tbuckley/cabot-search huggingface dataset:
A randomized prospective study of low-dose interleukin-2 (IL-2) in combination with interferon-alpha (IFN) and 5-fluorouracil (5-FU) for metastatic renal cell carcinoma: Final results
Authors: L. Demidov, G. Kharkevich, I. Tsimafeyeu
Journal: Journal of Clinical Oncology (2007)

15643 Background: High and intermediate IL-2 regimens are difficult to recommend because of great toxicity. Based on previous activity of combination low-dose cytokines (including 1 MIU IL-2) in metastatic renal cell carcinoma (MRCC) patients (pts) (J Europ Urol, Supp. 2006;5 (2):286), we performed this randomized study. The primary endpoint was response rate. The secondary endpoints were median overall survival (OS) and toxicity in groups. Methods: Eligibility criteria included histopathologically confirmed MRCC, ECOG PS 0- 2, no autoimmune diseases, no brain metastases, and normal organ function. All pts are randomized to IL-2 alone, 1 MIU, iv, t.i.w., weeks 1–3 or IL-2, 1 MIU, iv, t.i.w., weeks 1–3 plus IFN 5 MIU, sc, t.i.w, weeks 1–3 or biochemotherapy group 5-FU, 500 mg/m 2 , iv, once a week, weeks 1–3 plus IL-2 and IFN. Cycles were repeated every three weeks. Response evaluation was performed according to RECIST every 2 cycles. Results: From Jan 2003 to Jun 2006, 66 pts with any type of MRCC histology were randomized. Median age of the pts was 55.4 years (range 16–74). 43.9% of the patients had been previously treated by chemo- or immunotherapy. 54.5 percent of the pts had poor prognosis by MSKCC criteria. Bone metastases were present in 52.4% pts. Baseline characteristics were well balanced in groups. Pts treated with IL-2+IFN or 5-FU+IL-2+IFN had a statistically longer survival than those treated with IL-2 alone ( Table ). OS and TTP of pts in combined arms were not statistically different. There were no toxicity grade 3 and 4. Conclusions: Low-dose IL-2 alone is not effective. 5- FU does not improve efficacy of the cytokine combination. Low dose IL-2 and IFN demonstrate reasonable efficacy and could be recommend for MRCC pts outside clinical trials and available target therapy. All regiments are well tolerated. [Table: see text] No significant financial relationships to disclose.
Phase II randomized trial of radiotherapy (RT), cetuximab (E), and pemetrexed (Pem) with or without bevacizumab (B) in locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Authors: Athanassios Argiris, James Ohr, Greg J. Kubicek, Uma Duvvuri, Dwight Earl Heron, Athanasios Panayotis Kotsakis, Christina Spencer, Seungwon Kim, Jennifer R. Grandis, Jonas Talmadge Johnson, Julie E. Bauman, Michael K. Gibson, Robert L. Ferris
Journal: Journal of Clinical Oncology (2013)

6043 Background: We previously developed a novel regimen by the addition of Pem to RT and E (Ann Oncol 2011;22:2482). The current study evaluated PemE in the phase II setting and assessed the addition of B, an anti-VEGF monoclonal antibody, to PemE based on promising data with Pem/B (JCO 2011;29:1140) and E/B (Ann Oncol 2013;24:200) in recurrent/metastatic SCCHN. Methods: Patients (pts) with previously untreated stage III/IV SCCHN of the oropharynx, larynx or hypopharynx, performance status (PS) 0-1, no history of bleeding, and adequate laboratory parameters were randomized after stratification for PS, stage and site to: RT 2 Gy/day to 70Gy, E 250mg/m 2 weekly, after a loading dose of 400 mg/m 2 1 week prior starting RT, and Pem 500mg/m 2 every 21 days x 3 cycles (arm A, PemE), or the same regimen plus B 15mg/kg every 21 days x 3 cycles during RT followed by B maintenance x 8 cycles (arm B, B-PemE), with antibiotic prophylaxis. The primary endpoint was progression-free survival (PFS) with a target of 64% at 2 years; planned sample size was 80. Results: 79 pts were randomized of whom 77 were eligible and analyzable (arm A/B:36/41); oropharynx 65/larynx 12; HPV+ 38/HPV- 15/HPV unknown 24; stage IV 54/stage III 23. 31 pts were enrolled in community centers. Treatment delivery of E and Pem was similar between arms: E, median number of doses 8 (range, 5-11); Pem 3 (2-3); and B 3 (1-3). 5 deaths occurred: 3 due to progression; 1 from unknown cause; 1 pt died from hemoptysis after bronchoscopy within 4 weeks of the 8th cycle of B leading to elimination of B maintenance after the 6th pt was enrolled. 9 pts (2 HPV+) progressed. With a median follow-up of 18 months, the 2-year PFS was 81% vs 87% and the 2-year overall survival (OS) was 96% vs 86% for arm A vs B. Grade 3/4 acute toxicities for arm A vs B (N=59) : dermatitis 3/1 vs 4/1; mucositis 13/2 vs 13/0; neutropenia 7/4 vs 7/3; rash 6/1 vs 8/1; fatigue 1/0 vs 3/0; weight loss 2/0 vs 5/0. Conclusions: Both regimens are feasible in academic and community practice settings with expected toxicities. Preliminary efficacy results are very promising and better than projected, however, the addition of B does not appear to improve outcomes. Clinical trial information: NCT00703976.
Ptch2 loss drives myeloproliferation and myeloproliferative neoplasm progression
Authors: Claudius Klein, Anabel Zwick, Sandra Kissel, Christine Ulrike Forster, Dietmar Pfeifer, Marie Follo, Anna Lena Illert, Sarah Decker, Thomas Benkler, Heike Pahl, Robert A.J. Oostendorp, Konrad Aumann, Justus Duyster, Christine Dierks
Journal: The Journal of Experimental Medicine (2016)

JAK2V617F+ myeloproliferative neoplasms (MPNs) frequently progress into leukemias, but the factors driving this process are not understood. Here, we find excess Hedgehog (HH) ligand secretion and loss of PTCH2 in myeloproliferative disease, which drives canonical and noncanonical HH-signaling. Interestingly, Ptch2−/− mice mimic dual pathway activation and develop a MPN-phenotype with leukocytosis (neutrophils and monocytes), strong progenitor and LKS mobilization, splenomegaly, anemia, and loss of lymphoid lineages. HSCs exhibit increased cell cycling with improved stress hematopoiesis after 5-FU treatment, and this results in HSC exhaustion over time. Cytopenias, LKS loss, and mobilization are all caused by loss of Ptch2 in the niche, whereas hematopoietic loss of Ptch2 drives leukocytosis and promotes LKS maintenance and replating capacity in vitro. Ptch2−/− niche cells show hyperactive noncanonical HH signaling, resulting in reduced production of essential HSC regulators (Scf, Cxcl12, and Jag1) and depletion of osteoblasts. Interestingly, Ptch2 loss in either the niche or in hematopoietic cells dramatically accelerated human JAK2V617F-driven pathogenesis, causing transformation of nonlethal chronic MPNs into aggressive lethal leukemias with &amp;gt;30% blasts in the peripheral blood. Our findings suggest HH ligand inhibitors as possible drug candidates that act on hematopoiesis and the niche to prevent transformation of MPNs into leukemias.
Abstract 12199: Impact of Aortic Valve Calcification Severity and Impaired Left Ventricular Function on Three-Year Results of Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Ralf Koos, Andreas Horst Mahnken, Sebastian Reinartz, Ralf Herpertz, Shahram Lofti, Rudiger Autschbach, Nikolaus Marx, Rainer Hoffmann
Journal: Circulation (2012)

Introduction: Transcatheter aortic valve replacement (TAVI) has been established in high-risk patients with severe aortic valve stenosis. We aimed to evaluate clinical predictors of three-year outc...
Biologic behavior for patterns of recurrence and survival in ovarian versus uterine papillary serous carcinoma
Authors: B. de Souza
Journal: Journal of Clinical Oncology (2006)

15056 Background: Papillary serous carcinoma of the ovary (OPSC) and uterus (UPSC) are relatively uncommon malignancies with similar histological features. Information for their comparative behavior is lacking, hence a review was done to compare patterns of recurrence, disease-free and overall survival between the 2 groups. Methods: A retrospective review of 352 consecutive patients (pts) at a single institution with ovarian and uterine malignancies from 1991 through 2004 was done. Of these, 48 patients were identified with OPSC (n = 32) and UPSC (n = 16). To control surgeon as a prognostic factor, only pts undergoing surgery by a single surgeon were included. Stages at diagnosis, patterns of recurrence and survival for FIGO stages I-III with a minimum follow-up of 8 months were obtained from tumor registry, hospital and office records. The median follow-up for UPSC was 25 months and for OPSC was 46 months. Stage IV pts were excluded. Results: The mean age for OPSC and UPSC was 64 and 63 years respectively. Of the 32 OPSC pts, 94% had optimal debulking. In the UPSC group 88% had proper staging with lymph node dissection. The pts with OPSC had a mean overall survival of 60 months and a mean disease-free survival of 38 months for all stages combined. The pts with UPSC had a mean overall survival of 51 months and a mean disease-free survival of 40 months for all stages combined. Ten (31%) pts with OPSC had no recurrence. The remaining 22 (69%) pts had a total of 36 recurrences, the most common (17%) being pelvic masses (mean interval of 24 months). In the UPSC group, 9 (56%) had no recurrences. The remaining 7 (44%) had a total of 10 recurrences, the most common (30%) being peritoneal implants (mean interval of 17 months). Conclusions: UPSC is detected at an earlier stage twice as often as OPSC and yet it has lower overall survival. The disease-free interval is comparable, which shows that even after recurrence, the survival for OPSC is longer. Although OPSC and UPSC share similar histological features UPSC behaves more aggressively. [Table: see text] No significant financial relationships to disclose.
False alarms: Negative invasive procedures and negative additional imaging after the introduction of a CT-based follow-up program in lung cancer patients treated with curative intent
Authors: Niels-Chr. G. Hansen
Journal: European Respiratory Journal (2014)

The chance of a second curative treatment against recurrent lung cancer has increased 3-fold after the introduction from mid-2010 of the national post-therapy follow-up program in the county of Funen (484,500 inhabitants). The program recommends a contrast enhanced CT of thorax and upper abdomen every 3 months for two years and then every 6 months for three years. A population based quality assurance analysis has been performed to study potential disadvantages of the program. All new lung cancer patients from Funen in the 4-year period from July 1, 2008 were identified in the Danish Lung Cancer Registry and for those treated with curative intent the relevant data were extracted from hospital records in February 2014. After exclusion of patients, who died after surgery or had a relapse during therapy, 434 patients were included: 200 from the two years prior to the introduction of the follow-up program (group A) and 234 from the two years after (group B). No signs of over diagnosis have been found: The cumulated risk of recurrence has reached a “plateau” at 57% in both groups with a median time to recurrence = 35.2 months (group A) vs. 24.7 months (group B). A complete comparison of the first two years of follow-up for both groups will be possible in August 2014, but until February 2014 the fraction of patients having had at least one negative invasive diagnostic procedure during the first two years of follow-up has increased from 9.5% (group A) to 14.6% (group B) (p = 0.129, Fisher9s Exact test). The use of PET-CT has increased more than 3-fold after the introduction of the CT-based follow-up.
Antibodies in Human Sera to Soluble and Viral Antigens Found in Burkitt Lymphoma and Other Lymphoblastoid Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Vladimir Vonka, M.D., Matilda Benyesh-Melnick, M.D., Robert M. McCombs, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1970)

Human sera were examined for antibody to complement-fixing (CF) antigens derived from lymphobiastoid cell lines. Two CF antigens were used: a soluble cell extract (S) antigen, nonsedimentable at 100,000 × g for 2 hours, and a partially purified Epstein-Barr (EB) virus particle (V) antigen. The results of CF tests were compared with those of an indirect immunofluorescence (IF) test using fixed EB3 Burkitt lymphoma cells. Screening (at 1:10 dilution) of 177 sera indicated that, in 128 sera positive by the IF test, 106 reacted in the CF test with V antigen and 72 with the S antigen. Virtually all sera reactive with the S angiten also reacted with the V antigen. Forty-nine sera negative in the IF test were also negative when examined for CF-S and CF-V antibodies. Titration of positive sera by the 3 tests revealed a high correlation between the IF and CF-V antibody titer. On the other hand, many CF-S antibody-negative sera had high IF and CF-V antibody titers. The reactivity of human sera in the 3 tests suggests that the antigens detectable by the IF and CF-V tests are closely related, while the S antigen is immunologically distinct. In EB virus-containing cells, no correlation existed between the concentration of S antigen and virus particles or percent of IF-positive cells. The S antigen was also detected in preparations derived from AMC30 cells, free of detectable EB virions, but not in preparations of KB, HeLa, or human embryonic lung cells.
MPs find no evidence that Cancer Drugs Fund was spent wisely
Authors: Nigel Hawkes
Journal: BMJ (2016)

A total of £1.27bn (€1.7bn; $1.9bn) has so far been spent on the Cancer Drugs Fund in England, but no data exist to show whether it has been spent wisely, the House of Commons Public Accounts Committee says in a new report.1

Despite the Department of Health noting when the fund was set up in 2010 that it was important to collect clinical outcomes from the drugs it pays for, few data exist. The department encouraged NHS trusts to collect data but did not require them to do so. When NHS England took over the fund in April 2014 it made data collection mandatory, but the committee still found gaps for 2014-15, with 93% of records having no summary of outcomes.

The health department and NHS England “have not managed the fund effectively” the …
Epstein-Barr Virus-Related Lymphocyte Stimulation Inhibitor: A Possible Prognostic Tool for Undifferentiated Nasopharyngeal Carcinoma
Authors: L S Kamaraju, P H Levine, S K Sundar, D V Ablashi, A Faggioni, G R Armstrong, G Bertram, G R Krueger
Journal: JNCI Journal of the National Cancer Institute (1983)

It is demonstrated in this study that a serum factor, a lymphocyte stimulation inhibitor (LSI), which inhibits Epstein-Barr virus (EBV)-induced lymphocyte stimulation, is a potentially useful tool in the diagnosis and monitoring of nasopharyngeal carcinoma (NPC). In a study of 25 patients with undifferentiated NPC, 20 healthy controls, and 20 patients with other head and neck tumors, LSI was found only in the NPC patients with active disease. In a more complete study of 8 patients longitudinally followed up for at least 20 months, a comparison of LSI with antibodies to a variety of EBV antigens including viral capsid antigen, early antigen, and nuclear antigen indicated that LSI levels provided a reliable and sensitive indicator of disease activity that should be added to clinical markers currently in use as monitors of disease activity in NPC.
Recovery of overall and local lung function loss 18 months after irradiation for malignant lymphoma.
Authors: L J Boersma, E M Damen, R W de Boer, S H Muller, R A Valdés Olmos, N van Zandwijk, J V Lebesque
Journal: Journal of Clinical Oncology (1996)

To determine the local and overall pulmonary injury 3 to 18 months after irradiation and to investigate whether the changes in overall lung function can be predicted using the three-dimensional (3-D) dose distribution in combination with dose-effect relations for local injury; and to study the influence of chemotherapy on the injury.Local perfusion (Q), ventilation (V), and tissue density were measured in 25 patients treated for malignant lymphoma, before, 3 to 4 months after, and 18 months after irradiation. Dose-effect relations for local injury, calculated using correlated single-photon emission computed tomographic (SPECT) and computed tomographic (CT) data, were combined with the 3-D dose distribution, to calculate the estimated mean local changes over the complete lung for each patient. The result was correlated with the actual changes in pulmonary function.A dose-dependent increase with injury was observed at 3 to 4 months after irradiation, which at 18 months had recovered by approximately 50% to 60%. The estimated mean relative reduction of local Q predicted the change in overall lung function within 10% of the actually observed values in 63% to 73% of patients. Chemotherapy given before radiotherapy enhanced radiation-induced reduction of local Q significantly, with dose-modifying factors of 1.22 and 1.37 at 3 to 4 months and 18 months, respectively.Partial recovery of radiation-induced reduction of local and overall lung function was observed at 18 months after irradiation. The overall functional outcome of most patients could be well predicted, based on the estimated mean local injury over the complete lung. Chemotherapy given before radiotherapy enhanced the radiation-induced reduction of local Q.
A phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumors (EORTC 16041)
Authors: A. Heerschap, W. Fiedler, S. Marreaud, H. van Laarhoven, A. Govaerts, M. Peters, S. Toma, C. Bordignon, K. Punt, C. Van Herpen
Journal: Journal of Clinical Oncology (2007)

14074 Background: NGR-TNF is a novel agent exploiting a tumour homing peptide (cNGRCG) that selectively targets CD13 that is expressed on the neovasculature of solid tumors. Preclinical data show that its antitumour activity is achieved by a change of vascular permeability (at low doses) and damage of tumour-associated blood vessels (at high doses). This phase I study is being conducted to assess its safety, PK, PD, MTD, and optimal biological dose in patients (pts) with advanced solid tumours. Methods: NGR-TNF was administered once every 3 weeks by a 20 min IV infusion to cohorts of 3–6 pts. The starting dose was 0.2 μg/m 2 . Dose escalation was performed with a doubling of the dose until grade 2 toxicity was observed; thereafter a modified Fibonacci schedule was used. PK and PD analysis in blood was performed during the first 4 cycles. DCE-MRI was performed in cycle 1 at baseline and 2 hours after start of the infusion to document modification of the tumour vascularity. Anti-tumour activity was assessed by CT scan every 2 cycles. Results: 45 pts were treated and 133 cycles of treatment completed up to now. 12 DLs have been visited (0.2 to 14.36 μg/m 2 ). One DLT (bronchospasm G 3) was observed at DL4 (1.3 μg/m 2 ) and the DL was extended to 7 pts. As no other DLT was observed, dose escalation was continued. Since then no additional pt experienced dose-limiting toxicity. As 3/18 first pts experienced chills G 2 during injection time, the study was amended and infusion time increased to 1 hour. Since then 1/14 next pts had G 2 chills. Overall most frequently related adverse events reported in the first 34 pts: chills 76%, fever 44%, nausea 20%, constipation 12%, diarrhea 9%, anorexia and hypotension 6%. PK/PD analysis for the plasma levels of TNF-RI and TNF-RII showed a better profile for the 60 min compared with the 20 min infusion. At DL = 1.3 μg/m 2 most pts showed a decrease in k ep and the number of pixels with a low fraction of k ep and K trans significantly increased (p&lt;0.05), as seen with other anti- vascular agents. Stable disease was observed in 39% of pts, with a median duration of 11 wks (range 5–36). No responses were observed. Conclusions: NGR-hTNF is well tolerated and some biological activity was observed by DCE-MRI. Study enrollment is ongoing. [Table: see text]
Intellectual and academic achievement status after CNS relapse: a retrospective analysis of 40 children treated for acute lymphoblastic leukemia.
Authors: R K Mulhern, J Ochs, D Fairclough, A L Wasserman, K S Davis, J M Williams
Journal: Journal of Clinical Oncology (1987)

We determined the intellectual and academic status of 40 children with acute lymphoblastic leukemia who had experienced a primary isolated relapse in the CNS by analyzing the results of psychoeducational tests administered a median of 6.1 years after the relapse. Mean scores for full-scale IQ (87.5), verbal IQ (86.7), performance IQ (90.3), as well as academic achievement in reading (89.8), spelling (83.9), and mathematics (83.5) were significantly below normal expectations for age. Twenty percent of the group were mentally retarded and were receiving special educational assistance. The best clinical predictors of full-scale IQ were the number of radiation therapy courses, age, and the presence or absence of cerebral pathology as measured by computed tomography (CT). Children who were younger at the time of treatment, who received two courses of radiation therapy, and who had clinical seizures and structural abnormalities of the brain as detected by CT had the poorest psychological outcome. Although the psychoeducational consequences of CNS relapse and its attendant treatment are significant, these must be balanced by consideration of the relatively low probability of long-term survival without aggressive therapy. Recognition of this type of delayed morbidity with systematic surveillance and prompt attempts at rehabilitation may decrease or at least minimize these sequelae.
Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection
Authors: Abigail S. Caudle, Wei T. Yang, Savitri Krishnamurthy, Elizabeth A. Mittendorf, Dalliah M. Black, Michael Z. Gilcrease, Isabelle Bedrosian, Brian P. Hobbs, Sarah M. DeSnyder, Rosa F. Hwang, Beatriz E. Adrada, Simona F. Shaitelman, Mariana Chavez-MacGregor, Benjamin D. Smith, Rosalind P. Candelaria, Gildy V. Babiera, Basak E. Dogan, Lumarie Santiago, Kelly K. Hunt, Henry M. Kuerer
Journal: Journal of Clinical Oncology (2016)

Purpose Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone. Methods A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND). Results Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7). Conclusion Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.