tbuckley/cabot-search huggingface dataset:
Primary prophylaxis of febrile neutropenia using long-acting granulocyte colony-stimulating factors in female patients receiving dose-dense biweekly chemotherapy in the clinical routine.
Authors: Christian M. Kurbacher, A. Tabea Kurbacher, Katja Monreal, Claudia Schweitzer, Sandra Sperling, Gabriele Kolberg, Jutta A. Kurbacher
Journal: Journal of Clinical Oncology (2015)

e20693 Background: Dose-dense q2w chemotherapy (ddCtx) which gains increasing importance in the treatment of breast (BC) and other gynecologic cancers (GC) requires primary prophylaxis (PP) with granulocyte colony-stimulating factors (G-CSFs) to prevent febrile neutropenia (FN). This retrospective analysis was initiated to yield detailed information on the use of long-acting (LA) G-CSFs as FN PP in the clinical routine. Methods: 53 pts with BC or GC were included, 27 received pegfilgrastim (cohort P), and 26 received lipegfilgrastim (cohort L). Both cohorts were well balanced in terms of tumor types and the proportion of pts with metastatic disease. In all pts, 1-4 ddCtx cycles (C) were evaluated. G-CSF-related toxicities were scored according to CTCAE 4.03. Hematological efficacy was determined by calculating the mean values for white blood cells (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) at baseline and for C 1-4. Additionally, the incidence of FN and G3-4 hematological toxicities during all ddCtx cycles was recorded. Results: Mean baseline values for WBC, ANC, and ALC were equal in both cohorts. Mean values for WBC, ANC, and ALC [109/L] for cohort P vs L were: cycle 1, 5.88 vs 12.67, 4.06 vs 12.57, 1.06 vs 1.70; cycle 2, 6.49 vs 12.34, 3.60 vs 10.03, 1.03 vs 1.37; cycle 3, 4.88 vs 17.10, 3.41 vs 12.37, 0.92 vs 1.55; cycle 4, 4.99 vs 8.65, 3.18 vs 6.91, 1.11 vs 1.15 with most these differences favoring L over P showing statistical significance. The incidence of FN, G3-4 neutropenia, and G3-4 lymphocytopenia was: cohort P, 2.2%, 5.6%, 5.6%; cohort L, 0%, 3.5%, 7.0% with none of these differences reaching statistical significance. C-CSF-related toxicities were generally manageable and did not significantly differ between both cohorts with: fever, 2 (7.4%) vs 1 (3.8%) pts; chills 2 (7.4%) vs 0 (0%) pts; bone pain, 2 (7.4%) vs 4 (15.4%) pts. Conclusions: LA G-CSFs were safe and effective as FN PP and other severe forms of ddCtx-related leukopenia. The higher hematological efficacy of lipegfilgrastim vs pegfilgrastim did not translate into a higher incidence of side-effects.
Immunoscore as new possible approach for the classification of melanoma.
Authors: Mariaelena Capone, Gabriele Madonna, Noemi Sebastiao, Jean Bird, Fabrizio Di Ayala, Corrado Caraco, Gennaro Ciliberto, Bonnie LaFleur, Nicola Mozzillo, Gerardo Botti, Alisa Tubbs, Paolo Antonio Ascierto
Journal: Journal of Clinical Oncology (2014)

e20020 Background: Immune cells infiltrating the tumor microenvironment (TILs) may either limit or promote tumor progression. Increasing evidence demonstrate that the number, type and location of TILs in primary tumors may have a prognostic role. These observations have led to the development of potential new scoring systems derived from the immune context in tissue and based on the identification and evaluation of specific lymphocyte populations. We explored the potential prognostic value of CD3, CD8, CD20, and FOXP3 as an 'Immunoscore' for melanoma patients which would utilize widely accessible, standardized technology. Methods: We collected FFPE lymphadenectomies from 34 melanoma patients, analyzing a total of 150 lymph nodes. We have characterized the Immunoscore by IHC expression of CD3, CD8, CD20 and Foxp3. 3-4 mm serial tissue sections have been cut for H&E and stained with a multiplex of all markers including tumor marker for melanoma (S100). Tissue sections were stained using novel multiplex staining protocols on a VENTANA Benchmark ULTRA instrument as well as serial staining. The number of positive cells has been evaluated by counting them in 5 peritumoral and 5 intratumoral non-overlapping fields using X400 magnification. The expression of each marker as well as combinations of markers have been matched with the most important clinical informations of patients evaluating correlation with clinical outcome. Results: For each case, manual cell counts and regional annotation were taken. The data for each patient were summarized as a median expression across sampled nodes, and these values were then compared between relapse and no relapse groups. There were statistically significant differences in the peri/intra ratio for both CD3 and CD8, with the ratio being higher in no relapse patients compared to relapse patients for both proteins. These trending differences also seemed apparent for both FoxP3 and CD20, although our limited sample size limited some conclusions. We then hypothesized a high/low risk score which we now plan to validate on a larger melanoma cohort. Conclusions: Our results indicate that if proven in additional studies the CD3, CD8, CD20, and FoxP3 panel could be useful as prognostic marker in high risk melanoma patients.
Meta-analysis of the risk of secondary neoplasm in patients treated for non-Hodgkin lymphoma with rituximab.
Authors: Isabelle Fleury, Sylvie Chevret, Sandy Amorim, Emanuele Zucca, Michael Herold, Michele Ghielmini, Pauline Brice, Bertrand Coiffier, Gilles A. Salles, Catherine Thieblemont
Journal: Journal of Clinical Oncology (2014)

e19541 Background: Rituximab has improved outcome of patients with CD20+ non-Hodgkin lymphoma (NHL). Rituximab induces a transient B-cell depletion and a dose-dependent T-cell inactivation predisposing to T-cell dependent infections. T-cells contribute to immunosurveillance, but rituximab has not been associated with secondary neoplasm (SN) in NHL. We performed a systematic review of published trials comparing chemotherapy with or without rituximab to evaluate SN risk. Methods: Primary endpoint was SN risk associated with rituximab in induction and/or maintenance for NHL treatment. We searched PubMed and Embase databases for randomized controlled trials on rituximab and lymphoma where treatment arms differed only from rituximab use and where SN incidence or related death were reported. Authors were asked for rituximab associated SN if not detailed. Chronic lymphocytic leukemia and HIV-related lymphomas were excluded due to increased SN risk. Updated follow-up presented at American Society of Clinical Oncology or American Society of Hematology meetings were retrieved. Data were extracted independently by two authors. A random effects DerSimonian-Laird meta-analysis was performed to estimate the summary effect of rituximab on the hazard of SN. Past rituximab therapy was allowed if shared in both trial arms and taken into account by the summary effect. Statistical heterogeneity was tested using Woolf test. Results: Among the 257 trials screened, 24 compared chemotherapy with or without rituximab. Rituximab associated SN data could be retrieved in only 8 trials cumulating 3399 patients, 1702 treated with rituximab and 1697 not. Median age was 57 years. Histology were diffuse large B cell (n=3), follicular (n=4) and marginal zone (n=1) lymphomas. At a median follow-up of 72 months [interquartile range: 57.5-91.5], rituximab did not increase SN risk (summary odds ratio = 0.88; 95%CI: 0.66-1.19) with no significant heterogeneity across trials (p= 0.93). Sex, histology and rituximab use in first line or length of exposure did not influence SN risk. Conclusions: Based on a 6 years follow-up, rituximab did not predispose to SN. Longer follow-up is warranted, with exhaustive reporting of SN in published trials.
Efficacy of oral vinorelbine (NVBo), capecitabine (X) and trastuzumab (H) triple combination (NVBoXH) in HER2-positive metastatic breast cancer (MBC): First results of an international phase II trial
Authors: A. Chan, V. Ganju, D. Becquart, P. Conte, L. Petruzelka, D. Aubert, G. Villanova, N. Tubiana-Mathieu
Journal: Journal of Clinical Oncology (2007)

1052 Background: Chemotherapy (CT) plus H is the standard first-line treatment for HER2-positive MBC. H plus vinorelbine is an active and well-tolerated regimen in this setting. The all-oral combination of NVBo and X also appears active and well-tolerated in MBC. We report efficacy and safety results from the first 34 patients (pts) included in an international trial evaluating NVBoXH in HER2-positive MBC. Methods: In this multicenter trial, main eligibility criteria included: HER2-positive disease (IHC 3+ or FISH+), documented measurable MBC previously untreated by CT, relapse 6 months after completing neoadjuvant or adjuvant CT, Karnofsky PS = 70, age =18 years. Pts received 3-weekly cycles of NVBo 60 mg/m 2 (cycle 1) escalating to 80 mg/m 2 (from cycle 2) days 1 and 8; × 1,000 mg/m 2 bid (750 if = 65 years) days 1–14; H 4 mg/kg day 1 as a loading dose then 2 mg/kg i.v. weekly starting on day 8. Treatment was continued until progression or unacceptable toxicity. Primary endpoint is overall response rate. Results: Baseline characteristics: median age 54 years (20% = 65); prior (neo)adjuvant CT 21 pts (62%); type of CT: anthracycline 52%, anthracycline + taxane 29%, CMF 14%, taxane 5%; visceral involvement 29 pts (85%), &gt;2 metastatic sites 13 pts (38%). Treatment administered: median 8 cycles, median relative dose intensity: NVBo 77%, X 81%, H 95%; NVBo dose escalation to 80 mg/m 2 in 91% of pts. Safety (n=34, G3/4 NCI CTC v2 adverse events): neutropenia 22 pts (65%), diarrhea 4 pts (12%), febrile neutropenia 3 pts (9%), vomiting 3 pts (9%), hand-foot syndrome 3 pts (9%), asthenia 3 pts (9%), infection without neutropenia 2 pts (6%), LVEF decline 2 pts (6%), stomatitis 1 pt (3%), nausea 1 pt (3%), constipation 1 pt (3%). Efficacy (n=31 evaluable pts): objective response rate (RECIST) 71% (95% CI [52–86]), CR 13%, PR 58%, SD 23%, PD 6%, disease control (CR+PR+ SD for =6 months) 84%. Progression-free survival, overall survival and duration of response data are not yet mature. Conclusions: This is the first trial, in pts with HER2-positive MBC, to show high efficacy with first-line NVBoXH therapy. This regimen can be safely administered in this pt population. No significant financial relationships to disclose.
Clinical significance of intratumoral HER2 heterogeneity (IHH) using endoscopic biopsy specimens in patients with HER2-positive gastric cancer (GC) who received T-mab-based chemotherapy.
Authors: Shusuke Yagi, Takeru Wakatsuki, Noriko Yamamoto, Keisho Chin, Daisuke Takahari, Mariko Ogura, Takashi Ichimura, Izuma Nakayama, Tomohiro Matsushima, Hiroki Osumi, Mitsukuni Suenaga, Masato Ozaka, Eiji Shinozaki, Yuichi Ishikawa, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2017)

81 Background: We recently reported the clinical significance of IHH in trastuzumab (T-mab) based chemotherapy using surgical specimens; namely homogeneously HER2 positive GC was associated with longer survivals compared with heterogeneously HER2 positive GC (ASCO-GI 2015). However, three quarters of patients were diagnosed as having GC by endoscopic biopsy and no data are available as to whether IHH using endoscopic biopsy specimens predict T-mab efficacy. In this study, we addressed clinical usefulness of IHH using endoscopic biopsy specimens. Methods: Patients who received T-mab based chemotherapy and had endoscopic biopsy specimens available for IHC test were retrospectively examined. When all biopsy specimens which contained cancer cells were diagnosed HER2 IHC3+, it was defined as “Inter-specimens homogeneously HER2 positive (Inter-homo)”, and the others were defined “Inter-hetero”. When all tumor cells showed HER2 overexpressed within a specimen, it was defined “Intra-specimen homogeneously HER2 positive (Intra-homo), and the others were defined “Intra-hetero”. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods and compared using the log-rank test. Results: 57 patients were enrolled in this study. The median age was 67 years old and 70% were male. PS 0, GEJ cancer, intestinal type histology, and visceral metastasis (lung or liver) were found in 74% , 25% , 60% , and 53% , respectively. After the median follow-up period of 12.1 months, the median PFS and OS were 7.6 and 16.9 months, respectively. Significant survival differences were shown only in the comparison between inter-homo and inter-hetero; inter-homo group (n = 34) showed significantly longer PFS (8.5 vs. 5.1 months, HR 0.52 95%CI 0.27-0.98, p = 0.038) and OS (27.6 vs. 12.1 months, HR 0.27 95%CI 0.12-0.61, p = 0.001), respectively. Conclusions: Our data suggest that, in contrast to surgical specimens, the assessment of HER2 heterogeneity using endoscopic biopsy specimens may be useful for negative selection of patients who are unlikely to benefit from T-mab based chemotherapy.
Targeting microenvironment-mediated resistance in leukemias: Phase I trial of mobilization and elimination of FLT3-ITD+ acute myelogenous leukemia (AML) stem/progenitor cells by plerixafor/g-CSF/sorafenib.
Authors: Michael Andreeff, Zhihong Zeng, Mary A Kelly, Rui-Yu Wang, Teresa J McQueen, Seshagiri Duvvuri, Gul Nowshad, Gautam Borthakur, Jan Andreas Burger, Tapan M. Kadia, Elias Jabbour, Jorge E. Cortes, Hagop Kantarjian, Marina Konopleva
Journal: Journal of Clinical Oncology (2012)

TPS6635 Background: FLT3-ITD AML are associated with poor prognosis. We identified Sorafenib (S) as potent inhibitor of FLT3-ITD (Zhang W, JNCI, 2008; Borthakur G., Haematologica, 2010). FLT3-ITD is associated with overexpression of chemokine receptor CXCR4 and we found increased in vivo activity of S combined with CXCR4 inhibitor Plerixafor (P) and G-CSF (G) (Zeng Z et.al. Blood 2009). Here we report first data testing this concept in patients with R/R FLT3-ITD AML. Methods: G (10 ug/kg) and P(240 ug/kg) were given s.c. QOD on days 1 – 13, S (400-600mg), S on d 1 - 28(one cycle). G/P was held when blasts &gt; 5x10 4/ uL. CD34, 38, 123, CXCR4 (1D9, 12G5), VLA4, CD44 and phospho-proteins were measured by flow cytometry. Results: 10 patients have been treated so far : 2 achieved CRp, 4 PR and 4 failed (NR), for an overall response rate of 6/10; 3/6 responders and 4/4 NR were previously treated with FLT3 inhibitors. 4/10 pts. developed hyperleukocytosis (and missed 1 to 5 doses of G/P), 6 skin rash and 3 hypertension. Analysis of cells mobilized in 22 cycles revealed a 29-fold increase in WBC, 41-fold in absolute blasts, 77-fold in granulocytes. Increase in circulating stem/progenitor cells was as follows: CD34+: 231-fold, CD34+/38- : 90-, CD34+/38-/123+(LSC) : 148-, CXCR4+: 139-, VLA-4+ : 68- and CD44+: 82-fold. Increase in LSC was correlated with baseline blasts and VLA4, not with CXCR4. FISH confirmed mobilization of leukemic cells. Increased levels of pERK and pAKT were observed in mobilized cells. Conclusion: The combination of G-CSF+Plerixafor appears superior in increasing circulating leukemic blasts and stem/progenitor cells in FLT3-ITD AML, as compared to Plerixafor alone in R/R AML(blast increase 2.1-fold; Uy et al. Blood, in press). Treatment resulted in 2/10 CRp and 4/10 PRs. Mobilized stem/progenitor cells displayed increased MAPK/AKT signaling and increased CXCR4 expression. This is the first clinical report of G-CSF/Plerixafor for the “mobilization” of AML cells, aimed at removing them from their protective bone marrow microenvironment. The initial results are providing proof-of–principle of this concept.
Use of modafinil to moderate the relationship between cancer-related fatigue and depression in 541 patients receiving chemotherapy: A URCC CCOP study.
Authors: Claire Conley, Charles E Heckler, Gary R. Morrow, Karen Michelle Mustian, Charles Stewart Kamen, Michelle Christine Janelsins, Luke Joseph Peppone, Anthony Joseph Scalzo, Howard M. Gross, Shaker R. Dakhil, Oxana Palesh
Journal: Journal of Clinical Oncology (2013)

9572 Background: Over 50% patients with cancer report symptoms of depression; 15% meet diagnostic criteria for Major Depressive Disorder. Depression is associated with increased insomnia, fatigue and reduced quality of life. We previously found that modafinil is effective for reducing high levels of fatigue among patients undergoing chemotherapy. This study aims to test whether modafinil can alleviate symptoms of depression by reducing fatigue. Methods: This study is a secondary analysis of 541 cancer patients receiving chemotherapy and experiencing fatigue (Brief Fatigue Inventory (BFI) &gt;=3) that were randomized to receive either 200 mg of modafinil (N=260) or placebo (N=281) daily from baseline (Cycle 2) until post-test (Cycle 4). Depression was measured by the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and post-test. The CES-D total score and its subscales (Positive Affect, Negative Affect, Somatic Symptoms, and Interpersonal Symptoms) were analyzed. A linear model with CES-D post (outcome) and BFI baseline, Arm, and BFI*Arm interaction term (independent variables) was used to address the hypothesis; p&lt;0.05 indicates significance. Results: We found no overall effect of modafinil on depression; however, the model demonstrated a significant moderating effect of modafinil on the relationship between baseline fatigue and CES-D total scores (p = 0.04). For subjects with severe fatigue (BFI ≥ 7), the drug reduced CES-D scores by 3-4. Modafinil also significantly moderated the relationship between baseline fatigue and Positive Affect subscale scores (p = 0.003), but not the relationship between baseline fatigue and Somatic, Negative Affect, or Interpersonal subscales. Conclusions: Modafinil differentially impacts depression based on a patient’s level of fatigue; reduced depressive symptoms occurred in those with extreme fatigue. This effect is driven by increases in positive affective symptoms. These results have significant implications for intervention; in patients with high levels of fatigue, modafinil might also reduce depression. Future RCTs are needed to confirm these results. Funding: U10CA37420, K07CA120025, K07CA132916.
Erratum for the Research Article: “Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients” by R. J. Morrison, S. J. Hollister, M. F. Niedner, M. G. Mahani, A. H. Park, D. K. Mehta, R. G. Ohye, G. E. Green
Journal: Science Translational Medicine (2015)
Breast cancer in Uruguayan young women less than 40 years old: Frequency and clinical-pathological characteristics.
Authors: Silvina Malvasio, Andrea Schiavone, Natalia Camejo, Cecilia Castillo, Maria Isabel Alonso, Lucia Beatriz Delgado, Roberto Notejane
Journal: Journal of Clinical Oncology (2015)

e11547 Background: To investigate the frequency, clinical pathological characteristics and prognosis of young women with breast cancer (BC) less than 40 years old and estimate disease free survival (DFS) for all patients and according to the biological subtype . Methods: Observational retrospective multicentric analysis of patients less than 40 years old treated between January 1st,2006 and December 31st, 2011. Data about clinical pathological characteristics was collected and DFS was estimated for all subjects and by tumor subtype using the Kaplan-Meier method. Subtypes were defined by immunohistochemistry Results: The analysis included 107 patients; median age was 35 years old (range 24 -39 years). Most patients were premenopausal at diagnosis (75%). Eighteen percent (19) of the patients had a strong family history of breast and/or ovarian cancer. The most frequent histological subtype was ductal infiltrating carcinoma (87.8%) most of them of a high histological grade (66%) .Distribution by stage was: 23 patients stage I, 47 patients stage II, 33 patients stage III and 4 patients stage IV. Fifty seven patients (53 %) were HER2- and estrogen receptor (ER) and/or progesteron receptor (PR) +, 24,5 % were HER2+ ( 13% HER 2+ RRHH + ;11,5 % HER2 + RRHH) and the rest (22,5 %) was classified as triple negative (TN). After a median follow up of 56 months, DFS at 3 years was 88% for all patients, 96% for the ER/PR + / HER2 - subgroup, 93% for the HER2 + and 60% for the TN subgroup. Kaplan Meier curves for DFS by subtype were similar for ER/PR +/HER2 -and HER2 + and significant different for the TN patients (p ˂ 0.0001) which showed a worst DFS. Conclusions: Our results shows that breast cancer arising in young Uruguayan women is characterized by the presence of less favorable subtypes such as HER2 +and TN breast cancer. Estimated DFS seems worse than that observed in older women. These results agree with those reported by US and European studies. Although it has been reported that the worse prognosis of young women is related in part to a delay in the diagnosis based on a low suspicion of the disease, we found that most of our patients were at a localized stage so we could just explain it because of the biological profile.
Neither vitamin E nor selenium prevents dementia, researchers find
Authors: Jacqui Wise
Journal: BMJ (2017)

Taking vitamin E or selenium supplements did not prevent dementia in asymptomatic older men, research published in JAMA Neurology has found.1

Oxidative stress has been implicated in Alzheimer’s disease, but it is unknown whether the use of antioxidant supplements can prevent dementia.

The Prevention of Alzheimer’s Disease by Vitamin E and Selenium (PREADViSE) trial was piggybacked onto a …
Contrasting vascular response to sunitinib as measured by DCE-CT, DCE-MRI, and DCE-US in renal cell carcinoma (RCC) patients (pts).
Authors: John M. Hudson, Ross Williams, Laurent M. Milot, Colleen Bailey, Alex Kiss, Mostafa Atri, Greg J. Stanisz, Peter N. Burns, Georg A. Bjarnason
Journal: Journal of Clinical Oncology (2013)

4583 Background: Imaging (DCE-MRI, DCE-CT, DCE-US) provides information about the integrity and hemodynamics of the tumor microvasculature. Methods: 34 treatment (Rx) naive pts with RCC and abdominal tumor suitable for imaging received sunitinib 50 mg on a standard 4/2 schedule. DCE-US, DCE-CT, and DCE-MRI were done at baseline, during the first course and after 2wks off Rx. Imaging parameters included vessel permeability (Ktrans), extracellular volume fraction (v e ) and Ktrans/v e =Kep (by DCE-MRI), permeability surface product (PS) by DCE-CT, blood volume (BV), by DCE-CT and DCE-US and blood perfusion (by DCE-US). A morphology parameter (MP) was developed that relates flow kinetics of the microbubble contrast agent to tumor vascular morphology by DCE-US. Results: Several imaging parameters predicted for progression free survival (PFS) in responding pts (N=26). Baseline imaging parameters correlated with PFS: Ktrans by DCE-MR (Spearman r= 0.53, p=0.01, N=24), BV by DCE-CT (r=0.48, p=0.02, N=25) and disorganized vessel morphology (large MP) by DCE-US (r= - 0.45, p=0.02, N=24). Changes from baseline imaging parameters correlated with PFS: BV by DCE-US at 2 wks (r= -0.46, p=0.02, N=24), Kep by DCE-MR at 2 wks (r= -0.45, p=0.03, N=24) and MP at 1wk (r=0.67, p=0.02, N=12). There was a correlation between imaging methods: BV measured by DCE-CT correlated with BV by DCE-US (r=0.46, p=0.03, N=23) and Kep by DCE-MR (r=0.59, p=0.003, N=22); Permeability measured by DCE-MR (Ktrans) and DCE-CT (PS) correlated at 2wks (r=0.56, p=0.01, N=21). A combination of baseline US and MR parameters identified responders and non-responders with a sensitivity of 83% and specificity of 90%. Conclusions: This is the first study to contrast DCE-US, DCE-CT and DCE-MRI imaging in pts receiving antiangiogenic therapy. Baseline parameters for all three methods can predict for PFS. Changes from baseline in DCE-US and DCE-MRI parameters also predict for PFS. There is a correlation between imaging methods in parameters that measure BV and permeability. A novel DCE-US parameter was developed (MP) that quantifies the degree of tumor vascular disorganization. Baseline values in MP and changes during Rx correlate with PFS. Clinical trial information: OCT1205.