tbuckley/cabot-search huggingface dataset:
Utility of immunohistochemistry tissue array in the prediction of epithelial ovarian carcinoma response to therapy
Authors: T. O. Kirby, W. K. Huh, R. S. Seitz, J. E. Kendrick, Y. Wang, R. Beck, S. Defoe, B. Z. Ring, D. T. Ross
Journal: Journal of Clinical Oncology (2005)

5033 Background: Ovarian carcinoma is generally associated with poor prognosis, yet there exists significant variability in outcome amongst patients with similar pathological diagnoses. Robust markers to predict response to therapy are lacking. We sought to define prognostic categories for epithelial ovarian cancer using immunohistochemistry tissue microarray (TMA) technology. Methods: All patients from 1995- 2003 with epithelial ovarian or primary peritoneal carcinoma undergoing initial debulking at a single institution were included. TMA’s were constructed using 0.6mm cores obtained from paraffin embedded blocks and according to standardized protocols using an ordinal scoring system. Antibodies were selected based on targets suggested by large-scale gene expression studies. Univariate analyses were used to identify IHC biomarkers associated with increased disease free survival (DFS), platinum sensitivity (PS), and optimal debulking status. Significant or near-significant variables (p<0.10) were then used in an unsupervised two-step cluster analysis to identify patient groups distinguished by patterns of IHC staining. These cluster groups were analyzed for association with DFS and PS using Cox and logistic regression analysis controlling for stage, grade, histology, and debulking status. Results: 161 (127 St III/IV, 23 St II, 9 St I, 2 unk) patients were evenly distributed with respect to debulking status (75 optimal, 72 suboptimal, 14 unknown). Of the 22 proteins analyzed by univariate analysis, 5 were found to be significantly associated with DFS and 2 with debulking status. Two-step cluster analysis distinguished 3 patient clusters of which membership in cluster 1 (n=82, 50.9%) was associated with significantly longer DFS, optimal debulking and PS. Cox regression analysis demonstrated that the association with DFS was independent of stage, grade, histology, and debulking status. Conclusions: TMA based technology represents a cost-effective method for discovery of prognostic IHC classifiers for epithelial ovarian cancer. Univariate analysis combined with cluster analysis of TMA data has the ability to discriminate classifiers with clinical prognostic significance. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Applied Genomics
Correlation of New Method for Measuring Plasma Myeloperoxidase with Clinical Behavior in Acute Myeloid Leukemia and Myelodysplastic Syndrome.
Authors: Adam Abdool, Xiugiang Wang, Iman Jilani, Weidong Zhou, Hagop Kantargian, Elihu Estey, Francis Giles, Maher Albitar
Journal: Blood (2007)
Association of genome-wide copy number alterations with metastasis of clear cell renal cell carcinoma.
Authors: Banumathy Gowrishankar, Venkata Jaganmohan Thodima, Ana M. Molina, Charles Ma, Asha Guttapalli, Theresa Margaret Gold, Robert J. Motzer, Raju S.K. Chaganti, Jane Houldsworth
Journal: Journal of Clinical Oncology (2015)

428 Background: About one-third of patients with clear cell renal cell carcinoma (ccRCC) exhibit metastasis at the time of diagnosis and show poor prognosis. The genetic and epigenetic alterations associated with metastasis in ccRCC have variably been studied, and their role in the metastatic process is unclear. The goals of the current study were to identify genomic copy number alterations (CNAs) associated with ccRCC metastasis and examine their clinical utility. Methods: In this IRB-approved study, genome-wide copy number profiling was performed on DNA from 144 ccRCC (81 primary and 63 metastatic lesions). Differential CNAs between primary and metastatic lesions and between different metastatic sites were identified using Fisher’s exact test. Associations between CNAs and overall survival (OS) were tested using the log rank statistic and Kaplan-Meier method. Genomic profiling data of 437 and 240 primary ccRCC (TCGA and PMID: 23797736, respecitively) were used for verification. Results: Between primary and metastatic lesions, 25 CNAs were significantly different (p&lt;0.05). Of the 11 more frequent in metastatic lesions, nine retained significance when comparing stage IV and stage I TCGA ccRCC. For 368 TCGA locally-invasive tumors (stages I, II, and III), three CNAs (loss of 9p24.3-p13.3, 9p12-q11, and 9q21.12-q21.33) were associated with inferior survival (p=0.002). In the second dataset of 214 locally-invasive lesions, loss of 18q11.2-q23 correlated with shorter OS (p=0.025). Across metastatic lesions, nine CNAs were found to be significantly enriched in lung lesions and three in bone. In a subset of 127 ccRCC with known metastatic status at 5 years after diagnosis, two of these CNAs (gain of 7q36.1-36.3 in lung and loss of 22q13.2 in bone) were significantly enriched in the corresponding primary specimens. Conclusions: This study identified CNAs associated with ccRCC metastasis and common sites of metastasis that have the potential to serve as biomarkers to assist in better risk stratification of patients with this disease. Integrated analyses of genes mapping to the loci of genomic imbalance would further our understanding of the biology of metastasis in renal cancer.
Nomograms for prognostication of patients with esophageal and gastroesophageal carcinoma undergoing definitive chemoradiotherapy.
Authors: Akihiro Suzuki, Lianchun Xiao, Yuki Hayashi, Mariela Anabel Blum, James Welsh, Steven H. Lin, Jeffrey H Lee, Manoop S. Bhutani, Brian Weston, Dipen Maru, David C. Rice, Wayne Lewis Hofstetter, Jeremy J. Erasmus, Stephen Swisher, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2012)

82 Background: Level-1 evidence for definitive chemoradiotherapy (bimodality therapy or BM therapy) has been established for patients with esophageal and gastroesophageal junction cancers (EGEJC) who otherwise do not qualify for surgery; however, tools to estimate individual patient’s prognosis are unavailable. We used a number of clinical pre-treatment and post-treatment parameters to establish two nomograms (for overall survival [OS] and relapse-free survival [RFS]). Methods: From 2002 through 2010, 257 consecutive patients with EGJEC who received BM therapy and had pre- and post-treatment positron emission tomography (PET) and post-treatment endoscopic biopsies among other assessments were analyzed from a prospectively maintained database. Standard statistical methods were used to generate the nomograms. Results: The median follow -up time was 39.2 months (95% confidence interval [CI], 35.7 – 50.1). None of 257 patients underwent surgery. Persistent or recurrent cancer was documented in 187 (72.8%) patients. The estimated median survival duration for all 257 patients was 21.1 months (95% CI, 18.9-27.1) and median RFS duration was 11.6 months (95% CI, 9.43-15.0). The estimated OS and RFS rates at 3 years were 37.3% (95% CI, 31.2%-44.7%) and 25.1% (95% CI, 19.9%-31.6%), respectively. After BM therapy, 155 (60.3%) patients achieved a clinical complete response (cCR). In the multivariate analyses, initial standardized uptake value maximum and cCR were independent prognostic variables for OS (P=0.038, P&lt;0.001). Nomogram concordance indices of 0.70 for OS and 0.77 for RFS were established by 200 bootstrap resampling for each of the two outcomes. Conclusions: Our data suggest that in patients with EGEJC, pre- and post-treatment clinical parameters contribute to the establishment of OS and RFS prognostic nomograms. Upon validated, these nomograms could prove useful in the clinic to individualize therapy.
Do pre-treatment haemoglobin levels predict for response to neoadjuvant chemotherapy in breast cancer?
Authors: M. J. Beresford, M.-L. Ah-See, R. Burcombe, J. Dixon, P. Ostler, M. Harrison, M. Pittam, R. Ravichandran, A. Makris
Journal: Journal of Clinical Oncology (2005)

809 Background: A low pre-treatment haemoglobin (Hb) level has been shown to negatively influence outcome in the management of tumours of the cervix, bladder and head and neck. In a previous study in breast cancer, low Hb levels prior to neoadjuvant chemotherapy (NAC) were associated with a poor response. The purpose of this study is to further assess the influence of Hb levels on NAC for breast cancer. Methods: 139 patients receiving NAC for operable breast tumours (T2–4, N0–1, M0) were accessed from our prospective database. Patients were treated between March 1999 and June 2004. Median age was 47 (range 25–70). 90 patients (64.7%) were oestrogen receptor (ER) positive, 40 (28.8%) were ER negative and 9 (6.5%) of unknown ER status. Chemotherapy regimens included FEC (5-fluorouracil, epirubicin, cyclophosphamide - 122 patients), AC (doxorubicin, cyclophosphamide - 9 patients), MMM (methotrexate, mitomycin and mitoxantrone - 5 patients) and docetaxel (3 patients). Patients received 4–6 cycles of chemotherapy prior to surgery. The clinical measurement of response was defined according to UICC criteria. Baseline Hb levels were compared for responders (partial or complete) and non-responders (stable or progressive disease) using the Mann-Whitney U test. Results: Overall response rate was 84.9% (118/139) with a clinical complete response rate of 15.8% (22/139). Median Hb levels were 13.4 in responders and 13.5 in non-responders (range 7.9 to 15.8). The distributions of the Hb levels were not significantly different when comparing either responders with non-responders or complete responders with those that did not achieve complete response (p=0.79 and p=0.51 respectively). Conclusions: Pre-treatment Hb levels appear to have no influence on response to neoadjuvant chemotherapy in breast cancer. It is unlikely that correction of anaemia above that which is warranted clinically will improve response rates. No significant financial relationships to disclose.
Symptomatic presentation as a predictor of recurrence in gastroenteropancreatic neuroendocrine tumors: A single institution experience over 15 years.
Authors: Gillian G. Baptiste, Lauren McLendon Postlewait, Cecilia G. Ethun, Nina Le, Mia R. McInnis, Maria C. Russell, Joshua H. Winer, David A. Kooby, Charles A. Staley, Shishir Kumar Maithel, Kenneth Cardona
Journal: Journal of Clinical Oncology (2016)

228 Background: The prognostic implications on outcomes of symptomatic presentation of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) remains unclear. Methods: Patients who underwent curative-intent resection of nonfunctional, well-differentiated GEP NETs from 2000-2014 at a single institution were analyzed. Patients were classified as symptomatic if clinical symptoms were present at diagnosis. Primary end points were distant recurrence-free survival (DRFS) and overall survival (OS). Results: A total of 339pts were identified, of which 208pts (61%) were symptomatic at presentation. Symptomatic presentation was associated with younger age at presentation (55vs59yrs, p = 0.001), higher tumor grade (38vs21%, p = 0.027), LVI (58vs33%, p &lt; 0.001), PNI (53vs30%, p = 0.002), and advanced disease (T3/T4/N1/M1 63vs44%, p = 0.002), but not tumor size (2.6vs2.5cm, p = 0.74). Symptomatic presentation was associated with decreased DRFS but not OS. When accounting for race, tumor size, positive resection margins, presence of metastatic disease, and positive lymph nodes on multivariate analysis (MVA), symptomatic presentation remained independently associated with reduced DRFS (HR 3.51, p = 0.007). On subgroup analysis of patients only with advanced disease (T3/T4/N1/M1), symptomatic presentation was still associated with decreased 3-yr DRFS (67vs79%, p = 0.012), but not OS. On MVA, symptomatic presentation persisted as an independent factor associated with decreased DRFS in patients with advanced disease (HR 2.89, p = 0.014). Conclusions: Symptomatic presentation of GEP NETs is associated with more aggressive pathologic features and worse DRFS than incidentally diagnosed NETs irrespective of tumor size. As our armamentarium of therapeutic agents for NETs expands and improves, trials assessing the value of adjuvant therapy for advanced GEP NETs are needed, and symptomatic presentation may be considered as one inclusion criterion. Following resection, symptomatic presentation should be taken into account when planning follow-up strategies, as these patients may require closer surveillance than their incidentally diagnosed counterparts.
Phase I trial of concurrent erlotinib, celecoxib, and reirradiation for recurrent head and neck cancer.
Authors: J. Kao, S. H. Packer, M. Teng, V. Gupta, K. Misiukiewicz, E. M. Genden
Journal: Journal of Clinical Oncology (2010)

5561 Background: Concurrent inhibition of EGFR and COX-2 has previously been shown to be an active and well tolerated regimen in recurrent head and neck cancer (Wirth, JCO 23: 6976, 2005). Based on robust preclinical data, we tested concurrent erlotinib and celecoxib as radiosensitizing agents. Methods: Patients with unresectable or high risk adjuvant (microscopic positive margins or extracapsular extension) head and neck cancer and M0 requiring reirradiation were eligible. Eligible patients received celecoxib (200 to 600 mg BID) and erlotinib (150 mg QD) starting 14 days prior to and concurrent with reirradiation (IMRT 60 to 72.4 Gy in 2.2 Gy QD M-F). The primary objective was to determine the safety, tolerability, and maximum tolerated (MTD) dose of celecoxib. The starting dose was celecoxib 200 mg BID escalated to 400 mg BID and 600 mg BID using a 3+3 design with an expanded cohort at the MTD. Results: Between 3/07 to 12/09, 15 pts were enrolled with a median follow-up of 10 months. Patient characteristics include median age 68 (6 age >75); 11 male; 10 with ECOG PS 2, 9 had unresectable disease, 3 with second primaries, 8 received prior chemotherapy and median prior RT dose was 62 Gy. There were no dose limiting toxicities (DLTs) in dose levels (DL) 1 and 2. Two of three patiens at DL3 developed DLTs consisting of gr 3 bone necrosis and trismus. Therefore, celecoxib 400 mg BID was declared the MTD with concurrent erlotinib and reirradiation. Overall gr ≥3 toxicities were uncommon and consisted of gr 3 mucositis (n=3), gr 3 dermatitis (n=2), and gr 3 pain (n=3). At last follow-up, five are alive with no evidence of disease (NED), three developed locoregional progression, three had distant progression, one had both local and distant progression and three are NED but succumbed to comorbid illness. Maintenance erlotinib 150 mg QD until progression was allowed but only 3 patients participated. Conclusions: Concurrent erlotinib, celecoxib and reirradiation is a well tolerated regimen that demonstrates activity in a difficult to treat population of previously irradiated patients. These data suggest that this regimen warrants further study particularly in patients who failed chemoradiation or elderly patients with PS 2. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Genentech, sanofi-aventis OSI, Pfizer
Monitoring the Therapy of Extensive Osseous Sarcoidosis With FDG PET/CT
Authors: Hua Yang, Shah Numani, Shuang Liu
Journal: Clinical Nuclear Medicine (2017)

FDG PET/CT was performed in a 47-year-old man to evaluate possible malignancy of the spine revealed by MRI. The PET images revealed numerous focal FDG activity throughout the skeletal system. In addition, multiple foci of the increased activity in the mediastinal and hilar nodes were noted, suggestive of sarcoidosis, which was proven following biopsy. Therapy for sarcoidosis was initiated. In the subsequent 4 follow-up FDG PET/CT scans, the activity in both the bones and mediastinal/hilar regions fluctuated. However, anatomical abnormality in the bones on the CT images was never visualized during the entire clinical course.
Incidence and natural history of bone metastases in neuroendocrine tumors.
Authors: Jennifer Keiser, Eric K. Nakakura, Laurel Imhoff, Margaret A. Mayorga, Sarah Bobiak, Alan Paul Venook, Emily K. Bergsland
Journal: Journal of Clinical Oncology (2012)

340 Background: Bone metastases (BM) occur in carcinoids and other neuroendocrine tumors (NET), however, a comparative analysis of the incidence and natural history of BM across different NET subtypes has not been performed. We retrospectively characterized BM incidence, complications, and management across five subtypes: carcinoid/unknown primary (CARC), pancreatic NET (PNET), pheochromocytomas/paragangliomas (PHEO), adrenal cortical carcinoma (ACC) and high grade NET (HGNET) using data collected in the context of the NCCN NET Outcomes Database. Methods: 296 NET patients (pts) presenting at UCSF from 2004 to 2007 were retrospectively identified. Eligibility criteria included presentation on or after Jan 1, 2004, continued management at UCSF within one year of consultation, age over 18, and pathological confirmation of an eligible NET subtype. BM identified radiographically and/or pathologically, and classified as symptomatic (pain, pathologic fracture, or spinal cord compression) or asymptomatic. BM treatments (tx) included radiation, surgery, bisphosphonate and/or denosumab. Results: BM identified in 36/296 (12%): 29% pts with HGNET (5/17), 10% pts with CARC (12/121), 7.4% pts with PNET (6/81), 17% pt with PHEO (11/66), 18% pt with ACC (2/11). BM occurred in 21 men/15 women; median age 54. 30/36 (83%) had stage IV disease at diagnosis (dx); 69% had BM at dx. 69% pts were eventually symptomatic: bone pain (24/25, 96%), cord compression (3/25, 12%) and/or pathologic fracture (6/25, 24%); 8/25 (32%) had more than one symptom from BM. Median survival from BM: 28 mo (21.1 mo if symptomatic; 34.3 mo if asymptomatic). Overall, 81% (29/36) pt received tx for BM: 53% XRT (19/36), 25% surgery (9/36), 39% bisphosphonate (14/36), and/or 11% denosumab (4/36). Conclusions: 12% of pts with NET in this database developed BM. Most pts with BM experienced pain. Serious complications such as cord compression and/or pathological fracture occurred in 36% (9/25) suggesting that bisphosphonate and/or denosumab tx may be of value in these patients. Accrual to the database is ongoing.
Utilization of radiotherapy for prostate cancer according to urologists’ practice patterns.
Authors: Stephen Bentley Williams, Jinhai Huo, Benjamin D. Smith, Karen E. Hoffman
Journal: Journal of Clinical Oncology (2016)

11 Background: Physician practices that offer ancillary medical services may refer their patients for such services, a process known as self-referral. Self-referral for radiation therapy according prostate cancer risk and cost of care is not known. We evaluated how utilization and cost of care differ for men diagnosed with prostate cancer in a self-referring urologic practice (SRP) compared to a traditional urologic practice. Methods: 17,982 men 66 years and older diagnosed with localized prostate cancer from 2006 to 2009 were identified from the Texas Cancer Registry. Disease was classified as favorable if low-grade and clinical T1 or T2. The diagnosing urologist was classified as being affiliated with a SRP if their practice owned a linear accelerator. Multilevel logistic regression models evaluated the odds of receiving a specific type of treatment adjusted for diagnosis year, age, comorbidities, race/ethnicity, income, education, clinical tumor stage, and tumor grade. Cost of care was calculated from Medicare expenditures within 12 months of diagnosis. Results: Diagnosis in a SRP increased from 2.2% of prostate cancers in 2004 to 24.5% in 2009 (p&lt; 0.001). Men diagnosed in SRPs were more likely to receive upfront treatment (vs. watchful waiting/active surveillance) than men diagnosed by traditional practices (92.7% vs. 89%; AOR 1.61, p&lt;0.001) and were more likely to be treated with external beam radiation (47.4% vs. 34.1%; AOR 1.59, P&lt;0.001). This persisted for both favorable and unfavorable risk cancer. Men diagnosed in SRPs were more likely to receive upfront treatment (favorable: 92.9% vs. 87.1%; AOR 1.89, p&lt;0.001; unfavorable: 97.9% vs. 95.0%; AOR 2.07, p=0.002) and more likely to be treated with EBRT (favorable: 41.2% vs. 31.1%; AOR 1.45, p=0.002; unfavorable: 49.0% vs. 38.1%; AOR 1.53, p&lt;0.001). Median annual prostate cancer care cost was $2,460 (95% CI $1,663-$3,368) higher for men diagnosed by SRPs. Conclusions: Older men diagnosed with prostate cancer in SRPs are more likely to undergo upfront treatment and to receive radiation treatment. This may increase appropriate treatment of unfavorable disease but contribute to overtreatment of favorable disease.
A phase 1 study of repeat radiation, minocycline, and bevacizumab in patients with recurrent glioma (RAMBO).
Authors: Adam Louis Cohen, Christopher James Anker, Karen Salzman, Randy L. Jensen, Dennis C. Shrieve, Howard Colman
Journal: Journal of Clinical Oncology (2014)

2066 Background: There are no proven therapies for glioblastoma after progression on bevacizumab. Mesenchymal shift mediated by microglia-mediated NF-kappaB activation is one mechanism of treatment resistance in recurrent glioblastoma. Minocycline inhibits NF-kappaB activation and can restore radiation sensitivity to glioblastoma in vitro and in vivo. Methods: RAMBO is a phase 1 study of reirradiation, bevacizumab, and minocycline in people with glioblastoma that has progressed on bevacizumab who are at least one year away from prior radiation. The minocycline is dose escalated in a 3+3 design with planned cohorts of 100mg PO BID (cohort 1), 200mg (cohort 2), and 400mg PO BID (cohort 3). Results: Cohorts 1 and 2 have been completed. Completion of cohort 3 is expected by the meeting. No dose limiting toxicities have been encountered. Two people dropped out because of clinical progression and decision to go to hospice, and one person dropped out after 1 week due to unwillingness to take antiemetics for grade 1 nausea. No grade 3 toxicities unrelated to tumor progression have been seen other than one case of grade 3 asymptomatic hypertension attributed to bevacizumab and one case of grade 3 hypokalemia. Grade 2 toxicities have included 3 cases of fatigue, one case of anemia, one case of hiccups, three cases of hypertension, one case of intracranial hemorrhage, one case of nausea, one case of thrush, and one case of vertigo. Of these, only the nausea, fatigue, and thrush were thought possibly related to the minocycline. Conclusions: Minocycline can be safely combined with radiation and bevaciuzmab in glioblastoma patients who have progressed on bevacizumab. Clinical trial information: NCT01580969.