tbuckley/cabot-search huggingface dataset:
Association of high T-cell immune infiltrate and low hemorrhage in melanoma brain metastases (MBMs) with prolonged survival.
Authors: Michal Tadeusz Krauze, Ronald H. Hamilton, Marjorie Romkes, Stephanie Bortoluzzi, Malgorzata Harasymczuk, Todd Reinhard, Beth Fallert Junecko, Tomoko Nukui, Panagiotis Konstantinopoulos, Dorothea Becker, Douglas Kondziolka, Ahmad A. Tarhini, Theresa Whiteside, Arlan H. Mintz, Hussein Tawbi, Soldano Ferrone, John M. Kirkwood, Stergios J Moschos
Journal: Journal of Clinical Oncology (2012)

8528 Background: Despite the poor prognosis of patients (pts) with MBM several pts have prolonged survival. We hypothesized that the heterogeneity of BrMM is determined by differences in melanoma biology and its brain microenvironment. Methods: We identified pts who have undergone craniotomy for MBMs. Evaluation entailed complete clinical information, acquisition of archived melanoma brain metastases, histopathologic analysis of hematoxylin and eosin-stained sections (n=101), whole genome expression profiling (WGEP, Illumina DASL) in 29 archived tissues. Results were validated by immunohistochemistry (IHC) or in situ hybridization (ISH). Results: In univariate analysis (log-rank) factors significantly associated with prolonged survival were high immune infiltrate (HII) plus low hemorrhage (hazard ratio, HR, 2.71, p&lt;0.001), present melanin (1.67, p=0.03), and recursive partitioning analysis (RPA) class 1 (0.37, p&lt;0.0001). No association between HII and use of immunotherapy prior to craniotomy was noted. Only RPA class 1 (p=0.029) and HII plus low hemorrhage (p=0.002) remained significant in Cox proportional hazards model analysis. Gene set analysis of WGEP data confirmed that Encarta pathways related with T-cell activation and differentiation were significantly associated with prolonged survival whereas Y branching of actin filaments, presenilin action in Notch and Wnt signaling, G-protein signaling through tubby protein, lissencephaly gene in neuronal migration and development are among the gene categories associated with worse survival. IHC and ISH analysis of tumor sections for various markers (n=40) showed that high peritumoral CD3+ (3.31, p=0.009), high peritumoral CD4+ (4.41, p=0.014), and high peritumoral CD8+ (3.02, p=0.030) are associated with prolonged survival whereas neither CD14+ nor FoxP3+ infiltrate, nor high melanoma expression of antigen presentation molecules are associated with survival. Conclusions: Our study is the first to document that high peritumoral T-cell infiltrates are associated with prolonged survival. High tumor hemorrhage, an adverse prognostic sign, reflects aggressive melanoma cells that migrate and invade in the brain.
Biomarker (BM) evaluations in the phase III AVAglio study of bevacizumab (Bv) plus standard radiotherapy (RT) and temozolomide (T) for newly diagnosed glioblastoma (GBM).
Authors: Ryo Nishikawa, Frank Saran, Warren Mason, Wolfgang Wick, Timothy Francis Cloughesy, Roger Henriksson, Magalie Hilton, Josep Garcia, Tobias Vogt, Celine Pallaud, Oliver L. Chinot
Journal: Journal of Clinical Oncology (2013)

2023^ Background: Bv plus 1st-line standard of care (SoC; T+RT) achieved a PFS benefit in the AVAglio phase III, randomized, double-blind, placebo [P]-controlled trial in patients (pts) with newly diagnosed GBM. AVAglio includes BM evaluation to identify pts benefiting most from Bv. Analysis of plasma VEGF-A and VEGFR-2 was prioritized based on encouraging findings in Bv trials in several tumor types. Methods: AVAglio includes an optional, exploratory correlative BM analysis; participating pts provided informed consent for BMs. Baseline (BL) plasma samples were analyzed using the Roche IMPACT platform, based on multiplex ELISA technology. Pts were dichotomized according to BM levels using either Q1, median or Q3 cut-offs. Potential interactions between BL BM levels and PFS were tested using Cox regression analyses. Results: Of 921 patients enrolled, 571 (62%) were evaluable in the BM study. Baseline characteristics and PFS outcome were comparable in the ITT and BM-evaluable populations. Median BL VEGF-A and VEGFR-2 levels were 77.0 pg/mL and 12.6 ng/mL, respectively. No significant interaction for PFS was seen at α=0.025. Conclusions: The potential predictive (VEGF-A, VEGFR-2) and prognostic (VEGF-A) value seen in breast, pancreatic and gastric cancers was not apparent in BL BM samples from AVAglio using a median, Q1 or Q3 cut-off. Additional plasma and tumor BM analyses are ongoing. Clinical trial information: NCT00943826. [Table: see text]
Sensitivity of Medicare claims to identify recurrence.
Authors: Joan L Warren, Angela Mariotto, Danielle Melbert, Deborah Schrag, Paul Doria-Rose, David F. Penson, K. Robin Yabroff
Journal: Journal of Clinical Oncology (2013)

6522 Background: Cancer registries do not collect recurrence data. As a result, researchers have used health claims to impute recurrence for cancer patients by identifying cancer therapy or metastatic disease after initial treatment. The validity of this approach has not been established. We used the linked SEER- Medicare data to assess the sensitivity of Medicare claims for cancer recurrence. Methods: Although the SEER-Medicare data do not explicitly capture recurrence, we applied criteria to identify patients likely to have had a recurrence, defined as patients diagnosed with Stage II/III colorectal (CRC) and female breast cancers from 1994-2003 who received initial cancer surgery, had at least a 90-day break in treatment following initial treatment, who then died from cancer in 1994-2008. For these patients, we reviewed all claims from the end of the treatment break to death for indicators of recurrence. Indicators included additional therapy (cancer surgery, chemotherapy, RT), diagnosis codes for metastasis, and end-of-life care. We used multivariate logistic regression analysis to evaluate patient factors associated with receipt of additional cancer therapy. Results: The first indicator of recurrence for CRC patients (n=6,910) and breast patients (n=3,826) was additional therapy (38.8% and 35.2%), metastasis diagnosis codes (36.0% and 45.7 %), or end-of-life care (16.7% and 12.8 %). Eight percent of patients had no indicator of recurrence before death; 40% of patients had no additional cancer therapy before death. Patients age 70 and older were less likely to have additional therapy (p&lt;0.05), in adjusted analyses. Conclusions: Identifying recurrence through additional cancer therapy will miss about 40 percent of patients with recurrences; particularly older patients. Over 20% of patients with recurrence were first identified by hospice admission, late in the course of their illness, or had no indicator of recurrence in the claims. We conclude that Medicare data have limited potential to identify cancer recurrence. These findings may not apply to younger cancer patients, who are more likely to undergo additional cancer treatment for recurrence.
IL23R Arg381Gln Variant in the Donor Confers Strong Protection Against Acute Graft-Versus Host Disease after Hematopoietic Stem Cell Transplantation in Children with Hematological Malignancies.
Authors: Bernd Gruhn, Juliane Intek, Nadine Pfaffendorf, Susan Wittig, Ilona Wolff, Isabella Schiller, Astrid Voigt, Ralf Häfer, Dietlinde Fuchs, Felix Zintl
Journal: Blood (2007)
Cost effectiveness of maintenance bevacizumab in patients with metastatic colorectal cancer.
Authors: Joel Lange, Rahul Rajeev, T. Clark Gamblin, Kiran Turaga
Journal: Journal of Clinical Oncology (2017)

718 Background: Observation alone after initial treatment of unresectable metastatic colorectal cancer is often anxiety provoking for physician and patient alike. The CAIRO 3 trial suggested the efficacy of maintenance capecitabine and bevacizumab in improving overall survival for such patients. We hypothesized that the cost effectiveness for maintenance capecitabine and bevacizumab would be worse than accepted population thresholds. Methods: Data from the CAIRO-3 trial was used to populate a semi-markov model, in which patients transitioned between different disease and complication based states. Transition probabilities were extratcted from the trial. Costs were determined from a thirs payer persective from the Medicare part B ASP drug pricing file. Utility was converted from the global quality of life scale. Incremental cost effectiveness ratios were calculated. Results: Cost of the maintenance arm after 10 cycles was $108,848 with a gain in 14.93 quality adjusted life months, while the quality adjusted life months gained at no cost in the observation arm was 13.67. This yielded an ICER of $1,036,648/QALY. Two way sensitivity analyses demonstrated dominance of observation across a wide range of parameters unless the cost per cycle was &lt; $6250. Conclusions: Maintenance capecitabine and bevacizumab is not cost effective and is higher than the willingness to pay threshold for any developed nation. Reducing drug pricing is the only way to financially support the argument for this treatment strategy.
Gender differences in hormonal statuses of patients with esophageal squamous cell carcinoma.
Authors: Evgeniy N. Kolesnikov, Oleg Ivanovich Kit, Elena Mikhaylovna Frantsiyants, Valeria Bandovkina, Margarita Kozlova, Natalia D. Cheryarina, Stanislav Stanislavovich Mezentsev, Alexander V. Snezhko
Journal: Journal of Clinical Oncology (2017)

85 Background: Esophageal squamous cell carcinoma (ESCC) is 4-8 times more frequent in men than in women, with poorer prognosis. The purpose of the study was to analyze systemic and local hormonal statuses in patients with ESCC in dependence on their gender. Methods: The study included 34 ESCC (G2, рT1-2N0-1M0) patients: 21 men and 13 women. 11 men (52.4%) had lymph node metastases. Levels of sex steroids – total (T) and free (fT) testosterone, progesterone (P4), estradiol (E2), estrone (E1), prolactin (PRL), LH, FSH and sex steroid-binding globulin (SSBG) – were studied in the peripheral blood, tumor and resection line by the standard RIA and ELISA methods. Results: Men showed a decrease in the blood T concentration by 1.4 times, P4 by 2 times, and E2 increase by 2.5 times, while women showed 1.3 times increase in T and 2 times decrease in P4. Metastases in men were accompanied by an increase in blood levels of anterior pituitary hormones: PRL by 2.5 times, LH by 2.3 times and FSH by 2.2 times compared to patients without metastases. Analysis of the local saturation with sex hormones in visually unchanged esophageal tissues of ESCC patients did not reveal any significant gender difference. However, women were characterized by a higher content of anterior pituitary hormones, PRL, LH and FSH, in esophageal tissues compared to men. Men with metastases showed local hyper-androgenization of tumor and surrounding tissues, as the fT to E1 ratio was increased. Conclusions: The results confirmed the data on T-stimulation of malignant growth in the esophagus and the possible protective effect of estrogens. The free testosterone to estrogens ratio in esophageal tissues can probably serve as one of prognostic factors for the disease course.
Ceritinib in anaplastic thyroid cancer (ATC) with ALK abnormalities.
Authors: Saad A. Khan, Julie E. Bauman, Barbara Burtness, Arthur E. Frankel, Jessica Harper, Randall S. Hughes, Pamela Kurian, Larry L. Myers, Lucien Alexander Nedzi, David L. Schwartz, Baran D. Sumer, John Truelson, Hong Zhu
Journal: Journal of Clinical Oncology (2015)

TPS6085 Background: ATC is a rare tumor of thyroid epithelium affecting several hundred patients annually, but causing death in almost 100% of them. It has a dismal prognosis with currently ineffective treatment options, particularly in metastatic disease. BRAF V600E mutations have been identified and then targeted with novel agents, which led to striking activity in patients (Rosove et al, NEJM 2013). ALK overexpression and mutation have also been identified in ATC in 11% of patient samples (Murugan et al, Cancer Res 2011). Patients treated with ALK inhibitors show dramatic tumor response (Godbert et al, JCO 2014). Ceritinib is a well-tolerated, highly potent oral ALK-inhibitor that is FDA-approved for use in ALK-rearranged lung cancer. It is critical to develop a framework by which anaplastic tumor samples can be collected, actionable mutations identified and novel agents rapidly tested. Methods: This multicenter, open label trial (NCT02289144) is collecting tissue from 100 patients with ATC/UTC. A genomic profile will be created by next generation sequencing of all 100 tumor samples. 10 of these patients are predicted to demonstrate ALK abnormalities; either by overexpression, mutations or rearrangements. Upon confirmation of metastatic or unresectable disease, patients with ALK-abnormalities will get 750 mg ceritinib daily. Prior therapy does not affect eligibility. Primary endpoint is progression free survival of 3.5 months, compared to historical controls. As patients are screened, their tumor tissue genomic profile will be collected and analyzed for future targets. As genomic profiling provides more information about actionable targets in ATC patients, additional therapeutic arms/sub-studies with other novel agents will be added to this trial. This protocol may serve as the basis by which newer therapies may be tested in this challenging disease. Clinical trial information: NCT02289144.
Relevance of platinum (plat) sensitivity status in previously treated extensive-stage small cell lung cancer (ES-SCLC) in the modern era: A patient level analysis of SWOG trials.
Authors: Primo Lara, James Moon, Mary Weber Redman, Karen Kelly, Jeffrey Warren Allen, Barbara Jennifer Gitlitz, Philip C. Mack, David R. Gandara
Journal: Journal of Clinical Oncology (2013)

7511 Background: ES-SCLC patients (pts) with progressive disease (PD) following plat-based chemo are traditionally categorized as plat-sensitive (PD &gt;/= 90 days from last plat dose) or refractory (PD &lt; 90 days). This practice arose from seminal observations in the early 1980s of worse survival in refractory pts. Subsequent trial designs accounted for plat-sensitivity status, resulting in higher sample sizes and increased resource use. Whether this relationship holds in the modern era is less clear. Methods: Updated data from recent SWOG trials in 2nd and/or 3rd line ES-SCLC (S0802: topotecan + aflibercept: S0435: sorafenib; and S0327: PS-341) were pooled. Accrual goals were specified for sensitive and refractory in each trial. Hazard ratios (HRs) for overall (OS) and progression-free survival (PFS) were calculated using Cox Proportional Hazard (PH) models [unadjusted and adjusted]. Results: Of 329 pts, 151 were classified as sensitive, 178 refractory; median age = 63 years; males = 52%; PS 1 = 67%; weight loss &gt;5% = 28%; &gt; 2 prior chemo = 16%; and elevated LDH = 43%. HRs from unadjusted Cox models for OS for refractory vs. sensitive were 1.0 (95% CI 0.81-1.25, p=0.98) and 1.24 (95% CI 0.99, 1.57; p=0.06). Cox PH models adjusted for baseline prognostic factors for PFS and OS are shown. Conclusions: In this large database analysis, plat-sensitivity status is no longer a significant independent variable for OS or PFS. Baseline PS, sex, LDH, and weight loss remain independent OS variables. These data have critical implications in the design of future trials in ES-SCLC. [Table: see text]
HCV-INFECTION-SPECIFIC MIRNAS CAPABLE OF REGULATING HCV REPLICATION
Authors: Takayoshi Shirasaki, Masao Honda, Kazunori Kawaguchi, Tetsuro Shimakami, Rika Horii, Hikari Okada, Junichi Saito, Norihiro Tokumaru, MinKyung Yi, Stanley Lemon, Shuichi Kaneko
Journal: Hepatology (2010)

HCV-INFECTION-SPECIFIC MIRNAS CAPABLE OF REGULATING HCV REPLICATION: 1038  Takayoshi Shirasaki;Masao Honda;Kazunori Kawaguchi;Tetsuro Shimakami;Rika Horii;Hikari Okada;Junichi Saito;Norihiro Tokumaru;MinKyung Yi;Stanley Lemon;Shuichi Kaneko; Hepatology
Interest of pretreatment quantification of anti-cetuximab IgE to prevent severe hypersensitivity reaction to cetuximab.
Authors: Benoit Dupont, Delphine Mariotte, Audrey Emmanuelle Dugue, Benedicte Clarisse, Jean-Michel Grellard, Emmanuel Babin, Bruno Chauffert, Stephanie Dakpe, Cristian Moldovan, Jean-Marie Reimund, Frédéric Di Fiore, Sylvie Zanetta, Marian Degardin, Pascal Do, Annie Peytier, Marie-Pierre Galais, Carmen Florescu, Roland Schott, Brigitte Le Mauff, Radj Gervais
Journal: Journal of Clinical Oncology (2014)

6028 Background: Hypersensitivity reactions (HSR) are dreaded and relatively frequent adverse events associated with cetuximab (CTX). High pretreatment levels of anti-CTX IgE have been observed in patients (pts) who experienced a grade 3-4 reaction (NCI CTCAE v3.0) after CTX administration. We hypothesized that dosage of anti-CTX IgE prior to treatment in pts naive to CTX may be used for therapeutic decisions to reduce the incidence of severe HSR. Our main objective was to compare the incidence of severe HSR during the first injection of CTX among pts with low levels of anti-CTX IgE, compared to an incidence of 5.2% retrospectively observed among 213 pts previously treated in our centre. Methods: We conducted a multicentre prospective diagnostic trial among pts with a colon or head-and-neck cancer, candidate to a first treatment by CTX. The pre-treatment level of anti-CTX IgE was measured. An IgE level lower than 30 EAU (IgE Arbitrary Unit) did not interfere with the therapeutic decision whereas for pts with levels of 30 EAU or higher, CTX indication was either revised or maintained provided that the 2 first injections were done under closer medical monitoring. Results: 300 of 303 included pts were assessable. Median age was 60 years old, sex ratio was 4.3 and 77% had head-and-neck cancer. Prevalence of high levels of anti-CTX IgE was 22% (66 pts): 38 (58%) of which received CTX vs 208 (89%) among low level pts. Severe HSR during the first injection were noted in 8 pts (5 grade 3 and 3 grade 4). No death was observed following HSR. The incidence among low level pts was significantly lower than the retrospective one (1.4%, p=0.03). The incidence of severe HSR was significantly higher among pts with high levels of IgE rather than low levels (5/38 vs 3/208; odds ratio=10.4, p=0.0027) Pts with severe HSR had higher levels of anti-CTX IgE (median 45 vs. 5 EAU, p=0.006). No significant relation was noted between severe HSR and gender, age, history of allergies or tumor localization. Conclusions: Our findings support the role of an allergic mechanism in CTX reactions. Detection of anti-CTX IgE prior to treatment is a feasible and helpful strategy to predict HSR and adapt care. Clinical trial information: NCT01436617.
End-of-life care for Medicare beneficiaries with ovarian cancer: Evaluation of intensity and rate of hospitalizations.
Authors: Alexi A. Wright, Craig Earle, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2013)

9523 Background: Patients with advanced cancer are receiving increasingly aggressive medical care at the end-of-life (EOL). Population-based studies have not examined the medical care that ovarian cancer patients receive near death. Methods: We identified a national cohort of 6,956 Medicare beneficiaries who were living in Surveillance, Epidemiology, and End Results (SEER) areas, were diagnosed with epithelial ovarian cancer between 1996 and 2007, and died from ovarian cancer by December 2007. Using multivariable models, we examined rates of aggressive medical care within 30 days of death over time and examined indications for hospitalizations near death. Results: Adjusted rates of intensive care unit (ICU) admissions and emergency department (ED) visits increased significantly between 1996 and 2007 (ICU: 6.4% to 16.6%, p&lt;0.0001 and ≥2 ED visits: 19.7% to 32.1%, p&lt;0.0001). In contrast, late (within 7 days death) or absent hospice referrals decreased (63.1% to 47.8%, p&lt;0.001) and chemotherapy use within 30 days of death decreased slightly (8.1% vs. 7.1%; p=0.04). Although terminal hospitalizations decreased (28.0% to 19.1%, p=0.001), rates of hospitalizations near death increased over time (41.4% vs. 45.3%, p=0.01). The most common indications for hospitalization included: bowel obstructions (20.0%), infections (10.4%), fluid or electrolyte abnormalities (9.2%), and malignant effusions (8.1%). Conclusions: Despite significant increases in the use of hospice near death, utilization of ICUs, EDs, and acute inpatient care at the EOL rose significantly between 1997 and 2007 for older ovarian cancer patients. Future studies should examine whether this high-intensity health care is avoidable given evidence that high-intensity care is associated with lower patient quality-of-life near death and increased complications in bereaved caregivers.
A “specialist first” system would increase waiting times
Authors: Rammya Mathew
Journal: BMJ (2017)

Greenfield and colleagues argue that gatekeeping is associated with delayed diagnosis and adverse outcomes for patients.1 But they do not present a strong enough argument that a “specialist first” system would reduce the waiting time from onset of symptoms to receipt of an appropriate diagnosis and treatment plan. If more patients self refer to specialist services without a simultaneous increase in the supply of specialists, …
MAGNIFY: A phase 3B, randomized trial of lenalidomide plus rituximab induction and maintenance therapy followed by lenalidomide single-agent versus rituximab maintenance in patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL).
Authors: David J Andorsky, Patricia E Cataruozolo, Jorge L Mouro, Ju Li, Pierre Fustier, Kenneth A. Foon, Jeff Porter Sharman
Journal: Journal of Clinical Oncology (2014)

TPS8617 Background: Immunomodulation with lenalidomide (L) + rituximab (R) is a promising treatment approach for patients (pts) with indolent NHL. In indolent NHL, frontline L+R provided a 90% overall response rate (ORR) and 64% complete response/complete response unconfirmed (CR/CRu) (Fowler, ASH, 2012). In phase 2 trials of L+R in relapsed/refractory (R/R) disease, pts with mantle-cell lymphoma (MCL) achieved 57% ORR and 36% CR (Wang, Lancet Oncol, 2012); pts with follicular lymphoma (FL) treated with L+R had a higher response rate (73% ORR, 36% CR) compared with those receiving L alone (51% ORR, 13% CR; Leonard, ASCO, oral presentation, 2012). Methods: The phase 3b MAGNIFY study will compare the efficacy and safety of 12 cycles of combination L+R for induction with randomization to L+R (Arm A) vs R (Arm B) maintenance in pts with R/R FL, MCL, or marginal zone lymphoma (MZL). Target enrollment is ~500. Pts will be randomized 1:1 to 28-day (d) treatment cycles. In both arms, pts will receive induction L (20 mg/d on d 1-21; 12 cycles) + R (375 mg/m2 on d 1, 8, 15, 22 in cycle 1; d1 of cycles 3, 5, 7, 9, 11). In Arm A, pts will receive maintenance L (10 mg/d on d 1-21; cycles 13-30) + R (375 mg/m2 on d1 of every other cycle from 13-29), followed by L (10 mg/d on d 1-21) until progression. Following 12 cycles of induction with L+R, pts in Arm B will receive maintenance R (375 mg/m2 on d1 of every other cycle from 13- 29). Eligible pts must have R/R grade 1, 2, or 3a FL, MZL, or MCL; have completed previous systemic therapy; have ≥1 measurable lesion; and have adequate bone marrow, liver, and renal function (moderate renal impairment acceptable). The primary endpoint is progression-free survival. Key secondary endpoints include rate of CR/CRu, overall survival, ORR, duration of response, duration of CR/CRu, and safety. Health-related quality of life, as measured by the FACT-Lym questionnaire, will be assessed as an exploratory endpoint. This trial is currently enrolling pts. Clinical trial information: NCT01996865.