tbuckley/cabot-search huggingface dataset:
Phase II study of genexol (paclitaxel) and carboplatin as first-line treatment of advanced or metastatic non-small-cell lung cancer (NSCLC)
Authors: C. Kim, S. Bae, N. Lee, K. Lee, S. Park, D. Kim, J. Won, D. Hong, H. Park
Journal: Journal of Clinical Oncology (2006)

17049 Background: Genexol is a polymeric micelle loaded paclitaxel without Cremophor EL (CrEL). CrEL has been shown to cause hypersentivity reaction and neuropathy. To evaluate and efficacy, we conducted a phase II study of CrEL-free paclitaxel (genexol) and carboplatin in patients (pts) of advanced or metastatic NSCLC. Methods: Eligibility criteria included: stage IIIB or IV NSCLC without previous chemotherapy and radiotherapy; written informed consent; measurable lesion; age 18–75; ECOG PS 0–3; adequate bone marrow, liver, and renal function; and no CNS disease. The patients received genexol 225 mg/m 2 IV on day 1, followed by carboplatin AUC = 6 IV on day 1 every 3 weeks. Primary end points are response and toxicity. Response evaluations were performed after cycles 2, 4, and 6 of chemotherapy according to the RECIST criteria. Results: 36 pts were enrolled between November 2002 and November 2005. Pts characteristics: median age 63 years (range 45–73), median ECOG PS 1 (range 0–3), 13 stage IIIB and 23 IV, 21 adenocarcinoma and 14 squamous cell carcinoma, and 1 large cell carcinoma. At present, 30 pts were evaluable for response and toxicity. Meidan number of treatment cycles was 4 (range 1–6). Seven pts needed dose reduction. Thirteen pts achieved partial response and 13 pts had stable disease. The response rate 43.3%. Grade (gr) 4 neutropenia occurred in 11 pts (36.7%). Gr 1/2 sensory neuropathy occurred in 13 pts (43.3%) and gr 3/4 sensory neuropathy occurred in 5 pts (50%) among 10 pts over 65 year old. Other toxicities included neutropenic fever in 9 pts (30%), gr 4 thrombocytopenia 3 patients (10%), gr 2 hepatic dysfunction 3%, and gr 3 fatigue 10%. Treatment related mortality was not occurred. Complete analysis will be presented. Conclusions: In this trial, the combination of genexol and carboplatin showed a significant activity with acceptable and manageable toxicities as first line treatment for patients with advanced or metastatic NSCLC and dose reduction needed in older patients. No significant financial relationships to disclose.
Localized Colon Cancer, Version 3.2013
Authors: Al B. Benson, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Marwan G. Fakih, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Ahmed Kamel, Lucille A. Leong, Edward Lin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small, Constantinos T. Sofocleous, Alan P. Venook, Christopher G. Willett, Kristina M. Gregory, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2013)

The NCCN Clinical Practice Guidelines in Oncology for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions regarding the treatment of localized disease for the 2013 update of the guidelines.
Abstract 16821: Impact of Patient Transfers on Outcome Evaluations Following Acute Myocardial Infarction
Authors: Melissa Pak, Mona Izadnegahdar, May K Lee, Min Gao, Karin H Humphries
Journal: Circulation (2014)

Introduction: Patients hospitalized for an AMI are commonly transferred to tertiary care facilities to receive advanced procedures. In the United States, transferred patients are often excluded from outcome evaluations due to limitations in ascertaining outcomes. In Canada, centralized administrative and clinical databases allow for linkage of outcomes across institutions. This study evaluated the influence of excluding transferred AMI patients on estimates of age and sex-specific 30-day mortality rates over a 10-year period. Methods: All incident AMI hospitalizations (ICD-9: 410 and ICD-10: I21, I22) to acute care hospitals in British Columbia from 2000 to 2009 were identified through the Discharge Abstract Database and linked to mortality through the Vital Statistics registry. A transfer was identified as a discharge from the index AMI admission hospital to another hospital. Thirty-day mortality was defined as any death within 30 days of the index hospitalization. A logistic regression model was used to compare transfer rate by age (20-55, 56-64, 65-74 and ≥ 75 years), sex and admission year. Thirty-day mortality rates by sex and age were calculated with and without transferred patients. Results: Of the 67,444 AMI hospitalizations identified, 38.6% involved at least one transfer. Overall, younger patients were more likely to be transferred. Transfer rates increased over time in all age groups but with different slopes (p = 0.02) regardless of sex, and differed significantly between sexes only in those ≥ 75 (p &lt; 0.001; Fig. A). Thirty-day mortality rates were overestimated in each age-sex category when transferred patients were excluded, compared to rates that included all patients, irrespective of transfer status (Fig. B). Conclusions: The rate of patient transfers post AMI has increased over time. Excluding transferred patients results in overestimates of 30-day mortality, and thus impacts outcome assessments. This impact is expected to increase over time.
Imaging capillary tumor-cell migration, deformation and extravasation in live mice
Authors: R. M. Hoffman, K. Yamauchi, N. Yamamoto, M. Yang, P. Jiang, M. Xu, H. Tsuchiya, K. Tomita, A. R. Moossa
Journal: Journal of Clinical Oncology (2005)

6628 Background: The mechanism of cancer cell migration and extravation in narrow vessels is incompletely understood. Methods: In order to visualize cytoplasmic and nuclear dynamics of cells migrating in capillaries, red fluorescent protein (RFP) was expressed in the cytoplasm, and green fluorescent protein (GFP), linked to histone H2B, was expressed in the nucleus of cancer cells. Immediately after the cells were injected in the heart of nude mice, a skin-flap on the abdomen was made and spread on a flat stand. We could observe highly elongated cancer cells in capillaries in the skin-flap in living mice with a color CCD camera. Results: The migration velocities of the cancer cells in the capillaries were measured by capturing images of the dual-color fluorescent cells over time. The cells in the capillaries elongated to fit the width of these vessels. The average length of the major axis of the cancer cells in the capillaries increased to 3.97 times their normal length. The nuclei increased their length 1.64 times in the capillaries. Cancer cells that were arrested in capillaries over 8 μm in diameter could migrate up to 48.3 μm/hr. The data suggest that the minimum diameter of capillaries where cancer cells are able to migrate is approximately 8 μm. Extravasation was found to be infrequent in the HT1080 cells which were visualized by dual-color imaging to be frequently undergoing apoptosis. Mouse mammary tumor cells, in contrast, frequently extravasated beginning approximately 18 hours after cell injection. The cytoplasm of the MMT cells exited the vessels first and subsequently the whole cancer cell extravasated. Conclusions: The use of the dual-color cancer cells differentially-labeled in the cytoplasm and nucleus and associated fluorescent imaging provide a powerful tool to understand the mechanism of cancer cell migration and deformation in small vessels and extravasation. No significant financial relationships to disclose.
Sequential high-dose chemotherapy with autologous stem cell rescue for children with high-risk medulloblastoma and supratentorial primitive neuroectodermal tumours
Authors: C. Dufour, V. Minard-Colin, J. Grill, E. Benhamou, G. Goma, O. Hartmann, C. Kalifa, D. Valteau-Couanet
Journal: Journal of Clinical Oncology (2008)

10019 Background: Prognosis of high-risk meduloblastoma (HR MB) and supratentorial primitive neuroectodermal brain tumours (sPNET) is poor. In an attempt to improve outcome, we have developed strategies based on sequential high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) and radiotherapy for thirteen years. Patients and methods: Seventy-nine children (median age, 3.95 years) were treated with HDC/ASCT (59 HR MB; 20 sPNET). All patients received induction chemotherapy with one or two cycles of carboplatin-etoposide. Treatment strategy was modified with time and according to the age. Eighteen children were treated by two courses of high dose melphalan (100mg/m2) and one course of busulfan thiotepa combination (regimen 1). Two myeloablative courses of melphalan (100mg/m2) with ASCT were performed in twenty-one children (regimen 2). Nine patients were planned to receive two courses of high dose thiotepa (600mg/m2;) with ASCT (regimen 3). Thirty-one children received five sequential courses of chemotherapy followed by ASCT : melphalan (100 mg/m2) at day 43, cisplatin (100 mg/m2) at day 64, melphalan at day 85, cisplatin at day 106 and thiotepa (720 mg/m2) at day 127 (regimen 4). Treatment was completed by age-adapted craniospinal irradiation plus local boost in HR MB and age-adapted local irradiation only in sPNET. Results: Two hundred forty two cycles of high-dose chemotherapy with stem cell rescue were administered. At the end of chemotherapy, 6 pts were in CR in regimen 1, 8 CR in regimen 2, 3 CR in regimen 3 and 14 CR in regimen 4. The visceral toxicity of the regimen 1 was unacceptable with 3 toxic deaths secondary to multiorgan failure and 7 hepatic veno-occlusive disease. The toxicity was manageable in regimen 2, 3 and 4. Conclusion: Sequential high-dose chemotherapy improves survival rates in patients with HR MB and sPNET. This approach can be used to alleviate the use of craniospinal radiotherapy particularly in young children. No significant financial relationships to disclose.
Osteosarcoma in pediatric and young adult patients: The Singapore experience
Authors: L. Aung, Y. H. Chan, A. M. Tan, P. S. Wong, R. W. Pho
Journal: Journal of Clinical Oncology (2009)

e21522 Background: There is limited information on treatment and survival regarding these tumors in the South East Asia region. We thus attempted to investigate the incidence, the treatment modalities used and the outcome of OS patients treated at the two major pediatric oncology hospitals in Singapore. Methods: A comprehensive list of patients with OS treated at the Department of Pediatrics National University Hospital and KK Women's and Children's Hospital, Singapore between April 1980 and May 2006 was generated. During the study interval, patients received neoadjuvant chemotherapy followed by definitive surgery consisting of either limb-salvage or amputation followed by adjuvant chemotherapy. Chemotherapy included combination of cisplatin and doxorubicin as per the European Osteosarcoma InterGroup (EOI) and as per the Memorial Sloan-Kettering Cancer Center's (MSKCC) T12 protocols. Treatment of subsequent relapses consisted of various combinations of methotrexate, ifosfamide, etoposide, other, and/or surgery. Results: Of the total 49 patients with OS, 14 (29%) patients presented with metastatic OS (lungs, n=13; skip lesion, n=1). The median age of diagnosis of OS was 12.4 (range, 6.6 - 17.9 years). Mean survival after diagnosis of OS was 13.4 years (95% CI, 9.1 - 17.8 years). The two and five-year overall survival were 56.4 % ± 86.9 % (se) and 37.5 % ± 73.9 % (se) respectively for the entire cohort. The two and five-year overall survival were 77.9 % ± 100 % (se) for patients who were treated as per the MSKCC T12 protocols. The two and five-year overall survival were 51.8 % ± 86.2 % (se) and 33.8 % ± 72.6 % respectively for patients who were treated as per the EOI regimen. Conclusions: Survival from OS in Singapore appears to be improving since the multi-drug combination chemotherapy was introduced in 2002. The rarity and complexity of OS makes it crucial for patients diagnosed with this tumor to seek a centralized multi-disciplinary Musculoskeletal Oncology team. No significant financial relationships to disclose.
AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases: Preliminary phase 1 results
Authors: E. Martinelli, C. H. Takimoto, A. T. van Oosterom, J. Tabernero, E. Rowinsky, P. Schöffski, J. Huang, E. Casado, A. Mita, H. Dumez
Journal: Journal of Clinical Oncology (2005)

3039 Background: AEE788 is an oral inhibitor with potent activity against multiple tyrosine kinases including EGFR, HER2, and VEGFR2. This phase 1 study was to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), MTD/DLT dose levels, and optimal biologic dose of AEE788. Methods: Patients (pts) with advanced solid tumors were enrolled. Doses were escalated in a standard Phase I design with 3–6 pts/cohort. Safety monitoring included extensive cardiac assessments. All but 1 pt were naïve to EGFR and VEGF inhibitory therapy. Pharmacodynamic markers were analyzed in pre- and post-treatment skin and tumor biopsies. A 24-hr PK profile was obtained on days 1, 15, and 28, with trough sampling on days 8 and 22. Each cycle (cyc) is 28 days. Results: To date, 69 pts, median age 55 years (range 20–78), have been treated with once daily AEE788 at doses of 25 (5), 50 (6), 100 (5), 150 (5), 225 (6), 300 (8), 400 (14), 450 (5), 500 (6), and 550 mg (9) per day. Tumor types treated were breast (10), colon (9), medullary thyroid (7), head and neck (6), melanoma (4), NSCLC (4), RCC (3), angiosarcoma (3) and other tumor types (23). Two pts had DLT (grade ([gr] 3 diarrhea) at both 500 and 550 mg. The most common adverse events (> 20%) were diarrhea (67%), fatigue/asthenia (51%), anorexia (49%), rash (43%), nausea (42%), and vomiting (28%). Most AEs were mild to moderate. Six pts had gr 3 LFT elevation. LFTs of one pt remained normal when rechallenged at a lower dose. Three pts (2 at 500 mg and 1 at 550 mg) withdrew in < 1 cyc due to AEs. There was no QTcF > 500 ms with no change of QTcF ≥ 60 ms in over 1980 post-treatment ECGs. Serum concentrations of parent (AEE788) and active metabolite (AQM674) increase with dose and dose duration. Exposure of AEE788 increases overproportionately with increased dose while AQM674 exposure increases proportionally. The metabolite/parent ratio (range 0.2 to 2) appears to decline with dose and duration to an average of 0.3–0.4 at steady state (by day 15). 1 pt with angiosarcoma at 400 mg achieved a partial response. 28 pts had stable disease in 2 cycs (range 2–10). The median number of cyc of AEE788 was 2 (range <1–10). Conclusions: AEE788 is well tolerated. DLT dose levels were defined at 500 and 550 mg. Enrollment continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Aventis, Bristol-Myers Squibb, Lilly, Merck KgaA, Novartis, Pfizer, Pharma Mar, Roche Novartis Aventis, Novartis, Pfizer, Roche ILEX Oncology, Novartis
A common sense approach to radiation treatment planning of temporal lobe GBM
Authors: F. Bokstein, F. Kovner, Z. Ram, H. Templehoff, A. A. Kanner, D. T. Blumenthal, B. Corn
Journal: Journal of Clinical Oncology (2007)

2044 Background: Irradiation remains the cornerstone of management for glioblastoma multiforme (GBM). Guidelines adopted by the RTOG and EORTC advocate encompassing the primary tumor (sometimes with edema), and a 2 cm margin in the high dose volume. These recommendations have emerged from imaging studies and post-mortem analyses. A shortcoming of this approach is the exposure of critical structures (e.g. optic apparatus) to doses of radiation that may exceed organ tolerance. We sought to determine whether the temporal bone (rather than the aforementioned 2 cm radius) serves as a barrier to tumor spread when regarded as the anterior margin for temporal lobe lesions. We hypothesized that toxicity could be reduced without compromising tumor control. Methods: During the period 2003–2006, 250 patients with GBM were treated with surgery and primary irradiation at our institution. Chemotherapy (e.g., Stupp regimen) was given to approximately one-third of patients. 31 patients had lesions confined to the temporal lobe. All patients had MRI at baseline and at monthly intervals following a course of 60 Gy delivered by conformal techniques. The Clinical Target Volume included the primary lesion, the edema when present and a 2 cm margin except in the direction of the temporal bone. At follow-up (median = 10 months), patients were judged to have stable disease, local progression (i.e. failure within the temporal lobe), distant progression (i.e., brain failure beyond the temporal lobe) or combinations of the latter 2. Results: 11 patients have remained with stable disease. 17 have failed locally. 3 have manifested distant failure. Of the latter, only one patient failed in the infratemporal fossa. Conclusions: An acceptable level of recurrence (e.g., &lt;5% beyond the temporal bone) is seen when the temporal bone, rather than a 2 cm margin is employed as the anterior border of the CTV. As GBM patients live longer in the era of combined modality therapy, a greater opportunity will exist to express radiation damage. The strategy proposed herein provides tumor control while respecting optic tolerance without resorting to complex, expensive approaches such as IMRT. No significant financial relationships to disclose.
TPF induction chemotherapy followed by concurrent radiochemotherapy in the first line therapy of advanced carcinomas of the larynx and pharynx (phase IIb trial)
Authors: R. Knecht, M. Baghi, M. Hambek, N. Zamboglou, H. Tesch
Journal: Journal of Clinical Oncology (2006)

5562 Backround: Concurrent radiochemotherapy has become a standard procedure for the organ preservation treatment of advanced laryngeal cancer. According to the RTOG 91–11 protocol 2 years larynx preservation and disease free survival rates of 88% and 61% have been described (N Engl J Med 2003;349:2091–8). We perform a phase IIb study answering the question if the addition of triple induction therapy with docetaxel, cisplation and 5FU (TPF) to this regimen is feasible and able to enhance larynx preservation and the disease free survival. Methods: Eligibility criteria have been untreated measurable (RECIST) Stage III/IV carcinomas of the larynx and pharynx in ECOG 0–2 pts. with sufficient organ functions. Planned treatment consisted of 3 cycles induction chemotherapy (every 3 weeks) with docetaxel 75 mg/m 2 /d1, cisplatin 100 mg/m 2 /d1 and 5 Fluorouracil 1000 mg/m 2 /d1–4 (TPF) followed by concurrent radiochemotherapy according to the RTOG 91–11 protocol. Controls have been treated with concurrent radiochemotherapy (RTOG 91–11). One stage design, primary endpoint is recurrence free survival, planned sample size is 250 with 192 events to have a power of 80% to detect a relative risk = 1,432 using a one sided test, alfa = 0.05. Results: 103 patients have been evaluated up to know. Completion of therapy was equivalent in both groups (1/5 drop out rate). Main grade 3/4 toxicities (CTC) during induction chemotherapy were neutropenia (95%) and renal toxicity (25%) and during chemoradiation mucositis (40%) in the chemoradiation group and mucositis (43%), neutropenia (46%) and renal toxicties (24%) in the induction chemotherapy group The toxicities were reversible. After induction chemotherapy the ORR was 84% with a CR of 55%. After the completion of therapy the ORR in the induction chemotherapy group (IC) was 97% versus 93% in the chemoradiation group (RC). After a median follow up of two years the larynx preservation rates and the disease free survival rates are as follows:91% (IC) vs. 87% (CR), n.s., and 85% (IC) vs. 66% (RC), p = 0.017. Conclusion: Addition of TPF induction therapy to the RTOG 91–11 concurrent radiochemotherapy protocol may enhance the disease free survival. No significant financial relationships to disclose.
Does delaying the onset of pap smear screening in Newfoundland (NL) impact on cervical cancer rates?
Authors: C. Popadiuk, J. Rose
Journal: Journal of Clinical Oncology (2010)

e12002 Background: Cervical cancer (CC) rates have declined with the advent of pap smear screening. In most organized programs, screening starts by 18 to 25 years of age. The 2009 American College of Obstetrics and Gynecology guidelines increased the age of first screening to 21 years regardless of the onset of sexual activity. NL is known for the highest CC incidence and mortality rates in Canada. Until 2001, NL has offered screening opportunistically. Since then, all women have been offered screening within 3 yrs of sexual intercourse or by the age of 18. Methods: All cases of invasive CC affecting women up to 29 years were identified from the NL Cancer Registry from 1992 – 2008. Age at diagnosis, gravidity, smoking, disease stage, histology, screening history and outcome data were collected. The total number of pap smears in the under 25 year old (yo) demographic and corresponding abnormalities requiring follow up were reviewed. Results: From 1992 – 2008, 37 women aged 19 to 29 had invasive CC. The incidence ranged from 0 to 10.81 per 100,000 women/yr under 25 yo, and from 0 to 32.3 per 100,000 women/yr aged 25-29. Two women aged 19 and 21 had invasive CC, both stage 1B1 and both presenting with symptoms. No woman under 21 had CC since 1995. For the 22 to 24 yo subset, 7 women had invasive CC: 5 stage 1A, 4 stage1B1, and 1 stage 4a. None died of their disease. In the 25-29 yo subset: 15 were stage 1A, 11 1B, 4 2B, and 1 3B. 3 women aged 26 to 28 died from their cancer presenting with stages 1B2 to 2B. From 1992 – 2008, from 1744/100 000 women to 4591/100 000 women under 25 had abnormal pap smears requiring further follow up and intervention. Since 2001, no invasive cancer was diagnosed in a woman under 25. Various models were constructed, none of which showed any significant difference in incidence and mortality between the younger and older groups, the use of organized screening or other variables. Conclusions: Increasing the age of first pap smear to 21 or 25 in NL will decrease the number of pap smears and corresponding followup and treatment for abnormal smears without significantly impacting on incidence or mortality of invasive cervical cancer. Delaying the start of screening may therefore spare the deleterious effects of over treatment and anxiety in younger women. No significant financial relationships to disclose.