tbuckley/cabot-search huggingface dataset:
Tegwondo: Development of a novel near-continuous dose-dense temozolomide regimen for the treatment of recurrent brain tumors
Authors: H. M. Strik, J. H. Buhk, C. Bock, A. L. Hoffmann, A. Wrede, C. Marosi, U. Kaiser, M. Christmann, B. Kaina, M. Bähr
Journal: Journal of Clinical Oncology (2008)

13016 Background: We report on activity and feasibility of a rechallenge of recurrent gliomas with temozolomide (TMZ) in a dose- dense 21/28-day regimen and development of a novel 5/7-day schedule. Methods: 40 recurrent glioma-patients received TMZ 100mg/m2 with individual dose adaptation: 21 pts. received 148 cycles day 1–21/28 (18 WHO IV [GBM], 3 WHO III). GBM-pts. had a mean age of 54.4y, median KPS was 60%. Patients with critical blood counts (∼50%) were switched to a 1–5/7-day regimen. Better tolerability led us to treat 19 subsequent patients initially day 1–5/7: 13 GBM, 2 WHO-III, 4 WHO-II; 55.5 y, KPS 70%, total 61 cycles. All malignant gliomas were pretreated with temozolomide. Results: Nausea and fatigue were less frequent than with the 5/28-day schedule. Blood counts usually decreased continuously. Dosage was reduced in approx. 50% of patients and increased to up to 130 mg/m2 in 3 patients. Hematotoxicity grade ¾ (asymptomatic): 2/21 pts. (21/28-day) and 2/19 pts. (5/7-day); nonhematological ¾°: 4/21 Pts. (21/28), 0/19 (5/7). Efficacy of 21/28-day application in GBM was: 2 CR (11%), 2 PR (11%), 7 SD (39%) and 7 PD (39%) after at least 3 months. 38.8% were progression-free at 6 months. Survival after relapse was 34.8 weeks, overall 17.9 months. MGMT-status was available from 7 tumors: 2/4 pts. with unmethylated MGMT were progression-free after 12 months, but only 1/3 with methylated MGMT. Conclusions: Rechallenge of recurrent gliomas with dose-dense temozolomide at 100 mg/m2 and individual dose adaptation is feasible and active. 22% objective long-term responses demonstrate that this strategy is effective even with unfavorable prognostic criteria. Dose adaptation is most appropriate with a near-continuous application day 1–5/7, which is expected to cause permanent depletion of the alkylation-resistance factor MGMT. In fact, also patients with unmethylated MGMT had long-term responses, indicating that chemotherapy resistance may be overcome with this strategy. We therefore consider TEGWONDO (Temozolomide in the Goettingen WOrkiNgday Dose-dense regimen) to be active and feasible also in TMZ-pretreated patients with critical blood counts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough
Pretreatment pulmonary function tests predict risk of mortality following fractionated total body irradiation without lung dose reduction prior to stem cell transplant
Authors: J. R. Mansueti, A. K. Singh, S. E. Karimpour, P. Guion, H. Ning, B. Savani, C. Wu, R. Altemus, J. Barrett
Journal: Journal of Clinical Oncology (2006)

6550 Background: Peripheral blood stem cell transplantation (PBSCT) is a key component in the treatment of various malignancies. Preparatory regimens for PBSCT often include total body irradiation (TBI). Pulmonary toxicity is often prominent, and is felt to be related to total lung dose and dose rate. The Radiation Oncology Branch of the National Institute of Health initially administered TBI without lung shielding, however shielding was added in 2002. Pulmonary function testing (PFT) was undertaken both before and after stem cell transplant and TBI for all patients. The PFT results were analysed to test the hypothesis that TBI patients with pre-treatment combined ventilation/diffusion capacity deficits, defined as both FEV1 and DLCO below 100% predicted, would benefit most from reduction of lung dose. Methods: From 1997–2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. The first 85 patients were treated without lung dose reduction to 13.6 Gray (Gy). Thereafter, total body dose was decreased to 12 Gy (1.5 Gy BID for 4 days). Initially, lung dose was limited to 9 Gy by use of lung shielding. Later lung dose was reduced to 6 Gy. All patients received PFTs prior to treatment, 90 days after treatment, and annually. Results: Median F/U was 44 months (range 12–90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV1) and a diffusion capacity of carbon dioxide (DLCO) less than 100% predicted. Of these 61, 27 had lung dose reduction and 34 did not. One-year survival was 71% versus 50% with and without lung dose reduction respectively (log rank test p=0.042). Eighty-five patients had FEV1 and/or DLCO greater than or equal to 100% predicted; 34 were treated with lung dose reduction and 51 without. In both groups, 1 year survival was 70%. Conclusions: Among patients treated without lung dose reduction, survival was significantly worse among those with pretreatment combined ventilation/diffusion capacity deficits. Among those with combined ventilation/diffusion capacity deficits, lung dose reduction significantly improved survival. No significant financial relationships to disclose.
Characteristics of Refractory and Relapsing Patients with Diffuse Large B-Cell Lymphoma
Authors: Bertrand Coiffier, Gilles Salles, Andre Bosly, Philippe Gaulard, Corinne Haioun, Olivier Casasnovas, Nicolas Mounier, Marie Helene Delfau, Catherine Sebban, Pierre Feugier, Christian Recher, Richard Delarue, Nicolas Ketterer, Herve Tilly, Christian Gisselbrecht
Journal: Blood (2008)
THU0611 Anakinra treatment in patients with familial mediterranean fever: a single-centre experience
Authors: B. Ergezen, S. Ugurlu, H. Ozdogan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Approximately 5 to 10% of FMF patients do not respond to colchicine treatment and/or intolerant to colchicine due to side effects. Several case reports and case series have pointed out the efficacy of IL-1 blockade in colchicine resistant FMF subgroup. <h3>Objectives</h3> To review the patients followed in our centre with FMF who received anakinra, an anti-IL-1 receptor antagonist, because of insufficient colchicine response. <h3>Methods</h3> FMF patients who were treated with anakinra were retrospectively reviewed with regard to indication, effect on disease activity and acute phase response, adverse events. Patient global assessment was recorded before and after anakinra treatment. <h3>Results</h3> There were 48FMF patients with FMF who were treated with anakinra for various indications (colchicine resistant recurrent febrile attacks in 42, colchicine related side effects in 6). The mean age of the group was 31.8±9.2 years. The mean duration of the disease was 12.3±7.9 years. There were various co-existing pathologies among this study group like multiple sclerosis,<sup>1</sup> ankylosing spondylitis,<sup>1</sup> SLE,<sup>1</sup> Behçet's disease,<sup>1</sup> low grade lymphoma,<sup>1</sup> psoriasis,<sup>2</sup> vasculitis<sup>2</sup> and PAN.<sup>2</sup> The mean colchicine dose was 2,13±0,51 mg/d. The mean duration of anakinra treatment was 14.47±10.8 months. Twenty seven patients reported no attacks after anakinra treatment whereas 10 patients reported at least 50% decrease in the attack frequency. There are 4 patients who were primarily irresponsive to the therapy, whereas in 5 patients response to therapy ameliorated during the course of the treatment. Mean patient global assessment decreased from 8.58±1.2 to 2.72±3.16 under anakinra treatment (p=0.001). Four patients had severe allergic reactions (severe disseminated rash in 1 patient and severe injection site reaction in 3 patients) and therefore the drug was stopped. Two patients had infections (one had genital warts and urinary tract infection, the other had sinusitis and folliculitis) and the treatment was terminated. One of our patients reported that her psoriatic lesions got worse on anakinra. Forty one patients reported no adverse events during the treatment. Conclusions: Anakinra was effective in controlling the symptoms in colchicine-resistant FMF cases. It was also effective in FMF related amyloidosis. The major cause of treatment termination was injection site reactions. Anakinra seems to be an effective alternative in patients who have insufficient response to colchicine. <h3>Disclosure of Interest</h3> None declared
Bus Rounds: An innovative model of patient-based teaching for palliative care delivery
Authors: D. S. Zhukovsky, N. Dhillon, D. Fullerton, M. Greer, E. Bruera
Journal: Journal of Clinical Oncology (2005)

8214 Background: Physicians (MD), nurses (RN) and other health care professionals (HCP) receive minimal education in palliative care delivery, with emphasis on acute care. Taking clinicians of diverse backgrounds into patient’s homes and other community settings, Bus Rounds (BR) provides an intensive, patient-based interactive model of palliative care delivery (PCD) during a single 4 hour session. Methods: The study was a prospective survey of BR conducted over 1 year. Participating clinicians anonymously completed a questionnaire regarding achievement of educational goals (EG), themes addressed during individual BR and demographic variables. Successful achievement of EG was defined as percent that agreed or strongly agreed that they had learned to: 1. Identify symptoms commonly experienced by patients with advanced cancer 2. Describe an approach to the assessment of symptoms and quality of life 3. Discuss in detail the management of one symptom experienced by a patient seen on BR 4. Identify similarities in the provision of palliative care (PC) and hospice (H) 5. Identify differences in the provision of PC and H. Analysis was descriptive. Administrative approval was obtained from the Institutional Review Board. Results: 5 BR with 107 HCP occurred over 1 year. 11 surveys were missing, yielding 96 for analysis. Participating HCP included MD (16%), RN (37%), administrator (6%), pastoral care (9%) and social work (18%). 69% (n=93) were female. Practice was H-based (n=87) in 59% and hospital-based in 30%. Years in practice were <1 in 13% and ≥6 in 23%. Time spent in H/PC (n=82) was >75% in 45% and <30% in 23%. Successful achievement of EG 1: 90%, 2: 98%, 3: 94%, 4: 79% and 5: 77 %. ≥75% identified pain, psychosocial distress, cognitive impairment, communication, interdisciplinary approach to patient care, spirituality, and symptom assessment and management as themes discussed, with ≥50% in each BR identifying ≥8 of 12 specified themes. Conclusions: BR are perceived as effective in teaching PCD to diverse HCP. A broad range of themes is addressed on each BR. More emphasis on identifying similarities and differences between PC and H care is needed. No significant financial relationships to disclose.
The National Cancer Institute's cancer Biomedical Informatics Grid (caBIG™): Linking research and care
Authors: M. Deering, B. Duggan
Journal: Journal of Clinical Oncology (2008)

17539 Background: The National Cancer Institute's (NCI) cancer Biomedical Informatics Grid, or caBIG, is a virtual informatics infrastructure and tools to enable the seamless exchange of information between clinical research and care delivery. caBIG supports basic and translational research, clinical trials research, in vivo imaging, and tissue banking and pathology. Its standards-based grid technology supports linkages with compatible electronic health records (EHRs). Methods: An oncologist should be able to ask “what are the treatments and outcomes of other patients who have similar characteristics to my patient.” caBIG makes this possible on multiple levels: local, institutional, regional, national, and beyond by leveraging grid infrastructure to scale beyond traditional query systems. NCI is partnering with key organizations to develop the technical basis for interoperable oncology EHRs and promote the adoption of interoperable EHRs in oncology practices. It is working with community cancer centers to use linked databases to support ongoing basic, clinical, and population-based cancer research. Results: Over 40 NCI-designated Cancer Centers and many smaller community cancer centers are deploying caBIG technologies and adopting or adapting specific tools to strengthen their research and care. These efforts will bring the latest scientific advances and the highest level of innovative and integrated multispeciality care to a larger population of cancer patients. Conclusions: Research and care can be strengthened through the use of standards-based, interoperable electronic medical records integrated with research-oriented modules. There are tools immediately available to aid clinical oncologists through the NCI caBIG initiative. Enhanced clinical analyses are made possible by EHRs working interoperably with caBIG tools and resources. No significant financial relationships to disclose.
Palliative radiotherapy versus palliative chemoradiotherapy in treatment of NSCLC stage IIIA and IIIB: Phase II randomized trial
Authors: S. Nawrocki, M. Krzakowski, E. Wasilewska-Teńluk, D. Kowalski
Journal: Journal of Clinical Oncology (2007)

18128 Background: The optimal treatment for stage IIIA/IIIB NSCLC patients who do not qualify for radical treatment has not been identified. Different palliative radiotherapy regimens and chemotherapy are used but have not been compared. We decided to combine short chemotherapy and radiotherapy (CT-RT) in order to improve therapeutic index of radiotherapy (RT). Methods: Eligibility criteria: Locally advanced, inoperable patients (pts) in IIIA (N2 positive) -IIIB clinical stage with tumor larger than 8 cm in longest diameter or/and FEV1 smaller than 40%, PS: 0–2 (ECOG), non-eligible for radical CT-RT. Treatment: RT arm - 3-D radiotherapy, 30 Gy/3 Gy, 2 weeks. CT-RT arm - two cycles of CT (cisplatin: 80 mg/m2; d 1, 22; vinorelbine: 25 mg/m2 iv; d 1,8,22,29) followed by RT as in Arm 1 with concurrent third cycle of CT (cisplatin 80 mg/m2, d 43; vinorelbine 25 mg/m2 iv., d 43, 50). Study design: Phase II, two-center, randomized study, stratification IIIA vs. IIIB, PS 0–1 vs. 2, treating center (Warsaw vs. Olsztyn). Two-stage design, a and β errors = 0,1; p1 minus p0 = 0,20. Planned sample size - 46 pts/arm. Primary endpoint: response rate (RECIST). Secondary end-points: overall survival (OS), toxicity, progression free survival (PFS). Results: During 2 years 104 pts randomized, 98 eligible for toxicity and survival/progression analysis, 82 for response assessment. Demographics: median age - 65 (45–78), IIIA/IIIB: 27/71 pts. PS 0–1/2: 72/26. Well balanced between arms. Response rate: RT arm- 26%, CT-RT arm- 46%, median OS for RT arm - 195 days, CT-RT arm 2 - 385 days, log-rank test p=0,047, median PFS for RT arm - 140 days, CT-RT arm - 172 days, log-rank test p=0,16. Toxicity: deaths - 2 in RT arm, 2 in CT-RT arm; hematological G3–4 - 0 in RT arm, Arm CT- RT: anemia - 2, thrombocytopenia - 6, neutropenia - 11, esophagitis - 2. Other G3–4: RT arm -3, CT-RT arm -1. Conclusions: Palliative radiotherapy (30Gy) with chemotherapy postponed to progression is a suboptimal treatment for patients with locally advanced NSCLC. 2 cycles of cisplatin/vinorelbine plus RT concomitantly with 3 cycle increases clinical response rate and significantly prolongs survival at the cost of acceptable toxicity in palliative setting. No significant financial relationships to disclose.
Therapeutic Relevance of CD34 Cell Dose in Blood Cell Transplantation for Cancer Therapy
Authors: Salvatore Siena, Roberta Schiavo, Paolo Pedrazzoli, Carmelo Carlo-Stella
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To review recent advances in peripheral-blood progenitor-cell (PBPC) transplantation in order to define the optimal cell dose required for autologous and allogeneic transplantation. MATERIALS AND METHODS: A search of MEDLINE was conducted to identify relevant publications. Their bibliographies were also used to identify further articles and abstracts for critical review. RESULTS: The CD34 + cell content of a graft is regarded as an accurate predictor of engraftment success. Postchemotherapy autologous PBPC transplantation with ≥ 5 × 10 6 CD34 + cells/kg body weight leads to more rapid engraftment than does transplantation of lower cell doses. Further increases in transplant cell dose further accelerate platelet but not neutrophil engraftment. Evidence that long-term hematopoietic recovery may be more accurately predicted by the subpopulation of primitive progenitors transplanted suggests that the content of CD34 + CD33 − and long-term culture-initiating cells in cell collection samples may be important for predicting successful engraftment, particularly in patients with poor mobilization. Allogeneic transplantation has been limited by concerns regarding graft-versus-host disease and the use of hematopoietic growth factors in donors. The risk of graft rejection and engraftment failure after HLA-mismatched allogeneic transplantation may be overcome by intensive chemoradiotherapy and the infusion of large numbers of T cell–depleted hematopoietic stem cells. CONCLUSION: An optimal cell dose of ≥ 8 × 10 6 CD34 + cells/kg seems to be recommended for autologous PBPC transplantation. This dose facilitates the administration of scheduled chemotherapy on time and reduces the demand for other supportive therapies. A combination of growth factors may enable patients with poor mobilization to achieve a collection sufficient to allow transplantation. The optimum PBPC dose for allogeneic transplantation remains to be defined.
Impact of pomegranate extract on NF-κΒ activation and emerge of androgen-independent prostate cancer
Authors: M. B. Rettig, D. Heber, J. An, T. Klatte, N. Seeram, H. Liu, J. Y. Rao, S. Henning, A. S. Belldegrun, A. J. Pantuck
Journal: Journal of Clinical Oncology (2008)

16099 Background: Constitutive NF-κB activation is observed in prostate cancer and represents a predictor for biochemical recurrence after radical prostatectomy. Heightened activation of NF-κB is observed during the transition to androgen independence. Dietary agents such as pomegranate extract (PE) have received increasing attention as potential agents to prevent the onset or progression of many malignancies, including prostate cancer. We sought to determine whether extracts from the pomegranate fruit could inhibit NF-κB activation and growth of prostate cancer and delay the emergence of androgen independence in in vitro and in vivo models. Methods: The effects of PE on prostate cancer growth, proliferation, and apoptosis were assayed in vitro in multiple androgen- dependent and androgen-independent prostate cancer cell lines. NF-κB activity was measured by reporter gene and electrophoretic mobility shift assays. To evaluate the in vivo effects of PE, we also employed the LAPC4 xenograft model of androgen-independence. Tumor growth, proliferation and angiogenesis were measured. Results: PE inhibited NF-κB and cell viability in a dose- dependent fashion in vitro in DU145, LAPC4, CL1, and LNCaP-AR cell lines. In experiments in which NF-κB activity was maintained during PE exposure by transfecting NF-κB family member, we demonstrated that inhibition of NF-κB activation by PE is required for maximal apoptosis induced by PE. Moreover, in the LAPC4 xenograft model of androgen-independence, PE inhibited the heightened NF- κB activation that results from the emergence of androgen independence and reduced the growth of androgen-independent xenografts; this growth reduction was associated with an inhibition of proliferation and induction of apoptosis. Conclusions: PE extracts inhibit the growth of prostate cancer cells both in vitro and in vivo. Our study represents the first description of PE as a promising dietary agent for the prevention of the emergence of androgen independence through a mechanism that is at least in part driven by heightened NF-κB activity. No significant financial relationships to disclose.
Incidence of grade 3/4 adverse events in imatinib resistant/intolerant chronic phase CML (CP-CML): A comparison of nilotinib and dasatinib
Authors: K. T. Carpiuc, J. M. Stephens, S. Y. Liou, M. F. Botteman
Journal: Journal of Clinical Oncology (2007)

17501 Background: Toxicities of new treatments may increase the care and resources required to manage patients (pts). The objective of this study was to compare the rates of Grade 3/4 AEs reported for nilotinib and dasatinib, the second generation tyrosine kinase inhibitors (TKIs) in imatinib resistant/intolerant CP-CML pts in preparation for an economic analysis. Methods: A systematic literature review was conducted to identify published articles, registration documents, or abstracts of clinical trials in CP-CML for nilotinib 400 mg bid and dasatinib 70 mg bid. The base case incidence rates were selected from the most rigorous sources, specifically data from the dasatinib product label and the nilotinib phase II trial, both populations having a median drug exposure of slightly &gt;5 months. The AEs selected for the comparison were based on frequency (&gt;5%) and/or high likelihood of incurring incremental costs for medical treatment/monitoring. The full ranges for the incidence of AEs (if available) were summarized from other papers/abstracts for sensitivity analyses in future economic analyses. Results: The Grade 3/4 hematologic AEs were the most common AEs (table below) and were ∼2 times higher for dasatinib than for nilotinib. Common Grade 3/4 biochemistry abnormalities included lipase elevations in 5% of nilotinib pts (1 pt developed a Grade 1/2 pancreatitis; no Grade 3/4 pancreatitis) and hypophosphatemia in 11% of dasatinib pts. Rates of Grade 3/4 non-hematologic AEs such as pleural effusion, GI bleeding, arrhythmia, and pneumonia/infection were &gt;2–7 times higher for dasatinib than nilotinib, though they occurred in &lt;5% of the population. Conclusions: The toxicity profiles of the second generation TKIs for imatinib resistant/intolerant CP-CML appear to be different and favor nilotinib with its reduced rates of Grade 3/4 AEs. Further analysis is required to understand the cost impact to health care payers of the differences in safety profiles among the new TKIs. [Table: see text] No significant financial relationships to disclose.
Chemoradiation for esophageal cancer (EC) in elderly patients over 75 years: A phase II study
Authors: F. Lorchel, M. Bosset, G. Crehange, J. Buffet-Miny, M. Puyraveau, M. Mercier, J.-F. Bosset
Journal: Journal of Clinical Oncology (2004)

4155 Background: 10–20% of patients (pts) with EC are older than 75 years. They are generally excluded from surgery, and there is no data on the feasibility nor on the efficacy of chemoradiation applied in a curative intent. Methods: Aim of study: Evaluating feasibility, efficacy and consequences on quality of life of chemoradiation in old patients. We report on the feasibility. Main inclusion criteria: age ≥ 75years WHO status 0–2; ambulatory condition; weight loss <15% from baseline; disease-stages II-III assessed by CT scan; squamous or denocarcinomas; written informed consent. Treatment scheme: Radiation: 50 Gy over 5 weeks; chemotherapy: Cisplatin 75 mg/m2 on day 1 and day 22 of radiation. Treatment delivered in an out-patient basis. Results: Between 3/00 and 9/03, 17pts have been recruited: 13 males; 4 females; mean age 80 y (75–89 y); WHO status 1: 13 pts; 2: 4 pts; mean weight loss at entry: 6% (0–18%). Squamous: 14 pts; adeno: 3 pts; Stage II: 13 pts; Stage III: 4 pts. Twelve pts had one or more associated comorbidity. Compliance with radiation, doses and timing: 100%; with chemotherapy: 100%. ≥ Grade 2 acute toxicity: vomits: 4 pts; granulopenia: 5 pts; anemia: 2 pts; esophagitis: 3 pts. No grade 4 nor toxic death. Tumour response (15 pts evaluable): CR: 12 pts; local progression: 3 pts. By december 03, 10 pts are free of disease from 4, up to 44 months. Conclusions: Selected old patients with EC are suitable for curative chemoradiation. The study is still recruiting to assess further efficacy and Quality Of Life. Supported by a grant from the French Research Ministry (PHRC 1999). No significant financial relationships to disclose.