tbuckley/cabot-search huggingface dataset:
Use of T-cell infiltrate to predict long-term survival following local therapy in tongue cancer patients.
Authors: J. Kim, S. Kim, J. Choi, B. Shin, S. Yoon, J. Seo, S. W. Shin, Y. H. Kim, J. S. Kim, K. Park
Journal: Journal of Clinical Oncology (2010)

5547 Background: Oral tongue squamous cell cancer (OTSCC) is one of the most aggressive subtypes in head and cancers. Currently, the most reliable prognostic indicator for OTSCC patients is the status of cervical lymph nodes. Identification of differences in tumor microenvironment might be of prognostic value in this type of cancer. Of those, the clinicopathologic significance of the tumor-infiltrating lymphocytes (TIL) in various human cancers has been an issue of great interest. However, importance of TIL in OTSCC has rarely been reported. The purpose of this study was to investigate whether the degree of TIL in the surgical specimens of OTSCC can be used to predict the clinical outcome following resection. Methods: We performed an immunohistochemical study to identify and count the number of CD4+ T cells, Foxp3+ regulatory T cells, Ki-67+ cells, and CD105+ cells in cancer nests and stroma in surgical specimens obtained from 53 OTSCC patients. Microvessel density (MVD) was measured with a light microscope in a single area of invasive tumor (200x field or 0.74 mm2) representative of the highest microvessel density. Correlation between the degree of TIL and clinicopathological variables, and survival rate were analyzed. Results: Patients with high TIL in cancer nests had significantly longer survival time than those with low TILs (5-year survival rate; 70% vs 33.9%, p=0.039). High density of TIL was observed more frequently in the patients who were current smokers or alcohol drinkers. Subsequent multivariate analysis revealed that degree of TIL was an independent prognostic factor in the patients with smoking associated cancers only (p=0.023 in Cox proportional hazard model), but not in non-smokers. In addition, higher MVD was observed in patients with high TIL. However, ratio of foxp3+ regulatory T cell did not correlate with survival in our patient series. Conclusions: Our data show that total T cell infiltrate in the invasive tumor is significantly correlated with overall survival time in patients with OTSCC after resection. Significant impact on survival of TIL was found only in patients with smoking-related cancer, suggesting immune response may play an important role in prognosis of smoking-related OTSCC. No significant financial relationships to disclose.
Shedding of distinct cryptic epitope (HU177) in sera of melanoma patients
Authors: J. Zakrzewski, B. Ng, M. Warycha, P. Christos, R. Shapiro, R. Berman, A. Pavlick, L. Liebes, P. Brooks, I. Osman
Journal: Journal of Clinical Oncology (2007)

8550 Background: Our preclinical data suggest that a newly identified cryptic epitope HU177 within collagen regulates endothelial and tumor cell adhesion in-vitro and angiogenesis and tumor growth in-vivo. We investigated whether 1) HU177 shedding can be measured in melanoma patients’ sera, and 2) if HU177 concentration correlates with clinicopathological features, recurrence and survival. Methods: Sera from 291 melanoma patients (primary Stage I, n=140; II n=41; III n=29; recurrent/metastatic n=81) and 30 normal volunteers prospectively enrolled at the NYU School of Medicine were analyzed for HU177 epitope concentration (ng/ml) by ELISA. Microtiter plates were incubated overnight with monoclonal antibody (anti-HU177 epitope). Patients’ sera and standards (denatured type-IV collagen) were added in duplicate followed by dilutions of biotinylated anti-collagen type IV polyclonal and HRP-labeled anti-biotin antibodies with multiple washes after each incubation. Absorbance was monitored at 400 nm. Results: The mean concentration of anti-HU177 epitope was 5.8 ng/ml (range 0.1 to 139.8). Normal volunteers were 1.6±0.3 (mean ± SEM). A significant correlation was observed between HU177 concentration and tumor thickness in patients who presented with primary melanoma (=1.00 mm, n=113, 3.8±0.4; 1.01–3.99 mm, n=72, 8.9 ±2.1; =4.00 mm, n=22, 10.3±2.2; P=0.003 by ANOVA test) and nodular melanoma histological subtype (nodular, n=47, 10.5±3.1; superficial spreading, n=95, 4.4±0.5; others, n=68, 6.0±2.1; P=0.02, ANOVA). Multivariate analysis confirmed the independent correlation between higher HU177 concentration and nodular subtype after controlling for tumor thickness (P=0.04). Primary patients with ulcerated melanomas and those who developed recurrences both showed higher HU177 epitope levels, however, the difference was not significant (P&gt;0.05). Conclusions: This is the first study on HU177 epitope shedding in melanoma patients. Data demonstrate the clinical feasibility of HU177 testing in melanoma patients’ sera and suggest that HU177 epitope shedding correlates with thicker primary melanomas. Longer follow-up is required to better define the prognostic value of HU177 epitope shedding in melanoma patients. [Table: see text]
Long-Term Results of Combined-Modality Therapy for Locally Advanced Breast Cancer With Ipsilateral Supraclavicular Metastases: The University of Texas M.D. Anderson Cancer Center Experience
Authors: Rogelio A. Brito, Vicente Valero, Aman U. Buzdar, Daniel J. Booser, Frederick Ames, Eric Strom, Merrick Ross, Richard L. Theriault, Debra Frye, Shu-Wan Kau, Lina Asmar, Marsha McNeese, S. Eva Singletary, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine outcomes in local-regional control, disease-free survival, and overall survival in patients with locally advanced breast cancer (LABC) who present with ipsilateral supraclavicular metastases and who are treated with combined-modality therapy. PATIENTS AND METHODS: Seventy patients with regional stage IV LABC, which is defined by our institution as LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease, received treatment on three prospective trials of neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil, or cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection (ALND) or segmental mastectomy and ALND before or after irradiation. Patients with no response to neoadjuvant chemotherapy were treated with surgery and/or radiotherapy. After completion of local therapy, chemotherapy was continued for four to 15 cycles, followed by radiotherapy. Patients older than 50 years who had estrogen receptor–positive tumors received tamoxifen for 5 years. RESULTS: Median follow-up was 11.6 years (range, 4.8 to 22.6 years). Disease-free survival rates at 5 and 10 years were 34% and 32%, respectively. The median disease-free survival was 1.9 years. Overall survival rates at 5 and 10 years were 41% and 31%, respectively. The median overall survival was 3.5 years. The overall response rate (partial and complete responses) to induction chemotherapy was 89%. No treatment-related deaths occurred. CONCLUSION: Patients with ipsilateral supraclavicular metastases but no other evidence of distant metastases warrant therapy administered with curative intent, ie, combined-modality therapy consisting of chemotherapy, surgery, and radiotherapy. Patients with ipsilateral supraclavicular metastases should be included in the stage IIIB category of the tumor-node-metastasis classification because their clinical course and prognosis are similar to those of patients with stage IIIB LABC.
Phase I study of recombinant human IL-18 (rhIL-18) administered as five daily intravenous infusions every 28 days in patients with solid tumors
Authors: M. J. Robertson, J. M. Kirkwood, T. Logan, H. M. Blair, J. R. Weisenbach, J. M. Shipe-Spotloe, L. Kirby, L. Thurmond, M. M. Dar, P. T. Ho
Journal: Journal of Clinical Oncology (2005)

2513 Background: rhIL-18, a potent immunomodulatory cytokine, has demonstrated anti-tumor activity in a variety of preclinical models. Depending on the model employed, multiple mediators appear to be critical to the anti-tumor activity of rhIL-18 including CD4+, CD8+, & NK cells as well as the Fas/FasL pathway & INFγ. In a previously completed phase I dose escalation study, rhIL-18 was found to be well-tolerated as a single cycle administered as 5 daily IV infusions without exceeding a maximum tolerated dose (MTD) at doses up to 1000 μg/kg/day. Methods: We conducted a phase I dose-escalation study to determine tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and clinical activity of rhIL-18 (SB485232) administered as a 2 hr infusion daily for 5 consecutive days (d) repeated every 28d, for at least 6 cycles in the absence of disease progression, to patients (pts) with solid tumors. Results: Nine pts (M/F 6/3), median age 56yrs (range 41–67 yrs), were enrolled to 3 sequential cohorts (100, 500, 1000 μg/kg/day). Tumor types enrolled included metastatic melanoma M1b(1)/M1c(5) and metastatic renal cell cancer (3). Three pts were withdrawn from the study due to progressive disease (1 at 100 μg/kg/day after Cycle 2; 1 at 100 μg/kg/day during Cycle 6; 1 at 1000 μg/kg/day after Cycle 4). The most common drug-related toxicities observed on this study included (total events): Grade (G) 1–3 fevers (10); G1–2 chill/rigors (12); G1–2 headaches/myalgias/arthralgias (9); G1–2 nausea (6). Three pts (1 in each dose cohort) developed anti-SB485232 antibodies (Abs) following exposure to rhIL-18 by Cycle 2. Ab levels generally did not increase with repeat dosing. Three subjects maintained stable disease per RECIST through the end of Cycle 6 (1 at 100 μg/kg/day and 2 at 500 μg/kg/day). Two pts remain on-study with stable disease at 1000 μg/kg/day through the end of Cycle 5. Conclusions: This is the 1st study to examine repeat cycle IV rhIL-18 dosing. rhIL-18 administered as 5 daily IV infusions every 28d was well-tolerated and did not exceed a MTD at doses up to 1000 μg/kg/day. A phase II study evaluating this schedule in metastatic melanoma is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline Chiron, GlaxoSmithKline
Role of the FDA in Affordability of Off-Patent Pharmaceuticals
Authors: Jeremy A. Greene, Gerard Anderson, Joshua M. Sharfstein
Journal: JAMA (2016)

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Prediction of early death risk in the elderly with cancer: Results of a prospective multicentric study of 364 patients under chemotherapy
Authors: P. Soubeyran, M. Rainfray, S. Mathoulin-Pélissier, C. Blanc-Bisson, C. Mertens, J. Blanc, J. Ceccaldi, Y. Imbert, J. Dauba, M. Fonck
Journal: Journal of Clinical Oncology (2007)

9040 Background: When it is time to decide for or against chemotherapy in elderly patients (pts) with cancer, physicians face the difficult balance of risks and benefits. Too much often, decision is based on empirical feelings rather than reliable and objective factors which are frequently lacking. Yet, elderly pts can benefit from chemotherapy in many situations. Method: To help physicians in the decision process of chemotherapy through identification of factors predicting early death (&lt; 6 months) from the onset of chemotherapy, we performed a prospective accrual of pts older than 70 with various types of cancer treated by 1st line chemotherapy. Baseline geriatric assessment (GA) (MMS, Get up and go, ADL, IADL, MNA, GDS15 , CIRS-G). Treatment was applied by the oncologist according to current standards disregarding GA results. Factors tested were: age, sex, advanced disease, renal and cardiac function, blood counts, performance status (PS), comorbidities and GA data. Results: 364 pts were accrued in 12 centres. Localisations were: lymphomas (110), colon (101), stomach (37), lung (37), pancreas (23), prostate (20), bladder (18), ovary (14) and unknown origin carcinomas (4). Main characteristics: median age (77.5 y. - range: 70- 99), sex ratio H/F (1.43), advanced tumours (66% - metastatic cancer or aaIPI 2–3 for lymphomas), PS&gt;1 (28%), creatinine clearance &lt;50 ml/mn (42%). GA showed 32% of pts ADL-dependent, 70% IADL-dependent, risk of falls in 12.4%, 19.2% MMS&lt;24, 30% GDS15 &gt;6, 63.4% MNA&lt;23.5, 38.2% = 1 CIRS-G gr. 3–4 category. 357 pts have been followed up for more than 6 months and 59 pts died during this period. Only advanced disease (OR: 4.2 - CI95:1.7–10.3) and MNA score (OR: 4.5 - CI95: 1.75–11.6) predicted early death in logistic regression model. In advanced tumours, risk of early death varied from 11% in pts with MNA&gt;23.5 to 40% in pts with MNA&lt;17. Conclusions: In pts older than 70 with cancer, disease extension and MNA could predict for early death. MNA, performed by a trained nurse, should probably be added to routine pre- treatment work-up in these pts to screen for multidisciplinary assessment and management by oncologists and geriatricians. Sponsored by PHRC, sanofi-aventis, Amgen, Pfizer [Table: see text]
Efficacy of reduced dose intensity FOLFOX-4 as first line palliative chemotherapy in elderly patients with advanced colorectal cancer (CRC)
Authors: D.-Y. Oh, Y.-J. Kim, S.-W. Han, I.-S. Choi, J. H. Kim, D.-W. Kim, S.-A. Im, T.-Y. Kim, D. S. Heo, Y.-J. Bang, N. K. Kim
Journal: Journal of Clinical Oncology (2005)

3720 Background: Elderly patients are underrepresented in clinical trials, and are often denied of palliative chemotherapy due to limited evidence of efficacy and fear of toxicities. To minimize toxicity and improve compliance of chemotherapy in elderly patients with advanced CRC, reduced dose intensity (mini-) FOLFOX-4 regimen was used as a first-line palliative chemotherapy. Methods: Using a prospective database, we analyzed efficacy and toxicity of mini-FOLFOX-4 regimen as first-line palliative chemotherapy in advanced CRC patients (older than 70 years of age) in Seoul Municipal Boramae Hospital and Seoul National University Bundang Hospital between Jan 2001 and Aug 2004. Schedule: L-OHP 65 mg/m2 on D1 + 5FU 300 mg/m2 iv bolus on D1, 2 + 5FU 450 mg/m2 continuous infusion over 22 hours on D1, 2 + Leucovorin 150 mg/m2 iv on D1, 2, every 2 weeks until progression, unacceptable toxicity or patient refusal. Response was assessed according to WHO criteria, and toxicity to NCI/CTEP CTC. Results: 27 patients were enrolled. M/F = 22/5, metastatic/recurrent = 9/18, colon/rectal = 17/10, PS = 1 in 16 patients, 2 in 10, and 3 in 1. Median age was 74 years (70–83). Total of 117 cycles were delivered. 22 patients were evaluable for response with an overall response rate of 31.8% (1 CR, 6 PR, 11 SD and 5 PD). Median progression-free survival was 7.1 months (95% CI: 4.3–9.9). Overall survival was 13.5 months (95% CI: 10.8–16.2). The main side effect was grade (G) 1/2 anemia and neutropenia, observed in 24.3% and 13.5% of total cycle given. There were no G4 toxicities and only one patient suffered from G3 neuropathy and vomiting. There was one episode of febrile neutropenia. Performance status and body weight was maintained throughout chemotherapy cycles. Conclusions: "Mini-FOLFOX-4" is well tolerated with acceptable toxicity without compromising objective response rate or survival in elderly patients with advanced CRC. No significant financial relationships to disclose.
Impact of weight and creatinine measurements in carboplatin dosing.
Authors: Feriel Boumedien, Youri Arsenault, Nathalie LeTarte
Journal: Journal of Clinical Oncology (2012)

e13027 Background: Controversy surrounding weight in Carboplatin dosing is still current. Also, new methods of measuring serum creatinine have raised more questions regarding the precision of Carboplatin dose calculations. The two objectives of this study were to evaluate the impact of alternative weight indicators (actual and adjusted body weight) in the Cockcroft–Gault equation and the use of different creatinine measurements (standard and IDMS) in order to accurately predict Carboplatin dose. Methods: We performed a retrospective chart review on all patients who received at least one dose of Carboplatin between March 7 th and May 8 th 2010. The patients were divided into two groups according to their body mass index (BMI): 20 &lt; BMI &lt; 27 and BMI ≥ 27. The differential creatinine clearance and Carboplatin dose were assessed in each group using the actual body weight and the adjusted body weight with IDMS creatinine. Moreover, for patients who had their creatinine measurement at the CHUM hospital, we calculate the difference in Carboplatin dose by using the standard creatinine (SC) measurement and IDMS creatinine with the same weight. Results: A total of 95 patients, representing 119 Carboplatin doses, were included in the analysis. 82% were women and median age was 63. The average BMI was 26,6. The Carboplatin expected AUC was 5 for 89% of patients and Carboplatin was associated to Paclitaxel in 78% of patients. In patients with a 20&lt;BMI&lt; 27 (44%), the average difference between the calculated dose using their actual body weight and adjusted body weight was +6.03% (95% CI, 5.2 to 6.9%). For patients with a BMI ≥ 27 (43%), the mean dose difference was +20.6% (95% CI, 18.8 to 22.5%). The use of SC or IDMS creatinine led to a discrepancy in doses of 5.2% (95% CI, 4.7 to 5.7%) for patients with BMI &lt;27 (35 patients) and 5.5% (95% CI, 4.9 to 6.2%) for those with BMI ≥ 27 (23 patients). Conclusions: Based on these findings, we decide in our clinic, to use the actual body weight for patients with a BMI between 20 and 27, and the adjusted body weight for those with a BMI ≥ 27. We also chose not to modify our doses based on the type of the serum creatinine measurement.
Clofarabine Salvage Therapy Prior To Allogeneic Hematopoietic Stem Cell Transplantation (HCT) In Patients With Relapsed Or Refractory Acute Leukemia
Authors: Josefina Serrano, Diana Buenasmañanas, P Herrera, Mari Luz Amigo, Marisa Calabuig, Eusebio Martin, Maria-Belén Vidriales, Adolfo de la Fuente, M Santero, Silvia Negri, Jose Gonzalez-Campos, Carmen Albo, Sonia Gonzalez, Jose J. Rifon, M Cruz Viguria, V Garcia-Gutierrez, Carmen Martin, Joaquin Sanchez-Garcia
Journal: Blood (2013)
p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes
Authors: F. Bidard, M. Mathieu, P. Chollet, I. Raoefils, C. Abrial, J. Dômont, M. Spielmann, S. Delaloge, F. André, F. Penault-Llorca
Journal: Journal of Clinical Oncology (2008)

608 Background: We hypothesized that, among molecular subclasses of breast cancer, p53 status may have a differential predictive value for the efficacy of anthracyclines/alkylating agents-based regimen. We analyzed the efficacy of a preoperative combination between 5-fluorouracil, anthracyclines and cyclophosphamide according to both p53 status and molecular classification. Methods: Two hundred ninety-three patients were retrospectively selected to have received 3 to 6 cycles of preoperative FEC regimen (5-FU: 500 mg/m2, farmorubicine: 50 to 100 mg/m, cyclophosphamide: 500 mg/m2) for a stage II-III breast adenocarcinoma. Estrogen receptor (ER), progesterone receptor (PR), HER2 and p53 status (IHC, DO7 monoclonal antibody, Dako, cut-off: 1% tumor cells) were determined by immunohistochemistry. A logistic regression model was used for multivariate analysis of predictors for pathological complete response (pCR). Results: p53 positivity (54%) was associated with high grade (p=0.002) and ER negativity (p=0.04). p53 was detected in 59% of triple-negative tumors (ER-/PR-/Her2-, n=120). In the overall population, pCR (9.6%) was independently predicted by high tumor grade (p=0.002) and ER/PR/HER2 triple negativity (p=0.0004), but not by p53 status (p=0.12). p53 immunostaining was associated with a higher rate of pCR in triple-negative tumors (RR=2.5, 95%CI=[0.8–7.5], p=0.09), but not in nontriple-negative tumors (RR=0.73, 95%CI=[0.16–3.3], p=0.69). Conclusions: This study suggests that p53 status may have a different predictive value for efficacy of anthracycline/alkylating agents-based regimen in each molecular subclass. This data suggests that predictive biomarker would be optimally investigated in homogeneous molecular classes. No significant financial relationships to disclose.
Shedding of EGFR is mediated by the ERK MAP kinase pathway
Authors: Blanca L. Valle, Nita J. Maihle, Elsa M. Cora
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4504 

We have detected a soluble isoform of EGFR in the conditioned culture media (CCM) of the breast adenocarcinoma cell line, MDA-MB-468. Amino acids sequence analysis of tryptic digest from this EGFR soluble isoform demonstrated that it arises from proteolytic cleavage of the membrane bound receptor. In this regard, proteolytic cleavage of EGFR was recently reported in the vulvar adenocarcinoma cell line A-431 by Zhen et al. (Biochemistry Journal, 42 (18):5478-5492; 2003). We named this protein as proteolytic soluble isoform of EGFR (PI-sEGFR). We have demonstrated that the release of PI-sEGFR into the CCM of MDA-MB-468 cells is stimulated by phorbol 12-myristate 13-acetate (PMA), epidermal growth factor (EGF), transforming growth factor alpha (TGF-a), fetal bovine serum and pervanadate. Moreover, our data suggest that the action of PMA on EGFR shedding is mediated by protein kinase C (PKC). We are interested to study if the action of PKC is mediated through the ERK MAP kinase signaling cascade. In this regard, the ERK MAP kinase signaling cascade mediates the PMA and growth factor induced ectodomain shedding of many transmembrane proteins (Fan H and Derynck R. The EMBO Journal, 18 (24):6962-6972, 1999). To examine the participation of ERK MAP kinase in the EGFR shedding, MDA-MB-468 cells were incubated with the MEK inhibitor, PD 98059 in the presence and absence of PMA. The released of PI-sEGFR was assessed by immunoblot analysis and by acridinium linked immunosorbent assay (ALISA) using antibodies specific for the extracellular domain of EGFR. The inhibition of ERK by PD 98059 was examined by immunoblot analysis using phospho-specific ERK antibodies. The results of these experiments shown that PD 98059 inhibited, as expected, the activation of Erk p42-44 and abolished the PMA-induced shedding of EGFR. Together, our results suggest that the shedding of EGFR in MDA-MB-468 cells is a regulated process and that the ERK MAP kinase signaling cascade might be involved. Supported by the NIH/NCI (CA73859, and CA85133), NIH/MBRS-SCORE (2-806GM08224), and NIH/COBRE (P200RR016439).