tbuckley/cabot-search huggingface dataset:
Impact of concomitant immunosuppression on the presentation and prognosis of patients with melanoma
Authors: A. Frankenthaler, M. Lee, V. Seery, S. Renzi, M. Kinnaman, V. Liu, E. Friedman, M. B. Atkins
Journal: Journal of Clinical Oncology (2009)

9070 Background: Melanoma has been reported to be susceptible to immune control. Therefore, we hypothesized that concomitant immune suppression might impact the course of the disease. Methods: We examined the Beth Israel Deaconess Medical Center Cutaneous Oncology Program database for pts with immune suppression at the time of melanoma diagnosis. The demographics and stage of these pts were compared to those in the database as a whole. In addition, 3 controls matched for age, gender, stage and tumor location were identified for each case and disease outcome was compared between cases and controls. Results: 19 pts were identified with melanoma and concomitant immune suppression in a database of 1820 melanoma pts. Other diagnoses included renal transplant (4) inflammatory arthritis (8), Multiple Sclerosis (2), and ulcerative colitis (3). Immunosuppressive meds included methotrexate, azothioprine, cyclosporine, prednisone, infliximab, and natalizumab. Melanoma stages at diagnosis were in situ 1, IB 7, IIA 1, IIB 1, IIIB 3, IIIC 5, and IV 1. Compared to the database as a whole, cases were more likely to be female (84% vs 45%) and have a higher disease stage (42% stage IIIB/C vs 26%). In addition, more cases appeared to have an amelanotic primary (21% vs. 5.4%) or an atypical mole syndrome (21% vs 10.2%). For pts who relapsed, the cases had a shorter disease free interval (DFI) (2.1 vs 9.7 yrs) than the controls. At a median f/up of 52 mos, 37% of the cases had relapsed and all of these pts had died. At a median f/up of 76 mos, 30% of the controls had relapsed yet only 47% of these pts had died. As a consequence, cases appeared more likely to have died of their disease than controls (42% vs 23%) (p=0.10). Conclusions: Compared to the general melanoma population, pts with concomitant immune suppression appear more likely to be female, have an amelanotic primary or atypical mole syndrome and more advanced disease at presentation. Although pts with concomitant immune suppression are equally likely to relapse compared to matched controls, those that relapse appear to have a shorter DFI and to be less likely to be salvaged, suggesting more aggressive tumor behavior in this setting. Thus, diagnosis and treatment of a primary melanoma at an early stage appears especially important in an immunosuppressed population. No significant financial relationships to disclose.
Effect of first-line treatment and CHFR and 14–3-3σ methylation status on survival to second-line chemotherapy or EGFR tyrosine kinase inhibitors (TKIs) in stage IV non-small-cell lung cancer (NSCLC)
Authors: J. Sánchez, M. Molina, T. Moran, R. A. Stahel, J. Ramírez, F. Salazar, P. Garrido Lopez, J. Bertran-Alamillo, M. Tarón, R. Rosell
Journal: Journal of Clinical Oncology (2008)

8068 Background: We analyzed the outcome of second-line chemotherapy vs EGFR TKIs in 179 of 366 patients (p) who had been included in an ERCC1-based customized cisplatin trial and correlated the results with first-line treatment and with CHFR and 14–3-3σ methylation status. Methods: CHFR and 14–3-3σ methylation in circulating DNA was examined by methylation-specific assay. A panel of seven human EGFR wild-type NSCLC cell lines was characterized for their sensitivity to sequential treatment with cisplatin and erlotinib, and the results were correlated with CHFR and 14–3-3σ. Results: Median survival (MS) for 105 p who received chemotherapy as second-line treatment was 10.8 months (m), while for 74 p who received EGFR TKIs, it was 19 m (P = 0.0002). MS for p with unmethylated CHFR was 21.4 m with EGFR TKIs and 11.2 m with chemotherapy (P = 0.0001). MS for p with methylated 14–3-3σ was 21.3 m with EGFR TKIs and 10.2 m with chemotherapy (P = 0.0004) (table). In the only lung tumor cell line not expressing CHFR, pretreatment with cisplatin was antagonistic with erlotinib, while it was synergistic in the other six lines. Conclusions: Second-line EGFR TKIs improved survival in p receiving first-line cisplatin-based treatment. Methylated 14–3-3σ and unmethylated CHFR increased survival to EGFR TKIs. CHFR expression predicted synergism to sequential cisplatin/erlotinib in lung tumor cell lines. Second line Chemo- therapy N Second line Chemo- therapy MS (m) EGFR TKIs N EGFR TKIs MS (m) p Total no. of patients 105 10.8 74 19 0.0002 First-line therapy Docetaxel/Cisplatin 79 10.68 56 19.21 0.0002 Docetaxel/Gemcitabine 26 10.84 18 14.84 0.29 CHFR Methylated 32 11.50 20 14.12 0.21 Unmethylated 59 11.21 43 21.36 0.0001 14–3-3 Methylated 33 10.18 28 21.36 0.0001 Unmethylated 54 11.50 35 18.58 0.01 No significant financial relationships to disclose.
Oxaliplatin/folinic acid/5-fluorouracil [24h] (OFF) plus best supportive care versus best supportive care alone (BSC) in second-line therapy of gemcitabine-refractory advanced pancreatic cancer (CONKO 003)
Authors: H. Oettle, U. Pelzer, J. Stieler, A. Hilbig, L. Roll, I. Schwaner, M. Adler, S. Detken, B. Dörken, H. Riess
Journal: Journal of Clinical Oncology (2005)

4031 Objective: Gemcitabine (G) is standard first line therapy in advanced pancreatic cancer. After disease progression no standard regime is available. Our phase II study (Pelzer et al; ASCO 2002; A: 684) showed activity of the OFF regimen in 23 patients (pts). To confirm these data we started a multicenter phase III study to determine the efficiency, toxicity and quality of life of OFF vs. BSC. After 46 pts. out of 165 planned pts. the BSC arm had to be closed because BSC alone was not longer accepted by participating centers. Methods: Following confirmed failure with G in 1st line we randomized pts. to BSC with OFF (A) or BSC (B) alone. Stratification included duration of 1st line therapy, Karnofsky Performance Status (KPS) and tumor stage. OFF as outpatient regimen: FU 2g/m2 (24h)/FA 200 mg/m2 (30min) on d1, d8, d15, d22 in combination with Oxaliplatin 85mg/m2 (2h) on day 8 and 22. Therapy paused on days 23 to 42. Eligibility criteria were KPS>60%, adequate hematological, renal and liver functions. Results: 46 pts. were randomized between 12/02 and 12/03. Both arms were well balanced regarding age, tumor stage, sex and KPS. The OFF regimen was tolerated with moderate toxicities similar to our phase II study. Median 1st line therapy (G) was Arm A/B 19,9/20,7 weeks. Median survival time of second line therapy in Arm A was 21 [95%CI; 18,7; 23,3] weeks; in Arm B 10 [95%CI; 7,7; 12,3] weeks; p=0,0077. Overall survival time in Arm A was 40 [95%CI 30,4; 48,8]weeks; in Arm B 34,4 [95%CI; 21,6; 47,2] weeks; p=0,0312. Conclusion: OFF regimen as second line therapy after G is feasible with acceptable toxicity in advanced pancreatic cancer. We showed a significant difference between OFF and BSC regarding survival after first line therapy and overall survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi/ Ribosepharm
Analysis of third-line and fourth-line chemotherapy for recurrent ovarian cancer treated with first-line platinum/taxane regimens
Authors: S. Nishio, N. Katsumata, K. Matsumoto, H. Tanabe, Y. Kato, K. Yonemori, T. Kouno, C. Shimizu, M. Ando, Y. Fujiwara
Journal: Journal of Clinical Oncology (2006)

15045 Background: Limited information is available regarding to the usefulness of third-line chemotherapy (TLC) and forth-line chemotherapy (FLC) for recurrent ovarian cancer treated with first-line platinum/taxane (PT) regimens. Methods: We retrospectively reviewed the medical records of patients (pts) with ovarian cancer treated with PT regimens at the National Cancer Center Hospital from 1998 to 2004. The aim of this study is to investigate the important clinical factor such as response rate (RR), time to treatment progression (TTP), overall survival (OS) and predictor of response to TLC and FLC. Kaplan-Meier method was used for estimating TTP and OS. Wilcoxon test was performed for survival times and p-values &lt; 0.05 were considered to be statistically significant. Results: There were 183 pts received first-line PT regimens in study period, 77 of 183 pts received second-line chemotherapy (SLC), 61 of 77 progressed after SLC and 55 of 61 pts received TLC. The RR to TLC was 34.5%. The median TTP was 5 months (mo) (range; 1–19 mo) and the median OS was 12 mo (range; 2–38 mo). The TLC regimen was consisted of P and/or T regimens of 36 pts and the other regimens of 19 pts. The RR according to the duration of response of previous chemotherapy (DRPC) (&lt; 6 mo and ≥ 6 mo) were 31.4% and 37.3%, respectively. The median OS of DRPC (&lt; 6 mo and ≥ 6 mo) were 8 mo (range; 2–33 mo) and 12 mo (range; 2–38 mo), respectively (p = 0.002). After TLC 47 pts progressed and 29 pts received FLC. The RR to FLC was 27.5%. The median TTP was 3 mo (range; 0–11 mo). The median OS of 18 pts who didn’t receive FLC and 29 pts received FLC were 2 mo (range; 2–16 mo) and 7 mo (range; 2–25 mo), respectively (p = 0.01). The RR according to DRPC (&lt; 4 mo and ≥ 4mo) were 22.2% and 30%, respectively. The median OS of DRPC (&lt; 4 mo and ≥ 4 mo) were 3 mo (range; 2–23 mo) and 6 mo (range; 2–25 mo), respectively (p = 0.4). Conclusions: The DRPC is considered to be predictor of response to TLC but not to FLC. Giving TLC and FLC if the pts have tolerable may improve OS, however this analysis is prone to several well-established potential biases and limitations. Further prospective study is warranted. [Table: see text]
Expression and Function of Class II Antigens on Gastric Carcinoma Cells and Gastric Epithelia: Differential Expression of DR, DQ, and DP Antigens&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K Sakai, M Takiguchi, S Mori, O Kobori, Y Morioka, H Inoko, M Sekiguchi, K Kano
Journal: JNCI Journal of the National Cancer Institute (1987)

The expression of human histocompatibility leukocyte antigen class II antigens on gastric epithelia and gastric carcinoma (GaCa) was studied with the use of murine monoclonal antibodies to DR, DQ, and DP antigens. DR and DP antigens but not DQ antigens were demonstrated in fundic glands of normal gastric epithelia, and DP+ cells were located in part of the DR+ epithelia. Of 15 GaCas examined, 11 expressed DR antigen, and the degree of the expression varied considerably among the specimens. DP antigen was found in 3 of the 11 DR+ carcinomas, and the DQ antigen was found in one of the 3 DR+ DP+ specimens. Thus the expression of class II antigens in normal gastric epithelia and GaCas appears to be in the order of DR, DP, and DQ. Studies on 3 GaCa cell lines (Kato III, MKN28, and MKN45) demonstrated that 1 line (Kato III) expressed DR antigen only, and the remaining lines were negative. Interferon (IFN)-γ treatment enhanced the expression of DR antigen on Kato III cells and induced expression of DQ and DP antigens. The IFN-γ treatment also induced expression of DR antigen but not DQ or DP antigens in 1 of the 2 negative cell lines. The induction of the class II antigens by IFN-γ was shown to be dose dependent. However, maximal induction of DQ and DP antigens on the Kato III cells and DR antigens on MKN45 cells required 10 times more IFN-γ than that needed for the maximal expression of DR antigen on Kato III. Northern blot analyses of cytoplasmic RNA from these cells were in agreement with and affirmed the above-described expression of the class II antigens on the cell lines. The DR antigen on the Kato III cells was capable of stimulating allogeneic lymphocytes in MLR, and its stimulatory activity was significantly enhanced by IFN-γ. These results demonstrated a differential expression of class II antigens in the “DR, DP, and DQ order” in normal gastric epithelia, GaCa cells, and GaCa cell lines, suggesting different mechanisms acting discordantly on the expression of each of these antigens and that the DR antigen on the GaCa cell lines possesses MLR-stimulatory ability.
Safety of the Synthetic Retinoid Fenretinide: Long-Term Results From a Controlled Clinical Trial for the Prevention of Contralateral Breast Cancer
Authors: Tiziana Camerini, Luigi Mariani, Giuseppe De Palo, Ettore Marubini, Maria Gaetana Di Mauro, Andrea Decensi, Alberto Costa, Umberto Veronesi
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To describe the pattern of occurrence of adverse events commonly arising during treatment with fenretinide, a synthetic retinoid under investigation for cancer prevention. PATIENTS AND METHODS: The series includes 2,867 women accrued in a trial aimed at assessing the effect of fenretinide on the prevention of second breast malignancy. Women were randomly assigned to receive no treatment (1,435 patients) or 5-year fenretinide treatment (1,432 patients). In terms of disease recurrence in the breast, the trial showed a possible beneficial effect of the compound in premenopausal women, and an opposite trend in postmenopausal women. End points considered for safety assessment were the occurrence of diminished dark adaptation, dermatologic disorders, gastrointestinal symptoms, disorders of the ocular surface, and abnormal laboratory values. RESULTS: The most common adverse events were diminished dark adaptation (cumulative incidence, 19.0%) and dermatologic disorders (18.6%). Less common events were gastrointestinal symptoms (13.0%) and disorders of the ocular surface (10.9%). In comparison, incidence figures in the control arm were 2.9% for diminished dark adaptation, 2.9% for dermatologic disorders, 5.4% for gastrointestinal symptoms, and 3.2% for disorders of the ocular surface. Symptoms occurring during fenretinide treatment tended to recover with time. No between-group difference was observed for the occurrence of laboratory data abnormalities. Overall, 63 (4.4%) treatment discontinuations were caused by adverse events. CONCLUSION: Given the number of patients involved in the study and the prolonged intake of the drug, the experience on fenretinide tolerability can be considered sufficiently reassuring to justify further testing of the retinoid.
New approaches in dendritic cell vaccination design and efficacy tests for patients with advanced ovarian cancer: Prospects for a phase I clinical study.
Authors: M. Imhof
Journal: Journal of Clinical Oncology (2010)

TPS158 Background: Ovarian cancer can be characterized by initial responsiveness to surgery and chemotherapy followed by high recurrence and mortality rates. Vaccination with autologous dendritic cells offers a treatment option that may delay or even prevent recurrent and metastatic disease. In this study, three substantial immunological novelties are introduced to improve monitoring and clinical results of the dendritic cell based vaccination: 1) Autologous dendritic cells are loaded with two tumor associated antigens (TAAs) via two different pathways to elicit in parallel CD4+ and CD8+ T cells. 2) This is the first time loaded peptides can be verified directly on the surface of the dendritic cells. 3) A method is proposed to quantify cycling tumor cells (CTCs) in peripheral blood as diagnostic marker specific for ovarian cancer. Methods: 20 patients with advanced ovarian cancer will be enrolled eight weeks after standard treatment (surgery and chemotherapy). Each patient will be vaccinated intradermally on a weekly or fortnightly basis with 6×106 double loaded autologous mature dendritic cells. Autologous dendritic cells are loaded with two universal TAAs: TERT-mRNA and Survivin-peptide. Evidence of presentation of loaded petides in corresponding MHC complexes on the surface of the cells is provided by confocal fluorescence microscopy images. The primary objective of the study is to investigate the safety and tolerability of the active investigated autologous dendritic cell vaccine. The secondary objective of the study is to collect preliminary information of additional clinical and non-clinical parameters about the efficacy of the investigated immunotherapy in terms of expression of specific tumor markers, survival rate, time-to-progression and monitoring of CTCs specific for ovarian cancer. Results of peptide presentation via the two pathways in MHC complexes on dendritic cell surface and preliminary data of CTC analysis specific for ovarian cancer will be presented. No significant financial relationships to disclose.
Abstract 11770: Cardiac Biomarker Elevation during Stem Cell Mobilisation, Apheresis and Intramyocardial Delivery is Common but does not Impact Incidence of Long-Term MACE: An Analysis from ACT34-CMI
Authors: Thomas J Povsic, Douglas W Losordo, Kenneth Story, Candice E Junge, Richard A Schatz, Robert A Harrington, Timothy D Henry
Journal: Circulation (2012)
Promoting patient safety in primary care
Authors: G. Ness, C. Cordess, S. Ruffles
Journal: BMJ (2002)

Promoting patient safety in primary care Honesty and openness may not be best policyEditor-We were both surprised by Wilson et al who, in their editorial, ask everybody to send in reports of their errors. 1Our concerns remain regardless of whether or not such accounts are published anonymously.After all, the police have used anonymous medical research data in their investigations.A conviction of culpable and reckless behaviour was secured against a man after he had sexual intercourse with his girlfriend without telling her he was infected with HIV.The scientific evidence that secured the conviction came from confidential research data that were obtained with a police warrant. 2 Furthermore, Wilson et all say that for doctors to report their errors, patient consent will be needed.This means that the patient will know that an account of his or her care is to be published and may read it.He or she may ask his lawyers to read it.The lawyers may then be able to substantiate this published account as a confession of guilt or negligence.Wherever and whoever we are, we must be careful as doctors what we say.For example, although we understand that no charges were brought, an incident last year highlights this point.Police are to hold a murder inquiry into the case of Peter Brand, a Member of Parliament for the Liberal Democrat Party for the Isle of Wight and a general practitioner, who mentioned during a parliamentary debate that he had withdrawn treatment from a two year old boy with leukaemia at the parents' request, to save him any more distress. 3This case had occurred in 1973, when he was a house officer.However regrettable, we do live in a culture of blame.To admit professional mistakes of a minor nature may be straightforwardly forgivable.The admission, however, of a serious offence or negligence by doctors may result in litigation against them.Before discussing such matters in public, doctors should seriously consider whether honesty and openness are the best policy.
Prognostic role of HER2 loss after neoadjuvant therapy in patients with HER2-positive operable breast cancer.
Authors: Valentina Guarneri, Elena Barbieri, Federico Piacentini, Maria Vittoria Dieci, Claudia Omarini, Guido Ficarra, Stefania Raffaella Bettelli, Pier Franco Conte
Journal: Journal of Clinical Oncology (2012)

631 Background: Emerging literature data are consistently showing that a change in HER2 status adversely affect the prognosis of breast cancer patients. Aim of the present analysis is to evaluate the prognostic impact of HER2 loss in breast cancer patients with HER2 positive disease treated with neoadjuvant therapy with or without anti-HER2 agents. Methods: A total of 94 HER2 positive patients were identified from a prospectively maintained database. The first cohort (A) includes 40 patients treated with chemotherapy alone (enrolled before 2005). The second cohort (B) includes 54 patients treated with neoadjuvant chemotherapy in combination with anti-HER2 agents (trastuzumab and/or lapatinib). HER2 expression was evaluated by IHC or FISH on pre-treatment core biopsy and on surgical specimen after neoadjuvant therapy. Patients were considered as having HER2 positive disease in case of IHC 3+ or FISH amplification. Results: No imbalance in terms of age, stage at diagnosis, tumor grade and expression of hormone receptor was observed in the two cohorts. In detail, 67% and 61% of the patients have a co-expression of HER2 and hormone receptor in cohort A and B, respectively. The rate of breast conservation was significantly higher in cohort B (chemotherapy+anti-HER2 agents) as compared to cohort A (chemotherapy alone) (59% vs 38%, p=0.048). Similarly, the rate of pathologic complete response (pCR) was significantly higher in cohort B (42.6% vs 7.5% in cohort A, p&lt;0.001). A change in HER2 expression from biopsy to post-therapy samples was observed in 35% of the patients in cohort A vs 9% of the patients in cohort B (p=0.04). No patients achieving a pCR have recurred so far vs 25% of the patients with less than pCR (p=0.005). The rate of recurrence was significantly higher for patients experiencing a change in HER2 expression (47% vs 15% in patients with no change, p=0.007). At 5 years, 53% of the patients with Her2 change and 75% of the patients without Her2 change were alive and free of recurrence (log rank test: p=0.03). Conclusions: The rate of HER2 loss was significantly higher in patients not receiving anti-HER2 agents as a part of the neoadjuvant therapy. In this series, the change in HER2 status has a negative prognostic impact.
Augmented Berlin-Frankfurt-Muenster (ABFM) regimen for children with standard-risk acute lymphoblastic leukemia (SR-ALL) and slow early response (SER)
Authors: Y. H. Matloub, A. Angiolillo, B. Bostrom, L. Stork, S. P. Hunger, J. Nachman, H. Sather, M. La, W. L. Carroll, P. S. Gaynon
Journal: Journal of Clinical Oncology (2007)

9511 Background: Numerous studies have shown that SER in ALL has a negative impact on outcome. Children's Cancer Group CCG-1882 demonstrated that post-induction intensification greatly improved the outcome of children with high-risk ALL and SER. Five year event-free-survival (EFS), and overall survival (OS) for the augmented regimen was 75 ± 4% vs 55 ± 4.5%, and 78 ± 4% vs 67 ± 5% for the standard regimen, p &lt;0.001 and 02 respectively (N Engl J Med 1998; 338:1663–71). Methods: Therefore, COG-1952 and COG- 1991, studies for patients with SR-ALL, assigned the slow early responders to augmented therapy, while others were randomized according to the study design. Study eligibility criteria were similar for both, and included newly diagnosed children with National Cancer Institute SR criteria. COG-1952 accrued a total of 2,027 patients and COG-1991 accrued 3,054. In COG-1952 patients were deemed SER if their day-7 marrow had &gt;5% blasts, and their day-14 marrow &gt;25%. COG-1991 used the same criteria for SER, but also added patients whose day-7 marrow had &gt;25% blasts and their day-14 marrow had &gt;5% blasts to the SER group. This was based on the unfavorable outcome of this subgroup in COG-1952. The augmented therapy in COG-1991 like the CCG-1882 and COG-1952, was based on a COG-modified ABFM, but differed in using dexamethasone as the sole steroid and pegylated asparaginase as the asparaginase preparation, as compared to prednisone in induction and maintenance, and native E coli asparaginase. Results: Comparative groups with days 7 and 14 M3 marrows and unfavorable cytogenetics included 126 patients from COG-1991 and 81 from the COG-1952 were assigned to their corresponding ABFM regimens. Four year EFS and OS were 85% ± 5% and 90 ± 4% for CCG-1991 vs 61 ± 5.6% and 75 ± 5% for CCG-1952, p = 0.003 and 0.04 respectively. Conclusion: We conclude that the use of dexamethasone, and pegylated asparaginase greatly improves the outcome of children with NCI-SR with SER treated on a modified augmented BFM therapy, thus supporting the use of these agents in ALL therapy. No significant financial relationships to disclose.