tbuckley/cabot-search huggingface dataset:
Implication of the alternative NF-kappa B pathway in prostate cancer progression.
Authors: I. Labouba, S. Mehairi, M. Latour, A. Mes-Masson, F. Saad
Journal: Journal of Clinical Oncology (2010)

10592 Background: Our previous study on prostate cancer (PCa) tissues shows that the alternative NF-kB proteins RelB and p52 localize to the nucleus more frequently than classical NF-kB proteins RelA and p50. We also reported on a small cohort that the nuclear localization of RelB correlates with increasing Gleason scores. The present study attempts to confirm this observation in a larger cohort and determine if this pathway may be implicated in the stage progression of prostate cancer. Methods: To evaluate RelB expression and cellular localization, archival formalin-fixed, paraffin-embedded prostate specimens were used to construct a first tissue microarray (TMA) containing non-malignant tissue adjacent to the tumor (n = 55), prostatic intraepithelial neoplasia (PIN) (n = 31) and hormonosensitive PCa samples (HS; n = 63). A second TMA was also built including hormonorefractory tumor specimens (HR; n = 36). Statistical analyses were used to evaluate the correlations between RelB and clinical and pathologic disease progression. Results: Our immunohistochemical analysis showed a differential expression between non-malignant and tumor tissues. Indeed, RelB was largely expressed in the cell cytoplasm of tumors, including HS (87.3%) and HR (91.7%) samples compared to non-malignant tissue adjacent to the tumor (49.1%; p < 0.001) and PIN (48.4%; p < 0.001). Moreover, RelB was more frequently localized in the nucleus of HR PCa (97.2%) than in HS (63.5%; p < 0.001), non-malignant tissue adjacent to the tumor (51%; p < 0.001) and PIN (48.4%; p < 0.001). Conclusions: RelB is over-expressed in PCa tissues with a frequent nuclear localisation that increases with PCa stage progression. This extremely high nuclear expression in HR PCa tissues suggests that activation of the alternative NF-kB pathway may be implicated in the PCa progression from HS to HR status. Ongoing studies including on the other alternative NF-kB p52 will hopefully shed light on the role of both NF-kB pathways in prostate cancer progression, its use as a potential prognostic marker as well as a possible therapeutic target for the future. No significant financial relationships to disclose.
Epidemiological data of cancer of the only cancer center of the western Black Sea region of Turkey
Authors: H. Engin, S. Ozdamar, B. Gun, B. Bahadir, G. Kertis, G. Numanoglu, Y. Ustundag, G. Kuzey
Journal: Journal of Clinical Oncology (2006)

16041 Background: 600 patients diagnosed as having cancer between years 2000–2005 at Zonguldak Karaelmas University were evaluated. Methods: All information pertaining to patient characteristics were retrieved from files of the Pathology and Medical Oncology Departments. Results: 383 (63,83%) were male and 217 (36,17%) were female. The most common malignancies among males are; prostate cancer 21,40 %, stomach cancer 14,62%, tumors of the bronchi and the lungs 12,10%, colorectal cancers 10,70%, skin tumors (non-melanoma 8,90%, melanoma 1,30%), malignancies of the lymphatic and hematopoietic system 7,83%, bladder cancer 6,52%, metastasis of unknown origin 3,40%, laryngeal cancer 2,61%, tumors of the hepatobiliary system 2,61%, brain tumors 2,00%, tumors of the bone and soft tissues 1,82%, tumors of the oral cavity and pharynx 1,31%, esophagus cancers 1,04%, thyroid cancers 1,04%, testicular cancers 0,52%, renal tumors 0,26%, tumors of the small intestine 0,26%. The most common malignancies among females are: breast cancer 22,11%, skin tumors (non-melanoma 15,60%, melanoma 0,92%), colorectal cancers 12,37%, stomach cancers 8,29%, malignancies of the lymphatic and hematopoietic system 5,99%, endometrial cancers 5,52%, ovarian cancers 3,22%, thyroid cancers 5,06%, metastatic tumors of unknown origin 4,14%, brain tumors 3,22%, tumors of the hepatobiliary system 2,76%, tumors of the bronchi and the lungs 2,30%, tumors of the bones and soft tissues 2,30%, esophagus cancers 1,38%, tumors of the oral cavity and pharynx 0.92%, tumors of the cervix uteri, vulva and vagina 0,50%, renal tumors 0,46% and tumors of the small intestine 0,46%. Conclusions: Although Turkish Health Department data demonstrates that the tumors of the bronchi and the lungs are the most common malignancies in the general Turkish population, prostate cancer was found to be the most common malignancy among our patient population. Additionally, colorectal tumors were also found to be more prevalent in our patient population than in the general Turkish population. Breast cancer was the most common malignancy among female patients in our patient population, as it is in general. While stomach and colorectal tumors among women were more prevalent than in the general population, gynecological tumors were rare. No significant financial relationships to disclose.
Gene expression profiling (GEP) analysis of CD138-purified plasma cells (PC) obtained from MRI-defined focal lesions (FL) under CT guidance: Applying the 70 gene risk model and comparison with data generated on random samples (RS) from multiple myeloma (MM) treated with total therapy 2, 3, 4, and 5 (TT2, TT3, TT4, and TT5).
Authors: Y. Qiang, R. van Hemert, T. Brown, J. D. Shaughnessy, F. Van Rhee, A. Hoering, B. Barlogie
Journal: Journal of Clinical Oncology (2010)

8126 Background: We have reported on the superior performance of RS-based GEP to distinguish 85% with low-risk (LO) and 15% with high-risk (HI) MM (Shaughnessy, Blood 2008). MM sometimes presents as macrofocal disease so that RS is uninformative. Here we report on a comparison of concurrent FL and RS GEP data from 69 patients, 3 of whom were enrolled in TT2, 22 in TT3, 40 in TT4 and 4 in TT5. Methods: GEP risk scores were compared, heat-map hierarchical clustering was applied to determine the relative vicinity of RS and FL samples, and overall survival (OS) and event-free survival (EFS) were compared applying the RS-derived 70-gene model. Results: Congruence in risk designation applied to 56 patients with LO/LO and 4 with HI/HI features, whereas 5 displayed RS-LO/FL-HI and 4 displayed RS-HI/FL-LO. Unsupervised hierarchical clustering placed 46 patients' RS and FL next to each other. OS and EFS comparisons were performed according to tertile 70-gene risk scores with RS and FL samples: OS and EFS were significantly inferior in the 12 patients exhibiting top-tertile risk scores in both RS and FL samples with 3-yr estimates of 73% and 49% compared to the remaining 59 patients with 3-yr OS and EFS estimates of 95% each (p<0.001). Conclusions: Genomic features in FL contributed to outcome prediction. Whether FL-GEP in macro-focal disease, absent RS-GEP, has similar independent outcome implications awaits additional accrual and follow-up of such patients. No significant financial relationships to disclose.
Phase I/II dose escalation trial of patupilone every 3 weeks in patients with non-small cell lung cancer
Authors: K. Østerlind, J. M. Sánchez, P. Zatloukal, J. Hamm, C. P. Belani, E. Kim, E. Felip, A. Johri, M. Berton, I. Sklenar
Journal: Journal of Clinical Oncology (2005)

7110 Background: Patients (pts) with newly diagnosed advanced non-small cell lung cancer (NSCLC) usually receive a platinum-containing doublet. However, these regimens do not produce a marked improvement in survival and many are associated with cumulative toxicity. Patupilone, a natural epothilone, is a microtubule-targeting cytoxic agent that causes cell death and is active in a variety of tumors, including those that are resistant to taxanes. In a phase I/II study, we are investigating the safety, efficacy, and maximum tolerated dose (MTD) of patupilone in pts with stage IIIB/IV NSCLC. Methods: Pts who have relapsed after 1 prior platinum-containing regimen and did not have symptomatic brain metastases have been enrolled. During the phase I study, pts receive patupilone at a starting dose of 6.5 mg/m2 via 10- to 20-min IV infusion once every 3 weeks with dose escalation in 0.5-mg/m2 increments and proactive diarrhea management. Severe toxicities occurring in cycle 1 were considered dose-limiting toxicities (DLTs). Results: To date, 39 pts have been enrolled in 10 cohorts receiving 6.5 (n = 3), 7.0 (n = 3), 7.5 (n = 6), 8.0 (n = 6), 8.5 (n = 6), 9.0 (n = 3), 9.5 (n = 3), 10.0 (n = 3), 10.5 (n = 3), and 11.0 (n = 3) mg/m2 patupilone. Median age was 57 years (range, 38 to 77 years) and median performance status was 1. DLTs were not observed until the 7.5 mg/m2 cohort wherein 1 pt reported grade 3 asthenia. The 8.0- and 8.5-mg/m2 cohorts had 1 pt each with grade 3 diarrhea. No other DLTs have been reported up to 11.0 mg/m2 and pts are currently being enrolled in the 11.5 mg/m2 cohort. The most common adverse events were diarrhea (54%), abdominal pain (36%), fatigue (31%), and nausea (31%). Only 9 (26%) pts had grade 3 adverse events of any kind; 5 pts with grade 3 diarrhea. Alopecia (grade 1) occurred in only 3 pts and 11 pts had grade 1 or 2 peripheral neuropathy. Grade 3 hematologic toxicity was uncommon (< 10%) and there were no grade 4 adverse events. According to RECIST, 4 pts had a partial response and 9 pts had stable disease; median duration of stable disease was 4.2 months (95% CI: 4.0 to 5.4). Conclusions: The MTD has not yet been reached. Preliminary results suggest that patupilone is safe and there is evidence of antitumor activity in pts with advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Novartis Pharmaceuticals, AG Novartis Novartis, Novartis Pharmaceuticals, AG Novartis
K-ras status and response in patients with advanced or metastatic cholangiocarcinoma treated with cetuximab plus gemcitabine-oxaliplatin (GEMOX): a single center phase II study
Authors: B. Gruenberger, J. Schueller, D. Tamandl, K. Kaczirek, G. Schernthaner, T. Gruenberger
Journal: Journal of Clinical Oncology (2009)

4586 Background: As known, the mutation status of the K-ras gene affects the response to cetuximab in colorectal cancer. Less is known about K-ras status and outcome in cholangiocarcinoma. Patients with advanced cholangiocarcinoma have a poor prognosis and until now, no standard palliative chemotherapy has been defined. The purpose of this prospective single-centre phase II study was to investigate the therapeutic efficacy and K-ras status dependence of cetuximab in combination with gemcitabine and oxaliplatin in the palliative first line treatment of these patients. Methods: Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder cancer were treated with cetuximab 500 mg/m 2 followed by 1000mg/m 2 gemcitabine (day 1) and 100mg/m 2 oxaliplatin (day 2) biweekly as first line therapy. Tumour samples were obtained from 25 of 30 patients (83%). We studied the k-ras mutation status and analyzed the association between k-ras mutation and tumor response, progression-free survival (PFS) and overall survival (OS). Results: From October 2006 until July 2008 thirty patients (15 male, 15 female) with a median age of 68 were enrolled. The overall response rate of evaluable patients (30) was 63,3%, including three patient with a complete response. 5 patients (16,7%) achieved stable disease and only 6 patients (20%) progressed under chemotherapy. K-ras mutation was detected in 3 patients (12%). All three patients did not progressed under chemotherapy. Neither PFS nor OS were affected by K-ras status. The median PFS of all 30 patients was 8.3 months (95% CI 5.85–10.81) and median OS was 12.7 months (95 CI 7.96–17.37). After a mean number of 7.5 cycles any WHO grade 3 drug-related adverse events occurred in 13 patients (43%), consisting of skin toxicity in 4 patients, thrombopenia in 3, neutropenia in 1, nausea in 1, diarrhoe in 1 and PNP in 4 patients; no grade 4 side effects were noticed Conclusions: Cetuximab in combination with GEMOX induces impressive response rates which were unrelated to k-ras status. PFS and OS were remarkably improved and therefore cetuximab in combination with GEMOX deserves further evaluation in prospective randomized trials. [Table: see text]
Large international multicenter evaluation of the clinical significance of L1-CAM expression in FIGO stage I, type 1 endometrial cancer.
Authors: A. G. Zeimet, S. Abdel-Azim, D. Reimer, E. Mueller-Holzner, B. Winterhoff, U. Puistola, A. Ben-Arie, L. vanKempen, F. Amant, E. Petru, S. Jahn, S. Polterauer, P. Oppelt, M. Weigert, P. Altevogt, M. Huszar, C. Marth, M. Fogel
Journal: Journal of Clinical Oncology (2011)

5091 Background: Endometrial cancer, especially when diagnosed in stage I, is associated with an excellent prognosis. Although, special histological types or poor differentiation characterize a “high risk” group, these factors do not sufficiently explain recurrence. The present multicenter study was undertaken to investigate whether the expression of the neural cell adhesion molecule L1-CAM, even in small tumor areas, is able to identify early endometrial cancers with such a particular aggressive behavior. Methods: A total of 1031 endometrial cancers classified as “endometrioid” in the pathological examination were retrospectively assessed for L1-CAM expression by means of immunohistochemistry using the monoclonal mouse antibody L1 clone 14.10 [Covance, Princeton, NJ] on paraffin embedded specimens. Cancers with ≥ 5% of positive cells or circumscribed L1-CAM expressing islets were considered as L1-CAM positive. Blinded evaluation of the specimens was done by two independent pathologists. Results: 22.1% of the specimens were rated L1-CAM positive. Tumors classified as “high risk” and “low risk” in the intraoperative risk assessment were positive in 27.2% and 19.3%, respectively (p=0.0001). L1-CAM positivity was associated with histopathological grading (p=0.0001). Of special note is that L1-CAM was a reliable predictor for local (HR=2.134; p=0.05) and especially distal recurrence (HR=5.431; p=0.0001), but not for lymph node relapse. In addition to histopathological grading and age at diagnosis, L1-CAM expression was shown to be the most prominent independent predictor for disease-free (HR=5.411; p=0.0001) and overall survival (HR=4.154; p=0.0001). Subgroup analyses showed that even in “low risk” patients L1-CAM was a strong predictor for disease-free and overall survival (p=0.0001 and p=0.0001, respectively). Conclusions: L1-CAM expression in stage I, type 1 endometrial cancers reliably identifies a subset of cancers with high risk for recurrence and with poor survival. These cancers are candidates for trials evaluating the value of adjuvant treatment. We propose L1-CAM in early type 1 endometrial cancer as a novel tool for therapeutic decision-making.
UAB 0210: A phase I/II trial of induction chemotherapy followed by concomitant docetaxel/radiotherapy with subcutaneous amifostine for advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: L. M. Nabell, G. Peters, R. Meredith, W. Carroll, J. Bonner, R. Ove, S. Spencer
Journal: Journal of Clinical Oncology (2009)

6061 Background: Attempts to improve the outcome of locally advanced SCCHN have generally added chemotherapy to radiation, though the optimal manner of integration has been controversial. To impact distant and local control, we utilized neoadjuvant chemotherapy followed by concomitant boost radiation (CBR) with docetaxel as a radiosensitizer. To improve cytoprotection, subcutaneous amifostine was added during radiotherapy. Methods: From April 2003-March 2007 46 patients with stage III or IV newly diagnosed SCCHN were enrolled (30 Caucasian, 16 African-American). Treatment consisted of 3 cycles of neoadjuvant chemotherapy with cisplatin 75 mg/m 2 and docetaxel 75 mg/m 2 intravenously at 21 day intervals followed by CBR and concurrent dose-escalated weekly docetaxel starting at 20 mg/m 2 . Standard 2D radiotherapy was used in the majority of patients. Subcutaneous amifostine was administered at 500 mg during each day of radiation. Results: 39 patients were evaluable. The neoadjuvant chemotherapy was well tolerated by the majority of patients and appeared effective; no patient had progressive disease while on therapy. Three patients required a change to carboplatin due to toxicity. Weekly docetaxel during all weeks of CBR was not tolerable due to severe mucositis and the phase I component defined the MTD of concurrent docetaxel as 20 mg/m 2 for 4 cycles during CBR. 4 patients (10%) had persistent disease at completion of treatment. Amifostine administration was well tolerated though 4 patients required discontinuation of the drug. The majority of recurrences have been localized at the primary site (6 patients). 3 patients developed isolated pulmonary metastasis. Only 2 patients remain PEG dependent with median follow-up of 24 months. Conclusions: Induction chemotherapy using cisplatin and docetaxel is feasible and easy to administer in the outpatient setting; those patients who had a major radiographic and clinical response did particularly well in follow-up. Weekly docetaxel can be safely and effectively administered during CBR with good local control. Amifostine can be safely administered via the subcutaneous route; the benefit in locally advanced patients is difficult to assess. No significant financial relationships to disclose.
JGOG2033: Randomized phase III trial of whole pelvic radiotherapy vs cisplatin-based chemotherapy in patients with intermediate risk endometrial carcinoma
Authors: S. Sagae, Y. Udagawa, N. Susumu, K. Niwa, R. Kudo, S. Nozawa
Journal: Journal of Clinical Oncology (2005)

5002 Background: Optimal adjuvant therapy for intermediate risk endometrial cancer patients is poorly defined. Methods: A Japan Gynecologic Oncology Group (JGOG) conducted a multi-center randomized Phase III trial of whole pelvic irradiation (WPI) vs. cyclophosphamide-doxorubicin-CDDP (CAP) chemotherapy in women with endometrial carcinoma with deeper than 50% myometrial invasion postoperatively. 425 pts were entered from 1/1994 to 12/2000. Of the 385 evaluable endometrioid adenocarcinoma, 193 were to receive WPI and 192, CAP. WPI arm employed at least 40 Gray (Gy) in 20 fractions. CAP arm consisted of cyclophosphamide (333 mg/m2), doxorubicin (40 mg/m2) and cisplatin (50 mg/m2) every 4 weeks for 3 or more courses. Results: Pt Characteristics: The treatment arms were well balanced in terms of patient and tumor characteristic, with G1 55%, G2 30%, and G3 15%. Median follow-up was 1825 days (range 65–1825). Response and Survival: There were no statistically significant differences in progression-free survival (PFS) and overall survival (OS) between the 2 regimens for all pts. The PFS of WPI and CAP arms was 84.0% and 82.1%, and the OS of WPI and CAP arms was 85.9% and 87.1%, respectively. Especially, among 229 pts with intermediate risk as stage pTIc, the PFS of WPI and CAP arms was 89.6% and 87.2%, and the OS of WPI and CAP arms was 88.9 and 88.9, respectively. Recurrence in each WPI and CAP arm was 15.1%, 16.5%, respectively, with 30% pelvic and 70% extrapelvic recurrent sites. Toxicity: Adverse effects were not significantly increased in the CAP arm, compared to WPI arm. Conclusions: Adjuvant cisplatin-based combined chemotherapy might have potential as an alternative to radiotherapy for intermediate risk endometrial cancer, such as only deeper than 50% myometrial invasion. No significant financial relationships to disclose.
Outcome for breast cancer patients with congestive heart failure after epirubicin treatment
Authors: M. Ryberg, D. Nielsen, G. Nielsen, T. Skovsgaard
Journal: Journal of Clinical Oncology (2005)

622 Background: Patients (pts) treated with Epirubicin (EPI) are at risk for development of cardiomyopathy and congestive heart failure (CHF). Only limited data are available for the outcome of these pts. Methods: In a retrospective study, the history of 1122 consecutive pts with metastatic breast cancer (BC) was retrieved. All were treated with EPI alone or EPI in combination with other cytostatics from November 1983 - November 2003. Pts with cardiac disease New York Heart Association (NYHA) Class II were included. Statistical analyses included Kaplans-Meiers plot and Cox multivariate analysis. Results: 116 pts (10.3%) developed CHF. Time from discontinuation of EPI to onset of CHF was 3 mths (range 0–58). The median total dose of EPI among pts with CHF was 933 mg/m2 (range 260–1433). The median age was 60 years (range 38 - 79). 25.9% of the pts had symptoms according to NYHA II, 31.9% to NYHA III, 33.6% to NYHA IV and for 8.6% the exact NYHA class was unknown. The pts were treated with a single drug or with a combination of digoxin (56%), diuretics (78%), and ACE inhibitors (53%). 42.2% of the pts had benefit of the treatment, for 25.9% the symptoms were unchanged, the symptoms progressed in 24.1%, and in 7.8% the outcome was unknown. The median follow-up for pts with CHF was 73 mths (range 0 - 124 +). The median survival after CHF was 5.9 mths (range 0 - 124 +). 9.5% of the pts is still alive, 23.3% died of CHF, 41.4% of BC, 16.4% of a combination of CHF and BC, and for 8.6% the cause of dead was unknown. The following factors became significant for survival in a univariate analysis: the BC status at onset of CHF and the pts NYHA classification. In a Cox multivariate analysis only BC status became significant, p-value= 0.007. Conclusions: The number of pts who developed CHF after treatment with EPI was substantial. Only pts BC status was predictive for the survival after the onset of CHF. No significant financial relationships to disclose.
Peace of mind and sense of purpose as core existential issues among parents of children with cancer
Authors: J. W. Mack, J. Wolfe, E. F. Cook, H. E. Grier, P. D. Cleary, J. C. Weeks
Journal: Journal of Clinical Oncology (2008)

9518 Background: Little is known about how parents of children with cancer come to terms with the child’s illness. We sought to evaluate the core existential issues experienced by parents of children with cancer, and to determine factors that supported parents’ ability to find peace of mind. Methods: We surveyed 194 parents of children with cancer (response rate 70%) in the first year of cancer treatment at Dana-Farber Cancer Institute and Children’s Hospital, Boston, Mass. We used the FACIT-Sp sense of meaning subscale to evaluate core existential issues among parents, and assessed personal, disease, and care attributes associated with parents’ states of mind. Results: Principal components analysis of responses to the FACIT-Sp subscale identified two distinct constructs, which we termed peace of mind (Cronbach’s α=0.83) and sense of purpose (α=0.70). Each domain was converted to a score ranging from 1 to 5, with 5 representing the greatest experience of either peace or purpose. The two domains were moderately related (r=0.45). However, 82% of parents (146/179) scored 4 or greater for questions related to a sense of purpose (mean 4.4, SD 0.6). In contrast, only 22% of parents (40/178) had scores in the same range for peace of mind (mean 3.2, SD 0.9, P<0.0001). Because few parents experienced peace of mind, we focused multivariable binary logistic regression on this attribute, with the outcome of a peace score of 4 or greater. Parents tended to have higher scores for peace of mind when they also reported that they trusted the oncologist’s judgment (OR 3.94, 95% CI 1.19–13.18, P=0.02), that the oncologist had disclosed detailed prognostic information (OR 2.11, 1.05–4.25, P=0.04) and that the oncologist had provided high quality information about the child’s cancer (OR 2.89, 1.28–6.54, P=0.01). Peace of mind was not associated with the child’s prognosis (P=0.34) or time since diagnosis (P=0.78). Conclusions: Most parents report a strong sense of purpose as they care for their children with cancer. Peace of mind, however, may be harder to achieve. Physicians may be able to facilitate formulation of peace of mind by giving parents high quality medical information and serving as a trusted provider. No significant financial relationships to disclose.