tbuckley/cabot-search huggingface dataset:
Radiation therapy after breast-conserving surgery: When are we missing the mark?
Authors: Mohammed Nassif, Nora Trabulsi, Kristen Reidel, Sarkis H. Meterissian, Robyn Tamblyn, Nancy Mayo, Ari-Nareg Meguerditchian
Journal: Journal of Clinical Oncology (2012)

43 Background: Postoperative radiotherapy (RT) after breast conserving surgery (BCS) represents the standard of care for local control of breast cancer (BC). Despite wide dissemination of clinical guidelines, variations in practice persist. Our objective was to identify patient, disease, and physician characteristics that predict lack of consideration for RT after BCS. Methods: Cancer registry data and administrative claims for all BCs diagnosed in Quebec from 1998 to 2005 were collected. Receipt of a consultation for RT in women with non-metastatic BC treated with BCS was measured. Multivariate logistic regression was used to assess the association between patient, disease, and physician characteristics and having an RT consult. Results: 27,483 women were included. Mean age was 59 years, 76.5% had no comorbidities, and 27.6% had stage III BC. Overall, 90.1% of women were considered for RT within 1 year of diagnosis. Patients at age extremes were less likely to be considered as compared to women 50-69: those 30-49, 70-79 and 80+ had odds ratios (OR) of 0.82 (CI 0.73-0.93), 0.54 (CI 0.48-0.61) &amp; 0.11 (CI 0.09-0.12), respectively. Women with any ER visit and women with a hospitalization (unrelated to BC) had 15% and 17% lower odds of having an RT consult, respectively. In patients with advanced disease, receiving a consultation for chemotherapy within 4 months of BCS increased the likelihood of also being considered for RT within 1 year (OR 1.54, CI 1.19-2.00). Increases in physician BCS volume in the year prior to patient diagnosis increased the chance of their patient receiving an RT consult by 7% for every additional 10 BCS performed. Conclusions: Patient age, use of non- BC-related health services and physician volume of BCS predicts use of RT. Guideline deviations in chemotherapy administration also predicts variation in RT use.
A randomized, double-blind, phase II study of first-line FOLFOX plus bevacizumab with onartuzumab versus placebo in patients with metastatic colorectal cancer (mCRC).
Authors: Johanna C. Bendell, Howard S. Hochster, Lowell L. Hart, Irfan Firdaus, Joseph Ronald Mace, Joshua Jemison McFarlane, Mark Kozloff, Daniel Virgil Thomas Catenacci, Jessie J. Hsu, Stephen Paul Hack, David S. Shames, See-Chun Phan, Allen Lee Cohn
Journal: Journal of Clinical Oncology (2015)

663 Background: In mCRC, MET overexpression has been associated with poor prognosis and resistance to anti-VEGF therapy. We initiated a phase II study to evaluate the combination of onartuzumab (O), a ligand-blocking monoclonal antibody directed against the MET receptor, plus bevacizumab and FOLFOX, in first-line mCRC (GO27827; NCT01418222). Methods: This double-blind, randomized, multicenter phase II study randomized patients 1:1 to receive O (10 mg/kg iv) or placebo (P), plus mFOLFOX6 and bevacizumab (5 mg/kg iv). Stratification was by prior adjuvant therapy. All treatments were given on day 1–3 of a 2-week cycle. Oxaliplatin was given for up to 8–12 cycles; all other agents were continued until progression, unacceptable toxicity or death. Primary endpoint was progression-free survival (PFS) in ITT and MET+ subgroup by immunohistochemistry (IHC). MET status was determined by central laboratory IHC evaluation, with scores of 2+ or 3+ considered MET+. Results: From September 2011 to November 2012, 194 patients were enrolled. A recommendation was made to stop O after an interim efficacy and safety analysis in September 2013, due to lack of efficacy. The final analysis (cut-off Feb 2014) found that O did not improve PFS vs. P in the ITT (HR 0.75 [0.52–1.08]; p=0.12) or MET IHC+ populations (n=79; HR 1.03 [0.56–1.89]; p=0.93), although improvement was noted in the MET IHC− population (n=108; HR 0.60 [0.37–0.97]; p=0.03). Neither overall survival (OS) nor response rate (RR) was improved with O vs. P in any of the groups (OS HR 0.96 [0.61–1.50], p=0.85 for ITT; OS HR 1.24 [0.63–2.43], p=0.54 for MET IHC+; OS HR 0.83 [0.44–1.56], p=0.56 for MET IHC−; RR 57.3% vs. 57.7% for ITT, 43.2% vs. 57.1% for MET IHC+, 66.1% vs. 60.8% for MET IHC−). More edema (65.7% vs. 12.9%) and venous thromboembolic events (30.3% vs. 16.1%) were seen with O vs. P, respectively. Grade ≥3 events were similar (86.9% vs. 84.9%) and events leading to discontinuation were increased (48.5% vs. 37.6%) with O vs. P. Conclusions: Adding onartuzumab to FOLFOX/bevacizumab did not prolong PFS in first-line unselected or MET IHC+ mCRC. A trend towards PFS benefit was seen in those with MET IHC− mCRC, contrary to prior reports in other tumor types. Clinical trial information: NCT01418222.
Docetaxel (T) given concurrently with or sequentially to anthracycline-based (A) adjuvant therapy (adjRx) for patients (pts) with node-positive (N+) breast cancer (BrCa), in comparison with non-T adjRx: First results of the BIG 2–98 Trial at 5 years median follow-up (MFU)
Authors: J. P. Crown, P. Francis, A. Di Leo, M. Buyse, A. Balil, M. Anderson, B. Nordenskjöld, R. Jakesz, J. Gutierrez, M. Piccart
Journal: Journal of Clinical Oncology (2006)

LBA519 Background: The activity of T in metastatic BrCa mandated evaluation as adjRx. We compared the efficacy of T with, or after A, both followed by CMF (cyclophosphamide/ methotrexate/ 5-fluorouracil), versus non-T adjRx. Methods: Random assignment trial in resected N+ pts, 18–70 yrs, stratified by: center, 1–3 vs &gt;3 nodes and age &lt;50 vs ≥50. The treatment arms were (mg/m 2 , intravenously unless otherwise stated): Ia: A 75 q 3 weeks × 4 ⋄ CMF ×3 (oral C 100 day 1–14, F 600 + M 40 d 1+8; q 28 days). Arm Ib; AC 60/600 × 4⋄CMF × 3. Arm II: A75 × 3 ⋄T100 ×3 ⋄CMF ×3. Arm III: AT 50/75 ×4 ⋄ CMF × 3. Pts subsequently received hormono-(receptor+), and radiotherapy per local guidelines. Randomization was in the ratio (1:1:2:2). The trial was designed to have 80% power to detect a 78% hazard ratio (HR) for relapse in II+III v I, with final analysis at 1215, and interim at 405 and 810 events. The primary comparison between the II+III and I would be done at a one-tailed significance level of 0.025. Secondary comparisons of II vs Ia and III vs Ib would be done using a closed testing procedure at a one-tailed significance level of 0.025. The 95% confidence limits of the HR of III v II would be calculated. Due to a low relapse rate, the plan was amended with main analysis after 810 events or 5 years MFU. Results: 2887 pts were enrolled (6/1998–6/2001). Characteristics were well-balanced, 46% had &gt;3N+. Grade 3/4 toxicity occurred in 22.9, 24.7, 35.3 and 28.6 % of pts in Ia, Ib, II and III respectively. At 62.2 months MFU (3/2006), 732 pts (25%) had events. Planned event-free survival (EFS) comparisons were: Conclusion: In this study, the HR for T v non-T adjRx was of borderline significance. There were possibly important differences related to schedule, sequential but not concurrent appearing superior to non-T adjRx. Overall survival analysis will require longer follow-up. Translational studies are underway. [Table: see text] [Table: see text]
Appropriate endpoints for superficial bladder cancer clinical trials.
Authors: L A Kalish, M B Garnick, J P Richie
Journal: Journal of Clinical Oncology (1987)

Many protocols for treatment of superficial bladder cancer include periodic cystoscopic examinations with resection of visible lesions. This allows pathological restaging of the disease at each examination. For example, this type of follow-up is common in clinical trials evaluating intravesical therapies. In such trials, clinical outcome is typically summarized using end-points that measure failure to control superficial disease. Alternative endpoints measuring failure to prevent progression to invasive disease are often ignored. In this report, the rationale for ignoring the invasive disease endpoints is given and flaws in the rationale are described. Evidence from actual data sets support the view that superficial disease endpoints may not be appropriate surrogates for invasive disease endpoints. It is recommended that time to invasive disease should be considered a major endpoint when designing and analyzing trials in superficial bladder cancer.
Microvesicular-mediated gene transfer of prostate tumor markers
Authors: J. F. Renzulli, G. Dooner, C. Owens, G. Colvin, M. Dooner, M. Del Tatto, L. Goldstein, P. Quesenberry
Journal: Journal of Clinical Oncology (2009)

e16076 Background: Microvesicles have been a subject of research for many years. Recent work has focused on the potential for cancer vaccines via microvesicles. It has also been demonstrated that various cell-specific phenotypes can be transferred from one cell type to another through microvesicle transfer. Studies in our laboratory have demonstrated that co-culture of murine lung tissue with marrow cells across a cell impermeable membrane can induce elevations in lung-specific mRNA expression in human donor marrow stem cells. Our objective is to determine whether there is transfer of genetic or transcriptional factors via microvesicles from human prostate cancer cells to fresh human marrow cells. Methods: Fresh prostate tissue was harvested from surgical specimens following radical retropubic prostatectomy. Samples were histologically confirmed to contain prostatic adenocarcinoma. Co-cultures were established using a transwell system in which 0.05–0.100 grams of prostate tissue was minced and co-cultured with 1–3 million normal, human donor marrow cells for 2–7 days. Marrow not co-cultured with tumorserved as a control. Target cells were collected and total RNA was analyzed for prostate-specific gene expression byReal Time RT-PCR. Fold differences in expression of the genes were analyzed, using TaqMan®, gene assays (Applied Biosystems) and were expressed in relation to the marrow control. Results: We have observed significant increases in gene expression in marrow cells co-cultured with prostate tumor cells (Gleason grades 6–9). Variable increases in expression were seen in 3 patient samples, as high as 7-fold for ERG, greater than 10-fold for ACPP and greater than 100-fold for STEAP, PART, TMPRSS2, PSCA and ETV1. Conclusions: These studies demonstrate that prostate specific genes are present in fresh human marrow cells after co-culture with tumor tissue. This establishes a base to begin evaluating the significance of microvesicle-mediated genetic transfer, mechanisms of transfer and therapeutic options for blocking or manipulating such transfer to influence the disease process. No significant financial relationships to disclose.
Carboplatin: an active drug in metastatic breast cancer.
Authors: M Martín, E Díaz-Rubio, A Casado, P Santabárbara, J M López Vega, E Adrover, L Lenaz
Journal: Journal of Clinical Oncology (1992)

PURPOSE The study was undertaken to assess the antitumor activity of carboplatin 400 mg/m2 intravenously every 4 weeks in metastatic breast cancer (MBC). PATIENTS AND METHODS Thirty-four MBC patients without any prior exposure to chemotherapy entered the study. All patients had measurable disease in at least one site and were assessable for response and toxicity. RESULTS Of 34 assessable patients, 12 obtained a complete (one) or partial (11) response to carboplatin, resulting in an overall response rate of 35% (95% confidence interval, 19.8% to 53.5%). The median duration of response was 8 months (range, 2+ to 12 months). Responses were seen in lymph nodes (four of six), lung (five of nine), skin and soft tissues (four of nine), breast (two of eight), and liver (three of 11), but not in measurable lytic lesions of the bone. Toxicity was mild, mainly consisting of emesis (81% of the patients; 66% of the courses), leukopenia of World Health Organization (WHO) grade 1 to 2 (47% of the patients; 18% of the courses), and thrombocytopenia (12% of the patients; 3% of the courses). There were no cases of life-threatening toxicity, although one patient developed grade 4 thrombocytopenia without bleeding. Of 22 patients who did not respond to carboplatin, 18 received salvage therapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF; 15 patients); cyclophosphamide, methotrexate, and fluorouracil (CMF; one patient); or hormones (two patients). Objective responses to CAF and hormonal therapy were seen in 11 of 15 and two of two patients, respectively. The remaining patient did not respond to CMF salvage chemotherapy. Overall, the response rate to either first-line carboplatin or second-line salvage therapy was 73.5% (25 of 34 patients). After a median follow-up time of 22 months, the median survival was 19 months. CONCLUSIONS Carboplatin is an active drug in MBC patients without previous exposure to chemotherapy. In our study, the use of an experimental drug as first-line single-agent treatment in MBC did not have a negative influence on patient survival, as the majority of the carboplatin nonresponding patients could be salvaged with a conventional therapeutic regimen.
Prognostic significance of proliferation markers and telomerase activity in gastrointestinal stromal tumors.
Authors: A. Augustinakova, H. Brizova, I. Hilska, M. Kalinova, R. Kodet
Journal: Journal of Clinical Oncology (2010)

10078 Background: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, represent a heterogeneous group of neoplasms with an unpredictable biological behavior ranging from benign to malignant. It is difficult to determinate their aggressive behavior despite known prognostic factors such as tumor size, mitotic activity and tumor location or mutation status of genes c-kit or PDGFRα. Molecular markers including mechanisms of proliferation (Ki67 and TPX2) or cellular senescence (reactivation of telomerase activity) may provide an additional information on biological behavior of these neoplasms. Methods: We measured Ki67 and TPX2 mRNA levels as proliferation markers and hTERT (human Telomerase Reverse Transcriptase) mRNA level as a marker of telomerase activity using absolute quantification real time RT PCR. Normalized levels of proliferation markers Ki67, TPX2 and hTERT (normalized to mRNA levels of ABL housekeeping gene) was correlated between the different groups of tumors such as GIST, leiomyoma and a group of tumors with aggressive and high proliferation status, and finally, between risk categories of GIST. Results: The group of patients with agrressive and high proliferate Burkitt lymphoma (n=19) expressed significantly higher levels of Ki67 (p<0.0001), TPX2 (p<0.0001) and telomerase subunit hTERT (p<0,0001) than a group of patients with GIST (n=89, 90 and 58 respectively) or leiomyoma (n=9, 9 and 4 respectively). Statistical correlation was also found in the levels TPX2 and high risk category of GIST, a subgroup of patients with high risk GIST (n=36) expressed significantly higher levels of TPX2 proliferation marker (p=0.0101) than patients in the group with very low (n=4), low (n=3) and intermediate risk (n=5). Conclusions: Molecular evaluation of telomerase activity and biological markers involved in proliferation of cells may define an increased risk of aggressive behavior and to help to predict prognosis of GISTs. Assessement of the expression of TPX2 proliferation marker may become a suitable tool to determine biological behavior of GISTs. Supported by VZ FNM MZO 00064203/6704. No significant financial relationships to disclose.
Prognostic impact of hypoxia imaging with <sup>18</sup>f-fluoroerythronitroimidazole with integrated positron emission tomography and computed tomography in non-small cell lung cancer.
Authors: M. Hu, J. Yu, Y. Ma, W. Yang, D. Mu, L. Kong, L. Xing, G. Yang, P. Xie
Journal: Journal of Clinical Oncology (2010)

e21088 Background: Tumor hypoxia is considered to be an independent predictor of poor prognosis, as well as associated with an increased likelihood of local recurrence and distant metastasis. The study investigated the prognostic effect of pretherapy 18F-Fluoroerythronitroimidazole (18F-FETNIM) integrated positron emission tomography and computed tomography (PET/CT) on survival and analyzed whether 18F-FETNIM uptake of tumor tissue could predict tumor recurrence and distant metastasis in non-small cell lung cancer (NSCLC). Methods: Twenty patients with pathologically confirmed NSCLC who had not undergone treatment were enrolled in the study. Tumour tissue oxygenation was measured with 18F-FETNIM PET/CT. Patients received 357 MBq (range, 274 to -369 MBq) of 18F-FETNIM intravenously and then rested for approximately 120 minutes before undergoing PET/CT. The maximum standard uptake value (SUVmax) of tumor tissue was calculated. There were 24 months in the follow-up period. PET data were correlated with clinical follow-up data. Results: Patients with a SUVmax greater or equal to the median (1.7) had significantly worse survival than those with a SUVmax less than 1.7 (p = 0.048). The SUVmax was found to have a statistically significant correlation with the risk of tumor recurrence or (and) distant metastasis (p = 0.028). Conclusions: Our preliminary results indicate that 18F-FETNIM uptake of tumor tissue shows a strong trend to be a prognostic measure, and SUVmax could predict tumor recurrence or distant metastasis in NSCLC. No significant financial relationships to disclose.
Two years of tamoxifen followed by 3 years of anastrozole versus 5 years of tamoxifen alone in postmenopausal women with hormone-responsive early breast cancer: Efficacy results from 3,714 patients from the Austrian Breast and Colorectal Cancer Study Group (ABCSG) trial 8.
Authors: P. C. Dubsky, R. Jakesz, R. Greil, D. Heck, H. Stoeger, W. Kwasny, C. Menzel, C. F. Singer, M. Medl, M. Gnant
Journal: Journal of Clinical Oncology (2010)

534 Background: Anastrozole (ANA) alone delivers significant DFS benefits over tamoxifen (TAM) therapy in postmenopausal women with early ER+ breast cancer. Limited data have been published concerning the sequence strategy of TAM followed by letrozole vs. TAM alone. ABCSG trial 8 is the only clinical trial addressing a sequence strategy containing ANA in comparison to 5 years (y) of TAM. Methods: Postmenopausal patients with ER+ and/or PgR+ - and G1/2 tumors were eligible for this prospective randomized phase III trial. After surgery, patients were randomized to 5 y of TAM or 2 y of TAM followed by 3 y of ANA. Adjuvant chemotherapy, G3 - and T4 tumors were exclusion criteria. Intention to treat (ITT) and exploratory, censored analyses of primary endpoints DFS and OS were carried out. Censored analyses excluded events after cross over of 348 patients originally assigned to 5 years of TAM. Results: Information from 3,714 eligible patients with a median follow-up of 76.7 months (ITT) was available for this analysis. Patient characteristics were well balanced. Median age was 63.8 years, 75% were node negative, and 75% had T1 tumors. ITT analysis of DFS revealed a decrease of 326 to 299 events translating to a HR of 0.89 (95%CI 0.77-1.05; p = 0.17) in favor of ANA. The sequence strategy decreased deaths from 182 to 150 (HR:0.82; 95%CI 0.66-1.01; p = 0.06). Exploratory censored analyses of both primary endpoints carried out with respect to cross over, further decreased the respective HRs, suggesting significant effects on OS (HR:0.79; 95%CI 0.64-0.98) in favor of ANA. DFS and OS benefits from ANA were mainly driven by a subgroup of highly endocrine responsive patients. Treatment toxicity did not differ from previous reports concerning adverse event rates from ANA and TAM. Conclusions: Analytic bias of trial results stem mainly from selective cross over and extended adjuvant ANA therapy of patients. In this low to intermediate risk population treated without chemotherapy the adjuvant sequence strategy of TAM followed by ANA leads to moderate survival benefits over TAM alone. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
National Campaign for early diagnosis of retinoblastoma in Brazil
Authors: S. Epelman, C. Epelman, C. Erwenne, R. Melaragno, L. F. Teixeira, M. Adde, I. Magrath
Journal: Journal of Clinical Oncology (2004)

8561 Background: The incidence of retinoblastoma is higher in developing countries than in Europe and United States. In some developing countries, incidence rates per million may be two to six times higher or even more, since very little information is available from rural areas, where retinoblastoma appears to be particularly common. This tumor is characterized by a rapid growth rate. When the disease is detected at early stages and confined to the eye, children have a good prognosis. However, in children with disease that extents beyond the eye, specially to distant parts of the body, the five-year disease free survival is poor. The percentage of children with extraocular disease at diagnosis is much higher in developing countries (approximately 35 to 50%). Methods: The commonest early sign observed in children is leukocoria (cat's eye reflex). This easy sign to recognize offer a unique opportunity to call attention for retinoblastoma when it is still curable. Therefore a National Campaign for early diagnosis of Retinoblastoma in Brazil was initiated in September 2002 with the support of TUCCA (Children Brain Tumor Association) and INCTR(International Network for Cancer and Treatment Research). The campaign includes educational material for the population, for the primary health care workers and for ophtalmologists. A toll free number is available for information to the entire country. The video is on in different public channels in Brazil and was translated to 10 different languages. Results: More than 20 cases were already diagnosed through the campaign Conclusions: The initiative is cost effective. This experience can be a model to other coutries with similar problems. Routine dilated funduscopic examination is recommended. No significant financial relationships to disclose.