tbuckley/cabot-search huggingface dataset:
Survival of complete responder patients treated for esophageal cancer with chemoradiotherapy followed by surgery as compared to chemoradiotherapy alone: Case-control study.
Authors: M. Messager, G. Millet, N. Briez, G. Piessen, J. Triboulet, C. Mariette
Journal: Journal of Clinical Oncology (2010)

4089 Background: Exclusive chemoradiotherapy and chemoradiotherapy (CRT) followed by surgery are two optional strategies for curative treatment of oesophageal cancer. The aim of this study was to compare survival in case of complete response after exclusive CRT versus after neoadjuvant CRT. Methods: Between 1995 and 2007, 1,176 patients were treated for oesophageal cancer in our center. A case-control study was achieved among complete morphological responders after exclusive CRT (ECRT group) and complete histological responders after neoadjuvant CRT followed by surgery (control group, NCRT). Fifty five patients from the ECRT group were matched according to age, gender, tumoural location, TNM stage, ASA score, histological type and weight loss to 111 patients from the NCRT group. Response to CRT was assessed with endoscopy + biopsy and tomodensitometry in the ECRT group, and with histology of the primary tumour in the NCRT group. Results: The two groups, ECRT and NCRT respectively, were similar in terms of patients medium age (59 vs. 57 years), squamous cell carcinoma rate (87% vs. 91%), ASA score 2 or 3 (65% vs. 76%), infracarinal location (71% vs. 77%) and locally advanced disease (64% vs. 60%). After a median follow-up of 29.5 months, there were significant differences regarding median time to recurrence (10 vs. 18 months, p = 0.012), incidence of overall (67.2% vs. 34.4%) and loco-regional recurrences (33% vs 15%, p < 0.001). Median and 5-year survival rates were 25 vs. 61 months and 19% vs. 50% (p = 0.001), respectively. Conclusions: Survival in the situation of complete response is far better after CRT followed by surgery than after CRT alone. It is then convincing to promote surgical resection for these selected patients regarding to better locoregional control, and above all because evaluation of complete morphological response appears to be inefficient. No significant financial relationships to disclose.
Preclinical breast MRI findings in inflammatory breast carcinoma
Authors: F. Nakhlis, M. Duggan, M. Golshan, E. Levin
Journal: Journal of Clinical Oncology (2005)

899 Background: Inflammatory breast carcinoma (IBC) is an uncommon form of mammary cancer, known for its aggressive local and systemic behavior. The classic presentation of IBC is a large palpable breast mass associated with overlying skin erythema and warmth over at least one third of the breast, skin dimpling (peau d’orange) with or without thickening. In equivocal cases a punch biopsy of the affected skin can be helpful, however, when the latter is negative, the diagnosis of IBC can be quite difficult. We proposed that breast MRI, being a highly sensitive test for abnormal tissue enhancement, may be useful in evaluating dermal involvement by the underlying breast mass. Methods: Five patients with primary breast carcinoma and clinical exam findings equivocal for IBC were referred for a bilateral breast MRI. Results: are shown in the table below. In all five patients breast MRI documented diffuse skin thickening and abnormal enhancement on average 6.8 days before the clinical diagnosis of IBC was unequivocally confirmed. Conclusion: Breast MRI can be a useful tool in diagnosing IBC with equivocal clinical features. Moreover, breast MRI findings suggestive of IBC should not be ignored, since this diagnosis has significant therapeutic and prognostic implications. No significant financial relationships to disclose.
Effect of denosumab treatment in postmenopausal women with osteoporosis: eight-year results from the freedom extension, phase 3 clinical trial
Authors: E Lewieck, S Papapoulos, K Lippuner, C Roux, C Lin, D Kendler, M Brandi, E Czerwinski, E Franek, P Lakatos, S Minisola, Jean-Yves Reginster, S Jensen, N Kaizadeh, A Wang, M Gavin, R Wagman, H Bone
Journal: Endocrine Reviews (2014)
The role of activating mutations in the common signalling subunit of the receptors for interieukin-3, interleukin-5 and granulocyte-macrophage colony stimulating factor in polycythemia vera.
Authors: C. M. Butcher, P. G. Bardy, J. Gecz, T. Gonda, L. Cosgrove, R. J. D'Andrea
Journal: Blood (2003)
Therapy of palmar-plantar erythrodysesthesia after continual fluoropyrimidin administration with 10% uridin ointment
Authors: I. Netikova, E. Sedlackova, B. Konopasek, L. Petruzelka
Journal: Journal of Clinical Oncology (2009)

e20690 Background: Palmar-plantar erythrodysesthesia, so called hand -foot syndrom (HFS), is a common side effect and in many cases the limiting factor of chemotherapy with continual fluoropyrimidine administration. The exact mechanism of keratinocyte damage by fluoropyrimidins is as yet unknown, as well as effective therapy. Uridin was one of several chemicals that could influence cell metabolism of pyrimidins and is effective in case of HFS skin toxicity. The detailed pharmacological explanation of selective effect of uridin rescue has been missing. The local skin administration of uridin is proved to be efficient in patients with HFS; however, it works well only after 5-FU or capecitabine administration, but not as a prevention. This phenomenon is so far explained by displacing 5-FU from intracellular metabolic pathways due to the increased offer of uridine. Usage of an uridin ointment in spite of encouraging practical experiences has not been so far supported by any prospective randomized study. In many countries, including the Czech Republic, uridin is not registered for routine medical treatment. Methods: During the 2 years period 84 patients were treated with a fluoropyrimidin based chemotherapy (mainly capecitabin) with the 10% uridin ointment, 2–3 times daily and were followed. Number of chemotherapy cycles, a grade of HFS and it´s site, time of uridin local administration and a grade of HFS after treatment, were evaluted. Results: 16 patients have finished uridin treatment after first unit pack (100g). The reason was a change of therapy after tumor progresion or change of hospital. Next we evaluated a group of 68 patients. In 23 patients (34 %) we havent´t seen any effect. In 45 patients (66 %) decreasing of HFS intensity after 2 - 4 weeks of local administration about 1- 2 grades.1 pacient with alergic anamneses has developed atypical small white skin papulas. Other local or systemic allergic reactions were not observed. Conclusions: The 10% uridin ointment seems to be suitable as a supportive treatment for HFS. No significant financial relationships to disclose.
Effect of 25 hydroxy vitamin D status on serological response to influenza vaccine in cancer patients
Authors: M. K. Chadha, M. G. Fakih, L. Tian, T. Mashtare, M. Nesline, W. Davis, C. Silliman, D. L. Trump
Journal: Journal of Clinical Oncology (2009)

e20575 Background: Increasing epidemiologic data suggest association of vitamin D deficiency with influenza epidemic. Vitamin D acts as an immune modulator and stimulates the expression of protective anti-microbial peptides. We conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to flu vaccine in cancer patients. Methods: Cancer patients at Roswell Park Cancer Institute were offered trivalent (H1N1, H3N2, B/Malaysia) Flu vaccine (Fluzone, 2006–7) and sera collected for hemagglutination inhibition (HI) assay titers. Response to vaccination was defined as ≥ 1:40 titer ratio or a 4 fold increase in HI titer at 3 months post vaccination, against any of the 3 strains. Chi-square tests were performed to compare serological response between the groups with lowest and highest quartiles of baseline 25 (OH) vitamin D (D) level. Logistic regression model was used using other covariates such as age, gender, cancer type, and chemotherapy (CT) as controls. Results: 85 patients with colorectal, 35 with prostate, 1 with anal and 1 with gastric adenocarcinoma participated in the study. Median age was 62 years (range: 24–87 years), 85 (70%) were males. Overall serological response was 59%. Median baseline D level was 42.9 ng/mL (range: 4.0–92.8 ng/mL); lowest and highest quartiles were 26.9 and 53.4 ng/mL. There was no association between serological response and baseline D level (p=0.42) or the lowest and highest quartiles of D level (p=0.6). The odds of response did not vary by sex (p=0.95). CRC patients (OR-0.051; 95% CI-0.013 to 0.209; p&lt;0.0001) were less likely to respond. Few patients (n=20; 16%) were D deficient (&lt;20ng/mL), 43 had D &lt; 32ng/mL .70 patients (54.7%) were on vitamin D supplements. Among those in whom the dose of supplement was known (46),the median daily vitamin D supplement dose was 2000 IU (800–9000 IU).There was no association between serological response and dose (p=0.09). There was no difference in the response rates among patients on D supplement 44/70 (62.9%) versus those not on any D supplement 28/52 (53.8%)(p=0.32). Conclusions: Vitamin D status, in a population in which vitamin D supplementation was commonly used, did not affect serological response to influenza vaccine. No significant financial relationships to disclose.
BKM120 combined with vemurafenib in vemurafenib-refractory BRAF mutant metastatic melanoma: Two cases.
Authors: Alain Patrick Algazi, Christian Posch, Susana Ortiz-Urda, Alyson Cockerill, Pamela N. Munster, Adil Daud
Journal: Journal of Clinical Oncology (2013)

e20010 Background: PTEN loss and PI3K activation are common in BRAF mutant metastatic melanoma, and PI3K activation has been implicated as a cause of acquired resistance to BRAF inhibitors. Two vemurafenib refractory were treated with the potent BRAF inhibitor, vemurafenib, and the pan-class I PI3K inhibitor BKM120. Methods: The study enrolled BRAF-V600E/K mutant metastatic melanoma patients with an ECOG PS ≥ 2 and adequate organ function. Vemurafenib refractory BRAF-V600E/K mutant melanoma patients started both vemurafenib twice daily and BKM120 daily on cycle 1, day 1 after a vemurafenib washout of at least 14 days. Serial biopsies prior to treatment, on cycle 1 day 15, and at progression were obtained for pharmacodynamics analysis in patients with visible or palpable tumors. Results: 3 BRAF inhibitor refractory patients were treated on study with vemurafenib 720 mg PO bid and BKM120 60 mg PO daily. One patient was inevaluable due to non-compliance and had minimal exposure to study drug. Pre-treatment biopsy specimens were available in the remaining 2 vemurafenib-refractory patients. Both patient expressed PTEN at baseline and had demonstrable pAKT and pS6 staining. One patient had a mixed response to treatment with a 35.9% reduction in target lesions and two new small subcutaneous lesions. This patient also developed dose limiting febrile neutropenia on trial. The second patient tolerated treatment well but had widespread disease progression at 8 weeks. Conclusions: Combination therapy with vemurafenib and BKM120 in BRAF-V600E/K mutant melanoma led to substantial regression of several tumors in a PTEN+ patient with prior disease progression on vemurafenib alone. A phase I dose escalation trial in ongoing. Clinical trial information: NCT01512251.
Multimodal management of locally advanced (N2) non-small cell lung cancer (NSCLC): Is there a role for surgical resection? A single institution experience.
Authors: J. Bosch-Barrera, C. García-Franco, F. Guillen, M. Moreno-Jiménez, J. M. López-Picazo, A. Gurpide, J. L. Perez-Gracia, J. Aristu, J. Garcia-Foncillas, I. Gil-Bazo
Journal: Journal of Clinical Oncology (2010)

7064 Background: The treatment of locally advanced (N2) NSCLC is a controversial topic. Concurrent chemotherapy plus radiotherapy (CT-RT) is considered the standard of care for these patients (pts). Recently, no overall survival (OS) benefit was shown in pts receiving trimodality treatment (surgical resection after CT-RT). We present a single institution experience managing stage III (N2) NSCLC pts to determine if surgery (S) improves survival compared to definitive CT-RT alone. Methods: From 1996 to 2006, 71 stage IIIA/IIIB (N2) NSCLC pts were treated. 34 received cisplatin-based concurrent CT and hyperfractioned 3D-CRT [1.2 Gy b.i.d.; median dose: 66.5 Gy (range: 64-74)] and 37 underwent S [32 lobectomy (L) and 5 pneumonectomy (P)] preceded by neoadjuvant and/or followed by adjuvant therapy. Survival curves were estimated by Kaplan-Meier analysis. Results: Most pts (87%) were men. Median age was 59. A statistically significant correlation between T4c and definitive CT-RT (p=0.027), as well as between T1c and S (p=0.024) was noted. After a median 31.5 mo follow-up (range 5-140), median OS was 42 mo (IC 95: 26.7-57.3) for the S group vs. 41 mo (IC 95: 36.3-45.7) for CT-RT pts (p=0.974). The estimated survival at 5 years was 25.1% after S vs. 21.2% after CT-RT. Median PFS was 24 mo (IC 95: 6.9-41.1) after S and 49 mo (IC 95: 41.5-105.5) after CT-RT (p=0.401). Pts responding to CT-RT had a 43 mo OS (IC 95: 36.7-49.2) compared to 21 mo (IC 95: 10.9-31.0) for non-responders (p=0.007). pN0 status at thoracotomy was present in 14 (37.8%) pts after induction therapy, but no significant differences were found in OS between pN0 and pN2 pts. In the S group, subjects undergoing L showed a 33 mo PFS (IC 95: 0-77.7) vs. 18 mo (IC 95: 4.3-31.7) in P pts (p=0.21). Both arms were generally well-tolerated but 2 (5.4%) treatment-related deaths occurred in the S group. Conclusions: According to published data, S rendered no OS benefit compared to CT-RT in stage III N2 NSCLC. Any radiological response to CT-RT prognosticated an OS benefit. Even though pts selected for S seemed to have less locally advanced tumors, they showed similar survival outcomes to those exclusively treated with definitive CT-RT. No significant financial relationships to disclose.
Serum HAAH level in NSCLC is a diagnostic and could be a predictive factor of clinical response
Authors: D. Khayat, R. Mouawad, M. S. Lebowitz, H. A. Ghanbari
Journal: Journal of Clinical Oncology (2008)

22135 Background: The human aspartyl (asparaginyl) β-hydroxylase (HAAH) is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins. It was recently reported that the serum HAAH level in lung cancer can facilitate an earlier diagnosis of lung cancer and increase the rate of survival (Specificity amongst smokers of 90% and sensitivity of 98%). In this study we firstly compared HAAH serum levels in NSCLC patients vs. healthy individuals. Subsequently a follow-up of this marker was made in order to understand the possible implication of this protein with clinical response to treatment. Methods: Using an experimental double monoclonal antibody sandwich ELISA, HAAH level was measured in the sera of 46 patients with non small cell lung cancer (NSCLC) in comparison to 15 healthy controls. A further follow-up of HAAH level was performed on 22 patients before and after the treatment. Results: Serum HAAH was detectable and variable in 92% of NSCLC patients (n=43). Serum HAAH was found to be undetectable in healthy donors. When patients were compared to healthy donors the pretreatment median level of serum HAAH was significantly higher in NSCLC patients (P=0.00059). HAAH level did not correlate with gender or age. At the end of the treatment a decrease of HAAH level was noted. When patients were classified according to the clinical response pre-treatment HAAH levels were higher in patients that had progressive disease despite treatment (n=19) as compared to responder (n=9) or stable disease patients (n=14). At the end of treatment, a decrease of serum HAAH level was noted specifically in responder patients. Conclusion: Our results suggest that determination of pre-treatment serum HAAH levels could be helpful in the stratification of patients according to their clinical response and their follow-up. Due to the small number of patients, these results must be considered preliminary and a study in a higher number of patients is ongoing in order to confirm these interesting results. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Panacea Pharmacceuticals Panacea Pharmaceuticals Panacea Pharmaceuticals Panacea Pharmaceuticals Panacea Pharmaceuticals
A New Abl Kinase Inhibitor (AMN107) Has In Vitro Activity on CML Ph+Blast Cells Resistant to Imatinib.
Authors: Giovanni Martinelli, Alberto M. Martelli, Tiziana Grafone, Gianantonio Rosti, Irina Mantovani, Alessandra Cappellini, Pier Luigi Tazzari, Emanuela Ottaviani, Matteo Renzulli, Marilina Amabile, Angela Poerio, Simona Soverini, Carolina Terragna, Cristian Taccioli, Simona Bassi, Michele Baccarani
Journal: Blood (2004)
Initial safety report of NSABP C-08, a randomized phase III study of modified 5-fluorouracil (5-FU)/leucovorin (LCV) and oxaliplatin (OX) (mFOLFOX6) with or without bevacizumab (bev) in the adjuvant treatment of patients with stage II/III colon cancer
Authors: C. J. Allegra, G. Yothers, M. J. O'Connell, S. Sharif, N. Wolmark
Journal: Journal of Clinical Oncology (2008)

4006 Background: Bev with FOLFOX is active in advanced colorectal cancer (CRC). The C-08 trial investigates the effectiveness of adding bev to mFOLFOX6 for post-op adjuvant treatment of pts with stage II or III CRC. Methods: Pts were randomized 1:1 to receive either mFOLFOX6 q2w x 12 alone (OX 85 mg/m2, LCV 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 hours - Group A) or mFOLFOX6 plus bev (5 mg/kg q2w x 26 - Group B). The primary endpoint is disease- free survival. Results: From September 2004 to October 2006, 2,710 pts were randomized: Group A: 1,356, Group B: 1,354. Demographic factors were well balanced: 50% of pts female, 58% < age 60, and 25% stage II. 75% of pts completed at least 10 cycles of OX and 64% at least 19 doses of bev. Toxicities were well balanced in the 2 groups, overall rate of grade 4/5 toxicities 15.2% and 15.3% for groups A and B, respectively (Arm A: 13 deaths, Arm B: 17, 1.0% and 1.3%, respectively). Toxicities that occurred more often in arm B (table): sensory neuropathy (grade 2: 29 v 33%; grade 3: 14 v 16%; grade 4: < 1% each), hypertension, wound complications, pain (joint, muscle, chest and bone), proteinuria, and hand-foot syndrome. Wound complications (grade 3) were primarily the result of abdominal hernias or port dehiscence. Significantly fewer thrombocytopenia and allergic reactions were observed in arm B. Conclusions: With mean time on study of 22.4 mos, bev with mFOLFOX6 is well tolerated in the surgical adjuvant setting in pts with stage II/III CRC. Specifically, no significant increases in GI perforation, hemorrhage, arterial or venous thrombotic events or deaths with the addition of bev to mFOLFOX6 has been observed. Long-term followup for potential delayed side effects is ongoing. Supported by PHS grants U10CA-12027, -69974, -37377, and -69651 from the NCI and a grant from Genentech, Inc. Grade 3+ toxicities occurring at significantly different rates Toxicity Arm A (%) Arm B (%) P Neurosensory (grade 2+) 43.2 49.4 0.002 Hypertension 1.8 12.7 <0.001 Wound complications 0.3 1.7 <0.001 Pain (joint, muscle, chest, bone) 3.4 6.9 <0.001 Proteinuria 0.2 0.9 0.035 Hand-foot syndrome 1.4 2.5 0.047 Thrombocytopenia 3.4 1.4 0.002 Allergic reaction 4.7 3.0 0.033 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, sanofi-aventis
Ex-vivo culture with γchain cytokines restores defective maturation and activation of tumor infiltrating lymphocytes in indolent non-Hodgkin’s lymphoma
Authors: M. A. Di Nicola, C. Carlo-Stella, R. Mortarini, A. Anichini, A. M. Gianni
Journal: Journal of Clinical Oncology (2005)

9589 This study was aimed at investigating the development of T cell-mediated immune response in B cell tumor patients and at defining the optimal conditions for developing adoptive immunotherapy protocols. The following assessments were carried out utilizing T cells isolated from involved lymph-nodes (LN), peripheral blood or bone marrow of patients with indolent NHL (40 follicular, 32 CLL, 8 MCL): 1. distribution of TCRBV repertoire; 2. analysis of the activation profile; 3. analysis of the differentiation phenotype along the naïve to effector and memory stages by expression of CD45RA, CCR7 and cytolytic factors perforin and granzyme B. The analysis of TCRBV repertoire of CD4+ and CD8+ cells indicated very limited T cell expansions in CD4+ cells in a fraction of patients. This data suggested a reduced effect of neoplastic tissue in shaping the TCRBV repertoire in the LN. Therefore, in most instances, both CD4+ and CD8+ cells were not in a resting condition with high expression of CD69, HLA-DR and CD95 associated to a low expression of CD25 and CD122. Finally, both CD4+ and CD8+ T cells in either periphery, or at tumor site, expressed mainly the early stages of differentiation. The skewed maturation of CD4+ and CD8+ T cells was further confirmed by the low/absent expression of perforin and granzyme B. In contrast, the differentiation phenotype of CD4+ and CD8+ T cells from a panel of 47 healthy donors showed all four T cell maturation stages. T cell culture for 1 to 2 weeks, in the presence of cytokines of the γc family, led to down modulation of CCR7 and expression of perforin and granzyme B in T cells from either peripheral blood and tumor site. Co-culture of T cells isolated from tumor-containing LN with irradiated autologous NHL B cells (n=10) in the presence of IL-2+IL-15 led to an average 45-fold increase of number of CD3+ T-lymphocytes and to activation of tumor-specific T cells as assessed by IFN-γ release and tumor lysis assays. Thus, cytokine-driven functional maturation of tumor-specific T cells from B cell tumor patients could represent an option for reversal of impaired differentiation/activation and for development of adoptive immunotherapy strategies. No significant financial relationships to disclose.
Cross-Reactivity Between Cell-Surface Antigens of Different Murine Carcinogen-Induced Tumors, Demonstrated by a Modified Isotopic Antiglobulin Test2
Authors: James F. Burdick, Samuel A. Wells
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Cross-Reactivity Between Cell-Surface Antigens of Different Murine Carcinogen-Induced Tumors, Demonstrated by a Modified Isotopic Antiglobulin Test Get access James F. Burdick, James F. Burdick Search for other works by this author on: Oxford Academic PubMed Google Scholar Samuel A. Wells, Jr. Samuel A. Wells, Jr. Tumor Immunology Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 4, October 1973, Pages 1149–1156, https://doi.org/10.1093/jnci/51.4.1149 Published: 01 October 1973 Article history Received: 07 March 1973 Accepted: 19 June 1973 Published: 01 October 1973
Abstract 12163: Prognostic Value of Stress Perfusion Computed Tomography in Comparison With Coronary Computed Tomographic Angiography in Patients With Known or Suspected Coronary Artery Disease
Authors: Shiro Nakamori, Kakuya Kitagawa, Katsuya Onishi, Masaki Ishida, Hiroshi Nakajima, Motonori Nagata, Kaoru Dohi, Takashi Tanigawa, Mashio Nakamura, Hajime Sakuma, Masaaki Ito
Journal: Circulation (2012)

Introduction: Contrast enhanced computed tomography (CT) with vasodilator stress can provide comprehensive assessment of coronary arterial stenosis and myocardial ischemia. However, no data are ava...
Influence of Drug Exposure and Genetic Variation on Paclitaxel–Induced Neurotoxicity
Authors: A.M. De Graan, L. Elens, A. Sparreboom, L.E. Friberg, B. van der Holt, P.J. De Raaf, E.A.C. Wiemer, J. Verweij, R.H. van Schaik, R.H.J. Mathijssen
Journal: Annals of Oncology (2012)