tbuckley/cabot-search huggingface dataset:
Risk of depression, anxiety, and somatization one month after diagnosis in children with standard risk ALL on COG AALL0331
Authors: N. Buchanan, K. Maloney, S. Tsang, L. C. Stork, J. P. Neglia, N. S. Kadan-Lottick
Journal: Journal of Clinical Oncology (2008)

10052 Background: Symptoms of depression, anxiety and somatization are found in internalizing 2 disorders; characterized by intense fears concerning one’s social world and physical outcomes. Children with Acute Lymphoblastic Leukemia (ALL) experience stressors and receive medications that may increase symptoms of internalizing disorder, but rarely receive psychological intervention during leukemia therapy. Past studies have been limited by lack of prospective data and representative samples. Methods: In the current study of psychosocial outcomes in patients enrolled on AALL0331 for standard risk ALL at 38 Children’s Oncology Group sites, the child’s caregiver completed the Behavior Assessment System for Children, Second Edition (BASC-II). All evaluations were done one month after diagnosis. There were 95 participants (88% of those eligible) with a mean age of 4.9 years, 46% female and 58% Caucasian, 20% Hispanic, 5 % African American and 11% other. Consistent with BASC-II validation studies, patients with T-scores over 84% of the normative population were categorized as having internalizing symptoms in the at risk/clinical range. The proportion of study patients with clinically significant scores was then compared to the expected 16% in the normative population. Results: Overall, 39% of the sample demonstrated at risk/clinical internalizing symptoms (p<.00001) including; anxiety (27%, p=.006), depression (24%, p=.03) and somatization (41%, p=.0001). Females were more likely (34%) than males (21%) to experience anxiety. Children younger than 6 years at diagnosis had higher risk of anxiety (32%), depression (27%) and somatization (35%) than older children (18%, 18% and 29%, respectively). Children with annual family incomes of less than forty thousand dollars had higher rates of anxiety (35% vs. 20%, p=.007) and depression (31% vs. 11%; p=.02) than those with higher incomes. Conclusion: Children with ALL, one month after diagnosis, endorsed internalizing symptoms at twice the expected proportion in the general population. These symptoms can potentially affect a patient’s well being, medical compliance and the trajectory of their treatment, suggesting that more rigorous psychological treatment and assessment are warranted. No significant financial relationships to disclose.
Increased Proportions of CD39+ Infiltrating T-Cells Contribute to Adenosine Mediated T-Cell Hypo-Responsiveness within Human Follicular Lymphoma.
Authors: Shannon P. Hilchey, James J. Kobie, Matthew R. Cochran, Shelley Secor-Socha, Jyh-Chiang E. Wang, Ollivier Hyrien, W. Richard Burack, Tim R. Mosmann, Sally A. Quataert, Steven H. Bernstein
Journal: Blood (2009)
Characterization of family history profiles in a large series of Lynch syndrome carriers.
Authors: Devki Saraiya, Sara J. Wiyrick, Barry S. Tong, Kelsey Moyes, Elizabeth Garner
Journal: Journal of Clinical Oncology (2014)

414 Background: The identification of Lynch syndrome carriers is an unmet medical need. Large studies characterizing family history profiles of unaffected individuals diagnosed with Lynch syndrome in the absence of a known family mutation have not been reported. Methods: We queried our laboratory database for unaffected patients who underwent Lynch syndrome genetic testing between September 2010 and May 2013 and had a positive test result. All individuals underwent full sequence and large rearrangement analysis of MLH1 and MSH2, and full sequence analysis of MSH6. Some patients also underwent full sequence and large rearrangement analysis of PMS2 and large rearrangement analysis of MSH6 and EPCAM. Those being tested for a known mutation in the family and patients undergoing single gene testing were excluded. We assessed family history profiles in 200 unaffected patients with genetically confirmed Lynch syndrome. Results: Of the 200 patients, 162 female and 38 male Lynch syndrome carriers were identified. Mutations in MLH1 and MSH2 were the most common (30.0% and 32.5%) while mutations in MSH6, PMS2, and EPCAM accounted for 21.0%, 13.5%, and 3.0% of all deleterious mutations, respectively. Eighteen patients did not have a first or second degree relative with colorectal cancer. Only 37.8% (73/193) of individuals had a first- or second-degree relative meeting the Amsterdam II criteria and 76.8 % (149/194) of individuals had a first or second degree relative meeting the Revised Bethesda criteria. The average PREMM 1,2,6 score was 10.0% with 43.5% (87/200) falling below 5%. In this large cohort, 15.5% (31/200) had neither a first or second degree relative who met the Amsterdam II or Revised Bethesda criteria nor a PREMM 1,2,6 score of 5% or greater. Conclusions: In order to improve detection of Lynch syndrome in the population, it is important to consider genetic testing in unaffected individuals even in the absence of a known family mutation. Development of guidelines that include having a single affected relative and extra-colonic cancers is needed to support healthcare providers in identifying appropriate patients for testing.
Impact of stereotactic body radiation therapy on patient-reported quality of life in patients with unresectable or recurrent pancreatic cancer.
Authors: Lauren M. Rosati, Zhi Cheng, Scott P. Robertson, Megan N. Kummerlowe, Amy Hacker-Prietz, Christopher Lee Wolfgang, Timothy M. Pawlik, Dung T Le, Lei Zheng, Dan Laheru, Joseph M. Herman
Journal: Journal of Clinical Oncology (2016)

413 Background: The impact of fractionated stereotactic body radiation therapy (SBRT) on patient-reported quality of life (QOL) and physician-reported toxicity in patients with recurrent or locally advanced pancreatic cancer (PCA) was prospectively evaluated. Methods: Forty-two PCA patients were treated with 25-33 Gy using SBRT in 5 fractions on a single-institution study. Both patient- and physician-reported outcomes were evaluated prior to SBRT and 4-6 weeks post-SBRT. Eight outcomes were consistently evaluated among both groups—performance status, fatigue, pain, anorexia, nausea, vomiting, constipation, and diarrhea. Patient-reported QOL metrics were assessed using a 4-point Likert scale on the EORTC QLQ-C30 and QLQ-PAN26, while physician-reported toxicities were graded using the NCI CTCAE version 4.0. Comparisons between those with paired patient- and physician-reported outcomes collected prior to and 4-6 weeks after SBRT were made using the Wilcoxon signed-rank test. Results: Of the 42 patients currently enrolled onto the study, 29 had both patient- and physician-reported outcomes collected prior to and 4-6 weeks after SBRT. Fifty-five percent were female and 83% were Caucasian. The median age at diagnosis was 65.6 years (range, 40.8-86.6). There was no significant impairment of any of the 8 physician-reported toxicities, nor were significant changes observed in patient-reported overall health (p = 0.66) or QOL (p = 0.18) scores following SBRT. Patients felt less worried about their future health (mean change [mD] = -0.45, p = 0.02), and an improvement in feeling less attractive as a result of disease and treatment reached borderline significance (mD= 0.31, p = 0.09). However, patients felt limited in planning activities in advance (mD= 0.45, p = 0.02) and were more constipated (mD= 0.38, p = 0.01) 4-6 weeks post-SBRT. Conclusions: Although the numbers are small, patients with unresectable or locally recurrent PCA do not appear to suffer any detriment of overall health or QOL after receiving a five-day course of SBRT. Moreover, this regimen may lead to a more optimistic point of view on future health and/or level of physical attraction. Clinical trial information: NCT01781728.
The predictive value of single nucleotide polymorphisms in the vascular endothelial growth factor system in patients with metastatic colorectal cancer treated with bevacizumab plus chemotherapy as first-line treatment: Results of the phase III ACT trial NCT00598156 translational study.
Authors: T. Hansen, R. d. Christensen, R. F. Andersen, K. G. Spindler, A. Johnsson, A. K. M. Jakobsen
Journal: Journal of Clinical Oncology (2011)

3600 Background: The combination of bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim of the present study was to investigate the possible predictive value of single nucleotide polymorhisms (SNPs) in the vascular endothelial growth factor (VEGF) system in relation to this treatment. Methods: Paired blood samples and response evaluations were available from 218 of the 249 included patients. All patients were diagnosed with mCRC and received bevacizumab and chemotherapy consisting of fluorouracil and leukovorin or capecitabine in combination with either oxaliplatin (FOLFOX or XELOX, n = 183) or irinotecan (FOLFIRI or XELIRI, n = 66). Genomic DNA was isolated from whole blood, and 5 SNPs in the VEGF-A gene, 1 SNP in the VEGF receptor 1 (VEGFR-1) gene and 3 SNPs in the VEGFR-2 gene were analysed by polymerase chain reaction. Response was evaluated according to RECIST version 1.0. The association between response and genotypes was analysed using the Fishers Exact test. Results: The VEGFR-1 319 C/A SNP was significantly associated with response to bevacizumab plus chemotherapy. Objective response was observed in 36% of the patients with the CC genotype, 40% with CA and 56% with AA, p=0.048, respectively. The response rates also differed significantly between patients with C allele containing genotypes (CC+CA), (39%), and patients homozygous for the A allele (AA), (56%), p=0.015. There was no correlation between response rates and the remaining SNPs. At present no data on survival are available. Conclusions: The VEGFR-1 319 C/A SNP is a potential predictive marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. Similar findings have recently been demonstrated in pancreatic cancer. The results call for validation.
Are St. Gallen endocrine response classes predictive for recurrence rates over time?
Authors: R. H. Koornstra, K. J. Beelen, A. Vincent, P. J. van Diest, S. C. Linn
Journal: Journal of Clinical Oncology (2011)

576 Background: Three endocrine response classes are defined in the St. Gallen guidelines: highly endocrine responsive (ER-H) (expression of both ER and progesterone receptor (PgR) in >50% of tumor cells); incomplete endocrine responsive (ER-I) (expression of ER and/or PgR in <50% of tumor cells); non responsive (ER-N) (no detectable receptors). EBCTCG data show that more than half of the recurrences arise in the period after accomplishing adjuvant tamoxifen. Whether recurrence rates over time vary between the response classes is unknown. This might have implications for optimal treatment duration. We investigated whether the St. Gallen endocrine response classes have different recurrence rates after adjuvant tamoxifen. Methods: We collected primary tumor tissue blocks from patients who had been randomized between tamoxifen (1 to 3 years) vs. no adjuvant therapy (TAMOX trial), with a median follow-up of 9.6 years. Tumor grade, ER and PgR were revised centrally and after constructing a tissue microarray, 646 patients were evaluable. St. Gallen response classes were defined and associated with recurrence free interval (RFI). Schoenfeld residuals and piecewise constant Cox models were used to assess hazard ratios (HRs) in the different time periods. Results: We found a strong association between ER-class and both grade and HER2 (both p < 0.001). A distinction between different time periods in tamoxifen effect was also found, with a loss of the carry-over effect after 6 years (p = 0.02). Despite the association with favorable prognostic factors (N0, low grade, HER2−), patients with higher receptor levels had a higher tendency for late recurrences (p=0.04). This difference was seen in both tamoxifen treated and untreated patients. Conclusions: We suggest grade and HER2 should be taken into account when defining endocrine response classes. ER-H status initially is protective for recurrence, but this changes within 3 years, with even a slightly increased risk later in time. The data support the hypothesis that patients with higher receptor levels may be candidates for prolonged endocrine therapy. HRs for different time periods. 0-2 yrs 2-4 yrs 4-6 yrs 6+ yrs ER-H vs. ER-I 0.5 1.0 1.2 1.4 ER-I vs. ER-N 0.4 0.6 0.7 0.7 Tamoxifen 0.7 0.7 0.3 2.6
Clinical benefit as a critical prognostic factor in metastatic androgeno-independent prostate cancer (AIPC)
Authors: S. Bagattini, G. Gravis, C. Mimoun, N. Salem, B. Esterni, M. Marcy, S. Brunelle, J. Walz, D. Blaise, P. Viens, F. Bladou
Journal: Journal of Clinical Oncology (2008)

16046 Background: Several prognostic factors have been identified with worse outcome in men with metastatic AIPC like Hb, PSA, Alkalin Phosphatase (AP), LDH. In different sequential phase II trials clinical benefit was evaluated using Kanofsky performance scale (KPS) and pain determinate by visual analogic scale (VAS) and morphinic consumption. We explored the impact of these three variables on survival. Methods: Data from 5 phase II trials conducted at our institution were pooled. Eligible patients (pts) had metastatic AIPC with symptomatic disease: KPS ≤ 70%, or VAS ≥ 2 or morphinic consumption ≥ 10 mg/day. Prior hormonal therapy and chemotherapy was allowed. The cox proportional hazard models were used to explore the prognostic significance of clinical benefit response and other important baseline prognostic factors. Results: 84 pts were evaluable for analysis, median age 68 years (44.7–81.5) with a median PSA of 73 ng/ml (0–5835). Median KPS was 80 (60–100), VAS 3 (0–10) and morphinic consumption 0 (0–11760) mg/day. 75% of pts received docetaxel based chemotherapy. In univariate analysis several of the following variables were significant: visceral metastatic sites at baseline, morphinic consumption at baseline, Hb, LDH, AP and albumin at baseline, PSA response at 3 months, tumoral response, VAS response and clinical benefit response. Several independent prognostic factors were identified in multivariate cox proportional hazard analysis including clinical and biological baseline characteristics. There was a statistically significant association between clinical benefit response and survival when categorized as responder vs not responders (HR: 0.3 p=0.006). The median survival in men who had clinical benefit response was 20.9 months for non responders pts median survival was 12,4 months. Visceral metastatic site (p=0,01) KPS at baseline [p=0,013], Hb at baseline [ 0,08–0,45, p=0,00012], AP at baseline [p=0,0003] were also independant prognostic factors in multivariate analysis. Conclusion: Clinical benefit response is a strong predictor of a good overall survival in metastatic AIPC. These results need to be validated prospectively. No significant financial relationships to disclose.
A phase I trial of a recombinant CEA yeast-based vaccine targeting CEA-expressing cancers.
Authors: Marijo Bilusic, James L. Gulley, James W. Hodge, Kwong Tsang, Philip M. Arlen, Christopher Ryan Heery, Myrna Rauckhorst, Sheri McMahon, Chiara Intrivici, Theresa A. Ferrara, Allen Cohn, David Apelian, Alex Franzusoff, Zhimin Guo, Jeffrey Schlom, Ravi A. Madan
Journal: Journal of Clinical Oncology (2012)

458 Background: Saccharomyces cerevisiae (yeast) has been genetically modified to express CEA protein and employed as a heat-killed immune-stimulating, vector-based vaccine. Preclinical studies have shown that yeast CEA vaccine can induce a strong CEA-specific T-cell immune response (IR) and anti-tumor activity. Methods: Patients (Pts) were enrolled in this phase I trial at 3 dose levels: 4, 16, and 40 yeast units (each unit =10 7 yeast particles). The vaccine was administered equally at 4 sites subcutaneously in bilateral inguinal and anterior chest wall regions. Vaccine was administered at 2 week intervals for 3 months, then monthly. Eligible pts were required to have a serum CEA &gt; 5 ng/ml or &gt; 20% CEA+ positive tumor block and no autoimmune history. An expansion cohort of 10 pts was enrolled to focus on IR. Pts had re-staging scans at 3 months, then bimonthly. Peripheral blood was collected for analysis of IR including the Effector/Regulatory T-cell ratio, ELISPOT assay, changes in the myeloid-derived suppressor cells (MDSC) and natural killer cells (NK). Results: 25 pts with progressive metastatic CEA-expressing carcinoma were enrolled; 22 had colorectal adenocarcinoma. Vaccine was well tolerated with no dose limiting toxicities. The most common adverse event was grade 1/2 injection site reaction. Overall, 7 patients had stabilization or declines in serum CEA after treatment. Of them, 5 pts (3 with colorectal cancer) had stable disease beyond 3 months and 1 is still on-going (14 +, 8, 8, 4.5 and 4 months). No anti-CEA antibodies were detected. Post vs. pre-vaccination: a) five out of 9 evaluable pts showed evidence by ELISPOT of CEA-specific T-cell IRs b) 8/16 pts had increased and 8/16 pts had decreased CD4 Effector/Treg ratio and c) 6/13 pts had increased and 2/13pts had decreased NK frequency. Conclusions: Saccharomyces cerevisiae-CEA demonstrated an acceptable safety profile. Although this is an advanced disease population of pts which is not ideal for immune-based therapy, CEA serum stabilizations and CEA-specific IRs were seen in some pts. Randomized studies are required to determine the clinical benefit of this vaccine in a more appropriate patient population for vaccine therapy.
Understanding male breast cancer in the community setting.
Authors: A. L. Ginsburg, D. A. Patt, J. Flinn, J. L. Espirito, M. A. Neubauer, T. H. Cartwright, J. R. Hoverman, L. T. Busby, B. D. Brooks, M. A. Kolodziej, M. A. Sitarik, R. W. Anderson, R. A. Beveridge
Journal: Journal of Clinical Oncology (2011)

e16526 Background: Male breast cancer (BC) affects <1% of the male population and accounts for <1% of the breast cancer cases diagnosed in the United States annually. An estimated 1,970 male patients were diagnosed in 2010, with 390 dying. Although male and female breast cancer patients share disease characteristics, they differ in stage at diagnosis and hormone receptor status, therefore, initial treatment choices. Limited research has been conducted due to the rarity of the disease. Methods: Male patients with invasive and noninvasive BC identified within the US Oncology iKnowMed (iKM) database between January 2006 and January 2010 were included. Patterns of diagnosis and treatment were characterized by the median age; distribution of stage and grade; estrogen receptor (ER), progesterone receptor (PR), HER2neu status; and treatment characteristics of the neoadjuvant and adjuvant chemotherapy prescribed. Results: Of the 146 patients identified within the iKM database, the median age at diagnosis was 62 years. The distribution by stage was 15% stage I, 29% IIa, 13% IIb, 7% IIIa, 9% IIIb, 5% IIIc, and 16% IV, with 6% of patients missing staging information. Consistent with published literature, hormone receptor positivity was higher than seen in women; 88% ER+, 72% PR+, but Her2neu status was lower; only 10% positive. The majority of patients with early-stage disease received neoadjuvant/adjuvant therapy: 71% stage I, 60% Ia, 69% IIa, 63% IIb, 80% IIIa, 77% IIIb, 75% IIIc, and 13% stage IV. Conclusions: In our study, the median age at diagnosis was 62 years, which is less than the previously characterized age of 67. Similar to other studies, the overwhelming majority of patients were positive for ER, and Her2neu amplification was lower than among women. While the majority of patients (54%) presented with stage I and II disease, a high percentage of patients had advanced-stage disease. Chemotherapy utilization was high among all stages of disease. (Jemal A, et al. CA Cancer J Clin 2010;60: 277-300; Giordano SH, et al. Cancer 2004;101: 51-57; Gomez-Raposo et al. Cancer Treat Rev 2010;36: 451-457; Korde LA, et al. JCO 2010;28: 2114-2122.)
Investigation of thrombopoietin (TPO) function in primary chronic lymphocytic leukemia cells.
Authors: R. D. Loberg, S. Wang, S. D. Patterson, I. McCaffery
Journal: Journal of Clinical Oncology (2011)

6613 Background: Immune thrombocytopenia purpura (ITP) is associated with poor prognosis of chronic lymphoid leukemia (CLL). TPO mimetics have been approved for the treatment of chronic ITP and have been suggested for the use in CLL-related ITP. Before testing this hypothesis in the clinic, the hypothesized role of TPO function in CLL cells was investigated. TPO mimetics stimulate platelet production via activation of the TPO receptor, c-Mpl, thus we analyzed c-Mpl cell surface expression and functional response to TPO in primary CLL cells in samples collected from early and late stage CLL patients. Methods: Peripheral blood was collected from CLL patients and mononuclear cells isolated by Ficoll separation. CLL cells were analyzed by flow cytometry and gated based upon viability and CD5+/CD19+ expression. c-Mpl expression was measured using a tested and validated novel c-Mpl-specific monoclonal antibody by flow cytometry. CLL samples were stimulated with TPO (10 ng/mL for 10 min) and induction of pSTAT5 was measured by intracellular flow cytometry. Platelets (CD41a+) provided internal controls for c-Mpl expression and response to TPO and phorbol myristate acetate was used as a control stimulation to demonstrate that CLL cells were responsive. Results: Analysis of expression and function of c-Mpl was performed on CLL samples (n=89) including 14 patients with thrombocytopenia. While robust c-Mpl expression was observed consistently in platelets from normal and CLL patients (normal: 31.90 ± 2.83, CLL: 26.76 ± 3.31; mean ± SEM), no significant expression of c-Mpl was observed on CD5+/CD19+ CLL cells (1.06 ± 0.01; mean ± SEM). No activation of downstream signaling (pSTAT5) was detected in CLL cells in any of the samples stimulated with TPO (normal: 0.90 ± 0.007, CLL: 1.04 ± 0.02; mean ± SEM), while robust pSTAT5 was detected in platelets (normal: 10.22 ± 0.29, CLL: 6.21 ± 0.23; mean ± SEM). Conclusions: A robust/sensitive platform was developed to profile biologically relevant c-Mpl expression and function in platelets. Using this platform we demonstrate a lack of c-Mpl expression and functional response to TPO challenge in CLL cells suggesting that CLL cells are unlikely to be activated in patients treated with TPO mimetics.