tbuckley/cabot-search huggingface dataset:
Perceived stress to predict for acute radiation-induced skin toxicity: The mind-body connection.
Authors: Bree Ruppert Eaton, Tian Liu, Xiaofeng Yang, Donna Mister, Yize Zhao, Andrew H. Miller, Qi Long, Mylin Ann Torres
Journal: Journal of Clinical Oncology (2013)

62 Background: Previous studies have reported that breast cancer patients with high stress levels at diagnosis develop more frequent and severe side effects of chemotherapy treatment. However, the relationship between stress and radiotherapy (RT) related treatment toxicity has not been evaluated. We investigated whether baseline stress is associated with worse acute skin toxicity in women undergoing breast RT. Methods: Between March 2010 and April 2013, 80 post-lumpectomy breast cancer patients were enrolled on a prospective study prior to undergoing definitive whole breast RT (50 Gy plus a 10 Gy boost). Prior to RT (baseline), at week 6 of RT (T2), and 6 weeks post RT (T3), subjects completed the Perceived Stress Scale (PSS) and underwent objective ultrasound measurements of epidermal thickness over the lumpectomy cavity and in all four quadrants of the treated breast. A skin thickness ratio (STRA) was generated by normalizing for measurements taken of the untreated breast. RT-induced skin toxicity was assessed by measuring the change in STRA from baseline to T2 and T3. Results: Mean STRA increased by 23% (SD 27%) and 33% (SD 25%) from baseline to T2 and T3, respectively. Univariate analysis revealed PSS score at baseline (p=.04), body mass index (p=.03), maximum RT dose (Dmax) (p=.02) and whole breast volume (p&lt;.001) were significantly associated with increased changes in STRA during RT. Depression, fatigue, race, chemotherapy, patient age, and tumor stage were not associated with changes in STRA. On multivariate analysis, PSS (p=.05), breast volume (p=.004), and Caucasian race (p=.04) were associated with greater acute changes in STRA from baseline to T2. Breast volume (p=.01), but not PSS, predicted for greater changes in STRA 6 weeks after RT was completed. Conclusions: In women with breast cancer, a high level of perceived stress prior to RT is associated with more severe acute skin toxicity during RT but not after RT is completed. Strategies to reduce stress prior to RT may improve tolerance of treatment.
Effect of everolimus treatment on chromogranin A, neuron-specific enolase, gastrin, and glucagon levels in patients with advanced pancreatic neuroendocrine tumors (pNET): Phase III RADIANT-3 study results.
Authors: E. De Vries, L. B. Anthony, L. Sideris, L. Chen, J. Lebrec, Z. Tsuchihashi, R. E. Winkler, J. C. Yao, K. E. Oberg
Journal: Journal of Clinical Oncology (2011)

10624 Background: Chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, and glucagon are important biomarkers in pNET. The goals of this analysis were to characterize serum CgA, NSE, gastrin, and glucagon concentration changes from baseline in response to treatment with oral everolimus or placebo in patients with advanced pNET in the phase III RADIANT-3 trial (ESMO 2010, Abstract #LBA9). Methods: Patients with progressive, advanced low- or intermediate-grade pNET were randomized to everolimus 10 mg/d orally (n=207) or placebo (n=203). Serum samples were collected and analyzed for CgA, NSE, gastrin, and glucagon at baseline and, if elevated (>ULN), were repeated on day 1 of each subsequent cycle. Changes from baseline over time were analyzed using a mixed-effects model including least squares estimates and P values of treatment effect. Results: Patients with elevated baseline values had biomarkers assessed for a median number of 10 cycles in the everolimus arm and 4 cycles in the placebo arm. Everolimus vs placebo resulted in greater reductions of CgA (P<0.0001), NSE (P<0.0001), gastrin (P<0.0001), and glucagon (P<0.0001) over time. During the first cycle, the ratio in fold change from baseline for everolimus vs placebo was 0.617/1.081=0.57 (95% CI, 0.45-0.73) for CgA, 0.478/0.951=0.50 (95% CI, 0.32-0.80) for NSE, 0.581/0.833=0.70 (95% CI, 0.52-0.94) for gastrin, and 0.679/1.034=0.66 (95% CI, 0.49-0.89) for glucagon. This positive treatment effect with everolimus was maintained over subsequent treatment cycles; the ratio in fold change from baseline for everolimus vs placebo groups ranged from 0.39-0.57 for CgA, 0.23-0.51 for NSE, 0.46-0.70 for gastrin, and 0.45-0.66 for glucagon. Conclusions: In addition to the improvement in PFS seen in RADIANT-3, these results demonstrate that treatment with everolimus resulted in early, sustained decreases in serum levels of CgA, NSE, gastrin, and glucagon in patients with pNET.
Bone-targeted therapy consisting of zoledronate, thalidomide, and gamma interferon in renal cell carcinoma: a phase II study
Authors: E. Jonasch, S.-M. Tu, N. M. Tannir, L. C. Pagliaro, P. Mathew, A. O. Siefker-Radtke, S. Wen, R. General, S.-H. Lin, C. J. Logothetis
Journal: Journal of Clinical Oncology (2005)

4769 Purpose: Evaluate the efficacy and safety of a bone-targeted regimen consisting of zoledronate, thalidomide, and gamma IFN in patients with renal cell carcinoma and bone metastases. Patients and Methods: Fifteen patients were enrolled on the study between 11/14/02 and 11/7/03. Impending pathological fractures or spinal cord compressions were controlled by surgery or radiation therapy prior to study. Zoledronate (4 mg) was given intravenously once every 4 weeks. Thalidomide (300 mg) was taken orally once every day. Gamma IFN (100 mcg) was given subcutaneously once every week. Patients were evaluated for the presence of calcification in osteolytic metastases, time to skeletal-related events, and levels of bone formation and resorption markers (i.e., bone-specific alkaline phosphatase, urine N-telopeptide and deoxypyridinoline). Results: Twelve patients had previously received surgery, radiation, or embolization for their bone metastases. Eleven patients had multiple (more than three) sites of bone involvement. Nine patients also had non-osseous metastases in the lungs, liver, lymph node, pancreas, and/or adrenal gland. The median time to progression was 8.3 weeks (range, 2.1–48 weeks). The median time to skeletal-related event was 13.7 weeks (range, 3.1 - 46.4 weeks). Two patients discontinued treatment because of adverse drug reactions (deep venous thrombosis or myocardial infarction). Two patients had pain improvement and developed calcification in the osseous metastases. They also had increased bone formation marker or decreased bone resorption marker. Conclusions: A bone-targeted regimen combining zoledronate, thalidomide, and gamma IFN is well tolerated and may provide clinical benefit for selected patients with renal cell carcinoma and bone metastases. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Merck, Pfizer Celgene, Eli Lilly, Novartis
Role of Intensive Conditioning Regimens Followed by Allogeneic Stem Cell Transplantation in Patients with Acute Lymphoblastic Leukemia: A Long-Term Follow-Up.
Authors: Jiro Minami, Osamu Asai, Nobuaki Dobashi, Shingo Yano, Hiroshi Osawa, Yutaka Takei, Yuichi Yahagi, Shinobu Takahara, Yoji Ogasawara, Hiroko Otsubo, Yuko Yamaguchi, Takeshi Saito, Dai Maruyama, Tatsunosuke Kobayashi, Yasutaka Hoshi, Noriko Usui
Journal: Blood (2006)
5-Azacytidine in the Treatment of High Risk Myelodysplastic Syndromes: Clinical Response Can Occur without Demethylation of the CDKN2B, CDKN1A or TP73 Gene Promoters.
Authors: Kavita Raj, Alison John, Aloysius Ho, Nicholas Shaun B. Thomas, Ghulam J. Mufti
Journal: Blood (2004)
Epidermal growth factor expression affects clinical outcome in colorectal cancer
Authors: G. F. El-Wahidy, S. Eteba, R. Abdelatif, N. El-Ghawalbi, I. El-Desoki
Journal: Journal of Clinical Oncology (2008)

15125 Background: To elucidate the level of ECFR expression in colorectal cancer and the impact of chemotherapy on survival according to this expression. Methods: 50 patients with CRC staged II and III (AJCC). Group I (20) cases with negative expression subjected to adjuvant chemotherapy Mayo clinic regimen. Group II with expressed EGFR (30) case sub classified to 2 subgroups (A) (17 cases) received Mayo Clinic regimen and subgroup (B) (13 cases) received intensive protocol (FOLFOX or FOLFIRI). Both groups were well balanced. Results: Table (1). Conclusions: 1- EGFR expressed in 60% of our cases 2- RFS was significantly higher in group I with -ve expression versus +ve expression. 3- OAS was higher in group I with -ve expression versus + ve expression but this increase didn't reach statistical significance. 4- In those subsets of patients with expressed EGFR the mean value of survival was better in the group received intensive chemotherapy than those received conventional protocol (Mayo regimen) although the difference didn't reach statistical significance. Patient Characteristics NO % No 50 . Mean age y. 45 . Male 19 38 Female 31 62 EGFR +ve 30 60 EGFR −ve 20 40 Stage II 26 52 Stage III 24 48 Histology: Adenocarcinoma Histology: 38 72 Mucinous Histology: 11 22 Signet Ring 1 2 No significant financial relationships to disclose.
EGFR/KRAS mutations in African Americans (AA) versus Caucasians (CA) in patients with NSCLC: A comparative analysis of the South Carolina experience.
Authors: M. M. Goodman, K. Shirai, E. Hill, G. R. Simon
Journal: Journal of Clinical Oncology (2011)

e18018 Background: AAs with NSCLC has inferior survival compared to CAs (Abidoye, Nature 2007). We sought to discern whether differences in incidence of EGFR or KRAS mutations between races could partly explain these differences. Methods: Pts with NSCLC who were seen at the Hollings Cancer Center (HCC) and underwent EGFR and KRAS mutation testing in 2010 were included. Microdissected formalin-fixed paraffin-embedded tumors from 89 patients with NSCLC were analyzed for EGFR/KRAS mutations by allele-specific PCR. Data were compared with previously reported experiences from Memorial Sloan Kettering Cancer Center (MSKCC), (Reinersman et al), Case Western Reserve (CWR), (Leidner et al) and Louisiana State University Health Sciences Center (LSU) (Hunt et al). We estimated the percentage of EGFR+ and KRAS+ AA and CA subjects using exact binomial confidence intervals, and compared proportions using Fisher’s exact test. Aggregate estimates were obtained using inverse variance-weighting and random-effects modeling to account for study heterogeneity. Results: Of the 89 pts, 63 were CAs and 26 were AAs. In AA population, 24/26 pts had successful EGFR and KRAS analysis. In the CA population 59/63 pts and 61/63 pts had successful EGFR and KRAS testing, respectively. Data are in the table below. A weighted aggregate are also compiled. Conclusions: Overall, the incidence of EGFR and KRAS mutations were similar for AAs and CAs. The observed differences in survival between AAs and CAs cannot be explained by differences in the molecular entities examined. Detailed demographic and survival data will be provided at the meeting. EGFR Status KRAS Status N+/total N (%; 95% CI) N+/total N (%; 95% CI) p N+/total N (%; 95% CI) N+/total N (%; 95% CI) p AA CA AA CA HCC 2/24 (8; 1, 27) 10/59 (17; 8, 29) 0.49 6/24 (25; 10, 47) 16/61 (26; 16, 39) >0.99 MSKCC 23/121 (19; 12, 27) 61/476 (13;10, 16) 0.11 21/121 (17; 11, 25) 125/476 (26; 22, 30) 0.04 CWR 1/53 (2; 0, 10) 15/89 (17; 10, 26) 0.005 12/53 (23; 12, 36) 16/76 (21; 13, 32) 0.83 LSU NR NR 22/60 (37; 25, 50) 10/51 (20; 10, 33) 0.06 Aggregate 26/198 (10; 0, 21) 86/624 (14; 11, 16) 0.51 61/258 (25; 16, 33) 167/664 (25; 22, 28) 0.92 Abbreviation: CI, confidence intervals; NR, not reported.
Emesis as a predictor of bacteremia in immunocompromised children with central venous catheters and fever
Authors: M. Richardson
Journal: Journal of Clinical Oncology (2008)

20566 Background: Children receiving cancer therapy and those with aplastic anemia often require indwelling central venous catheters (CVC) and commonly develop fever. Clinical observations led to the hypothesis that emesis was associated with bacteremia in these patients. Although previous studies have identified clinical and laboratory features at presentation of fever that help predict who is likely to have bacteremia, none have included vomiting as a predictor. Methods: Retrospective chart review of children admitted to Baystate Children’s Hospital between Jan 1, 2006 and Sept 30, 2007 with a diagnosis of cancer or aplastic anemia, a CVC, and fever. Vomiting was considered present if noted in the admission history, review-of-systems, or within 24 hr of admission and absent if the history/ review-of- systems documented its absence. Data were collected on culture results, type of CVC (subcutaneous port vs. tunneled external), and absolute neutrophil count (ANC) at presentation (less than or greater than 500 cells/mm3). Results: There were 122 admissions for fever; 121 had complete data for analysis. Emesis was present in 31, absent in 90. 34 (28%) had culture-proven bacteremia. Bacteremia was present in 17 (55%) of the emesis group and 17 (19%) of the no-emesis group (p=.0003). The RR of bacteremia with emesis was 2.90 (95% CI, 1.70 - 4.95), positive predictive value 55%, negative predictive value 81%. Gram negative organisms were more common in the emesis group (13 of 17) than in the no-emesis group (6 of 17), (p=.038). The emesis and no-emesis groups had no significant differences in frequency of ANC <500 or type of CVC. Frequency of ANC <500 was not significantly different between culture positive and negative groups. Conclusions: Immunocompromised children with CVC and fever presenting with emesis are significantly more likely to have bacteremia, especially Gram negative bacteremia, than those without emesis. This sign could be an important additional factor in deciding if a child is at high or low risk of serious bacterial illness, location of treatment (in vs. outpatient) and in choosing initial empiric antibiotics. Further studies may incorporate these findings into risk stratification and management algorithms. No significant financial relationships to disclose.
Predictive factors for additional vascular procedures in patients with germ cell tumors (GCT) and residual tumor resection (RTR): A multicenter analysis of the German Testicular Cancer Study Groups (GTCSG).
Authors: C. Winter, D. J. K. P. Pfister, C. Bingoel, J. Busch, U. Ranft, M. Schrader, K. P. Dieckmann, A. Heidenreich, P. Albers
Journal: Journal of Clinical Oncology (2011)

e15050 Background: The aim of this analysis was to identify parameters to predict additional vascular procedures during RTR in a multicenter setting in patients (pts) with GCT after chemotherapy. Methods: A retrospective analysis was performed in 411 GCT pts who underwent RTR in multiple centers. 380 of 411 pts had a sufficient follow-up and were evaluable with complete data sets. The RTR database was queried for additional vascular procedures (cava resection, aortic prosthesis) and correlated to IGCCCG classification and residual tumor volume. The median age of patients was 32 yrs (14-67). 44% of patients initially had IGCCCG intermediate/poor prognosis features. Results: In 34 RTRs a vena cava resection was necessary. The necessity of vena cava resection was significantly correlated with initial IGCCCG classification (16.6% intermediate/poor vs. 4.5% good; p<0.001) but not with tumor size (9.2% residual tumor size <5cm vs. 17.2% residual tumor size >5cm; p=0.0624). In 5 patients an aortic resection and prosthesis during RTR was required. There was no significant correlation to IGCCCG (2.2% intermediate/poor vs. 0.7% good; p=0.2877) but to tumor size (0.6% residual tumor size <5cm vs. 4.5% residual tumor size >5cm; p=0.0340). Conclusions: The necessity for additional vascular procedures (cava resection, aortic prosthesis) during RTR is correlated to the residual tumor size and initial IGCCCG classification. Patients with high volume residual tumors (>5cm) and with IGCCCG intermediate/poor risk features can be initially identified as high risk patients for vascular procedures and therefore should be referred to specialized surgical centers with ad hoc possibility of vascular interventions.
Compliance with ASCO guidelines in the treatment of stage IV non-small cell lung cancer.
Authors: A. S. Marr, F. R. Loberiza, M. A. Kessinger, J. McGarry, A. K. Ganti
Journal: Journal of Clinical Oncology (2011)

e16614 Background: Limited data exist on practice pattern variations within the US for stage IV non-small cell lung cancer (NSCLC). ASCO developed treatment guidelines for these patients, but the adherence to them is not known. Methods: Treatment data of stage IV NSCLC patients included in a database based on chemotherapy software, IntelliDose were obtained. Providers were categorized as academic (AC), community (facility manages infusion center) (C), or private practice (physicians manage infusion center) (PP) based on self reporting. First-line chemotherapy regimens were compared according to provider category. Chemotherapy regimens were classified as adherent or non-adherent based on the 2009 ASCO guidelines. Multivariate logistic regression was used to compare adherence in the provider groups while controlling for known confounding factors. Results: Of the 1131 patients receiving first-line chemotherapy recorded into the database in 2008-2009, AC treated 88 (8%), while C and PP treated 492 (43%) and 551 (49%) patients, respectively. AC had a lower adherence rate compared to C and PP (61% vs. 82% and 77%, respectively; p<0.0001). In multivariate analysis, C and PP had a higher likelihood of adherence compared to AC [odds ratio (OR) 3.45 (95%CI 2.10-5.70, p<0.001); OR 2.21 (95%CI 1.36-3.59, p 0.001), respectively]. PP were less likely to adhere compared to C [OR 0.64 (95% CI 0.46-0.89, p<0.007)]. The most common regimens given in AC were carboplatin/gemcitabine (19%) and carboplatin/pemetrexed (17%) as compared to carboplatin/paclitaxel (37%; 34%) and carboplatin/paclitaxel/bevacizumab (14%; 11%) in C and PP, respectively. AC administered investigational therapy to 9% of patients compared to <1% for C and PP (p<0.001). Other factors predicting for adherence included younger age and increasing number of NSCLC patients seen at the facility. Conclusions: C and PP were more likely to adhere to the ASCO guidelines for treatment-naïve stage IV NSCLC. Further studies should examine the cause of lower adherence rates in academic centers and its clinical implications, if any. Source: data from IntrinsiQ, LLC. Research Market Share Data: 2007-2010. Information on proprietary and non-published data available at www.intrinsiq.com.
An innovative model for palliative care at home for 100,000 patients with cancer since 1985 in Italy: A social partnership for a public health system integrated and sustainable.
Authors: Raffaella Pannuti, Silvia Varani, Franco Pannuti
Journal: Journal of Clinical Oncology (2014)

113 Background: In Italy, like in most Western countries, the number of elderly people with a chronic disease is constantly increasing and it causes a growth in disability and frailty. However, the Public Health Service is unable to provide all the services needed. Therefore it is necessary to find urgent actions to fill in the gaps of the Public Health Service and to think about appropriate solutions for a sustainable future. Methods: Since 1985, ANT has assisted at home more than 100,000 cancer sufferers, completely free of charge, thanks to its 20 oncological teams in 9 Italian regions. There are currently about 4,000 patients receiving care every day throughout Italy. ANT offers specialized care provided by 400 healthcare professionals, including doctors, nurses, psychologists, nutritionists, physiotherapists, social-health workers, who are able to provide patients with round the clock care, 365 days a year. Results: The quality of the model of ANT home care is supported by the following outcomes: 78% of the patients (ANT National average) choose to die at their own home in contrast with the National average of cancer death at home equal to 57,9%. In the last 30 days of life, 74% of the patients assisted by ANT aren’t admitted to hospital, 12% have an hospitalization lasting less than 7 days and only 14% remain in hospital for over a week. The customer satisfaction, assessed through a questionnaire sent to families about a month after death, shows that 90% of respondents are very satisfied with the assistance received. ANT spends about 2,090 euro for each patient assisted. Given that each patient is cared for an average of 132 days, the cost is about 30 euro a day. This charge is much lower than a recovery for a day in a palliative care residential facility (240 euro) and it is lower also than an admission for a day in a public hospital (780 euro). Conclusions: The situation calls for a change in strategies in health policy, stimulating integration between public and social institutions. The model of ANT home care is an example of a social buffer that offers an integrated health and social assistance able to meet the increasingly complex needs of patients and their families.
A phase I study of once-weekly aminoflavone prodrug (AFP464) in solid tumor patients.
Authors: M. P. Goetz, J. M. Reid, Y. Qi, A. Chen, R. M. McGovern, M. J. Kuffel, P. D. Scanlon, C. Erlichman, M. M. Ames
Journal: Journal of Clinical Oncology (2011)

2546 Background: AFP464 (NSC 710464) is a lysyl derivative of aminoflavone metabolized by cytochrome P450 (CYP)1A1 and CYP1A2 (Kuffel et al, Mol Pharmacol 62:143, 2002) to reactive species that covalently bind DNA, with preclinical activity in breast, renal, and ovarian cell lines. Methods: We performed a phase I study to define the maximally tolerated dose (MTD), pharmacokinetics (pk) and pharmacodynamics of AFP-464 when given as an infusion on days 1, 8, and 15 of a 28-day cycle in patients (pts) with advanced solid tumors. Pulmonary function tests were performed during cycle 1 and prior to subsequent cycles. Advanced cancer pts with good performance status and organ function were eligible. DLTs were grade 4 neutropenia, grade 3 thrombocytopenia or ≥ grade 3 non-hematologic toxicities including carbon monoxide diffusing capacity (DLCO). An accelerated titration design was used until grade 2 toxicity, followed by a cohorts of 3 design. AFP464 and AF plasma concentrations were measured by a lc/ms/ms assay and pk determined by non-compartmental analysis. At the MTD, paired tumor biopsies were obtained for analysis of tumor CYP1A1 induction. Results: 24 evaluable pts received a median of 2 cycles (range 1-8) across 7 dose levels ranging from 10 to 74 mg/m2. Five DLTs were observed among 3 pts including grade 3 AST, Alk Phos, and bilirubin (14 mg/m2), grade 4 thrombosis (53 mg/m2), and grade 4 DLCO (> 5 unit drop in DLCO with pneumonitis) (74 mg/m2). Because pulmonary toxicity was observed in a European AFP 464 study (day 1, 8 schedule) at a similar dose level (68 mg/m2/week), accrual to 74 mg/m2 was terminated early. No tumor responses were observed. AFP464 and AF pk were characterized for 27 pts over the 10 – 74 mg/m2 dose range. AFP464 clearance is linear with a mean value of 259 L/h/m2 (range, 143 – 444 L/h/m2). AF exposure increased in proportion to dose. Half-life values for AFP-464 and AF are 5.6 h (range (0.2 – 25.3 h) and 3.4 h (range (0.9 – 7.0 h), respectively. Conclusions: The MTD of AFP-464 is 53 mg/m2 which will be studied in a CTEP sponsored phase II study in ER positive breast cancer. Pulmonary toxicity is dose limiting. Tumor CYP1A1 biomarker studies are ongoing. Supported by NCI U01 (CA69912), MM01-RR00585 and Tigris Pharmaceuticals.