tbuckley/cabot-search huggingface dataset:
Identification of therapeutic targets in angiosarcoma
Authors: V. Ravi, S. Kim, D. Dim, D. Hicks, C. Aggarwal, G. Hostetter, R. T. Cheney, M. Bittner, D. L. Trump, M. K. Wong
Journal: Journal of Clinical Oncology (2007)

10030 Background: Human angiosarcoma is an aggressive malignancy with ability to invade locally and metastasize widely. Even with a multimodality approach, the local recurrence rate is 81% and 5 year disease-free survival is 17% for all comers. Durability of the responses to treatment options such as paclitaxel is 4 to 5 months. Our previous work shows that enhanced cell migration and invasion are integral to the chemoresistant angiosarcoma phenotype. However the molecular mechanism of this is unknown. Methods: In order to address this and to identify new therapeutic strategies, we analyzed formalin fixed paraffin embedded (FFPE) archival angiosarcoma specimens from 17 consecutive patients at our institution to identify aberrations at the DNA level that were highly prevalent. DNA was extracted from FFPE angiosarcoma specimens using the proteinase K method. Good quality DNA with an yield more than 5 micrograms was obtained from 10 out of 17 patients and these samples were assayed for DNA dosage differences compared to genomic reference DNA using array comparative genomic hybridization. High density 244K Agilent arrays were used to evaluate these specimens to enhance the precision of the estimates in this rare disease. Results: Statistically significant (p&lt;0.001) aberrations with prevalence greater than 50% were noted in several genes including NOTCH2, MAML1 (notch signaling intermediate), oncomodulin, calnexin, sequestosome1, zinc finger proteins and ADAMTS2. This is particularly important since Notch and its ligand Jagged are developmental genes critical to tumorigenesis and there is emerging evidence of their role in endothelial activation. Conclusions: Aberrations involving the notch signaling pathway occur with a high prevalence in angiosarcomas and may serve as a target for therapeutic intervention. No significant financial relationships to disclose.
A genome-wide linkage study of lethal prostate cancer predisposition gene in a set of high-risk pedigrees.
Authors: Lisa A Cannon-Albright, Craig Teerlink, Anitha Alex, Frederick S. Albright, Robert A Stephenson, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2015)

159 Background: Using the unique Utah genealogical resource that links 12 generations of genealogy data to a statewide cancer registry from 1966 and statewide death certificates from 1904 we have identified a set of high-risk prostate cancer pedigrees with multiple cases having died from prostate cancer. Methods: Clusters of prostate cancer cases descended from a common ancestor, among whose descendants is observed a statistical excess of prostate cancer (high-risk prostate cancer pedigrees) were recruited and sampled. Pedigrees with 4 or more cases dying from prostate cancer (as evidenced by inclusion as a cause of death on a Utah death certificate) were genotyped with 720k high-density SNPs across the genome. Linkage analysis with markers not in linkage disequilibrium was performed to identify regions hypothesized to contain a prostate cancer predisposition gene. Results: A single extended Utah high-risk prostate cancer pedigree including 6 distantly related sampled prostate cancer cases who went on to die as a result of their cancer showed significant evidence for linkage at chromosome arm 4q24 (LOD score = +3.28), with 5 of the 6 cases having inherited the same region of chromosome 4 from a common ancestor. Conclusions: The inability of association studies to identify prostate cancer predisposition genes has returned focus to linkage studies of highly informative high-risk pedigrees, which provide power for identifying and localizing regions of interest for predisposition genes. A focus on only those cases who are members of high-risk prostate cancer pedigrees, who also went on to die as a result of their prostate cancer, has resulted in the identification of evidence for a prostate cancer predisposition gene on chromosome arm 4q24, confirming a previous GWAS that reported association with prostate-cancer-specific-survival (Pomerantz MM et al., 2011) in this region harboring TET2 (a tumor suppressor gene involved in pathogenesis of acute myeloid leukemia, myelodysplastic syndrome, and myeloproliferative neoplasms), and PP2A (implicated in androgen receptor regulation in prostate cancer cell lines).
Quality of life (QOL) and cognitive performance among irradiated brain cancer patients.
Authors: M. J. Naughton, L. D. Case, C. A. Meyers, M. E. Loghin, E. G. Shaw, T. J. Saphner, B. G. Sleckman, J. K. Giguere, G. J. Lesser, S. R. Rapp
Journal: Journal of Clinical Oncology (2010)

9131 Background: Cognitive symptoms are reported among cancer patients following treatment. QOL can be affected by cognitive problems, treatment-related fatigue and other symptoms. We examined the relationship between cognitive performance and the QOL of brain cancer patients, after adjusting for fatigue, demographic and clinical characteristics. Methods: Baseline data were analyzed from 82 participants of a phase III trial of the acetylcholinesterase inhibitor, donepezil, following whole or partial brain irradiation at least 6 months prior to initial QOL and cognitive testing. Multiple regression analyses were used to examine the association of demographic variables (age, education, sex, race), diagnosis (primary vs. metastatic), ECOG performance status (PS) (0-2), fatigue (FACIT-Fatigue subscale), and a cognitive performance composite score (CSS) (comprised of the Controlled Oral Word Association Test, Hopkins Verbal Learning Test-Revised, Digit Span Test, Trail Making Test, Grooved Pegboard) on QOL, measured by the Fact-Brain (FACT-Br) total score. Results: Patients had a mean age of 52 (range 19–85), half were male (50%), and 83% had ≥ a high school education. ECOG PS was predominantly 0 (51%) or 1 (41%), and 37% had metastatic disease. In regression analyses predicting the FACT-Br total score, better cognitive performance (CSS) predicted higher QOL (p=.01), and fatigue predicted lower QOL (p<0.0001). Age (p=0.36), sex (p=0.16), education (p=0.22), race (p=0.94), diagnosis (p=0.70), and ECOG PS (p=0.96), were not significant predictors of QOL. In subanalyses further exploring the relationship between the Fact-Br subdomains (social, emotional, functional, physical, brain symptoms) and the CSS, only the brain symptoms subscale was related to poorer cognitive performance. Conclusions: Among brain cancer patients who had undergone brain irradiation at least 6 months prior to cognitive testing, cognitive performance was significantly associated with patients' self-reported brain symptoms, but no other domains of QOL. Fatigue was significantly associated with poorer QOL. Interventions to improve cognitive functioning and decrease fatigue may improve the QOL of irradiated brain cancer survivors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Pfizer Eisai Eisai, Pfizer
Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer
Authors: V.F. Semiglazov, E.E. Topuzov, J.L. Bavli, V.M. Moiseyenko, O.A. Ivanova, I.K. Seleznev, A.A. Orlov, N.Y. Barash, O.M. Golubeva, O.F. Chepic
Journal: Annals of Oncology (1994)

A phase III randomized trial was activated to evaluate the efficacy of preoperative combined chemotherapy and radiotherapy as compared to preoperative radiation therapy alone, in patients with breast cancer presenting with a clinical stage of IIb-IIIa (TNM classification).From 1985 to 1990, 271 patients, aged 27-55 years, with stage IIb-IIIa breast cancer were randomized to receive either one or two courses of thiotepa 20 mg (i.m. injection) on the days 1, 3, 5, 7, 9, 11 (total dose per course 120 mg), methotrexate 40 mg/m2, i.v. on days 1 and 8, and 5-fluorouracil 500 mg/m2, i.v. on days 1 and 8 (TMF regimen) plus radiotherapy (Group I, 137 patients), or preoperative radiation therapy only (Group II, 134 patients). After the preoperative treatment all patients underwent mastectomy and complete axillary clearance, and then received 4-6 courses of TMF. The trial was conducted in a single institution (N.N. Petrov Research Institute of Oncology, St. Petersburg).Histopathological assessment of the mastectomy specimens showed complete regression of the tumour in 29.1% of the patients in group I and in 19.4% of the patients e.c. in group II. The estimated 5-year overall survival percentages were 86.1% for group I, and 78.3% for group II (P > 0.05). 5-year disease-free survival percentages were 81.0% and 71.6%, respectively (p < 0.05).Despite the low number of the patients included in the trial, we were able to detect a significant improvement in treatment results with a combination of chemotherapy and radiation therapy given prior to mastectomy over those of local therapy alone with radiation therapy followed by mastectomy, for average- and high-risk patients with operable breast cancer.
Defining Auditory-Visual Objects: Behavioral Tests and Physiological Mechanisms
Authors: Jennifer K. Bizley, Ross K. Maddox, Adrian K.C. Lee
Journal: Trends in Neurosciences (2016)

Crossmodal integration is a term applicable to many phenomena in which one sensory modality influences task performance or perception in another sensory modality. We distinguish the term binding as one that should be reserved specifically for the process that underpins perceptual object formation. To unambiguously differentiate binding form other types of integration, behavioral and neural studies must investigate perception of a feature orthogonal to the features that link the auditory and visual stimuli. We argue that supporting true perceptual binding (as opposed to other processes such as decision-making) is one role for cross-sensory influences in early sensory cortex. These early multisensory interactions may therefore form a physiological substrate for the bottom-up grouping of auditory and visual stimuli into auditory-visual (AV) objects.
Pathologic correlation of 18F-16β-fluoro-5α-dihydrotestosterone (FDHT) and FDG PET in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Jarett L. Feldman, Josef J. Fox, Danny F. Martinez, Karen A. Autio, Jeremy C. Durack, John Humm, Heiko Schöder, Somali C. Gavane, Kristen Rebecca Curtis, Samantha Meredith Balakirsky, Rachel Mathilda Cohen, Howard I. Scher, Steven M. Larson, Michael J. Morris
Journal: Journal of Clinical Oncology (2014)

5016 Background: We have demonstrated the feasibility, pharmacokinetic properties, tumor targeting, and the preliminary prognostic value of FDHT as a PET tracer for prostate cancer (PCa). As part of an imaging trial, we performed biopsies (bx) to assess the tumor-detection rate of FDHT and compared it with FDG PET. Methods: Pts with progressive mCRPC identified on standard imaging (CT, MRI, and bone scintigraphy) from 2007 to 2013 underwent FDHT and FDG PET/CT. Bx locations were selected by a consensus panel prioritized on the basis of: FDHT & FDG positivity, FDHT & FDG mismatch, and standard imaging positivity & any PET mismatch. Bx were considered positive (pos) if PCa was identified and negative (neg) if benign tissue or a secondary malignancy was sampled. Results: A total of 64 bx (28 soft tissue, 36 bone) were obtained from 54 pts of which 62 were evaluable (2 were non-diagnostic). 53/62 (85%) bx were pos and 9/62 (15%) were neg for PCa. FDHT and pathology correlated (pos/pos or neg/neg) in 56/62 (90%). FDG and pathology correlated in 57/62 (92%). All 47 FDHT pos lesions were pos for PCa. Notable mismatches were: FDHT neg/biopsy pos appeared in 6/53 (11%) cases of which 3 displayed neuroendocrine (NE) features and 2 were poorly-differentiated (PD) adenocarcinoma. FDG pos/bx neg for PCa appeared in 5/62 (8%) cases; 3 were secondary malignancies. The histopathologic correlation is provided in the table below. Conclusions: FDHT is highly effective at identifying adenocarcinoma of the prostate as demonstrated by pathology. A subset of lesions that are not detected on FDHT, but present on FDG imaging, represent neuroendocrine/poorly-differentiated PCa; these require further investigation in regards to prognosis and response to treatment. Clinical trial information: NCT00588185.Biopsy correlation of evaluable lesions with imaging findings (N=62). Imaging results Biopsy pos for PCa Biopsy neg for PCa Total lesions (# of ptsa) FDHT FDG CT/MRI or BS Soft tissue Bone Soft tissue Bone + + + 18 29 0 0 47 (44) + - + 0 0 0 0 0 - + + 4b 2c 5d 0 11 (10) - - + 0 0 1 3 4(4) a8pts obtained > 1 bx b2bxs had NE features and 2bxs had PD PCa c1bx had NE features d 3bxs had a secondary malignancy (2 gastrointestinal, 1 sarcoma) and 2 had benign pathology.
Doxorubicin (DXR) and prolonged infusion gemcitabine (GMC) as first-line treatment in advanced soft tissue sarcomas (STS). A phase II trial of the Spanish Group for Research in Sarcomas (GEIS)
Authors: A. Lopez-Pousa, J. Buesa, A. Casado, J. Garcia Del Muro, A. Poveda, J. Maurel, J. Martin, C. Balaña, J. Martinez
Journal: Journal of Clinical Oncology (2004)

9033 Background: Results from a previous phase I trial (ASCO 2003, abst.3317) demonstrated MTD for GMC 800 mg/m2 by 10 mg/m2/min perfusion associated to DXR 60 mg/m2 Methods: April'02 to December'03 36 patients were included in a phase II trial of first-line treatment in advanced STS with DX at 60 mg/m2 (d 1), followed by GMC 800 mgr/m2 administered in 80 minutes (d 1,8) every 3 weeks. Results: 36 patients ECOG 0–2, metastatic/unresectable STS entered the trial. Results from 23 patients: male/ female 13/10; ECOG 0 = 5 pts, 1 = 15 pts, 2 = 3 pts. Median age 56 (23–76)y. Histology: Lipos. 6, MFH 4, Leiomio 2, other 11. Primary tumor: extremities 8, retroperitoneal 7, uterine 2, truncal 2, other 4. A median of 6 (1–9) and a total of 93 cycles (cy) were administered. Toxicity by patient (23): neutropenia grade(G)IV 7 (30%), GIII 9 (39%); anemia GIII 4 (17%), GII 7 (30%); thrombocytopenia GIV 2 (8%), GIII 3 (13%), GII 4 (17%) pts. Neutropenic fever in 5 (21%) pts. Grade III/IV mucositis in 14 (60%) pts. Toxicity by cy (93): neutropenia GIV 16 (17%), GIII 24 (26%), GII 10 (10%); anemia GIII 7 (7%), GII 18 (19%) of cy; GIII/IV thrombocytopenia in 8 (8%); Neutropenic fever in 8 (8%) cy. Mucositis GII in 12 (13%) and GIII/IV in 17 (18%) of cy. Dose reduction was performed in 47/93 cy. There were no toxic deaths. In 20 evaluable patients 2 PR and 13 SD were obtained. Conclusions: DXR and GMC delivered by prolonged infusion has some activity in advanced STS. Hematological toxicity and mucositis are relevant and limiting adverse effects. No significant financial relationships to disclose.
Long-term toxicity monitoring via electronic patient reported outcomes in end-stage chemotherapy patients
Authors: E. M. Basch, A. Iasonos, A. Barz, A. Culkin, M. G. Kris, D. Artz, P. Fearn, J. Speakman, H. I. Scher, D. Schrag
Journal: Journal of Clinical Oncology (2007)

9025 Background: In cancer trials, clinicians are required to report patient toxicity symptoms using the NCI's Common Terminology Criteria for Adverse Events (CTCAE). Alternatively, patients could provide this information directly as patient-reported outcomes (PROs). This strategy is advocated by the FDA and is standard in non-oncology trials. But it remains unclear if this approach is feasible over long periods, or in patients with high symptom burdens. Methods: Lung cancer patients starting chemotherapy were selected for this feasibility assessment because they are relatively older, sicker, and less web avid than other cancer populations. A patient adaptation of the CTCAE was uploaded to a web portal for self-reporting, including 15 items common in this population. Over 16-months, participants were encouraged but not required to login and complete an online questionnaire at clinic visits via a touchscreen computer. Optional home access was provided without reminders. Results: Beginning in June 2005, 125 patients were approached and 107 enrolled. Reasons for refusal included “too distressed” and “dislike computers.” Mean enrollment was 42 weeks (1–71), during which 35% of participants died. The average number of clinic visits was 12 (1–40). At each consecutive visit most patients (75–85%) logged in without significant attrition over time, even up to the 40th visit. Reasons for failure to login included “lack of reminder” and “inadequate time.” Prior computer experience was associated with greater adherence (p=0.017), but there was no relationship with sex, age, education, stage, or performance status. Most (90%) found the system useful and would recommend it to others, but only 77% felt it improved communication. Although 76% had access to home computers, only 15% voluntarily self-reported from home. Conclusions: Self-reporting is a feasible long-term strategy for toxicity symptom monitoring in most chemotherapy patients, including those with high symptom burdens. In future evaluations, adherence may be improved with more consistent personal encouragement to login in clinic, electronic reminders for home users, consistent staff response to patients’ symptom reports and alternative data collection methods for those who fail to report electronically. No significant financial relationships to disclose.
Oral adjuvant treatment choices and local recurrence risk in early stage breast cancer
Authors: S. A. Russo, M. Akbari, V. R. Grann, J. S. Jacobson, C. Chen
Journal: Journal of Clinical Oncology (2006)

10625 Background: Among women (W) with early-stage breast cancer (BC) treated with lumpectomy and radiation therapy (RT), those who also receive oral adjuvant therapy (OAT) have a lower risk of local recurrence (LR). The purpose of this study was to evaluate the associations of age (A), race/ethnicity (RE), education (E), socioeconomic status (SS), LR rate, and knowledge about potential side effects (SE) with W’s willingness to receive OAT. Methods: Between 6/05 and 9/05, we asked W with (+) and without (−) BC to participate in an IRB-approved survey. The survey questionnaire presented W with clinical vignettes including information about RT ± 5 years of OAT and the LR and SE associated with treatment options. It then asked W to choose between the treatment options and to rate them, using a time trade-off method, given LR and SE. Results: The distribution of the 161 respondents (55 (+)BC and 106 (−)BC) by A, RE, E, SS is shown in the table below. A and RE were associated with a W’s choice of combined modality treatment (CMT) consisting of RT and OAT, to decrease the risk of LR (p &lt; 0.009 and p &lt; 0.056). Stratified analysis showed an association between CMT and E (p &lt; 0.006) in W (+)BC; A (p &lt; 0.04) and SS (p &lt; 0.04) were associated with CMT choice when SE were described. In W (−) BC, RE (p &lt; 0.02) and SS (p &lt; 0.04) were associated with CMT choice when SE were described. Compared to W who had used oral contraceptive agents (OCA), women who did not use OCA were 45% less likely to trade time to decrease their risk of LR by taking OAT when told about similar SE between OCA and OAT (OR = 0.55, 95% CI 0.28, 1.09), but this association was not statistically significant. Conclusions: W of various A, RE, E and SS who were given information about treatment choices with LR rates chose therapies that gave them the best chance of disease-free survival. For W (+) BC history, level of E significantly influenced the choice to proceed with CMT. A, RE and SS influenced CMT choice when SE were described. W who had used OCA in the past may have been less concerned than others about potential side effects of OAT. [Table: see text] No significant financial relationships to disclose.
Tumor-targeting human L19IL2 monoclonal antibody-cytokine fusion protein in combination with DTIC in chemotherapy-naïve stage IV melanoma patients.
Authors: B. Weide, T. K. Eigentler, A. Romanini, F. G. De Braud, L. Giovannoni, D. Neri, H. Menssen, C. Garbe
Journal: Journal of Clinical Oncology (2010)

8555 Background: L19IL2 is a tumor targeted immunocytokine constituted by a single chain Fragment variable (scFv) format directed against the extradomain-B of fibronectin and the human cytokine interleukin-2 (IL2). The recommended dose for monotherapy of advanced solid cancer patients was established to be 22.5 Mio IU L19IL2 on days 1, 3, and 5 of a 21-day cycle in a previous dose escalation study. Methods: Chemotherapy-naive patients with advanced melanoma and normal LDH were treated with L19IL2 as an i.v. infusion at a dosage of 22.5 Mio IU L19IL2 on days 1, 3 and 5 every 21 days in combination with DTIC 1,000 mg/m2 on day 1 for up to 6 treatment cycles. In the subsequent maintenance phase 22.5 Mio IU L19IL2 was applied biweekly, while DTIC was omitted. Tumor assessment was performed every 6 weeks. Data on safety and efficacy were evaluated using CTC v3.0 and RECIST criteria, respectively. Results: 22 patients were evaluable. Median age was 54.5 years (20-83). Treatment was well tolerated. There were no treatment related deaths; details of CTC evaluation will be presented. Median number of applied induction cycles was 6 (range 2-6), 6/22 patients entered the maintenance phase. Several RECIST-confirmed tumor responses and durable disease stabilizations were observed. Updated efficacy data will be available for presentation. Conclusions: L19IL2 at a dose of 22.5 Mio IU L19IL2 on days 1, 3, and 5 of a 3-weekly schedule can be safely combined with standard DTIC in metastatic melanoma patients. Toxicity was manageable and reversible. Preliminary evaluation suggests clinical activity of the L19IL2/DTIC regimen in metastatic melanoma patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Philogen Philogen, Bayer Philogen