tbuckley/cabot-search huggingface dataset:
CNTO328 (Anti-IL-6 mAb) treatment and hemoglobin (Hb) levels in renal cell cancer
Authors: M. Schipperus, M. Cornfeld, B. Rijnbeek, B. Berns, J. Rossi
Journal: Journal of Clinical Oncology (2009)

e20648 Background: CNTO328 is a chimeric monoclonal antibody against the inflammatory cytokine, IL-6, which is currently being studied in hematologic and solid malignancies. IL-6 is a potent inducer of hepatic production of hepcidin, which is the key regulator of iron homeostasis and causes anemia by blocking iron export from enterocytes and macrophages. Hepcidin is an important factor in the pathogenesis of ‘anemia of chronic disease‘. CNTO328 treatment has previously been shown to produce profound Hb increases in Castleman's disease, a disorder caused by deregulated IL-6 production. We subsequently conducted this retrospective review to assess whether CNTO328 treatment is associated with an increase in Hb level in renal cell cancer patients (pts). Methods: All laboratory results for pts with metastatic renal cell carcinoma in this open label phase 2 study were reviewed. Pts were treated with CNTO328 (6 mg/kg) IV infusions Q2 weeks and were evaluated for tumor response and markers of pharmacodynamic effect. The difference in Hb levels from baseline to end of study was calculated. Results: Twenty pts (19 males) with a median age of 62 yrs (range 50–77) were studied. The median number of infusions was 6 (1–13). Of 18 pts evaluable for tumor response, 11 (61%) had SD and 7 (39%) had PD. The median baseline Hb was 13.6 g/dL (10.8–17.1). Nineteen pts were evaluable for Hb response. No pts received ESAs or transfusions. Treatment with CNTO328 resulted in a sustained Hb increase in 16 of the 19 pts (84%), with 13 (68%) achieving a max Hb increase of ≥ 1 g/dL (median 1.9; range 1.0–3.5). Hb responses were early (by day 8) and independent of tumor response. No Hb overshoot or thromboembolic events were observed. A trend toward decreased platelet and neutrophil counts was observed. Conclusions: Though pts were not anemic at baseline, our results suggest that CNTO328 leads to sustained increase in Hb levels, not correlated with tumor response. This increase in Hb is presumably due to the reduction of hepcidin via IL-6 blockade and targeting the hepcidin pathway may lead to new therapies for anemia of cancer. This hypothesis warrants further evaluation with prospective mechanistic studies. [Table: see text]
Inhibition of Pd-L1 By Mpdl3280A Leads to Clinical Activity in Pts with Metastatic Urothelial Bladder Cancer (Ubc)
Authors: J. Bellmunt, D.P. Petrylak, T. Powles, F. Braiteh, N. Vogelzang, C. Cruz, H. Burris, J.P. Eder, G. Fine, M.S.L. Teng, X. Shen, J. Bruey, Z. Boyd, P. Hegde, D. Chen, Y. Loriot
Journal: Annals of Oncology (2014)
Survival of pediatric patients after relapsed osteosarcoma: The St. Jude Children’s Research Hospital experience
Authors: S. E. Leary, C. A. Billups, A. Watkins, J. Wu, D. Poe, M. N. Neel, B. N. Rao, N. C. Daw
Journal: Journal of Clinical Oncology (2008)

10516 Background: The use of chemotherapy has improved the outcome of patients with newly-diagnosed osteosarcoma, but its role in relapsed disease is unclear. Methods: We retrospectively reviewed the records of all patients who were treated for relapsed high- grade osteosarcoma at St. Jude Children’s Research Hospital between 1970 and 2004. Post-relapse event-free survival (PREFS) and post-relapse survival (PRS) were estimated using Kaplan-Meier method and comparisons were made using the exact log-rank test. Results: One hundred ten patients were treated for first relapse (RL1) of high-grade osteosarcoma after primary treatment with surgery and chemotherapy. Median age at initial diagnosis was 14.2 years; 56% were male and 75% were Caucasian. Most tumors (95%) arose in the extremity. Ten-year PRS and PREFS were 18% ± 4.5% and 12% ± 3.5%, respectively. Age, race, gender, metastasis at initial diagnosis (14%), and relapse in lung only (75%) did not significantly correlate with PREFS or PRS (p>0.1). Time from initial diagnosis to RL1 ≥ 18 months (42%), surgery at RL1 (75%), and ability to achieve a second complete remission (CR2) (56%) were favorably associated with PRS and PREFS (p<0.0001). In the 48 patients who did not achieve CR2, use of chemotherapy at RL1 was favorably associated with PREFS (p=0.005) but not with PRS (p=0.8). Median PREFS for the 38 patients who had a failure at any point after receiving four active chemotherapy agents (cisplatin, doxorubicin, ifosfamide, and methotrexate) was 3.7 months (95% CI, 2.2–5.2) and median PRS was 8.2 months (95% CI, 5.7–15.1). Conclusions: The outcome of patients with relapsed osteosarcoma is poor. Late relapse and surgical resection are positive predictors of survival. Chemotherapy may slow disease progression in patients with unresected tumors. Our data is useful for the design of clinical trials that evaluate novel agents, which are desperately needed in this patient population. No significant financial relationships to disclose.
Evaluation of one-step nucleic acid (OSNA) molecular assay for intra-operative diagnosis of sentinel lymph node metastasis.
Authors: Shramana Mitul Banerjee, Timothy Davidson, Nikolaus Michalopoulos, Nuala McDermott, Soha El Sheikh, My-annh Tran-Dang, Stephen Davison, Mohammed R. Keshtgar
Journal: Journal of Clinical Oncology (2012)

194 Background: One step nucleic acid (OSNA) is a recently developed molecular diagnostic assay to detect lymph node metastases. Aim of the present study was to assess OSNA for intra-operative detection of sentinel node metastases with use of standard histopathology as the “gold standard.” Moreover, discordant cases were further investigated to assess their impact on patients’ management. Methods: 157 breast cancer patients with clinically and ultrasonographically negative axilla underwent axillary staging with sentinel node (SLN) biopsy. 244 SLNs were evaluated by OSNA and standard histopathology (alternate slices were submitted to OSNA and standard test). The “turn-around time” taken for an intra-operative OSNA result was recorded. Results: Sensitivity and specificity of OSNA were 92.3% and 95.6% respectively with positive predictive value of 80% and negative predictive value of 98.4%. The average time taken for an intra-operative result in this group was 34 minutes. Concordance rate was 95% while 12/244 nodes showed discordant results between OSNA and Histology. The discordant cases were re-evaluated by histopathologists and characteristics of this subgroup analysed. Patient’s management was altered by OSNA alone in 5 patients as they underwent axillary lymph node dissection on the basis of a positive OSNA when histopathology did not show evidence of metastasis. Two patients with nodes negative on OSNA had histopathology results showing metastases requiring delayed axillary clearance. The rest of the discordant nodes belonged to patients who had other nodes biopsied concurrently that were concordant in OSNA and histology. Conclusions: OSNA is a fast, valuable and highly accurate standardised method for the intra-operative evaluation of axillary lymph node metastasis and is part of our routine intra-operative assessment tool for sentinel nodes in breast cancer.
A randomized placebo-controlled pre-clinical trial of the anti-angiogenic thromobspondin-mimetic peptide ABT-526 plus Lomustine chemotherapy versus Lomustine chemotherapy alone in pet dogs with relapsed non-Hodgkin's lymphoma
Authors: C. Khanna, E. Cozzi, R. Sharpee, D. Vail, J. Graham, B. Kitchell, T. Rusk
Journal: Journal of Clinical Oncology (2004)

3088 Background: Thrombospondin-1 (TSP-1) is a natural antiangiogenic protein that enhances apoptosis of activated endothelial cells (EC). A modified nonapeptide from thrombospondin-1, ABT-526, has been found to be active in mouse cancer models and in dogs with naturally occurring cancers. Methods: To assess the safety and efficacy of ABT-526 when given in combination with Lomustine chemotherapy, 94 pet dogs with naturally occurring non-Hodgkin's lymphoma (NHL), in their first relapse, were entered to a prospective randomized placebo controlled double-blinded clinical trial. Dogs were randomly assigned to receive ABT-526 plus Lomustine versus placebo plus Lomustine. Response rate, duration of response, time to progression, and incidence of toxicoses were compared between groups. Results: No significant ABT-526 specific toxicities were seen. Lomustine associated dose-limiting toxicities, including neutropenia, thrombocytopenia, gastroenteritis, and elevated alanine transaminase, were similar between treatment groups. No significant difference in the objective response rate was seen between treatment groups [ABT-526+Lomustine = 23/49 (47%) vs placebo+Lomustine = 23/37 (62%); P>0.25]. However, the median response duration was significantly greater in patients receiving ABT-526 plus Lomustine compared to placebo plus Lomustine (35 days vs 15 days; P=0.05). The time to progression for responding cases was also significantly greater in patients receiving ABT-526 plus Lomustine compared to placebo plus Lomustine (41 days vs 21 days; P=0.047). Conclusions: The significant activity of ABT-526 demonstrated in this preclinical trial appears to be associated with the maintenance of Lomustine induced treatment responses. Further studies of ABT-526, in this relevant naturally occurring model of NHL, are warranted and may be used to define biomarkers that predict responsiveness to antiangiogenic therapy and evaluate the activity of ABT-526 in combination with conventional and novel treatment agents. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott; Animal Cancer Institute Abbott Laboratories Abbott Abbott Laboratories
Association of alkaline phosphatase (ALP) with clinical outcomes in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results from COU-AA-302.
Authors: Evan Y. Yu, Fred Saad, Anil Londhe, Neal D. Shore, Hendrik Van Poppel, Dana E. Rathkopf, Matthew R. Smith, Christopher Logothetis, Paul L. De Souza, Karim Fizazi, Peter F.A. Mulders, Paul N. Mainwaring, John D. Hainsworth, Tomasz M. Beer, Scott A. North, Eric Jay Small, Howard I. Scher, Thomas W. Griffin, Margaret K. Yu, Charles J. Ryan
Journal: Journal of Clinical Oncology (2014)

27 Background: Prognostic models have been developed for men with mCRPC. In this analysis we undertook a pragmatic approach to focus on commonly obtained markers. Baseline ALP and normalization of elevated ALP post-docetaxel have prognostic value for overall survival (OS). We examined the association between ALP and prostate-specific antigen (PSA) elevation at baseline and after 4 cycles of therapy (C5D1), when both markers were assessed, with long-term clinical outcomes in COU-AA-302, a randomized phase 3 study of abiraterone acetate (AA) in chemotherapy-naive mCRPC pts. Methods: 1,088 pts were randomized 1:1 to AA (1 g) + prednisone (P) (5 mg BID) or placebo + P. Radiographic progression-free survival (rPFS) and OS were co-primary end points. The study design, as well as primary and secondary end point results obtained at the time of a prespecified interim analysis at 55% OS events, have been described in detail previously. The effect of elevated ALP (above upper limit of normal) and PSA (above 106.2 µg/mL, baseline third quartile) status on rPFS and OS was assessed retrospectively using a stratified Cox regression model that included treatment and baseline factors log (lactate dehydrogenase), hemoglobin, whether patient had only bone metastasis, and age. Results: Elevated status of ALP and PSA were independent significant predictors of increased risk for outcomes at baseline as well as after 4 cycles of therapy (Table). Conclusions: These post hoc analyses of data from COU-AA-302 suggest that elevated ALP and PSA at baseline and during treatment confers individual and additive risk for adverse clinical outcomes in chemotherapy-naive mCRPC. Clinical trial information: NCT00887198. [Table: see text]
Resolution of venous thrombo-emboli (VTE) with a factor Xa inhibitor: Initial safety and efficacy results of a randomized, phase III trial of anticoagulation plus inferior vena cava (IVC) filter versus anticoagulation alone in patients with cancer and VTE
Authors: M. F. Barginear, D. R. Budman, R. J. Gralla, I. Shapira, T. P. Bradley, M. Akerman, C. Greben, M. Strakhan, A. Chandok, M. Lesser
Journal: Journal of Clinical Oncology (2008)

20544 Background: Cancer-associated thrombosis is a major cause of death in patients (pts) with cancer. The 1-year survival in pts with cancer with VTE is 12% (vs. 36% without VTE). More than 20% of pts have VTE propagation and re-thrombosis on standard therapeutic anticoagulation (AC) (Prandoni 2007). The role of IVC filters in terms of efficacy, safety, prevention of pulmonary embolism (PE), and impact on survival remains controversial. Resolution of DVT takes an average of 6 months in non-cancer pts (Asbeutah 2004) and thrombi remain detectable in half of pts after a year (Kearon 2004). Methods: Pts with malignancy were eligible if they had an acute VTE (DVT and/or PE), and were randomized to standard fondaparinux sodium (FS) alone [5mg SC for pts <50 kg, 7.5mg SC for pts 50–100 kg and 10mg SC for pts >100 kg] vs FS+IVC filter. A total of 106 pts are planned. The primary endpoint is survival without recurrent VTE. Secondary endpoints include safety and clot resolution, given in this report. Due to safety review in pts ≥ 65 yrs, the dose of FS was reduced to 5mg during the conduct of the study. Pts were evaluated q 2 weeks for 4 weeks then q 4 weeks. Results: To date 33 pts were randomized and treated. All have stage IV extent, 94% are on chemotherapy; median age 67 (range 38–89%). Diagnoses include: lung (25%), GI (22%), and breast (19%); 9% have brain metastases. Of pts re-evaluated with DVTs: 15/20, 75% [95% CI: 44–90%] had complete clot resolution at an average of 45 days. Of those with PE: 8/9, 89% [95% CI: 52–100%] had complete clot resolution. Toxicities were more prominent in pts ≥ 65, 1 with marked ecchymosis and 1 with fatal hemorrhage into a brain metastasis. Conclusions: This study is ongoing and remains blinded as to treatment arm; however, current observations are important: 1) complete clot resolution has been observed in many, despite past studies using low molecular weight heparins not reporting such resolution in cancer patients; 2) the factor Xa inhibition may be responsible for this clot resolution effect; 3) the FS was well tolerated and appears safe in those over age 65 at a lower dose. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline
p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases.
Authors: C Belluco, J G Guillem, N Kemeny, Y Huang, D Klimstra, M F Berger, A M Cohen
Journal: Journal of Clinical Oncology (1996)

To determine whether p53 protein expression is similar within primary colorectal cancer (CRC) and synchronous regional and distant metastases and to assess whether p53 nuclear protein expression could predict outcome in patients with synchronous unresectable liver metastases treated by hepatic artery infusional (HAI) chemotherapy.Paraffin sections from tumor and corresponding normal mucosa representative of 50 consecutive advanced CRC cases were examined for p53 nuclear protein expression by immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53 nuclear expression were correlated with standard clinicopathologic variables and outcome, including response to HAI and survival. In a subset analysis, the pattern of nuclear p53 immunoreactivity was compared between primary CRC and lymph node and liver metastases.Positive nuclear immunoreactivity for p53 protein was found in 72% of cases. The pattern of p53 protein expression in lymph node and liver metastases was identical to that of the primary tumor. The median survival time was 21.0 months in patients with p53-positive tumors and 53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two-year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant difference was found in the response rates to HAI chemotherapy between the two groups. By multivariate analysis, p53 protein status was the single best predictor of survival, with a relative risk of 6.312.Our results indicate that nuclear p53 protein status in primary CRC is similar to that in metastatic sites and may be the dominant predictor of survival in patients with advanced hepatic metastases.
An exploratory analysis of comprehensive geriatric assessment results and overall survival in 233 consecutive elderly cancer patients
Authors: D. Poon, H. H. Lee, L. L. Chan, R. Yap, W. H. Koo
Journal: Journal of Clinical Oncology (2009)

9504 Background: Performance status (PS) is the main clinical parameter used by most oncologists to assess the ability of elderly cancer patients to tolerate chemotherapy and estimate prognosis. The results of comprehensive geriatric assessment (CGA) for elderly cancer patients were analyzed to investigate the impact of each CGA functional, physical, cognitive, and affective domain on overall survival in relation to performance status. Methods: CGA was used for 233 consecutive elderly cancer patients aged 70 and above. CGA tools included the Katz index of daily activities independence (ADL), instrumental activities of daily living (IADL), mini-mental state examination (MMSE), geriatric depression scale (GDS), Charlson comorbidity risk index, get up and go test, and mini-nutritional assessment. Geriatric syndrome is defined as any high risk of falls, depression, dementia, increased functional dependence, or malnutrition. Eastern Cooperative Oncology Group (ECOG) scale was used to grade PS. Cancer type and stage were also analyzed. Log rank test was used to compare overall survival and hazard ratio (HR) derived using Cox regression method. Univariate and multivariate analyses were done to assess impact of ECOG status, presence of geriatric syndrome, stage of disease and cancer type on overall survival. Results: All 233 patients were included in the analysis, median age 77 (70 - 93), all had solid tumors and predominant tumors comprising 79% of diagnoses were colorectal, lung and breast, 50% had advanced metastatic disease. ECOG grades 2,3,4 (HR 0.28, 95% CI 0.14 - 0.55), dependent IADL status (HR 0.30, 95% CI 0.11 - 0.83), presence of geriatric syndrome (HR 0.42 95% CI 0.26 - 0.69), poor cognition (HR 0.53 95% CI 0.36 - 0.77), or advanced disease (HR 0.30 95% CI 0.14 - 0.65) was associated with inferior overall survival in univariate analysis. Only poor ECOG status, presence of a geriatric syndrome and advanced disease predicted adversely for overall survival in multivariate analysis. Poor cognition (MMSE score &lt;24) in those with borderline ECOG 2 status was associated with poorer survival (HR 0.38 95% CI 0.33 - 0.90). Conclusions: Utility of CGA will improve the assessment of the elderly cancer patient. No significant financial relationships to disclose.
Neoadjuvant Chemotherapy and Hormonal Therapy Followed by Radical Prostatectomy: Feasibility and Preliminary Results
Authors: Curtis A. Pettaway, Louis L. Pisters, Patricia Troncoso, Joel Slaton, Laury Finn, Kazumi Kamoi, Christopher J. Logothetis
Journal: Journal of Clinical Oncology (2000)

PURPOSE: We assessed the feasibility and efficacy of integrating chemotherapy and androgen ablation with radical prostatectomy in patients with locally advanced prostate cancer. The neoadjuvant approach was adopted because it allows an in situ assessment of antitumoral activity. PATIENTS AND METHODS: Thirty-three patients were enrolled who met the clinical criteria of stage T1–2, Gleason score of ≥ 8 or T2b-T2c, Gleason score of 7 and prostate-specific antigen (PSA) level greater than 10 ng/mL (n = 15), or clinical stage T3 (n = 18). Therapy consisted of 12 weeks of ketoconazole and doxorubicin alternating with vinblastine, estramustine, and androgen ablation followed by prostatectomy. The ability of neoadjuvant chemotherapy and hormonal therapy to induce a 20% rate of pT0 in the prostatectomy specimen as well as surgical feasibility were assessed. RESULTS: Chemotherapy complications were comparable to those reported with this regimen previously. No major intraoperative complications occurred. Postoperative complications occurred in 10 (33%) of 30 patients. One patient died at home after discharge (postoperative day 17; no autopsy was performed). Ten (33%) of the 30 patients had organ-confined disease, and 20 (70%) of 30 had extraprostatic extension; 11 (37%) of the 30 had positive lymph nodes. Only five (17%) of 30 exhibited positive surgical margins. All patients achieved an undetectable PSA level postoperatively, and 20 of the surviving 29 patients remain without disease recurrence with a median follow-up of 13 months (range, 9 to 18 months). CONCLUSION: Chemotherapy and androgen ablation followed by radical prostatectomy was feasible in patients with locally advanced prostate cancer. Although the goal of achieving a 20% rate for pT0 status was not achieved, we believe this type of integrated therapeutic strategy should be investigated further for its ability to alter the course of regionally advanced prostate cancer.
Sinonasal poorly differentiated carcinoma presenting clinically as esthesioneuroblastoma
Authors: A. Kumar, T. Bentley
Journal: Journal of Clinical Oncology (2004)

5605 Background: Sinonasal undifferentiated carcinoma presenting clinically as esthesioneuroblastoma is a rare finding. Method: A 54 year old white male presented with progressive double vision, left nasal congestion, proptosis of left eye and intermittent pain in left eye and frontal sinus region of 7–8 months duration. Examination revealed a large deforming mass involving the left proximal nasal cavity extending into the mid forehead protruding through the frontal bone. Intranasal cavity revealed edematous mucosa with soft tissue mass filling mid aspect of nasal cavity on the left. Neurological examination was non focal. CT scan revealed a large destructive mass involving the left nasal cavity and ethmoid sinus extending into the left orbit with displacement of the globe and destruction of the anterior cranial fossa including the frontal bone. MRI revealed a large sinonasal tumor (5.2x7x7.5cm) extending through the cribriform plate, anteromedial floor of the middle cranial fossa and through the inner and outer table of the frontal bones, more to the left than to the right of midline. A mass effect on the brain was noted but primarily appeared to be displacing rather than invading the brain. Result: Biopsy revealed poorly differentiated carcinoma. IHC stains showed cytokeratin positivity and were negative for CD99, NSE and synaptophysin. He is currently being treated with combined radiation therapy and chemotherapy (carboplatin/paclitaxel). Conclusion: Here we describe a patient who initially presented with signs and symptoms clinically and radiologically highly suspicious for esthesioneuroblastoma(ONB) but found to have carcinoma as per histology, which is a rare presentation. ONB is a rare tumor located in the roof of the nasal cavity and paranasal sinuses. Immunohistochemically, it typically exhibit positive staining for NSE, synaptophysin and chromogranin. These are negative for a variety of other markers, including CD99. Sinonasal undifferentiated carcinoma(SUC) cells are reactive for cytokeratin (90%) and EMA (65%). SUC behaves aggressively. Most patients have locally extensive disease and often, distant metastases at diagnosis. Multimodality approaches (eg, sequential chemotherapy, radiation therapy and craniofacial resection) can cure some patients with localized disease. No significant financial relationships to disclose.