tbuckley/cabot-search huggingface dataset:
Staging and prognostic factors for stage IV melanoma: Initial results of an American Joint Committee on Cancer (AJCC) international evidence-based assessment of 4,895 melanoma patients
Authors: J. E. Gershenwald, D. L. Morton, J. F. Thompson, J. M. Kirkwood, S. Soong, C. M. Balch, A. M. Eggermont, V. K. Sondak, M. M. Johnson, C. Warneke
Journal: Journal of Clinical Oncology (2008)

9035 Background: In response to a charge to develop potential revisions of the current AJCC/UICC melanoma staging system, the AJCC Melanoma Task Force employed an evidence-based approach to assess disease-specific survival in patients with distant metastatic (i.e., AJCC stage IV) melanoma. Methods: A first-in-kind international AJCC/UICC stage IV melanoma database containing clinicopathologic and survival data for 4,895 patients with stage IV melanoma at 6 melanoma centers or cancer cooperative groups in North America, Europe, and Australia was developed. Patients were included in the analysis if they presented with or later developed stage IV disease. LDH levels at the time of initial stage IV diagnosis were available for a subset of patients (n = 1,282). Results: Among 4,436 stage IV patients with sufficient data for survival analysis, AJCC M-categories were associated with statistically significant differences in survival (p < 0.0001). One-, two-, and five-year survival rates were 54%, 36%, and 19% for M1a (distant skin, soft tissue, and/or lymph nodes) patients, 53%, 31%, and 15% for M1b (lung), and 35%, 18%, and 9% for M1c (visceral). Compared to survival of patients with normal LDH levels, patients with abnormal LDH levels had significantly worse overall survival (P < 0.0001). One-, two-, and five-year survival for abnormal versus normal LDH were 33% vs. 61%, 18% vs. 33%, and 10% vs. 18%, respectively). Overall survival of patients with stage IV melanoma diagnosed since 1997 was significantly better than that of patients diagnosed prior to 1997 (median survival 1.11 years versus 0.74 years, p < 0.0001). Conclusions: These initial results from this large international dataset confirm key aspects of the current AJCC stage IV melanoma staging system. Ongoing analyses will evaluate whether additional refinements are warranted, assess the role of new markers of prognosis, and determine the effect of systemic and localized interventions on survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration American Joint Committee on Cancer
Abstract 9307: Does Preparedness Planning Improve Attitudes and Completion of Advance Directives in Patients with Symptomatic Heart Failure?
Authors: Marjam Motie, Lorraine S Evangelista, Dawn Lombardo, Jennifer Ballard-Hernandez, Shaista Malik, Solomon Liao
Journal: Circulation (2012)

BACKGROUND: Limited research exists to support the impact of preparedness planning on attitudes toward and completion of advance directives (ADs) in patients with symptomatic heart failure (HF). OBJECTIVE: We conducted this descriptive-correlational study to assess the impact of a palliative care (PC) intervention that facilitates preparedness planning on attitudes and completion of ADs in patients hospitalized for HF exacerbation. METHODS: Thirty-six patients (mean age 54 ± 8 years; predominantly male [72%]; White [61%]; married [69%]; New York Heart Association class II [69%]) from single tertiary care facility completed telephone interviews pre- and post-implementation of a PC consultation to facilitate preparedness planning and discussion of patient preferences. RESULTS: Mean attitude scores on the Advance Directive Attitude Scale (ADAS) improved from 57 ± 13 at baseline to 80 ± 7 at three months ( P &lt; .001). Figure 1 illustrates changes in variables of interest over time. Completion of ADs was associated with race, marital status, higher ADAS scores, and better health perceptions at baseline; except for marital status, these associations were also observed post-intervention (Table 1). In addition, knowledge about ADs and discussions related to ADs with family and physicians were associated with completion of ADs post-intervention (all P s &lt; 0.05). CONCLUSION: A PC consultation enhanced attitudes toward and increased the rate of completion of ADs in patients with symptomatic HF. However, larger scale randomized clinical trials to assess impact of preparedness planning on completion of ADs and outcomes are needed.
Pulmonary nocardiosis in a teaching hospital in the Central Anatolia of Turkey: Clinical experience in 26 patients
Authors: Fatma Sema Oymak, Nuri Tutar, Duygu Percin, Orhan Yildiz, Aydin Unal, Afra Yildirim, Fatih Kurnaz, Asiye Kanbay, Hakan Buyukoglan, Inci Gulmez, Ramazan Demir
Journal: European Respiratory Journal (2012)

Pulmonary nocardiosis (PN) is an uncommon but severe infection caused by Nocardia spp., which can behave either as opportunistic or primary pathogens. The diagnosis of PN can easily be missed. The purpose of this retrospective study is to review the predisposing factors, clinical symptoms, microbiologic, radiographic characteristics, diagnostic procedures, treatment and outcome of the patients with PN confirmed positive culture, diagnosed in a teaching hospital over the last 11 years. Twenty- six (20 men and 6 women) adult patients with a mean age at time of 49 years (range:21 to72 years) were identified with PN. Half of the patients had disseminated nocardiosis (8 with dissemination to central nervous system, 5 with soft tissue and cutaneous abscess). The predisposing conditions were treatment of steroids (88%), chronic lung diseases (31%), transplantation (19%) and malignancy (19%). Mean time to diagnosis was 31 days. In 21 patients (80%), the infection occurred outside the hospital setting. Respiratory tract sampling using noninvasive techniques had a diagnostic yield of 81%, while specimens from invasive methods had a yield of 37%. The radiological changes were diverse and non-specific. Nocardia asteroides type VI (N.cyriacigeorgica) and N.farcinica were the commonest species.Treatment was started empirically, modified according to the antimicrobial susceptibility pattern, and then continued for 6–12 months. Overall mortality was 58%, with death being caused by the Nocardia infection in 7 patients (27%).PN is a rare infection and mainly affects immunocompromised patients. Higher index of suspicion is needed for earlier diagnosis and treatment to improve prognosis.
Chemoradiation and Adjuvant Chemotherapy in Cervical Cancer
Authors: L. C. Wong, H. Y.S. Ngan, A. N.Y. Cheung, D. K.L. Cheng, T. Y. Ng, D. T.K. Choy
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Radiotherapy is the standard treatment for locally advanced cervical cancer, but treatment results remain disappointing, particularly for women with bulky central disease. We investigated the role of concurrent chemoradiation and adjuvant chemotherapy in a randomized trial. PATIENTS AND METHODS: Two hundred twenty patients with bulky stage I, II, and III cervical cancer were randomized to receive either standard pelvic radiotherapy or chemoradiation (epirubicin 60 mg/m 2 ) followed by adjuvant chemotherapy with epirubicin 90 mg/m 2 administered at 4-week intervals for five additional cycles. RESULTS: Fifty-nine patients have relapsed, with a median follow-up duration of 77 months. Patients whoreceived epirubicin radiation therapy showed a significantly longer disease-free (P = .03) and cumulative survival (P = .04). Patients who received radiation alone had significantly more distant metastasis than those who received chemoradiation (P = .012). There was no difference in long-term local tumor control (P = .99). CONCLUSION: Survival benefit has been demonstrated in patients treated with chemoradiation followed by adjuvant chemotherapy with epirubicin as compared with patients treated with standard pelvic radiotherapy alone.
A phase I study of TPI 287, a third generation taxane, administered every 21 days in patients with advanced cancer
Authors: M. Modiano, P. Plezia, J. Baram, R. Catane, A. Cohn, M. Basche, M. Kurman, G. Tapolsky, S. Yancik
Journal: Journal of Clinical Oncology (2007)

2569 Background: TPI 287 is a third generation taxane engineered to overcome multi-drug resistance and to bind to mutant tubulin. In preclinical studies, TPI 287 suppressed the growth of multiple human tumor xenografts in nude mice, including xenografts that expressed mdr- 1 and that were resistant to other taxanes. The safety and tolerability of TPI 287 when administered every 21 days was examined in this Phase 1 dose escalation study in patients (pts) with advanced neoplasms. Methods: TPI 287 was administered over 1 hour every 21 days in ascending doses to groups of 3 pts. Treatment cohorts were expanded to 6 pts in the face of dose-limiting toxicity (DLT); pts could remain on study until the development of progressive disease or an intolerable adverse event. DLT was defined as Gr 4 heme toxicity lasting 7 days; febrile neutropenia, Gr 3 thrombocytopenia with bleeding, Gr 3 elevation of transaminases lasting 7 days or any other Gr 3/4 toxicity other than nausea or vomiting. Results: 14 pts (M:F 5:9, median age 58.5, range 49 - 77) were enrolled in 5 dose levels ranging from 56 - 185 mg/m 2 . Pts’ cancers included colorectal (5 pts), esophageal (2), pancreatic (2), NSCLC (2), breast (2) and ovarian (1). All patients had received prior chemotherapy (median no. prior treatments: 3 (range, 2 - 10). Drug related adverse events included mucositis, vomiting, diarrhea, neutropenia, thrombocytopenia, myalgias and peripheral neuropathy. Only 1 pt. experienced Gr 4 neutropenia. DLT of Gr 3 peripheral sensory neuropathy was observed at a dose of 185 mg/m 2 . At a dose of 160 mg/m 2 no DLT was observed. 1 pt with pancreatic cancer had a confirmed response to TPI 287 that has persisted for 2.5 months and continues as of this writing. PK data reveal that AUC is generally dose linear. At a dose of 126 mg/m 2 , clearance was 24.7 + 12.2 L/hr/m 2 and t 1/2 was 10.6 + 7.1 hrs. Conclusions: TPI 287 can be safely administered in a dose of 160 mg/m 2 every 21 days. The dose limiting toxicity was Gr 3 peripheral neuropathy. Anti-neoplastic activity was seen in a patient with pancreatic cancer. PK is dose linear and predictable. Several Phase 2 studies of TPI 287 are being planned. No significant financial relationships to disclose.
Enhancement of human cancer cell migration and invasion by anaphylatoxin C5a viaaberrantly expressed C5a-receptor.
Authors: Hidetoshi Nitta, Hiroshi Takamori, Takahisa Imamura, Hideo Baba
Journal: Journal of Clinical Oncology (2012)

e21084 Background: Accumulated evidence has revealed implications of chemokines and their receptors in the pathophysiology of cancer. Anaphylatoxin C5a, a fragment of the complement 5th component (C5), is a potent chemokine for leukocytes that express the C5a receptor (C5aR). Recent reports indicate production of C5a by proteases of various origins, besides a by-product of activation of the complement system, and expression of C5aR in non-myeloid cells, suggesting an involvement of C5a in these cell biology. However, little is known about roles of C5aR in human cancer. Aim of our study was to investigate the expression and the role of C5aR on cancer cells in proliferation and invasion. Methods: Surgically resected cancer tissues and cancer cell lines were investigated C5aR expression. The effect of C5a on cancer cell proliferation, cell shape and invasion activity were examined in vitro and in vivo. Results: By immunohistochemical analysis, C5aR was strongly expressed in human cholangiocarcinoma samples. Using RT-PCR, immunoblotting and flow cytometric analysis human cholangiocarcinoma cell line MEC but not HuCCT1 were found to express C5aR. Incubation of both cancer cells with C5a did not increase these cells, indicating no mitogenic effect of C5a on these cells. Interestingly, C5a stimulated invasion of MEC and C5aR-transgenic HuCCT1 when examined by Matrigel invasion assay, which was suppressed by anti C5aR antibody. F-actin staining and human MMPs array revealed that C5a induced actin polymerization and MMPs production, respectively, in MEC and C5aR-transgenic HuCCT1. In contrast, these C5a effects were not seen in HuCCT1. Conclusions: These results illustrate a novel activity of C5a-C5aR axis that promotes cancer cell invasion through cytoskeletal rearrangement and MMP release. Thus, targeting this signaling pathway may provide a useful therapeutic option for cancer treatment.
Phase II study of the cancer vaccine TG4010 in metastatic renal cell carcinoma
Authors: C. Linassier, S. Oudard, O. Rixe, J. P. Machiels, J. F. Rossi, F. Ringeisen, T. Velu, E. Banu, B. Acres, P. Squiban
Journal: Journal of Clinical Oncology (2005)

4653 Background: MUC1 is a glycoprotein located at the apical surface of glandular epithelial cells. In some tumors, MUC1 is often aberrantly over-expressed and hypoglycosylated, unmasking new antigenic epitopes. This makes it a potential target for tumor-specific vaccination. In renal cell carcinoma (RCC), MUC1 expression is associated with a poor prognosis. TG4010 is a cancer vaccine based on a modified vaccinia virus (MVA) expressing both MUC1 and Interleukin 2. The phase II study objective was to determine the overall response rate of TG4010 alone and in combination with cytokines in a two-step design. Methods: Patients (pts) with progressive metastatic RCC, expressing MUC1 in at least 50% of the tumour cells, received subcutaneous injections of TG4010 weekly for 6 weeks then every 3 weeks until progression, then the TG4010 was combined with Interferon alpha-2a (INF) and Interleukin 2 (IL2). Response to treatment was evaluated every 12 weeks according to the RECIST criteria. Median time to progression (TTP) and overall survival (OS) were estimated according to Kaplan-Meier method. Results: Between 01/2003 and 06/2004, 37 pts were included [intent-to-treat (ITT)], 36 being evaluable for response. No objective responses were observed, however, 6 pts (17%) remained stable for more than 6 months with TG4010 alone. After progression on TG4010 alone, 20 pts received TG4010 in combination with cytokines. Eleven of them (55%) have been stabilized, 6 of them (30%) more than 6 months. The interim values (ITT) for median TTP are 2.6 months for TG4010 alone, 4.7 months for the combination with IL2 and INF and 8.6 months for the total sequence of treatment. The 6, 12 and 18 months OS (ITT) was 75% (95% CI, 62%–89%), 58% (95% CI, 40%–77%) and 58% (95% CI, 40%–77%). The safety profile of TG4010 alone was favorable with minor to moderate injection site reactions as the most frequent side effect. The toxicities observed in combination were those usually observed with IL2 and INF. Conclusions: The association of the cancer vaccine TG4010 with IL2 and INF is feasible and does not result in increased toxicities. The benefit of TG4010 in patients with metastatic RCC could be a delay in the introduction of cytokines based treatments or a potentiation of these treatments. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Transgene SA
Docetaxel-carboplatin chemotherapy in combination with cetuximab in patients with locally advanced or metastasized non-small cell lung cancer (NSCLC): Interim results of the nonrandomized phase II study TaxErb
Authors: J. R. Fischer, F. Griesinger, T. Fink, E. Buchholz, T. Salm, A. Marseille, M. Wolf
Journal: Journal of Clinical Oncology (2009)

e19062 Background: Combination chemotherapy with carboplatin-docetaxel has been shown to be effective and safe for patients with locally advanced or metastasized NSCLC. The monoclonal anti-EGRF antibody cetuximab has the potential to improve response rates and survival without a substantial increase in toxicity when given in combination with chemotherapy. Methods: Open, non-controlled phase II study with a planned sample size of 70 pts. Pts with locally advanced or metastasized NSCLC, ECOG performance status ≤ 2 and no prior systemic chemotherapy were treated with carboplatin AUC5 (d 1) q4w for 4–6 cycles and docetaxel 35 mg/m 2 (d1, 8, 15) q4w; cetuximab 400 / 250 mg/m 2 (d 1) q1w until progression or intolerable toxicity (12 month max.). The primary endpoint was response rate defined as complete or partial remission according to RECIST. Secondary endpoints were toxicity, 1 year survival, median and progression free survival. Results: Subject of the interims analysis were 27 pts (25 stage IV, 2 stage IIIb). ECOG 0/1/2 was 33.3%/59.3%/3.7% (1 no data). 63% had prior surgery, 93% prior radiotherapy and all had adjuvant or inductive chemotherapy. Pts received a mean of 3 ± 1.4 cycles docetaxel-carboplatin-cetuximab. 49 adverse events were grade 1–2 and 12 grade 3–5. Skin toxicity (49%; 95%CI: 30%-68%; 41% G1/2, 8% G3/4), dyspnoea (35%; 95%CI: 17%-53%) and diarrhoea (23%; 95%CI: 7 %-39%; 19% G1/2, 4% G3) were most frequent. 11 pts (41%) had toxicity leading to dose reduction. 0 pts had complete and 11 pts had partial remission resulting in a response rate of 40.7% (95%CI: 22%-59%) based on intention to treat. 6 pts had stable disease (22.2%; 95%CI: 7%-38%). 5 pts were not evaluable for response. Conclusions: The combination of carboplatin-docetaxel-cetuximab has an overall acceptable tolerability. With a preliminary response rate of 40.7% the benefit risk assessment was found to be favourable and the study was continued. [Table: see text]
High-dose methotrexate and ifosfamide for CNS relapse of aggressive lymphoma
Authors: L. Fischer, A. Korfel, K. Jahnke, P. Kiewe, E. Thiel
Journal: Journal of Clinical Oncology (2007)

12524 Background: CNS involvement is a grave complication of malignant lymphoma. Therapy traditionally includes intrathecal chemotherapy, radiotherapy and systemic chemotherapy for concomitant systemic lymphoma. However, optimal therapy has not been established thus far for CNS lymphoma. In this pilot study a combination of systemic high-dose (HD) methotrexate (MTX) and ifosfamide (IFO) was evaluated for toxicity and response rate. Methods: 10 patients (pts.) with CNS relapses of aggressive lymphoma (5 nodal DLBCL, 4 PCNSL/PIOL and 1 T-NHL) were treated. Nine pts. had intracerebral lesions, the meningeal compartment was involved in three. Three pts. had systemic manifestations. Median age was 63 years (32 - 83). Therapy consisted of 4g/m 2 MTX (4h infusion on day 1) with dose adjustment for creatinine clearance (CC) &lt; 100ml/min (CC/100 * 4g/m 2 ) and 1.5 to 2g/m 2 /day IFO (3h infusion day 3 to 5). Supportive therapy included mesna and a leucovorin rescue beginning at 24h after start of MTX. Two pts. were treated with intrathecal chemotherapy before MTX/IFO. Results: A median of 4 cycles chemotherapy was administered. Treatment response was documented in 9 pts. (3 CR, 6 PR), and one patient had stable disease. The toxicity was mainly hematologic with grade 3/4 neutropenia in 6 pts., grade 3/4 thrombocytopenia in 4 pts. and grade 3 anemia in 2 pts. One pat. died from sepsis in neutropenia and one pat. with long-term corticosteroid therapy developed an aspergillus pneumonia grade 3. Nephrotoxicity grade 1/2 was observed in 6 pts.. Four pts. were further treated with HD chemotherapy followed by autologous stem cell transplantation or salvage radio-/chemotherapy. A median progression free survival of 6.5+ months (range 1–41+) for all pts. has been reached with persisting remission after 4 to 41 months in 5 pts.. Conclusions: Systemic combination therapy with MTX and IFO is feasible and exhibits a promising activity in CNS relapses of aggressive lymphoma. No significant financial relationships to disclose.
Effects on behavior of modulation of gonadal function in men with gonadotropin-releasing hormone antagonists
Authors: P T Loosen, S E Purdon, S N Pavlou
Journal: American Journal of Psychiatry (1994)

The effects of acute gonadal suppression on sexual function and behavior were studied in eight normal men. Administration of a newly developed, potent gonadotropin-releasing hormone antagonist induced azoospermia and reduced levels of serum testosterone, luteinizing hormone, and follicle-stimulating hormone. These effects coincided with a reduction in outward-directed aggression in all men. Self-reported measures of anxiety and sexual desire revealed less consistent change over time. Measures of anger control, inward-directed anger, and affective state were unaffected.
Immunological Characteristics of Radiation Chimaeras
Authors: P. L. T. Ilbery, P. C. Koller, J. F. Loutit
Journal: JNCI Journal of the National Cancer Institute (1958)

Journal Article Immunological Characteristics of Radiation Chimaeras Get access P. L. T. Ilbery, P. L. T. Ilbery Search for other works by this author on: Oxford Academic PubMed Google Scholar P. C. Koller, P. C. Koller Search for other works by this author on: Oxford Academic PubMed Google Scholar J. F. Loutit J. F. Loutit Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 20, Issue 6, June 1958, Pages 1051–1089, https://doi.org/10.1093/jnci/20.6.1051 Published: 01 June 1958 Article history Received: 05 November 1957 Published: 01 June 1958
Human colon cancer stem cells locate in hypoxic niche
Authors: Y. Zhang, W. H. Guo, T. Chen, X. M. Mo, Y. Lu
Journal: Journal of Clinical Oncology (2008)

22209 Background: It has been proposed that a small number of undifferentiated tumorigenic CD133+ cells from human colon carcinoma be defined as colon cancer stem cells (CSCs) based on their self-renewal and propagation properties. In order to further investigate the CSCs niche, we applied an approach to resolve the spatial organization of human colon cancer stem cells according to hypoxia and the impact of hypoxia on irradiation. Methods: Eight fresh samples of primary human colon cancers were implanted in immunocompromised mice. The percentage of hypoxic CD133+ cell population was detected and quantified by use of hypoxic maker pimonidazole (PIM) via flow-cytometry. Measurements were also made of CD133+ cell population and its change of hypoxic situation following irradiation with a single dose of 2 Gy, 5 Gy, 10 Gy, and 20 Gy, respectively. Results: CD133+ cells were found to be the most positive for binding of PIM. The percentage of hypoxic population of CD133+ cells were ranged from 51.6% to 87.0% with an average of 70.2%, whereas the other colon cancer cells labeled CD133- demonstrated an average of 20.2% ranged from 5.3% to 49.1%. Hypoxic population of CD133+ cells was 4.5 times (from 2 to 12 times) than that of CD133- cells. Compared with control, irradiation at 2 Gy to 20 Gy with a single fraction reduced the CD133+ cell population in period of 1 to 6 hours after treatment. Interestingly, it resulted in an increase of the percentage of hypoxic CSCs to different extent rather than other hypoxic colon cancer cells. Conclusions: Most population of human colon CSCs locate in hypoxic niche, and the hypoxic human colon CSCs resist radiotherapy to some extent. It is implicated that regionally defined hypoxia plays a fundamental role in both regulating human colon CSCs function and diminishing therapeutic response. No significant financial relationships to disclose.