tbuckley/cabot-search huggingface dataset:
Frequency, predictors, and outcomes of urine drug test among patients with advanced cancer on chronic opioid therapy at an outpatient supportive care clinic.
Authors: Joseph Anthony Arthur, Tonya Edwards, David Hui, Jessica Marie Waletich-Flemming, Suresh K. Reddy, Diane D Liu, Jimin Wu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

94 Background: Data on the utilization and outcomes of urine drug tests (UDT) among advanced cancer patients is limited. The main objective of this study was to determine the factors associated with UDT ordering and results in advanced cancer outpatients. Methods: A retrospective chart review of 1058 patients seen from March 2014 to November 2015 at an outpatient supportive care clinic was conducted. Sixty-one patients on chronic opioid therapy who underwent UDT were identified. A control group of 120 patients who did not undergo UDT was selected for comparison of information on demographic and clinical characteristics. Results: 61/1058 patients (6%) underwent UDT. 33/61 patients (54%) had abnormal results. Multivariate analysis found that the odds ratio for UDT ordering was 3.9 in CAGE positive patients (p = 0.002), 4.41 in patients less than 45years (p &lt; 0.001), 5.58 in patients with moderate to severe pain (ESAS pain score ≥ 4) (p &lt; 0.001), 0.27 in patients with advanced cancer stage, (p = 0.008), and 0.25 in patients with moderate to severe fatigue (p = 0.001). Among 52 abnormal UDT results in 33 patients, the most common opioid findings were: prescribed opioids absent in urine (14/52, 27%) and un-prescribed opioids in urine (13/52, 25%). Conclusions: UDT was used infrequently among advanced cancer patients receiving outpatient chronic opioid therapy. Younger age, CAGE positivity, early cancer stage or NED status, higher pain intensity, and lower fatigue were significant predictors of UDT ordering. More than 50% of UDTs were abnormal. More research is necessary to better characterize aberrant opioid use in advanced cancer patients.
SEASONS: A prospective study assessing the physical, psychosocial, spiritual, and financial needs of patients with breast and prostate cancer.
Authors: Nancy Jean Ehmke, Hilary Biddle, Breck Ann Hunnicutt, Stephanie Trenkner
Journal: Journal of Clinical Oncology (2016)

4 Background: Three distinct phases or "seasons" of survival have been described by Mulan (1985) including: acute (time of diagnosis to treatment), extended (intermittent treatment to surveillance), permanent (likelihood of recurrence diminishes). Each season is associated with unique physical, psychosocial, spiritual, financial, and educational needs. ASCO has identified education for survivors and their families as essential in achieving high-quality cancer survivorship care. As cancer centers expand survivorship services beyond the first tier (delivery of care plan) to provide educational programs and support services, it is critical to assess survivors' needs throughout their journey. The purpose of this prospective study is to identify the follow-up preferences and the educational, physical, psychosocial, financial, and spiritual needs of breast and prostate cancer survivors during the seasons of survival. Methods: Breast and prostate cancer patients completed the Pearlman-Mayo Survey at the start of treatment(T1), 4-6 weeks (T2)and 8-16 months(T3)after treatment then annually for four years(T4,T5,T6,T7). A series of paired t-tests determined if differences in needs existed between the various time periods. In addition, the Cronback alpha reliability estimation tool was used. Results: A total of 203 survivors were enrolled. 74 surveys were completed between T1 and T2. First Interim results revealed fatigue, nutrition, and sexual issues were of concern. Identified concerns at T3(n = 83) include fatigue, insomnia, hot flashes, and management of household activities. Depression decreased from T1 to T2 but increased at T3.Although decreased libido was reported at T1, more than 60% of respondents were concerned at T3.Respondants indicated a preference to be followed by nurse practitioner. Conclusions: As planning for the second tier of survivorship care begins at Parkview Comprehensive Cancer, educational and supportive programs on fatigue, nutrition, depression and sexuality will be implemented. Data collection and analysis will continue until participants have been followed for four years.
Association of ALDH-expressing cancer stem cells with survival in patients with resected pancreatic adenocarcinoma treated with adjuvant chemoradiation.
Authors: Rachit Kumar, Avani Satish Dholakia, Joseph M. Herman, Anirban Maitra, William H. Matsui, Seung-Mo Hong, Christopher Lee Wolfgang, Daniel A. Laheru, Christine A Iacobuzio-Donahue, Zeshaan Rasheed
Journal: Journal of Clinical Oncology (2014)

262 Background: We and others have identified aldehyde dehydrogenase (ALDH) activity as a marker of pancreatic cancer stem cells (or tumor-initiating cells). The presence of cancer stem cells (CSCs) has been associated with decreased survival and treatment resistance in pancreatic adenocarcinoma. We investigate the role of ALDH expression in predicting survival and patterns of disease recurrence in patients treated with chemoradiation (CRT) following pancreatectomy. Methods: Tissue microarrays using surgical specimens from 1998 to 2002 were stained for ALDH1 and scored as ALDH-positive or ALDH-negative by two expert pancreatic pathologists blinded to patient outcomes. Physician documentation and radiology reports were used to determine follow-up information. Time to local failure (TLF), time to distant metastases (TDM), progression-free survival (PFS), and overall survival (OS) were analyzed using SPSS software. Results: Previously we found that ALDH expression was associated with worse OS in a cohort of 269 patients with resected pancreatic adenocarcinoma (Rasheed, JNCI 2009). From this cohort, adjuvant treatment information was available for 87 patients with ALDH-negative tumors (48.6%) and 41 patients with ALDH-positive tumors (45.6%). In patients treated with adjuvant CRT, median overall survival was superior in the ALDH-negative cohort vs. the ALDH-positive cohort, 26.3 months vs. 18.2 months (p=0.011). Further, in patients treated with adjuvant CRT, ALDH-negative patients had statistically greater TLF, TDM, and PFS than their ALDH-positive counterparts (see table). On multivariate analysis, ALDH positive tumor staining (HR 1.94, p=0.004) and tumor grade (HR 1.54, p=0.041) predicted lower OS, and ALDH positive tumor staining (HR 1.83, p=0.008), tumor grade (HR 1.52, p=0.038), and tumor size &gt;3 cm (HR 1.65, p=0.023) predicted decreased PFS. Conclusions: This study suggests that adjuvant CRT improves TLF, TDM, PFS, and OS in patients with localized pancreatic adenocarcinoma not enriched with ALDH-expressing CSCs. Laboratory studies will help elucidate the mechanisms of treatment resistance in ALDH expressing CSCs.
A novel clinical-pathological score correlates with global outcome of locally advanced rectal cancer patients receiving neoadjuvant chemo-radiotherapy
Authors: R. Berardi, G. Mantello, M. Scartozzi, S. Del Prete, G. Luppi, R. Martinelli, M. Fumagalli, D. Tummarello, F. Grillo-Ruggieri, S. Cascinu
Journal: Journal of Clinical Oncology (2005)

3667 Background: The treatment of locally advanced rectal cancer consists of a multimodality approach, but which multimodality strategy is to be used still remains a point of controversy. Furthermore it is difficult to predict the outcome of this setting of patients. Methods: The study includes all the consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian Centers from June 1996 to December 2003. Results: Three hundreds and seventeen patients were eligible for our analysis. Median age at diagnosis was 64 years (range 26–88); male/female ratio was 184/133. Two hundreds and eighty-five patients (89.9%) were diagnosed with adenocarcinoma, whilst 32/317 (10.1%) with mucinous adenocarcinoma. Neoadjuvant treatments performed were as follows: radiotherapy alone in 74/317 patients (23.3%), radiotherapy plus chemotherapy in 242/317 patients (76.7%). In order to determine the importance of downstaging after neoadjuvant treatment we gave a negative or positive point respectively to each degree of increase or decrease from clinical to pathological T and N status and we identified a novel score, calculated by the sum of them. An univariate and multivariate analysis including the following factors: age, sex, type of neadjuvant treatment (radiotherapy vs chemo-radiotherapy), histotype (mucinous vs non-mucinous) was performed. An higher score was observed in males (p=0.02) and in those patients receiving neoadjuvant chemo-radiotherapy (p=0.0001). A worse time to progression was observed in patients with an higher score (p=0.04). Conclusions: Our results suggest that a novel score, calculated from pre-clinical and pathological tumor and lymph-nodal status, could represent an important parameter able to predict the outcome in patients receiving neoadjuvant treatment for rectal cancer. This information could be useful in order to select patients to receive adjuvant chemotherapy after neoadjuvant treatment and surgery for locally advanced rectal cancer. No significant financial relationships to disclose.
Pattern of in vitro chemotherapy response in pancreatic cancer and its clinical implication.
Authors: J. Franko, M. M. Bilimoria, S. Chalikonda, D. A. Iannitti
Journal: Journal of Clinical Oncology (2011)

229 Background: Gemcitabine and 5-fluorouracil (5-FU) with or without oxaliplatin are used to manage advanced or recurrent pancreatic cancer. Options are limited for patients who do not respond to these agents. This study determined the pattern of response to alternative agents using an in vitro chemotherapy assessment. Methods: From August 2006 to January 2010, 113 tumor specimens from pancreatic cancer patients were tested for response to gemcitabine, 5-FU, oxaliplatin, docetaxel, or irinotecan using an in vitro chemosensitivity assay (ChemoFx, Precision Therapeutics, Inc., Pittsburgh PA). Tumors were classified as sensitive or resistant based on in vitro dose response curves. Results: Thirty-five percent of tumors exhibited in vitro chemosensitivity to irinotecan, 23% to gemcitabine, 19% to 5-FU, 9% to oxaliplatin, and 8% to docetaxel. For tumors resistant to gemcitabine, 23% were sensitive to irinotecan, 6% (4/72) to 5-FU, 3% (2/68) to oxaliplatin, and 2% (1/64) to docetaxel (Table). Of the 68 tumors resistant to both gemcitabine and 5-FU, 11/59 (19%) were sensitive to irinotecan, 2/61 (3%) to oxaliplatin, and 0/57 (0%) to docetaxel. Forty-nine tumors were resistant to all tested agents. Conclusions: ChemoFx analysis of pancreatic cancer patient specimens indicates a high resistance rate to gemcitabine and 5-FU. The sensitivity of 19% of the gemcitabine/5-FU resistant specimens to irinotecan suggests that some patients who do not respond to standard therapy may respond to irinotecan. The potential of ChemoFx to identify the potentially most effective therapy in pancreatic cancer patients will be examined in future studies. [Table: see text] [Table: see text]
UGT1A1 genotype-based phase I study for recurrent and refractory gynecologic cancer patients treated with combination therapy of irinotecan and cisplatin (STB-06).
Authors: M. Takano, T. Goto, M. Miyamoto, A. Watanabe, M. Kato, K. Horie, H. Yokota, K. Kudoh, R. Konno, Y. Kikuchi
Journal: Journal of Clinical Oncology (2011)

e15503 Background: In addition to polymorphisms of UGT1A1*28, UGT1A1*6 has been recognized as a risk factor for severe irinotecal-related toxicities. We have conducted an UGT1A1 genotype-based dose-escalation study for recurrent and refractory gynecologic cancer patients (pts) treated with combination with irinotecan and cisplatin (CPT-P). Methods: Pts eligible for this study had histologically confirmed uterine cancer or ovarian cancers, who receive CPT-P; a course of therapy consisting of 30-80 mg/m2 of irinotecan on days 1, 8, and 15 and 60 mg/m2 of cisplatin on day 1, q4weeks. According to UGT1A1*28, *6, and *27 polymorphysms, pts were categorized into three groups (wild-type, hetoro-type, homo-type), and three-case cohort study was conducted. Pharmacokinetics of CPT-11, SN-38, SN-38 glucuronide (SN-38G), and platinums were also analyzed. Results: During August 2008 and December 2010, 19 pts were enrolled in this study; 14 ovarian cancers and 5 uterine cancers. Genotypes of UGT1A1 were wild in 7 pts, *28 in 4 pts, *6 in 5 pts, *6/*6 in 2 pts, and *6/*28 in 1pt. Recommended dose of irinotecan was determined as 50mg/m2 for wild-type patients, 40mg/m2 for hetero-type patients, and 30mg/m2 for homo-type patients, respectively. Pharmacokinetic analyses revealed both hetero-type and homo-type patients were associated with lower area under time-concentartion curve (AUC) SN-38G to SN-38 (AUCSN-38G/AUCSN-38) compared with wild-type cases, however, there was no significant difference of AUCSN-38 at the recommended dose. Conclusions: The recommended doses of irinotacan for phase II CPT-P regimen according to UGT1A1*28 and *6 genotyping were determined. The results and pharmacokinetic analyses suggested the need of individualized dose of irinotecan, even at a lower dose of the drug.
Phase I/II study of docetaxel, CDDP and S-1 in unresectable advanced gastric cancer
Authors: T. Takayama, Y. Sato, T. Okamoto, T. Sagawa, T. Abe, H. Ihara, H. Nagashima, J. Kato, Y. Niitsu
Journal: Journal of Clinical Oncology (2005)

4218 Purpose: Recently it has been reported that the combination of docetaxel, CDDP and 5-FU was effective in advanced gastric cancer. It has also been reported that S-1, a new oral fluorinated pyrimidine compound consisting of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, was significantly more effective as compared to 5-FU in advanced gastric cancer. Therefore, we conducted a phase I/II study of the combination of docetaxel, CDDP and S-1 in patients with unresectable advanced gastric cancer. Methods: Eligibility criteria were pathologically proven unresectable gastric cancer (stage IIIb - IV), PS 0 - 1, normal organ functions, and no prior treatment. Doses of S-1 (80mg/m2, d 1 - 14) and CDDP (60 mg/m2, d 8) were fixed. Docetaxel (d 8) was dose-escalated from 60mg/m2 (level 1) to 70 mg/m2 (level 2), and then 80mg/m2 (level 3). This treatment was repeated more than 3 times every 3 wks. Patients who achieved down staging underwent surgical resection. Results: Eleven patients were enrolled. Toxicity and efficacy data of all the patients are available. At level 1 (n=3), no patient developed grade 3/4 toxicity. At level 2 (n=5), two patients developed grade 4 neutropenia, and one patient developed grade 3 nausea /vomiting. At level 3 (n=3), two patients developed grade 4 neutropenia and grade 3 nausea/vomiting. Dose limiting toxicities (DLT) were neutropenia and nausea /vomiting. Recommended dose (RD) was determined as docetaxel 60mg/m2 (level 1). 91% of the patients achieved objective response consisting of 1 complete response and 9 partial responses, and only 1 patient showed disease stabilization. Three out of the 10 patients who achieved objective response underwent down staging, and received subsequent gastrectomy. On the other hand, 5 out of the 7 patients, who did not undergo down staging, have survived, and currently survival time is 10 - 16 months (median 14). One out of the 3 patients who received gastrectomy achieved complete response that was proven by histological examination. All the patients who received gastrectomy have survived, and currently survival time is 15 - 23 months (median 18). Conclusion: RD of this regimen was determined to be level 1. Our regimen is feasible and very effective with a high response rate (91%). No significant financial relationships to disclose.
Quality of life and mood in patients with advanced cancer: Associations with prognostic understanding and coping style.
Authors: Ryan David Nipp, Areej El-Jawahri, William F. Pirl, Joel Fishbein, Samantha M.C. Moran, Caitlin McCarty, Justin Eusebio, Emily R. Gallagher, Elyse R. Park, Vicki A. Jackson, Joseph A. Greer, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2015)

76 Background: Patients’ prognostic understanding and coping styles influence their treatment decisions, but how these factors relate to their quality of life (QOL) and mood has not been well described. We sought to examine the associations of patients’ prognostic understanding and coping style with their QOL and mood. Methods: As part of an ongoing trial of early palliative care, we are assessing baseline QOL (Functional Assessment of Cancer Therapy-General), mood (Hospital Anxiety and Depression Scale), coping (Brief Cope) and prognostic understanding in patients within 8 weeks of diagnosis of advanced lung or gastrointestinal (GI) cancer. To determine associations, we used linear and logistic regression, controlling for patients’ age, sex, cancer type and marital status. Results: Of 300 participants (mean age = 64.7 years; 138 (46%) female), 132 (44%) had GI cancer and 168 (56%) had lung cancer. Using cutoff score &gt; 7 for the HADS, 61 (20%) and 85 (28%) reported depression and anxiety. 138 (49%) reported their prognosis as terminal. A terminal perception of prognosis was associated with lower QOL and higher rates of anxiety. Emotional support, acceptance, and active coping styles were associated with better QOL and mood. Denial and self blame were associated with worse QOL and mood. Conclusions: These data demonstrate that acknowledging a terminal prognosis may be associated with greater physical and psychological distress, or conversely, patients with worse QOL and mood may better appreciate the gravity of their illness. Certain coping styles (self blame and denial) are associated with lower QOL and higher distress. Understanding the relationships among patients’ prognostic awareness, coping styles, QOL and mood will allow us to develop more effective supportive care interventions. Clinical trial information: NCT01401907. [Table: see text]
Analytical challenges in quantitative analysis (LC/MS/MS) of abiraterone: A validated assay to determine abiraterone in human plasma.
Authors: Mette Benoist, Eric van der Meulen, Inge Van Oort, Winald Gerritsen, Jack Schalken, David Burger, Nielka P van Erp
Journal: Journal of Clinical Oncology (2016)

329 Background: Abiraterone acetate is rapidly hydrolyzed to the active abiraterone in vivo. In order to study the relation between drug exposure and therapeutic effect an assay to determine plasma concentrations of abiraterone is required. A quantitative bioanalytical liquid chromatography tandem mass spectrometric (LC-MS/MS) assay with a BEH C 18 (2.1 × 50 mm, 1.7 µm) column was developed. Several analytical challenges were encountered. Methods: Protein precipitation with acetonitrile was used to pretreat the EDTA plasma samples. A stable isotope (D4-abiraterone) was used as the internal standard. During validation five quality controls were used (LLOQ, LQ, MQ, HQ, ULOQ). The method was validated according to EMA guidelines. Results: The LC-MS/MS method was validated over a concentration range from 1-500 ng/mL. Within – and between day precisions and accuracies were &lt; 5%. The LLOQ was 1 ng/ml and the ULOQ was 499 ng/mL. Abiraterone is stable in plasma for at least 7 days at ambient temperature and at 2-8°C. Stability at -40°C was demonstrated for at least 6 months. Abiraterone is only stable for 3 hours in whole blood at ambient temperature. Stock solution stability was demonstrated for at least 1 year. The concentration levels of the LQ, MQ and HQ were 5, 300 and 400 ng/mL, respectively. During method development several analytical challenges were encountered and solved: abiraterone adsorption on glass containers, limited stability in citrate plasma and whole blood, carry-over issues, very limited stability of abiraterone acetate in whole blood was demonstrated, curiously with proven stability in plasma. Throughout the method polypropylene vials and utilities were used. EDTA plasma was used for development and validation. The needle wash was adjusted and the runtime was prolonged with a longer time at 100% acetonitrile to address the carry over issues. Whole blood samples were treated on ice. The quantification of abiraterone acetate was abandoned. Conclusions: After different hurdles the method is successfully validated and applied to determine plasma concentrations of abiraterone in clinical studies and in regular patient care in patients with prostate cancer.
Presentation and pathology of breast cancer in patients with HIV.
Authors: Paula Rosenblatt, Sukhwant Nikki Singh, Lindsay Goicochea, Susan Kesmodel, Olga B. Ioffe, Saranya Chumsri, David Riedel
Journal: Journal of Clinical Oncology (2013)

39 Background: With the use of highly active antiretroviral therapy, it is postulated the prevalence of breast cancer will increase in the HIV infected population. Few studies have evaluated the presentation and pathological features of breast cancer in this population. Methods: Charts of approximately 5,000 HIV patients seen between 2000-2011 at the University of Maryland were reviewed to identify those diagnosed with breast cancer. Demographics, HIV data, cancer clinical presentation, family history, and pathologic findings were collected. Pathologic findings included receptor status (estrogen [ER], progesterone [PR], and human epidermal growth factor 2 [HER2]), grade, stage, lymphovascular invasion (LVI), multifocality/multicentricity (MF/MC), and presence of carcinoma in-situ. Results: Twenty cases of concomitant HIV and breast cancer were identified. At diagnosis of cancer, the median age, CD4 count, and duration of HIV infection were 48 years, 437 cells/mm 3 , and 6 years, respectively. 47% had a family history of breast or ovarian cancer. 79% self-palpated a mass. Pathologic findings included 18 invasive ductal carcinoma, 1 invasive lobular carcinoma, and 1 ductal carcinoma in-situ. 70% were ER-positive, 50% were PR-positive, and 47% were HER2-positive. 21% were Grade 1, 21% were Grade 2, and 57% were Grade 3. 21% luminal A (ER/PR+, HER2- and Ki67 ≤14%), 52% luminal B (ER/PR+, HER2+ or Ki67&gt;14% or grade 3), 5% HER2 enriched (ER/PR-, HER2+), and 21% triple-negative/basal (ER/PR-, HER2-). 5% were stage 0, 40% were Stage I, 30% were Stage II, 25% were Stage III, and none were Stage IV. LVI was present in 36%, MF/MC was present in 35%, and carcinoma in-situ was present in 82%. Conclusions: Compared to historical data of non-HIV infected individuals, our population presented at a younger age with a strong family history and a greater number of self-palpated breast masses. HIV-infected patients with breast cancer presented with more HER2 positivity, higher grade, less favorable luminal B subtype, and more MF/MC disease. Despite aggressive pathology, most patients still presented with a relatively early stage. Annual screening mammogram at earlier ages should be considered in HIV-infected patients, particularly in patients with positive family history.