tbuckley/cabot-search huggingface dataset:
Cancer information acquisition differs by patient characteristics
Authors: S. W. Gray, A. Romantan, B. Kelly, S. Ramirez, R. Stevens, N. Wong, A. Kim, J. S. Schwartz, R. Hornik
Journal: Journal of Clinical Oncology (2006)

16008 Background: While cancer patients have access to multiple sources of information, including mass media, the internet and personal and professional contacts, little is known about use of these sources in decision making. Methods: 43 patients with one of three cancer types (37% breast, 28% colon and 35% prostate, 58% stage 1) randomly recruited through the Pennsylvania Cancer Registry completed semi-structured in-person interviews about cancer related information acquisition and decision making. (Median age 59 (range 40–71), 47% male, 79% white, 74% married, mean education 14.6 years (SD = 2.48). Separate analyses were performed for actively looking for information (seeking) vs. passively coming across information (scanning). The primary endpoint was patient use of information sources in cancer related decision making. Results: All cancer patients reported use of both interpersonal and mass media information sources in making cancer related decisions. Patients with more advanced cancer (stage 3 vs. stage 1 or 2), higher education, and younger age were more likely to actively seek cancer information (χ 2 = 4.7, p = .095, χ 2 = 10, p = .04 and χ 2 = 8.6, p = .07). Breast cancer patients and women were more likely to report passively coming across information (χ 2 = 9.1, p = .058 and χ 2 = 5.1, p = .078). Conclusions: Cancer information acquisition varied according to patient characteristics. Seeking was reported more in younger patients and those with higher formal education, and more advanced cancer. Highly educated and younger patients may be better at navigating the information environment; patients with more advanced cancer may have increased anxiety causing them to actively seek information. Scanning was more common among breast cancer patients and women. Women may attend to general health related information more than men or information about breast cancer may be more accessible and pervasive than information on colon or prostate cancer. No significant financial relationships to disclose.
Hepatic veno-occlusive disease (VOD) after allogeneic hematopoietic cell transplantation (HCT) in adults conditioned with busulfan (Bu) and cyclophosphamide (Cy) at a single center: A retrospective comparison of oral vs. intravenous Bu
Authors: J. H. Lee, J. H. Lee, S. J. Choi, S. E. Kim, M. Seol, Y. S. Lee, C. J. Park, H. S. Chi, J. S. Lee, K. H. Lee
Journal: Journal of Clinical Oncology (2004)

6647 Background: Hepatic VOD is one of potentially fatal toxicities after allogeneic HCT and is caused by high-dose chemotherapeutic agents, one of which is Bu. High interpatient variability following oral administration of Bu (O-Bu), which is ascribed to unpredictable and erratic intestinal absorption, contributes to the occurrence of hepatic VOD. Intravenous administration of Bu (I-Bu) has shown dose assurance with predictable pharmacokinetics. We investigated the occurrence of hepatic VOD after allogeneic HCT in adults conditioned with Bu-Cy and retrospectively compared I-Bu with O-Bu. Methods: All 241 patients, who were conditioned with Bu-Cy and who underwent allogeneic HCT between December 1993 and August 2003 at the Asan Medical Center, were included in this study. The first 187 patients received O-Bu (1 mg/kg x 16 doses), and thereafter 54 patients received I-Bu (Busulfex®, 0.8 mg/dg x 16 doses). Various hemostatic parameters were determined at 5 time points (day –7, 0, 7, 14, and 21). A diagnosis of VOD was made according to clinical criteria. Results: Hepatic VOD occurred in 41.7% of O-Bu group and 18.5% of I-Bu group (P=0.002). Multivariate analysis of baseline clinico-laboratory variables revealed that O-Bu vs. I-Bu (P=0.008, OR 2.793, 95% CI 1.310–5.956) and CSA/MTX vs. CSA for GVHD prophylaxis (P=0.044, OR 2.281, 95% CI 1.022–5.087) were independent risk factors for the occurrence of hepatic VOD. Eleven patients (5.9%) of O-Bu group developed severe VOD, while none of I-Bu group developed severe VOD. On day 7 and thereafter, patients with VOD showed significantly lower levels of antithrombin III (AT3) and higher levels of tPA and PAI-1 when compared to patients without VOD. Levels of AT3 were significantly higher in I-Bu group on days 7, 14, and 21 than O-Bu group, but levels of tPA and PAI-1 were not significantly different between two groups. Conclusion: In adults conditioned with Bu-Cy, I-Bu showed significantly decreased incidence of hepatic VOD and less hypercoagulability after allogeneic HCT compared to O-Bu. No significant financial relationships to disclose.
Prostate-specific antigen velocity as a predictive biomarker in a prospective prostate cancer screening study (IMPACT study).
Authors: Christos Mikropoulos, Christina Selkirk, Sibel Saya, Elizabeth Bancroft, Tokhir Dadaev, Charles Brendler, Edward Saunders, Daniel Leongamornlert, Elizabeth Page, Clara Cieza Borrella, The IMPACT study Collaborators And Steering Group, Sue Moss, Zsofia Kote-Jarai, Brian Helfand, Ros A. Eeles
Journal: Journal of Clinical Oncology (2015)

16 Background: We retrospectively assessed the clinical application of Prostate Specific Antigen Velocity (PSA V) in the IMPACT study (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in men at higher genetic risk and controls). This is a case-control prostate cancer (PrCa) screening study for men with a known genetic predisposition to PrCa; participants with a single PSA reading above 3ng/ml are offered diagnostic TRUS prostate biopsies (PB). Methods: We calculated PSA velocity (PSA V) using all three validated methods, including the arithmetic mean, the linear regression and the first and last readings equations. Pearson chi-square test was used to compare PSA V between four genetic groups: BRCA1 carriers and BRCA1 negative controls and BRCA2 carriers and BRCA2 negative controls. Results: PSA V data were evaluated in 191 men who underwent a PB with a total of 57 PrCas diagnosed. PSA V using both a threshold of 0ng/ml/year and 0.75ng/ml/year in any of the three methods was not predictive of PrCa diagnosis in BRCA1/2 controls and BRCA1 carriers. Conversely, BRCA2 carriers with a PSA V over 0.75ng/ml/year (by linear regression) were 5 times more likely to be diagnosed with PrCa [95%CI=1.5-14; p=0.003]. Interestingly PSA V using linear regression was predictive of clinically significant tumours as defined by Gleason Score (GS) &gt;= 7. Regardless of their genetic status, men with a PSA V over 0.75/ng/ml/year were 3 times more likely to have a clinically significant PrCa [95% CI: 1.006-11.107; p=0.045] whereas men with a BRCA2 mutation were 12 times more likely [95%CI: 1.1-98; p=0.039]. Conclusions: PSA V is an important tool for identifying which men with a BRCA2 mutation would benefit from a prostatic biopsy and could be incorporated into a predictive model, along with the total PSA value. PSA V also predicts for tumour aggressiveness regardless of genetic predisposition, but more so for those with a known high risk gene mutation. Clinical trial information: NCT00261456.
Quality-of-life (QoL) impairment in melanoma patients receiving high-dose interferon alpha 2b (IFNa2b)
Authors: P. Mohr, A. Hauschild, K. Rass, U. Trefzer, A. Enk, T. Haalck, J. Koller, R. Gutzmer, T. Küchler, M. Weichenthal
Journal: Journal of Clinical Oncology (2009)

e20011 Background: High-dose interferon (HDI) for patients with malignant melanoma (MM) has consistently demonstrated benefits as an adjuvant treatment. Side effects and impairment of QoL have played a major role in patients motivation to continue treatment. The adjuvant, randomized, controlled phase III DeCOG MM-ADJ-5 trial evaluates QoL and tolerability of pulsed high-dose intravenous (iv) IFNα2b compared to standard HDI regimen. In the pulsed arm, 3 courses of IFNα2b, 20 Mio IU/m 2 iv 5 days a wk for 4 wks, repeated every 4 months was administered, whereas the subcutaneous (sc) treatment was 10 Mio IU/m 2 3 times a wk for 11 months, after 4 wks of iv therapy. As a secondary endpoint, health related QoL was evaluated during iv and sc treatment and during treatment free intervals. Methods: 631 patients have been recruited for an expected 300 events (distant metastasis) during 4 years of follow-up. A planned interim analysis was performed after a third of the expected events occurred. The EORTC QLQ-C30 questionnaire modified for typical IFN side effects, was administered to pts before therapy, at 4, 16, 24, and 40 wks of treatment. Global QoL questions were completed by pts weekly by a visual analogue scale over the entire year of treatment. Results: Out of 377 patients having completed treatment, 300 were evaluable for QoL analysis. The iv HDI treatment led to a globally decreased QoL score in 84% of patients. During the 4 wk course of iv IFN, impairment of QoL was mainly due to physical symptoms. During the sc treatment phase, global QoL remained reduced by an average of 24%, despite dose adjustments in a majority of patients. Analysis of particular dimensions of decreased QoL revealed that fatigue was the most important determinant, especially during continuous treatment. In contrast, depression only played a minor role, being less important than physical and cognitive impairment. Conclusions: QoL impairment caused by long term sc HDI is mostly mediated by chronic fatigue, and more likely to interfere with treatment adherence than short term iv HDI treatment. [Table: see text]
TOX3 as a novel biomarker in luminal B breast cancer.
Authors: Jenny Jimmy Hong, Akop Seksenyan, Xiaopu Yuan, Beatrice Knudsen, William Audeh, Jonathan Kaye
Journal: Journal of Clinical Oncology (2015)

130 Background: A breast cancer (BC)-associated SNP is found in an enhancer region of the TOX3 gene, which encodes a nuclear protein expressed in ER + mammary epithelial cells but with unknown biological function. As the disease-risk allele reduces TOX3 expression, we proposed that a decrease in TOX3 might favor a progenitor cell state that is more susceptible to tumorigenesis. However, in the context of BC, our data has implicated TOX3 as a tumor promoter. Indeed, high TOX3 gene expression is significantly associated with poor outcome among patients with luminal B (LumB) disease. The Oncotype DX assay predicts likelihood of distant recurrence in ER + early stage BC, improving patient selection for adjuvant chemotherapy. However, LumB subtypes often have an intermediate recurrence score (RS), where the absolute benefit of chemotherapy is unclear. Thus, we investigated whether TOX3 expression might provide additional discriminatory power. Methods: Tumor specimens were obtained from Cedars-Sinai Medical Center in a retrospective study. Tissue microarrays of 200 histologically-defined LumB breast tumors (ER + Her2 -/+ Ki67 &gt; 14%), half of which with associated Oncotype DX data, were stained with an anti-TOX3 monoclonal antibody, to correlate with RS and clinicopathologic outcomes. Results: TOX3 protein was expressed in a significant subset of LumB tumors. Using image analysis to create a histoscore, we found no correlation between TOX3 expression and RS. TOX3 expression was also not associated with frequency of Ki67 + cells, patient age, or tumor size. Further in-depth clinico-pathologic evaluation and prognosis data will be reported. Conclusions: Despite overall efficacy of adjuvant chemotherapy in early stage BC, many patients are exposed to the associated risks without deriving significant benefit. A number of lines of evidence suggest that TOX3 renders tumors more aggressive and metastatic. The lack of correlation of TOX3 expression and RS may suggest a facet of the biology of ER + aggressive cancers that may not be addressed by the Oncotype DX assay. Thus, prospective studies examining recurrence risk and chemotherapy benefit may need to be expanded to integrate TOX3 expression as an adjunct novel biomarker to guide optimal personalized therapy for BC.
Interstitial high dose rate brachytherapy and cervical dissection the management of recurrent head and neck cancers
Authors: A. C. Pellizzon, P. Novaes, J. Salvajoli, R. Fogaroli, M. Maia, R. Ferrigno
Journal: Journal of Clinical Oncology (2006)

15529 Background: The literature is scarce regarding the use of interstitial high dose rate brachytherapy (I-HDR) in this setting, most reports are focused on primary tumors. We performed a retrospective analysis of a single institutional polity of treatment using salvage surgery associated to I-HDR at the Radiation Oncology Departments, Hospital do Cancer A.C. Camargo, São Paulo, Brazil. Methods: All patients with recurrent cervical cancer treated with combination of surgery and I-HDR, with or without the addition a new second course of EBRT, biopsy proven squamous cell carcinoma (SCC), Karnofsky performance status up to 60 and, no evidence of distant metastasis. Patients treated from October, 1994 to June, 2004, were retrospectively selected. Results: Twenty-one patients with median age of 53.5 years (range 31–73) were included in the study. The ratio male to female was 3.2:1 and the follow up time ranged from 6 months to 82 months (median - 36 months). Thirteen (61.9%) had a previous course of irradiation, in whom the median total I-HDR dose was 25.8 Gy, inferior when compared to the median dose of 40.7 Gy given to patients without a previous course of EBRT (p = 0.011), but with no influence in OS (p = 0.9436). The only predictive factor for an improved LFRS and OS was margin status, p = 0.0007 and p = 0.0002, respectively Conclusions: Recurrent HNC should have aggressive salvage procedures as they they are life threatening. Although the number of patients is small, our preliminary results are inspiring, leading to a relative high local control rate with acceptable morbidity, No significant financial relationships to disclose.
Negative effects of melatonin on depression
Authors: J S Carman, R M Post, R Buswell, F K Goodwin
Journal: American Journal of Psychiatry (1976)

In order to test the efficacy of the pineal neurohumor melatonin on depression, the hormone was administered in varying doses to six moderately to severely depressed patients and two patients with Huntington's chorea in double-blind crossover study. Melatonin exacerbated symptoms of dysphoria in these patients, as well as causing a loss of sleep and weight and a drop in oral temperature. Melatonin increased cerebrospinal fluid 5-hydroxyindoleacetic acid and calcium in three of four patients studied. The authors discuss the implications of this finding.
Managing symptoms when “the first step or two isn’t working”: Provider and patient perceptions of the role of specialty palliative care in symptom management in gynecologic oncology.
Authors: Carolyn Lefkowits, Dio Kavalieratos, Janet Arida, Winifred Teuteberg, Heidi Donovan, Madeleine Courtney-Brooks, Robert Arnold, Joseph L. Kelley
Journal: Journal of Clinical Oncology (2014)

47 Background: Our objective was to describe gynecologic oncology (GO) providers’ and patients’ knowledge, attitudes and preferences related to utilization of specialist palliative care (SPC) for symptom management. Methods: Semi-structured qualitative interviews with 19 GO providers (7 physicians, 7 advanced practice providers, 5 nurses) and 30 patients with advanced or recurrent gynecologic cancer from an academic medical center. Key interview domains include: patient symptoms, perceived role of oncology team regarding symptom management, familiarity with SPC, and barriers and facilitators to utilization of SPC for symptom management. Qualitative analysis is underway. Results: 19 provider interviews and 29 patient interviews were completed. Preliminary findings indicate shared beliefs between providers and patients, including an overall willingness to involve SPC in symptom management. Although providers felt comfortable initially managing common symptoms, they expressed interest in involving SPC for complex or multiple symptoms. Patients do not expect their GO providers to manage severe symptoms, noting concerns of complex symptom management as burdensome to the GO team. Barriers to involving SPC in symptom management included: patients’ perceptions of SPC as synonymous with end-of-life care, and logistical issues (e.g., scheduling and transportation). When a distinction was drawn between SPC for symptom management and end-of-life care, patients were uniformly open to seeing SPC for symptom management. Conclusions: GO patients’ and providers’ perception of the role of oncology providers in symptom management is consistent with the concept of a primary palliative care provider, delivering initial management of common symptoms. Specialty palliative care services are seen as complementary to the GO providers’ skillset and particularly useful for severe or multiple symptoms. Implications include the importance of ensuring that oncology provider training includes dedicated attention to symptom management to enable them to fulfill the role of primary palliative care provider.
Diabetes and retinopathy11The following letter addresses an article that appeared in the January 2000 issue of the Journal: Bresnick GH, Mukamel DB, Dickinson JC, Cole DR. A screening approach to the surveillance of patients with diabetes for the presence of vision-threatening retinopathy. (Ophthalmology 2000;107:19–24)
Authors: Alexander R Gaudio
Journal: Ophthalmology (2000)
Clinical combination of the MEK inhibitor GDC-0973 and the PI3K inhibitor GDC-0941: A first-in-human phase Ib study testing daily and intermittent dosing schedules in patients with advanced solid tumors.
Authors: G. Shapiro, P. LoRusso, E. L. Kwak, J. M. Cleary, L. Musib, C. Jones, A. de Crespigny, M. Belvin, M. McKenzie, M. R. Gates, I. T. Chan, J. C. Bendell
Journal: Journal of Clinical Oncology (2011)

3005^ Background: The RAS/RAF/MEK and PI3K/AKT signaling pathways are both deregulated in many tumor types. Targeting both pathways may be more efficacious than targeting either pathway alone. In preclinical models, concurrent administration of GDC‐0973, a potent, selective, MEK1/2 inhibitor and GDC-0941, a potent class I PI3K inhibitor, shows improved efficacy compared to either alone when these agents are dosed either continuously or intermittently. Methods: A phase Ib dose-escalation study with 3+3 design was initiated in patients (pts) with advanced solid tumors to evaluate the safety and pharmacokinetics (PK) of oral combination dosing of GDC-0973 and GDC-0941. Pts received once daily (QD) GDC-0973 + GDC-0941 on a 21 day on/7 day off (21/7) schedule or intermittent GDC-0973 on Days 1, 4, 8, 11, 15, 18 of a 28 day cycle + GDC-0941 QD on a 21/7 schedule. Initial doses were 20 mg GDC-0973 + 80 mg GDC-0941 on 21/7 schedule; 100 mg GDC-0973 + 130 mg GDC-0941 on intermittent schedule. Serial plasma PK samples, FDG-PET and CT scans were obtained. Results: 30 pts have enrolled - 27 pts in 6 cohorts on 21/7 schedule; 3 pts on intermittent schedule. DLTs were grade 3 lipase (n=1) and grade 4 CPK elevation (n=1). Adverse events related to study drug combination were diarrhea (90%; all G1/2), fatigue (61%; 50% G1/2, 11% G3), nausea (61%; all G1/2), rash (50%; 45% G1/2, 5% G3), vomiting (33%; all G1/2), decreased appetite (17%; all G1/2), and dysgeusia (17%; all G1/2). Preliminary analysis indicates PK of GDC-0973 or GDC-0941 are not altered when dosed in combination. 6 of 15 pts had an FDG-PET partial metabolic response at one or more timepoints. Decreases in RECIST measurable target lesions were seen in 5 pts: 2 with melanoma (-75%; -27%), 1 prostate cancer (-21%), and 2 NSCLC (-18%; -13%). 3 pts had prolonged stable disease > 6 months. Conclusions: Combination dosing of GDC‐0973 and GDC-0941 is generally well tolerated, with toxicities similar to those observed in single agent GDC-0973 and GDC-0941 phase I trials. There are early signs of anti-tumor activity. Dose escalation on both schedules continues and updated data will be presented.
Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment of primary gastrointestinal B- cell lymphoma
Authors: D. Aguiar Bujanda, M. Á. Cabrera Suárez, I. Llorca Martínez, U. Bohn Sarmiento, S. Saura Grau, C. Rodriguez Franco, J. Aguiar Morales
Journal: Journal of Clinical Oncology (2008)

19536 Background: Cyclophosphamide, doxorubicin, vincristine, and prednisone, associated with the CD20 antibody rituximab (R- CHOP), is the standard of care for most nodal B-cell lymphomas. However little is known about R-CHOP in the specific subset of GI lymphomas. Methods: Retrospective review of medical records of all our patients with a diagnosis of primary GI lymphoma treated in first line with R-CHOP. Results: A total of 28 patients (20 men, 8 women) with a median age of 60 years (range 19 to 81). Presentation sites: stomach (n=21), colon (n=5), and small intestine (n=2). According to histology: diffuse large B-cell lymphoma (n=22), MALT lymphoma (n=4), follicular lymphoma (n=1), mantle-cell lymphoma (n=1). Stage at diagnosis (Lugano system) was I in 8 patients (29%), II in 14 patients (50%), and IV in 6 patients (21%). Pronostic index (IPI) was 0 in 5 patients, 1 in 11 patients, 2 in 5 patients, 3 in 6 patients, and 4 in 1 patient. R-CHOP was administered every 14 days in 19 patients and every 21 days in 9 patients. Patients received a total of 175 cycles, with a median of 6 cycles per patient (range 1 to 8). After completing R-CHOP, 4 patients recieved radiation therapy as consolidation. Toxicity was mainly haematological, with febrile neutropenia in 5 patients, neutropenia grade III-IV in 11 patients, and blood transfusion in 8 patients. There were not unexpected toxicities, and no gastrointestinal bleeding or perforation occurred. One patient died after the first cycle of R-CHOP because unknown cause (considered as a toxic death), and was not evaluable for response. Another 3 patients were not evaluable for response as they received chemotherapy after a complete surgery of the lymphoma. Thus, the response rate evaluable in 24 patients was 100%, with 22 patients (92%) showing a complete response, and 2 patients (8%) a partial response. After a median follow-up of 26 months, 27 of the 28 patients are alive (2-year survival 96%), 23 of them in complete response. Two patients have relapsed, at 11 and 27 months respectively. Conclusions: Our data indicate that R-CHOP is a highly effective regimen for the treatment of GI lymphomas. Security of R-CHOP in our population is high, even in cases of bulky and high grade gastric disease. No significant financial relationships to disclose.