tbuckley/cabot-search huggingface dataset:
The effect of delay in time to adjuvant chemotherapy (TTAC) on survival in breast cancer (BC): A systematic review and meta-analysis.
Authors: J. J. Biagi, M. Raphael, W. D. King, W. Kong, C. M. Booth, W. J. Mackillop
Journal: Journal of Clinical Oncology (2011)

1128 Background: The optimal timing from BC surgery to initiation of adjuvant chemotherapy (AC) is unknown. We report a systematic review and meta-analysis to determine the relationship between TTAC and survival. Methods: A systematic review of literature was completed to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. Publication bias was investigated using funnel plots and the trim-and-fill approach. Results: We identified 4 eligible studies for OS, and 5 for DFS, all fully published manuscripts. The OS studies involved 15,327 patients; two were randomized trials and 2 were cohort studies; one study reported TTAC as a binary variable and three had 4 TTAC categories. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with an OS HR of 1.06 (95% CI 1.02-1.10), and DFS HR of 1.08 (95% CI 1.03-1.14). The analyses for heterogeneity justified the use of a fixed-effect model. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the studies of largest weight. Conclusions: This study demonstrates a 6% increase in the risk of death for each 4 week delay to initiation of AC for BC. Our results were consistent for both OS and DFS, and remained significant after correction for publication bias. These findings indicate that clinicians and oncology health systems managers should monitor TTAC for quality assurance, and keep TTAC as short as reasonably achievable.
Detection of bone marrow metastasis in small-cell lung cancer by monoclonal antibody.
Authors: R A Stahel, M Mabry, A T Skarin, J Speak, S D Bernal
Journal: Journal of Clinical Oncology (1985)

A murine monoclonal antibody against a surface antigen of small-cell carcinoma of the lung (SM1 antibody) was investigated for its use in detecting bone marrow metastasis. Bone marrow cells of healthy volunteers and of patients with small-cell carcinoma of the lung (SCCL) were examined for reactivity with SM1 antibody and indirect immunofluorescence and the results compared to conventional histochemical staining (Wright-Giemsa stain of bone marrow aspirates and hematoxylin-eosin stains of bone marrow biopsies). No SM1 reactivity was found in marrow cells of eight healthy volunteers. Thirty-six samples from 33 patients with SCCL were examined; tumor involvement was found in 69% by SM1 antibody and in 16% by histochemical stains. All bone marrow samples from patients with SCCL that were unreactive with SM1 antibody also showed no evidence of tumor involvement by histochemical stains. Samples of 29 patients were investigated at initial staging; SM1 reactive cells were found in 50% of 16 patients with limited disease and in 77% of 13 patients with extensive disease. Overall, the proportion of patients recognized to have disseminated disease at diagnosis was increased from 45% to 72% by monoclonal antibody staining. Indirect immunofluorescence with SM1 antibody allows detection of bone marrow metastasis of SCCL that cannot be seen by conventional morphology and can identify disseminated disease in patients otherwise staged limited disease.
Increasing tripartite cooperation of ER-alpha, c-Src, and IGF-1R plays an important role in tamoxifen resistance
Authors: Y. Shu, Y. Yin, R. Guo, Y. Gu, L. Liu, R. Wang
Journal: Journal of Clinical Oncology (2007)

11037 Background: Acquired resistance to tamoxifen is a serious therapeutic problem that limits its clinical benefit. The precise mechanisms for acquired tamoxifen resistance, however, are still not fully understood. Our prior studies suggest that enhancement interaction between growth factors and ERa was associated with development of tamoxifen resistance. Cross-talk between growth factor receptors and estrogen receptor alpha (ERa) makes this problem more complicated. We hypothesized that some other proteins may be involved in this association between two kinds receptors in the development of TAM resistance. Methods: To test our hypothesis, MCF-7 breast cancer cells were continuously treated with TAM (10–7 M) until the cells resist to tamoxifen treatment, which were named as tamoxifen resistant cells (TAM-R). Results: TAM-R cells were more sensitive to E2 and IGF-1 stimulation to express higher level phospho-MAPK than that of control cells. Inhibitory effect of AG1024 on TAM-R cells was about as 2 folds as many as that of control cells. MAPK inhibitor caused dramatic inhibition of growth of TAM-R cells. It was interestingly found that ERa translocated from nucleus to cytosol and an increased amount of ERa was co-immunoprecipitated with IGF-1R from TAM-R cells even though there was no change in the levels of these receptors compared to the control cells. c-Src was an important adapter protein between these two receptors, which increasingly combined with both IGF-1R and ERa in TAM-R cells. Pure antiestrogen ICI, AG1024/IGF-1R SiRNA, and Src family inhibitor PP2 could inhibit the interaction between IGF-1R and ERa. However, only PP2 could completely inhibit ERa translocate from nucleus to cytosol and cytoplasm membrane. Conclusions: Our results suggested that IGF-1R/MAPK signaling pathway was very important for TAM-R cells to develop resistance. c- Src was an critical elements to form a ternary complex with IGF-1R and ERa. This may be one mechanism responsible for tamoxifen resistance in breast cancer cells. No significant financial relationships to disclose.
Retrospective analysis and chemotherapy results in extra-nodal NHL patients in a large super-speciality hospital in North India
Authors: S. Aggarwal, P. Prakhar, S. Kohli, A. Negi, M. Jauhari, S. Bhalla
Journal: Journal of Clinical Oncology (2009)

e19566 Background: We retrospectively analysed records of the Patients visiting the pathology department of Sir Ganga Ram Hospital, New Delhi a super-speciality hospital, between February 2007- February 2008. Out of a total of 16,500 cases, NHL was reported in 154 (0.93%)cases. The median age was 52 yrs and the no. of male patients were 104 and female were 50 making M:F = 2:1. The type of NHL was B-Cell type (CD-20+ve) in 132(85%) and T-Cell type (CD 3+ve) in 22 (15%) cases. Out of 154 patients, 77 were nodal and 77 were extra nodal. Additional features - HIV positivity in 2 patients, autoimmune haemolytic disease in 1 patient and thalessemia major in 1 patient. In extra-nodal group of NHL patients the no. Of male and female patients were 55 &amp; 22 respectively (M:F=2.5:1). Out of 77 extra-nodal cases, 31(20%) were GIT NHL (Stomach -16, Colon-8, Ileum-4, and Duodenum-3) and out of the rest 46 extra-nodal cases the site of origin was - head &amp; neck-14, skin n soft tissues -8, primary CNS-6, testicular-4, para-spinal- 3, breast mass-3, perinephric-2, bones-2 and 1 each in cervix, lung mass, liver and cervical plexus. Methods: A detailed analysis of 31 GIT NHL cases was carried out. 28 out of 31 were B-Cell type and 3 were T-Cell type. 26 out of 31 were diffuse large cell variety, 2 were mixed small &amp; large cell variety and 1 MALT variety. In 2 patients the type of lymphoma could not be ascertained. Bone marrow infiltration was present in 2 out of 31 cases of GIT Lymphoma. Surgery was carried out in 15 of 31 GIT NHL cases and these were arising from Colon, Ileum and Duodenum. No surgery was performed in patients with stomach lymphoma. Results: Of all the extra-nodal cases chemotherapy was given to 39 patients - R-CHOP = 20 patients, CHOP = 13 patients, high dose MTX in primary CNS NHL = 6 patients. CR was achieved 16 out of 20 R-CHOP patients (80%), 8 out of 13 CHOP Patients (61 %) and 4 out of 6 high dose MTX patients (66%). No significant financial relationships to disclose.
Estrogen receptor positivity improves breast cancer survival prognosis for all underserved ethnic groups except African Americans
Authors: V. Bhatia, E. Roldan, D. H. Moore, D. Hanks, J. Cheng, K. Lane, C. Benz, M. Knudson, J. Luce
Journal: Journal of Clinical Oncology (2005)

9591 Background: California Cancer Registry data from 1997–2001 indicate age-adjusted breast cancer mortality rates (per 100,000) for San Francisco County are highest for African Americans (AA; 43) compared to non-Hispanic Whites (W; 32), Hispanics (H; 16) and Asians/Pacific Islanders (A; 12). However, these data cut across heterogeneous socioeconomic strata and do not account for unequal access to care and diverse treatment practices. The San Francisco General Hospital (SFGH) Breast Clinic staffed by the same breast surgeon and medical oncologist for the past 12 years provides diagnostic and treatment services to the city’s underserved (low SES) and multiethnic population, enabling a breast cancer outcome comparison among low SES patients of different ethnicities uniformly offered treatment. Methods: Chart and registry review of 1014 invasive breast cancer cases diagnosed between 1992–2004, grouped by patient ethnicity (H, AA, W, A) and typed by tumor hormone receptor status (ER, PR). Results: Among ethnic groups there were no significant differences in median age at diagnosis(53y), age distribution(35–37% >60y), or tumor stage (20–30% Stage III/IV). Number lost to follow up equivalent in all groups. (see table) Conclusions: SFGH breast cancer survival while worse than SF County as a whole shows the same trend with respect to ethnic differences. AA women are least likely to be alive and disease free while A women are most likely. Analyses based on ER subtype suggest that the survival advantage of ER positivity is smaller for AA women than for other ethnic subgroups. This suggests that overall survival differences among ethnic groups cannot be fully explained by differences in SES or delivery of care. The comparative lack of benefit among ER+ AA cases cannot be accounted for by an excess proportion of ER+/PR- cases suggesting that ER+ breast cancers arising in AA possess other unique high-risk biological features. No significant financial relationships to disclose.
Abstract 15: Obstructive Sleep Apnea is a Risk Factor for Incident Diagnosed Diabetes: The Sleep Heart Health-Atherosclerosis Risk in Communities Study
Authors: Mako Nagayoshi, Naresh M Punjabi, Elizabeth Selvin, James S Pankow, Eyal Shahar, Hiroyasu Iso, Pamela L Lutsey
Journal: Circulation (2014)

Background: Sleep apnea has been associated with diabetes in many cross-sectional studies, but prospective data is sparse. Most prior studies defined sleep apnea by self-reported sleep symptoms. Hypothesis: Objectively measured obstructive sleep apnea is associated with greater risk of incident diabetes. Design: We conducted a prospective cohort study of 1,465 non-diabetic participants of the Sleep Heart Health-Atherosclerosis Risk in Communities Study with in-home polysomnography conducted in 1996-1998 (baseline). Participants were categorized into four groups according to number of events per hour, as defined by the apnea-hypopnea index: &lt;5.0 (normal), 5.0-14.9 (mild sleep apnea), 15.0-29.9 (moderate sleep apnea), and ≥30.0 (severe sleep apnea). Incident diagnosed diabetes or diabetes medication use was ascertained during annual follow-up calls through 2010. Cox proportional hazards models were used to examine the association between sleep apnea severity and incident diagnosed diabetes. Results: During a median follow-up of 12 years, there were 279 incident self-reported diabetes cases among the study participants (mean age 63 years, 99% white, 47% male). The risk of diabetes among those with moderate or severe sleep apnea was significantly higher than in those without sleep apnea after adjustment for demographics measures and other confounders. The association persisted among those with severe sleep apnea even after adjustment for body mass index and waist circumference. Across all models there was evidence of a dose-response association between the sleep apnea severity and the risk of incident diabetes ( Table ). There was no evidence for an interaction by sex. Conclusions: In this community-based study, persons with objectively measured obstructive severe sleep apnea were at higher risk of diabetes compared to persons without sleep apnea, independent of body mass index and waist circumference. Screening and treatment of sleep apnea may be beneficial for the prevention of diabetes.
Is linitis plastica a contraindication for surgical resection? A 7-institution study of the U.S. Gastric Cancer Collaborative.
Authors: Aaron Udell Blackham, Doug S. Swords, Edward Allen Levine, Nora Fitzgerald, Malcolm Hart Squires, George A. Poultsides, Ryan C. Fields, Mark Bloomston, Sharon M. Weber, Timothy M. Pawlik, Linda X. Jin, Gaya Spolverato, Emily Winslow, Carl Richard Schmidt, David A. Kooby, David J. Worhunsky, Neil Saunders, Clifford Suhyun Cho, Shishir Kumar Maithel, Konstantinos Ioannis Votanopoulos
Journal: Journal of Clinical Oncology (2015)

118 Background: Linitis plastica (LP) describes a diffusively infiltrative gastric adenocarcinoma that portends poor prognosis. Current treatment guidelines do not differentiate between LP and non-LP cancers and it is not known if the same staging system should be applied to both situations. Methods: Using the multi-institutional U.S. Gastric Cancer Collaborative database, 869 patients with gastric adenocarcinoma who underwent resection between 2000-2012 were identified. Clinicopathologic, perioperative and survival outcomes of the 58 patients with LP were compared to the 811 patients without LP. Results: Advanced disease (stage III/IV) at presentation was more common in patients with LP compared to non-LP patients (90 vs 44%, p&lt;0.01). Despite the fact that most LP patients underwent total gastrectomy (88% vs 57%, p&lt;0.01), positive margins were more common in LP patients (33 vs 7%, p&lt;0.01). There was no difference in perioperative complications (48 vs 43%, p=0.45) or mortality (7 vs 3%, p=0.12) between LP and non-LP patients. While survival correlated with stage in non-LP patients, there was no difference in median overall survival (OS) of LP patients based on stage (I/II, 17.3 mos; III, 10.6 mos; IV, 12.0 mos; p=0.46). Median OS was significantly worse in patients with LP (11.6 vs 37.8 months, p&lt;0.01) when margin status and extent of lymphadenectomy were not factored in the analysis. However, when analyzing only patients with optimal resections (R0, D2 lymphadenectomy), the median OS for stage III LP (n=22) and non-LP (n=185) patients was nearly identical (26.8 vs 25.3 mos, p=0.69). There were no independent prognostic factors identified to predict survival in LP patients undergoing curative resection. Conclusions: The poor prognosis of LP gastric cancer is due primarily to its advanced stage at diagnosis. However, LP patients who undergo optimal resections can expect similar long term survival compared to optimally resected non-LP patients with advanced stage disease. Patient selection and multidisciplinary management are paramount when considering surgical resection in patients with gastric LP.
Bevacizumab and erlotinib in the treatment of patients (pts) with metastatic carcinoma of unknown primary site: A Sarah Cannon Research Institute phase II trial
Authors: F. A. Greco, D. R. Spigel, D. L. Shipley, D. A. Yardley, S. Ramsey, V. Sutton, M. Thomas, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2005)

3088 Background: Bevacizumab (B) has anti-tumor activity in several advanced epithelial neoplasms including colorectal and renal. Erlotinib (E) has activity in lung and head/neck carcinomas. We previously reported promising results with the combination of B and E in patients with metastatic clear cell renal carcinoma. Unknown primary carcinoma is a heterogeneous group which frequently overexpresses epidermal growth factor and vascular endothelial growth factor. The objectives of this phase II trial were to evaluate the toxicity of the combination as well as the objective response rate in pts with unknown primary carcinoma. Methods: Eligibility criteria included: metastatic adenocarcinoma or poorly differentiated carcinoma of unknown primary site; 1 or 2 previous chemotherapies except for pts with either predominant liver metastasis, predominant bone metastasis, or ≥ 3 visceral sites of metastasis; measurable disease; ECOG PS 0–2; adequate organ function; no previous anti-angiogenic or epidermal growth factor inhibitors; no active brain metastasis; no bleeding abnormalities; no active thromboembolic disease; informed consent. All pts received B 10mg/kg IV q 2 weeks and E 150mg po daily. Pts were evaluated for response after 8 weeks and treatment continued until tumor progression. Results: From between 4/04 and 11/04, 25 pts have been treated. Accrual is expected to be completed within the next 3 months. Median age 61, male/female, 8/17; ECOG 0/1/2, 2/21/2. 16 pts (64%) were previously treated. 19 pts are evaluable for response (2 inevaluable, 4 too early). 1 pt had PR, 10 SD (includes 4 minor responses) and 8 PD. One pt discontinued treatment because of chest pain/anorexia (grade 3). Other grade 3 toxicity included: thrombosis (1 pt); diarrhea (1 pt); nausea/vomiting (1 pt); fatigue (1 pt); proteinuria (1 pt). Conclusions: These preliminary results show that the combination of B and E at full doses is relatively well tolerated and has activity against advanced unknown primary carcinoma. Updated results of this phase II trial will be presented. No significant financial relationships to disclose.
Relationship between fatigue and cytokine levels in patients age 50+ with acute myeloid leukemia (AML)
Authors: A. Panju, D. Kelvin, M. D. Minden, S. M. Alibhai
Journal: Journal of Clinical Oncology (2007)

19566 Background: Fatigue is the most common and disabling symptom affecting patients with AML; effective prevention or treatment measures have yet to be found. Cytokines, biological markers of inflammation, may represent a major cause of fatigue, but published data are limited. Methods: Patients age 50 or older with AML were recruited between May and September 2006. All patients were fluent in English, within one year of diagnosis, and free of any other active malignancy. Fatigue was measured using the Functional Assessment of Cancer Therapy (FACT) Fatigue subscale, a single-item global fatigue scale, and the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30. Blood was simultaneously drawn for quantitative measurement of a panel of 13 cytokines. Repeat measurements were done 4–6 weeks later. Correlational analysis was used to examine relationships between individual cytokines and fatigue scores. Changes in fatigue scores between time points were correlated with changes in cytokine levels. Results: 34 patients (23 men; 11 women) were enrolled (mean age 67 y; range 52–84). 27% had not started chemotherapy or were receiving best supportive care, while the rest were undergoing active chemotherapy. At baseline, a weak correlation (r=0.332, p=0.059) was seen with interleukin (IL)-6 and at least one fatigue measure. No correlations (r&lt;0.30) were observed with any of the other cytokines (interferon (IFN)-?, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, MiG, and tumor necrosis factor-a) and any fatigue measure. Follow-up data were available for 29 patients. A statistically significant correlation with fatigue was seen with IL-2 (r=0.407, p=0.032), and clinically-important correlations that did not achieve conventional statistical significance were seen with IFN-? (r=0.331, p=0.085), IL-5 (r=0.344, p=0.073), and IL-10 (r=0.326, p=0.091). Conclusions: Based on these data, the most promising cytokine-fatigue relationship was noted with IL-2. However, IFN-?, IL-5, IL-6, and IL-10 also showed potentially important relationships with fatigue. Given our small sample size and patient enrolment at differing time points during their treatment course, further controlled studies are warranted. No significant financial relationships to disclose.
High dose therapy (HDT) and autologous stem cell transplantation (ASCT) in diffuse large B cell lymphoma (DLBL) patients with secondary central nervous system (CNS) involvement
Authors: T. S. Chan, T. Latif, B. Pohlman, K. Theil, P. Elson, R. Sobecks, B. Bolwell, M. Kalaycio
Journal: Journal of Clinical Oncology (2004)

6658 Background: The prognosis of patients with secondary CNS involvement in DLBL is universally poor. Although randomized studies have shown that ASCT improves survival in relapsed DLBL patients, limited data is available to ascertain its role in those with secondary CNS disease. In this single institution experience, we evaluated whether HDT with ASCT improved outcomes in DLBL patients with secondary CNS involvement. Methods: Our institutional database was searched for all cases of DLBL with pathologic confirmation of secondary CNS involvement diagnosed over the last 10 years. Patients receiving ASCT subsequent to CNS diagnosis were identified and a comprehensive chart review was done to obtain information regarding clinical characteristics, prognostic variables, treatment and outcomes. Similar information was also collected for the remaining DLBL patients with secondary CNS disease who did not receive ASCT. Results: 21 patients with DLBL and secondary CNS disease were identified. Of these, 6 patients received HDT with ASCT. The median age at diagnosis was 44 years (range 22–52 years) and 4 were male. 2 had International Prognostic Index (IPI) scores of 2, while 4 had IPI scores of 3 at diagnosis. 3 received directed CNS radiation therapy and 4 received intrathecal chemotherapy. The median time to CNS involvement from diagnosis was 3.5 months (range 0–11 months). Two patients had died at 7 and 10 months after the diagnosis of CNS disease while 4 (67%) patients are alive at 50 48, 46, and 22 months following diagnosis of CNS disease. One year survival from the time of CNS diagnosis was 67%. This compares favorably to the remaining 15 patients with DLBL and CNS involvement (0 % one year survival) and historic controls (mean survival 3.5 months)1. Conclusions: HDT with ASCT can potentially improve the long-term survival in DLBL patients with secondary CNS involvement and warrants further studies. 1Hoerni-Simon G. Oncology. 1987; 44(2):98–101. No significant financial relationships to disclose.