tbuckley/cabot-search huggingface dataset:
Comparative PARP enzyme inhibition of PF-01367338, olaparib, and MK-4827.
Authors: K. A. Kern, S. Zhang, D. R. Shalinsky, D. D. Wang
Journal: Journal of Clinical Oncology (2011)

e13552 Background: Within the past several years multiple PARP inhibitors have been entered into clinical trials, in a variety of tumors types with defective homology-directed DNA repair. An understanding of the degree of PARP inhibition produced by these inhibitors is critical in understanding potential drug effectiveness. Pharmacodynamic (PD) data, specifically PARP inhibition in peripheral blood lymphocytes (PBLs), have been reported for PF-01367338, olaparib and MK-4827, which provides an opportunity to compare the PD effect of these compounds. The objective of this study was to compare PARP inhibition following PF-01367338 daily IV dosing to those achieved by olaparib and MK-4821. Methods: PARP inhibition (percent change of PAR from baseline) data for PF-01367338 were obtained from the Phase 1 study of PF-01367338 given daily in combination with temozolomide for 5 days. Olaparib and MK-4821 data were obtained from the exposure or dose/response curves reported in the literature. Comparisons were made using PD data from PF-01367338 matched to those reported for each compound, including (a) the average PARP inhibition over the dosing interval for comparison with olaparib, and (b) the PARP inhibition at the end of dosing interval for comparison with MK-4827. Maximum inhibition (Emax), the endpoint used for the comparison of inhibitory performance, was either determined by PK/PD modelling (PF-01367338 and Olaparib) or obtained from the average inhibition at the dose levels where PARP inhibition in PBLs reached plateau (MK-4827). The corresponding range for Emax was obtained from observed data for the relevant comparison at the dose or exposure level(s) where Emax was achieved. Results: Comparison of Emax achieved (see table). Values for Olaparib and MK-4827 were read off the published figures thus approximate. Conclusions: PF-01367338 provides an average increase of 22-27% in PARP inhibition with less inter-patient variability compared to olaparib or MK-4827. Future studies are planned to determine if this finding translates into an increase in anti-tumor response. PF-01367338 vs. olaparib PF-01367338 vs. MK-4827 PF-01367338 Olaparib Difference PF-01367338 MK-4827 Difference Emax (%) 92 70 22 Emax (%) 92 65 27 Range 90-97 40-95 Range 92-99 40-82
Acute hospitalizations in cancer patients treated with definitive radiotherapy: A retrospective cohort study with implications for an urgent care clinic.
Authors: Abigail T. Berman, Peter Edward Gabriel, Daniel Owen, Melody Ju Xu, Charles B. Simone, John Peter Plastaras, John Paul Christodouleas, Wei-Ting Hwang, Neha Vapiwala
Journal: Journal of Clinical Oncology (2016)

312 Background: Reasons for hospitalizations in patients undergoing curative-intent radiotherapy (RT) have not been well characterized previously. Implementation of urgent cancer care clinics could decrease rates of hospitalization, but the reasons for acute visits must be better understood. This retrospective cohort study investigates emergency department (ED) visits or admissions in patients treated with definitive RT. Methods: Under an IRB-approved protocol, the cohort was defined as all consecutive patients &gt;=18 yo who began RT (RTSTART) between 7/1/11 and 12/31/13 for nonmetastatic disease with curative intent. An acute encounter was defined as an ED visit or inpatient admission during RT or 30 days after the conclusion of RT (30DA). Results: A total of 1852 unique RT courses from 1823 patients were identified, within which there were 666 RT unique courses (657 patients) who had at least one acute encounter. There were 1006 acute encounters, comprising 287 ER and 719 inpatient visits. The number of admissions per RT course ranged from 1 to 9, with &lt;13% with &gt;3. The mean difference between post- and pre-RT ECOG performance status was greater for patients with acute encounters than those without (0.47 vs. 0.06). For those admitted, the median days from RTSTART to admission were 36 (0-81) and 68.2% received concurrent chemotherapy. Conclusions: In this large analysis from a single quaternary cancer center,over one-third of patients receiving curative-intent RT had an acute encounter, a high percentage of whom received chemotherapy. Further investigations are needed to classify which admissions were unanticipated, which in turn would guide design of urgent cancer care centers for RT patients and improve quality of care. [Table: see text]
Outcomes after local recurrence following breast-conserving therapy for early-stage breast cancer.
Authors: Maha Saada Jawad, Jessica Wobb, Michelle Wallace, Inga S. Grills, Arielle Pietron, Kimberly Marvin, Joshua T. Dilworth, Peter Y. Chen
Journal: Journal of Clinical Oncology (2014)

66 Background: Limited data exist for patients who develop local recurrence (LR) following breast conserving therapy (BCT) for early stage breast cancer (ESBC). This study is to evaluate outcomes and predictors of failure following LR in patients treated with BCT. Methods: 1,654 women with ESBC underwent BCT from 1980 – 2013 at a single institution. All patients had breast-conserving surgery followed by whole breast irradiation (WBI) or accelerated partial breast irradiation (APBI). Subset analysis was performed for patients who developed LR as a first event. Clinical outcomes analyzed include contralateral breast failure (CLBF), regional recurrence (RR), distant metastases (DM), cause-specific survival (CSS), and overall survival (OS). Continuous variables were analyzed with an independent samples t-test and categorical variables with χ 2 . Univariate analysis was performed to determine factors predictive for events after LR. Results: 112 (7%) patients developed LR (87 WBI; 25 APBI), with median time to LR of 6.6 yrs (0.1-28). Median follow-up for the LR group was 14 yrs (0.7-31) overall; 10 (0.7-19) and 16 yrs (1.4-31) for APBI and WBI, respectively (p=0.01). A change from initial to LR pathology was seen for: ER status 21%, PR status 25%, HER2 status 13%, grade 38%, histology 40%, and LVSI 38%. Salvage treatment following LR was mastectomy ± chemotherapy (CHT) in 75%, wide local excision ± RT in 19%, CHT in 2%, and other in 4%. Outcomes following salvage treatment for LR are shown in the table. No differences were seen in outcomes between patients treated with APBI v WBI. Univariate analysis failed to demonstrate any factors predictive for events following LR. Conclusions: Patients who developed LR following BCT for ESBC had excellent clinical outcomes at 5 and 10 yrs, demonstrating effective salvage treatment in this cohort of patients. No differences were noted between patients undergoing APBI v WBI. Further identification of histopathologic patterns between first cancer and LR is currently underway. [Table: see text]
Patient-reported benefits of massage therapy as treatment for chemotherapy-related pain.
Authors: Alvaro G. Menendez, Alejandro Ramon Carvajal, Regina Cobb, Tanmay Sahai, Diane D'Ambra, Kathi Healey, Maria Soriano-Pisaturo
Journal: Journal of Clinical Oncology (2016)

192 Background: Massage Therapy (MT) has been suggested to provide symptom relief of chemotherapy related side effects. Its impact on pain improvement, prevention, and overall quality of life (QoL) is characterized in this study and 2 different pain scales are being compared. Methods: Patients who were on active chemotherapy and agreed to receive at least one MT session over a 10-week period were included. Wong-Baker Pain scale (WBPS) and Numerical Pain Scale (NPS) were assessed pre and post every session. Results: 62 pts were included. 25 pts were on analgesics (Opiates 64%, Gabapentin 24%, NSAIDs 12%). 34/62 pts had no complaints of pain on enrollment and only 9% (3/34) developed pain as per WBPS on subsequent visits. In 27/28 pts (97%) who had pain initially according to WBPS (0-4 scale), improvement was reported from X = 1.25 (5±5, M = 0, SD 2.31) to X = 0.32 after one MT session (4±4, M = 0, SD 1.16) (p &lt; 0.05). 25/28 pts (89%) had maintained improvement from 1st to 2nd session with an average of 50%. 11% (3/28) reported worsening of pain symptoms with an X increase average of 2.66 (3±1, M = 2). NPS was positive for 37 patients on initial visit. NPS revealed a similar trend with pre-massage X of pain from 2.76 (5±5, M = 2, SD 2.87) to 1.18 (4±4, M = 0, SD 2.01) after 1st session (39.5% improvement) (p &lt; 0.05). 18/25 (72%) saw a decrease in pain level per NPS (X = 2.27) between each session, whereas 28% noted worsening of pain by the end of their participation. Conclusions: MT is a high-value, low-risk intervention for reducing cancer pain and cancer treatment-related pain. MT could be used to address patients' need for emotional and physical human connection at a time when their quality of life is fragile. MT may offer pain prophylaxis when provided in a cumulative manner. NPS appears to be more sensitive than WBPS for pain screening in oncologic patients. Further studies are necessary to confirm the suggested findings of massage therapy for pain prevention and treatment.
Patient-reported fatigue in head and neck cancer survivors.
Authors: G. B. Gunn, T. R. Mendoza, A. S. Garden, X. S. Wang, W. H. Morrison, S. J. Frank, E. Y. Hanna, C. Lu, B. M. Beadle, K. K. Ang, C. S. Cleeland, D. I. Rosenthal
Journal: Journal of Clinical Oncology (2011)

5523 Background: Previously we reported that 1/3 of patients had moderate to severe (MS) levels of fatigue 2 months after completing radiation therapy (RT) or chemoradiation (CRT) for head and neck cancer (HNC) as measured by the M. D. Anderson Symptom Inventory – Head and Neck Module (MDASI-HN). However, the rate and severity of patient-reported fatigue beyond this and particularly in long term survivors has not been established. We collected long term patient-reported fatigue using the Brief Fatigue Inventory (BFI), a validated fatigue assessment tool. Methods: Patients treated with RT or CRT for HNC, with no evidence of disease at last follow up were eligible for this cross sectional study using the BFI. Patient, tumor and treatment characteristics were collected. Moderate to severe (MS) responses were defined as patient ratings of 5 or greater on a 0-10 scale. We report the prevalence and pattern of fatigue using descriptive statistics. Chi-square test was used to determine differences by treatment group. Results: 167 patients participated. Median time from RT/CRT to completion of BFI was 5.2 years (range 6 mo to 14 years). The majority of patients had been treated with IMRT for oropharynx cancer. 99/167 received chemotherapy. 11% of patients reported feeling unusually tired over the past week. 6% reported MS fatigue “right now”. Regarding “usual level” and “worst level” of fatigue over the past 24 hours, 8% and 10% of patients reported MS fatigue, respectively. The proportion of patients with MS fatigue varied by quartile of time in follow up: (6 mo to 2.5 y) = 12%; (2.51 to 5.2 y) = 2%; (5.21 to 6.6 y) = 5%; (>6.6 y) = 20%. There were no significant differences in MS fatigue by treatment group, including chemotherapy and radiation technique (IMRT vs. 3DRT). Conclusions: Overall, 10% of patients have MS persistent fatigue well after completing treatment with RT or CRT for HNC. Aside from treating any reversible medical cause and other commonly associated symptoms, there are no established treatments for these patients. We plan to conduct a phase II trial investigating a CNS stimulant in reducing patient-reported fatigue.
Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial
Authors: Estelle C Nijssen, Roger J Rennenberg, Patty J Nelemans, Brigitte A Essers, Marga M Janssen, Marja A Vermeeren, Vincent van Ommen, Joachim E Wildberger
Journal: The Lancet (2017)
Long-term survival (LTS) and competing risks within a prospective multi center German randomized trial comparing induction chemotherapy (CTx) followed by concurrent (cc) chemoradiation (CTx/RTx) plus surgery (SURG; TRIMODALITY) supplemented by PCI versus local treatment (Tx) alone (SURG + RTx) in operable IIIA NSCLC.
Authors: T. C. Gauler, C. Poettgen, H. Wagner, S. Korfee, R. Hepp, G. Stamatis, J. Von Pawel, B. Passlick, V. Budach, H. Wilke, S. Seeber, M. Stuschke, W. E. E. Eberhardt
Journal: Journal of Clinical Oncology (2011)

7042 Background: we have already reported cumulative probability (prob) of brain relapse as first site of failure within our randomized trial that investigated TRIMODALITY + prophylactic cranial irradiation (PCI) versus SURG + RTx alone in operable IIIA NSCLC (Pöttgen, JCO 2007). Here we report LTS for these arms, look for exploratory subgroups and investigate competing risks. Methods: Pts with histopathologically (mediastinoscopy) proven operable IIIA (1-2 LN involved, no clinical N2, no bulky/extranodal disease, central T3N0-1, WHO 0,1) NSCLC were stratified (TN-group, center) and randomized. Arm B received three CTx cycles cis (60 mg/m2 d 1+7 or 8) and eto (150 mg/m2 d 3,4,5) qd 22. This was followed by cc CTx/RTx including cis 50 mg/m2 d 2 + 9 and eto 100 mg/m2 d 4-6 cc with 45 Gy (1.5 Gy bid). 3-5 weeks after end of RTx SURG was performed if possible and PCI given thereafter. Arm A had local treatment alone (SURG + RTx) and no PCI. Results: Pts accrual 1/95 to 10/01; eligible 106/112 randomized; Pts characteristics: gender m 90; f 16; age median 57 (37-71); PS 0-1; histo: adeno (ADC) 35; squamous cell (SCC) 50; large cell (LCC) 16; ADSCC 5 TN-groups: T3N0-1 6 T1-2N2 83 T3N2 17. Med S of pts still alive on f-up: 130 mo. LT exploratory OS analysis (2-y-OS %; 5-y-OS %, 10-y-OS %); B: 54.6 20.0 12.5; A: 44.2 23.5 10.0 (ns log rank, Wilcoxon); PFS: B: 36.4 14.6 12.7 A: 29.4 17.3 10.4 (p = 0.30/0.14 log rank/Wilcoxon) Disease-specific survival: B: 40.5 25.0 25.0 A: 32.5 23.1 18.5 (p = 0.16/0.059 log rank/Wilcoxon), Cumulative 10-y prob %: non-disease-related events (tox, comorbidity, second cancer): B: 56.3 A: 67.7 (ns); brain relapse as first site of failure: B: 16.6 A: 30.4 (p = 0.059/0.020 log rank/Wilcoxon). Conclusions: LTS after Tx in stage IIIA is significantly hampered by cumulative competing risks (toxicities, comorbidities, second cancers) regardless of Tx intensity. Initial pts selection based on comorbidity profiles may be most important in improving LTS with aggressive protocols based on TRIMODALITY (+/- PCI).
Measuring and reporting on system performance across the Canadian cancer control continuum.
Authors: Rami Rahal, Tonia Forte, Julie Klein-Geltink, Gina Lockwood, Carolyn Sandoval, Heather E. Bryant
Journal: Journal of Clinical Oncology (2012)

254 Background: The Canadian Partnership Against Cancer’s System Performance initiative is a national, collaborative effort, aimed at reporting pan-Canadian system performance indicators across the cancer control continuum to inform system-wide quality improvements. Methods: This work involved prioritizing indicator development to address quality and cancer continuum dimensions, defining and adopting standardized methodologies, and collecting validated, comparable data from provincial and national sources. Results have been disseminated though a number of general and special topic reports and have been used by policy makers and planners to identify and interpret gaps, variations, and trends to inform quality improvement strategies. An independent evaluation of the impact of this work was conducted in 2012. Results: The Reports, published annually since 2009, include a broad range of performance indicators on prevention, screening, diagnosis and treatment, research, patient experience, survivorship, supportive care, and long-term outcomes. Results show notable differences in performance by province, age and gender, geography (urban/rural), and socio-economic status, including significant variations in clinical practice patterns and concordance with evidence-based surgical, radiation, and systemic therapy guidelines. These are examined along with population risk factors, screening rates, and wait times, to assess relationships with outcome measures, including patient reported outcomes. Special studies, including chart reviews, have been conducted to explain variations, set performance targets, and to help focus quality improvement efforts. The impact evaluation identified substantial uptake of system performance information across the country and a range of specific initiatives informed by the work. Conclusions: This work represents one of the most comprehensive efforts of its kind involving all provincial and national jurisdictions in the sharing and dissemination of standardized performance results, the development of evidence-based national performance targets, and coordinated efforts to use this information to inform system-wide quality improvements in cancer control.
Biweekly cetuximab (C), oxaliplatin (Ox), and capecitabine (Cape) in first line therapy of metastatic colorectal cancer (mCRC): Preliminary results on toxicity and K-ras status
Authors: D. Cohen, H. Ma, Y. Yuan, T. Hochman, H. S. Hochster
Journal: Journal of Clinical Oncology (2008)

15060 Background: In a novel q2w schedule, this trial combined Ox and flat dosing of cape with C in first line therapy of mCRC. C was given weekly until more recent data suggested q2w dosing was equally effective, and the study was amended. Recent retrospective analyses have shown that K-ras mutation is associated with a decreased efficacy of C. We will report on the relationship between K-ras status, rash development and response rate in previously untreated mCRC. Methods: Patients (pts) with previously untreated histologically confirmed metastatic colon adenocarcinoma, ECOG performance status (PS) 0–1, and adequate organ function were eligible. K-ras mutation status was determined by isolating DNA from paraffin embedded tumor biopsies. Pts were treated with C (initially 250mg/m2 weekly and later amended to 500mg/m2 q2w) and Ox (85mg/m2) combined with flat dose cape (2500mg bid × 7days) in a q2w schedule. Endpoints included response (RECIST) and toxicity rates (with special attention to cutaneous reactions) and how these relate to k- ras status. Results: Between Aug 2004 and Dec 2007, 22 pts were enrolled, M/F (13/9), PS 0/1 (8/14), and median age 66 yrs (37–80). 12 pts received weekly and, following protocol amendment, 10 pts received q2w C. The most common grade 3/4 toxicities were diarrhea (23%), hypersensitivity reaction (9%), hand-foot syndrome (9%), rash (9%) and neuropathy (9%). The toxicity profile between the two C schedules was comparable. Of 17 pts evaluable for response, there were 3 CR, 5 PR, and 2 SD with an ORR of 47% and disease control rate of 52%. K-ras data are currently being analyzed and will be related to response and toxicity rates. Conclusions: The novel combination of q2w C, Ox, and flat dose cape was well tolerated as first line treatment in mCRC and the ORR is comparable to other first-line C regimens. C 500 mg/m2 q2w appears to have equal toxicity and activity as weekly dosing. The relationship between K-ras status and response rates will be presented. [Supported in part by grants from BMS and Sanofi Aventis.] Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, sanofi-aventis Bristol-Myers Squibb, sanofi-aventis
Secukinumab in Active Rheumatoid Arthritis: A Phase III Randomized, Double‐Blind, Active Comparator– and Placebo‐Controlled Study
Authors: Francisco J. Blanco, Rüdiger Möricke, Eva Dokoupilova, Christine Codding, Jeffrey Neal, Mats Andersson, Susanne Rohrer, Hanno Richards
Journal: Arthritis & Rheumatology (2017)

To evaluate the efficacy and safety of secukinumab in patients with active rheumatoid arthritis (RA) who had an inadequate response to or intolerance of tumor necrosis factor (TNF) inhibitors.In this phase III study, 551 patients were randomized (1:1:1:1) to receive intravenous secukinumab at a dose of 10 mg/kg (at baseline and weeks 2 and 4) followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks or, alternatively, abatacept or placebo on the same dosing schedule. The primary end point was the proportion of patients achieving 20% improvement in disease activity according to the American College of Rheumatology response criteria (ACR20) at week 24 in the secukinumab 150 mg or 75 mg treatment groups as compared with placebo. Key secondary end points included change from baseline to week 24 in the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) and the Health Assessment Questionnaire disability index (HAQ DI), as well as the ACR 50% improvement (ACR50) response rate at week 24.The primary efficacy end point was met in patients receiving 150 mg secukinumab, in whom the ACR20 response rate at week 24 was significantly higher than that in the placebo group. The ACR20 response rates at week 24 were 30.7% in patients receiving 150 mg secukinumab (P = 0.0305), 28.3% in those receiving 75 mg secukinumab (P = 0.0916), and 42.8% in those receiving abatacept, compared with 18.1% in the placebo group. A significant reduction in the DAS28-CRP was seen in patients treated with 150 mg secukinumab (P = 0.0495), but not in patients treated with 75 mg secukinumab. Improvements in the HAQ DI and ACR50 response rates were not significant in the 2 secukinumab dose groups compared with the placebo group. The overall safety profile was similar across all treatment groups.Secukinumab at a dose of 150 mg resulted in improvement in signs and symptoms and reduced disease activity in patients with active RA who had an inadequate response to TNF inhibitors. Improvements observed with abatacept were numerically higher than with secukinumab. There were no new or unexpected safety signals with secukinumab in this study.