tbuckley/cabot-search huggingface dataset:
FIP200 and Rb1 expression in CNS metastasis from breast cancer (CNS met): Potential predictors of patient outcome.
Authors: Nooshin Hashemi Sadraei, Ilya Ulasov, Monica Burgett, Amy S Nowacki, Richard Prayson, Robert J. Weil, Niladri Kar, Manmeet Singh Ahluwalia, Ga‘lle Muller-Greven, Ting Shi, Maciej S. Lesniak, Candece Gladson
Journal: Journal of Clinical Oncology (2012)

2014 Background: Patients with CNS met have a poor outcome with significant variation in overall survival. No marker to predict survival exists. Rb1 is a negative regulator of the cell cycle, and FiP200 is an upstream signaling node that is distributed between the nucleus and cytoplasm. Nuclear FIP200 inhibits cell proliferation by promoting expression of Rb1, whereas cytoplasmic FIP200 promotes cell survival through autophagy. Previously FIP200 deletion/mutation has been reported in 20% of primary invasive breast cancer [BR ca] patients. FIP200 cellular localization and genetic alterations have not been examined in CNS met. Methods: A retrospective analysis of BR ca and CNS met was performed based on tissue availability from 2 institutions. FIP200 and Rb1 expression and localization was evaluated by immunohistochemistry. Genetic alterations were evaluated by DNA array analysis. Results: 80 patients (42 BR ca and 38 CNS met) were identified. Overall CNS met samples had significantly higher levels of cytoplasmic FIP200 as compared to BR ca (52% vs 24% respectively, p=0.0002) and increased expression of FIP200 around areas of hypoxia/necrosis, consistent with increased autophagy. There was also a significant increase in expression of nuclear FIP200 and Rb1 in the CNS met compared to BR ca (p=0.0007 and p=0.0055 respectively). Median survival from development of CNS met was longer in the group with high levels of nuclear Rb1; 14 (3-27) vs 20 (12-33) months (low expression &lt; 20% vs high ≥ 20%, p=0.1). The same finding was observed with FIP200, longer survival was observed with high nuclear expression; 16 (7-33) vs 19 (0.4-27) months (low expression &lt;20% vs high ≥ 20%, p=0.2). Our DNA analysis for copy number variation and LOH in CNS met revealed no deletion in Rb1 or FIP200. Conclusions: The pattern of expression of Rb1 and FIP200 in CNS met is different from BR ca. Notably, cytoplasmic FIP200 which promotes cell survival is highly expressed in CNS mets vs BR ca. This suggests metastatic breast cancer cells utilize autophagy as a survival mechanism. In addition, there is a trend to better survival of those patients with CNS met who express high nuclear FIP200 and Rb1, both of which have anti-proliferative roles in the nucleus.
Revascularization and outcomes in Veterans with moderate to severe ischemia on myocardial perfusion imaging
Authors: David E. Winchester, Alexander J. Bolanos, Anita Wokhlu, Rebecca J. Beyth, Leslee J. Shaw
Journal: Military Medical Research (2017)

The prevalence of ischemia on nuclear myocardial perfusion imaging (MPI) has been decreasing. Recent research has questioned the benefit of invasive revascularization for patients with moderate to severe ischemia. We hypothesized that patients with moderate to severe ischemia could routinely undergo successful revascularization.We analyzed data from 544 patients who underwent an MPI at a single academic Veterans Affairs Medical Center. Patients with moderate to severe ischemia, defined as a summed difference score (SDS) 8 or greater, were compared to the rest of the cohort.Of the total cohort (n = 544), 39 patients had MPI studies with resultant moderate to severe ischemia. Patients with ischemia were more likely to develop coronary artery disease (74.4% versus 38.8%, P < 0.0001) and have successful revascularization (38.5% versus 4.0%, P < 0.0001) during the following year. Revascularization was attempted in 31 patients with moderate to severe ischemia, though only 15 (47%) of these attempts were successful. Ischemia was predictive of myocardial infarction (5.1% versus 0.8%, P = 0.01) within 1 year.Moderate to severe ischemia is an uncommon finding in a contemporary nuclear laboratory. Among patients with ischemia, revascularization is typically attempted but is frequently unsuccessful.This trial does not appear on a registry as it is neither randomized nor prospective.
Randomized phase-2 study of sipuleucel-T with or without radium-223 in men with asymptomatic/minimally symptomatic bone-metastatic castrate-resistant prostate cancer (CRPC).
Authors: Jong Chul Park, A. Oliver Sartor, Rana Sullivan, Serina King, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2015)

TPS5076 Background: Sipuleucel-T is an autologous cellular immunotherapy indicated for men with asymptomatic/minimally symptomatic metastatic CRPC. Recent analysis of immune responses in men treated with sipuleucel-T showed that antigen-specific immune responses to sipuleucel-T may be associated with survival, confirming the immune-based mechanism of action and suggesting the possibility that producing a stronger immune response may translate into the better clinical outcomes. Radiopharmaceutical agents have been shown to enhance immune modulation through a variety of mechanisms including enhanced display of tumor-associated antigens. Based on the immunomodulatory effects of radiopharmaceutical drugs, we hypothesized that combined use of radium-223 and sipuleucel-T may enhance the sipuleucel-T-induced immune response and improve clinical outcomes. Methods: This is a randomized phase 2 study comparing antigen-specific immune responses of sipuleucel-T used alone versus sipuleucel-T plus radium-223 in CRPC patients with bone metastases but no visceral involvement. Patients will be randomly assigned (1:1) to receive sipuleucel-T plus radium-223 (Arm 1) or sipuleucel-T alone (Arm 2); men in Arm 2 will receive 3 infusions of sipuleucel-T alone, while men in Arm 1 will receive 6 infusions of radium-223 plus 3 infusions of sipuleucel-T starting after the second radium-223 dose. The primary study objective is to determine whether addition of radium-223 to sipuleucel-T enhances immune response, as measured by peripheral PA2024-specific T-cell proliferation using a tritiated thymidine incorporation assay at 6 wks after the first sipuleucel-T infusion. With 15 men per arm, there is 80% power to detect a 3.6-fold increase in mean proliferation response between the two arms. PSA responses and radiographic responses (in men with measurable disease) will also be assessed. Incidence and severity of AEs will be graded according to CTCAE v4.0. Various immune parameters, both humoral and cellular, will be analyzed at multiple time points during the treatment period, and an exploratory assessment of antigen spread will also be performed.
Renal cell carcinoma avatar mouse models for the personalized cancer therapy era.
Authors: Cristina Suarez, Mar Martinez, Enrique Trilla, Gabriela Jimenez-Valerio, Ines de Torres, Rafael Morales, Jose Jimenez, David Lorente, Ana Vivancos, Paolo Nuciforo, Juan Morote, Joan Carles, Oriol Casanovas
Journal: Journal of Clinical Oncology (2015)

e15627 Background: Anti-angiogenic (AA) drugs are the cornerstone of fist-line (FL) treatment in renal cell carcinoma (RCC). While several mechanisms of resistance to AA have been described, second line (SL) therapies are disappointing with short PFS reported. A recent strategy makes use of individual patient-derived tumor models in animals for drug testing simultaneously with that patient’s FL and SL treatments (AVATAR). The predictive value of each specific AVATAR for that same original patient will be key in order to predict SL treatment response in the clinic trying to help in decision making in this setting. Methods: We generated a unique panel of patient-derived RCC mouse models based on orthotopic implantation of primary renal tumor biopsies or metastasis directly obtained from patients. Sunitinib FL treatment followed by different SL treatments are evaluated in each mouse model. Response to treatments in these models and molecular profiling in search of predictive factors of response/resistance will be performed. Results: In these RCC patients, tumor take rate in mice to develop AVATARs was 80% at 3 months after implantation. Previous data demonstrated positive association of grafting capacity with tumor stage and Fuhrman grade (p < 0.0001). AVATAR models faithfully reproduced each patient’s histological characteristics and metastatic capacity. These AVATARs are treated FL with AA drugs and, at the moment of emergence of resistance to therapy, treatment is switched to known and experimental SL treatments in different animal cohorts. Updated results on AVATAR treatment and prediction of patient’s responses will be presented. Conclusions: Thorough characterization of these AVATAR models together with their response to AA treatments we will be able to predict response/resistance to new SL treatments for our RCC patients as a personalized cancer therapy approach Patient Tumorgraft Histology Generation Time Drug Testing 1 REN 95 ccRCC G4 pT3c 45 2nd Line 2 REN 96 ccRCC G4 pT3b 29 2nd Line 3 REN 98 ccRCC G4 pT3a pNx 100 2nd Line 4 REN 100 ccRCC G3 pT2 N0 66 1st Line 5 REN 101 ccRCC G4 pT4 pN0 (80% sarcomatoid) 70 2nd Line 6 REN 102 ccRCC G2 pT3a pNx 62 1st Line 7 REN 103 Sarcomatoid RCC G4 pT4 pN0 pM1 - 2nd Line 8 REN 104 Papillary type 2 RCC pT1a pN1 pM0 - 1st Line
Biochemical profile and clinical characteristics of patients with suspected deep vein thrombosis and pulmonary embolism treated at the Barretos Cancer Hospital.
Authors: Lucio Flavio Barbour Fernandes, Adhemar Longatto-Filho, José Humberto Fregnani, Celia Maria Cassaro Strunz, Cleyton Zanardo de Oliveira, Marcia Maria Chiquitelli Marques Silveira, Henrique Cesar Santejo Silveira
Journal: Journal of Clinical Oncology (2015)

e20648 Background: vein thromboembolic events (VTE) significantly affect oncological patients, leading to increased morbidity and mortality. Early diagnosis could reduce these complications. Methods: 300 participants with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) were recruited. A questionnaire was conducted and if there was indication, a blood collection was performed. After reviewing the imaging examinations, they were classified into positive (presence of VTE) and negative (absence of VTE) cases, in order to compare their laboratory differences. Results: 297 participants were evaluated, 268 with suspected DVT, 101 positive and 29 cases of PE with 6 positive. Using the ROC curve analysis, the best cut-off was determined in order to discriminate the positive and negative groups: hemoglobin > 10g/dL (p = 0.003), hematocrit > 32% (p < 0.001), platelet 243k/mm3 (p = 0.108), creatinine > 0,80mg/dL, fibrinogen > 393mg/dL, tumor necrosis factor-alpha > 12,9pg/mL, factor Xa > 104%, ultrasensitive C reactive protein > 20,6mg/L, IL-6 11,3pg/ml, D-dimer > 633ng/ml and P-selectin > 21,6ng/ml. Predictive models were adjusted by distant metastasis and use of the oral contraceptive. The following variables were significant: ECOG-PS classification 2, 3 and 4, platelets, D-dimer and P-selectin. Two other regression models were prepared, Model 1: without P-Selectin, and Model 2: without D-dimer. The following results obtained: area under the curve 0.781 (p < 0.001) and 0.801 (p < 0.001), sensitivity 85.71% and 71.43%, specificity 50.88% and 78.72%, positive predictive value 30.00% and 60.00%, negative predictive value 93.55% and 86.09% and accuracy of 61.54% and 76.47%, respectively. Conclusions: both models of proposed scores were able to help in the diagnosis of the VTE in cancer patients.
A new paradigm in CLL: Minimizing toxicity by using the minimum effective dose (MED) of lenalidomide for older patients with CLL.
Authors: Nicole Lamanna, Mark L. Heaney, Peter George Maslak, Joseph G. Jurcic, Todd L. Rosenblat, Ariela Noy, Maria Lia Palomba, Mark Adam Weiss
Journal: Journal of Clinical Oncology (2012)

6609 Background: While CIT has proven active for younger patients with CLL; studies from Germany and MDACC with fludarabine or fludarabine- based regimens did not benefit the patient over the age of 65 or 70. As the median age of diagnosis is 72, the development of safe, active therapies for older patients is an unmet need in CLL. Lenalidomide is an active drug in CLL. The current clinical trial was designed to assess whether low-dose continuous lenalidomide therapy can provide long-term disease control with minimum toxicity in patients older than 65. Methods: Patients initiate lenalidomide at 2.5mg daily (28-day cycle) and only dose escalate for progressive disease (POD). Results: 18 patients have been enrolled: 12 men and 6 women, med age 70 (range 65-84) with Rai-intermediate (7 pts) or high-risk (11 pts; 61%) disease; med WBC 50.5 (6.7-326.3), HGB 10.3 (8.9-13.9), PLT 121 (44-215), β-2 microglobulin 4.9 (3.0-10.2). 16 (89%) patients had chromosomal abnormalities: 3 with 13q, 6 with tris 12, 3 with 11q, and 4 with 17p. 13 (72%) patients have unmutated IGHV. 5 (28%) patients were previously untreated; 13 (72%) had prior therapy (range 1-5; med 2). Median dose of lenalidomide is 2.5mg (range 2.5mg-10mg); median no. cycles is 7 (range 1-28). 11 patients (61%) are still on therapy (7 previously treated): 6 at 2.5mg; 4 at 5mg, and 1 at 10mg. 7 have discontinued therapy: 1 for ITP; 3 for POD including one with Richter’s, 2 for desquamating rash; and 1 withdrew consent. Only 2 patients had tumor lysis and 10 had tumor flare (8 given steroids briefly). In these older patients on long-term continuous treatment, therapy has been generally well tolerated. There have been no deaths on study. Pneumonia developed in 4 patients (3 of these had prior therapy). 1 patient with history of atrial fibrillation developed DVT/PE. Main hematologic toxicity is neutropenia seen in 11 patients but transient. Grade 3/4 thrombocytopenia and anemia was seen in 5 and 0 patients, respectively. Conclusions: Low-dose continuous lenalidomide therapy iappears to be well-tolerated and may offer long term disease control in some patients with CLL. Additional accrual and longer follow-up will be required to further assess the utility of this strategy.
Validity and utility of the University of Texas M. D. Anderson Symptom Inventory (MDASI) among prostate cancer patients: Data from E2Z02: Symptom Outcomes and Practice Patterns (SOAPP).
Authors: Linda J. Patrick-Miller, Fengmin Zhao, Charles S. Cleeland, Lynne I. Wagner, Michael Fisch, Tito R. Mendoza
Journal: Journal of Clinical Oncology (2012)

e15173 Background: Optimal treatment outcomes for patients (pts) with prostate cancer are dependent upon rigorous symptom assessment. The MDSAI, a patient-reported outcome measure of symptoms (sxs) and their impact validated in a sample of patients of diverse cancer types has the potential to inform symptom experience and guide treatment specific to prostate cancer pts. Methods: SOAPP, an Eastern Cooperative Oncology Group (ECOG) study, was conducted at academic and community medical oncology clinics and included pts with prostate cancer of all stages and phases of care. At baseline and 4 weeks, pts completed a measure of symptom severity and functional interference (MDASI). Symptom experiences and psychometric properties of the MDASI in prostate cancer pts (n = 320) were analyzed. Results: The 5 most prevalent moderate/severe sxs reported at baseline were fatigue (34%), disturbed sleep (25%), drowsiness (18%), pain (17%), and dry mouth (15%); moderate/severe nausea (5%) and vomiting (2%) were the least prevalent. At baseline ECOG performance status (PS) was ≥2 in 9% of pts. Pain, sadness, and difficulty remembering things occurred in 17%, 14%, and 13% respectively, and among pts whose PS worsened, severity of these sxs had the highest change scores at follow-up. Internal consistency and test-retest reliability of the MDASI were good, with Cronbach coefficient alphas ≥0.84 and intra-class correlations ≥0.78 for all subscales. Significantly higher scores and moderately large effects for the MDASI severity scale were reported by pts with poorer PS (2.2 vs 1.0, ES=.83) and tumor progression (2.4 vs 1.2, ES=.73) p&lt;.05. Results were similar for the interference scale, demonstrating MDASI known-group validity. Pts whose quality of life declined showed significantly greater increase in severity (1.1 vs .14, p&lt;.01) and interference (1.9 vs .28, p&lt;.004) from baseline to follow-up than pts whose quality of life was unchanged, demonstrating MDASI sensitivity to change. Conclusions: The MDASI is a valid, reliable, and sensitive symptom assessment method for descriptive and clinical studies, and patient care in medical oncology outpatients with prostate cancer.
Phase II study of FK228 in patients with hormone refractory prostate cancer (HRPC)
Authors: R. Molife, S. Patterson, C. Riggs, C. Higano, W. M. Stadler, D. Dearnaley, C. Parker, W. McCulloch, A. Shalaurov, J. S. De-Bono
Journal: Journal of Clinical Oncology (2006)

14554 Background: FK228 is a bicyclic depsipeptide that inhibits histone deacetylase (HDAC). HDAC inhibition results in accumulation of hyperacetylated histone proteins resulting in G1 and G2/M arrest, differentiation of transformed cells and apoptosis. FK228 can also inhibit HSP90, ablating androgen receptor expression. Methods: FK228 was administered intravenously at 13mg/m 2 on days 1, 8 and 15 of a 28-day schedule for up to 6 cycles. Sixteen patients were treated in stage 1. If ≥ 1 response was seen, an additional 9 patients were to be recruited. Eligibility criteria included: no prior chemotherapy, metastatic disease, ≤3 lines of hormonal therapy, QTcB &lt;500 msec, Karnofsky PS ≥80. The primary endpoint was to measure rate of disease control (complete response [CR], partial response [PR], stable disease [SD] for 6 months). Secondary endpoints were PSA response rate, time to PSA and objective disease progression, safety profile, effect on disease related symptoms and pharmacokinetics (PK) of FK228. Results: Interim results are available after 16 patients were enrolled in stage 1 and 5 patients in stage 2. Median age (n = 21): 65 years (range 43–77). 3 patients have completed 6 cycles of treatment, 4 are ongoing and 14 have discontinued. 16 patients are evaluable for radiological response and 18 for PSA response: 1 has achieved a confirmed radiological PR (6 months [m]), and 6 have confirmed SD (2 for 6m, 1 for 5 m, 1 for 4 m+, 1 for 3 m+). 2 of 18 have had a 50% fall in PSA (6 m, 4 m+) and another a 40% fall (5m). Most common drug related adverse events are (grade [gr],%): fatigue (gr 1–2, 88%), nausea (gr 1–2, 77%; gr 3, 10%), anorexia (gr 1–2, 72%), vomiting (gr 1–2, 55%; gr 3, 10%), non-specific asymptomatic ECG changes (gr 1–3, 44%), diarrhoea (gr 1–2, 38%), thrombocytopaenia (gr 1–2, 33%) and weight loss (gr 1, 20%). Conclusions: Interim results of treatment with FK228 suggest clinically relevant antitumor activity with an 18% disease control rate and a 11% PSA response rate. Toxicity is manageable. Accrual into the study continues. [Table: see text]
Outcomes and predictors of survival in testicular sarcomas.
Authors: Samer Alsidawi, Gustavo Figueiredo Marcondes Westin, Scott H. Okuno
Journal: Journal of Clinical Oncology (2017)

404 Background: Testicular sarcomas represent less than 1% of all testicular tumors in adults. Because of their rarity, little is known about the features and outcomes of these tumors. We present an analysis of the prognosis and survival predictors in patients with testicular sarcomas from the Surveillance, Epidemiology, and End Results Program (SEER). Methods: Using the SEER registry, we identified adults with testicular sarcomas between 1980 and 2013. Cases were identified using a combination of ICD-O-3 site and histology codes. The JMP and SEER*STAT 8.3.2 were used for statistical analysis. Overall survival (OS) was analyzed using the Kaplan-Meier method. The prognostic effect of variables was studied using Cox proportional hazards models. Results: We identified 264 patients with testicular sarcomas with a median follow-up time of 9.2 years. The median age at diagnosis was 55 years (range 15-94) and the median tumor size was 6.6 cm (range 0.7-45). 20% of patients with documented staging presented with de novo metastatic disease. Rhabdomyosarcomas were the most common histology (37%). The median OS was 129 months (95%; CI 85-180). OS rates at 1 year and 5 years were 85% and 62% respectively. 53% of deaths were related to cancer. 1-year OS rates for localized, locally advanced and metastatic disease were 91%, 93% and 53% (P&lt;0.0001). Variables that were significant for survival in univariate analysis included age, histology, stage, and surgical resection. Factors that negatively affected survival in multivariate analysis were age &gt;55 years (HR 2; 95% CI, 1.1-3.7), advanced stage (HR 4.8; 95% CI, 2.7-8.4) and surgical unresectability (HR 3.7; 95% CI, 1.1-9.3). Patients with rhabdomyosarcoma had favorable outcomes compared to other histologies (59% vs 17% alive at 10 years, P=0.01). Conclusions: Testicular sarcomas are rare entities with overall good prognosis after surgical resection. Patients presenting with distant metastases, however, have worse outcomes with only about 50% of the patients alive at 1 year. Rhabdomyosarcomas are the most common histology encountered and have relatively better survival. Younger age, earlier stage and surgical resection are factors associated with significantly better outcomes.
Pemetrexed (Pem) in combination with cisplatin (CP) or carboplatin (CB) for stage IV NSCLC: A single-institution experience.
Authors: Santiago Ponce Aix, Maria Blazquez, Lara Iglesias, Juan A. Núñez, Jon Zugazagoitia, Cesar Muñoz, Lucia Parrilla, Cristina Pernaut, Irene Otero, Eva Andres, Hernan Cortes-Funes
Journal: Journal of Clinical Oncology (2014)

e19160 Background: In phase III trials CP/Pem showed a significant improvement in survival in patients (p) with non-squamous histology. Moreover CP and CB differ slightly for toxicity and efficacy; thus, clinicians can individualize therapy. The objective of this retrospective study is to evaluate efficacy of Pem in combination with CP or CB in daily practice. Methods: We reviewed 105 p stage IV NSCLC (January 2008-March 2013) treated with CP (75 mg/m2) or CB (AUC5) plus Pem (500 mg/m2) every 3 weeks. After doublet p received Pem (500 mg/m2) maintenance or best supportive care (BSC) until disease progression or unacceptable toxicity. Results: 105 p, 26,6% female and 73,3% male. PS 0-1 in 80,2% of p and PS 2 in 17,1%. Median (M) age 63 y.o. Smoking status: 38,7% current smokers, 50% former smokers, 10,2% never smokers and 1% unknown. Histologic type: 66,9% adenocarcinoma, 26,2% large-cell carcinoma and 6,7% others. EGFR 46,6% wild type, 48,5% unknown and 4,7% mutated. M number of doublet cycles: 4 (1-9); 77,1% p received CB and 22,8% CP. 34 p (32,3%) received maintenance. M cycles of maintenance 4 (1-34). Response rate was 51% (CR 4,3% + PR 46,7%) and 21,7% SD, 72,7% p with clinical benefit. Median time to disease progression (MTP) 6,6 months (m) (95% CI 4,9 to 7,7 m) in all p. MTP of 7,8 m (95% CI 6,9 to 8,7 m) in pt with CB. MTP of 8,6 m (95% CI 7,6 to 9,6 m) in p with PS 0-1 and 5,5 m (95% CI 4,3 to 6,6 m) in p with PS 2, although were not significant (p<0,19). MTP was 9,7 m (95% CI 8,5 to 11,5 m) in maintenance and 4,2 m (95% CI 3,4 to 5,3 m) in BSC (p<0,004). Median overall survival (MOS) 10,3 m (95% CI 8,1 to 12,2 m) in all pt. MOS 12 m (95% CI 10,4 to 13,6 m) with CB/Pem. MOS of 12,3 m (95% CI 10,3 to 14,4 m) in p PS 0-1 and 6,6 m (95% CI 4,8 to 8,3 m) in p PS 2, but differences were not significant (p<0,15). MOS of 14,7 m (95% CI 11,6 to 18 m) in maintenance group and 8,1 m (95% CI 6,3 to 10,1 m) in BSC group (p<0,0009). Conclusions: Doublet platinum/pem and maintenance pem is effective achieving good response rates and prolonging overall survival in patients with non-squamous NSCLC. In our data of clinical practice, Pem in combination with CB is an acceptable option for medically unfit patients (PS 2 or renal impairment).