tbuckley/cabot-search huggingface dataset:
Multicenter phase II trial of carboplatin (Cb) and gemcitabine (G) followed by concurrent chemoradiation in patients with unresectable stage III non-small-cell lung cancer (NSCLC): FEV1 as prognostic marker
Authors: P. R. Germonpré, A. Janssens, L. Van Moorter, D. Verresen, D. Galdermans, R. Devogelaere, H. Ottevaere, Y. Mentens, C. De Pooter, C. Goor
Journal: Journal of Clinical Oncology (2008)

7558 Background: In patients (pts) with unresectable stage III NSCLC concurrent chemoradiotherapy (CRT) results in improved survival compared to sequential CRT, but comes at the cost of increased toxicity. Data from the recent HOG 01–24 trial suggest that survival of stage III NSCLC patients is correlated with the FEV1. Methods: Pts (PS 0–2) with unresectable stage III NSCLC and FEV1 ≥1.5L were treated with 3 cycles of induction chemotherapy (Cb AUC 5 on d1 and G 1,200 mg/m2 on d1 and d8 Q3 wks) followed by conventional radiotherapy (2.0 Gy/fraction, 5 fractions a week, up to a total dose of 60 Gy) with concurrent weekly cisplatin (Cis 30 mg/m2). The primary endpoint was overall survival at 2 years. An exploratory analysis the effect of FEV1 (expressed as % of predicted value) on survival was performed. Results: Between 02/2003 and 11/2005, 45 pts were enrolled. The demographics were as follows: 34/11 male/female, 14/31 stage IIIA/IIIB, median age 62 y (range 41–81 y), 31/12 FEV1 ≥70%/<70%, 42% squamous cell and 33% adenocarcinoma. All pts received at least 1 cycle CbG. CRT was started in 36 pts: median total radiation dose and duration was 60 Gy and 43 days. The overall response rate was 58% (2% CR, 56% PR). Primary grade 3/4 toxicities were neutropenia (36%), thrombocytopenia (18%), febrile neutropenia (1%). No treatment-related deaths were observed. The median progression-free (PFS) and overall survival (OS) are 11.1 m and 20.4 m. The 1-, 2- and 3-yr OS rates are 62%, 38% and 17%. An FEV1 ≥70% was associated with a better survivall: median OS of 21.6 m vs 9.0 m and 2-yr OS of 48% vs 17% in pts with FEV1 ≥70% vs FEV1 <70% (HR 0.37; 95% CI 0.09 - 0.58). The HR (95%CI) was 1.10 (0.56 - 2.18) for PS 0–1 vs 2 and 0.92 (0.47 - 1.79) for stage IIIA vs IIIB. Conclusions: Induction chemotherapy with CbG followed by CRT with concurrent weekly Cis is well tolerated and results in promising overall survival in pts with unresectable stage III NSCLC. In these pts FEV1 appears to be a important prognostic marker. No significant financial relationships to disclose.
Optimizing smoking cessation resource awareness among patients and providers.
Authors: Laura Ma, Caitlin C. Donohue, Tina Denofrio, Lillian Vitale Pedulla, Robert I. Haddad, Joseph O. Jacobson, Guilherme Rabinowits
Journal: Journal of Clinical Oncology (2014)

85 Background: Despite receiving a cancer diagnosis, many patients continue to smoke during treatment, negatively affecting their outcomes and putting them at risk for secondary cancers. We witnessed that limited smoking cessation (SC) discussions were occurring among patients and providers (MDs/NPs) and hypothesized that this was partially due to the providers' lack of awareness of the current SC resources available. Methods: We surveyed the head and neck oncology (HNO) providers at Dana-Farber Cancer Institute to evaluate their awareness about existing SC resources within the community. We performed a 6-month chart review of active smokers to evaluate frequency of documented SC discussions in clinic, and developed several targeted interventions: we educated the HNO providers on available SC resources within the community; developed a SC resource teaching sheet for smoking patients; placed a provider alert page in exam rooms to remind the providers to discuss the SC teaching sheet with the patient; and built a SC discussion template in the electronic medical record to ease documentation. Four weeks post intervention we resurveyed providers and performed chart reviews of active smokers to reevaluate the frequency of SC discussion documentations. Results: Pre-intervention, only 13% of HNO providers were aware of SC resources available within the community and the mean SC discussion documentation was 33%. Post-intervention, 100% of HNO providers became aware of the SC resources available, and the mean SC discussion documentation increased to 76% at 7 weeks. Identification of active smokers in clinic increased from 2-5 smokers per week pre-intervention to 4-13 smokers per week post intervention. Eighty-eight percent of HNO providers felt the intervention prompted them to discuss SC with their patients. Conclusions: The limited number of SC discussions among patients and providers is at least partially due to unawareness of SC resources available within the community. Educating providers, and alerting them to their active smoking patients at the time of their clinic visits, successfully prompted providers to discuss the importance of SC, and empower patients with resources to help them quit.
Correlation of <i>KIT</i> and <i>PDGFRA</i> mutational status with clinical benefit in patients (pts) with gastrointestinal stromal tumor (GIST) treated with sunitinib (SU) in a worldwide treatment-use (TU) trial.
Authors: Peter Reichardt, George D. Demetri, Hans Gelderblom, Piotr Rutkowski, Seock-Ah Im, Sudeep Gupta, Yoon-Koo Kang, Patrick Schoffski, Jochen Schuette, Denis Soulieres, Jean-Yves Blay, David Goldstein, Kolette D. Fly, Xin Huang, Massimo Corsaro, Mariajose Lechuga, Jean-Francois Martini, Michael C. Heinrich
Journal: Journal of Clinical Oncology (2014)

10549 Background: This study retrospectively explored the role of KIT and PDGFRA mutations in response to SU therapy in pts with imatinib (IM)-resistant/intolerant GIST in a worldwide TU trial. Methods: SU was administered at a starting dose of 50 mg/day on a 4-week-on, 2-week-off schedule in the TU study. Clinical outcome data (PFS and ORR, both investigator-assessed per RECIST 1.0, and OS) from the TU study were correlated with KIT/PDGFRA mutational data obtained with IRB approval in the present correlative study. Tumor tissue utilized for molecular status determination was obtained pre-IM, post-IM−pre-SU, or post-SU treatment. All available data were used in all analyses regardless of time of collection. Mutational status was provided by investigators following local laboratory analyses. The primary analysis compared median PFS in pts with primary KIT exon 11 vs. exon 9 mutations using a 2-sided log-rank test. Similar methods were used for OS; ORRs were compared using a 2-sided Pearson χ2 test. Results: Of 1124 pts in the TU study, genotyping data were available or generated for 230 (20%), all of which were included in the present study. Study population and clinical outcomes were representative of the full TU study population. Prior IM therapy was discontinued due to resistance in 92% of pts and intolerance in 8%. 197 pts (86%) had primary KIT mutations, mainly in exon 11 (62%) or exon 9 (18%). Of 101 pts with additional KIT mutation data (44%), 26 (26%) had another KIT mutation (12% in exon 13, 12% in exon 17, 1% in exon 11, and 1% classified as
Double blind, placebo controlled trial of oral lactoferrin in combination therapy for first line non-small cell lung cancer (NSCLC)
Authors: Y. Wang, E. Yankee, A. Varadhachary
Journal: Journal of Clinical Oncology (2005)

7141 Background: Recombinant human lactoferrin (rhLF) is a novel immunostimulatory agent with demonstrated anti-cancer activity in animals and NSCLC patients in Phase I/II trials. Oral rhLF has been administered to over 350 people and appears safe and well tolerated. We evaluated oral rhLF in combination with standard chemotherapy in first line NSCLC patients in this trial. Methods: 110 chemo-naive patients with advanced or metastatic NSCLC from eleven cancer centers were randomized to receive standard therapy (carboplatin + paclitaxel; C/P) plus either rhLF or placebo. C/P was administered in 3-week cycles. RhLF (or placebo) was administered orally, 1.5 g B.I.D., in 35-day cycles until radiological progression for a maximum of three cycles, starting the day following C/P dosing in cycles 1, 3 and 5. The primary end point is Best Overall Response (BOR) by CT using RECIST criteria. Secondary end points include Progression Free Survival (PFS) and Overall Survival by Kaplan-Meier curves and Quality of Life Assessments (EORTC QLQ C30, QLC LC 13) at Weeks 0, 6, 12, 18. Data will be unblinded for preliminary analysis in February 2005. Results: All 110 patients have been enrolled for over ten weeks. Study drug appears to be safe and well tolerated, with only one Grade 3/4 toxicity (abdominal pain) that is possibly rhLF/placebo related. 100 patients have had at least one post-therapy CT, and are evaluable for response rate (RR). So far, there have been 37 (37%) partial responses (PR) and an additional 53 patients (53%) had stable disease on their 6-week CT or later. Median PFS has not been reached. The five major published randomized trials evaluating 3-weekly first line C/P in Stage IIIB/IV NSCLC report an average RR of 25.9%. The 37% blended response rate observed in this trial is significantly better than that expected in this patient population. Conclusions: Oral rhLF is a safe and well-tolerated immunostimulatory drug. If the response rate of placebo patients in this study is consistent with the published literature, the blinded data suggests that rhLF may significantly enhance the response to first line C/P chemotherapy in advanced NSCLC without increasing toxicity. We will present unblinded data at ASCO. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agennix
Outcomes After Related and Unrelated Umbilical Cord Blood Transplantation for Congenital Bone Marrow Failure Syndromes Other Than Fanconi Anemia.
Authors: Renata Bizzetto, Carmen Bonfim, Gerard Socie, Franco Locatelli, Ka Wah Chan, Oscar Ramirez, Jerry Stein, Samir Kanaan Nabhan, Eliana C.M. Miranda, Jakob R. Passweg, Eliane Gluckman, Carmino Antonio De Souza, Vanderson Rocha
Journal: Blood (2009)
Clinicopathologic and genetic features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC).
Authors: F. Liu, W. Wei, P. Nan, X. Li, Y. Xu
Journal: Journal of Clinical Oncology (2011)

382 Background: Hereditary non-polyposis colorectal cancer (HNPCC) is the most common hereditary colorectal cancer (CRC). At least five mismatch repair genes, majorly hMLH1and hMSH2 gene mutations, are associated with this syndrome. Given the geographical and racial differences, Chinese HNPCC patients have some special characteristics compared with patients in West countries. Based on our former studies, we developed a criteria, the Fudan Criteria, for clinical diagnosis of Chinese HNPCC. The aim of this study is (1) to understand the relationship between genotype and phenotype in Chinese HNPCC; and (2) to investigate the clinical value of Fudan Criteria. Methods: 116 unrelated probands of HNPCC or suspected HNPCC families from the Fudan Colorectal Registry were studied. 32 families fulfilled the Amsterdam criteria (AC group), 28 families fulfilled the Fudan Criteria (FD group). 56 families met the revised Bethesda guideline (BG Group). Direct DNA sequencing of all exons of hMSH2 and hMLH1 genes were performed. Mutation and clinicalpathological features were compared between the groups. Results: 32 pathological germline mutations were identified. 16/32 mutations were located at hMLH1 and 16/32 located at hMSH2. The sensitivity of Amsterdam Criteria was 50%, specificity was 81% and Youden's index was 31%. The sensitivity of Fudan Criteria was 75%, specificity was 58% and Youden's index was 33%. In AC group, there were no significant clinicopathological differences in patients with or without mutation. However, families with hMSH2 mutation had a higher ratio of synchronous and metachronous CRC than families with hMLH1 mutation (33% vs. 6%; P=0.04). Families in AC group share the same clinicopathological features with families in FD group, except multiple relative tumors (21.6% vs.6%; P=0.001). Conclusions: There seems no close relation between genotype and phenotype, except patients with hMSH2 mutation more frequently harbor synchronous and metachronous CRC. Fudan Criteria had a little higher sensitivity and accuracy than Amsterdam Criteria for identification of Chinese HNPCC. No significant financial relationships to disclose.
6q Deletion Helps in the Discrimination Between Symptomatic Waldenström's Macroglobulinemia and Asymptomatic Forms of IgM Monoclonal Gammopathies
Authors: Ramón García-Sanz, Roberto JP Magalhaes, Enrique M Ocio, Pilar Giraldo, Natalia de las Heras, Carmen Aguilera, Jose Mariano Hernández, Alfonso Garcia de Coca, Noemi Puig, Ilda Murillo, Elena Sebastian, Marcos González, Jesus F. San Miguel, Norma Gutierrez
Journal: Blood (2012)
Outcomes in adults and children with end-stage kidney disease requiring dialysis in sub-Saharan Africa: a systematic review
Authors: Gloria Ashuntantang, Charlotte Osafo, Wasiu A Olowu, Fatiu Arogundade, Abdou Niang, John Porter, Saraladevi Naicker, Valerie A Luyckx
Journal: The Lancet Global Health (2017)

The burden of end-stage kidney disease (ESKD) in sub-Saharan Africa is unknown but is probably high. Access to dialysis for ESKD is limited by insufficient infrastructure and catastrophic out-of-pocket costs. Most patients remain undiagnosed, untreated, and die. We did a systematic literature review to assess outcomes of patients who reach dialysis and the quality of dialysis received.We searched PubMed, African Journals Online, WHO Global Health Library, and Web of Science for articles in English or French from sub-Saharan Africa reporting dialysis outcomes in patients with ESKD published between Jan 1, 1990, and Dec 22, 2015. No studies were excluded to best represent the current situation in sub-Saharan Africa. Outcomes of interest included access to dialysis, mortality, duration of dialysis, and markers of dialysis quality in patients with ESKD. Data were analysed descriptively and reported using narrative synthesis.Studies were all of medium to low quality. We identified 4339 studies, 68 of which met inclusion criteria, comprising 24 456 adults and 809 children. In the pooled analysis, 390 (96%) of 406 adults and 133 (95%) of 140 children who could not access dialysis died or were presumed to have died. Among those dialysed, 2747 (88%) of 3122 adults in incident ESKD cohorts, 496 (16%) of 3197 adults in prevalent ESKD cohorts, and 107 (36%) of 294 children with ESKD died or were presumed to have died. 2508 (84%) of 2990 adults in incident ESKD cohorts discontinued dialysis compared with 64 (5%) of 1364 adults in prevalent ESKD cohorts. 41 (1%) of 4483 adults in incident ESKD cohorts, 2280 (19%) of 12 125 adults in prevalent ESKD cohorts, and 71 (19%) of 381 children with ESKD received transplants. 16 studies reported on management of anaemia, 17 on dialysis frequency, eight on dialysis accuracy, and 22 on vascular access for dialysis INTERPRETATION: Most patients with ESKD starting dialysis in sub-Saharan Africa discontinue treatment and die. Further work is needed to develop equitable and sustainable strategies to manage individuals with ESKD in sub-Saharan Africa.None.
Multicenter randomized phase II clinical trial of preoperative chemoradiotherapy by S-1 versus UFT to rectal cancer for personalized therapy (UMIN ID: 000001704).
Authors: Takashi Iwata
Journal: Journal of Clinical Oncology (2013)

499 Background: Preoperative chemoradiotherapy (CRT) in rectal cancer reduces the local recurrence rate after operation and preserves the anus, but it is difficult to predict the effects of CRT. Multicenter randomized phase II clinical trial of preoperative chemoradiotherapy by S-1 vs UFT for rectal cancer was conducted to compare the toxicity and efficacy of CRT using oral DPD-inhibitory fluoropyrimidines (UFT versus S-1, (UMIN ID: 000001704)) in patients with locally advanced rectal cancer. Methods: In this randomized phase II study, during April 2008 to October 2010, rectal cancer patients (n=59) who underwent preoperative CRT were randomly divided into two groups; S-1 group (n=30, 80 mg/m 2 /day, 5 days/w x 4 w), and UFT (n=29, 300 mg/m 2 /day, 5 days/w x 4 w). Both groups were combined with 40Gy radiotherapy (2 Gy ×5 days/w × 4 weeks,total 40 Gy). The pathological response rate, clinical response rate by RECIST, and frequency of adverse events of CRT were compared between S-1 group and UFT group. Results: Response to CRT determined by histopathologic examination of surgically resected specimens and RECIST were as follows: responders (grade 2 or 3) were 60% (S-1) and 52% (UFT) (p=0.52). S-1 group showed 54% of response rate in pathological response, whereas UFT group showed 45% (p=0.43). In adverse events, frequence of Grade 2 and 3 diarrhea was significantly higher in S-1 group compared with UFT group. There was no difference between the two groups in compliance (S-1group: 83%, UFT group: 97%). Conclusions: Both S-1 and UFT were safely used for preoperative CRT. S-1 tended to show higher response rate than UFT, although diarrhea in S-1 was higher than in UFT. Clinical trial information: 000001704.
Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: First results of the German CAO/ARO/AIO-04 randomized phase III trial.
Authors: C. Roedel, H. Becker, R. Fietkau, U. Graeven, W. Hohenberger, T. Hothorn, M. Lang-Welzenbach, T. Liersch, L. Staib, H. Christiansen, C. Wittekind, R. Sauer
Journal: Journal of Clinical Oncology (2011)

LBA3505 Background: The German CAO/ARO/AIO-94 trial established preoperative chemoradiotherapy (CRT), surgery, and postoperative chemotherapy with 5-FU as standard treatment for locally advanced rectal cancer. With this approach local relapse rates are below 10%. The development of distant metastasis is the predominant mode of failure. Integrating more effective systemic treatment into combined modality therapy was the goal of CAO/ARO/AIO-04. Methods: Between 7/2006-2/2010, patients with rectal cancer within 12 cm from the anal verge and clinical evidence of perirectal fat or lymph node involvement were randomly assigned to receive preoperative CRT, surgery, and adjuvant chemotherapy with 5-FU according to CAO/ARO/AIO-94 (arm 1), or preoperative CRT (50.4 Gy in 28 fractions) with 5-FU (250 mg/m 2 /days 1-14 and 22-35) and oxaliplatin (50 mg/m 2 /days 1, 8, 22, 29), surgery, and 8 cycles of adjuvant chemotherapy according to modified FOLFOX6 regimen (arm 2). Disease-free survival was the primary endpoint. We present early secondary endpoints, including acute toxicity, treatment compliance, and pCR-rates. Results: 637 patients were randomly assigned to arm 1 and 628 to arm 2. Full dose preoperative RT and full dose concurrent chemotherapy was delivered in 97% and 74% of patients in both arms, respectively. Preoperative grade 3/4 toxicity occurred in 21.6% in arm 1 and in 22.9% in arm 2. The R0-resection rate was 95.4% in both arms, and abdominoperineal resections were limited to 11.9% and 12.2% in arms 1 and 2, respectively. Overall postoperative complications were not different between both arms (21.0% and 21.9%). The pCR rate (ypT0N0) was 13.1% in arm 1 and 17.6% in arm 2 (p = 0.033, Cochran-Mantel-Haenszel Chi-Squared Test without continuity correction for conditional independence of pCR rate in the two treatment arms in each stratum). Conclusions: Inclusion of oxaliplatin to 5-FU based CRT was well tolerated and associated with increased pCR-rates compared with 5-FU-CRT alone. Longer follow-up is necessary to evaluate the primary endpoint, disease-free survival.
Accuracy in targeted therapy prescription: An observational retrospective study.
Authors: M. Marri, O. Nanni, M. Altini, L. Valmorri, M. Guidoboni, G. Cruciani, A. Ravaioli, S. Tamberi, M. Faedi, D. Amadori
Journal: Journal of Clinical Oncology (2011)

e16553 Background: Targeted therapy has led to a greater need for detailed information on the disease, and several biological markers have become crucial for the identification of the best treatment option. Although international guidelines provide evidence-based recommendations and national and local laws regulate the prescription process, physicians are often faced with situations that can lead to a not fully appropriate use of drugs in daily clinical practice. Methods: An observational retrospective study on 341 cancer patients at different treatment stages was carried out at the Cancer Institute of Romagna (I.R.S.T.) from January to June 2010. A panel of innovative drugs utilized for the therapy of four tumor types was evaluated to assess the accuracy of the drug prescription process (Table). Major international guidelines were reviewed to identify the biological markers recommended for evaluation in each disease, and Italian and regional reference documents pertaining to treatment indications were consulted to identify the markers whose determination was mandatory. Results: Erb-2 was investigated in all the breast cancer patients and K-Ras was evaluated in 32 (72.2%) of the 44 advanced/metastatic colon cancer patients. A small number of patients eligible for treatment with a drug indicated for his/her disease did not receive the drug. In NSCLC, although the use of Erlotinib did not require biological marker evaluation, EGF-R determination was performed in 23 (31%) of the 74 advanced/metastatic patients. Conclusions: Our study showed that the drugs evaluated were appropriately prescribed in all cases. EGF-R evaluation would still not appear to be closely correlated with the use of erlotinib in NSCLC. Similar analyses are planned and outcome indicators are undergoing evaluation in other centers to compare the degree of drug prescription compliance among the hospitals of the Wide Area of Romagna network. Partially funded by Novartis SpA. Disease Marker Drug No. markers investigated/no. pts Positive marker (no. pts) No. pts treated Breast cancer Erb-2 amplif. Trastuzumab 195/195 58 55 Colon cancer K-Ras w/t Cetuximab 32/58 20 13 GIST C-Kit amplif. Imatinib 6/6 6 6 NSCLC EGF-R amplif. Erlotinib 23/84 5 19