tbuckley/cabot-search huggingface dataset:
Surgery and adjuvant chemotherapy (CT) compared to surgery alone in non-small cell lung cancer (NSCLC): A meta-analysis using individual patient data (IPD) from randomized clinical trials (RCT)
Authors: L. A. Stewart, S. Burdett, J. F. Tierney, J. Pignon
Journal: Journal of Clinical Oncology (2007)

7552 Background: A previous IPD meta-analysis (BMJ 1995;311:899) that suggested CT may have a role in the treatment of NSCLC has been updated. This includes RCTs, regimens and outcomes that were not available in 1995. The meta-analysis examines the role of CT in 7 treatment comparisons. Here we report on the effectiveness of surgery plus adjuvant CT compared with surgery alone. Methods: We conducted a systematic search for RCTs followed by the central collection, checking and re-analysis of updated IPD. Results from RCTs were combined using the stratified (by trial) log rank test to calculate individual and pooled hazard ratios (HRs). Previously included RCTs using long-term alkylating agents were excluded from this analysis due to their antiquity. Results: IPD were obtained on 8147 patients from 30 RCTs. 15 RCTs used a cisplatin combination without Tegafur/Tegafur+Uracil (UFT), 8 RCTs used Tegafur/UFT without cisplatin and 7 RCTs used Tegafur/UFT and cisplatin. This represents 95% of all known randomised patients and adds 18 trials and 5835 patients to the 1995 analyses. The results show a highly significant benefit of CT on survival (HR=0.86 95% CI 0.81–0.93, p&lt;0.000001), with an absolute benefit of 4% (from 60% to 64%) at 5 years. Results were similar for recurrence-free survival and time to distant recurrence, but there was a larger effect on time to local recurrence ( Table ). There was no clear difference in effect by type of CT given. There was no clear evidence that any patient subgroup defined by age, sex or histology benefited more or less from CT. There was a suggestion of a trend in effect by stage (p=0.047), this will be explored further. Conclusion: The results demonstrate conclusively and consistently a benefit of adjuvant CT in resected NSCLC, irrespective of the regimen used, the patient subgroup treated or the endpoint assessed, thus providing reliable estimates on which to base future policy and research. [Table: see text] [Table: see text]
Phase IIb/III double-blind randomized trial of BIBW 2992, an irreversible, dual inhibitor of EGFR and HER2 plus best supportive care (BSC) versus placebo plus BSC in patients with NSCLC failing 1–2 lines of chemotherapy (CT) and erlotinib or gefitinib (LUX- Lung1): A preliminary report
Authors: C. Yang, V. Hirsh, J. Cadranel, Y. Chen, K. Park, S. Kim, T. Chao, M. Oberdick, M. Shahidi, V. Miller
Journal: Journal of Clinical Oncology (2009)

8062 Background: No approved therapy exists for NSCLC patients (pts) who have failed chemotherapy (CT) and the reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), erlotinib (E) or gefitinib (G). The efficacy of BIBW 2992 (Tovok), a potent, irreversible inhibitor of EGFR and human epidermal growth factor receptor 2 (HER2) with preclinical activity against the secondary resistance mutation T790M, in pts progressing after initial clinical benefit on E/G is being assessed in this randomized trial. Methods: Pts with advanced adenocarcinoma of the lung (Stage IIIB/IV; ECOG 0–2), who have failed one or two lines of CT (including platinum) and progressed following at least 12 weeks of E or G are randomized in a 2:1 ratio to receive BSC plus either oral BIBW 2992 50 mg qd or placebo until disease progression or unacceptable toxicity. Primary endpoint is overall survival, with progression-free survival, objective response and clinical benefit rate and duration, safety and quality of life being secondary endpoints. Enrollment of 400 pts is planned (HR=0.70, 85% power). An unblinded interim analysis of tumor response and safety by the independent Data Monitoring Committee (DMC) after the first 40 evaluable pts treated with BIBW 2992 will determine continuation to full accrual. Results: From May to November 2008, 145 pts have been randomized and 76 are still on treatment. Demographics (n=145): median age 59 (range: 30–82); female 68%, current/ex-smokers 38%; metastatic disease 91%, ECOG 0–1 92%; Asian origin 68%. 50% had one prior line of CT. Main prior EGFR-TKI was G in Asians (70%) and E in non-Asians (85%). 40% of pts had achieved a PR or CR on previous treatment with E/G. Duration of prior E/G treatment was &gt;24 weeks and &gt;48 weeks in 80% and 40% of pts, respectively. As expected, diarrhea, rash, anorexia, stomatitis, paronychia, nausea and vomiting were the most frequently observed adverse events. Conclusions: The trial is continuing recruitment after DMC review of efficacy and safety and updated demographics and blinded safety data will be reported. [Table: see text]
A novel fully human monoclonal antibody against epidermal growth factor receptor (EGFR). First clinical and FDG-PET imaging results from a phase I/II trial conducted by the Danish Head and Neck Cancer Study Group (DAHANCA) in patients with squamous cell carcinoma of the head and neck (SCCHN)
Authors: L. Bastholt, L. Specht, K. Jensen, E. Brun, A. Loft, J. Petersen, H. Kastberg, J. G. Eriksen
Journal: Journal of Clinical Oncology (2005)

5530 Background: The fully human IgG1κ monoclonal antibody 2F8 (HuMax-EGFr) targets the EGFR. 2F8 competitively inhibits ligand binding and ligand-induced receptor phosphorylation and it induces significant antibody-dependent cellular cytotoxicity in vitro. Methods: A phase I/II single dose escalation study followed by a repeat dose extension. 24 patients with histologically confirmed recurrent or metastatic SCCHN received i.v. infusions in doses of 0.15, 0.5, 1, 2, 4, or 8 mg/kg. Four patients were included at each dose level. At day 28 the single dose was followed by 4 weekly infusions at the same dose. The primary objective was safety. Efficacy was evaluated by FDG-PET and by CT-scans one week after last dose. Results: Data is presented from 24 patients. 6 patients were withdrawn prior to repeated dosing due to disease progression. No patients experienced dose limiting toxicities and maximum tolerated dose has not been reached. The frequency of acneiform rashes increased with dose. Hence, 7 of 8 patients receiving 4 or 8 mg/kg experienced rash. At these 2 dose levels, pharmacokinetic data showed constant clearance indicating saturation of compartments. Response evaluation by FDG-PET in 15 evaluable patients showed 6 partial metabolic responses (PMR) and 3 stable metabolic disease (SMD), all occurring in the 2, 4, and 8 mg/kg dose groups. In fact, all 8 patients at 4 or 8 mg/kg obtained PMR or SMD. Response evaluation by CT in 16 evaluable patients showed 2 patients with partial response and 8 with stable disease all occurring in the 1, 2, 4, and 8 mg/kg dose group. 6 out of 7 patients treated with 4 or 8 mg/kg thus obtained partial response or stable disease. Conclusions: 2F8 has a favorable safety profile in doses up to 8 mg/kg. Encouraging efficacy data using FDG-PET and CT imaging are demonstrated, particularly in the 4 and 8 mg/kg dose groups. The study is currently extended at the 8 mg/kg dose level. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genmab Genmab
Influence of different laboratory methods on MELD calculation in the Belgian liver transplant centres
Authors: Jeoffrey Schouten, Peter Starkel, Sven M. Francque, Hans Van Vlierberghe, Isabelle Colle, Frederik Nevens, Jean Delwaide, Michael Adler, Dirk Ysebaert, Alain Gadisseur, Peter P. Michielsen
Journal: Hepatology (2007)
A randomized phase II study of pemetrexed (P) versus pemetrexed-carboplatin (PC) as second line treatment for patients (pts) with advanced non-small-cell lung cancer (NSCLC)- NVALT 7
Authors: E. F. Smit, H. J. Groen, H. J. Smit, B. Biesma, P. Eppinga, A. C. Dingemans, N. C. van Walree, A. Vincent, N. van Zandwijk
Journal: Journal of Clinical Oncology (2008)

8050 Background: The role of platinum compounds as part of second line therapies in advanced NSCLC is ill defined. We performed a randomized phase II trial comparing P and PC in pts relapsing after platinum-based chemotherapy. Methods: Main eligibility criteria: histological or cytological proof of advanced NSCLC, relapse > 3 months (mo) after (first-line) platinum-based chemotherapy, normal organ reserve, ECOG PS 0–2, age >18 years and signed informed consent. After stratification, pts were randomized to (A) P 500 mg/m2 i.v. q 3 wks or (B) C AUC 5 and P 500 mg/m2 both iv q 3 wks. Response was assessed 6 weekly according to RECIST and toxicity 3 weekly according to NCI-CTC criteria. The primary endpoint was time to progression (TTP). Secondary endpoints: objective response rate (ORR), overall survival (OS), toxicity. The study was designed to detect a 33% decrease in hazard of progression in the combination arm with 80% power (at α=0.05 two-sided log-rank test). Results: From October 2005 to May 2007 151 males and 89 females, median (range) age 59 (36–84), ECOG PS 0/1/2 33%/58%/9% were enrolled. With data 90% complete and after a median follow up of 10.6 mo, median TTP for arm A was 5.7 mo and for arm B 6.9 mo (HR = 0.8 [0.60, 1.07], p=0.12). ORR: 4% in arm A and 9% in arm B. Median OS: 7.3 mo versus 8.1 mo. Toxicities grade 3/4 was 29% in arm A and 44% in Arm B, mainly hematological without clinical sequel. No patient discontinued treatment due to toxicity. One fatal toxicity was encountered in arm A, none in arm B. Conclusions: PC as second line treatment for relapsed NSCLC resulted in a non significant 20% reduction of hazard of progression as compared to P alone. Based on the statistical assumptions of the study, further testing of CP in phase III setting is not warranted. The role of platinum combinations in relapsed NSCLC seems limited. No significant financial relationships to disclose.
The prognostic effect of hemoglobin levels on survival for patients with high-grade gliomas
Authors: B. E. Lally, J. M. Colasanto, J. P. S. Knisely
Journal: Journal of Clinical Oncology (2004)

1565 Background: We conducted a retrospective study of patients with high grade glioma treated with radiotherapy (XRT) at our institution to evaluate the prognostic impact of hemoglobin (HGB) levels on overall survival. Methods: Between 1992 and 2001, 97 adult patients with glioblastoma multiforme (GBM) and 24 patients with anaplastic astrocytoma (AA) were treated at our institution with XRT and had a HGB available for review. The HGB used for this analysis was the peak HGB available, whether obtained at the initiation of XRT or obtained at some time during XRT. These peak HGB values ranged from 8.8 gm/dl – 16.6 gm/dl. The median was 13.40 gm/dl and the standard deviation was 1.5136. Two groups were created for subsequent analysis; patients with HGB > 13.5 gm/dl and patients with hemoglobin ≤13.5 gm/dl. The primary endpoint was overall survival calculated from the time of initial surgery. Results: The median follow-up was 10 months, with a range of 1–120 months. Cox stepwise regression analysis was performed on the cohort. Age was found to be the most significant variable with older patients having a poorer prognosis (RR = 1.049; 95% CI = 1.033–1.065; P<0.0001). HGB was also found to be prognostic, with patients failing to reach a peak HGB of 13.5 gm/dl having a poorer prognosis (RR = 1.975; 95% CI = 1.231–3.167; P<0.0485). Patients with GBM pathology did worse than those with AA pathology (RR = 2.031; 95% CI = 1.132–3.645; P=0.0779). Lastly, patients who received either a subtotal or gross total surgical resection had a better survival than those patients treated with biopsy only (RR = 1.592; 95% CI = 1.021–2.483; P=0.0553). Conclusions: In patients with high grade gliomas, elevated hemoglobin levels may influence clinical outcome. This data may provide an additional prognostic factor useful to physicians, and potentially offer a means of improving therapy for these patients. No significant financial relationships to disclose.
Motexafin gadolinium (MGd) combined with whole brain radiation therapy prolongs time to neurologic progression in non- small cell lung cancer (NSCLC) patients with brain metastases: Pooled analysis of two randomized phase III trials
Authors: W. R. Shapiro, M. P. Mehta, C. Langer, A. Bezjak, R. Timmerman, D. Brachman, J. Suh, J. A. Smith, S. Phan, M. F. Renschler
Journal: Journal of Clinical Oncology (2007)

2010 Background: In 2 randomized trials, whole brain radiation therapy (RT) plus MGd prolonged time to neurologic progression (TNP) in NSCLC patients (pts) with brain metastases (BM). In this report, results of a pooled analysis from both trials are presented. Methods: In trial 9801, 401 pts with BM from solid tumors were randomized to RT (30 Gy) or RT+MGd, 5 mg/kg qd x 10 days. The subgroup of 251 pts with NSCLC is included in this analysis. In trial 0211, 554 pts with BM from NSCLC were randomized to the same treatments. In both trials, eligibility included a KPS = 70, no liver metastases, and = 1 site of extracranial metastasis. In both trials, a primary endpoint was time to neurologic progression determined by a blinded events review committee (ERC), incorporating data from neurologic exams, neurologic symptom collection, and neurocognitive tests. Results: 805 pts received RT (N=403) or RT+MGd (N=402). Most pts had multiple BM (80%), extracranial metastases (47%) and presented with neurologic deficits (84%). Treatment with MGd was well tolerated, with 93.3% of intended doses administered. Most common MGd-related grade 3+ adverse events were hypertension (4.6%), and fatigue (2.8%). TNP in the RT+MGd group was 15.4 mo, significantly longer than the 9.0 mo for the RT alone group, p=0.016, HR=0.74 (95% CI 0.57–0.95). The results of both studies are consistent, as shown in the table below. Similar results were observed in time to investigator-determined neurologic progression (p=0.015, HR=0.76) and time to neurocognitive progression (memory: HR=0.80, p=0.047, executive function: HR=0.74, p=0.028, all tests combined: HR=0.78, p=0.020). Conclusions: Motexafin gadolinium significantly prolonged time to neurologic progression and neurocognitive progression in NSCLC patients with brain metastases undergoing whole brain radiation therapy in a pooled analysis of 2 randomized phase III trials. [Table: see text] No significant financial relationships to disclose.
Hospital characteristics associated with surgery for non-small cell lung cancer
Authors: K. S. Virgo, S. A. Fedewa, A. Y. Chen, A. K. Stewart, W. D. Flanders, E. M. Ward
Journal: Journal of Clinical Oncology (2009)

6543 Background: Previous research suggests that black patients are less likely to undergo curative-intent surgery for early stage non-small cell lung cancer (NSCLC) compared to whites, holding all else constant. Among Medicare beneficiaries 65 and older, the likelihood of patients undergoing surgery is significantly reduced in hospitals with racial compositions of &gt; 30% black patients after controlling for hospital and patient characteristics. This study analyzes whether hospital racial composition is associated with curative-intent surgery among early stage NSCLC patients of all ages. Methods: All adult patients ages 19–104 diagnosed with an invasive initial primary early stage (TNM I-II) NSCLC during 2003–2005 were selected from the National Cancer Data Base (NCDB). Facility characteristics were extracted from the NCDB and American College of Surgeons (ACoS) Commission on Cancer (CoC) Facility Information Profile System (FIPS). Hospital racial composition of lung cancer patients, operationalized as percent black, was initially divided into tertiles; sensitivity analyses used dichotomous definitions. Generalized estimating equations with a logistic model were used to control for clustering by facility. Results: Of 52,853 evaluable patients seen at CoC-approved hospitals, blacks were primarily (74%) seen at hospitals with a racial composition of &gt; 11% black patients. Hispanics (72%), non-Hispanic whites (69%), and Asians or other (72%) were primarily seen at hospitals with &lt; 11% black patients. In sensitivity analyses, irrespective of the cutpoint used to classify hospitals by racial composition of black patients (10, 20, or 30%), black patients seen at hospitals with a high black racial composition were significantly less likely to undergo curative-intent surgery than black patients seen at hospitals with a lower black racial composition. After controlling for patient characteristics in multivariate models, however, high black racial composition at the facility level was no longer significant. Conclusions: Hospital racial composition (% black) was not predictive of reduced likelihood of curative-intent surgery among patients &gt; 18 years of age with NSCLC. Patient-level predictors accounted for the majority of the variation in likelihood of curative-intent surgery. No significant financial relationships to disclose.
Derek Hubert Patrick Cope
Authors: Andrew P Cope
Journal: BMJ (2015)

Derek Hubert Patrick Cope was educated at Epsom College, where he excelled in sciences in the classroom and on the rugby playing fields of the college. On leaving Epsom in 1940, he was awarded the Freer Lucas entrance scholarship to the Middlesex Hospital. After qualifying he completed his first appointment as house surgeon at Selly Oak Hospital, Birmingham. From September 1945 to April 1948 he worked as general duty orderly in the Royal Army Medical Corps. This was when he discovered his interest in, and aptitude for anaesthetics.

He was released from active military duty in May 1948 and started training in earnest, obtaining …
Availability of sentinel node as predictive index of lymph node metastases to early-stage gastric cancer surgery.
Authors: S. Kamiya, H. Takeuchi, M. Niihara, T. Kaburagi, R. Nakamura, T. Oyama, T. Takahashi, N. Wada, Y. Saikawa, Y. Kitagawa
Journal: Journal of Clinical Oncology (2011)

10 Background: Recently, the less invasive surgery for the early gastric cancer attract considerable attention, in particular, sentinel node navigation surgery (SNNS) is expected to be a new strategy. We analyzed the feasibility of sentinel node (SN) biopsy and its accuracy in predicting the lymph node status in patients with early gastric cancer. Methods: Between 1999 and 2009, we have performed the gastrectomy with SN biopsy during an operation in over 500 cases. We focused attention on 115 patients with cT1N0, less or equal 40 mm in size, and isolated gastric cancer and they had undergone the individualized minimizing gastrectomy. Proximal, pylorus-preserving gastrectomy and wedge resections were performed in 51, 54 and 10 patients, respectively. We used a dual procedure with dye- and gamma probe-guided techniques for SN mapping and resected SN and non-SN as was conventionally done for the safety. Results: Subjects were 85 males and 30 females with a mean age of 63.4 years. 53 patients had undergone laparoscopy-assisted gastrectomy. The mean number of SNs was 4.3/case. Of the four patients were SN positive and false-negative was found in one case. The sensitivity of detecting metastases was 80.0% (4/5) and the accuracy was 99.1% (114/115). One case had a recurrence in the liver and no cases without SN metastasis were confirmed any recurrences and metastases. Conclusions: This study showed the diagnostic accuracy of metastasis based on SN was very high, and the minimized resection and lymphadenectomy could be performed safely. No significant financial relationships to disclose.
Changing behavior of cutaneous melanoma
Authors: E. G. Elias, J. H. Hasskamp, B. K. Sharma, S. L. Beam, E. C. McCarron, J. L. Zapas
Journal: Journal of Clinical Oncology (2008)

22197 Background: The non-surgical management of cutaneous melanoma remains blighted by poor and variable results. Cytokines and growth factors (Factors) at the tumor site may act as autocrines and paracrines that stimulate tumor growth and invasion. To identify some of these Factors, we initiated 2 studies. Methods: 1. The 7-day spent medium of 25 cultured human melanoma cell lines were tested in triplicate by ELISA assay for the levels of 24 Factors (14 cytokines and 10 growth factors). In addition, recurrences of three patients were repeatedly biopsied and cultured at different intervals, from different metastatic sites, and similarly tested. 2. Immunohistochemistry (IHC) studies performed on 30 fixed melanoma tissues from primary lesions, local recurrences, intransit metastases, lymph node metastases and distant metastases for the expression and over-expression of the same Factors. Results: (1) 18 Factors were detected in the spent medium of melanoma cell lines. Each cell line secreted from 5–13 Factors. All tested cell lines secreted IL-8 (n=16) and TGFβ-1 (n=25), and 95% secreted VEGF1 (n=22). The other 15 Factors were secreted at frequency from 7% to 87%, and 6 Factors were not detected. In addition, the cell lines from the tumors of the 3 patients who had their recurrences repeatedly biopsied, cultured and tested, showed significant differences in the secretion and levels of these Factors in tumor cells obtained from different sites and at different time intervals. (2) The IHC results showed different levels of expression of the Factors tested that varied from the primary lesions, recurrences to whether the metastases were regional or distant. Conclusions: Such findings may reflect on the therapeutic approaches in melanoma. It will be difficult to target and down-regulate all these Factors or their kinase pathways in a given case, and more so when these Factors vary from one case to another. Repeated biopsies of recurrences and metastases for IHC studies may be required to redirect therapy. No significant financial relationships to disclose.
Costs and benefits of dose-dense chemotherapy scheduling in Hong Kong Chinese patients with primary breast cancer
Authors: J. Tsang, T. Yau, A. T. Chan, R. H. Liang, W. Yeo, R. J. Epstein
Journal: Journal of Clinical Oncology (2007)

11054 Background: Routine prophylactic administration of recombinant granulocyte colony-stimulating factor (G-CSF, filgrastim) has enabled more frequent scheduling of adjuvant cytotoxic drugs in primary breast cancer. Dose-dense chemotherapy of this kind has become popular in recent years, but few studies have compared the costs and benefits of this treatment approach. Methods: We conducted a retrospective comparison of 150 Hong Kong Chinese primary breast cancer patients treated with either conventional 3-weekly chemotherapy or G-CSF-supported 2-weekly (dose-dense) chemotherapy using similar cytotoxic regimens (four cycles of doxorubicin and cyclophosphamide, followed by four cycles of taxane) between April 2004 and May 2006 in two teaching hospitals. Assessments of treatment tolerance, toxicity, scheduling, and expense were applied to both patient cohorts. Results: Compared to conventionally treated patients (n = 117), dose-dense patients (n = 33) benefited from 52.3% fewer chemotherapy delays (21.2% vs. 44.4%; p = 0.02), 79.3% fewer hospital admissions for febrile neutropenia (3.0% vs. 14.5%; p = 0.07), and 54.8% enhancement of cytotoxic dose intensity (p &lt; 0.001). Dose-dense patients also developed less nausea (p &lt; 0.001) and stomatitis (p = 0.01) but more frequent bone pain (p &lt; 0.001). After subtracting costs saved by fewer hospital admissions, dose-dense patients incurred higher total expenses approximating US$500 per cycle. Conclusion: Routine G-CSF administration to Hong Kong Chinese patients with primary breast cancer is associated with major improvements in cytotoxic drug delivery, which could plausibly translate into greater therapeutic efficacy in some patients. In addition, dose- dense treatment is shorter, safer, and more reliably scheduled, and is associated with unexpected improvements in nausea and stomatitis. The extent to which these gains justify the rise in net costs needs to be further defined in prospective randomized studies, both in different adjuvant patient subsets and in differently resourced socioeconomic contexts. No significant financial relationships to disclose.