tbuckley/cabot-search huggingface dataset:
Diabetic Retinopathy: A Position Statement by the American Diabetes Association
Authors: Sharon D. Solomon, Emily Chew, Elia J. Duh, Lucia Sobrin, Jennifer K. Sun, Brian L. VanderBeek, Charles C. Wykoff, Thomas W. Gardner
Journal: Diabetes Care (2017)

Diabetic retinopathy diagnostic assessment and treatment options have improved dramatically since the 2002 American Diabetes Association Position Statement (1). These improvements include the widespread adoption of optical coherence tomography to assess retinal thickness and intraretinal pathology and wide-field fundus photography to reveal clinically silent microvascular lesions. Treatment of diabetic macular edema is now achieved by intravitreous injection of anti–vascular endothelial growth factor agents, and the same drugs are now used for proliferative diabetic retinopathy. Improvements in medications and devices for the systemic therapy of diabetes have also improved the ability of patients to optimize their metabolic control. This Position Statement incorporates these recent developments for the use of physicians and patients.

Diabetic retinopathy is a highly specific neurovascular complication of both type 1 and type 2 diabetes, the prevalence of which strongly correlates to both the duration of diabetes and level of glycemic control. A pooled meta-analysis involving 35 studies conducted worldwide from 1980 to 2008 estimated global prevalence of any diabetic retinopathy and proliferative diabetic retinopathy (PDR) among patients to be 35.4% and 7.5%, respectively (2). Diabetic retinopathy is the most frequent cause of new cases of blindness among adults aged 20–74 years in developed countries. Glaucoma, cataracts, and other disorders of the eye occur earlier and more frequently in people with diabetes.

In addition to diabetes duration, factors that increase the risk of or are associated with retinopathy include chronic hyperglycemia (3,4), nephropathy (5), hypertension (6), and dyslipidemia (7). Intensive diabetes management with the goal of achieving near-normoglycemia has been shown in large prospective randomized studies to prevent and/or delay the onset and progression of diabetic retinopathy (8,9).

Lowering blood pressure has been shown to decrease retinopathy progression in people with type 2 diabetes, although tight targets (systolic blood pressure <120 mmHg) do …
Survival analysis in gastric cancer patients of the Colombian coffee zone at the Oncologos del Occidente clinic during 2014.
Authors: Gustavo A. Rojas Uribe, Jose Martinez, Jaime Calvache
Journal: Journal of Clinical Oncology (2016)

148 Background: The risk of death for gastric cancer in Colombia is lightly higher for 2013 compared to 1998. Even though Risaralda has an irregular pattern for the risk of death, it was also higher compared to 1998, for these reasons the survival analysis was made with the information of gastric cancer patients treated in Oncólogos del Occidente clinic during 2014. Methods: A cohort study was made whose exposure is the treatment of gastric cancer. The time variable is the interval between the first medical appointment and the final control, interview or date of death, and the outcome makes reference to a death attributable to cancer gastric or surviving. The source of the cases were the clinical histories found in SAHICO data base, of the patients attended in the clinic Oncólogos del Occidente, to make univariate and bivariate analysis using Stata software. Results: There were 173 patients, from which 69.9% were male; the age group with highest incidence was 60 to 69 years old group (32.2%); 21.38% of the patients had family members with gastric cancer and 53.1% were diagnosed during advanced stages (III-IV). As far as the survival analysis, it was 207 days long, lessen if the patient only receives palliative treatment (122 days long) and increasing if surgery, chemotherapy and radiotherapy were done (252 days long). Conclusions: In a national and international level, the epidemiological data correlates with the findings in this study; with respect to the diagnosis, in Colombia, it is made during advanced stages, meanwhile in developed countries the diagnosis is made during earlier stages because of the screening tests. The oncological surgery increased the patient’s survival, also for the patients who underwent surgery when they received chemotherapy or radiotherapy.
First-in-human, safety, pharmacodynamic (PD) and pharmacokinetic (PK) trial of a first-in-class dual RAF/MEK inhibitor, RO5126766, in patients with advanced or metastatic solid tumors.
Authors: S. O. Dolly, J. Albanell, F. Kraeber-Bodere, U. Banerji, R. Bahleda, M. Martinez Garcia, Z. X. Xu, E. Guarin, J. Tessier, E. Shochat, J. Deutsch, S. Blotner, V. Meresse, J. Soria
Journal: Journal of Clinical Oncology (2011)

3006^ Background: The Ras-Raf-MEK-extra-cellular signal-regulated kinase 1 and 2 (ERK1/2) pathway is frequently deregulated in human cancer. RO5126766, a first-in-class, dual Raf/MEK inhibitor was tested in a phase I (Ph1) study. Objectives were determination of maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), recommended phase II dose (RP2D), safety/tolerability, PK/PD and clinical activity. Methods: Patients (pts) with advanced or metastatic solid tumors received oral RO5126766 once daily (QD) in 28 day cycles. To increase the therapeutic window, 2 intermittent regimens were also evaluated: 7 days on/7 days off (7/7) and 4 days on/3 days off (4/3). PK and PD samples (PBMCs) were collected after a single run-in dose and on cycle 1 day 15 (C1D15). Paired skin and tumor biopsies (baseline, C1D15) were analyzed for mutational status and target inhibition. FDG-PET scans (baseline, C1D15, and C3D1) were performed. Results: 52 pts (25 QD, 13 4/3 and 14 7/7) were enrolled in 13 cohorts (QD: 0.1 - 2.7 mg, 4/3: 2.7 - 4 mg and 7/7: 2.7 - 5 mg). Mean age 50yrs, ECOG 0-1, median previous chemotherapy lines 3 (0-12). Common tumors were melanoma (21), ovarian (6) and CRC (10). Ten reversible DLTs were observed: 3 blurred vision (QD, 4/3 and 7/7), 3 CK elevations (2x QD, 7/7), 1 transaminitis (QD); 1 capillary leak syndrome (7/7), 1 febrile neutropenia (7/7) and 1 serous retinal detachment (7/7). MTDs were defined as 2.25 mg QD, 2.7 mg 7/7 and 4 mg 4/3. Most common related adverse events were skin (94%), GI (71%), metabolic (67%) and eye (58%) disorders. No cases of cutaneous squamous cell carcinoma were reported. PK was linear with plasma half-life (t ½) of 40 to 60 hrs. Tumor /skin biopsies demonstrated target modulation with inhibition of pERK/pMEK in PBMCs approaching 100%. Of 40 evaluable pts, 3 melanoma pts had PR and 9 pts had SD > 16 wks associated with reduction in SUVmax (mean: -35%) at C1D15. Conclusions: RO5126766 has a manageable safety profile. MTD was defined for all regimens and RP2D is 2.7 mg 4/3. Favorable PK/PD profile with encouraging biological and antitumor activity were demonstrated. Full safety, efficacy, PK/PD profile will be presented.
Anxiety in cancer caregivers: A pilot study in the Indian population.
Authors: C. D. Deshmukh, M. Patwardhan, A. V. Bakshi, A. s. Parasnis, D. s. Kelkar
Journal: Journal of Clinical Oncology (2011)

e19652 Background: There is little data about the psychological problems in caregivers of cancer patients on the caregivers’ quality of life. The American Medical Association’s stress questionnaire is not valid for Indian population. We conducted a pilot study to assess the anxiety faced by primary caregivers of cancer patients using a modified State-Trait-Anxiety (STA) inventory. Methods: Primary care givers were administered the STA (C.D. Spielberger-1983, Indian Adaptation by Dr. S.W. Deshpande, and Dr. Alizapurkar) which had 20 questions assessing the individual’s state anxiety (current anxiety level) and another 20 assessing trait anxiety (general anxiety level). An anxiety state score > 36 indicated anxiety
Role of Ki67 labeling index (LI) in subdividing homogeneous ER-positive grading groups of early breast cancer (EBC) in distinct biologic entities.
Authors: A. Ferro, M. Barbareschi, C. Eccher, A. Caldara, D. Aldovini, R. Triolo, L. V. Cuorvo, F. Berloffa, S. Brugnara, O. Caffo, M. C. di Pasquale, M. Frisinghelli, V. Murgia, B. Soini, F. Valduga, A. Veccia, E. Galligioni
Journal: Journal of Clinical Oncology (2011)

539 Background: Ki67LI is a relevant marker EBC. The 2009 St Gallen Consensus considered Ki67LI as an important parameter for the addition of chemotherapy to endocrine therapy in hormonereceptor-positive EBC, suggesting three cutoffs: low <15%, intermediate 15-30% and high >30%. Our study aimed to evaluate if these cutoffs can be used in different subgroups of EBC, or if to apply different cutoffs in distinct biological setting. Methods: Ki67LI 1 was identified by immunohistochemical staining in 3802 EBC pts treated from 1995 to 2008. Median age was 61. The relationship with clinic-pathological parameters and the prognostic significance of KI67LI was investigated in all EBCs and in subgroups of ER+ cases based on homogeneous grading (656 G1, 1535 G2, 1113 G3). Results: Median Ki67LI values were 22% in all cases and 10, 20 and 36% in ER+ G1, G2 and G3 respectively. High Ki67LI was significantly (p<0.001) associated with younger age, ductal type, greater size, positive N, poor G, absent or low ER /PR, positive HER-2, triple negative subtypes, larger use of chemo±hormonotherapy. At median f-up of 51 months DFS and OS were 84 and 85% respectively in high, 89 and 90% in intermediate, 92 and 94% respectively in low Ki67LI group (p <0.001). There were 456 relapses (12%): 207 (5.4%) in high, 136 (3.6%) in intermediate and 113 (3%) in low Ki67LI group. Using median ki67LI value for different homogenous ER+ grading groups (ER+GG) we stratified these populations in low and high risk. The results are shown in the table. Conclusions: Ki67 LI confirms to be a significant prognostic biomarker for DFS and OS in EBC, associated with other clinical-pathological characteristics. Cutoffs are different into ER+GG. They can cathegorize at least two biological entities in every grading group providing additional prognostic information in planning therapies and outcome prediction. Subgroups At median follow-up DFS (%) P value At median follow-up OS (%) P value G1 High Low 90 95 0.058 93 97 0.005 G2 High Low 93 87 <0.001 94 90 0.001 G3 High Low 87 88 NS 85 87 0.008
Correlation of <i>DPC4</i> status with outcomes in pancreatic adenocarcinoma patients receiving adjuvant chemoradiation.
Authors: J. M. Herman, C. C. Hsu, E. K. Fishman, R. H. Hruban, S. H. Lin, A. Hacker-Prietz, J. L. Cameron, D. Laheru, C. L. Wolfgang, C. A. Iacobuzio-Donahue
Journal: Journal of Clinical Oncology (2011)

168 Background: In an autopsy series of patients with advanced pancreatic cancer (PCA), loss of DPC4 was highly correlated with disseminated metastasis. The purpose of this study was to determine if DPC4 gene status predicts for survival and patterns of recurrence following adjuvant (adj) chemoradiation (CRT). Methods: 101 patients who underwent surgery followed by adjuvant 5-FU or gemcitabine-based CRT were studied. Imaging studies were reviewed to assess patterns of recurrence and tumor tissue obtained to determine DPC4 immunolabeling status. DPC4 status was graded as intact or lost/mutated. Kaplan-Meier estimates were used to compute survival and Cox proportional hazards were used to compare risk factors. Results: Median overall (mOS) and progression-free survival (PFS) was 22.6 mos (95% CI 18.8 to 31.6) and 14.0 mos (95% CI 11.5 to 18.4). The mOS and 1-yr OS for patients with DPC4 intact vs. lost status was 21.9 mos (95% CI 16.8-32.4) and 78.4% vs. 22.6 mos (95% CI 18.4-32.6) and 78.2%, respectively (HR: 1.05, p=0.82). After adjusting for node, margin status, tumor grade, tumor size, and age, DPC4 status did not predict for mOS (RR 1.04, 95% CI: 0.62-1.74, p=0.89). Time to first progression at any site for PCA with DPC4 intact vs. lost status was 13.8 vs. 14.0 mos (p=0.79). Local recurrence was more common in PCA with DPC4 loss than with intact status (34.4% vs. 13.7%, p=0.012). There was no difference in the rates of distant recurrence in PCA with intact vs. loss of DPC4 expression (62.8% vs. 55.7%, p=0.45); however, DPC4 loss was more commonly associated with liver recurrence (27.9% vs. 19.6%, p=0.31). Conclusions: In pancreatic cancer patients receiving adj CRT, loss of DPC4 labeling in their resected PCA indicates a greater likelihood of developing local recurrence despite having received adj CRT. Efforts to improve loco-regional control are therefore needed for these patients following surgery and adj CRT. No significant financial relationships to disclose.
Myeloid growth factor utilization in a commercial and Medicare population: Phase 1 of a quality improvement initiative.
Authors: Edward C. Li, Barry A. Peterson, Cecilia Tran, Michael Sturgill, Dudley Gill, Stanley Forston, Romano Bastianpillai
Journal: Journal of Clinical Oncology (2014)

242 Background: Some clinical practice guidelines encourage the judicial use of myeloid growth factors (MGFs) in the prevention of chemotherapy-induced febrile neutropenia (FN) because of efficacy and safety concerns. For example, the ASCO guidelines state that a dose reduction of myelosuppressive chemotherapy in patients with incurable disease rather than prescribing a MGF for secondary prophylaxis is a reasonable alternative. Because there is wide variation in MGF prescribing, New Century Health (NCH) conducted a quality improvement analysis of MGF requests in a commercial and Medicare population. The objectives are to: (1) describe the cohort demographics, (2) identify areas of improvement to promote cost-effective use, and (3) measure the economic impact from interventions. Methods: MGF authorization requests for oncology indications to NCH in 2013 were analyzed for cohort demographics: age, weight, tumor diagnosis, and treatment intention (e.g., metastatic/palliative, curative, etc.). Requests were analyzed for concurrent use with chemotherapy, approval status of the request (including reason for withdrawal), and cost saving associated with interventions. Results: There were 7,958 requests for a MGF; 81% were for pegfilgrastim and 19% for filgrastim. Average age of the cohort was 66 years, weight-based dosing (&gt;70 kg) was appropriate in 43% of patients receiving 300 mcg and 72% of patients receiving 480 mcg. MGFs were most commonly requested in: breast (18%), lung (17%), lymphoma (14%), and gynecologic (8%) tumors. 40% of requests were for metastatic/recurrent disease and 38% for curative intent. 6,724 (84%) of requests were authorized based on established-use criteria. The main reason for not authorizing was lack of compendia support for both primary and secondary prophylaxis; this resulted in approximately $3.5 million in cost savings. Conclusions: There is opportunity to improve efficiency of MGFs use in this population through a dose rounding protocol and by promoting chemotherapy dose reductions, as advocated by the ASCO guidelines. Further analysis will assess the concordance of MGF use with guidelines, specifically in regard to chemotherapy regimens and their risk of FN.
What determines adjuvant chemotherapy use after neoadjuvant chemoradiotherapy for rectal cancer?
Authors: George J. Chang, Chung-Yuan Hu, Y. Nancy You, Cathy Eng, Miguel A. Rodriguez-Bigas, John Michael Skibber
Journal: Journal of Clinical Oncology (2012)

546 Background: The treatment standard for rectal cancer patients after neoadjuvant chemoradiotherapy (CXRT) and radical resection includes adjuvant chemotherapy (CT). The purpose of this study was to evaluate patient demographic and clinicopathologic characteristics in relation to adjuvant CT use. Methods: A retrospective cohort study of patients ≥ 65 years old with rectal cancer treated by neoadjuvant CXRT and radical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (1998-2007, Medicare Part A/B only) was performed. Multivariate logistic regression was used to assess CT utilization in relation to patient, tumor and treatment response characteristics. Results: Among 1344 patients who met study criteria, 748 (55.6%) received adjuvant CT with 5-fluorouracil (FU) including 189 (25.3%) who also received oxaliplatin (Ox). ypStage was the strongest determinant of both any post-operative CT (43.1% stage I, 51.3% stage II, 73.4% stage III). Other associated factors included age, comorbidity, marital status and surgery type. In addition, age, socioeconomic status, and grade were associated with Ox use. These effects persisted even after exclusion of patients with comorbidities. Conclusions: Although standard treatment guidelines for locally advanced rectal cancer include postoperative CT for all patients after neoadjuvant CXRT and radical resection, nearly 1 in 2 patients failed to receive adjuvant CT. Despite the absence of established evidence, treatment decisions appear to be influenced by the findings at surgical pathology. [Table: see text]
Phase II study of cixutumumab (IMC-A12, NSC742460; C) in hepatocellular carcinoma (HCC).
Authors: G. K. Abou-Alfa, B. Gansukh, J. F. Chou, J. Shia, M. Capanu, M. Kalin, H. X. Chen, N. J. Zojwalla, S. Katz, D. L. Reidy, D. P. Kelsen, L. Saltz
Journal: Journal of Clinical Oncology (2011)

4043 Background: C is an anti-IGF-1R monoclonal antibody. IGF-IR is implicated in hepatic carcinogenesis. A phase I study of C yielded a partial response in HCC. Methods: Patients (pts) with advanced HCC, Child-Pugh A-B8, and KPS ≥ 60%, received 6 mg/kg of C weekly. The trial had a planned accrual of 50 pts in a two-stage design. Primary endpoints were PFS at 4 months (futility 42%) and response rate (RR), by RECIST (futility 5%). IGF-1R staining was evaluated by immunohistochemistry (IHC), and serum free IGF-I, total IGF-II and IGFBP-1 and -3 were measured by ELISA (Beckman Coulter/DSL) at baseline, and studied for correlation with PFS, OS, and stable disease (SD). Child-Pugh, CLIP, and GETCH scores were similarly measured and studied. Results: The study accrued to the first stage only because of futility. N= 24 with no prior systemic therapy including no sorafenib: median age 67.5 years (range 49-83), KPS 80%(70-90%), 20 males (83%), 9 stage III (37%)/15 stage IV (63%), 11 HBV (46%) /10 HCV (42%), 10 (42%) were diabetic and 5 (21%) became diabetic while on study. The median number of doses was 7 (range 1-140 doses). Grade 3 and 4 toxicities noted in more than 10%: hyperglycemia (46%) which required dose reduction in 3 (12%) pts; elevated liver functions tests: ALT (12%), AST (25%), alkaline phosphatase (12%), and bilirubin (12%); hyponatremia (25%), and lymphopenia (12%). Therapy was discontinued in 2 pts, due to ALT/AST elevation, and hyperglycemia. One pt died after 4 doses due to clinical progression of disease (POD). PFS at 4 months was 30% (95% CI 13-48). There were no objective responses. Of 22 evaluable pts, 7 (29%) had SD for at least 4 months, and 9 (41%) had POD. Median OS was 8 months (95%CI 5.8-14). Within the limitation of the sample size, there was noted a positive correlation between elevation of IGFBP-1 and PFS (1.2 [95%CI 1-1.4]; p 0.009) and OS (1.2 [95%CI 1.1-1.4]; p 0.003). Worse CLIP (3.8 [95%CI 1.3-11.6]; p 0.02) and GETCH (4.6 [95%CI 1.3-16]; p 0.02) scores correlated with worse OS. Conclusions: C is inactive as monotherapy in HCC. Grade 3-4 hyperglycemia occurred in 46% of pts. Within the limitation of the sample size, an elevation of IGFBP-1 did correlate with PFS. Similar to prior reports, worse CLIP and GETCH scores correlated with worse OS.
RTOG 1119: Phase II randomized study of whole brain radiotherapy with concurrent lapatinib in patients with brain metastasis from HER2-positive breast cancer—A collaborative study of RTOG and KROG (NCT01622868).
Authors: David M. Peereboom, Kathryn A. Winter, In Ah Kim, Jennifer F. De Los Santos, Paul W. Sperduto, Julia R. White, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2014)

TPS664 Background: The addition of trastuzumab to cytotoxic chemotherapy has improved outcomes for patients with HER2 positive breast cancer. Increased survival coupled with limited blood-brain barrier (BBB) penetration of trastuzumab may contribute to the increased incidence of brain metastasis in these patients. Half of these patients die of intracranial disease progression rather than extracranial disease. Therefore, strategies to improve survival must include increased CNS disease control in these patients. Lapatinib crosses the BBB and demonstrates modest activity against intracranial metastases. Based upon preclinical data and results of a phase I study, we hypothesize that lapatinib plus WBRT can improve the intracranial disease control compared to WBRT alone. Methods: We initiated a randomized phase II trial of WBRT (37.5 Gy/3 weeks) plus or minus concurrent lapatinib (1000 mg qd x 21 during WBRT and for 21 days after). Non-CNS penetrating HER2 targeted therapy is permitted throughout the study, but patients not on trastuzumab, pertuzumab or any other breast cancer therapy at study entry are not permitted to begin this therapy while on protocol treatment, but may begin it 24 hours after completion of protocol treatment. Eligibility includes HER2+ breast cancer with at least one measurable, unirradiated parenchymal brain metastasis (≥10 mm on enhanced MRI). The two populations targeted for accrual include patients with 1) newly diagnosed, multiple brain metastases or 2) progressive brain metastases after stereotactic radiosurgery (SRS) or surgical resection of 1-3 metastases. Patients are stratified by breast-specific graded prognostic assessment; use of non-CNS penetrating HER2 targeted therapy; and prior SRS or surgical resection. The primary endpoint is complete response rate in the brain 12 weeks after WBRT. Secondary endpoints include objective response rate, lesion-specific response rate, CNS progression free survival, and overall survival. 29 of 143 planned patients have enrolled. Supported by NCI U10 grants CA21661 & CA37422. Clinical trial information: NCT01622868.