tbuckley/cabot-search huggingface dataset:
Cetuximab (C) and bevacizumab (B) in patients with recurrent or metastatic head and neck squamous cell carcinoma (SCCHN): An interim analysis
Authors: M. S. Kies, M. K. Gibson, S. W. Kim, P. Savvides, G. R. Blumenschein, F. Worden, H. Chen, J. R. Grandis, A. E. Argiris
Journal: Journal of Clinical Oncology (2008)

6072 Background: Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor (VEGF) represent therapeutic targets in SCCHN. Cetuximab (C), an IgG1 monoclonal antibody against EGFR, has single agent activity. Upregulation of VEGF has been associated with C resistance, thus, combined targeting may enhance anti-tumor activity. This phase II trial of bevacizumab (B), an anti- VEGF humanized monoclonal antibody, with C was designed to test this hypothesis. Methods: Eligible patients (pts) have recurrent or metastatic SCCHN, measurable disease (RESIST), ECOG performance status (PS) 0–2, and no history of bleeding or thrombosis. Up to 1 regimen (chemotherapy, but not EGFR inhibitors) for recurrent or metastatic disease and prior chemoradiotherapy with curative intent are allowed. Treatment consists of weekly C, 250 mg/m2 (after a loading dose 400 mg/m2 ) and B, 15 mg/kg given intravenously every 21 days, until disease progression. The primary endpoint is objective response rate, with a null hypothesis 13% and target 30%. The one-stage design (sample size 48) included an interim safety analysis after 12 pts enrolled. Specific biomarkers relating to EGFR and angiogenesis are to be evaluated in tumor tissue and blood samples. Results: With 18 eligible pts, the median age is 57 years (range 33–92), male 14, female 4; PS 0, 5 pts; PS 1, 11 pts and PS 2, 2 pts. All pts have had prior RT and 17 had chemotherapy. A median of 4 treatment cycles were administered. Best response in 15 eval pts: 4 (27%) partial response, 8 (53%) stable disease, and 3 (20%) progressive disease. Grade (G) 3 adverse events: hypertension, 1; stomatitis, 1; rash, 2; and fatigue, 1. One pt developed G 4 proteinuria. One pt died of aspiration pneumonia, with possible cardiac ischemia of uncertain relationship to study drugs. No hemorrhagic events were observed. Conclusions: Preliminary results show that cetuximab and bevacizumab is an active regimen in SCCHN. There has been no associated bleeding. Study accrual continues and a biomarker analysis is planned. (Supported by U01 CA099168–01) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems Incorporated Bristol-Myers Squibb Genentech™ BioOncology Bristol-Myers Squibb, Genentech™ BioOncology, ImClone Systems Incorporated
Cost-effectiveness analysis of initial management strategies for low-risk prostate cancer.
Authors: Alan E. Thong, Justin K. Lee, Sigrid V. Carlsson, Behfar Ehdaie
Journal: Journal of Clinical Oncology (2016)

58 Background: A proportion of men with low-risk prostate cancer managed expectantly with active surveillance (AS) go on to definitive treatment in part due to initial understaging during transrectal ultrasound (TRUS) guided biopsy. Newer diagnostic tools including genomic tumor profiling, magnetic resonance (MR) imaging, and MR-ultrasound fusion biopsy have been advocated as effective strategies to risk-stratify men prior to entry into AS. We developed a decision analytic model to determine the cost-effectiveness of various initial management options for low-risk prostate cancer. Methods: A decision tree was constructed with repeat TRUS guided biopsy, MR imaging, genomic tumor profiling, and radical prostatectomy as initial management options with downstream Markov nodes to model annual recurring risks of continued AS, definitive treatment, and death from other causes. Value was optimized from the societal perspective over a lifetime horizon. We evaluated model heterogeneity and assumptions on the probability of understaging and test performance characteristics using Monte Carlo microsimulation and probabilistic sensitivity analysis. Results: At a willingness-to-pay (WTP) threshold of $100,000 per quality adjusted life year (QALY), immediate radical prostatectomy and genomic tumor profiling were dominated strategies with higher costs and lower effectiveness. MR imaging with MR-ultrasound fusion biopsy when targetable lesions are identified was the optimal strategy across 93% of simulations with an incremental cost-effectiveness ratio of $1,096 per QALY. Eliminating uncertainty in our model would lead to cost savings and increased effectiveness. This expected value of perfect information was $516 per patient. Conclusions: With multiple initial management options for low-risk prostate cancer, clinical decision-making can be challenging. Cost-effectiveness analysis demonstrates that image-guided biopsy techniques deliver optimal value from both a patient and societal perspective. However, given the prevalence of low-risk prostate cancer, there is value to be obtained from additional research to optimize management strategies.
Patient perspectives on a treatment plan and summary program in community oncology care.
Authors: V. S. Blinder, V. W. Norris, N. W. Peacock, J. J. Griggs, D. P. Harrington, A. Moore, R. L. Theriault, A. H. Partridge
Journal: Journal of Clinical Oncology (2011)

6027 Background: Routine use of treatment plans and summaries has been recommended as an important step in improving the quality of cancer care. However, limited data exist about their impact on quality indicators such as patient satisfaction and coordination of care. We evaluated perceptions of treatment plans/summaries of patients in the ASCO Breast Cancer Registry (BCR), a program piloted in 20 diverse community oncology practices to implement and evaluate satisfaction with a formal treatment plan/summary. Practices were instructed to enter clinical data into the BCR on each new patient with stage 0-III breast cancer. Individualized treatment plans/summaries were created, printed and shared with each patient. Methods: Patients were eligible to participate if they were enrolled in the BCR. Each practice was asked to consent patients until 10 had completed a survey. Patients treated with chemotherapy were offered surveys twice, 2-4 weeks after receiving a treatment plan and 2-4 weeks after the summary. Others were surveyed once, 2-4 weeks after receiving a combined plan/summary. Results: Of 318 consented patients, 175 (55%) responded to at least one survey; 8 completed two surveys. The median age of respondents was 59 years; 11% had stage 0 disease, 38% stage I, 30% II, 9% III, 12% unknown. Of 158 who recalled receiving a treatment plan/summary, 149 (94%) felt it improved communication with their doctors; 129 (82%) felt it improved communication between their doctors; and 114 (72%) said it gave them greater peace of mind, while 2 (1%) had less peace of mind. Of 153 (97%) who still had their plan/summary, 148 (97%) felt it was useful; 95 (62%) had given the form to another doctor or planned to do so. All 63 patients surveyed after receiving a summary recommended that their practice continue to provide plans/summaries to patients. Conclusions: Patient participants in the BCR pilot expressed high levels of satisfaction with treatment plans/summaries. Additional research is needed to study the implementation of the BCR on a broad scale and to evaluate the impact of routine use of treatment plans/summaries on the quality of cancer care delivered as well as costs and potential risks. This research was funded by Susan G. Komen for the Cure.
Cost-effectiveness of FOLFIRINOX for first-line treatment of metastatic pancreatic cancer.
Authors: Cheryl L. Attard, Stephen Brown, Karine Alloul, Malcolm J Moore
Journal: Journal of Clinical Oncology (2012)

199 Background: The ACCORD 11/0402 trial demonstrates that FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is significantly more efficacious than the current standard of gemcitabine (G) monotherapy in the first line treatment of metastatic pancreatic cancer (mPC). This study assesses for public payers the cost-effectiveness of first-line FOLFIRINOX compared to first-line G in Canadian mPC patients. Methods: A Markov model was used to estimate how patients progress through the following states: ‘stable’, ‘progressed’, ‘dead’. OS and PFS data were derived from the trial data. Published utility data and Canadian cost data were applied based on time in each state and treatment related adverse event (AE) rates. Costs included first and second-line therapy, monitoring, AE and end of life costs. Costs and outcomes are discounted at 5%. Two separate analyses were made. Analysis 1: Based on trial data (First-line FOLFIRINOX → second-line G versus First-line G → second-line platin-based chemo, G-CSF usage allowed). Analysis 2: Current Ontario Treatment Patterns (first-line FOLFIRINOX → second-line G vs first-line G → best supportive care, no G-CSF usage). Results: All analyses found that using first-line FOLFIRINOX produced more life years and QALY than treatment strategies that used first-line G. The probabilistic sensitivity analysis results for both analyses support the use of FOLFIRINOX for first-line treatment of mPC. FOLFIRINOX has a greater than 95% and 90% probability of being cost effective at an $80,000 threshold for Analysis 1 and Analysis 2 respectively. Conclusions: First-line FOLFIRINOX significantly prolongs median OS by more than 4 months over G (11.3 vs 6.8 months, HR=0.57). Given the favorable costs per QALYs, the improvement in clinical efficacy and the limited available treatment options, FOLFIRINOX represents an attractive cost-effective treatment for mPC. [Table: see text]
Clinical results of combined therapy of super-selective arterial infusion chemotherapy and irradiation for head and neck cancers: Comparison of two different anticancer agents
Authors: N. Uchida, M. Moriyama, A. Kawaguchi, M. Yokokawa, S. Ikeda, T. Yoshizako, H. Kitagaki
Journal: Journal of Clinical Oncology (2008)

17018 Background: Super-selective arterial infusion chemotherapy (SAI) delivers higher anticancer agent dosages than conventional systemic chemotherapy. The purpose of this study was to retrospectively evaluate and compare the efficacy and toxicity of multidisciplinary treatments with radiotherapy and SAI using carboplatin or docetaxel. Methods: 30 cases received concurrent radiotherapy and SAI from July 1995 to May 2003. Patiens backgound are shown in table. Histological diagnoses; epidermoid (29), adenoid cystic (1). Using a trans- femoral procedure, we selected tumor feeding vessels, for administering dosages of carboplatin (300-400 mg/body) or docetaxel (35-80 mg/body). All cases received external or intracavital irradiation by liner accelerator to the tumor and involved regional lymph nodes. Median follow-up duration was 20 months. We evaluated the sub-acute side-effect data according to the NCI-CTCAE ver. 3 classification. Results: There were no significant differences in patients’ characteristics and radiation total dosages between the D-G and C-G. The response rate (RR) was 92.8% (82% in C-G vs. 100% in D-G). D-group patients showed a trend toward a longer 2 year-survival rate (OS; 92% in C-G vs. 100% in D-G). The 2-year cumulative incidence of local recurrence was 17.5% in C-G and 28.6% in D-G. Grade 3 or greater side effects;23 mucositis (C-G: 8 vs. D-G: 15), and 8 leukopenia (C-G: 3 vs. D-G: 5). There was no significant difference as to toxicity, and all side effects were cured by conservative treatment. Conclusions: In the present study, the two treatment groups showed similar activity (response rates and overall survival rates). Our data suggest that these two regimens are feasible SAI drugs for treatment of head and neck cancers, but further evaluation is required to confirm these findings. Patients Background C-G D-G Patients (NO.) 13: Male (10), Female (3) 17: Male (13), Female (4) Age (mean) 67 56 Primary Lesions buccal 1 2 gingiva 3 oral floor 2 2 oropharynx 2 2 tongue 4 13 maxilalry sinus 1 Clinical stages T/UICC stage) T2 (8) T2 (12) T3 (2) T3 (2) r (3)/II (5) r (3)/ II (11) III (3) III (3) IV (2) r (3) r (3) C-G, carboplatin group; D-G, docetaxel group; r, recurrence. No significant financial relationships to disclose.
Monitoring of chemotherapy response in multiple disseminated malignant pleural mesothelioma using fluorodeoxyglucose positron emission tomography
Authors: T. Kimura, S. Kudoh, N. Yoshimura, S. Mitsuoka, K. Matsuura, K. Koyama, J. Kawabe, M. Okamura, K. Hirata, S. Shiomi, J. Yoshikawa
Journal: Journal of Clinical Oncology (2005)

7177 Background: The management of malignant pleural mesothelioma (MPM) is being important because of its increasing incidence in worldwide. Patients with MPM frequently present with malignant unilateral pleural effusion or pleural thickness. To date, it is not clear the analytic methods such as CT and MRI are the most accurate to provide monitoring response in patients with MPM. Fluorodeoxyglucose positron emission tomography (FDG-PET) is able to make biologic images of tissues. FDG-PET molecular imaging of tumor response to chemotherapy and irradiation has been usefully evaluated for patients with variety of cancers. The purposes of our studies were prospectively to evaluate the role of FDG-PET for monitoring response to the chemotherapy in patients with MPM. Methods: All patients proven a diagnosis of MPM histologically treated with chemotherapy. Each patient underwent both PET imaging and CT scanning before treatment, after first and second courses of chemotherapy. Each patient had multiple thickness lesions, and standardized uptake value (SUV) by PET and perpendicular diameters of pleural thickness by CT images were calculated for all lesions. FDG uptakes in lesions were compared with those of baseline scan. Results: A total of 34 lesions out of 7 patients with MPM were studied between 1999 and 2004. The median age was 60 years. One patient was female and 6 were males. Two patients were stage IV and 5 were stage III. Six patients received chemotherapy of cisplatin containing regimens and one patient received gemcitabine alone. Three patients had a PR and 4 had a SD. There were 9 lesions out of 7 patients exhibited a response based on CT images, 15 lesions exhibited progression, and 19 lesions exhibited a no response. The mean SUV of the response lesions were significantly decreased from 3.78±1.42 to 2.73±0.70 (p=0.0023). The mean SUV of progression lesions were significantly increased from 2.37±0.95 to 2.91±0.90 (p=0.0005). Interestingly, the mean SUV of no response lesions were significantly decreased from 3.72±1.90 to 3.01±1.67 (p=0.0037). Conclusions: FDG-PET is a highly sensitive and specific imaging modality in the evaluation of MPM during or after therapy. No significant financial relationships to disclose.
PSA outcomes in patients with adenocarcinoma of the prostate with presenting PSA &gt; 20 ng/ml.
Authors: Daniel Shasha, Brock John Debenham, Robert Salant, Louis Benjamin Harrison
Journal: Journal of Clinical Oncology (2013)

241 Background: Optimal treatment of prostate cancer with presenting PSA &gt;20 ng/mL is debated within and between specialties, as reflected by variable PSA outcomes reported. We present our clinical outcomes in irradiated patients for this population. Methods: With IRB approval, we analyzed patient, disease, treatment, and PSA data of 149 patients with presenting PSA &gt; 20 ng/mL radiated with curative intent 1997-2012 by a single physician (DS) at Beth Israel Medical Center (New York City). External beam radiation therapy (EBRT) was delivered first to prostate, seminal vesicles (SV) and draining pelvic lymph nodes to 45 Gy, then 5.4 Gy cone down, then a boost with either brachytherapy (BT) or 30.6 Gy conformal EBRT. BT was withheld in large volume of SV invasion by either DRE or by MRI. Hormonal therapy (HT) consisted of LHRH agonist +/- antiandrogen therapy. PSA was checked every 6 mos. Biochemical Failure (BF) was defined as post-treatment PSA nadir + 2 ng/mL. Results: 41% of patients were African American, 27% Hispanic, 21% Caucasian, and 6% Asian. The median patient age, Gleason score (GS), PSA, and T stage were 68 yrs (range 42-87), 30 ng/mL (range 20–280), 7 (range 5-10) and stage II (8% Tx, 29% T1, 32% T2, 22% T3a/b, 8% T3c). Combined EBRT and BT (CMT) were used in 70% (N=104); EBRT alone in 28% (N=42); BT alone in 2% (N=3). HT was given to 87% (N=129), (median duration 25 mos). Of CMT patients, 77% (N=81) had I-125 permanent seed implant, 22% (N=23) had Pd-103 implant, and 1% (N=1) had HDR temporary Ir-192 implant. With a minimum follow-up (FU) 2 years and median FU 4.9 years (range 2.0-14.1), overall BF was 18% (N=27), and median time to failure was 4 yrs (range 0.4–9.3). Of failures, median age was 64 (range 48-83), and 40% were African American; median pre-treatment PSA was 40 ng/mL (range 20–238), median stage was 3. BF occurred in 17/104 (16.3%) CMT patients (13/17 I-125 and 3/17 Pd-103), 9/42 (21.4%) EBRT patients, and 1/3 (33%) BT alone patients (1/1 I-125). All patients who failed received HT. Conclusions: Excellent overall biochemical outcomes in patients with presenting PSA &gt; 20 ng/ml are reported, with only approximately 18% experiencing BF at a median FU of 4.9 years. Of all treatments analyzed, CMT yielded superior biochemical control.
Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates
Authors: Pi-Xiao Wang, Yan-Xiao Ji, Xiao-Jing Zhang, Ling-Ping Zhao, Zhen-Zhen Yan, Peng Zhang, Li-Jun Shen, Xia Yang, Jing Fang, Song Tian, Xue-Yong Zhu, Jun Gong, Xin Zhang, Qiao-Fang Wei, Yong Wang, Jing Li, Lu Wan, Qingguo Xie, Zhi-Gang She, Zhihua Wang, Zan Huang, Hongliang Li
Journal: Nature Medicine (2017)
Effects of denosumab on bone resorption in patients with solid tumors and bone metastases: Comparison of serum-C telopeptide levels from two randomized, active-controlled, phase II trials
Authors: J. R. Gralow, A. Lipton, K. Fizazi, J. Body, G. G. Steger, G. Gao, H. Yeh
Journal: Journal of Clinical Oncology (2008)

9574 Background: Patients with bone metastases have a high risk of skeletal morbidity and high rates of bone remodeling, both mediated by RANKL-stimulated osteoclasts. Denosumab, a fully human monoclonal antibody that is being investigated for the treatment of bone metastases, suppresses bone resorption by inhibiting RANKL. Methods: In 2 recently completed phase II studies, patients with solid tumors and bone metastases were randomly assigned to receive intravenous bisphosphonates (IV BP) or subcutaneous denosumab. Patients were either IV BP-naïve or had evidence of increased levels of bone resorption despite treatment with IV BPs. We evaluated the effects of the 2 treatments by comparing changes in serum-C telopeptide (sCTx), a biochemical marker of bone resorption, from baseline to week 25. Our objective was to determine whether denosumab-induced suppression of bone turnover was affected by previous exposure to IV BPs. Results: In both studies, denosumab was associated with similar rates of suppression of bone resorption, indicated by reductions in sCTx (Table), whether or not patients had previously received IV BPs. The incidence of serious adverse events was similar across treatment groups in both studies (Table). Conclusions: In cancer patients with bone metastases, regardless of IV BP exposure, denosumab suppressed bone resorption and had an adverse event profile similar to that for patients treated with IV BPs. Phase III trials are in progress. Reduction in Bone Turnover with Denosumab and IV BPs Parameter Bisphosphonate-Naive Previously Treated With IV BPs IV BPa N = 43 Denosumabb N = 212 IV BPc N = 35 Denosumabd N = 69 Age, years - mean (SD) 52 (11) 58 (11) 62 (12) 62 (12) Median (Q1, Q3) reduction −80% −85% −45% −80% in sCTx at week 25 (−66%, −88%) (−75%, −90%) (−28%, −71%) (−69%, −90%) Serious adverse events - n (%) 15 (35) 75 (36) 18 (51) 36 (49) Serious treatment-related adverse events - n (%) 0 (0) 0 (0) 0 (0) 1 (1)e a > 80% zoledronic acid b Denosumab every 4 weeks (Q4W; 30, 120, 180 mg) or every 12 weeks (Q12W; 60 or 180 mg) c > 90% zoledronic acid <d Denosumab 180 mg Q4W or Q12W e One patient experienced hypophosphatemia, deemed treatment-related by the investigator. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen, AstraZeneca, Bristol-Myers Squibb, Ipsen-Beaufour, Merck, Novartis, Pfizer, Pharmion, sanofi-aventis Amgen Inc. Amgen, AstraZeneca, Ipsen-Beaufour, Novartis, Pfizer, sanofi-aventis, Takeda Amgen, Novartis, Oncogene Sciences/Bayer, Pfizer Novartis
Psychosocial distress screening in the health care safety net.
Authors: Margot Albert, Theora Cimino, Anne Kinderman, Leslie Safier, Heather A. Harris
Journal: Journal of Clinical Oncology (2016)

91 Background: Recognizing that psychosocial distress (PSD) is underestimated in patients with cancer, the Commission on Cancer mandated screening using a validated tool. Studies of PSD screening exist, but none to date in a diverse, multicultural safety net setting where patients face challenges such as homelessness, mental illness, and substance abuse, which may augment PSD. Methods: We performed a retrospective cohort study of patients with cancer offered PSD screening during 2015. Overall distress scores and problems in each domain were analyzed. Chart review identified potential predictors of distress including age, gender, race, language, housing, psychiatric illness, substance abuse, and cancer stage. Results: Of 177 eligible patients, 113 (64%) completed screening. The most common reasons patients were not screened were refusal, too symptomatic (physically or emotionally), or language barriers. Of screened patients, 40.7% were female, 57.5% male, and 1.7% transgender. 31% were Caucasian, 27% Asian/Pacific Islander, 25% Hispanic, and 17% African American. 35% were non-English speaking. 29% had history of mental illness and 34% of substance abuse. 23% were marginally housed or homeless. 63% reported moderate to severe levels of PSD as defined by the NCCN as ≥ 4. Patients with mental illness were nearly twice as likely to report PSD ≥ 4 (p = 0.012) and had higher mean PSD scores (5.78 vs. 4.03, p = 0.002). English speaking patients had a mean PSD score of 5.01 compared to 3.6 and 3.2 for Spanish and Chinese speaking patients, respectively (p = 0.02 for English v. Chinese) and more domains causing PSD (p = 0.028 for English v. Chinese). Lack of stable housing also correlated with more domains causing PSD (p = 0.05). Conclusions: This proved to be an ethnically diverse cohort with high rates of mental illness, substance abuse, and homelessness, with the majority reporting moderate to severe distress. Even with a small cohort, English language and mental illness were significant predictors of PSD, and housing status correlated with more domains contributing to PSD. Several other variables trended toward significance, suggesting a larger cohort may be needed to determine if additional characteristics predict higher levels of PSD.