tbuckley/cabot-search huggingface dataset:
Survival difference in octogenarians with resectable gastric GIST: Surgery versus nonsurgical management.
Authors: Dhaval Chauhan, Atuhani S. Burnett, Taufiek Konrad Rajab, Philip Ernst, Donald A. McCain, Suyog A. Mokashi
Journal: Journal of Clinical Oncology (2014)

171 Background: Surgical resection of gastric GIST (Gastro-Intestinal Stromal Tumor) in octogenarians is a morbid procedure. There is limited data in literature about the survival of octogenarians after resection of gastric GIST. In this study we focused on the outcome in terms of survival in octogenarians with resectable gastric GIST. Methods: Our study demonstrates that octagenarians as a whole do not experience a survival benefit from surgical resection for HCC. Subgroup analysis, however, may ultimately identify benefit in specific disease stages or patients with fewer comorbidities. Results: The mean survival in the patient group undergoing surgery was 31.30 months and the mean survival in the patients opting for non-surgical management was 33.89 months. The survival benefit in avoiding surgery in this population was 2.59 months with a p-value of &lt;0.0001 and a confidence interval of 1.35 to 3.83 months. Conclusions: The mean survival in the patient group undergoing surgery was 31.30 months and the mean survival in the patients opting for non-surgical management was 33.89 months. The survival benefit in avoiding surgery in this population was 2.59 months with a p-value of &lt;0.0001 and a confidence interval of 1.35 to 3.83 months.
Outcomes of cancer patients who do not satisfy conventional clinical trial eligibility criteria (CTEC).
Authors: Winson Y. Cheung, Khodadad Rasool Javaheri, Caroline Speers
Journal: Journal of Clinical Oncology (2013)

128 Background: Trials have stringent inclusion and exclusion criteria to maintain internal validity. However, study findings are often applied to patients in routine practice who do not meet CTEC. Our aim was to characterize the outcomes and magnitude of treatment benefit in these patients. Methods: Patients diagnosed with stage III colon cancer from 2006 and 2008, referred to 1 of 5 regional cancer centers in British Columbia, and assessed for adjuvant chemotherapy (AC) within 12 weeks of surgery were analyzed. Patients were considered trial-eligible (TE) if aged 18 to 79 years, ECOG 0/1, CEA &lt;10, did not receive prior chemotherapy or radiation, and had adequate blood counts and normal cardiac, liver and kidney function. All other patients were deemed trial-ineligible (TI). Results: A total of 820 patients were identified: median age was 69 years (range 60-76), 423 (52%) were men, 365 (45%) were ECOG 0/1 and 592 (72%) received AC. Among patients treated with AC, 370 (63%) were TE and 222 (37%) were TI. Compared to TI patients, those who were TE were younger (63 vs. 70 years, p &lt; 0.01) and more likely to receive combination regimens rather than single agent AC (56 vs. 33%, p &lt; 0.01). Outcomes were significantly different among patients who were TE, TI, and those who did not receive AC (Table). In multivariate analyses that adjusted for known prognostic factors such as age, ECOG and T and N stages, both TI patients and those not treated with AC had worse outcomes than TE patients (HR for colon cancer death 1.32, 95%CI 0.86-2.02 and 2.77, 95%CI 1.92-3.99, respectively, p trend &lt; 0.01; HR for all cause death 1.24, 95%CI 0.85-1.80 and 2.95, 95%CI 2.17-4.00, respectively, p trend &lt; 0.01). Conclusions: In this population-based cohort, colon cancer patients who did not fit CTEC were frequently treated with AC. Outcomes in this TI group were inferior to those in the TE group, but they were better than the subset that did not receive AC. Broadening CTEC to include a segment of the TI population should be considered as there appears to be benefit in selected individuals. [Table: see text]
Therapeutic drug monitoring of 5-fluorouracil (5-FU) in the treatment of patients with colorectal cancer (CRC).
Authors: Gaurav Goel, Rajesh Sehgal, Dennis James Meisner, Min Sun, Gurleen Pasricha, Edward Chu, James J. Lee
Journal: Journal of Clinical Oncology (2015)

563 Background: 5-FU continues to serve as the backbone of systemic combination chemotherapy for treatment of CRC in the adjuvant and metastatic disease settings. The dosing of 5-FU has traditionally been based on body surface area (BSA). Growing evidence suggests that BSA-based 5-FU dosing has several limitations, and that pharmacokinetic (PK)-guided dosing of 5-FU improves clinical efficacy with reduced toxicity. We conducted a QI study to evaluate the clinical feasibility of PK-guided 5-FU dose adjustment and its impact on clinical outcome. Methods: CRC patients treated with combination chemotherapy regimens containing infusional 5-FU who underwent PK-guided optimization of 5-FU dosing using an antibody-based immunoassay (OnDose or MyCare) were included in the analysis. Results: A total of 58 patients (34 males, 24 females) meeting the entry criteria have been identified to date. The median age was 61 years (range, 27-85). Fifteen patients had stage III disease, and the remaining 43 patients had stage IV disease. The 5-FU infusional regimens included mFOLFOX6 (n=45) and FOLFIRI (n=13). A total of 143 5-FU PK tests were performed for these 58 patients. The median number of tests performed per patient was 2 (range, 1-5). On initial testing, only 36% (n=21) patients had 5-FU systemic exposure, measured as area under the curve (AUC), within the suggested target range of 20-30 mg . hr/L. Fifty-five percent of the patients were below the target AUC while 9% (n=5) patients were above the target range. Of the 32 patients below the target range on 5-FU AUC test, the 5-FU doses were increased in 22 patients for the subsequent treatment cycle. The median number of dose modifications required to achieve the target AUC levels in these patients was 1 (range, 1-2). The majority of these patients (86%, n=19) tolerated the increased 5-FU dose well without worsening of 5-FU related toxicity. Conclusions: Our data provides further evidence that 5-FU dosing based on BSA results in sub-optimal 5-FU exposure levels for the majority of patients (64%). PK-guided dose adjustment of 5-FU appears to be a practical and feasible approach that can be applied in routine clinical practice.
Correlation of lymphovascular invasion and staging in patients undergoing lymphatic mapping for colon cancer.
Authors: Alpesh K. Korant, Vikrom K. Dhar, Gregory Johnston, Supriya Kumar Saha, Mohammed Shaik, David Wiese, Sukamal Saha
Journal: Journal of Clinical Oncology (2014)

498 Background: Lymphovascular invasion (LVI) is known as a negative prognostic factor in colon cancer (CCa) patients (pts). Sentinel lymph node mapping (SLNM) is known to upstage more pts than conventional surgery. A retrospective study was undertaken to determine the relationship between LVI and other known prognostic factors in CCa pts undergoing SLNM. Methods: Pts with CCa underwent SLNM. Data was collected for tumor (T) and node (N) stage, distant metastasis (M), size, grade, recurrence, and 5-year overall survival (5yrOS). Chi-square analysis was used to calculate the association between categorical variables with a p value of 0.05 as significant. Kaplan-Meier method was used to calculate 5yrOS. Results: We studied 310 CCa pts undergoing SLNM. Success rate was 100%. Nodal positivity was 46%. LVI was present in 34% of pts overall, in 66% node +ve pts versus only 7% in node -ve pts (p&lt;0.001). Pts with LVI were proportionately of higher grade, larger size, higher T-stage, node +ve and higher AJCC stage. Pts with LVI had significantly higher recurrence and lower 5yrOS (Table). Conclusions: Presence of LVI positively correlated with all known prognostic factors in CCa pts undergoing SLNM, with higher recurrence and significantly lower 5yrOS. [Table: see text]
RTOG 0913: A phase I study of daily everolimus (RAD001) in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.
Authors: Prakash Chinnaiyan, Minhee Won, Patrick Y. Wen, Amyn Rojiani, Merideth M Wendland, Thomas A. DiPetrillo, Benjamin W. Corn, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2013)

2047 Background: To determine the safety of the mTOR inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (TMZ) (75 mg/m 2 /day). Everolimus was escalated from 2.5 (Dose Level 1), to 5 (Dose Level 2), to 10 mg/day (Dose Level 3). Maintenance TMZ was delivered at 150-200 mg/m 2 on days 1 to 5 every 28 days for up to 12 cycles with concurrent everolimus at the previously established daily dose of 10 mg/day. Dose escalation continued if a dose level produced DLTs in ≤ 2 of the first 6 evaluable patients. Results: Between October 28, 2010 and July 2, 2012, the Radiation Therapy Oncology Group (RTOG) 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria, receiving drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined MTD of 10 mg/day. Two of the first 6 eligible patients experienced a DLT at each dose level. DLTs included: gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were Grade 1/2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was one death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation therapy and TMZ followed by maintenance TMZ, is well tolerated, with an acceptable toxicity profile. A phase II randomized clinical trial with mandatory correlative biomarker analysis is currently underway, designed to both determine the efficacy of this regimen and identify molecular determinants of response. Supported by RTOG U10 CA21661 and CCOP U10 CA37422 grants from NCI and Novartis. Clinical trial information: NCT01062399.
Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity
Authors: Dania Zhivaki, Sébastien Lemoine, Annick Lim, Ahsen Morva, Pierre-Olivier Vidalain, Liliane Schandene, Nicoletta Casartelli, Marie-Anne Rameix-Welti, Pierre-Louis Hervé, Edith Dériaud, Benoit Beitz, Maryline Ripaux-Lefevre, Jordi Miatello, Brigitte Lemercier, Valerie Lorin, Delphyne Descamps, Jenna Fix, Jean-François Eléouët, Sabine Riffault, Olivier Schwartz, Fabrice Porcheray, Françoise Mascart, Hugo Mouquet, Xiaoming Zhang, Pierre Tissières, Richard Lo-Man
Journal: Immunity (2017)
Patient and clinician perspectives on treatment decision-making for African American men with prostate cancer.
Authors: Nina A. Bickell, Sarah Abramson, Daniel Walker, Lindsey Sova, Jenny J Lin, Kezhen Fei, Rebeca Franco, Ann Scheck McAlearney
Journal: Journal of Clinical Oncology (2016)

186 Background: Prostate cancer is the most common cancer for men in the US, yet the burden of this disease falls disproportionately on African Americans (AAs). The disparity’s etiology is complex. Surgery and radiotherapy offer similar survival but historically have different rates of performance with younger and white men more likely to undergo surgery and AAs more likely to experience underuse. This study aims to examine treatment decision-making (TDM) processes for AA men from patient and physician perspectives. Methods: At 1 academic and 1 municipal urban hospital, pathology records and a tumor registry from 2007-2012 were used to identify 359 AA and 282 white men with locally advanced prostate cancer, a Gleason score of 7-10, and receipt of definitive treatment. 15/17 treating physicians of participating patients were interviewed. Underuse overall was 4%, AA had higher rate of underuse compared to whites (6% vs. 1% respectively, p = 0.0002). 14 patients with longer times between diagnosis and treatment were recruited for 4 focus groups &amp; 2 interviews lasting 60-90 minutes eliciting perspectives on themes related to TDM. Transcripts were coded and analyzed using a grounded theory approach. Results: Preliminary analysis of patient interviews suggests that patients primarily base their treatment decisions on physician recommendations. Patients were often unaware of treatment side effects. However, some patients felt this deficit helped them decide to receive treatment, whereas if they had known about possible impotence and incontinence, they would have refused treatment. Physicians recognized that patient concerns about side effects were a critical TDM factor. Physicians attributed prolonged delays between diagnosis and treatment to waiting times for tests of possible tumor spread and medical comorbidities. Conclusions: Understanding decision making and care processes for AA men with local advanced prostate cancer is critical to reducing the treatment and outcome disparities in this population. This study identifies several patient and physician/system factors that contribute to this process. These data can help inform interventions to improve prostate cancer care for AA men.
Clinical and behavioral characteristics of active smokers with squamous cell carcinoma of the head and neck (SCCHN) in an urban setting: Attitudes underlying high-risk disease.
Authors: J. W. Chuy, A. Moadel, H. Haynes, M. Garg, B. A. Schiff, R. V. Smith, C. Sarta, Y. Eng, N. Schlecht, A. Negassa, M. Haigentz
Journal: Journal of Clinical Oncology (2011)

e16027 Background: Cigarette smoking is associated with 85% of SCCHN, and active smoking has been associated with poor prognosis. The objective of this study was to examine the clinical, behavioral and psychosocial factors associated with tobacco use in patients (pts) with SCCHN undergoing curative-intent radiotherapy (RT). Methods: Self-report questionnaires were administered to 24 pts with SCCHN undergoing curative-intent RT at Montefiore Medical Center who had reported smoking within 6 months prior to diagnosis. Data collected at baseline included demographics, smoking behaviors and attitudes, mood state using MHI-5, and quality of life (QoL) using EORTC QLQ-C30 and QLQ-H&N35 questionnaires. Results: Most participants (79%) were male, 38% were married, and 70% had a high school education or less. Forty-six percent were African American and 21% were Hispanic. Most pts had oropharyngeal (33%) or laryngeal (42%) cancers, and 67% had stage IV disease. The mean number of cigarettes smoked per day was 21.6. Average duration of tobacco use was 39.3 yrs. Eight pts (33%) reported concomitant alcohol use. Only 57% felt that smoking was somewhat or very much related to their cancer diagnosis, though 92% were in action or contemplative stages of change. Most (63%) had tried to quit at least once in their lifetime but without formal guidance; 33% had used a form of nicotine replacement. Mean MHI-5 score was 52, previously shown to correlate with depression. Pts scored lower on the social functioning scale (71.4) relative to the general head and neck cancer population (82.6). The worst symptom scale scores were pain killer use, weight loss, coughing, swallowing difficulties, and financial difficulties. Five pts (21%) did not complete RT or had treatment delays ≥ 5 days. After a median of 16 months of follow-up, 5 (21%) have died of disease and 2 (8%) are alive with recurrence. Conclusions: Active cigarette smokers with SCCHN represent a population with impaired QoL at risk for poor outcomes despite curative-intent RT. Interventions targeting community education on cancer prevention and smoking cessation and addressing QoL in smokers with SCCHN are indicated.
Retrospective analysis of sorafenib as first- or second-line targeted therapy in patients with mRCC: Three-year Italian experience.
Authors: Giuseppe Procopio, Lisa Derosa, Angela Gernone, Franco Morelli, Teodoro Sava, Vittorina Zagonel, Ugo De Giorgi, Vittorio D. Ferrari, Cristina Masini, Donatello Gasparro, Alessandra Felici, Rossana Berardi, Nicola Calvani, Giovanni Lo Re, Helga Lipari, Maria Pia Brizzi, Michele Sisani, Camillo Porta, Enzo Galligioni, Antonio Silverio Contu
Journal: Journal of Clinical Oncology (2013)

415 Background: The Retrospective analysis of Sorafenib (So) as the first- or second- target therapy (RESET) study in metastatic renal cell carcinoma (mRCC) patients assessed the use and safety of sorafenib under daily-life treatment conditions in a community-based patient population in Italian centers. Methods: RESET was a retrospective, observational, non-interventional field study in mRCC patients. Treatment decisions were determined by each physician according to local prescribing guidelines and clinical practice. Patients for whom a decision to treat with sorafenib single agent as first- or second- target therapy (TT) for mRCC has been made, were eligible for inclusion. Patients that started So treatment between January 1, 2008 and December 31, 2010 were included. Data collection started retrospectively in 2012, in order to have a period of observation of at least 1 year up to 31st Dec 2011. Endpoints included safety, overall survival (OS), progression-free survival (PFS), response rate (RR), and treatment duration. Subgroup analyses included age, Eastern Cooperative Oncology Group performance status, prior therapy, number of metastases, and line of TT with So. Results: From February to Jululy 2012, 358 pts from 37 Italian centers were enrolled. The most common ≥ grade 3 drug-related adverse events were hand-foot skin reaction (6.3%), rash (2.3%), hypertension, fatigue, and diarrhea (1.7% each). In the overall population, median OS was 17.2 months (mos) (95% CI 15.5 – 19.6 mos) and median PFS was 5.9 mos (95% CI 5.0-6.8 mos). Median duration of treatment with So was 5.09 mos. Complete response was observed in 3 (0.8%) pts, partial response in 53(15.0%) pts and stable disease in 139(39.4%) pts. In pts receiving So as first- or second- TT, median OS was 19.9 mos (95% CI 15.4-25.3 mos) and 16.6 mos (95% CI 13.1-18.4 mos) respectively, and median PFS was 6.6 mos (95% CI 4.9-9.3 mos) and 5.3 mos (95% CI 4.4-6.2 mos) respectively. Conclusions: The efficacy and safety of So under routine clinical practice conditions in the setting of community-based practice in Italy were similar to that reported in prospective clinical trials. The efficacy of So was observed in the subgroup of pts receiving So as either the first or second TT for mRCC.
Development of a new photonumeric scale for acute radiation dermatitis in patients with breast cancer.
Authors: Dean Shumway, Eleanor M. Walker, Nirav S. Kapadia, Thy Thy Do, Kent A. Griffith, Mary Uan-Sian Feng, Bonnie DePalma, Yolanda R. Helfrich, Erin Gillespie, Alexandria Miller, Reshma Jagsi, Lori J. Pierce
Journal: Journal of Clinical Oncology (2015)

86 Background: The Common Terminology Criteria for Adverse Events (CTCAE) is frequently used to grade the severity of acute radiation dermatitis (ARD), but has not been validated despite decades of clinical use. We sought to develop a photonumeric scale to consistently describe ARD in breast cancer patients undergoing radiation (RT). Methods: Patients enrolled on a prospective study that included photographs and quantitative measurements of erythema and hyperpigmentation using colorimetry. 209 photographs from 35 patients with white skin and 369 photographs from 50 patients with skin of color were used to develop two photonumeric scales. Predominant erythema (in white skin) OR hyperpigmentation (in skin of color) were rated on a 4 point scale, with grading of desquamation on a separate 3 point scale. Four raters used both CTCAE and photonumeric scales to independently score all photographs. Intra- and inter-rater agreements were assessed using weighted kappa scores. Results: Using the CTCAE, 95% of photos were rated as grade 1 or 2. There was a trend toward higher grade in patients with skin of color, with grade 2 toxicity in 43% vs. 24%. Intra-rater agreement for CTCAE ratings was 65—87% (kappa 0.34—0.67), with a wide range of inter-rater agreement (56—81% agreement fraction, kappa 0.04—0.58). Using the photonumeric scale, intra-rater agreement was high for erythema/hyperpigmentation in patients with white skin (74—82%, kappa 0.49—0.70) and skin of color (69—86%, kappa 0.55—0.79), along with desquamation (78—87%, kappa 0.52—0.66). There was moderate inter-rater agreement for erythema/hyperpigmentation (51—82%, kappa 0.15—0.71) and desquamation (63—88%, kappa 0.36—0.58). Colorimetric measurements correlated strongly with photonumeric grade. Conclusions: We report a new photonumeric scale for ARD in breast cancer patients with satisfactory reliability across the spectrum of skin pigmentation. Intra-physician ratings were consistent, with moderate inter-physician agreement. The CTCAE functions as a binary scale, with 95% of ARD rated as grade 1 or 2 toxicity. Future work includes correlation with patient-reported outcomes and physician ratings at the point-of-care. Funded by a Munn Idea Grant (G011480).
Inhibiting Histone Deacetylase as a Means to Reverse Resistance to Angiogenesis Inhibitors: Phase I Study of Abexinostat Plus Pazopanib in Advanced Solid Tumor Malignancies
Authors: Rahul Aggarwal, Scott Thomas, Nela Pawlowska, Imke Bartelink, Jennifer Grabowsky, Thierry Jahan, Amy Cripps, Armand Harb, Jim Leng, Anne Reinert, Ilaria Mastroserio, Thach-Giao Truong, Charles J. Ryan, Pamela N. Munster
Journal: Journal of Clinical Oncology (2017)

Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC). Results Fifty-one patients with RCC (N = 22) were enrolled, including 30 (59%) with one or more lines of prior VEGF-targeting therapy. Five dose-limiting toxicities, including fatigue (n = 2), thrombocytopenia (n = 2), and elevated AST/ALT (n = 1), were observed with schedule A; one dose-limiting toxicity was observed (elevated AST/ALT) was observed with schedule B. Grade ≥ 3 related adverse events included fatigue (16%), thrombocytopenia (16%), and neutropenia (10%). The recommended phase II dose was established as abexinostat 45 mg/m2 twice a day administered per schedule B plus pazopanib 800 mg/d. Objective response rate was 21% overall and 27% in the RCC subset. Median duration of response was 9.1 months (1.2 to > 49 months). Eight patients (16%) had durable control of disease for > 12 months. Durable tumor regressions were observed in seven (70%) of 10 patients with pazopanib-refractory disease, including one patients with RCC with ongoing response > 3.5 years. Peripheral blood histone acetylation and HDAC2 gene expression were associated with durable response to treatment. Conclusion Abexinostat is well tolerated in combination with pazopanib, allowing prolonged exposure and promising durable responses in pazopanib- and other VEGF inhibitor-refractory tumors, which supports epigenetically mediated reversal of treatment resistance.