tbuckley/cabot-search huggingface dataset:
Impact of dose reductions of platinum compounds on survival in stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: P. F. Yumuk, M. Teomete, F. Dane, D. Cabuk, G. Basaran, N. S. Turhal
Journal: Journal of Clinical Oncology (2009)

e19055 Background: Platinum compounds are the main component of the CT in NSCLC. Standard recommended doses of cisplatin/carboplatin is usually couldn’t be administered and dose reductions are necessary because of side effects. We aimed to determine the effect of dose reductions of platinums on outcome of stage IIIB/IV NSCLC. Methods: Data of 420 patients were retrospectively reviewed. A platinum analogue was used in combination with vinorelbine, gemcitabine, paclitaxel, docetaxel or etoposide as first line treatment in 85% patients. Cumulative platinum doses and dose reduction ratios compared to standard doses were calculated. Patients with decreased GFR were excluded from the analysis. Results: Median age was 60 years (range: 28-87), 79% of patients were male, 31% were 65 yearsold/older, 55% had PS of 0, and 27% had stage IIIB disease. Histological subtypes were squamous cell in 32%, adenocarcinoma in 34%, and NSCLC in 31%. Median dose of cisplatin used per cycle was 67mg/m2 and carboplatin was 287mg/m2. 51% of the patients received standard or less than 10% reducted doses of platinum, while dose reductions were 10–20% in 19%, 21–30% in 24% of patients, and more than 31% in 6%. Median overall survival (OS) was 11 months, 1- year and 2-year OS ratios were 56% and 25%, respectively. Median time to progression was 5 months; 1-year progression free survival ratio was 18%. Gender, age, histologic subtype, and treatment with lower dose of platinum didn’t have any statistically significant impact on survival in univariate analysis. Patients with PS of 0, no weight loss, stage IIIB disease, receiving combination CT with docetaxel-cisplatin, and having partial response to treatment lived significantly longer. On multivariate analysis weight loss, stage and type of response to treatment had an impact on OS. Conclusions: Using lower doses of platinum compounds in combination chemotherapy for stage IIIB/IV non-small cell lung cancer might not have a negative impact on survival and definitely have a better toxicity profile. No significant financial relationships to disclose.
Immunohistochemical biomarkers in patients with early-onset breast carcinoma by tissue microarray
Authors: D. H. Choi, S. Kim, D. L. Rimm, D. Carter, B. G. Haffty
Journal: Journal of Clinical Oncology (2004)

9589 Background: Young women with breast cancer have a poor prognosis and the role of biologic markers in young women is not well defined. The purpose of the current study is to investigate estrogen receptor (ER), progesterone receptor (PR), bcl-2, HER-2/neu, p53, and Ki-67 for their relation with clinicopathologic features and outcome. Methods: A cohort of early-onset breast cancer patients ( 105 patients) treated with conservative surgery and radiotherapy were entered in this study. Age range was 25–45 and median follow-up was 8.7 years. Each of the paraffin-embedded specimens was immunologically stained for 6 biomarkers by recently developed tissue microarray method. Results: The 10 year overall, breast relapse free and distant relapse free survival rates were 82.7%, 83.4%, and 68.1%, respectively, with 13 local relapse and 26 distant metastasis. The expression of ER, PR, bcl-2, HER-2/neu, p53 and Ki-67 were 42.7%, 48.5%, 35.6%, 28.0%, 36.9%, and 39.7%, respectively. PR negativity (p<0.05), Ki-67 positivity (p<0.05), co-expression of HER-2, p53 (p<0.05), T-stage (p<0.05), and node status (p<0.001) were associated with distant relapse free survival rate. No parameters were associated with local control. Statistically significant correlation were not observed between 6 markers and T-stage, 6 markers, and lymph node status. Bcl-2 expression was well correlated with ER, PR, and HER-2/neu. Ki-67 was strongly associated with p53 (p=0.0003). Conclusions: PR, Ki-67, co-expression of HER-2/neu and p53,T-stage and node status were prognostic factors for distant failure in early stage, young patients with breast cancer. Further studies are needed to find other biologic markers related with local failure in these group of patients. No significant financial relationships to disclose.
Autoantibodies in early breast cancer
Authors: J. F. R. Robertson, C. Chapman, K.-L. Cheung, A. Murray, S. E. Pinder, M. R. Price, R. L. Graves
Journal: Journal of Clinical Oncology (2005)

549 Background: Immune responses to a number of tumour-associated antigens have been reported, although their suitability, individually, as diagnostic indicators has not been demonstrated. This study has taken a panel approach to demonstrate the diagnostic potential afforded by the detection of multiple auto-antibodies to known tumour-associated proteins. Methods: Auto-antibodies to MUC1, p53, c-myc and c-erbB2 were measured in serum, by ELISA, in five groups - normal controls (n = 100), primary breast cancer patients (PBC) (n = 200), patients with benign breast disease (n = 50), women deemed to be ‘at risk’ of breast cancer from whom serum samples had been taken at least 6 months prior to clinical diagnosis (n = 9) and patients with auto-immune disorders (n = 25). The value of adding other antigens eg BRCA1 and BRCA2 is currently being assessed. Results: Elevated levels of auto-antibodies were seen in 82% of PBC patients compared to normals. No significant differences were seen in overall detection when these patients were sub-divided either by detection methodology (screen-detected vs symptomatic presentation), lymph node status at diagnosis or menopausal status. Of those individuals with pre-diagnosis samples, 60% had elevated auto-antibodies: in this group, the lead-time for cancer detection with auto-antibodies, over clinical/ mammographic detection, ranged from 6 to 36 months. Conclusion: This study raises the possibility of using a combination of assays to detect auto-antibodies to cancer-associated antigens for screening and early diagnosis of breast cancer. While very interesting, these findings need to be confirmed in another group of patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OncImmune OncImmune OncImmune
Incidence of interval cancers of an annually screened population in a community cancer screening program: 17-year experience at Audrain Medical Center
Authors: S. Waheed, K. A. Wilson
Journal: Journal of Clinical Oncology (2004)

1036 Background: A community-based cancer screening program was started in 1985 in our institution to provide cancer screening, detection, education, and prevention. The program is supervised by a physician director with exams carried out by nurse practitioners and registered nurses. It is a multi-organ screening program which includes skin, breast, cervix, prostate, and colorectal. There is excellent participation by the community and a high rate of return. Meticulous record is kept of detected cancers and interval cancers, which are those diagnosed between annual screenings. Methods: Asymptomatic women age 35 and over, and men age 50 and over are enrolled. Women undergo physical exam that includes skin, breast, and pelvic exam in addition to mammogram and Pap test. Men receive physical exam including the skin and prostate. Both men and women receive digital rectal exam. During the past seventeen years, a total of 32,542 exams were performed. 4,760 women (88%) and 669 men (12%) were screened. Cancer detection is recorded by following all abnormal findings and outcomes. Interval cancer rates are discovered when the patient returns for subsequent screenings. Records are kept for breast, cervical, skin, prostate, and colorectal cancers. Results: Detected and interval rates for cancers screened are given below. Conclusion: Community screening programs are an excellent way to detect early cancers. The incidence of interval cancers are low and acceptable with annual screening for breast, cervix, colorectal, skin and prostate cancers. No significant financial relationships to disclose.
End-linked homodimers in fibrinogen Osaka VI with a Bβ-chain extension lead to fragile clot structure
Authors: Teruko Sugo, Chizuko Nakamikawa, Nobuhiko Yoshida, Kazuki Niwa, Masazumi Sameshima, Jun Mimuro, John W. Weisel, Akira Nagita, Michio Matsuda
Journal: Blood (2000)
Clinical experience of bendamustine treatment for non-Hodgkin lymphoma and chronic lymphocytic leukemia: Spanish Registry.
Authors: B. Sanchez-Gonzalez, F. Peñalver, H. Guillen, M. Calleja, R. de Ona, A. Canovas, M. Gironella, R. Arranz, J. Loscercales, I. de la Fuente
Journal: Journal of Clinical Oncology (2010)

e18526 Background: Bendamustine (B) is a purine analog/alkylator hybrid that has demonstrated clinical activity in relapsed indolent non-Hodgkin lymphoma (NHL), including those refractory to other alkylating or purine analog agents, chronic lymphocytic leukemia (CLL), and multiple myeloma patients. Methods: Retrospective analysis of efficacy and toxicity of B for NHL and CLL treatment in the setting of compassionate use in Spain. Patients with relapsed or refractory NHL or CLL after at least 1 prior treatment regimen were eligible. Any B regimen was included. Results: 91 patients (pts) from 18 institutions were included in the registry. The median age was 69 years (range: 36-88). Histology: 30 pts CLL; 16 pts aggressive NHL (13 mantle cell lymphoma and 3 diffuse large B-cell lymphoma); 45 pts indolent NHL (36 follicular lymphoma, 6 extranodal marginal zone B-cell lymphoma of MALT type and 3 lymphoplasmocytic lymphoma); Ann Arbor III-IV: 79% and IPI score >3: 48% in NHL, and Binnet B-C in CLL: 96%. Median time from diagnosis to B treatment was 4.6 years (range 1-19.2) and median prior treatment regimens was 3 (range 1-11). 31 pts were refractory to prior treatment. The most frequent used regimen was rituximab plus B (RB). 60% of pts had adverse events grade 3-4; hematologic toxicity was the most frequent adverse event (54% neutropenia, 33% leucopenia, 30% thrombocytopenia, and 20% anemia). 15% cycles of B required pts admission in hospital. Sixty-nine pts were assessable for response at the time of analysis. Response rate was: overall response 64% (73% indolent NHL, 36% CLL, 85% aggresive NHL). 22 pts died (7 infection, 11 progression, 2 infection plus progression, 1 infection plus respiratory insufficiency and 1 isquemia). Conclusions: The most common regimen was B at dose 90 mg/m2 associated with rituximab. Treatment with B produced a high response rate, independently of the histology in this population of heavily pretreated NHL and CLL pts, including refractory to prior therapies. Treatment with B produced durable objective responses with acceptable toxicity in this population NHL and CLL pts, including refractory to prior therapies. Updated data will be submitted at the Meeting. No significant financial relationships to disclose.
Description and prevalence of palliative care in patients: a prospective study in 14 Belgian hospitals
Authors: M Desmedt, Y De La Kethulle, Myriam Deveugele, Manu Keirse, Joannes Menten, D Paulus, Steven Simoens, Pieter Vanden Berghe, C Beguin
Journal: Annals of Oncology (2010)
Time-related predictors of suicide in major affective disorder
Authors: J Fawcett, W A Scheftner, L Fogg, D C Clark, M A Young, D Hedeker, R Gibbons
Journal: American Journal of Psychiatry (1990)

The authors studied 954 psychiatric patients with major affective disorders and found that nine clinical features were associated with suicide. Six of these--panic attacks, severe psychic anxiety, diminished concentration, global insomnia, moderate alcohol abuse, and severe loss of interest or pleasure (anhedonia)--were associated with suicide within 1 year, and three others--severe hopelessness, suicidal ideation, and history of previous suicide attempts--were associated with suicide occurring after 1 year. These findings draw attention to the importance of 1) standardized prospective data for studies of suicide, 2) assessment of short-term suicide risk factors, and 3) anxiety symptoms as modifiable suicide risk factors within a clinically relevant period.
Definitive chemoradiotherapy may be standard treatment options in clinical stage I esophageal cancer
Authors: T. Ura, K. Muro, Y. Shimada, K. Shirao, H. Igaki, Y. Tachimori, H. Kato, Y. Ito, A. Imai, Y. Kagami
Journal: Journal of Clinical Oncology (2004)

4017
Risk of cancer treatment-related osteoporosis and fractures among women with breast cancer receiving aromatase inhibitors
Authors: B. Mincey, M. Duh, S. Thomas, E. Moyneur, M. Marynchencko, S. Boyce, E. Perez
Journal: Journal of Clinical Oncology (2006)

557 Background: Aromatase inhibitors (AIs) are a novel hormonal therapy for breast cancer. However, AIs can cause bone loss by blocking estrogen production. This study aims to assess the association between AIs and treatment-related bone loss in a large managed care population of women with breast cancer. Methods: Using medical and pharmacy claims data from over 5 million beneficiaries between 01/01/1998 and 01/31/2005, we identified 12,368 patients with ≥ 2 breast cancer claims in a 6-month period, who also had no bone metastasis and no prior osteoporosis or fracture claims. Patients who received anti-estrogen therapy were also excluded to remove the protective confounding effects. 1,354 patients receiving an AI (anastrozole, exemestane, letrozole) were compared to 11,014 controls who did not receive an AI with respect to their risk of bone loss. The observation start date for the AI and control groups was defined as the service date of the first AI claim and breast cancer claim, respectively. The bone loss endpoints analyzed were osteoporosis (including osteopenia) and clinical fractures. Results: The univariate analysis found that the prevalence of osteoporosis was 8.7% in the AI group vs. 7.1% in the control group, resulting in a statistically significant relative risk of 1.3 (95% CI=1.1–1.6, p=0.01). The prevalence of bone fracture was also statistically significantly elevated in the AI group compared to the controls (13.5% vs. 10.3%) with a relative risk of 1.4 (95% CI=1.2–1.6, p=0.001). Multivariate Cox proportional hazards regressions showed that after adjusting for age and comorbidities, the risk of bone loss remained statistically significantly higher in the AI group than the non-AI group, with 27% (95% CI=4%-55%, p=0.02) and 21% (95% CI=3%-43%, p=0.02) increase in the risk of osteoporosis and fractures, respectively. Conclusions: This retrospective longitudinal analysis of a large cohort of breast cancer patients corroborates previous findings from smaller clinical trials and demonstrates that AI therapies carry an increased risk of bone loss. Monitoring and treatment management strategies to alleviate bone loss risk are warranted in women receiving AI for breast cancer. [Table: see text]
A phase II trial of gemcitabine and S-1 therapy in patients with resected pancreatic cancer: Japanese study group of adjuvant therapy for pancreatic cancer (JSAP-03).
Authors: Hiroshi Ishii, Hideki Ueno, Tomoo Kosuge, Yutaka Matsuyama, Akio Saiura, Rintaro Koga, Yoshihiro Sakamoto, Kazuaki Shimada, Akimasa Nakao, Ryuichiro Doi, Masao Tanaka
Journal: Journal of Clinical Oncology (2012)

e14506 Background: Gemcitabine plus S-1 (GS) for metastatic pancreatic cancer (PC) resulted in a high response rate of 44.4%. We have previously conducted a phase I trial of adjuvant GS in patients (pts) with resected PC, and determined a recommended dose of this regimen for the current trial. Methods: Eligibility criteria included macroscopically curative resection of invasive ductal PC and no earlier chemotherapy. The pts received gemcitabine (800 mg/m 2 /week) intravenously over 30 min on day 1 and S-1 (60 mg/m 2 /day) orally twice daily from days 1 to 7 every 14 days for 12 cycles. The primary endpoint was overall survival (OS). A total of 55 pts were required based on the assumption of an expected 2-year OS rate of 60% and the threshold rate of 40%, with an α-error of 5% (two-sided) and a β-error of 10%. Results: A total of 55 pts were enrolled between April 2008 and September 2009. The efficacy and toxicity of the treatment were analyzed in 54 pts who had received at least one course of GS therapy. Of the 54, 40 (74%) completed the scheduled 12 cycles, 9 discontinued adjuvant GS within 6 cycles, and the remaining 5 discontinued between 6 and 12 cycles. The reasons for discontinuation were disease progression in 6 and adverse events in the remaining 8. The most common adverse reaction was neutropenia (G3/4: 59.2%, G4: 25.9%). There were no G4 adverse events except neutropenia (1.9%) and hyperkalemia (1.9%). At the time of analysis (median follow-up: 25.4 months), 22 pts were alive without disease, 15 were alive with disease, and the remaining 17 pts were dead. Median OS was not yet reached. The estimated 1-year and 2-year OS rates were 88.9% and 72.1%, respectively. The estimated 1-year and 2-year disease-free survival rates were 57.4% and 44.4%, respectively. Among potential prognostic factors, male gender, head tumor of the pancreas, and the primary tumor smaller than 3 cm were associated with favorable prognosis in a proportional hazard model. Conclusions: Adjuvant GS therapy produced a good disease-free survival (DFS) and OS rates with an acceptable toxicity profile in pts with resected PC. A randomized phase III trial to confirm the efficacy of this regimen is ongoing (JSAP-04).
Imatinib as a possible therapy option for cervical carcinoma
Authors: S. Kuemmel, H. Heidecke, C. Denkert, P. Wimberger, A. Koeninger, J. Hecktor, K. Sabine, J. Blohmer, J. Sehouli, W. Lichtenegger, R. Kimmig
Journal: Journal of Clinical Oncology (2008)

16584 Background: In recent years considerable progress has been achieved in the treatment of cervical carcinoma by means of simultaneous platinous radiochemistry. Nonetheless, chemotherapeutic options are still lacking, above all for patients with relapse. Further, there are no data available that would allow an individualized therapy, adapted to the tumor biology. The goal of this Phase I study is to investigate alternative therapy possibilities to the common cytostatics for the treatment of cervical cancer, since patients suffering from this disease show considerable variability in their response to chemotherapy. Methods: A tumor chemosensitivity assay (TSA) was used to evaluate 8 substances with freshly isolated tumor cells of 23 patients [(carboplatin and cisplatin, topotecan, paclitaxel, as well as the two tyrosine kinase inhibitors imatinib and gefitinib and the two monoclonal antibodies cetuximab und trastuzumab)]. Results: The test was evaluable in 91% of the patients. 16 of the 22 tumor samples (72.7%) showed a sensitivity to imatinib. A sensitive response to therapy occurred already at an early stage (FIGO I, II). Also a sensitivity to Paclitaxel is given for 91.3%. An intra-individual comparison showed patient resistance in 90.9% of the cases for trastuzumab and 95% of the cases for carboplatin, in 90.9% for cisplatin, in 91.3% for cetuximab, and in 73.9% for topotecan and 95.6% for Gefitinib. Conclusions: Imatinib seems to be a therapy option for patients with cervical carcinoma, independent of the tumor sub-type. No significant financial relationships to disclose.
Effective treatment of 4T1 mammary adenocarcinoma by direct tumor injection and continuous systemic infusion of transferrin receptor antisense in mice
Authors: J. F. Head, X. Jiang, K. A. Fort, V. D. Dye, R. L. Elliott
Journal: Journal of Clinical Oncology (2007)

14113 Background: Transferrin receptors (TfR) on the cell surface are the major transporters of iron into cells. Tumor cells often have increased expression of TfR, compared to normal cells. TfR antibodies have been shown to inhibit the growth of tumor cells. We previously reported that human TfR antisense inhibited the proliferation of human breast cancer cell lines in vitro. Methods: In the present study, we used antisense oligonucleotides targeted to the mouse TfR gene to treat the 4T1 mammary adenocarcinoma mouse model. The antisense was either directly injected one time into the tumors or continuously infused systemically for 14 days through subcutaneous implantation of Alzet osmotic minipumps. The control group of mice received Hank’s balanced salt solution. Tumor sizes were measured twice a week. Tumor necrosis and metastasis were examined grossly at autopsy and by microscopy. Results: At 4, 7 and 10 days post- treatment, tumor volumes of treated groups, including direct injection and continuous infusion, were significantly smaller than the control group. At 14 days post-treatment, gross and microscopic pathology showed that the continuously systemically treated mice had significantly less lung metastases than the control group (p&lt;0.001 and p&lt;0.01, respectively). Although the group of mice treated with direct injection received an equal total dosage of TfR antisense as the continuously systemic treated mice, direct tumor injection of TfR antisense did not suppress lung metastasis. Primary tumors had varying degrees of necrosis in the treated and control groups, but there was no statistical difference between groups. Summary: TfR antisense effectively inhibited tumor growth and metastasis of 4T1 mammary adenocarcinoma in mice. Furthermore, continuously systemic administration of antisense was more effective than direct tumor injection. No significant financial relationships to disclose.
Contrast Enhanced Cardiac CT Detects Coronary Artery Disease In 44% Of Asymptomatic Long-Term Adult Allogeneic Stem Cell Transplant Survivors
Authors: Natasha A Jain, Marcus Y Chen, Sujata Shanbhag, Kit Lu, Priyanka A Pophali, Sawa Ito, Eleftheria K Koklanaris, Christopher S. Hourigan, A. John Barrett, Minoo Battiwalla
Journal: Blood (2013)
Reticulocytes can represent an early indicator of the erythropoietic response to Darbepoetin alfa in the anemia by chemotherapy
Authors: M. Bindi, P. Montemaggi, M. Sabatino, L. Paolelli, R. Petrioli, R. Morelli, D. Piazza§, A. Cigno, I. Carreca
Journal: Journal of Clinical Oncology (2004)

8245 Background: Darbepoetin is a new drug active in anemia from chemotherapy and 2-to 3- times longer serum half life then recombinant-human Epo (rHuEPO). Reticulocytes can constitute an useful parameter to check the medullar reserve and give an indication of the erythropoietic answer. Methods: 42 patients in chemotherapy were randomised in 3 groups: the first two reported severe asthenia and have been deal respective with (I) darbepoetin 2.25μg/kg once weekly or (II) rHuEPO 150 U/Kg three times weekly; the third group (III), used like control, did not report relevant asthenic symptoms. The study evaluated time zero, after 4 and 8 weeks hemoglobin, reticulocyte count,serum ferritin, transferrin and iron. Results: The group treated with darbepoetin reported an increase of Hb after 4 weeks of approximately 2 g/dl if the starting value were >10 g/dl (8pts), instead patients with values of Hb <10g/dl evidenced a lower improvement of Hb (approximately 1 g/dl after 8 weeks). In the same group 13/15 pts reported an important improvement of reticulocytes. The mean value increased from 12,3 to 30,4μl (range 19–66); five patients exceeded the 14,5 g/dl of Hb. Group treated with rHuEPO showed a lower increase of reticulocytes after 8 weeks, the mean value increase from 17,2 to 22,6μl (range 13 - 34). In the control group reticulocytes moved by 15,0 to 12,0μl (range 2–16) and hemoglobin value decreased during chemotherapy from 10,5 to 9,7 g/dl. Conclusions: We reported a significantly increase of reticulocytes after four and eight weeks in the group treated with darbepoetin, higher than the group with rHuEPO and much more than the control group. Therefore our study show that darbepoetin is the sooner effective drug in the improvement of anemia. We besides suggest that reticulocyte count is a very important parameter in the prediction of response to the erythropoietic agents. No significant financial relationships to disclose.