tbuckley/cabot-search huggingface dataset:
Early operable primary breast cancer in elderly (age 70 and older) women (EPC): Changing pattern of management and clinical outcome over 36 years.
Authors: S. J. Johnston, B. M. Syed, L. Winterbottom, H. Kennedy, D. A. Morgan, K. Cheung
Journal: Journal of Clinical Oncology (2010)

624 Background: Over the last few decades, there has been changing availability/application of various factors (e.g., estrogen receptor [ER], axillary status) and evolving evidence from clinical trials (e.g., surgery versus primary endocrine therapy [PET]) that might have affected the outcome of EPC. The Nottingham unit established a dedicated EPC service in 1973. We now report changes in management pattern and clinical outcome since its inception. Methods: Over 36 years, 1,698 EPCs were managed according to a single set of clinical guidelines at any time point. For comparison 3 eras were noted based on changes in guidelines: (A) 1973-1989, (B) 1990-1999 (routine availability of ER, increasing use of adjuvant systemic therapy), and (C) 2000-2009 (axillary staging and adjuvant systemic therapy became standard). Results: The results are summarized (Table) at a median follow-up of 50 months (maximum=261). Conclusions: The overall outcome across the eras appears very good and has been further improved with changing management practice. This suggests that EPC is less aggressive and further work is required to optimize management taking into account its biological behavior and other factors (e.g., comorbidities) that potentially impact overall survival in this population. A B C N 248 677 762 Treatment N (%) N (%) N (%) Surgery 128 (52.9) 260 (38.7) 443 (56.9) PET 106 (43.8) 405 (60.3) 319 (40.7) Primary radiotherapy (RT) 7 (2.9) 2 (0.3) 12 (1.5) Adjuvant endocrine therapy 1 (0.8) 121 (46.7) 246 (55.7) Adjuvant RT 3 (2.8) 10 (7.8) 154 (38.4) Outcome (% per annum) A B A+B C Local recurrence† 2.9 2.0 2.3* 0.5* Regional recurrence† 2.5 1.1 1.8* 0.4* Metastasis 3.1 2.8 2.9* 1.9* 5-year survival A B A+B C Breast cancer-specific survival 84% 79% 80%* 90%* Overall survival 67% 52% 56%* 68%* † Surgery group only. * Significant improvement (p<0.05), 2000-2009 vs. 1973-1999 (C vs. A+B). No significant financial relationships to disclose.
Human epididymis secretory protein 4 in serum (HE4) as a marker of ovarian cancer
Authors: K. Z. Qu, H. Li, R. Whitmire, A. Sferruzza, R. A. Bender
Journal: Journal of Clinical Oncology (2008)

16554 Background: CA125 is the most widely used biochemical marker for detection of ovarian cancer. However, it is also frequently elevated in women with commonly diagnosed benign disease. Recently, human epididymis secretory protein 4 (HE4) has been identified as being over-expressed in ovarian cancer and has been suggested as a serological marker of ovarian cancer. We evaluated the sensitivity of HE4, with or without CA125, for detection of ovarian cancer. Methods: Serum samples from 35 patients with ovarian cancer and 20 patients with benign pelvic mass (BPM) were tested for HE4 using analyte-specific reagents (Fujirebio Diagnostics, Inc. Malvern, PA), and for CA125 using the IMMULITE automated analyzer (DPC, Los Angeles, CA). Results above the 97th percentile (determined in 119 healthy adults) were considered positive: HE4 = 80 pmol/L; CA125 = 35 U/mL. Results: HE4 was elevated in 22/35 (63%) patients with ovarian cancer and 7/20 (35%) with BPM (see Table). CA125 was elevated in 18/35 (51%) ovarian cancer patients and in 5/20 (25%) BPM patients. The combination of CA125 and HE4 yielded the highest sensitivity, identifying 26/35 (74%) cases; however, this combination was also positive in 9 of the 20 (45%) BPM patients. Conclusions: In this small patient sample, HE4 had higher sensitivity than CA125 for detection of ovarian cancer. The combination of HE4 and CA125 yielded higher sensitivity than either marker alone, but the issue of specificity will require additional patient numbers to fully evaluate. CA125 and HE4 Results in Subjects with Ovarian Cancer or Benign Pelvic Mass Marker(s) Ovarian Cancer (n = 35) Benign Pelvic Mass (n = 20) CA125+/HE4+ 14 (40%) 3 (15%) CA125-/HE4+ 8 (23%) 4 (20%) CA125+/HE4- 4 (11%) 2 (10%) CA125-/HE4- 9 (26%) 11 (55%) No significant financial relationships to disclose.
Improved antitumor therapy by dual targeting of estrogen and growth factor receptor signaling in human breast cancer cells
Authors: R. J. Pietras, D. C. Marquez, H. Chen, M. X. Sliwkowski, D. J. Slamon
Journal: Journal of Clinical Oncology (2006)

637 Background: Breast cancer growth is tightly regulated by interactions between growth factor and estrogen receptors. Dimerization is crucial for activation of HER receptors (EGFR, HER2, HER3, HER4) that contribute to modulation of tumor progression and the failure of antiestrogen therapy. HER2 is the preferred dimerization partner in a process stimulated by the several HER receptor ligands. HER2 antibody (trastuzumab) shows antitumor efficacy in HER2-overexpressing cancers. New antibodies that disrupt HER2 dimerization (pertuzumab) may be useful in treating cancers with normal HER2 levels. Methods: Estrogen receptor (ER)-positive tumor cells with normal HER levels (MCF-7, ZR75), as well as cells engineered for HER2-overexpression (MCF-7/HER2, ZR75/HER2) or tamoxifen resistance (MCF-7/TAM), were grown in vitro and as xenografts in nude mice and treated with tamoxifen, fulvestrant (Faslodex), trastuzumab or pertuzumab, alone or combined. Effects of agents on phosphorylation of ER and coactivator AIB1, ER-dependent transcripts, p27 and VEGF secretion were assessed. Results: Growth of ER-positive tumors with low HER is reduced by tamoxifen and fulvestrant. In contrast, HER2-overexpressing tumors are tamoxifen-resistant but retain sensitivity to fulvestrant and show greater, synergistic antitumor effects with trastuzumab-fulvestrant combined. Similarly, non-HER2-overexpressing tumors with or without tamoxifen resistance are sensitive to fulvestrant, but fulvestrant-pertuzumab elicits more profound antitumor effects (P&lt;0.001). Enhanced inhibitory action of fulvestrant-pertuzumab is related, in part, to changes in phosphorylation of ER and AIB1, leading to blockade of ER-induced transcripts, as well as nuclear localization of p27, a CDK-inhibitor that downregulates cell proliferation. Further, enhanced tumor secretion of VEGF after estrogen and HER signaling is markedly reduced by fulvestrant-pertuzumab as compared with either agent alone (P&lt;0.001). Conclusions: Pertuzumab promotes antitumor efficacy of the pure antiestrogen, fulvestrant, and dual disruption of ER and HER signaling may be a new way to optimize hormonal therapy and overcome antiestrogen resistance. Supported by US Army BCRP and Stiles Program. [Table: see text]
Evaluation of the Treatment of Peritoneal Carcinomatosis of Colorectal Cancer (crc) With Complete Cytoreduction and Hyperthermic Intraperitoneal Peroperative Chemotherapy (hipec) With Oxaliplatin: a Belgian Multicentre Prospective Phase Ii Clinical
Authors: D. Hompes, A. D'Hoore, Emmanuel Van Cutsem, W. Ceelen, Marie-Rose Peeters, D. Van der Speeten, C. Bertrand, Joseph Kerger, H. Legendre
Journal: Annals of Oncology (2009)
Phase I study of the investigational drug MLN8237, an Aurora A kinase (AAK) inhibitor, in patients (pts) with solid tumors.
Authors: E. C. Dees, J. R. Infante, H. A. Burris, I. A. Astsaturov, T. Stinchcombe, H. Liu, K. Galvin, K. Venkatakrishnan, H. J. Fingert, R. B. Cohen
Journal: Journal of Clinical Oncology (2010)

3010
Phase I study of everolimus (E) plus low-dose weekly cisplatin (C) for patients with advanced solid tumors.
Authors: M. G. Fury, E. J. Sherman, N. Wu, S. Haque, D. M. Lisa, D. Carlson, D. G. Pfister
Journal: Journal of Clinical Oncology (2010)

e13013 Background: Preclinical studies demonstrate synergistic antitumor activity with the combination of E + C. Methods: Part A used a standard 3 + 3 dose escalation scheme. There were 4 planned dose levels (DLs) of E: 2.5, 5, 7.5, and 10 mg/day. Regimen was E per oral for days 1-21 and C 20 mg/m2 intravenously (fixed dose) on days 1, 8, and 15 of a 28-day cycle. For pharmacokinetics (PK), blood samples were collected on Day 1 and Day 8 of Cycle 1 in Part A. After the phase II-recommended dose was established (Part A), 6 additional subjects with easily accessible tumors for office biopsy were enrolled for pharmacodynamic correlates (Part B). Response was assessed by RECIST q 2 cycles for all subjects. Results: 30 patients enrolled (29 treated): 18 M, 12F; median age 62 (31-79); median number of prior cytotoxic chemotherapy regimens 1 (0-3; 80% with prior RT). DLTs were: DL1, 1 (sudden death of unclear cause in patient with melanoma metastatic to liver); DL2, 1 (bowel obstruction); DL3, 0; DL4, 0. Most common adverse events (≥ grade 3) among 29 patients evaluable for toxicity: lymphopenia (33%), hypophosphatemia (13%), hemoglobin (10%), and hyperglycemia (11%). PK analysis of E demonstrated dose proportional increases in Cmax (mean 91.9 ng/ml at DL4) and AUC0-INF(mean 680.4 hr*ng/ml at DL4). Two objective responses were seen (CR, metastatic pulmonary carcinoid; PR, metastatic sinus carcinoma). Prolonged SD ≥ 6 cycles occurred in 2 pulmonary carcinoid subjects, and in oropharyngeal SCC, basal cell carcinoma, and esthesioneuroblastoma (n=1 each). In Part B, pretreatment and on-treatment biopsies (Day 20) obtained in the oropharynx SCC subject showed no significant changes in expression of p-AKT, p21, or p53 as assessed by immunohistochemistry. Conclusions: The phase II recommended dose is E 10 mg/day (days 1 - 21) + C 20 mg/m2 (days 1, 8, and 15) on a 28-day cycle. PK data demonstrate dose-proportional increases in exposure, as previously described for E monotherapy. Antitumor activity was observed in several tumor types, including metastatic sinus carcinoma that had been previously treated with C. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Thyroid dysfunction in patients (pts) with metastatic renal cell cancer (RCC) treated with sorafenib
Authors: P. Clement, P. Wolter, C. Stefan, B. Decallonne, H. Dumez, H. Wildiers, P. Schöffski
Journal: Journal of Clinical Oncology (2008)

16145 Background: Sorafenib is an oral multi-target tyrosine kinase inhibitor (TKI) approved for the treatment of metastatic RCC. A high incidence of thyroid dysfunction has been observed with sunitinib, another TKI with overlapping mechanism of action. We evaluated prospectively the incidence and severity of thyroid function abnormalities in pts with metastatic RCC treated with sorafenib. Methods: A total of 46 patients received sorafenib for metastatic RCC and 38 patients were eligible for our single-centre prospective observational study. Sorafenib was administered continuously at a dose of 400 mg orally twice daily. Thyroid function (TSH, free thyroxine index) was assessed at baseline and on day 1 of each treatment cycle. Results: Of the 23 patients with normal baseline thyroid function, 7 patients (30%) developed at least one elevated serum TSH and one patient (5%) developed low TSH without requiring therapy. Fifteen patients (65%) did not develop any TFT abnormality. In the group of 15 pts with thyroid dysfunction at baseline or previous treatment potentially interfering with thyroid function 2 pts with baseline subclinical hypothyroidism developed clinical hypothyroidism during sorafenib treatment requiring hormone replacement. Two other pts developed drug-induced thyroiditis under sorafenib, however following radiotherapy of the cervical spine due to bone metastasis. In one patient under substitution therapy no change in substitution dose was needed during the course of sorafenib treatment. In seven patients with prior sunitinib treatment only one patient developed at least one elevated serum TSH, however not requiring therapeutic intervention. Conclusions: Sorafenib induces thyroid dysfunction and the risk seems to be higher in patients with pre-existing thyroid function test abnormalities and/or radiotherapy to the neck. In our hands the incidence of thyroid dysfunction is lower than with sunitinib, nevertheless pts with underlying thyroid disease may develop overt hypo- or hyperthyroidism requiring treatment. Therefore screening of thyroid function is also warranted in pts treated with sorafenib, at baseline and repeatedly during the treatment, especially in those with underlying thyroid disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Pfizer Bayer, Pfizer Bayer, Pfizer
Tamoxifen: Too Much of a Good Thing?
Authors: V. Craig Jordan
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.9.2629 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561334 Tamoxifen: Too Much of a Good Thing? V. Craig JordanxV. Craig JordanSearch for articles by this author Show More Robert H. Lurie Comprehensive Cancer Center, Chicago, IL https://doi.org/10.1200/JCO.1999.17.9.2629 Full Text PDF Figures and Tables "Tamoxifen: Too Much of a Good Thing?." Journal of Clinical Oncology, 17(9), p. 2629© 1999 by American Society of Clinical Oncology
99 mTc-MIBI breast scintigraphy (Sc): An image method to predict response to neoadjuvant chemotherapy (NCT) in locally advanced breast cancer (BC) patients (pts)
Authors: M. T. Laloni, F. Moura Silva, C. Tosello, A. P. A. P. Bertozzi, M. T. de Arruda, P. V. Valente, C. M. B. L. Pereira, A. H. R. Garcia, M. G. M. Tavares, P. R. W. Vernaglia, J. C. S. Goes
Journal: Journal of Clinical Oncology (2005)

821 Background: As previously described by the literature, high expression of P-Glycoprotein (P-gp) in BC cells and resistance to chemotherapy have been related. Sc has been described as an image method to evaluate P-gp “in vivo”, since its radioligant is cleared by the same plasmatic membrane system. As a consequence we would have a promising image method to predict responses to NCT in locally advanced BC pts. Methods: Sc was performed in 31 pts enrolled with locally advanced BC before they started NCT. Images of the tumor ratio of 99 mTc-MIBI uptake at 10 minutes (m) (T early) and 240 m (T delay) were obtained. Fast wash-out was defined by a higher than 45% decrease in the difference uptake of T early and T delay. P-gp expression was obtained by IHC and graduated from 0 to 4. All pts received four cycles of NCT with FEC 75. Tumor measurements were obtained by physical exam and digital photography before the first and after the fourth cycle. Clinical response (CR) was defined as positive - tumor response higher than 50% and negative - lower than 50%. Statistical analysis were performed using the SSPS version 11. In this prospective study all pts signed inform consent. Results: Pts median age was 52.7 years old (ranging from 37 to 75). Left BC and right BC were verified in 68% and 32% of the pts respectively. ER, PR and Cerb-B2 positive were noted in 71%, 78% and 19% respectively. Our results have not demonstrated statistical correlation between Sc and P-gp. However, we could observe a statistical significance between Sc and CR (Fisher exact Test 0.046; Spearman’s rho 0.078). Furthermore, the predictive negative value, sensitivity and specificity were 80%, 73% and 66.6% respectively. This method has related with no toxicities or complications in our population. Conclusions: These data show that Sc could predict response to NCT in locally advanced BC pts submitted to FEC 75 regimen. Furthermore, Sc has demonstrated a safe profile and it did not cause delay in the first cycle of NCT. Our results, however, could not demonstrate correlation between Sc and P-gp. Larger studies are desirable in order to confirm our Results: It is our preliminary data and a larger study has been held in our institution. No significant financial relationships to disclose.
Outcome of advanced gastric cancer patients with disseminated intravascular coagulation and bone marrow metastasis is improved by weekly 24-Hour infusional high-dose 5-fluorouracil and leucovorin (HDFL)-based chemotherapy
Authors: T. Huang, C. Hsu, A. Cheng, K. Yeh
Journal: Journal of Clinical Oncology (2006)

14132 Background: Advanced gastric cancer (AGC) patients manifesting with acute disseminated intravascular coagulation (DIC) and diffuse bone marrow metastasis have inevitably led a fatal outcome within a median of 2–4 weeks. We previously reported that weekly 24-hour infusional high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (HDFL: 5-FU of 2,000–2,600 mg/m 2 /wk and LV 300 mg/m 2 /wk) chemotherapy with negligible myelosuppression has been successfully used in the treatment of these patients (Yeh KH &amp; Cheng AL, Br J Haematol 1998;100:769–72). The study planned to determine the treatment outcome in a larger group of this disease entity being treated with HDFL-based chemotherapy. Methods: This is a retrospective study. Bone marrow study is routinely done for gastric cancer patients with DIC in our institute. We searched for gastric cancer patients with DIC or bone marrow metastasis from 1994 to 2005. Results: A total of 21 AGC patients (M: 13, F: 8) who had unequivocal evidence of DIC or biopsy-proven bone marrow metastasis have been diagnosed at National Taiwan University Hospital between 1994 and 2005. At initial presentations, 18 patients had evident laboratory findings of DIC. Nine of them had symptomatic DIC and 8 patients had significant thrombocytopenia (&lt; 50,000/mm 3 ). All patients received HDFL-based chemotherapy as the initial treatment. Seventeen of them showed significant improvement in both clinical symptoms and laboratory abnormalities of DIC. The median overall survival (OS) of the whole group of patients since the diagnosis of DIC or bone marrow metastasis was 7 months (range: 1 week–3 years). Conclusions: Manifestations with acute DIC and bone marrow metastasis in AGC patients constitute a rare disease entity with a grave prognosis. Before introduction of HDFL for the treatment of AGC at our institute, this group of patients was extremely difficult to treat, and usually died within 2–4 weeks. Current analysis revealed that OS of this group of patients has been improved up to a median of 7 months, suggesting a significant improvement in the treatment outcome. No significant financial relationships to disclose.
Procalcitonin (PCT) as a diagnostic and prognostic marker in patients with solid tumors and febrile neutropenia
Authors: A. Jimeno, A. García-Velasco, O. Del Val, E. González-Billalabeitia, S. Hernando, R. Hernández, A. Sánchez-Muñoz, A. López-Martín, H. Cortés-Funes, L. Paz-Ares
Journal: Journal of Clinical Oncology (2004)

8037 Background: Cancer patients with febrile neutropenia (FN) are currently assessed on clinical grounds only. Procalcitonin (PCT) is a pro-hormone that demonstrated significant sensitivity and specificity as a marker of severe infection in patients with hematologic malignancies and FN. This study prospectively evaluated the efficacy of baseline PCT in the detection of bacteremia and in the prediction of outcome in patients with solid tumors and FN. Methods: PCT was determined at baseline and every 48 hours in 104 patients undergoing chemotherapy that developed fever and grade 4 neutropenia. Results: Median baseline PCT values were significantly higher in patients with microbiologically documented infections (MDI) compared with patients with clinically documented infections (CDI) or fever of unknown origin (FUO) (1.30 vs. 0.24 vs. 0.21 ng/mL, P <.01). Accordingly, a cut-off value of PCT of 0.5 ng/mL was more frequently reached in patients with MDI than in those with CDI or FUO (68.7% vs. 12.5%, P <.001). Furthermore, this threshold was also associated with an increased likelihood of treatment failure (70.0% vs 14.9%, P <.001). All four septic patients and all five patients that ultimately died presented baseline PCT values 5 to 10-fold over the median. An increment of at least 50% from baseline PCT values was observed in 45.5%, 19.0% and 12.0% of patients with MDI, CDI, and FUO (P = .034). Also, an increment of at least 50% from baseline PCT values was observed in 71.4%, 18.2% and 12.5% of patients experiencing treatment failure, success with modifications, and success without modifications (P < .001). Baseline PCT had an equivalent sensitivity and specificity in the detection of severe infection and treatment failure than standard clinical risk scales. Clinical evaluation in combination with baseline PCT appeared to improve clinical risk evaluation alone. Conclusions: Baseline PCT is higher in febrile neutropenic patients with bacteremia compared with those with a CDI or FUO. PCT identifies patients with microbiological infections and those at higher risk of treatment failure, and may constitute a complementary tool in their initial assessment. No significant financial relationships to disclose.
End-of-life quality-of-care indicators for medical oncology patients at a VA medical center
Authors: V. T. Chang, M. U. Bhatty, D. Hoover, M. A. Sikder, S. Gounder, M. L. Gonzalez, M. McPherson, F. Zhong, N. T. Nazha, B. S. Kasimis
Journal: Journal of Clinical Oncology (2008)

20580 Background: To assess quality indicators of end of life cancer care for patients(pts) at a VA medical center. Methods: In an IRB approved protocol, charts of pts followed by the Hematology/Oncology Service who died in the calendar years 2003 through 2006, were reviewed with criteria proposed by Earle et al (Int J Qual Health Care 2005;17:505). Results: There were 264 pts, with lung 99(37%) and prostate 40(15.2%) as the most common sites with a median (m) age 68 yrs. Patients (pts) were Caucasian 144(55.6%), African American 109(42.1%) (see Table). Pts were referred to hospice a median of 6(range 1–483) days before death, and 8(3.4%)pts were admitted to hospice within 3 days of death. Hospice services were given to 127(49.4%) medications for pain and symptoms were written for 245(95.0%), psychological support extended to 160(63.8%) and 242(93.1%) had shared decision making. Pts were made DNR a m 18.5(range 1- 1705) days before death and 41(16.0%) made a DNR within 1 week of death. Conclusion: These data may help provide a basis for future studies within the VA on end of life quality of cancer care. VA EOL Quality of Care Indicators Performance Indicator VA NJHCS Benchmark Proportion receiving chemotherapy in the last 14 days 7% <10% Proportion starting a new chemotherapy regimen in the last 30 days 5% <20% Proportion with multiple hospitalizations or ER visits in the last month 14% <4% Admission to ICU in the last month 18% <4% Death in an acute care institution 34% <17% Lack of admission to hospice 51% <45% Admission to hospice less than 3 days before death 3% <8% No significant financial relationships to disclose.