tbuckley/cabot-search huggingface dataset:
Regional models of care for systemic therapy: Standards for organization and delivery
Authors: T. Vandenberg, A. Smith, C. McLennan, L. Wilcock, J. Nayler, N. Coakley, C. DeGrasse, E. Green, C. Sawka, M. E. Trudeau
Journal: Journal of Clinical Oncology (2007)

17057 Background: Rapidly expanding indications for cancer systemic therapy combined with human resource and facility constraints require innovative approaches to deliver safe, patient-centred, and evidence-based care across Ontario, a province covering 1 million sq km, organized into 14 regions, each with about 1 million inhabitants. A systemic therapy project team recommended the best way to organize the delivery of ambulatory systemic therapy in Ontario. Methods: A core multidisciplinary panel reviewed the evidence and developed standards. The panel used evidence-based analysis of relevant publications, an environmental scan of other existing recommendations and expert opinion based on experience and consensus to formulate a standards document to guide treatment delivery. This was reviewed and amended by the full project team. The document was circulated to oncologists, family practitioners, internists, pharmacists, nurses and administrators who work in or have responsibility for systemic therapy in the regions for practitioner feedback. Results: A Regional Systemic Therapy Program (STP) Model was developed in which Integrated Cancer programs (ICPs) provide comprehensive cancer services, leadership of quality and overall organisation/coordination for the region. STPs include ICPs directly linked to satellite centres and also affiliated to centres with their own systemic therapy programs to provide appropriate systemic therapy services for all regions under a common set of standards. Five levels of care are recommended, with complexity and availability of services differentiating the levels. For each level, standards were established for; 1-Providers and their roles, 2-Education for providers, 3-Service type and complexity, 4-Service volumes, 5- Quality assurance and safety, 6-Facility requirements, 7-Administrative and organizational responsibilities. The intent is to provide the same standard of care in the most appropriate setting within the appropriate time frame. STPs will implement, monitor and evaluate quality indicators. Conclusions: A detailed review of the document including results of practitioner feedback as well as survey results from the 14 STPs to determine whether standards are being currently met will be presented. No significant financial relationships to disclose.
Combination of gemcitabine and carboplatin chemotherapy for recurrent nasopharyngeal carcinoma.
Authors: Y. Beldjilali, M. Yamouni, K. A. Benhadji, H. Khellafi, A. Abdelaoui, F. Betkaoui, A. Kaid, F. Z. Daim, L. Benchlef, L. Djellali
Journal: Journal of Clinical Oncology (2010)

e16006 Background: Although appropriate radiotherapy and combined treatments are widely used for the patients with primary nasopharyngeal carcinoma (NPC), regional or metastatic recurrence rates are still high. This study evaluated the efficacy and toxicity of combination gemcitabine plus carboplatin (GC) chemotherapy in recurrent nasopharyngeal carcinoma (NPC). Methods: Patients with recurrent NPC who have received previous cisplatinum based chemotherapy combined with radiation therapy were eligible for this study. Patients received GC combination: gemcitabine 1,250 mg/m2; days 1, and 8; carboplatin AUC 4 on day 1. Cycles were repeated every 28 days until progression or unacceptable toxicity. Primary endpoint was response rate. Results: 25 patients were enrolled (20 males and 5 females). Median age was 46.5 years. Majority of patients (20) had metastatic disease. 63% of patients have received one previous line of treatment. There were 8 partial responses (32%), 9 stable diseases (36%), and 8 progressive diseases (32%). The median duration of response was 4.3 months. The median overall survival was 8.2 months. Improved subjective symptom-control scores were found in 68 % of patients with pre-existing symptoms, while 64% of patients experienced improved general well-being scores. Toxicity was mainly hematological: grade III/IV anemia, granulocytopenia and thrombocytopenia were found in 6%, 3% and 10% of cycles, respectively. Conclusions: GC combination offers a satisfactory overall response rate, subjective patient symptoms improvement and acceptable safety profile for recurrent NPC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly
Structural changes in the internal domain of the CD20 antigen is associated with the development of rituximab resistance: Effects on signaling and redistribution of CD20 into lipid raft domains in rituximab-resistant cell lines (RRCL)
Authors: A. C. Gowda, F. J. Hernandez-Ilizaliturri, G. Connolly, M. S. Czuczman
Journal: Journal of Clinical Oncology (2004)

2502 Backgound: Following rituximab binding, CD20 antigen redistributes into lipid raft domains (LRD) and initiates signaling events leading to apoptosis in malignant B-cells. The development of resistance to rituximab has been observed clinically in lymphoma patients. To define the molecular basis for rituximab resistance we developed various RRCL and studied changes in CD20 structure, membrane reorganization and signaling events following rituximab therapy. Methods: RRCL were generated by chronic exposure of Raji cells to escalating doses of rituximab alone (2R) or with human complement (4RH). Changes in the structure of CD20 were determined by Western blotting using various antibodies recognizing epitopes located in the internal (GST77 and 1439) and external domain (B1) of CD20. Following rituximab exposure, LRD were extracted from Raji and RRCL. Redistribution of CD20 antigen and signaling events following rituximab exposure were evaluated by Western blotting. Results: No significant changes were observed in the expression of the external domain of CD20 antigen between rituximab-sensitive and RRCL, as demonstrated by flow cytometric analysis and Western blotting. However, significant changes in the internal domain of CD20 were observed in RRCL. Specifically, changes in the N-terminal, and to a lesser degree the C-terminal region of the internal domain of CD20 were observed in RRCL. While redistribution of CD20 into the LRD was similar between Raji cells and RRCL, a decrease in p38 expression was observed following rituximab therapy on RRCL. Conclusions: Our data strongly suggests that the acquirement of rituximab resistance is associated with significant changes in the structure of the internal domain of the CD20 antigen. The abnormal production of truncated forms of the CD20 antigen, while not affecting rituximab binding or redistribution of the CD20 antigen into LRD, results in a decrease in signaling events. Impairment of anti-CD20 signaling activation theoretically renders the cells resistant to rituximab. No significant financial relationships to disclose.
Beneficial effects of elective brain irradiation (BI) in limited disease inoperable non-small cell lung cancer patients treated with combined chemo-radiotherapy (CCRT)
Authors: T. Umsawasdi
Journal: Journal of Clinical Oncology (2007)

18033 Background: BI significantly decrease brain metastases (BM) and prolonged CNS relapse free (CRF) duration (J Neurooncol 2: 253, 1984). Studies of 5 CCRT protocols using chest irradiation with randomization to BI after 2–3 courses of chemotherapy showed that patients who had complete response (CR), partial response (PR), minor response (MR), or no change (NC) of the diseases with CCRT benefited from BI with significantly reduced BM, prolonged response (R) duration and time to progression (TTP). (Proc. ASCO 5: Abstract 728, 1986). The value of BI remains unclear. Methods: Re-evaluation of previously mentioned 5 CCRT protocols was done to determine the effects on S, duration of R, TTP, and CRF with evaluations at 75 th percentiles. Results: Of 138 patients (59 BI+), there was no significant difference between BI+ and BI- in terms of characteristics and response to CCRT. The effects of BI on S, duration of R, TTP, and CRF are as above. Conclusions: 1) BI significantly improved the duration of R,TTP, and CRF; 2) Although no S benefit was found in standard evaluation, BI patients had 37 weeks S advantage at 75 th percentiles; 3) Patients who had CR, PR, or MR had benefited from BI and the benefits were more when evaluated at 75 th percentiles; 4) The standard study of duration curves should be modified to look at a higher percentiles if the proposed treatment had low responses; 5) Awaiting for the results of RTOG 0214, our information could possibly favor BI in these patients. [Table: see text] No significant financial relationships to disclose.
The 782C → T (T254M) XHIM Mutation: Lack of a Tight Phenotype-Genotype Relationship
Authors: Esther de Vries, Jeroen G. Noordzij, E. Graham Davies, Nico Hartwig, Martÿn H. Breuning, Jacques J.M. van Dongen, Maarten J.D. van Tol
Journal: Blood (1999)
Hounded
Authors: Anna Reisman
Journal: JAMA (2014)

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Patient benefit from trastuzumab plus a taxane regardless of estrogen receptor (ER) status or prior adjuvant therapy for HER2+ metastatic breast cancer (MBC)
Authors: J. C. Reddy, S. Rai, G. Lieberman, P. Klein
Journal: Journal of Clinical Oncology (2004)

674 Background: Trastuzumab (Herceptin, H) is a humanized monoclonal antibody which showed a significant survival benefit in a randomized trial comparing chemotherapy plus H vs. chemotherapy alone in first-line treatment of HER2+ MBC. The effect of prior adjuvant therapy and ER status on response to H/chemotherapy is not well characterized. We performed subset analyses to determine whether patients (pts) responded differently to H/taxane therapy depending on ER status and prior adjuvant therapy. Methods: Pts had previously untreated HER2+ MBC (prior hormonal therapy allowed), normal left ventricular ejection fraction (LVEF), and measurable or evaluable disease. All pts received H (4 mg/kg load -> 2mg/kg q week) with either paclitaxel or docetaxel at standard doses. LVEF was measured at baseline, at week 16 of therapy and as indicated thereafter. Results: 401 pts have been enrolled. Baseline characteristics: median age 56, performance status 0–1 (90%), estrogen receptor (ER)+ (49%), ER- (49%), postmenopausal (55%). 352 pts were evaluable for best response within 6 months of starting combination therapy. The objective response rates (ORR) and clinical benefit rates (CBR) are shown below with 95% confidence intervals for the overall population and for subsets. Both taxane/H regimens were well tolerated. The median LVEF was 63% at baseline and 60% at week 16. 8 patients experienced clinical CHF (2%); 5/8 had significant pre-existing cardiac disease or risk factors. There was one case of fatal neutropenic sepsis. Conclusions: HER2+ MBC pts derive equal benefit from therapy with H plus a taxane regardless of ER status or prior adjuvant chemotherapy or hormonal therapy. There was a low incidence of clinical CHF. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc. Genentech, Inc.
Relationship between performance status and malnutrition in non-selected cancer patients: A nation-wide one-day survey
Authors: C. Mateus, W. Cacheux, E. Lemarié, M. Michalet, C. Beauvillain de Montreuil, X. Hébuterne, F. Goldwasser
Journal: Journal of Clinical Oncology (2007)

9126 Background: The evaluation of the performance status (PS) is universally used in oncology and a PS of 2 is known as associated with reduced survival and increased risk of toxicity following chemotherapy. The aim of the present study was to evaluate the prevalence of malnutrition in a non selected population of cancer patients (pts) and how malnutrition correlates with poor PS. Methods: A prospective one-day prevalence survey was carried out in 154 wards of private or public hospitals in 24 cities in France. Height, present and usual body weight were assessed in outpatients and inpatients who were present that day. Malnutrition was defined as a Body Mass Index &lt;18.5 or &lt;21 in pts of 75 yrs or more and/or as a loss of body weight &gt;10% from the beginning of the disease. The prevalence of malnutrition was studied in the overall population and stratified for the type of cancer and the PS. Results: 2,068 pts (1,189 men and 879 women) aged 60±13 yrs were evaluated and nutritional status was available in 1,903 pts. The PS was 0 or 1 in 52.3% of pts, 2 in 25.3%, 3 or 4 in 22.4%. Overall, 38% of pts were malnourished. Prevalence of malnutrition according to the primary tumor was: pancreas (n=42): 67%, oesophagus (n=41): 61%, stomach (n=41): 59%, head and neck (n=366): 49%, lung (n=247): 45%, ovary/uterus (n=87): 45%, colon/rectum (n=191): 39%, leukemia/lymphoma (n=377): 34%, breast (n=229): 21%, prostate (n=72): 14%. The prevalence of malnutrition was 14.4%, 31.4%, 52.3%, 53.6%, and 65.3% in pts with a PS ranging from 0 to 4, respectively. In comparison to PS-0 pts, Relative risk (RR) of malnutrition was 2.5 (p &lt; 0.0001) in PS-1 pts and 6.4 in PS-2 pts (p&lt;0.0001). Conclusions: Malnutrition is diagnosed in &gt;50% of PS-2 pts. Systematic screening and care of malnutrition is mandatory to improve the PS and subsequently treatment tolerability in these pts. No significant financial relationships to disclose.
Comorbidity and overall survival (OS) in cetuximab-treated patients with advanced colorectal cancer (ACRC)—Results from NCIC CTG CO.17: A phase III trial of cetuximab versus best supportive care (BSC)
Authors: E. D. Powell, T. Asmis, D. Jonker, D. Tu, C. Karapetis, M. Jeffery, C. O’Callaghan
Journal: Journal of Clinical Oncology (2009)

4074 Background: The interplay between comorbidity, age and performance status (PS) as predictors of outcome in ACRC is not well described. We examined these factors as predictors of treatment toxicity and outcome in cetuximab-treated patients with ACRC. Methods: Comorbidity was independently evaluated by 2 physicians using the Charlson Comorbidity Index (CCI), a previously validated measure of comorbidity based on the presence or absence of index medical conditions weighted according to their affect on mortality. CCI score was correlated with demographic data (age, gender), PS, site of primary, time from diagnosis to randomization, body mass index, hemoglobin, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine clearance, K-ras status and OS. Results: 572 patients were included. 41% were ≥65 years and 25% had comorbidities at randomization. CCI score was 1 in 21% and ≥ 2 in 4%. In multivariate analysis (MVA) of all covariates, only older age (≥65 years) was associated with greater comorbidity (p=0.005). OS was different among 3 comorbidity groups (CCI score 0, 1, ≥ 2) in univariate analysis (median OS 4.9 vs 5.9 vs 4.8 months;, logrank p=0.04) but not in MVA. Conversely, lower PS remained associated with better OS in MVA (HR 1.96 for PS=2 vs. PS=0, p&lt;0.0001). Age was not associated with OS (p=0.11). Other factors significantly associated with OS in MVA included time from diagnosis to randomization, LDH, ALP, hemoglobin, Kras status and cetuximab treatment. In the BSC arm, comorbidity was not associated with OS in MVA (HR 0.83 CCI 1 vs. CCI0, p=0.26 and HR 0.90 for CCI2 vs. CCI0, p=0.78) suggesting comorbidity is not prognostic in this setting. Patients with higher CCI score had a nonsignificant trend toward greater treatment effects. Patients ≥65 years had less gr≥3 vomiting (1.8 vs 7.9%, p=0.034) but more dyspnea (24.5 vs 11.2%, p=0.005). Patients with higher CCI scores had less vomiting (p=0.008) but more non-neutropenic infection (p=0.012). Conclusions: In this clinical trial, comorbidity and age were not independent predictors of survival, highlighting the difference between comorbidity and PS. [Table: see text]
A phase II second-line study of pemetrexed (pem) in combination with bevacizumab (bev) in patients with advanced non-small cell lung cancer (NSCLC): An NCCTG and SWOG study
Authors: A. A. Adjei, S. J. Mandrekar, G. K. Dy, J. R. Molina, A. A. Adjei, D. R. Gandara, K. L. Allen Ziegler, P. J. Stella, K. M. Rowland, S. R. Schild, R. G. Zinner
Journal: Journal of Clinical Oncology (2008)

8080 Background: This phase II study was performed to evaluate the clinical efficacy and toxicity of pem (500 mg/m2 iv) combined with bev (15mg/kg iv) given every 3 weeks in the 2nd-line therapy of patients (pts) with stage IV/IIIB (pleural effusion) NSCLC. Allelic variants in pem metabolizing genes were also evaluated and correlated with response and toxicity. Methods: The proportion of progression-free (and still on treatment) pts at 3 months (success) was the primary endpoint. Based on a one-stage Fleming design with an exact significance level of 0.09 and 90% power to detect an effective treatment if the true success rate was at least 70%, this treatment would be promising if at least 26 of the first 42 evaluable patients were successes. Based on FPGS re-sequencing and SNP data mining studies, ht-SNPs in pem metabolizing and transport genes (FPGS, GGH, SLC19A1) were constructed. Germ-line DNA was genotyped for these SNPs Results: 48 pts (14 females; 34 males), all evaluable for adverse events (AEs) were accrued. All except one pt are off active treatment. Grade 3+ and 4+AEs occurred in 32 (67%) and 10 (21%) patients respectively. The most common (occurring in 10% or more of patients) grade 3/4 non-hematologic AEs were fatigue (13%), dyspnea (10%), and thrombosis (10%), and grade 3/4 hematologic AEs were neutropenia (19%), leukopenia (17%), and lymphopenia (13%). 24 of the first 42 pts (57%, Exact CI: 41–72%) met the success criteria. The overall disease control rate was 50% (5 confirmed partial response (CPR), 19 confirmed stable disease). In the 5 pts with a CPR, the median response duration was 133 days (range: 84–213). The median follow-up on alive pts is 9 months (m), with a median survival of 8.6 m and a median PFS of 4.1 m. Haplotype-tagged SNPs in GGH (pem inactivation) and reduced folate carrier, SLC19A1(pem transport) were significantly correlated with overall survival, PFS and AE. Conclusion: With a median PFS of 4.1 m, this combination represents an improvement on the median PFS of 2.9 months for a number of single second-line agents and needs to be further studied. Pharmacogenetic studies in larger pt cohorts may predict for efficacy and/or toxicity to pem. No significant financial relationships to disclose.
Neoadjuvant capecitabine chemotherapy in women with newly diagnosed locally advanced breast cancer in a resource-poor setting (Nigeria): Efficacy and safety in a phase II feasibility study.
Authors: Olukayode Adeolu Arowolo, Uchenna O Njiaju, Temidayo O Ogundiran, Olukayode O Lawal, Millicent Obajimi, Adebayo Adetiloye, Hae Kyung Im, Akinbolaju Andrew Akinkuolie, Abideen Olayiwola Oluwasola, Kayode Adelusola, Abdulrusheed Kayode Adesunkanmi, Augustine Agbakwuru, Adeyinka Falusi, Muheez Durosinmin, Olusola C Olopade, Olufunmilayo I Olopade
Journal: Journal of Clinical Oncology (2012)

e11554 Background: The majority of clinical trials of neoadjuvant therapy for breast cancer have been conducted in resource-rich countries. We chose Nigeria, a resource-poor country, as the major site for a phase II feasibility open label multicenter clinical trial designed to evaluate the efficacy, safety and tolerability of neoadjuvant capecitabine in locally advanced breast cancer. Methods: Planned treatment consisted of 24 weeks of capecitabine at a dose of 1000mg/m 2 twice daily (2000mg/m 2 total per day). Each cycle consisted of a 14-day period of therapy followed by a 7-day pause, and patients were evaluated after 3 cycles and taken off study if no response was documented. Responding patients were treated for no more than 8 cycles. The primary endpoints were partial, complete clinical response and pathologic complete response. Results: A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first 3 cycles of therapy, partial clinical responses were seen in 5 of 16 patients (31%; 95% CI 11% - 59%). Of the remaining 11 patients, 8 had no response or stable disease, and 3 had progressive disease. Seven pateints proceeded with further therapy, two of them with stable disease but exactly in the border line of 25% increase. By physical examination, only 2 of the 6 patients had a documented complete clinical response, while by ultrasonomammography, partial responses were observed in 5 patients. Thus, overall response rate at the end of 8 cycles were 31.1% both by clinical examination and by ultrasonomammography. Clinical response by physical examination and radiologic response by ultrasonomammography were highly concordant (the spearman correlation between the two ratios was 0.70). The most common adverse effect was Grade 1 Hand and Foot Syndrome in 75% of patients. Conclusions: Despite several limitations, we successfully carried out this phase II feasibility study of neoadjuvant capecitabine for locally advanced breast cancer in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted.