tbuckley/cabot-search huggingface dataset:
Combined mutation pattern analyses of epidermal growth factor receptor and K-ras genes for the differential diagnosis of primary versus metastatic lung adenocarcinomas.
Authors: K. Takamochi, S. Oh, K. Suzuki
Journal: Journal of Clinical Oncology (2010)

e21010 Background: The differential diagnosis of multiple primary lung cancers (MPLCs) from pulmonary metastases (PMs) is sometimes difficult based solely on the Martini and Melamed's criteria. We investigated whether combined mutation pattern analyses of the epidermal growth factor receptor (EGFR) and K-ras genes were useful for differentiating between MPLCs and PMs. Methods: We conducted a retrospective review of 84 tumors (81 adenocarcinomas and three atypical adenomatous hyperplasias) in 36 patients with multifocal lung adenocarcinomas. Genomic DNA was extracted from paraffin-embedded tissue. The peptide nucleic acid (PNA)-locked nucleic acid polymerase chain reaction clamp method was used for EGFR mutation analysis. The PNA-mediated PCR clamping method was used for K-ras mutation analysis. We determined clonality status of secondary tumors based on the mutation patterns of EGFR and K-ras by comparing them with primary tumors. Correlations between the mutation status and the proportion of bronchioloalveolar carcinoma (BAC) component in a tumor were examined. Results: EGFR and K-ras mutations were detected in 38 (45%) and 24 (29%) of 84 tumors, respectively. Thirty-four (71%) of secondary tumors were diagnosed as a different clonality (MPLC). Seven (15%) of secondary tumors were classified into the same clonality (PM). Clonality status could not be determined for the seven (15%) remaining secondary tumors. A clonality assessment based on the EGFR and K-ras mutation status was possible in 41 (84%) of 48 secondary tumors, and it was consistent with the Martini and Melamed's criteria in 29 (71%) of 41 secondary tumors. The proportion of BAC component in a tumor did not correlate with the EGFR/K-ras mutation status. Conclusions: The combined mutation pattern analyses of EGFR and K-ras enabled a definite distinction between PMLCs and PMs in a large portion of multifocal lung adenocarcinomas. Mutations of EGFR and K-ras in multifocal lung adenocarcinomas frequently occurred randomly, which support the concept of “field cancerization.” No significant financial relationships to disclose.
Comparison of JAK2<sup>V617F</sup> prevalence in African American and caucasian patients with myeloproliferative disease (MPD)
Authors: D. A. Mobarek, J. L. Ascensao, D. Stroncek, M. Bennett, S. Adams, M. Kvanli, G. P. Schechter
Journal: Journal of Clinical Oncology (2008)

18001 Background: Prevalence of JAK2V617F in patients with MPD has been mainly estimated from cohorts of Caucasians (CAUC). Little information is available from African Americans (AA) with MPD. The Washington DC VA Medical Center population has approximately 75% AA patients providing an opportunity to compare the frequency of JAK2 V617F between the two groups. Methods: DNA extracts from the peripheral blood neutrophils of 33 male MPD patients (15 AA, 18 CAUC) attending the Hematology clinic in the last 18 months were tested by using DNA sequencing for JAK2V617F Results: Overall, the prevalence of MPD in this predominantly male veteran population appears to be approximately fourfold greater among CAUC than in AA. Distribution of the MPD subtypes and the frequency of JAK2V617F are shown in Table 1. There was no difference in the proportion of JAK2 V617F in the individual subtypes of MPD between the AA and CAUC patients. When all MPD groups were combined, there was a trend for a higher proportion of AA patients to have JAK2V617F (p=.06). Conclusions: These results find no significant difference in the prevalence of JAK2V617F among the MPD subtypes between AA and CAUC patients in this cohort. The trend to a higher incidence of the mutation in the AA group when the subtypes were combined (60% vs. 27%) likely represents the higher but non-significant difference in the AA ET group (44% vs. 20%) and the smaller numbers of patients in the other subsets of both groups. Additional studies are needed to expand and validate these observations, which may have potentially important implications for treatment. No. of JAK2 V617F patients/total (%) African- American (n = 15) Caucasian (n = 18) Chi-square p value Polycythemia Vera 3/4 (75%) 1/2 (50%) – EssentialThrombocythemia 4/9 (44%) 3/15 (20%) NS Primary Myelofibrosis 2/2 (100%) 1/1 (100%) – Total 9/15 (60%) 5/18 (27%) 0.06 No significant financial relationships to disclose.
Detection of breast cancerClinical breast examination is not an acceptable alternative to mammographyMammography should be availableSelf examination contributes to reduction in mortality
Authors: C J M de Wolf, G Querci della Rovere, A B Miller, Ruth Warren, C J Baines
Journal: BMJ (2001)

# Clinical breast examination is not an acceptable alternative to mammography {#article-title-2}

EDITOR—Clinical breast examination is not an acceptable alternative to mammographic screening, as Mittra et al say in their article.1 Screening for breast cancer is a public health intervention and needs objective criteria for evaluation and quality control. Clinical breast examination is a subjective method with variable interpersonal interpretation. For a public health screening intervention, the sensitivity and specificity of clinical breast examination are too low and variable to accept as a screening test. Clinical breast examination is a detection method acceptable in a doctor-patient relationship where the doctor has the full responsibility for the diagnosis.

The estimate that only 22% of the cancers are detected by mammography remains a hypothetical calculation. Bobo and Lee analysed in a retrospective study all the cancers found by mammography and clinical breast examination in the national programme for early detection of breast cancer in the United States.2 Of the 3780 cancers reported, on 2224 (59%) records the clinical breast examination was suspicious for cancer. On 1556 (41%) records, the clinical breast examination was normal. In other words, this examination “missed” 41% of cancers. This is almost twice the reported assumption.

Furthermore, it is a misconception that tumours grow exponentially. This is a mathematical projection of cells in virtual circumstances. The initial stage of solid tumour growth is limited by the ability of externally supplied nutrients to diffuse into the tumour. In a later stage the limiting factor for growth is the neovascularisation in the tumour tissue. The exponential growth of a …
Determinants of surgeon variation in local therapy for breast cancer
Authors: S. Hawley, T. Hofer, I. Lakhani, S. Katz
Journal: Journal of Clinical Oncology (2005)

6003 Background: Variation in receipt of local therapy for breast cancer has raised interest in whether treatment differences are attributable to surgeons. We assessed the amount of variation in receipt of mastectomy attributable to surgeons, and evaluated patient and surgeon factors associated with treatment variability. Methods: All women with DCIS and a 20% random sample of women with non-metastatic invasive breast cancer aged 79 and younger diagnosed in 2002 in Detroit and Los Angeles were surveyed shortly after receipt of surgical treatment (response rate 77.4%, N=1,844). Attending surgeons were surveyed (response rate 80%, N=365). Patient and surgeon survey data were merged with SEER (1547 patients and 318 surgeons). The dependent variable was mastectomy vs. lumpectomy. Independent variables related to patients included age, ethnicity, marital status, income, tumor size and behavior, and histologic grade. Surgeon factors included age, gender, years in practice, the proportion of total practice devoted to breast cancer and hospital setting). We used random effects modeling to determine the amount of treatment variation attributable to surgeons, and the amount of within-surgeon variability due to patient and surgeon factors. Results: The number of patients per surgeon ranged from 1 to 41 with a mean of 4.9. One-third of women received mastectomy. Younger and less educated women, and those seeing lower volume surgeons, were significantly more likely to get mastectomy. The amount of variation in mastectomy rates attributable to surgeons alone was 9.2%. Patient factors accounted for 14.1% of the variation; while surgeon factors accounted for an additional 27.9% of the surgeon variation. Surgeon practice characteristics were the strongest determinants of within-surgeon variation. Additional models will evaluate surgeon variability in receipt of radiation therapy after lumpectomy and breast reconstruction after mastectomy. Conclusions: Variability in mastectomy rates across surgeons can be attributed more to surgeon practice factors than to characteristics of their patients. These results suggest that patients may receive different treatment depending on characteristics of the surgeon and practice setting. No significant financial relationships to disclose.
Factors associated with depressive symptoms in patients with metastases from prostate cancer
Authors: J. Domont, K. Fizazi, F. Zesnasni, A. Plantade, C. Massard, B. Escudier, A. Chauchereau, S. Dauchy
Journal: Journal of Clinical Oncology (2007)

9131 Background: The purpose of this study was to identify predictive factors of depression in patients with metastases from prostate cancer. Methods: Patients with evidence of metastases from prostate cancer were prospectively screened for depression. Depressive symptoms were defined by the Beck Depression Inventory-Short Form (BDI-SF) with a low cut-off score of 4 to optimize sensitivity as a screening test (Lowe AW, 2004). Self-report questionnaires including BDI-SF were sent to pts through the mail and then given back to the oncologist. In case of a BDI-SF &gt; 4, a consultation with a psychiatrist was proposed, so that the diagnosis of depression could be made and treatment be started. Characteristics including marital status, spiritual well-being, educational level, ongoing treatment for prostate cancer, and the presence of pain requiring analgesic therapy were registered. Results: 92 patients were prospectively enrolled of whom 54 (60%) completed the self-report questionnaires. Median age was 69 years (range: 50–84). 31 pts (54%) had castration-refractory disease, of whom 30 were receiving chemotherapy: docetaxel (n=22), carboplatin-etoposide (n=6) and doxorubicin (n=2). Eighteen patients (33%) had a BDI-SF score &gt; 4, of whom 10 (18%) had a major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria. Logistic regression analysis showed that pain requiring analgesic therapy was the only predictive factor of depressive symptoms (OR=3.75; 95% confidence interval 1.1–12.4). In patients with pain requiring treatment, the incidence of depressive symptoms and MDD was 53% and 32%, respectively. In contrast to female with advanced breast cancer (Conforti R, 2004), marital status and belief in god were not predictive factors of depressive symptoms in this population of males. Conclusions: Pain requiring analgesic treatment was the only factor significantly associated with depressive symptoms in this sample of 54 patients with metastatic prostate cancer. A screening for depression should be systematically implemented at least in this subgroup of patients. No significant financial relationships to disclose.
Effect of gender on outcome in two randomized phase III trials of paclitaxel poliglumex (PPX) in chemonaïve pts with advanced NSCLC and poor performance status (PS2)
Authors: H. Ross, P. Bonomi, C. Langer, M. O’Brien, K. O’Byrne, L. Paz-Ares, A. Sandler, M. Socinski, F. Oldham, J. Singer
Journal: Journal of Clinical Oncology (2006)

7039 Background: Women with NSCLC are younger and are more likely to be non-smokers than the overall NSCLC population. Estrogen seems to contribute to these differences in lung cancer biology, but its effect on treatment efficacy has not been well described. Methods: Two phase III trials in chemo-naïve PS2 patients with advanced NSCLC compared PPX to either gemcitabine or vinorelbine (STELLAR 4), or PPX/carboplatin to paclitaxel/carboplatin (STELLAR 3). Eligibility criteria were identical and pts were stratified for gender and age. Analysis of overall survival (OS), the primary study endpoint, showed similar survival between treatment arms. A trend to improvement with PPX for females but not males in both studies prompted an exploratory combined analysis of the 198 women in STELLAR 3 (93/400 pts) and STELLAR 4 (105/381 pts) using univariate and multivariate Cox regression analysis of OS. Results: Combined log-rank analysis of STELLAR 3 and 4 shows improved OS for females receiving PPX vs control (9.5 mo vs 7.8 mo; HR=0.70; p=0.03) and no difference in males (7.3 mo vs 6.9 mo; HR=1.06; p=0.53). Cox multivariate analysis identified treatment with PPX (HR=0.64; p=0.019), smoking (HR=1.50; p=0.037), and presence of extra-thoracic metastases (HR=1.76; p=0.003) as independent prognostic factors in these women. In the combined analysis, median survival advantage for PPX-treated pts was greater in women &lt;55 years old (10.0 vs 5.2 mo, p=0.038) compared to women 55 or older (8.9 vs 8.6 mo, p=0.134). Pretreatment estrogen levels were available for 86 pts in STELLAR 3; pts with estrogen &gt;30 pg/dl had a significant survival benefit when receiving PPX compared to paclitaxel (10.2 vs 5.5 mo; p=0.039). Conclusions: While the efficacy of PPX is comparable to other treatment options in NSCLC, PPX may be more effective female pts, particularly premenopausal women, compared to females in the control arms. Preclinical data suggest that estrogen enhances PPX distribution to lung tissue and upregulates the rate-limiting metabolic enzyme cathepsin B in NSCLC. To prospectively test the effect of estrogen on OS, a phase III trial (PIONEER) has been initiated to compare PPX to paclitaxel in chemo-naïve PS2 females with NSCLC. [Table: see text]
Role of IL-1β and IL-4 in 5-fluorouracil- induced intestinal mucositis in mice
Authors: J. S. Mota, P. M. Soares, G. A. Brito, F. Q. Cunha, M. L. Souza, R. A. Ribeiro
Journal: Journal of Clinical Oncology (2007)

19551 Background: Intestinal mucositis is a frequent side-effect associated to 5-fluorouracil (5-FU) clinical use. The participation of cytokines in the 5-FU- induced intestinal mucositis was not completely elucidated. We evaluated the role of IL-4 and IL-1β in 5- FU induced- intestinal mucositis in mice. Methods: Wild-type C57BL/6 mice or IL-4 deficient mice (-/-) were treated with 5-FU (450 mg/Kg, i.p.). Other group were treated with the soluble receptor IL-1Ra (100 mg/Kg, i.p., per day) or saline. Then, received the 5-FU (450 mg/Kg, ip). After three days, animals were sacrificed and pieces of duodenum (D), jejunum (J) and ileum (I) were harvested for assessment of epithelial damage by morphometry, myeloperoxidase (MPO) activity and cytokines (both in duodenum) quantification by ELISA. Statistical analysis was performed with ANOVA and Bonferroni test. Significance was set at p&lt;0.05. Results: 5-FU induced a significant (p&lt;0.05) epithelial intestinal damage (reduction of villus height/crypts depht reason) in all segments (duodenum-C= 3.3±0.2, 5- FU= 1.0±0.1; jejunum-C= 2.3±0.2, 5-FU= 1.0±0.1; ileum-C= 2.1±0.1, 5-FU= 0.7±0.1), increased MPO activity (n° neutrophil/mg of tissue) (C= 663.5±76.6, 5- FU= 3579±492) and cytokines concentration (pg/ml) (IL-1β: C= 134.8±31.9, 5-FU= 280.3±41.5; KC: C= 123.9±27.3, 5-FU= 177.2±28.2; TNF-a: C= 9.9±0.4, 5-FU= 12.1±1.8). IL-1Ra protected all segments from 5-FU- induced intestinal injury (D= 1.7±0.1, J= 2.0±0.1, I= 1.1±0.1), reduced MPO activity (2061±308) and cytokines concentration (IL-1β= 8.6±41.7; KC= 100±17.1; TNF-a= 7±.1.1). IL4 -/- presented with less epithelial intestinal damage (D= 2.9±0.2, J= 2.0±0.2, I= 1.4±0.1), less MPO activity (1702±315) and cytokines concentration (IL-1β:=86.5± 29.6; KC=105.6± 21.6, TNF-a:=7.4±0.5) . Conclusions: Our data suggest that IL-4 and IL-1β participates in the 5-FU induced- intestinal mucositis in mice. No significant financial relationships to disclose.
Identification of melanoma-specific alterations in cell surface glycosylation.
Authors: Erica Brooke Friedman, John Frank Rakus, Jiri Zavadil, Eva Hernando, Lara K Mahal, Iman Osman
Journal: Journal of Clinical Oncology (2012)

e19018 Background: Cell surface glycans, oligosaccharides present on proteins and lipids, play important roles in a range of biological processes. Our group recently reported on the role of aberrant glycosylation in promoting melanoma cell invasion and immunosuppression (Cancer Cell, 2011). In this study, we further exploit the ability of glycomic profiling of melanoma, using lectin microarrays, to identify differences in melanoma-associated glycosylation for new melanoma biomarkers and/or targets of treatment. Methods: We utilized a ratiometric dual colored 90-lectin microarray to examine differences in glycosylation between 13 primary and 14 metastatic melanoma cell lines, 5 human melanoma tissues and 4 human epidermal melanocytes (HEM). One HEM was used as a biological reference for hybridization. A subset of melanoma cell lines (n=4) was used for comparison with the glycomic profiles of the NCI-60 lines using a mixed reference. Hierarchical clustering of lectins with significant differences in binding to the sample sets (t-tests, p&lt;0.05) was used to visualize and infer differences in glycosylation patterns. Results: A shift in the glycome related to reduction in expression of high mannose and core fucosylated complex N-glycans was seen in melanoma cell lines and tissues compared to HEMs. Glycomic profiles of primary and metastatic melanoma were similar. Interestingly, enrichment of high mannose and potentially a-2,3 sialic acid was seen in BRAF mutant (n=19) compared to BRAF wild type (n=8) cell lines. Our tested melanoma cell lines showed similar glycosylation patterns compared to melanoma lines of the NCI-60 panel, which all show higher expression of high mannose and complex N-glycans compared to other cancers. Comparison of melanoma cell lines to tissues shows similar glycomic profiles, suggesting that glycosylation of melanoma cells is not significantly altered (or blunted) due to culture. Conclusions: Our data suggest that alterations in cell surface glycosylation may be an early event in the malignant transformation of melanocytes to melanoma. Further analysis of the melanoma glycome will be needed to elucidate the biological implications and clinical potential of altered glycosylation.
Cetuximab, cisplatin and amifostine during accelerated radiotherapy for locally advanced head and neck cancer
Authors: P. G. Tsoutsou, V. Danielidis, M. I. Koukourakis
Journal: Journal of Clinical Oncology (2008)

14582 Background: This study reports on the tolerance and efficacy of cetuximab anti-EGFR monoclonal antibody administration in combination with accelerated cisplatin radio-chemotherapy and cytoprotection with amifostine in patients with locally advanced head and neck cancer (LA-HNC). Methods: Eligible patients had a LA-HNC of squamous histology and a good performance status (0–1). Nineteen patients with LA-HNC (5 treated with sub-optimal surgery) were recruited in a prospective trial of accelerated concomitant boost radiotherapy (2.7 Gy/day to a total dose of 59.4 Gy in 4.5 weeks, biological equivalent dose to 70 Gy) combined with weekly cisplatin (30 mg/m2) and cetuximab (400 mg/m2 day 1 and 250 mg/m2 weekly thereafter). Patients received cytoportection with amifostine (1000 mg/day subcutaneously). Primary endpoints were toxicities assessed by common toxicity criteria, delay in radiotherapy administration and response. Results: The regimen had an acceptable toxicity with mucositis grade 2 and 3 noted in 10/19 (53 %) and 3/19 (16 %) patients, respectively. Cetuximab- related acneiform rash grade 2 was noted in 5/19 (26%) and grade 3 in 1/19 (5 %) patients. Grade 3 non-febrile neutropenia was noted in 1/19 (5 %) patients. Mucositis was the cause of radiotherapy delay for 1 week in 6/19 (32%) patients. No severe late radiation sequelae have been observed. Out of 14 patients with measurable disease 12 (86 %) had a complete response, 1 partial (7 %) and 1 (7 %) minimal response. Within a median follow-up of 12 months, one patient progressed locally, one to distant organs and one died from intercurrent disease. Conclusions: The combination of cisplatin and amifostine with cetuximab during radiotherapy is feasible with acceptable toxicity and encouraging complete response rates. No significant financial relationships to disclose.
Circulating tumor cell analysis in patients with advanced non-small cell lung cancer treated with biweekly gemcitabine and docetaxel.
Authors: O. Juan Vidal, T. Fleitas, J. Garde, J. Muñoz, M. Martin, S. Maciá, S. Catot, J. Vidal, J. Gómez-Codina
Journal: Journal of Clinical Oncology (2010)

e18085 Background: Circulating tumor cells (CTC) may be useful to predict prognosis in lung cancer patients. The purpose of this study is the detection and quantification of CTC to assess its clinical significance in patients with advanced non-small cell lung cancer (NSCLC) treated with biweekly gemcitabine and docetaxel. Methods: Patients with advance (stage IIIB/IV) NSCLC treated with biweekly gemcitabine and docetaxel in a two parallel phase II trial for patients with performance status 2 and elderly patients were eligible. We used CellSerch System, which consist an immunomagnetic enrichment using anti-EpCAM antibodies and staining for cytokeratin 8, 18, 19, CD45 and DAPI. 7.5 ml of venous blood were collected at the baseline (before treatment) and after 2 cycles of chemotherapy (2 months) to quantify CTC. Results: At baseline, CTC were analyzed in 31 patients (11 pts from PS 2 study and 20 from Elderly study), although CTC quantification was available for both visits for 22 patients. CTC ≥1 was detected in 13 patients (42%). Patients were subdivided in four groups: Group 1 (CTC at baseline = 0; CTC at 2 months =0), Group 2 (CTC at baseline >0; CTC at 2 months =0), Group 3 (CTC at baseline = 0; CTC at 2 months >0) and Group 4 (CTC at baseline > 0; CTC at 2 months >0). 12 patients belong to Group 1 and 10 to Group 2. Characteristics of the patients for both groups are shown in the Table. Time to progression (TTP) was no significantly different for Group 1 (6.1 months) and Group 2 (8.3 months). Median overall survival for group 1 was 8.1 months while it has not been reached for the group 2. Conclusions: CTC measurement may be a useful as a surrogate marker for determining prognosis in advanced NSCLC patients treated with chemotherapy. The number of patients analyzed in this study is small and warrant further studies to drawn solid conclusions. Patients' characteristics Group 1 Group 2 Age (yr) Median 74 74 Range 55-77 56-82 Sex (%) Male 12 (100%) 9 (90%) Female 1 (10%) Histology (%) Adenocarcinoma 4 (33.3) 3 (30) Squamous 3 (30) Large cell 7 (58.3) 3 (30) Others 1 (8.3) 1 (10) Response (%) Partial response 3 (25) 2 (20) Stable disease 7 (58.3) 6 (60) Progressive disease 1 (8.3) 1 (10) No evaluable 1 (8.3) 1 (10) No significant financial relationships to disclose.