tbuckley/cabot-search huggingface dataset:
Underuse of anthracyclines in women with HER2-positive advanced breast cancer.
Authors: V. Rossi, F. Nole, S. Redana, M. Donadio, R. Martinello, E. Verri, G. Valabrega, M. Cossu Rocca, M. Aglietta, F. Montemurro
Journal: Journal of Clinical Oncology (2010)

1120 Background: Anthracyclines are among the most active drugs in breast cancer. Because of excessive cardiotoxicity, their use in combination with trastuzumab has been discouraged in patients with HER2-positive metastatic breast cancer. We sought to describe how this treatment paradigm influenced the utilization of anthracyclines in this patient setting. Methods: Analysis of a multi-institutional database containing the treatment history of 450 patients who received trastuzumab- based therapy for HER2-positive metastatic breast cancer. Eligibility to anthracyclines for metastatic disease was retrospectively assessed based on prior history of exposure. The use of anthracycline-based therapy after failure to the first trastuzumab-based regimen was assessed in eligible patients. Results: Three-hundred twenty-one patients (71%, 95% C.I. 67%-75%) were considered eligible to anthracyclines either because of no prior exposure (171 patients), or because of prior exposure in the neo- or adjuvant setting and metastatic progression occurring beyond 12 months of the last dose (150 patients). The use of anthracyclines before trastuzumab as treatment for metastatic disease declined sharply for patients diagnosed with metastatic disease in year 2000 onwards, with no patients treated in years 2006-2008 (Chii square test for trends p<0.001). Of 190 eligible patients who progressed during the initial trastuzumab-based therapy only 16 (8%, 95% C.I. 5%-13%) received an anthracycline as first salvage treatment. Another 24 (cumulative proportion 21%, 95% C.I. 16%-27%) received an anthracycline as further line of therapy. Of 119 eligible patients who died from breast cancer, only 30 (25%, 95% C.I. 18%-34%) ever received an anthracycline for metastatic disease. Conclusions: Despite two-thirds of patients receiving trastuzumab-based therapy for HER2-positive metastatic breast are eligible for anthracyclines, these drugs are nowadays infrequently used to treat trastuzumab-refractory disease. A role of these compounds should be redefined in this patient subset. No significant financial relationships to disclose.
Mechanisms of growth inhibition of chemo-surviving colon cancer cells by curcumin and resveratrol
Authors: B. Patel, D. Gupta, V. Sengupta, A. P. Majumdar
Journal: Journal of Clinical Oncology (2008)

15088 Background: 5-fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but produces incomplete response resulting in survival of cells (Chemo-surviving cells) that often leads to cancer recurrence. Thus, validation of a non-toxic chemopreventative agent that could prevent the recurrence of colorectal cancer would be highly desirable. Curcumin (diferuloylmethane; the yellow pigment of turmeric used in South Asian cuisine) and resveratrol (trans-3,5,4'- trihydroxystilben; found in many plant species, including peanuts and grapes), with no discernible toxicity, are known to inhibit initiation, promotion and progression of carcinogenesis. The present investigation was, therefore, undertaken to examine whether addition of curcumin or resveratrol to FOLFOX will be a superior therapeutic strategy for chemo-surviving cells. Methods: Cell growth in HCT-116 and HT-29 colon cancer cell lines were assessed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Western blotting was used to assess the relative levels of various proteins in EGFR and IGF-1R pathway. Results: Forty-eight-hour treatment of colon cancer HCT-116 or HT-29 cells with FOLFOX (25 μM 5-FU+0.625 μM oxaliplatin) resulted in 60–70% cell survival, accompanied by a marked activation of IGF-1R and minor to moderate increase in EGFR, HER-2 as well as AKT, COX-2 and Cyclin-D1. However, inclusion of resveratrol or curcumin to continued FOLFOX treatment for another 48 h greatly decreased the survival of these cells, compared to those subjected or not subjected to continued FOLFOX treatment (control). While resveratrol and curcumin are both effective in inhibiting the growth of colon cancer HCT-116 and HT-29 cells, curcumin appears to be superior in this respect. These changes are associated with concomitant reduction in expression and activation of EGFR, HER-2 as well as IGF-1R. Additionally, expression of down-stream signaling effectors such as AKT, COX-2 and Cyclin-D1 was down-regulated in a similar fashion. Conclusions: Inclusion of curcumin or resveratrol to conventional chemotherapeutic regimen could be one of the effective strategy to prevent the emergence of chemo-resistant colon cancer cells. No significant financial relationships to disclose.
Cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against tumor cell lines characterized for EGFR expression and K-ras mutation
Authors: J. Barriere, J. Fischel, P. Formento, N. Renée, M. Francoual, J. Formento, M. Chefrour, M. Etienne-Grimaldi, E. François, G. Milano
Journal: Journal of Clinical Oncology (2009)

e14583 Background: Mutated K-ras protein is a strong predictive factor of cetuximab resistance, bypassing the classical direct inhibitory effect on epidermal growth factor receptor (EGFR) signaling. However, cetuximab is also able to mediate ADCC, which may be part of the clinical response. The aim of this ex-vivo study was to quantify cetuximab-mediated ADCC on various human cancer cell lines characterized for EGFR-expression and K-ras mutation. Methods: Two K-ras mutated cell lines over-expressing EGFR and resistant to anti-EGFR tyrosine kinase inhibitor were tested (Capan-1 and Capan-2, pancreatic), along with 2 K-ras wild-type cell lines over- expressing EGFR (CAL166, head and neck; A431, epidermoid carcinoma) and an EGFR-negative cell line (OCM1, uveal melanoma). The tested monoclonal antibodies (mAbs) were: cetuximab (Merck, anti-EGFR IgG1 mAb), panitumumab (Amgen, anti-EGFR IgG2 mAb), and as a negative control, rituximab (Roche, IgG1 anti-CD20 mAb). ADCC ( 51 Cr release assay) was performed using freshly- isolated peripheral blood mononuclear cells from a healthy donor. Results were expressed as % of potentially maximum 51 Cr release. Results: Cetuximab mediates ADCC against EGFR-over-expressing cell lines CAL166 (38.4 ± 3.1 %), A431 (13.5 ± 1.7 %), Capan-1 (31.2 ± 0.8 %) and Capan-2 (27.8 ± 8.6 %) irrespective of the K-ras mutational status, but not against EGFR-negative OCM-1 (6.2 ± 1 %). Conversely, unlike IgG1 cetuximab, the anti-EGFR IgG2 panitumumab and the irrelevant antibody rituximab were both unable to induce significant ADCC (&lt; 10 % on all tested cell lines). Conclusions: Cetuximab-mediated ADCC is independent of the K-ras mutational status of the tumor cell lines. Present data suggest that cetuximab may remain of clinical interest in K-ras-mutated patients. Immunostimulation, as well as new generation anti-EGFR mAbs with improved ability to induce ADCC, may be promising in the management of K-ras-mutated patients. No significant financial relationships to disclose.
Recovery of spermatogenesis after treatment for Hodgkin's disease: limiting dose of MOPP chemotherapy.
Authors: M F da Cunha, M L Meistrich, L M Fuller, J H Cundiff, F B Hagemeister, W S Velasquez, P McLaughlin, S A Riggs, F F Cabanillas, P G Salvador
Journal: Journal of Clinical Oncology (1984)

The sperm production of 25 patients with Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was studied retrospectively. All but two patients also received radiotherapy treatment to pelvic and/or non-pelvic fields. Sperm counts were obtained from patients treated either with three or fewer (MOPP-2 group) or with five or more (MOPP-6 group) chemotherapy cycles. Recovery of spermatogenesis following treatment-induced azoospermia was significantly higher among the MOPP-2 patients (Mann-Whitney rank sum test, p = 0.001). Patients in this group who did not receive pelvic irradiation appeared to have greater recovery rates (p = 0.06). The results suggest that three cycles of MOPP chemotherapy represent a maximum exposure compatible with the recovery of spermatogenesis.
Ethnic disparities in head and neck carcinomas (HNC):“The Hispanic Paradox”
Authors: M. Escalon, C. J. Calfa, M. Farias, E. Lopez, S. Patel, V. Patel, L. E. Raez
Journal: Journal of Clinical Oncology (2008)

17023 Background: Although disparities between black and white in the incidence and mortality of head and neck cancers (HNC) have been reported, very little is known about the outcomes in the Hispanic population. National epidemiological data suggest that while some cancers may have higher rates in Hispanics, the HNC rates are lower in this ethnic, heterogeneous group. The “Hispanic Paradox,” where Hispanics exhibit similar or better outcomes than non-Hispanic whites, is far from being understood. We aim to identify differences in epidemiology, treatment modalities and outcome of Hispanics and White non-Hispanics patients (WNH) diagnosed and treated for advanced HNC at our institution from 2004–2005. Methods: We reviewed the medical records of 183 patients who were identified using the tumor registry. Standard statistical analyses, including Kaplan-Meier survival estimates for survival calculations and Chi-squared analysis for group comparisons were used. P value of <0.05 was considered for statistical significance. Results: 129 pts were white (70%) and 54 patients were Hispanics (30%). Cubans represented 70% and Puerto Rican 4%. There was no significant difference with respect to squamous cell histology, age at diagnosis, or performance status. More Hispanics had weight loss at presentation (P=0.04) and there was a trend for higher stage at presentation (P = 0.26). Hispanics were more likely to smoke and drink than WNH (P = 0.004 and 0.005 respectively) No differences were seen in disease free survival (DFS) (P=0.7). Kaplan-Meier estimate of median overall survival (OS) was16.2 months for Hispanics vs. 24.5 months for WNH but this difference did not reach statistical significance (P = 0.26). Multimodality approach with chemotherapy, radiation with or without surgery did not alter the outcome significantly, regardless of ethnicity. Conclusion: In our experience, Hispanics had higher exposure to smoking and ethanol, presented with more advanced disease and more weight loss at diagnosis and had a tendency for decreased DFS and OS which did not reach statistical significance. The described “Hispanic paradox” may be in part be due to relatively small sample size of Hispanics where even if a trend for poorer outcome may exist, it is difficult to prove. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Oncology, sanofi-aventis
Adverse association of expressed vascular endothelial growth factor (VEGF) with long-term outcome of stage I-III breast cancer (BrCa), with co-expression data of VEGF and Her2, Cox2, uPA and ER. Results from the British Columbia Tissue Microarray Project
Authors: J. Ragaz, K. Miller, S. Badve, Y. Dayachko, S. Dunn, T. Nielsen, A. Brodie, D. Huntsman, C. Bajdik, G. Sledge
Journal: Journal of Clinical Oncology (2004)

524 Background. Several prior studies have shown association of VEGF with inferior outcome of BrCa. However, only a few past studies had a large number of patients, or availability of multiple markers and prognostic factors.Methods. In this study, impact of VEGF was correlated with the outcome in a large cohort of Breast Cancer (BrCa) patients, enrolled between 1978–1990 in phase II-III British Columbia trials, who had tissue microarrays (TMA) built from paraffin, with 877 pts having VEGF expression tested by Immunohistochemistry (IHC, Biogenix polyclonal anti-VEGF Ab, Dako). For detection, the LSAB2 kit with the DAB as the chromogen, was used. Event at 15 years was any death (expressed as OS%), with the median survival and 95% confidence intervals (CI) expressed for 4 groups according to the stain intensity. Other markers (Her2, Cox2, uPA, ER, etc.) were tested for co-expression. Results. At a median follow up of 17.4 years (ranges 9.8, 28.7 years), 586 patients died (any death), and 502 had BrCa recurrence. Expression of VEGF showed progressively worse outcome according to intensity of expression. VEGF expression showed a positive coexpression with Her2 (49 vs 61% for Her2-ve vs +ve, p=0.006); Cox2 (47 vs 57%, for −ve vs +ve, p=0.004); uPA (43 vs 59%, for −ve vs +ve, p<0.001) and a negative coexpression with ER (55 vs 47%, for −ve vs +ve).Conclusion: Expression of VEGF, and its intensity, are associated with a significantly inferior outcome of early BrCa, and with co-expression of several markers of relevance in BrCa biology. VEGF, Her2, Cox2 and other markers can be successfully tested on TMA permitting interactive testing of multiple markers. These data indicate that diagnostic and therapeutic trials exploiting VEGF expression interacting with other markers are indicated for early BrCa. No significant financial relationships to disclose.
Effect of a new model for multidisciplinary breast cancer care on clinical metrics leading to efficiency and timeliness of access.
Authors: Rashmi Krishna Murthy, Susan E Ferguson, Welela Tereffe, Isabelle Bedrosian, Stacy L. Moulder
Journal: Journal of Clinical Oncology (2014)

107 Background: The multidisciplinary approach to breast cancer care provides a coordinated mechanism for evaluating and treating new patients. Improving the structure of clinic models may further enhance the delivery of cancer care. Methods: In May 2013, multi-team (MT) clinics were introduced in the breast center at the University of Texas MD Anderson Cancer Center. Local patients with newly diagnosed breast cancer were scheduled to be seen in a MT clinic with testing coordinated for the same day. Patient cases were first reviewed and examined concurrently by physicians from each discipline (surgical, medical, radiation), followed by sequential visits with each clinician for a more detailed discussion. The goal of this program was to determine whether a highly integrated multidisciplinary clinic model would improve the efficient delivery of cancer treatment. Results: From 5/2013 – 5/2014, 211 newly diagnosed and untreated breast cancer patients were seen in the MT clinic. Clinical metrics were reviewed retrospectively and compared to newly diagnosed and untreated patients who entered the clinic using the standard model (non-MT patients) (n=1944). Please see Table for details of the data. Conclusions: Multi-team clinics improved clinical metrics leading to efficiency and timeliness of access. The model enriched for a population of patients who were more likely to receive treatment within the breast center, utilize institutional resources, and enroll into clinical trials. [Table: see text]
Isolated hepatic iron deficiency despite abundant systemic iron in Mdr2(-/-) mice: Integrity of the bile transport system is important in normal liver iron homeostasis
Authors: A. Sobbe, K. Bridle, L. Jaskowski, L. Ostini, C. E. de Guzman, N. Santrampurwala, V. N. Subramaniam, L. M. Fletcher, D. H. Crawford
Journal: Hepatology (2011)
Biomarkers detected by proteomic analysis predicts breast cancer response to neoadjuvant chemotherapy
Authors: D. Shen, J. He, J. Gornbein, Z. Chen, K. F. Faull, J. P. Whitelegge, H. R. Chang
Journal: Journal of Clinical Oncology (2006)

669 Background: Neoadjuvant chemotherapy provides an excellent opportunity for objective assessment of treatment-induced tumor response and for studying biomarkers characteristic of therapy-induced tumor responses. Methods: Proteomic analysis of T3/T4 breast cancer was performed in patients with locally advanced breast cancer in a phase II clinical trial. The breast cancer specimen was obtained before and after four cycles of Taxotere/Carboplatin/±Herceptin treatment. Two proteomic approaches, SELDI mass spectrometry and Clontech Ab Microarray 500, were used to screen for protein biomarkers that predict response of breast cancer to chemotherapy. Results: Five tumors with pathologically complete response (pCR) and 29 tumors with various amounts of residual tumors (Non-pCR) were analyzed by SELDI-TOF using the NP 20 chip. The normalized mass signals were compared between pCR vs Non-pCR at each aligned location by Wilcoxon rank sum test. Statistically significant differences were found at 22 m/z locations using a liberal p &lt;0.20 criterion. The best univariate predictor occurred at m/z 14960 (p=0.004), which correctly classified 5/5 pCR spectra (100%) and 24/29 Non-pCR spectra (83%). A multivariate classification tree developed using m/z 14960 and m/z 12138 intensities correctly classified all 34 spectra. Ab microarray analysis was performed on five pCR tumors and in five tumors with the largest residual cancer. The Internal Normalization Ratio (INR) was calculated and used to compare the difference of protein expression between the two groups. Eight differentially expressed protein biomarkers were selected with the criteria of a statistically significant (Student t, p&lt;0.05) expression change of &lt;0.77 or &gt;1.3 fold. Three proteins (Tat-SF1, PYK2 and PTP1B) were higher, and five (E2F2, IL1b, FEN1, CDC37 and ACM1) were lower in tumors with pCR. The unsupervised hierarchical clustering of the 10 samples by these eight proteins completely separated the pCR tumors from the poor responders. Conclusions: Our study suggests that bothSELDImass spectrometry and antibody microarray may be used to predict the tumor response to neoadjuvant chemotherapy. Proteomic analysis may be useful in developing tailored chemotherapy for breast cancer. [Table: see text]
Final results of After-6 protocol 1: A phase III trial of observation versus 6 courses of paclitaxel (Pac) in advanced ovarian cancer patients in complete response (CR) after platinum-paclitaxel chemotherapy (CT)
Authors: P. F. Conte, G. Favalli, A. Gadducci, D. Katsaros, P. L. Benedetti Panici, A. Carpi, G. Scambia, M. Ballardini, O. Nanni, S. Pecorelli
Journal: Journal of Clinical Oncology (2007)

5505 Background: The majority of advanced ovarian cancer patients (pts) in CR after debulking surgery and Platinum/Paclitaxel will eventually relapse. Role of maintenance CT is still questionable even if a SWOG/GOG trial has shown an improved progression free survival (PFS) with 12 vs 3 cycles of maintenance Pac. In March 1999, the After 6 Italian Cooperative Group initiated a phase III study to determine if maintenance Pac could prolong PFS in pts with a clinical (cCR) or pathological CR (pCR) after first line CT Methods: Pts with advanced ovarian cancer in cCR or pCR after 6 cycles of Platinum/Paclitaxel, were randomised to observation or 6 cycles of Pac 175 mg/sqm iv q 3 wks. Primary end point: PFS; secondary end points: overall survival (OS) and toxicities. Planned sample size: 250 pts to detect a 15% absolute increase in 2-yr PFS. Results: From 03/99 to 07/06, 200 pts were randomised. Due to the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Main patient characteristics: median age 58 yrs, median PS 0 (neurotoxicity ≥ G 2 was an exclusion criteria), stage IIb/IIc 15%, stage III 79%, stage IV 6%; 105 pts (52.5%) were in pCR. 14% of pts randomised to observation received Pac; 22% of pts randomised to Pac stopped treatment after 2–5 cycles (progression or death: 3 pts; toxicity: 9 pts; refusal: 7 pts; others: 3 pts). A G ≥ 2 neurotoxicity was reported in 25% of pts treated with Pac; other toxicities were mild. After a median follow up of 44 months, 94 pts (47%) have relapsed and 42 pts (21%) died. Median PFS were 34 and 34.5 months in observation and Pac arm respectively; 3-yr OS was 88% in observation and 78% in Pac arm. Irrespectively of treatment arm, median PFS was 34.4 months for pts with pCR and 24.5 months for those with cCR; 3-yr survival rates were 87% and 79% respectively (p=0.04). Conclusions: Six courses of maintenance Pac do not prolong PFS or OS in pts in CR after first line platinum/paclitaxel. Irrespectively of assigned treatment, the outcome of these pts is more favourable than previously reported and significantly better in the pCRs. Maintenance CT remains an experimental treatment that should be tested in pts at high risk of relapse. [Table: see text]
Emerging role of laparoscopy in the diagnosis of lymphoma.
Authors: G B Mann, K C Conlon, M LaQuaglia, E Dougherty, C H Moskowitz, A D Zelenetz
Journal: Journal of Clinical Oncology (1998)

PURPOSE The results of laparoscopic procedures on patients with suspected or known lymphoma were analyzed to review the application and define the role of laparoscopy in lymphoma. PATIENTS AND METHODS The hospital records of 94 patients who underwent 101 procedures between June 1993 and October 1996 were reviewed for demographic and clinicopathologic information. RESULTS The procedure was diagnostic in 85 patients, either at primary presentation (48 patients), possible relapse (21 patients), in the course of treatment (eight patients), or of a liver lesion (eight patients). In the remaining 16 patients, it was used to stage possible intraabdominal disease. Twenty-seven patients had a previous unsuccessful diagnostic procedure. There were no operative deaths and eight postoperative complications (8%). The laparoscopy revealed non-Hodgkin's lymphoma (NHL) in 48 patients, Hodgkin's disease (HD) in 14 patients, other neoplastic conditions in six patients, and benign conditions in 33 patients. There was adequate information in all procedures in which lymphoma was diagnosed for treatment decisions. There was one false-negative and one nonresult for technical reasons. Ten patients commenced chemotherapy before discharge after a median delay of 3.5 days. In five of 24 patients (21%) with recurrent or persistent lymphoma, the precise diagnosis was significantly different from the original one. CONCLUSION From our experience, laparoscopy can safely provide tissue samples of suspected lymphoma for full diagnostic analysis. It should be considered when percutaneous biopsy is not technically possible, when chromosomal or genetic analysis is needed for treatment decisions, or when the results of percutaneous biopsy are inadequate to make therapeutic decisions.