tbuckley/cabot-search huggingface dataset:
Is the routine use of sentinel lymph node biopsy for ductal carcinoma in situ necessary?
Authors: J.-H. Yang, L.-J. Yi, S.-U. Woo, J.-H. Kim, S. Nam
Journal: Journal of Clinical Oncology (2005)

791 Background: Because of the incidence of lymphatic metastases in ductal carcinoma in situ (DCIS) has been small and its significance has been undefined. There were some controversies regarding the need for lymph node evaluation as part of the treatment for patients with DCIS. We reviewed our cases with DCIS to determine the node positive rate and evaluate the recurrence pattern in DCIS patients according to surgical modalities. And then we identified the value of sentinel lymph node biopsy for DCIS. Methods: Between Oct. 1994 and Nov. 2004, 371(9.9%) of 3729 patients with breast cancer were pure DCIS in Samsung Medical Center. We reviewed medical records retrospectively. Results: Median age was 46(21–80) year-old. Mastectomy and breast conservation surgery were performed 180(48.5%) and 191(51.5%) cases respectively. 108(29.1%) cases underwent sentinel lymph node biopsy. 27cases followed routine axillary dissection after sentinel lymph node biopsy during learning period. Only 1 case was found the metastases in sentinel lymph node. We underwent routine axillary dissection in 139(37.5%) cases and found axillary metastases in 3 cases. Remained 124(33.4) had been no axillary treatment. There were 10cases of local recurrences and 3 cases of contra-lateral breast cancer during follow-up periods. But, there were no distant metastases and lymphatic recurrence. Median follow-up were 27.9(1.1–115.2) months. Conclusions: No lymphatic recurrence was identified in whom local recurrence cases with previous lumpectomy only. There was a little value of sentinel lymph node biopsy for DCIS. We suggest that the routine use of sentinel lymph node biopsy for DCIS may be unnecessary. No significant financial relationships to disclose.
Continued use of trastuzumab (TRZ) beyond disease progression in the National Comprehensive Cancer Network (NCCN)
Authors: Y. Wong, R. Ottesen, J. Niland, M. Hughes, R. Theriault, S. Edge, D. Blayney, J. C. Weeks
Journal: Journal of Clinical Oncology (2008)

6522 Background: The role of continued TRZ treatment (tx) after progression in 1st line tx in women with HER2+ metastatic breast cancer (Br Ca) is controversial. There are no completed controlled clinical trials (CTs) that establish a benefit to continued TRZ use, and these trials have been difficult to complete. We use the NCCN Outcomes Database project to describe the use of 2nd line TRZ at NCCN centers. Methods: Our sample is 165 women treated with TRZ based tx as their 1st line of tx for newly diagnosed metastatic or relapsed HER2+ BrCa at 8 NCCN centers; who were treated between July 1997 and December 2004; and who had at least 450 days of follow up. Reason for tx changes were recorded by individual NCCN centers. In addition, women who were on single agent TRZ but later started chemotherapy or hormonal therapy were considered to have progressed. We also recorded the number of women who received TRZ on CTs. We used logistic regression to determine if age, sites of metastatic disease, year of diagnosis or NCCN Center were associated with a higher likelihood of receiving continued TRZ after disease progression. Results: See Table. 56 women discontinued 1st line tx due to progression and 6 pts discontinued for unknown reasons. Of these 62 pts, 46 (74%), continued TRZ. No prespecified candidate predictor variable was associated with 2nd line TRZ beyond progression. Of the 103 remaining of women, 35 (21.2%) discontinued 1st line tx for toxicity, 12 (7.3%) for other reasons and 46 (27.9%) for a planned treatment break. Conclusions: In these academic centers, despite the absence of evidence supporting the practice, 74% of patients who progressed while receiving TRZ continued TRZ as part of 2nd line therapy. Only 20% of these were treated on a clinical trial. Randomized CTs of new targeted therapies for all disease sites are needed to establish the role of treatment beyond progression Use of Trastuzumab (TRZ) in the NCCN N (%) Median duration of treatment in months (range) N (%) treated on a TRZ based clinical trial 1st line TRZ based tx (N=165) 5.62 (0*-37.9) 49 (29.7) Chemotherapy ± hormonal therapy and TRZ 150 (90.9) 5.39 (0*-29.2) 48 (32) Hormonal Therapy and TRZ 5 (3.0) 12.62 (0.8–37.9) 0 (0) TRZ alone 10 (6.0) 9.82 (2.9–30.1) 1 (10) 2nd TRZ based tx after progression (N=46)** 5.04 (0.5–40.3) 9 (19.6) Chemotherapy ± hormonal therapy and TRZ 31 (67.4) 4.80 (0.5–40.3) 6 (18.6) Hormonal Therapy and TRZ 3 (6.5) 2.7 (2.7–7.2) 1 (33.3) TRZ alone 12 (26.1) 7.95 (1.9–36.8) 2 (16.7) * Patient had 1-day course because of toxicity. ** Of 66 patients who stopped 1st line tx for progression or unknown reasons No significant financial relationships to disclose.
An update on phase I study of dose-escalating imatinib mesylate plus standard-dosed temozolomide for the treatment of patients with malignant glioma
Authors: S. Sathornsumetee, D. A. Reardon, J. A. Quinn, J. N. Rich, J. J. Vredenburgh, A. Desjardins, S. Gururangan, M. Egorin, A. Salvado, H. S. Friedman
Journal: Journal of Clinical Oncology (2006)

1560 Background: Imatinib mesylate, a kinase inhibitor of the PDGF receptor has been shown to decrease tumor interstitial pressure resulting in enhanced delivery of cytotoxic therapy. Recent phase II trial demonstrated promising anti-glioma activity of imatinib mesylate in combination with chemotherapy, hydroxyurea. Methods: The current phase I study is designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of imatinib mesylate when combined with temozolomide, a DNA methylator with established efficacy against gliomas. Eligibility criteria include: histologically confirmed malignant glioma; age of at least 18 years; KPS of at least 60%; less than grade 2 intratumoral hemorrhage; adequate hepatic, renal, and bone marrow function and lack of prior failure or significant toxicity following treatment with either imatinib mesylate or temozolomide. Temozolomide is dosed at 200 mg/m 2 on days 4–8 of each 28-day cycle. Imatinib mesylate is administered on days 1–8 of each cycle and the dose is escalated in successive cohorts of 3–6 patients via a standard “3+3” dose escalation design. Patients are stratified based on concurrent use of enzyme-inducing anticonvulsants (EIAC) and both strata are independently escalated. Results: To date 47 patients have been enrolled including 40 with GBM and 7 with anaplastic gliomas. Median age is 53.9 years (range 28 to 72); 66% are male and 51% are on EIAC. The MTD has yet to be defined for either stratum. To date DLT of ALT elevation has been observed in one patient from non-EIAC stratum. Two patients discontinued therapy due to toxicities with one asymptomatic intracerebral hemorrhage and one severe hematologic toxicity. Pharmacokinetic sampling has been performed in approximately half of the patients. One patient completed the study (12 cycles) with stable disease. Eleven patients remain on study with one partial response and three patients have undergone more than 10 cycles of therapy with stable disease. Twenty-eight patients (59%) have developed progressive disease and discontinued therapy. Conclusions: Combination of imatinib mesylate and temozolomide is safe and well tolerated. Further accrual and dose escalation are ongoing. [Table: see text]
Phase II trial of bevacizumab and irinotecan in the treatment of malignant gliomas
Authors: K. J. Goli, A. Desjardins, J. E. Herndon, J. N. Rich, D. A. Reardon, J. A. Quinn, S. Sathornsumetee, D. A. Bota, H. S. Friedman, J. J. Vredenburgh
Journal: Journal of Clinical Oncology (2007)

2003 Background: Recurrent malignant gliomas have low response rates to current treatments. Malignant gliomas have high concentrations of VEGF receptors which are poor prognostic indicators. Bevacizumab is a humanized IgG1 monoclonal antibody to VEGF, which is synergistic with chemotherapy for most malignancies. Irinotecan is a topoisomerase 1 inhibitor with modest activity against recurrent malignant gliomas. Methods: We report the mature data for our FDA approved phase II trial of bevacizumab and irinotecan for the treatment of recurrent malignant gliomas. We enrolled 68 patients (35 with grade IV tumors and 33 with grade III tumors.) All patients had progressive disease and received prior radiation therapy and temozolomide. The first 32 patients were treated every other week with bevacizumab 10 mg/kg and irinotecan 125 mg/m 2 (non EIAED) or 340 mg/m 2 (EIAED). The last 36 patients were treated with irinotecan 125 mg/m 2 (non EIAED) or 350 mg/m 2 (EIAED) on days 1, 8, 22, and 29 and bevacizumab 15 mg/kg on days 1 and 22. Results: The regimen was well tolerated. Only 1 CNS hemorrhage occurred after 10 cycles of treatment. Eight patients were taken off study for thrombotic complications (four PE, two DVT, one TTP, one thrombotic stroke) and 2 of these patients died (one with PE and one with thrombotic stroke). Two patients were discontinued secondary to grade 2 proteinuria and 3 were discontinued because they required non-neurosurgical surgery. The response rate was 59% (38 PRs and 2 CRs). In Grade IV, the median PFS was 23 weeks (95% confidence intervals 17–34). The 6 month PFS was 43% (95% confidence intervals 29%-63%), the median overall survival was 40 weeks (95% confidence intervals 34–50). In grade III patients the median PFS was 42 weeks, the 6 month PFS was 61% (95% confidence intervals 46%-80%), the medial overall survival was 60 weeks (95% confidence intervals 37%-73%). The follow-up for the second cohort is short with similar efficacy and more toxicity. Conclusion: The combination of bevacizumab and irinotecan is safe and demonstrates superior activity against malignant gliomas. [Table: see text]
Evaluation of epidermal growth factor receptor (EGFR) mutations as predictive and prognostic indicators in patients with adenocarcinoma of the lung treated with conventional chemotherapy
Authors: T. Fukui, Y. Ohe, T. Takano, K. Tsuta, K. Nomoto, K. Furuta, I. Sekine, H. Kunitoh, Y. Matsuno, T. Tamura
Journal: Journal of Clinical Oncology (2006)

7165 Background: EGFR mutations are associated with the responses to EGFR-tyrosine kinase inhibitors (TKI) in patients (pts) with adenocarcinoma of the lung. The E746-A750 deletion and L858R substitution mutations are the most common, as previously described. However, their implications in pts treated with conventional chemotherapy are unclear. To evaluate the predictive and prognostic value of the EGFR mutations, we studied pts with adenocarcinoma of the lung treated with conventional chemotherapy. Methods: We reviewed pts with advanced or recurrent chemotherapy naïve adenocarcinoma of the lung who received systemic chemotherapy between January 1999 and July 2001. Deletion in exon 19 and missense mutation (L858R) in exon 21 from small biopsy or cytology samples were analyzed by a high-resolution DNA melting analysis technique. Results: A total of 101 pts, all Japanese, could be analyzed. Patient characteristics were as follows: median age: 62 (37–84) years; female/ male: 39/ 62; never/ former/ current smoker: 47/ 23/ 31; and platinum-based/ non-platinum regimen: 81/ 20 (18 pts received EGFR-TKI later). 43 pts (42.6%) had EGFR somatic mutations; deletion in 24 pts, and a point mutation (L858R) in 19 pts. PR/ SD/ PD/ NE was observed in 11/ 24/ 7/ 1 pts with EGFR mutations and in 13/ 28/ 15/ 2 pts without the mutations, respectively. The response rate was similar (26% vs. 22%, p = .71) in the two subgroups. The median survival duration of the pts with EGFR mutations was 14.9 months (n = 43, including the 11 pts treated with EGFR-TKI later), as compared with 11.0 months (n = 58, including the 7 pts treated with EGFR-TKI later) in the pts without EGFR mutations (p = .09). Another analysis which handle the start of gefitinib administration as a censoring showed similar results (p = .24). Conclusions: EGFR mutations were not good predictors of tumor response to conventional chemotherapy. The overall survival tended to be longer in the pts with EGFR mutations, but prognostic value of these mutations for survival in pts with advanced adenocarcinoma of the lung was not statistically significant. No significant financial relationships to disclose.
In Vivo Anti-Tumor Activity of Atiprimod on SCID Models of Multiple Myeloma.
Authors: Paola Neri, Pierfrancesco Tassone, Masood A. Shammas, Ramesh B. Batchu, Simona Blotta, Sushma Samala, Laurence Catley, Makoto Hamasaki, Teru Hideshima, Gary S. Jacob, Donald H. Picker, Salvatore Venuta, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2005)
Changes in children's behavior after a natural disaster
Authors: J D Burke, J F Borus, B J Burns, K H Millstein, M C Beasley
Journal: American Journal of Psychiatry (1982)

Five months after a severe winter storm, a survey of children whose behavior had been assessed by means of a parent rating scale during a Head Start program 6 months before the disaster showed that some problem-behavior scores had increased significantly. The subgroups of children at higher risk were boys, whose Anxiety scale scores increased, and children accepted for Head Start only because their parents said they had special needs, whose Aggressive Conduct scale scores increased. For the entire group of children, school behavior improved. The findings support previous impressions that parents deny their children's problems after a natural disaster.
Cervical cancer in patients infected with human immunodeficiency virus (HIV)
Authors: M. M. Leitao, P. White, B. M. Cracchiolo
Journal: Journal of Clinical Oncology (2007)

5544 Background: The objective of this study was to compare the HIV viral load (VL), and CD4 counts (CD4) in patients infected with HIV with and without cervical cancer. We hypothesize that HIV positive women with inadequate HIV control, as reflected by the degree of immune suppression, will be at the highest risk of developing cervical cancer. Methods: We performed a case-control study of all patients seen at University Hospital from 1/1/95 - 4/30/06. All patients were HIV positive and were identified using an institutional electronic patient database and University Hospital Cancer Registry using ICD-9 codes. Cases were patients diagnosed with invasive cervical cancer and controls were patients without invasive cervical cancer. Patients were used as a control if there was documentation of a normal gynecologic exam without clinical or histopathologic evidence of cervical cancer. CD4 counts and viral loads were then abstracted from the electronic medical chart. Patients were kept as cases or controls if they had a CD4 count &lt;6 months before or &lt;1 month after the diagnosis of invasive cervical cancer (cases) or from the last gynecologic exam (controls). Controls were matched to cases on a 4:1 ratio according to current smoking history. Patients were considered immunocompetent if they had both CD4 counts &gt;200 and VL &lt;10,000. SPSS version 12.0 statistical software was used to analyze our data. Results: A total of 15 cases and 60 controls were identified. The majority (67 [89%]) of patients were African-American. The median CD4 count for the cases was 208 (range 18 - 1102) compared to 445 (range 20 - 1201) for the controls (p=0.03). The median VL was 16,918 (range 50 - 214,915) for the cases compared to 1,430 (range 50 - 571,000) for the controls (p=0.15). Only one (7.1%) of 14 cases was immunocompetent compared to 35 (63.6%) of 55 controls (OR 0.04 [95% CI: 0, 0.37; p&lt;0.001]). This significance was maintained after adjusting for current highly active antiretroviral therapy (HAART) use, number of years known to be HIV infected, and patient age (p=0.002). Conclusions: Patients with HIV who are diagnosed with invasive cervical cancer appear to have a much greater degree of immunosuppression than women with HIV without invasive cervical cancer. No significant financial relationships to disclose.
Characteristics of triple-negative metastatic breast cancer among older adults: A population-based analysis.
Authors: I. H. Zuckerman, E. Onukwugha, J. F. Gardner, D. L. McNally, B. S. Seal, C. D. Mullins
Journal: Journal of Clinical Oncology (2010)

1092 Background: The prognosis for women with metastatic breast cancer (MBC) is worse for those who have triple negative MBC (TNMBC). Few reports have examined TNMBC in an elderly population. The US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database provides information on estrogen receptor (ER) status and progesterone receptor (PR) status but does not record human epidermal growth factor receptor 2 (HER2) status, making identification and analysis of TNMBC patients challenging. Methods: Females over the age of 65 with stage IV breast cancer were identified in the SEER-Medicare database. Patients with a prior history of breast cancer were excluded. Those who were (1) ER negative, (2) PR negative, (3) had an administrative claim for HER2 test, and (4) did not receive trastuzumab were classified as potential TNMBC (p-TNMBC). Results: Of 1,755 MBC patients who met the inclusion/exclusion criteria, 313 (17.8%) were p-TNMBC. p-TNMBC were younger than other MBC (76.0 vs. 77.6 years, p<0.01). The proportion of p-TNMBC among African-American women was higher than in non-African-American women (22.2% vs. 17.2%; p=0.06). Compared to other MBC, p-TNMBC were more likely to have consulted with a medical oncologist (83.1% vs. 72.6%, p<0.01). Unadjusted median survival time was 7 months for both p-TNMBC and other MBC patients. Comparisons were similar when we excluded 218 patients who were classified as other MBC (not p-TNMBC); these MBC women were ER negative and PR negative but HER2 status was questionable since they did not have an administrative claim for a HER2 test and did not receive trastuzumab. Conclusions: As defined in this study, TNMBC occurred in approximately 18% of elderly MBC patients. TNMBC patients were younger and were more likely to have consulted a medical oncologist. TNMBC rates were slightly higher among African-Americans than other races. Unadjusted median survival was similar among p-TNMBC and other MBC. Knowledge of characteristics of TNMBC in the “real world” contributes to the understanding of the epidemiology and need for research and development of treatment strategies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis Amgen, Bayer, Genentech, Lilly, Novartis, Pfizer, sanofi-aventis sanofi-aventis Pfizer, sanofi-aventis Novartis, Pfizer, sanofi-aventis
Targeting SRC kinase (SRC) in melanoma cells.
Authors: A. J. Eustace, T. Mahgoub, S. Kennedy, J. Crown, A. Larkin, D. Tryfonopoulos, L. O'Driscoll, M. Clynes, N. O'Donovan
Journal: Journal of Clinical Oncology (2010)

8584 Background: The SRC family of tyrosine kinases have been implicated in melanoma progression. Dasatinib (D), a multitarget tyrosine kinase inhibitor, is a potent inhibitor of SRC, and has activity in melanoma cell lines. The aim of this study was to determine the frequency of expression of SRC in a large number of melanoma patient samples and to confirm the activity of D in an expanded panel of M cell lines. Methods: SRC levels were examined by immunohistochemical staining in tumour samples from 134 melanoma patients. Expression of SRC was assessed in melanoma cell lines by immunoblotting. The effects of D on proliferation were tested using the acid phosphatase assay and effects on invasion and migration were assessed by the Boyden chamber method. Results: SRC was detected in 75% (100/134) of M tumor samples. The frequency of SRC expression was higher in primary melanoma samples (81% [66/82]) than metastatic melanoma samples (67% [28/42]) (p = 0.089; not significant). SRC expression was significantly higher in tumors that were node- negative (19/22 [86%]) compared to node-positive tumors (16/28 [57%]) (p = 0.0252). SRC was detected in all 8 melanoma cell lines tested. 4 of the 8 cell lines were responsive to D. Lox-IMVI and WM-115 show greatest sensitivity with D IC50s of 35.4 nM (± 8.8 nM) and 79.3 nM (± 11.7 nM). HT144 and Malme-3M displayed moderate sensitivity with a maximum growth inhibition of 50% and 25%, respectively, in response to 300 nM D (Table). M14, Sk-Mel-5, Sk-Mel-28, and WM-266 were resistant to D. D also significantly decreased migration and invasion in both D responsive HT144 and D resistant M14 cells. Conclusions: Our results show that SRC is frequently expressed in melanoma and thus may be a rational target for treatment. The SRC inhibitor D has anti-proliferative and anti-invasive effects suggesting a rational for further study. Classification of cell lines as D responsive or resistant based on response to D (300 nM) Dasatinib responsive Dasatinib resistant Cell line % inhibition @ 300 nM Cell Line % inhibition @ 300 nM Lox-IMVI 90% Sk-Mel-28 −50%* WM- 115 60% Sk-Mel-5 −15%* HT144 50% WM-266-4 13% Malme-3M 25% M14 8% * Recorded values represent that D increased levels of proliferation compared to untreated cells. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Lymphorrea incidences after modified radical mastectomy with auto cut versus spray mode electro coagulation
Authors: S. Stäcker, M. Thill, K. Röder, K. Diedrich, D. Fischer
Journal: Journal of Clinical Oncology (2009)

e11571 Background: Lymphorrea is one of the most common side effects subsequent to mastectomy. It is a predicting factor for seroma, which are usually painless; however, lymphorrea is also linked to wound infection, wound healing complications and lymphedema. Electrocautery is a significant risk factor for lymphorrea and seroma. Two electrocautery methods—auto cut and spray mode electro coagulation—were compared in this prospective randomized study. Methods: 68 patients with operable breast cancer intended for modified radical mastectomy with axillary lymph node dissection or sentinel node biopsy were randomized into two groups by their date of birth. The patients in the first group were operated by using high frequency coagulation with auto cut, the members of the second group in spray mode. All wounds were drained by two self-regulating suction drainages. The drainages were removed as soon as the drain volume decreased to less than 30 ml/24 hours. Results: The mean drain volume amounted to 276 ml (range 20- 1,200 ml) in the auto cut group and 546 ml (range 100 -1,600ml) in the spray mode group. This difference is highly significant (significance level &lt;0.01, t= -2.9987; p=0.003896). The incidence of seroma formation was 5% in the auto cut group and 23.5% in the spray mode group. Patients who were treated with spray mode electrocautery in average had to be hospitalized two days longer. Conclusions: The lower need for instrument changes makes the spray mode electro coagulation more comfortable for the surgeon. Nonetheless the conventional electrocautery should be preferred to operate radical mastectomy in order to decrease the morbidity risk for patients. No significant financial relationships to disclose.