to 1-year), acute &amp; late toxicity, both the 5 &amp; 12 fr regimens are well tolerated. These UHR need to be compared to current SRTR in the context of a RCT with efficacy &amp; toxicity endpoints. Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, UG1CA189867 from the National Cancer Institute (NCI). Clinical trial information: NCT01434290. [Table: see text]
Diminished protein-bound ω-hydroxylated ceramides in the skin of patients with ichthyosis with 12R-lipoxygenase (LOX) or eLOX-3 deficiency
Authors: A. Dick, I. Tantcheva-Poór, V. Oji, K.A. Giehl, J. Fischer, P. Krieg, H. Schneider, M. Rauh
Journal: British Journal of Dermatology (2017)
Association between prayer activity, inflammation, and survival in advanced cancer patients (ACPs): A preliminary study.
Authors: Carlos Eduardo Paiva, Bianca Sakamoto Ribeiro Paiva, Camila Souza Crovador, Sriram Yennurajalingam, David Hui
Journal: Journal of Clinical Oncology (2012)

e19602 Background: Prayers represent an important coping strategy among ACPs. The Religion Practice Questionnaire (RPQ) is a self-reported measure of religiosity validated in the Brazilian population, and includes a question assessing prayer activity. In this cross sectional prospective study, we determined the association among prayer activity, inflammation and survival in ACPs. Methods: Consecutive ACPs presenting for initial consultation at our Palliative Care Outpatient Clinic between March and December 2011 were enrolled. RPQ was administered by a research nurse, and consists of 15 items rated on a 5-point Likertscale (0=none, 5=very much). High prayer score (HPS) was defined as &gt;3/5 for question 11 ("I make personal prayers – spontaneous communications with God"). Inflammatory markers included white blood cell (WBC), albumin and C-reactive protein (CRP). Correlation analysis was performed using Spearman test. Survival was calculated from study enrolment until death, and analyzed with log rank test and Cox regression model including age, sex, KPS, treatment type and HPS. Results: 112 patients were enrolled: average age 59 y (range 21-85), female 53% (N=59), Karnofsky performance status (KPS) ≤70 46% (N=51), most common cancers breast and upper GI (N=41, 37%), no longer on active cancer treatments 48% (N=54). All patients were Christians, and 77 (69%) had HPS. RPQ was not associated with WBC, albumin, CRP nor survival. HPS correlated with WBC (r=-0.24, p=0.02), and CRP (r=-0.26, p=0.01) but not albumin (r=0.18, p=0.08). Patients with HPS survived longer (median 198 d vs. 121 d, p=0.040), which remained significant in multivariate analysis (Table). Conclusions: The act of praying was associated with decreased inflammation and improved survival in ACPs. Further studies are necessary to confirm these findings. [Table: see text]
Distant disease-free survival (DDFS) discrimination capacity of various pathologic complete response (pCR) definitions according to breast cancer subtypes.
Authors: Masaya Hattori, Keitaro Matsuo, Mari Ichikawa, Takashi Fujita, Masataka Sawaki, Naoto Kondo, Akiyo Horio, Yasushi Yatabe, Hiroji Iwata
Journal: Journal of Clinical Oncology (2013)

162 Background: pCR has been postulated to be correlated with long-term clinical benefits in some subtypes of breast cancer. Here, we analyzed the discriminatory ability and the predictive power of various pCR definitions for distant disease-free survival (DDFS) according to breast cancer subtypes. Methods: We analyzed 326 (114 Luminal A: ER+/PR+/HER2-, 44 Luminal B/HER2-: ER+/PR-/HER2-, 51 Luminal B/HER2+: ER+/PR+ and/or -/HER2+, 51 HER2: ER-/PR-/HER2+, and 66 Triple negative: ER-/PR-/HER2-) non-metastatic breast cancer patients (pts) who had received neoadjuvant chemotherapy at our institution between January 2003 and June 2012. Four pCR definitions were used: ypT0ypN0, ypT0/isypN0, ypT0/isypN0/+, ypT&lt;1micypN0/+. DDFS was estimated by Kaplan-Meier method, and analyzed by log-rank test and Cox proportional hazard model. The receiver operating characteristic (ROC) curves analysis was used for comparing DDFS prediction models with and without various pCR definitions in addition to other covariates (tumor stage, nodal status, BMI, tumor grade, use of trastuzumab) as variables. Results: The pCR rate was comparatively low in Luminal A and high in HER2. 94.1% of HER2 and 74.5% of Luminal B/HER2+ received total 1 year of trastuzumab therapy. In multivariate analysis, no pCR definitions were associated with improved DDFS significantly in Luminal A, Luminal B/HER2-, Luminal B/HER2+ and HER2, whereas each pCR definition was associated with improved DDFS in Triple negative (ypT0ypN0: HR0.12, p=0.043, ypT0/isypN0: HR0.06, p=0.007, ypT0/isypN0/+: HR0.107, p=0.004, ypT&lt;1micypN0/+: HR0.104, p=0.003). In the ROC curves analysis of triple-negative, a DDFS prediction model including pCR defined as ypT0/isypN0 showed the highest accuracy, but low statistical significance (AUC: 0.834 vs.0.749 p=0.076). Conclusions: pCR could discriminate good and poor prognosis groups only in Triple negative and pCR defined as ypT0/isypN0 has the potential to provide better discrimination in this subtype. The predictive power of pCR for long term clinical benefit in other subtypes may not be obvious due to the influence of effective adjuvant therapies.
Trends in trastuzumab utilization in Ontario: A single payer system
Authors: M. E. Trudeau, L. Yeung, R. Iyer, S. Hertz, S. Gavura, C. Sawka
Journal: Journal of Clinical Oncology (2008)

11534 Background: Ontario, a province of 13 million, has a single payer system for new IV cancer drugs, the New Drug Funding Program (NDFP) of Cancer Care Ontario. Trastuzumab (T) is an NDFP drug with funding for both adjuvant (adj) and metastatic (met) breast cancer. Each patient (pt) is registered as adj, or met with line of treatment (tx). Adj T is funded for pts who receive adj chemotherapy (chemo) for node+ disease or node-, >1cm. Methods: Pts who received T were identified in the NDFP from 1999–2007. Funding for met disease was from 1999 onwards and for adj tx from 7/2005 (tx allowed for those whose adj chemo ended after 10/2004). For adj T, records of further chemo were identified for pts treated in Integrated Cancer Programs, for whom complete tx information is available, 50% of all adj pts. Results: About 5,300 cases of breast cancer are diagnosed annually in ON. 1,799 patients have received met T since 1999. Initially met tx was 1st, 2nd and 3rd line, including single agent T. Since 2005 tx is more likely to be 1st line with a taxane or vinorelbine. Median duration of tx with docetaxel (D) is 7 mos, range <1 mo –28.2 mos. Since 2005, 2,217 pts have received adj T. Of these, 866 pts have complete records available and completed adj T by the end of 10/2007. Only 19 have received further chemo for mets. At most 50% of relapses would receive either no tx or hormonal tx, so we estimate that 38/886 or 4.3% of pts have relapsed after adj T. Currently, 100 pts/mo are enrolled in the NDPF, 80 for adj T and 20 for met T. Conclusions: In Ontario 960/5,300 or 18% of pts receive adj T and chemo annually. Relapses have been very infrequent (<5%) after adj T to date. In the met setting most T is given in combination with D, with a median duration of use of 7 mos. No significant financial relationships to disclose.
Effects of interruptions of radiotherapy on outcomes of patients with prostate cancer.
Authors: Yanqun Dong, Tianyu Li, Thomas M. Churilla, Rosalia Viterbo, Mark L. Sobczak, Marc C. Smaldone, David Y. T. Chen, Robert G. Uzzo, Mark Hallman, Eric M. Horwitz
Journal: Journal of Clinical Oncology (2016)

37 Background: To evaluate if interruptions of radiotherapy have any effect on outcomes for men with localized prostate cancer (PCa) treated with definitive external beam radiation therapy (EBRT). Methods: We included men with localized PCa treated with definitive 3DCRT or IMRT of escalated dose (≥74 Gy in daily fraction of 2 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) between 1989 and 2013. Men receiving androgen deprivation therapy, or follow up &lt;1 year were excluded. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of therapy, to account for the difference in total RT dose and planned RT duration. NTDR was analyzed for each NCCN risk group. Results: A total of 1,796 men including 861 low risk, 821 intermediate risk, and 114 high risk were included, with median follow up of 53.5 m (range 12 to 185.8 m). The median NTDR was 31% (range 23.1%-71.2%), translating to approximately 2 breaks (each break represents a missed treatment that would be made up in the end) for an 8-week RT with 5 treatments per week. The 75th percentile of NTDR was 33.3%, translating to approximately 4 breaks, which was used as the cutoff to compare the outcomes with NTDR ≥33.3% vs &lt;33.3%. There were no significant differences in freedom from biochemical failure (FFBF), distant metastasis (DM), cancer-specific survival(CSS), or overall survival (OS) for men with NTDR ≥33.3% compared to NTDR&lt;33.3% for each risk group (Table). Multivariable analyses including NTDR, age, race, Gleason score, T stage, and PSA were performed using the PHREG procedure. NTDR ≥33.3% was not significantly associated with increased hazard ratio for outcomes in each risk group compared to NTDR &lt;33.3%. Conclusions: Interruptions of RT do not cause significant difference in outcomes in each risk group for men with localized PCa treated with definitive EBRT of escalated dose. [Table: see text]
Insuline like growth factor receptor-1 (IGFR-1), MET, and BRAF and primary resistance to cetuximab therapy in colorectal cancer patients
Authors: G. Finocchiaro, F. Cappuzzo, E. Rossi, L. Toschi, P. A. Janne, M. Roncalli, C. Ligorio, L. Rimassa, A. Santoro, M. Varella-Garcia
Journal: Journal of Clinical Oncology (2008)

4135 Background: Mechanisms for intrinsic resistance to cetuximab, a monoclonal antibody against EGFR, are not fully elucidated. KRAS mutations cannot account for all resistant cases. Preclinical data suggested that MET could interfere with anti-EGFR strategies and IGF1R mediate resistance to anti-EGFR therapies through continued activation of PI3K-Akt pathway. This study investigated molecular predictors for intrinsic resistance to cetuximab therapy in colorectal cancer patients. Methods: The study was conducted in a cohort of 85 metastatic colorectal cancer patients (mCRC) treated with cetuximab-based therapy in whom EGFR and KRAS status was known. We analyzed MET (fluorescence in situ hybridization-FISH), IGF1R (FISH and immunohistochemistry-IHC), BRAF (mutation) and PI3KCA (mutation). Results: In 76 cases successful for MET FISH analysis, increased copy numbers (mean ≥ 5) was observed in 7 patients (9.2%), including 2 (2.6%) with gene amplification and 5 (6.6%) with high polysomy. MET status was not associated with clinical characteristics nor response to cetuximab. IGF1R was successfully evaluated in 77 and 70 cases by FISH and IHC, respectively. No IGF1R amplification or high polysomy was observed. Using a cut off of 95 for IHC, determined by ROC analysis, no association with response or time to progression was observed. IGF1R IHC+ (N=52) had significantly longer survival (OS) than IHC- (16.1 versus 6.7 months, p=0.006). BRAF and PI3KCA mutation analyses were performed in 79 cases. BRAF was mutated in 4 (5.0%) and although not significantly associated with clinical end-points, individuals harboring such mutation did not respond to the therapy, with time to progression (TTP) and OS shorter than in BRAF wildtype (TTP: 1.2 versus 4.6 months, p=0.09; OS: 5.4 versus 9.8 months, p=0.3). No difference in response, TTP, and OS was observed in 14 patients (17.7%) harboring PI3KCA mutation versus wild type individuals. Conclusions: The rarity of MET and IGF1R gene amplification suggests a marginal role in intrinsic resistance to anti-EGFR therapy in mCRC. The role of BRAF mutations as responsible for cetuximab failure and the potential prognostic implication of IGF1R expression merits further evaluation. No significant financial relationships to disclose.
Comparison of Outcomes of Advanced Myelofibrosis Patients Treated with Ruxolitinib (INCB018424) to Those of a Historical Control Group: Survival Advantage of Ruxolitinib Therapy
Authors: Srdan Verstovsek, Hagop M. Kantarjian, Zeev Estrov, Jorge E. Cortes, Deborah A. Thomas, Tapan Kadia, Sherry Pierce, Mario Cazzola, Elisa Rumi, Enrica Morra, Ester Pungolino, Domenica Caramazza, Francesco Passamonti
Journal: Blood (2011)
An open-label phase II clinical trial of the RXR agonist IRX4204 in taxane-resistant, castration-resistant metastatic prostate cancer (CRPC).
Authors: Fairooz F. Kabbinavar, Nazy Zomorodian, Matthew Rettig, Faraz Khan, Daniel Reif Greenwald, Sheldon J. Davidson, Brian Anthony DiCarlo, Ravi Patel, Lalita Pandit, Rosh Chandraratna, Martin Sanders
Journal: Journal of Clinical Oncology (2014)

5073 Background: IRX4204 is a potent, selective, oral small compound agonist of RXR nuclear receptor pathways. In preclinical studies IRX4204 synergizes with insulin-like growth factor binding protein-3, to induce apoptosis in human prostate cancer cells and was effective in reducing human prostate tumor burden in a murine xenograft model. The only prostate cancer patient in a phase I trial of IRX4204 trial manifested a sustained >90% PSA reduction and a PR lasting over 7 months. These findings led to the current open label phase II trial of IRX4204 to evaluate safety and activity or futility, for treatment of advanced CRPC. Methods: The trial enrolled 23 men with metastatic CRPC, who had failed a taxane or declined chemotherapy, with ECOG 0-2 with evidence of biochemical or radiographic progression on bone scan, CT and/or MRI. Patients continued with androgen blockade and had to have adequate organ function. Patients were deemed to have demonstrated benefit of IRX4204 treatment if they had PFS >56 days, and/or a 50% PSA decrease, and/or PR or CR by RECIST. Futility defined as 4 or fewer patients demonstrating benefit in the planned enrollment of 37 patients. Patients received IRX4204 (20 mg/orally daily) . PSA was checked Q 4 weeks & radiographic assessments Q8 weeks. Radiographic not PSA progression was used to determine progression. Results: IRX4204 was well tolerated for up to 11 months. No drug related SAE have occurred. Manageable decreases in TSH and increases in triglycerides, both known adverse effects of RXR agonists, have been observed. Protocoldefined patient benefit was observed in 13/23 (57%) patients. PFS >56 days observed in 13/23 (57%). PFS >112 days observed in 9/23 (39%), range 113 to 330 days. PSA 50% response occurred in 3/23 (13%), including one additional PSA 90% response. No objective responses have occurred. Conclusions: This study demonstrates that IRX4204 treatment of taxane-resistant CRPC is well tolerated, & provides an activity signal warranting further evaluation of IRX4204as a treatment for chemo-refractory CRPC. Funding: Supported by Io Therapeutics, Inc. 1805 East Garry Ave., Suite 110, Santa Ana, 92705. Clinical trial information: NCT01540071.
First-line treatment of inoperable pancreatic adenocarcinoma with lipid complexed paclitaxel nanoparticles plus gemcitabine compared with gemcitabine monotherapy. A prospective RCT - phase II study
Authors: M. Löhr, S. Haas, W. Bechstein, M. Karrasch, A. Mescheder, I. Meyer, G. Bodoky, A. Pap, D. Jäger, U. R. Fölsch
Journal: Journal of Clinical Oncology (2008)

4618 Background: Cationic lipid complexed paclitaxel (EndoTAG-1[E]) is a novel therapy destroying tumor blood vessels. E targets activated endothelial cells due to its cationic carrier liposomes binding preferentially to negatively charged cells of tumor vessels. Methods: CT4001 is an open-label phase II RCT of 1st line combination treatment with weekly gemcitabine (G) (arm 1: G mono 1,000 mg/m²) and twice weekly E at 3 different dose levels (arm 2/3/4: G+E 11/22/44 mg/m²) in patients with inoperable pancreatic adenocarcinoma (PC). Treatment was at least 7 weeks with the option to continue in case of clinical benefit (SD or better), and follow-up for survival. Results: 100 patients from a planned interim analysis. According to TNM at screening, 80% had metastatic disease and 20% had locally advanced disease. Median sum of longest target lesion diameter (RECIST) at screening was 55 mm in arm 1, 93 mm in arm 2, 74 mm in arm 3, and 63 mm in arm 4. Patients were ECOG grade 0 (39%), 1 (52%) or 2 (9%) with slightly more patients with ECOG grade 2 in the E arms (4% in arm 1, 8% in arm 2, 13% in arm 3, 13% in arm 4). Serious treatment adverse events were in 7 patients (29%) in arm 1, 9 patients (36%) in arm 2, 10 patients (42%) in arm 3, and 11 (48%) patients in arm 4. The most frequent AEs attributable to E treatment were pyrexia and chills. The addition of E to G did not lead to elevated bone marrow toxicity. Blood and lymphatic system disorders were reported in 58% of arm 1, 52% of arm 2, 54% of arm 3, and 65% of arm 4. Neutropenia was 50% in arm 1, 24% in arm 2, 17% in arm 3, and 52% in arm 4. No death was related to study medication. Tumor response at end of treatment according to RECIST: PR was 21% in arm 1, 14% in arm 2, 12% in arm 3, 29% in arm 4. SD was 48% in arm 2 and 53% in arm 3 higher than 26% in arm 1 and 14% in arm 4. Pain and EORTC PAN-26 QoL assessments were initially lower in arm 1, suggestive of less tumor burden in arm 1. In all 4 arms, pain and PAN-26 QoL improved for the duration of the study. Conclusions: As in the phase I studies, E has a favourable safety profile. Addition of E to G monotherapy is well tolerated and may add clinical benefit to patients with advanced PC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Medigene AG
Health behaviors and coping among informal caregivers of lung and colorectal cancer survivors: Distribution and interrelationships.
Authors: Erin E. Kent, Kristin Litzelman, Julia Howe Rowland
Journal: Journal of Clinical Oncology (2015)

229 Background: Family/informal caregivers play a critical role in the palliative care and support of cancer survivors, yet are at risk of poorer health outcomes than non-caregivers. Self-care, including positive health behaviors and coping, are important for long-term caregiver well-being, and potentially that of care recipients. This study sought to evaluate the distribution of and interrelationships among health behaviors and coping strategies among cancer caregivers. Methods: This study used data from the Cancer Care Outcomes Research &amp; Surveillance Consortium (CanCORS). Caregivers reported by survey their health behaviors, coping, and sociodemographic and caregiving characteristics. Descriptive statistics assessed the distribution of caregivers’ health and coping behaviors, and multivariable linear regressions assessed the associations between health behaviors and coping styles. Results: Many caregivers reported positive health behaviors (i.e., moderate physical activity, adequate sleep, low rates of binge drinking). Caregivers most frequently reported using emotion-focused coping styles (religion, acceptance, positive reframing, emotional support). Caregivers reporting higher levels of physical activity or feeling less well-rested used problem-focused coping styles more frequently (Effect sizes [ES] up to 0.21, p &lt; 0.05) . Those with some physical activity (1-149 minutes/week vs none) scored higher on emotion-focused coping, while drinkers (1+ drink in the past 30 days vs 0) and binge drinkers (5+ drinks in a row vs 0) scored lower on this subscale (ES = 0.16, 0.12, and 0.25; p &lt; 0.05). Caregivers reporting current smoking (ES = 0.21), binge drinking (ES = 0.49), and feeling less well-rested (ES up to 0.48) scored higher on dysfunctional coping (p &lt; 0.05). Conclusions: Caregivers’ health behaviors and coping strategies were interrelated. Interventions targeting both factors concurrently may be particularly efficacious at improving family caregiver self-care, potentially improving caregiving quality and patient-centered palliative care. Future research is needed to design and test such interventions and the potential impact on palliative care.