tbuckley/cabot-search huggingface dataset:
Updated survival, toxicity, and biomarkers of nivolumab with/without peptide vaccine in patients naive to, or progressed on, ipilimumab (IPI).
Authors: Jeffrey S. Weber, Ragini Reiney Kudchadkar, Geoffrey Thomas Gibney, Bin Yu, PingYan Cheng, Alberto J Martinez, Jodi Kroeger, Donna Gallenstein, Allison Richards, Eric Welsh, Xiuhua Zhao, Xiaotao Qu, Ann Chen
Journal: Journal of Clinical Oncology (2014)

3009 Background: PD-1 antibodyNivolumab was administered with/without a multi-peptide vaccine to 105 patients (pts) with unresectable melanoma that failed at least one regimen and were IPI naïve, or progressed after IPI, to assess its toxicity especially in those with prior dose limiting immune related adverse events (irAEs) to IPI, and to update survival data, characterize T cell gene expression and immune cell subsets. Methods: HLA A0201 IPI-naïve pts received nivolumab at 1, 3 or 10 mg/kg (34 pts); additional pts that failed prior IPI received nivolumab at 3 mg/kg: two cohorts of pts were A*0201 positive and had either grade 2 or less IPI-related irAE (10 pts), or grade 3-4 dose limiting irAE (20 pts); 41 pts had grade 2 or less irAE, were not HLA restricted and received nivolumab alone. Pre- and 12 week post-treatment peripheral blood was analyzed. Results: Median follow-up for all pts was 15 months (mos);median progression-free survival (PFS) was 4.2 mos, and estimated median overall survival (OS) was 16.7 mos (95% CI: 14.4, not reached) with 1 year OS of 65%. Median OS was similar for IPI-naïve or IPI-relapsed pts (15.9 vs. 18 mos, p=0.6), older or younger than 62 (p=0.44) and by dose (p=0.86). ORR, median PFS and OS were longer in males than females (all p<0.05). Of 20 pts with prior IPI-induced grades 3-4 irAEs, only 1 had a subsequent grade 3-4 irAE with nivolumab and it was different than seen with prior IPI, but treatment emergent grades 1-2 rash and injection reactions were common. Biomarker studies showed that circulating HLA-DR lo/CD14+/CD11b+ myeloid-derived suppressor cells (MDSC, p=0.028), and FCRL2+ CD8 T cells (p=0.009) were associated with progression. Decreased regulatory molecules BTLA and LAG3 on CD8+ T cells were associated with response (p=0.04). Principal component analysis of genes expressed by flow sorted CD8 T cells showed clustering by response (p = 6.01E-10) Conclusions: Median OS of 16.7 mos and PFS of 4.2 mos with nivolumab was observed in previously treated melanoma patients naïve to or failing IPI. Prior irAEs to IPI were not replicated with nivolumab. Novel biomarkers of outcome were found on circulating blood cells, including MDSC and CD8 T cell FCRL2 pre-treatment. Clinical trial information: NCT01176461.
Direct comparisons of T cell costimulation and checkpoint blockade in the setting of tumor-targeted monoclonal antibody therapy
Authors: Danny Khalil, Taha Merghoub, Jedd Wolchok
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts T cell checkpoint blockade and T cell costimulation, two types of immunotherapy undergoing active clinical investigation, have led to improved outcomes for patients with different types of advanced cancer. Given that these approaches can result in durable remissions, there is
Correlation of DNA content of laryngeal epithelial lesions to degree of malignancy.
Authors: A Ispizua, A Baroja, C de la Hoz
Journal: Journal of Clinical Oncology (1994)

PURPOSE The aim of the present study was to determine the role of DNA content in laryngeal epithelial lesions of different degrees of malignancy. PATIENTS AND METHODS A total of 53 lesions were studied, which included five benign tumors, 18 dysplasias, and 30 carcinomas of different degrees of differentiation and clinical stage. In all cases, the DNA content was determined by microspectrophotometry of paraffin-embedded Feulgen-stained biopsies. RESULTS We found significant differences between the DNA-content histograms corresponding to each lesion group studied. Of special interest was the transition from moderate to severe dysplasia (characterized by a striking increase in the G2M-phase cells) and the transition from severe dysplasia to carcinoma (characterized by a brusque change in the modal ploidy of the lesion). CONCLUSION The determination of DNA content, and study of DNA histogram, will help to assess degree of malignancy in epithelial lesions of the larynx.
A phase II trial of lenalidomide for patients with AL amyloidosis
Authors: V. Sanchorawala, D. G. Wright, M. Rosenzweig, K. T. Finn, M. Skinner, D. C. Seldin
Journal: Journal of Clinical Oncology (2006)

7524 Introduction: A phase II trial was designed to evaluate the toxicity and response rate of lenalidomide (Revlimid, CC-5013), alone and in combination with dexamethasone in patients with AL amyloidosis. Patients with this plasma cell disorder have organ dysfunction that makes them more susceptible to drug toxicity. Methods: Planned enrollment, 35 patients. Regimen: 3 cycles of lenalidomide at 25 mg/d for 21d, with dexamethasone 10 mg bid for 4 days, 3 times a month, every other month, for those patients not responding to lenalidomide alone. Toxicity and responses were evaluated after 1, 3, 6, 9, and 12 months of treatment. Hematologic responses were based upon qualitative and quantitative measures of clonal plasma cell disease. Organ responses were scored according to published criteria. Results: 24 patients have been enrolled to date, age range is 47–76, M:F 18:6, κ:λ 7:17. Organ involvement: 75% renal, 38% cardiac, 18% hepatic or gastrointestinal, 17% neuropathy, 13% soft tissue or lymph node. 22 had been treated previously, and 12 had undergone treatment with HDM/SCT. After none of the first 6 patients tolerated 3 treatment cycles at 25 mg/day, the starting dose was reduced to 15 mg/day. A total of 112 cycles have been administered (1–14 cycles per patient). 2 patients were removed from study because of rashes; one because of gout and severe fatigue; one by choice; and one patient died in the first treatment cycle, apparently due to complications of the underlying disease. Grade 3 toxicities observed included fatigue (33%), hypoalbuminemia (29%), worsening performance status (29%), neutropenia (21%), rash (21%), dizziness (13%), gout (13%), dyspnea (8%), muscle weakness (8%), and pneumonia (8%). One patient (4%) had a DVT on lenalidomide and dexamethasone. 8 out of 13 have had a measureable hematologic response, of which 3 were complete or near complete. 8 patients had elevated free light chains (FLC) with a skewed κ:λ ratio, and 4 of these had ≥50% reduction in FLC level. 4 of 14 patients with proteinuria improved. Conclusion: Lenalidomide is reasonably well-tolerated in patients with AL amyloidosis, and alone or in combination with dexamethasone, can induce excellent hematologic responses and improvement in organ disease. No significant financial relationships to disclose.
The contribution of salvage surgery to the management of childhood osteosarcoma.
Authors: U Pastorino, M Gasparini, L Tavecchio, A Azzarelli, S Mapelli, V Zucchi, F Morandi, F F Bellani, M Valente, G Ravasi
Journal: Journal of Clinical Oncology (1991)

Between January 1970 and December 1988, 174 consecutive patients under the age of 20 years with curatively resected primary osteosarcoma were treated at our institute; 72 in the years of 1970 to 1981 and 102 in the years 1982 to 1988. In the latter period, adjuvant chemotherapy was replaced by neoadjuvant programs, and new criteria were adopted for the management of lung metastases, consisting in early bilateral surgical staging and lung resection through median sternotomy for all patients with purely intrathoracic relapse. Follow-up was updated in December 1989. During the last period, the overall 5-year survival improved significantly from 35% to 58% (P less than .001). The disease-free survival rose from 38% to 45% at 5 years, with median values of 15 months versus 33 months, while the frequency of isolated lung metastases dropped from 58% to the actuarial 48%. The proportion of patients who underwent complete resections of their pulmonary metastases rose from 17% (seven of 42) to 55% (27 of 49), without operative mortality. Due to such a high proportion of patients eligible for salvage surgery, the overall survival from detection of lung metastases improved from 0% to 28% at 5 years (P less than .001). Contralateral occult metastases were resected in three of 15 subjects with monolateral clinical lesions, and five patients underwent subsequent lung resections. These data indicate that systematic bilateral pulmonary resection plays an important role in improving the final cure rate of childhood osteosarcoma, beyond the benefit resulting from neoadjuvant chemotherapy.
A phase 1, dose-escalation trial of STA-5312, a microtubule inhibitor with a novel binding site, in advanced or metastatic solid malignancies
Authors: A. Desai, M. J. Ratain, K. Moshier, M. Tipton, W. Dooley, K. Hocknell, T. Dahl, M. Sherman, S. Limentani
Journal: Journal of Clinical Oncology (2006)

13040 Background: STA-5312 is a novel microtubule inhibitor with a distinct binding site from other agents such as vincristine, colchicine, or paclitaxel, which has demonstrated antitumor activity against a range of solid tumors in chemotherapy-resistant cancer. Methods: The trial assessed the safety, toxicity, pharmacokinetics (PK) and maximum tolerated dose (MTD) level of STA-5312 when administered as an IV infusion weekly for the first 3 weeks of a 4 week cycle. Assessment of activity is a secondary objective. The starting dose level was 6mg/m 2 . Dose escalation was based on evaluation of toxicity through the first cycle, with dose doubling in cohorts of 1–2 patients (pts) until a grade (gr) 2 or greater toxicity occurred, followed by at least 3 pts/cohort and 50% dose escalations. After a dose limiting toxicity (DLT), cohorts were expanded to at least 6 pts and subsequent escalations limited to 33%. The dose below the lowest dose at which 1/3 of 6 or more patients show DLT will be declared the MTD. PK sampling was performed during cycle 1. Results: To date, 25 pts have been treated: median age 58 years (35–77), ECOG performance status of 0–2, and median treatment duration 43 days. No serious drug-related toxicity was observed until a DLT (ataxia) was reported in the only patient treated at 64mg/m 2 , leading to de-escalation to 48 mg/m 2 , where the only patient experienced aphasia and ataxia. Enrollment is being expanded at a lower dose level of 32 mg/m 2 . Other adverse events attributable to STA-5312 include (&gt;10%) anemia, fatigue, constipation, nausea, and anorexia. Exposure (AUC) was linear with respect to dose. Five patients have had disease stabilization. Conclusions: STA-5312 appears to be well tolerated when given weekly in doses up to 32mg/m 2 . The MTD has not been determined and enrollment is ongoing. [Table: see text]
Supportive care organization: Patients and oncologist national survey comparison.
Authors: Florian Scotte, Christian Herve, Jean Marc Tourani, Roland Bugat, Fadila Farsi, Nicolas Jovenin, Moise Namer, Christophe Tournigand, Pauline Leroy, Stephane Oudard, Ivan Krakowski
Journal: Journal of Clinical Oncology (2014)

202 Background: The medical doctor's (MD) perspective of supportive care in cancer (SCC) in France was previously assessed on a national survey. However, the opinion of patients (P) has never been evaluated nor compared to MD’s perception.Wepromoted and compared P and MD awareness via national surveys to monitor implementation and information delivered to patients on SCC. Methods: The French Speaking Association for SCC (AFSOS) conducted two observational studies, analyzed with a Chi2 test: S1: a 30 points questionnaire sent to 2,263 physicians caring for cancer P (oncologists, radiotherapists, haematologists, gastroenterologists); and S2: a 40 points questionnaire performed by physicians to P, using a face-to-face method. Results: 711 MDs returned S1 and S2 was conducted with 1,562 P. In S1, MDs declared relying on SCC organization (81%) but 19% of P declared they were offered to benefit from an organization called SCC (54% at diagnosis, 35% after complication). The name SCC was known by 34% of P, most frequently described as complementary care to specific treatments (55%). Palliative Care word had been previously heard by 80% P, mostly considered as care to improve quality of life during cancer treatment for 59%. In S2, professional resources identified outside the hospital were: general practitioners (84%), nurses (58%), pharmacists (52%). According to P, the top 3 supportive care consultations proposed were psychology (61%), nutrition (55%) and announcement organization (55%), while MDs mentioned palliative care (98%), psychological care (98%), social care (98%), S2 showed that supportive treatment was prescribed to 63% of P, mostly by their oncologist (74%), and 64% of those P received information on side-effects. Epoetin was prescribed to 25% and analgesics to 73%, with discussion on adverse events respectively for 38% and 53%. MDs declared delivering information on adverse events to 49% of P receiving epoetin and to 74% of P running for analgesic treatment. Conclusions: Oncologist is the cornerstone of SCC organization. Information as well as treatment must be developed to further enhance SCC and patient quality of care.
Combined Neoplastic Effects of Vaccinia Virus and 3-Methylcholanthrene. I. Studies With Mice of Different Inbred Strains&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Maria L. Duran-Reynals
Journal: JNCI Journal of the National Cancer Institute (1972)

Mice of 8 inbred strains were resistant to dermal infection by vaccinia virus inoculated into the skin of the flank. Cortisone treatment before vaccinia inoculation followed by 5 paintings with α 3-methylcholanthrene (MCA) solution of 1% in benzene over flanks and back caused: 1) local skin ulceration by vaccinia, 2) enhancement of this lesion by MCA, and 3) evolution of ulcers into skin tumors. The mouse strains tested varied in their skin responses both to vaccinia and to MCA given separately or together in the same manner; these responses were severe in BALB/c and C3HeB/Fe mice, moderate in A mice, weak in C58 mice, very weak in DBA/1, DBA/2, and B10.D2 mice, and undetectable in AKR mice. Skin susceptibility to vaccinia inoculation and to MCA painting was low in those strains showing a high incidence of leukemia, either spontaneous (AKR and C58) or MCA-induced (DBA/1 and DBA/2). BALB/c and AKR mice, representing the observed extremes of susceptibility and resistance, respectively, had similar degrees of immunosuppression by cortisone and MCA, as judged by lymphocyte depletion of the thymus and spleen. This immunosuppression was apparently a major factor in the skin susceptibility of BALB/c mice to vaccinia but had no effect on the resistance of AKR mice to the virus.
Assessment and targeting of growth factor-binding heparan sulfate 6-<i>O</i>-sulfated motifs on lung cancer cell lines using human single chain antibody variable fragments
Authors: M. Delcommenne, T. R. Oegema, P. D. Bonomi
Journal: Journal of Clinical Oncology (2008)

14015 Background: Recent reports have indicated that several types of tumors express high levels of 6-O-sulfated motifs on heparan sulfate (HS) proteoglycans on their surface caused by the silencing of a cell surface 6-O-sulfatase, HSulf-1. These heparan sulfate motifs subsequently recruit, on the cell surface, high levels of heparin-binding growth factors, which in turn activate their cognate receptor to promote tumor survival and proliferation. One of these factors is Heparin-Binding EGF-like Growth Factor (HB-EGF). In lung cancer cells, expression and sulfation status of cell surface heparan sulfate proteoglycans is largely unknown and therefore this study was undertaken to examine these molecules. Methods: A panel of lung cancer cell lines was analyzed by flow cytometry using antibody variable fragments (scFvs) specific for HS 6-O-sulfated motifs. These antibodies were also tested against the same cell lines transfected with HSulf-1 to confirm their specificity. Tyrosine phosphorylation of the Epidermal Growth Factor Receptor (EGFR) was assessed on lung cancer cells treated with HB-EGF in presence or absence of HS 6-O-sulfated motif specific antibodies. Results: HS 6-O-sulfated motifs were expressed in 5 of the 7 lung cancer cell lines analyzed but were absent or dramatically downregulated in cells transfected with Hsulf- 1. The intensity of EGFR tyrosine phosphorylation induced by HB-EGF corresponded with the expression level of the HS 6-O-sulfated motifs on the different cell lines. Finally, our antibodies inhibited HB-EGF mediated activation of EGF receptors. Conclusions: This study indicates that a significant proportion of lung cancer cell lines express in vitro protumorigenic HS 6-O-sulfated motifs that could be effectively targeted by function-blocking therapeutic antibodies derived from our scFvs. No significant financial relationships to disclose.
Association of tobacco (T) use with risk of distant metastases (DM), tumor recurrence, and death in patients (pts) with HPV-positive (+) squamous cell cancer of the oropharynx (SCCOP)
Authors: F. P. Worden, J. Hooton, J. Lee, A. Eisbruch, G. T. Wolf, M. Prince, J. Moyer, T. Teknos, D. B. Chepeha, C. R. Bradford, T. Carey
Journal: Journal of Clinical Oncology (2009)

6001 Background: Chemoradiation (CRT) for HPV (+) SCCOP is associated with a more favorable prognosis than HPV-negative (-) SCCOP. However, the interaction of HPV and T in terms of etiology and disease progression remains unclear. HPV (+) SCCOP pts were prospectively studied to determine if T use was a key variable in discriminating which pts would develop DM, locoregional recurrences (LR), or second primaries (SP). Methods: From 1999–2007, 124 pts with stage III/IV SCCOP were enrolled in one of two CRT trials. Tumor specimens were analyzed for HPV presence and type. Use of T, determined via self-reporting and chart review, was recorded as both continuous (number of pack-yrs) and categorical (never, former, and current) variables. Former T users were subdivided into an early cessation group (quit ≥ 20 yrs prior to diagnosis) and a late cessation group (quit &lt; 20 yrs prior to diagnosis). T use and HPV status were analyzed with respect to survival &amp; the development of DM, LR, or SP. Results: Of the 124 pts, 100 (81%) were HPV (+), 22 of which developed disease progression (22%). Twenty-four were HPV (-), 12 of which had disease progression (50%). Seventeen of 124 pts (14%) developed DM [12 HPV (+), 5 HPV (-)]. Nine of 124 (7%) developed LR [5 HPV (+), 4 HPV (-)], and 8 of 124 (7%) developed SP [5 HPV (+), 3 HPV (-)]. Thirty-two HPV (+) pts were never-T users, 88% (28/32) of which remain alive with no evidence of disease; 3 died from other causes and 1 died of lung metastases from SCCOP. Sixty-eight were HPV (+) and had T exposure. Of 46 former T users, 37/46 (80%) are living. Twenty were HPV (+) and in the early cessation group, 35% (7/20) of which had disease progression [3 LR, 3 DM, 1 SP]. Twenty-six HPV (+) pts were former T users in the late cessation group, 11% (3/26) of which had disease progression [2 DM, 1 SP]. Of 22 HPV (+) current T users, 68% (15/22) are alive and 36% (8/22) have developed disease progression. Seventeen of the 24 HPV (-) pts were current T users, 47% (8/17) of which developed disease progression. Conclusions: Never-T users with HPV-positive SCCOP have improved survival &amp; reduced risk of disease progression compared to HPV (+) &amp; HPV (-) former &amp; current T users. No significant financial relationships to disclose.
THU0312 Fibromyalgia Frequency in Patients with Acne Vulgaris
Authors: L. Yazmalar, T. Çelepkolu, I. Batmaz, M.A. Sarıyıldız, B. Sula, I. An, Y.K. Burkan, M. Alpaycı, H. Uçak, R. Çevik
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Acne vulgaris is a widespread inflammatory disease of skin. Among the general population, acne occurs in about 80% of teenagers and 25% of adults.<sup>1</sup> Many factors such as stress, genetic predisposition, bacterial infections, hormonal disorders, cosmetics, sun exposure, smoking or diet can cause acne.<sup>2</sup> According to our knowledge, by this time, fibromyalgia syndrome-related clinical symptoms such as fatigue, sleep disorders or anxiety have been addressed in patients with acne vulgaris.<sup>3,4</sup> But, fibromyalgia syndrome has not been addressed. <h3>Objectives</h3> The aim of the study was to evaluate the frequency of fibromyalgia syndrome and specify fibromyalgia syndrome-associated clinical symptoms in patients with acne vulgaris. <h3>Methods</h3> Eighty-eight (60 females, 28 males) patients with acne vulgaris were enrolled in this study. In addition,76 age and gender-matched healthy controls (62 females, 14 males) were included in the study. Acne vulgaris was evaluated using Global Acne Scale. Diagnosis of fibromyalgia syndrome was determined using The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Hospital Anxiety and Depression Scale was used for evaluation of anxiety. <h3>Results</h3> There was no significant difference in age, gender or body mass index between two groups. The fibromyalgia syndrome frequency, sleep disturbance, anxiety, menstrual cycle disturbance and mean tender point counts were significantly greater among the acne patients relative to the controls. Although widespread body pain, fatigue, arthralgia, irritable bowel syndrome were more common among the acne patients, there were no significant differences between the acne patients and controls. <h3>Conclusions</h3> The results of our study showed that fibromyalgia syndrome frequency is greater among acne vulgaris patients in comparison to control subjects. <h3>References</h3> Chiu A, Chon SY, Kimball AB. The response of skin disease to stress: changes in the severity of acne vulgaris as affected by examination stres. Arch Dermatol. 2003 Jul;139(7):897-900. Albuquerque RG, Rocha MA, Bagatin E, Tufik S, Andersen ML. Could adult female acne be associated with modern life? Arch Dermatol Res. 2014 Oct;306(8):683-8. Misery L, Wolkenstein P, Amici JM, Maghia R, Brenaut E, Cazeau C, Voisard JJ, Taïeb C. Consequences of Acne on Stress, Fatigue, Sleep Disorders and Sexual Activity: A Population-based Study. Acta Derm Venereol. 2014 Nov 4. doi: 10.2340/00015555-1998. Silverberg JI, Silverberg NB. Epidemiology and extracutaneous comorbidities of severe acne in adolescence: a U.S. population-based study. Br J Dermatol. 2014 May;170(5):1136-42. <h3>Disclosure of Interest</h3> None declared