tbuckley/cabot-search huggingface dataset:
A modular phase I study of lenalidomide and paclitaxel in metastatic castration-resistant prostate cancer with prior taxane therapy
Authors: L. C. Pagliaro, N. M. Tannir, S. Tu, B. Moomey, C. M. Carter, N. Bekele, P. Mathew
Journal: Journal of Clinical Oncology (2008)

13545 Background: Thalidomide may enhance the clinical activity of docetaxel and reverse taxane-resistance in prostate cancer. Lenalidomide, a highly-potent immunomodulatory derivative of thalidomide, potentiates the action of paclitaxel in-vitro against prostate cancer cell lines in co-culture with mononuclear cells. A modular Phase I study of lenalidomide and paclitaxel in men with metastatic castration- resistant prostate cancer (CRPC) was conducted to assess PSA-kinetics with lead-in therapy and the feasibility of the combination. Methods: Men with metastatic CRPC with prior taxane chemotherapy were planned for single-agent “lead-in” lenalidomide for 21/28 days at dose levels: -1 (5mg), 0 (10mg), +1 (15mg), +2 (20mg), +3 (25mg); followed by lenalidomide at the same dose/schedule in combination with weekly intravenous paclitaxel 100mg/m2 on Days 1, 8, 15 every 28 days. A 3+3 dose-escalation design was utilized to assess the maximum tolerated dose, defined as a dose-limiting toxicity (DLT) rate ≥ 0.33 during lead-in and one cycle of combination therapy. Enteric-coated aspirin 81mg and warfarin 2mg was recommended for thromboembolic prophylaxis. Results: See Table. Five patients had therapy discontinued for toxicity between 3–34 weeks Progression-free interval varied from 9–35 weeks (n=5). With lead-in lenalidomide, 1 of 9 evaluable patients had a minor PSA-decline; one patient with lymph-node dominant metastatic disease had a 40% decrease in bulky neck adenopathy followed by progression-free survival of 8 months with combination therapy. Conclusions: The high DLT rates observed with lenalidomide and paclitaxel require exploration of alternate dose-schedules of the combination in the second-line setting of CRPC. Cohort Patients Lenalidomide Paclitaxel DLT DLT [type/grade (G)] 1 3 0mg 100 mg/m2 1 - vomiting, diarrhea: G3 2 3 10mg 100 mg/m2 3 - neutropenia: G 3 - neutropenia: G 3 - chest pain: G 3 3 3 5mg 100 mg/m2 2 - infection/neutropenia: G 3 - dehydration/infection: G 3 4 1 5mg 80 mg/m2 * 1 - pulmonary embolism: G4 * A lower paclitaxel dose-level was studied after a protocol amendment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Onyx Bayer, Onyx Celgene
SupportScreen: A prospective automated approach to real-time symptom and problem identification, triage, and tailored education.
Authors: Tricia Kassab, Matthew Loscalzo, Karen L. Clark, Joseph C. Alvarnas, Priscilla Avanessian, Alexandra M. Levine
Journal: Journal of Clinical Oncology (2013)

240 Background: The links among supportive care services quality of life, patient satisfaction, cost, quality and safety are well established. The Institute of Medicine 2008 report recommended that distress screening be instituted as the standard of cancer care. More recently, ASCO and ACOS created new standards for the universal distress screening. Parallel to this process have been advances in automated technologies that are efficient and easily tailored to the patient population. Methods: SupportScreen is a patient-friendly automated process that identifies, triages and provides educational information all in real time. SupportScreen also facilitates patient, physician and multi-specialist communication and is used to maximize the effectiveness of clinical encounters and overall cancer care. Results: Based on over 15 years of biopsychosocial screening experience, SupportScreen was implemented at the City of Hope as a standard of care in medical oncology, HEM/HCT and surgery outpatient clinics. SupportScreen is also being administered to caregivers and to collect patient satisfaction and research data. In a sample of 4,819 outpatients the top problems rated as high distress are: problems with finances (40%), sleep (38.3%), worry about the future (37.1%), fatigue (36.7%) and side effects of treatments (34.5%). In addition, patients requested assistance (meet with a member of team or educational materials) in many areas related to their quality and coordination of medical care: finances (33.6%), health insurance (27.5%), finding community resources (26.6%), talking with the health care team (26.3%), needing help coordinating my medical care (24%) and transportation (20.7%). Conclusions: Patients and their caregivers have a significant number of unmet needs that may directly impact the quality, safety, and cost of their care. Prospectively managing these barriers may enhance the quality and efficiency of care, especially in those patients who manifest high risk, cost and suffering characteristics.
External validation of multiparametric MRI and fusion-guided prostate biopsy: A matched cohort analysis.
Authors: Steven F. Abboud, Ardeshir Rastinehad, Arvin Koruthu George, Thomas P Frye, Richard Ho, Nabeel Ahmad Shakir, Raju Chelluri, Michele Fascelli, Annerleim Walton-Diaz, Sandeep Sankineni, Baris Turkbey, Peter L. Choyke, Maria J Merino, Peter A. Pinto
Journal: Journal of Clinical Oncology (2015)

155 Background: MRI/US fusion-guided biopsy has been shown to improve the detection of clinically significant prostate cancer (PCa). As adoption of this novel technology expands, the reproducibility of outcomes from expert centers becomes essential. The objective of our study was to validate the comprehensive NCI experience of multiparametric MRI and fusion-guided biopsy (FB) with an external, independent, matched cohort of patients. Methods: We compared 1,003 patients enrolled from August 2007 through February 2014 in a prospective trial comparing systematic 12-core biopsy (SB) to FB at the NCI to 256 patients that underwent an identical procedure at Long Island-Jewish Hospital (LIJH) from February 2012 to June 2014. Patients from LIJH were matched 1:1 for age, PSA, and MRI suspicion score to a corresponding cohort of NCI patients. Clinically-significant (CS) disease was defined as a Gleason score of ≥4+3 in any biopsy core. Results: The overall cancer detection rate was 564/1,003 (56%) of NCI patients and 167/256 (65%) of LIJH patients. In the matched cohort analysis, cancer detection rate (CDR) by FB between cohorts was 52% NCI vs. 54% LIJH (p=0.67). Both cohorts demonstrated a similar rates of upgrading by FB compared to SB, 29% NCI vs. 23% LIJH (p=0.42). This trend applied to patients that upgraded to CS disease by FB, 12.7% NCI vs. 12.6% LIJH (p=0.42) (Table). Conclusions: The improved detection of clinically-significant cancer by mpMRI and FB is reproducible in the hands of an experienced multi-disciplinary team. Our results suggest that with appropriate training in the interpretation of mpMRI and performance of FB, dissemination of this technology can render equivalent outcomes. [Table: see text]
Angiotensin converting enzyme inhibitor and angiotensin receptor blocker use and outcomes in patients with colorectal cancer.
Authors: Sherilyn Alvaran Tuazon, Gentry Teng King, Joanna Paula Pingol Sta. Cruz, Jean B. Ong Kian Koc, Young Kwang Chae, John Charles Leighton, Constantine Daskalakis
Journal: Journal of Clinical Oncology (2014)

544 Background: Increasing evidence implicates angiotensin in the pathophysiology of carcinogenesis. Both Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) have shown in-vitro activity in Colorectal Cancer (CRC) via inhibition of both VEGF and IGF-1 and present a novel therapeutic strategy. This study aimed to investigate the association of these agents in outcomes of patients with CRC. Methods: We reviewed the medical records of patients with stage I-III CRC from 2004-2008. ACEI and ARB use was defined as consumption for at least 3 months in patients with no evidence of disease after initial diagnosis and treatment. Outcomes were Disease Free Survival (DFS) and Overall Survival (OS). Kaplan-Meier and Cox proportional hazards regression were used. Results: A total of 222 patients were included, with a median follow up of 39 months. A total of 105 (47%) were identified as users of ACEI/ARBs. Multivariate analysis, adjusted to age, sex, race, stage, grade, tumor location, adjuvant chemotherapy, radiotherapy, statin and ASA use showed significantly improved DFS among users of ACEI and/or ARBs compared to non-users (HR = 0.44, p = 0.003). Considered separately, users of ACEIs only and users of ARBs only had better DFS than non-users (HR = 0.43 and 0.53, respectively). Compared directly, users of ACEIs did not have significantly different DFS than users of ARBs (HR = 0.81, p = 0.678). With regards to OS, multivariate analysis showed that, compared to non-users, patients with ACEI or ARB use had better OS, although non-significantly (HR = 0.59, p = 0.219). However, the magnitude of the impact on OS was comparable to that seen for DFS. Conclusions: The use of ACEIs and/or ARBs is associated with improved disease-free survival in CRC patients. There was a statistically insignificant trend toward improved OS, which may be related to the low power to the study. This observation warrants further exploration.
A prospective, randomized phase III trial of test doses vs. full doses in taxane-naïve patients
Authors: J. A. Krieger
Journal: Journal of Clinical Oncology (2005)

8203 Background: The taxanes paclitaxel and docetaxel are an important class of semi-synthetic anti-cancer agents known to induce first dose hypersensitivity reactions (HSRs), which often limit their utility. A pilot 1mg taxane test dose program at the University of New Mexico Cancer Center showed that HSR severity and drug waste was reduced. To corroborate these findings, a Phase III test dose trial was instituted at four clinical sites in New Mexico and Texas. Methods: In this prospective, two-arm, randomized study, eligible participants were greater than 18 years and scheduled to receive their first taxane with standard premedications. Patients were randomized to receive the full prescribed dose with or without or a 1mg initial test dose. For sufficient statistical power the projected enrollment was targeted to 100 patients per arm. The primary outcomes for comparison were HSR severity (using the NCI common toxicity criteria for allergy/immunology) and drug wastage. Additional comparisons were made by gender, type of taxane, and presence or absence of preexisting allergies. All comparisons were evaluated for statistical significance using the Pearson chi-square test. An exact p-value <0.05 was considered significant. Results: An initial test dose was administered to 103 patients and 100 received the full taxane dose without a test dose. Six HSRs were observed in each group (5.9% overall). Paclitaxel was administered to 129 patients and 74 received docetaxel with no significant difference in HSR incidence between the two agents (6.2% vs. 5.4%). Only gender showed a significant difference: 9.3% of females experienced an HSR compared to only 2.1% of males (p=0.037). Approximately $12,000 (2004 AWP) of taxane was wasted by the full dose arm. Conclusions: Administration of test doses to taxane-naïve patients substantially reduced drug wastage but not HSR. Significantly more female patients experienced a HSR in comparison to male patients. No significant financial relationships to disclose.
Clinicopathologic correlations of gallbladder cancer by ethnicity in New Mexico, 1980-2009.
Authors: Kathleen Madden, Charles Wiggins, Itzhak Nir, Ashwani Rajput, Katherine T. Morris
Journal: Journal of Clinical Oncology (2013)

160 Background: Gallbladder cancer (GBCA) is a rare malignancy; however, within the U.S. incidence varies geographically. GBCA has a higher occurrence in the American Indian (AI) population versus non-Hispanic whites (NHW) and Hispanics (H). The goal of the study is to determine if clinicopathologic features correlate with ethnicity. Methods: Incident GBCA diagnosed in New Mexico from 1980-2009 were identified from the population-based New Mexico Tumor Registry. Average age-adjusted incidence rates were calculated by direct method using the United States 2000 standard population. Chi-squared statistic was used to assess ethnicity differences in case distribution at diagnosis by sex, age, stage and grade. Cause-specific survival was calculated by the Kaplan-Meier method and assessed with log-rank statistic. Results: GBCA incidence rates in New Mexico are highest for AI (7.6 per 100,000–95% confidence interval (CI)=6.5-8.9), followed by H (2.8 per 100,000 – 95% CI=2.5-3.2) and NHW (1.0 per 100,000 – 95% CI=0.9-1.1). Females are predominantly affected (Table). Median ages varied among NHW (74 years), H (71 years) and AI (69 years). There are no appreciable differences with respect to stage and tumor grade. Cause-specific survival at 60 months is also similar among NHW (20.25%), H (17.94%), and AI (22.43%) (log-rank p-value=0.7388). Conclusions: GBCA has a higher prevalence in AI. Regardless it shares similar characteristics in all evaluated ethnicities as it is predominantly a disease of older females, with similar tumor grade and stage and with equally poor survival. [Table: see text]
Identification of breast cancer genomic subtypes that associate with prognosis and response to therapy in retrospective analyses.
Authors: D. Rhodes, S. A. Tomlins, J. K. Freshley, P. Wyngaard, S. Sadis, K. Oades, S. Chattopadhyay, H. Kim, L. Vo, D. Telford, Y. Wang, B. Lee, J. Monforte
Journal: Journal of Clinical Oncology (2011)

e21151 Background: Gene expression patterns in breast cancer can be used to stratify patients based on prognosis and response to therapy, but are impractical clinically because each test requires its own patient tumor sample. We sought to develop a method for identifying all major breast cancer subtypes in a single formalin fixed paraffin embedded (FFPE) reverse transcriptase polymerase chain reaction (RT-PCR) assay for use in the development of gene expression companion diagnostic assays. Methods: A co-expression meta-analysis on 5,339 breast cancer samples from Oncomine identified highly co-expressed sets of genes (modules) across multiple breast cancer microarray datasets, with each module consisting on average of 450 genes (range 11 – 962). These modules represented expected subclasses (e.g., basal, luminal A, luminal B), as well as additional subclasses (e.g., immune response, proliferation). Restriction of each module to fewer genes (3-5) was accomplished by initially characterizing 384 candidates in an FFPE RT-PCR assay, from which 96 genes were selected. The approach was tested on 65 FFPE samples with known histological parameters such as ER, PR, and HER2. Finally, we asked whether the patterns of module expression in retrospective studies match in expected ways with prognosis and drug response. Results: We demonstrate that this single test of 96 genes accurately identifies each of the individual modules, that different module combinations define molecular subtypes with greatly increased resolution over previous approaches, and that standard parameters such as ER, PR and HER2 are accurately identified using this approach. Specific data on the association of modules with prediction of overall survival, neoadjuvant chemotherapy response, and in-vitro sensitivity to MEK and PI3K inhibitors will be presented. Conclusions: A broad range of breast cancer heterogeneity on both gene expression and chromosomal amplification events can be summarized by combinations of core modules represented by 96 gene expression measurements. Multiplex RT-PCR assays capable of measuring these modules are expected to have broad application in the development of companion diagnostics.
Survivor pain: Experience at an oncology palliative care clinic.
Authors: Cristian Zanartu, Lisa Emond, Ann Wojtaszczyk
Journal: Journal of Clinical Oncology (2016)

260 Background: As of January 2014 there are an estimated 14.5 million cancer survivors in the United States. In observational studies of cancer survivors up to 40% report chronic pain. Opioids remain an important and effective treatment for active cancer pain. For survivors, however, we must take into account the paucity of data supporting long term benefits of opioids on pain and functional outcomes, and extensive evidence of potential harms. We present data from our palliative care clinic where we have established a nuanced approach to pain management in this population, which includes risk mitigation, consistent education, emphasis on non-pharmacological and non-opiate medications, and attempts to down-taper opioid analgesics when feasible. Methods: Retrospective, observational chart review of 62 patients identified as cancer survivors, who have been managed for pain, at an academically affiliated palliative care clinic embedded in the oncology department. Demographic information, baseline and latest visit pain scores and functional assessments, as well as pain regimen data were collected. Means for pain and functionality scores were compared for those patient’s with differing opioid regimens and nonpharmacological treatments. Results: Of the 62 patients reviewed, 48 were tapered off opioid medication. In the patients who were tapered off opioid medications, 8 (16%) showed an increase in average pain scores, 11 (22%) showed no change in average pain scores, and 29 (60%) showed improvement in average pain score. Conclusions: In 82% of the patients whose opioid medications were decreased, average pain scores either remained the same or actually improved over time. This is encouraging data to support the theory that decreasing opioids in cancer survivors does not worsen pain control in the majority of that population.
A randomized clinical trial comparing adjuvant radiation versus chemo-RT versus chemotherapy alone after radical cystectomy for locally advanced bladder cancer.
Authors: Mohamed S. Zaghloul, John Paul Christodouleas, Andrew Smith, Ahmed Abdalla, Hany William, Hussein Mustafa Khaled, Wei-Ting Hwang, Brian Christopher Baumann
Journal: Journal of Clinical Oncology (2016)

356 Background: There is growing interest in using adjuvant radiation therapy (RT) to reduce local failures (LF) after radical cystectomy (RC) for locally advanced bladder cancer. A previous RCT demonstrated significantly improved LF &amp; OS with adjuvant RT vs. RC alone. An RCT was performed to compare the efficacy of adjuvant RT vs chemo-RT vs chemo alone after RC. The primary endpoint was disease-free survival (DFS). Secondary endpoints were OS, LRFS, DMFS and toxicity. Methods: Patients ≤ 70 yrs with ECOG PS ≤ 2 with locally advanced bladder cancer and ≥ 1 high-risk feature who underwent RC with negative margins at the Egyptian National Cancer Institute from 2002 – 2008 were enrolled. High risk features included stage ≥ pT3b, grade 3, or positive nodes. Patients were randomized following RC to RT (45 Gy in 1.5 Gy/fx given BID with 3D-conformal RT), chemo-RT with 2 cycles of gemcitabine/cisplatin before and after RT, or 4 cycles of chemo alone. The chemo alone arm was added as a 2nd randomization in 2007. Patients were followed regularly with CT scans q 6 months in the first 2 years &amp; then yearly. Results: 198 patients were enrolled. 78 received RT, 75 chemo-RT and 45 received chemo alone. Median age was 54 (range 27 – 70) and the M:F ratio was 4:1. 53% had urothelial carcinoma, 41% had SCC and 6% other. Median follow-up was 19 mo (range 1 – 127 mo). The RT, chemo-RT and chemo alone arms had similar characteristics except for age (median 55, 52 and 55, respectively, p = 0.03) and tumor size (p = 0.02). There was no significant difference in DFS, DMFS or OS, although there was a trend toward improved DFS favoring the RT-containing arms with 3 yr rates of 63%, 68% and 56% in the RT, chemo-RT and chemo arms (p = 0.25). LRFS was significantly improved for the RT arms vs. chemo alone, with 3 yr rates of 87%, 96% and 69% (p &lt; 0.01), regardless of histology. Treatment was reasonably well-tolerated with late grade ≥ 3 GI toxicity of 8%, 7% &amp; 2%, respectively. Conclusions: This is the first RCT comparing adjuvant RT (+/- chemo) vs. adjuvant chemo following cystectomy for bladder cancer. RT was associated with significantly improved local control compared to chemo alone. There was no significant difference in DFS, DMFS, or OS. Clinical trial information: NCT01734798.
Predictive factors of early and late local toxicities in anal cancer treated by radiotherapy in combination with or without chemotherapy.
Authors: Jerome Doyen, Karen Benezery, Cecile Ortholan, Jean-Pierre Gérard, Jean-Michel Hannoun-Levi, Philippe Follana, Eric Francois
Journal: Journal of Clinical Oncology (2012)

667 Background: Treatment of anal cancer is based on combined radiotherapy and chemotherapy (CT). Some patients present early (&lt;2 months) and late (&gt;2 months) toxicities of grade 3 or greater which can strongly impair quality of life. We aimed to identify predictive factors of toxicities in 106 patients treated in a single center between January 2000 and February 2010. Methods: Retrospective analysis of our databases reported severe local toxicities (grade 3 or higher) during treatment of proven localized epidermoid carcinoma of the anal cancer. The following factors were screened as potential predictive factors: gender, age, irradiation dose, HIV status, type of boost (external vs brachytherapy), circumferential extension, type of chemotherapy, invasion of anal margin, clinical T and N stage, and clinical stage. Results: With a median follow-up of 54.1 months (46.8-61.4) early severe local toxicities occurred in 42 patients (pts) (39.6%) whereas late severe toxicities happened in 21 pts (19.8%). Both early and late toxicities were dominated by proctitis (diarrhea and/or rectal bleeding) (7 pts, 6.6% and 6 pts, 5.6% respectively) and recto-anal epithelial toxicities (27 pts, 25.4% and 17 pts, 16% respectively). Two patients got colostomia because of treatment toxicities (1,8%). Predictive factors of increased early toxicities were as follows: clinical stage III/IV (p=0.04), no brachytherapy boost (p=0.008) and type of CT (no CT, 5.9%, CT, 48.8% p=0.001). Brachytherapy boost and presence of CT retained their independency in multivariate analysis (respectively, p=0.001 and p=0.05). Only HIV positivity (p=0.02) was identified as a predictive factor of late toxicities. HIV positivity (p=0.02), invasion of anal margin (p=0.01) and circumferential extension &gt; 33% (p=0.007) correlated with epithelial ulcer. Invasion of anal margin (p&lt;0.001) and circumferential extension (p=0.02) were identified as independent factors in multivariate analysis. Conclusions: In this cohort absence of brachytherapy boost and CT correlated with more severe early local toxicities whereas HIV positivity was the only predictor of local late toxicities.