tbuckley/cabot-search huggingface dataset:
Insulin-like growth factor receptor-1 (IGF1R) and epidermal growth factor receptor (EGFR) amplification and expression in surgically resected NSCLC.
Authors: V. Ludovini, A. Flacco, F. Bianconi, F. R. Tofanetti, M. Ragusa, J. Vannucci, G. Bellezza, M. G. Mameli, R. Chiari, V. Minotti, L. Pistola, A. Siggillino, E. Baldelli, A. Sidoni, F. Puma, M. Varella-Garcia, L. Crinò
Journal: Journal of Clinical Oncology (2011)

10519 Background: IGF1R represents a novel molecular target in non-small cell lung cancer (NSCLC). IGF1R and EGFR activation is essential to mediate tumor cell survival, proliferation and invasion. This study investigates the prognostic role of IGF1R and EGFR copy number gain (CNG) by fluorescence in situ hybridization (FISH) and protein overexpression by immunohistochemistry (IHC) in surgically resected NSCLC. Methods: 114 NSCLC patients were evaluated; median age was 66y (range 40–84), Male/Female:96/18; squamous (SCC)/adeno/BAC/other:59/34/9/12; smoker/never smoker:105/9, and stage I/II/III:71/18/25. IGF1R and EGFR FISH were tested by customized and commercial probes, respectively; positive specimens showed gene amplification or polysomy (≥4 copies in ≥10% of tumor cells). IGF1R and EGFR protein expression were evaluated using mouse antibodies (clones 24-31 and 3147, respectively); overexpression was defined by ≥10% positive cells. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical and biologic variables using Cox model for multivariate analysis. Results: 46 tumors (40%) were IGF1R FISH+ and 76 (77%) were EGFR FISH+. IGF1R FISH+ was associated with EGFR FISH+ (p=0.03) and co-amplification was observed in 34 cases (30%). IGF1R and EGFR FISH+ were associated with SCC (p=0.01 and p=0.05, respectively). IGF1R and EGFR overexpression was detected in 36% and 55% of NSCLC patients and co-expression was detected in 25%. Co-amplification and co-expression of both receptors were significantly associated (p=0.045). IGF1R and EGFR co-amplification and co-expression associated with shorter disease free survival (DFS; p=0.05, p=0.05 respectively), also at multivariate analysis adjusting for stage (p=0.0002). Conclusions: IGF1R and EGFR are frequently co-amplified in NSCLC and CNG correlates with protein overexpression. Both co-amplification and co-expression of IGF1R and EGFR predicts shorter DFS. These results provide a strong rational for targeting simultaneously EGFR and IGF1R in clinical trials for NSCLC. We thank the Italian Association for Cancer Research (AIRC) for supporting the study (AF Fellowship).
Physician office visits for cancer survivors: Results from a national survey.
Authors: Michael T. Halpern, Brenda Vincent, Dana Wollins
Journal: Journal of Clinical Oncology (2016)

33 Background: Cancer survivors may require specialized medical care to address their unique needs. However, there are few reports of nationally-representative outpatient-care patterns among survivors. Methods: We examined adult cancer survivors’ outpatient medical visits using data from the 2010 &amp; 2012 National Ambulatory Medical Care Survey (NAMCS), a survey of U.S. physician office-based visits. Survivors were identified as individuals with medical visits related to cancer (based on physician diagnosis codes or patient-supplied reasons for visit) but who did not currently have cancer. Weights from the NAMCS were used to produce results corresponding to the overall U.S. population. Results: The NAMCS data included 477 survivor visits, corresponding to a two-year nationally-representative weighted total of 7,435,753 visits. Most survivors were White (75%); 13% were Black and 8% Hispanic. Most survivors had private insurance (49%) or Medicare (40%); 4% had Medicaid. Almost all (99%) saw a physician during the recorded visit. Only 20% of survivor’s outpatient visits were with oncologists; 20% were with primary care physicians, 12% with OB/GYN physicians, 5% with general surgeons, and more than one-third (35%) with other physician specialties. The most common services received during survivors' visits include general physical exams (57%) and imaging studies (20%). Visits with oncologists were less likely to include depression screening or counseling regarding nutrition, exercise, stress management, tobacco use, or weight reduction than were visits with other types of physicians. Conclusions: Cancer survivors experience diverse outpatient medical care interactions; only a minority of these are with oncologists. Oncologist visits are less likely to involve important counseling services. The NAMCS represents an important data source for examining outpatient care patterns among survivors.
Phase II trial of vorinostat, a histone deacetylase inhibitor to restore the hormone sensitivity to the anti-estrogen tamoxifen in patients with advanced breast cancer having failed prior aromatase inhibitor therapy
Authors: P. N. Munster, M. Lacevic, M. Schmitt, E. Bicaku, D. Marchion, A. Stephens, L. Sullivan, S. Minton
Journal: Journal of Clinical Oncology (2008)

3501 Background: Modulation of estrogen receptor signaling is one of the most successful modalities in the treatment of estrogen receptor (ER) positive breast cancers. Many estrogen receptor-positive tumors show primary or acquired resistance to anti-estrogen therapy. Histone deacetylases (HDAC) play a central role in transcriptional regulation and HDAC inhibitors have been reported to restore sensitivity to anti-hormonal therapy by modulation of estrogen as well as progesterone receptors. Here, we report preliminary findings from a Phase II trial evaluating the HDAC inhibitor, vorinostat and the anti-estrogen, tamoxifen, placed in context with correlative studies. Methods: Patients with ER-positive metastatic breast cancer who failed prior therapy with aromatase inhibitors and up to three chemotherapy regimes were administered vorinostat (SAHA) 400 mg daily for three of four weeks and tamoxifen 20 mg daily, continuously. Histone acetylation was evaluated in peripheral blood mononuclear cells and baseline HDAC enzyme expression was evaluated in tumor blocks. Results: To date, 19 patients [median age 56 years (36–71)] have been enrolled and 17 patients were evaluated for response. Two patients (2/18, 11%) had a pulmonary embolus./DVT. Three patients (3/18, 17%) had Grade 3 fatigue, and one patient each (1/18, 6%) had diarrhea, nausea/vomiting, weight loss, AST/ALT elevations, neutropenia or thrombocytopenia. Predominant Grade 2 toxicities included fatigue, nausea/vomiting, anorexia, bleeding and myelosuppression. Four patients had an objective response (1 complete, 3 partial responses: 4/17, 24%), of those 50% had prior chemotherapy and 75% had failed two aromatase inhibitors for metastatic disease, 50% had failed prior tamoxifen. One additional patient had stable disease for 12 months. H3 and H4 histone acetylation was seen at day 8 suggesting adequate PK levels. Histone acetylation, baseline HDAC expression and PK data will be presented. Conclusions: These findings suggest that the addition of an HDAC inhibitor to tamoxifen in patients who have failed prior aromatase inhibitors or adjuvant tamoxifen may restore hormone sensitivity. No significant financial relationships to disclose.
Postoperative complications as a predictor of 30-day hospital readmission following gastrointestinal cancer surgery.
Authors: Laurence E. McCahill, Mary May, Alan T. Davis, Wendy K. Taylor
Journal: Journal of Clinical Oncology (2012)

274 Background: Hospital readmissions have recently been identified as a benchmark for quality of care. Gastrointestinal (GI) cancer surgeries are complex and associated with higher rates of post-operative complications and hospital readmissions. Identifying factors associated with readmission could allow for strategies to reduce readmissions. Methods: Patients undergoing pancreatic (n=43), esophageal (n=20), gastric (n=14), and rectal (n=22) tumor resections were evaluated to assess if initial inpatient post-operative complications predispose patients to hospital readmission within 30 days. Patients’ charts were audited by a clinical quality specialist and complications stratified by using the Clavien Classification Schema. Hospital readmission causes were categorized as surgical procedure specific, general postoperative complication, failure to thrive, or general medical problem. Data were analyzed using the Fisher’s Exact test. Results: A total of 99 patients underwent GI tumor resections (Male:female 56:43, median age 65) between January 2010 and April 2012, and 20% were readmitted within 30 days. Of those readmitted, six had no complications in the initial hospitalization, eight had minor complications, and six had major complications, Table. When examining reasons for readmission, the majority of patients were surgical procedure specific (50%), such as anastomotic leaks or abscesses. Conclusions: Our data demonstrate that postoperative complications during initial hospitalization did not predict hospital readmissions. Readmissions, however, appear related to surgical specific complications that develop after an uneventful initial hospitalization. The goal of shorter hospitalizations following complex GI cancer surgery may result in unavoidable readmissions related to delayed presentation of procedure specific complications. [Table: see text]
Safety and Efficacy Results from a Phase I Trial of Single-Agent Lumiliximab (Anti-CD23 Antibody) for Chronic Lymphocytic Leukemia.
Authors: John C. Byrd, Susan O’Brien, Ian Flinn, Thomas J. Kipps, Mark A. Weiss, Kanti Rai, Thomas S. Lin, Jennifer Reid, Dee Wynne, Bryan R. Leigh
Journal: Blood (2004)
Predictors and outcomes of biochemical persistence versus recurrence after radical prostatectomy for prostate cancer diagnosed in the era of PSA screening.
Authors: S. Sukumar, M. Diaz, S. Kaul, C. Hwang, J. Peabody, M. Menon, C. Rogers
Journal: Journal of Clinical Oncology (2011)

e15041 Background: Biochemical persistence (BCP) and biochemical recurrence (BCR) after radical prostatectomy (RP) may portend poor outcomes. There is a paucity of data on patients with BCP after RP and no studies that compare patients with BCP and BCR. We evaluate clinical and pathologic characteristics, predictors, and outcomes of patients with BCP vs. BCR in a large contemporary cohort treated with RP. Methods:From 2001-2008, 4047 patients underwent robot-assisted RP (RARP) for localized prostate cancer at a single institution. After excluding 336 patients who were lost to follow up, there were 3711 patients for the study. BCR was defined as a PSA ≥ 0.2 ng/ml with a confirmatory value. BCP was defined as a detectable PSA at the first postoperative draw within 3 months of surgery. Patients with BCP and BCR were compared and multivariable regression analysis was used to identify factors predicting BCP and metastasis. Results: A total of 345 (9.2%) patients had a detectable PSA at a mean follow up of 33.4 months, of whom 114 (33%) had BCP and 231 (67%) had BCR. Patients with a BCP had a significantly higher preoperative PSA (11.7 vs. 8.3), biopsy high-grade disease (36 vs. 21%), biopsy perineural invasion (35 vs. 21%), final pathologic high-grade disease (58 vs. 29%), tumor volume (32 vs. 26%), pathologic angiolymphatic invasion (26 vs. 14%), seminal vesicle invasion (32 vs. 16%), and N1 disease (15 vs. 2.6%). Predictors of BCP on multivariable analysis of all recurrences were biopsy perineural invasion (OR-1.8, 95% CI- 1.02 to 3.1, p=0.043), seminal vesicle invasion (OR-2.7, 95% CI- 1.2 to 6.2, p=0.021), and N1 disease (OR-6.6, 95% CI- 2 to 21.5, p=0.002). 21 patients developed metastatic disease (BCP=14, BCR=7, p=0.01). Of all patients with post-RARP PSA elevation (BCP and BCR), only BCP (OR-3.2, p=0.022) and high-grade disease (OR-2.9, p=0.043) predicted metastasis. Conclusions: Patients with BCP have more aggressive disease on biopsy and pathology than patients with BCR and are more likely to develop distant metastasis. Only higher pathologic stage predicts BCP over BCR. Of all patients with a post-RARP PSA elevation, only BCP and ≥ Gleason 8 disease predicted metastasis.
Whole body MRI versus axial MRI in initial diagnosis of multiple myeloma and monoclonal gammopathy of undetermined significance
Authors: J. Hillengass, T. Baeuerle, K. Fechtner, K. Neben, T. M. Moehler, A. D. Ho, H. Kauczor, S. Delorme, H. Goldschmidt
Journal: Journal of Clinical Oncology (2008)

19501 Background: MRI of the spine is more sensitive in detecting bone marrow lesions of multiple myeloma (MM) than radiological skeletal survey. The number of focal lesions or diffuse infiltration is of prognostic significance. Recent developments of so called “whole body MRI” allow displaying nearly the whole bone marrow of a patient though at the expense of image resolution. While MRI of the spine is a widespread technique with reasonable costs, the application of whole body MRI is to date limited to a small number of specialized centers. Methods: In 30 individuals with monoclonal gammopathy of undetermined significance (MGUS) and 71 patients with untreated MM in all stages (Salmon and Durie-Classification) of disease we compared the findings of a standard MRI of the axial skeleton (spine and os sacrum) with the findings of whole body MRI. Results: In 40 patients axial lesions were found with 24 patients showing only intraosseous lesions (intra), 2 patients displaying exclusively lesions penetrating compact bone (pcb) and 14 patients showing both types of lesions (intra+pcb). Extraaxial lesions were found in 39 patients with exclusively intra lesions in 24 patients and intra+pcb lesions in 15 patients. In the MGUS group 6 patients (20%) showed axial intra lesions. In 2 patients extraaxial intra lesions were detected and in 2 patients even extraaxial intra+pcb lesions were found. In 11 patients exclusively axial and in 10 patients exclusively extraaxial lesions were detected. 29 patients displayed lesions in both locations. Conclusions: Our data show that a total of 39% of patients have developed extraaxial lesions which could not be detected by axial MRI. 10% of patients had solely extraaxial lesions. We conclude that whole body MRI is the new MR imaging standard at the time of initial diagnosis. No significant financial relationships to disclose.
EBV-positive diffuse large B-cell lymphoma of the elderly in Peru: Report of 33 cases.
Authors: J. J. Castillo, B. E. Beltran, D. Morales, P. Quinones, R. Miranda, A. Gallo, M. Lopez-Ilasaca, C. R. Desposorio, F. Hurtado de Mendoza, E. M. Sotomayor
Journal: Journal of Clinical Oncology (2011)

e18538 Background: EBV+ diffuse large B-cell lymphoma (DLBCL) of the elderly is a new entity included in the WHO Classification. It usually affects elderly patients and has a poor survival, and it is believed to be related to immunosenescence. The goal of this study was to evaluate clinical characteristics and survival of EBV+ DLBCL of the elderly from our institution. Methods: Between January 2002 and June 2008, 33 patients with EBV+ DLBCL of the elderly were identified and included in the analysis. All cases were positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization and CD20 and/or Pax-5 expression by immunohistochemistry (IHC). Clinical data were reviewed retrospectively and patients’ biopsies were analyzed for the expression of BCL6, CD10, CD30 and MUM-1/IRF4. The survival analysis was performed using the Kaplan-Meier method. Results: The median age was 70 years (range 25-85 years); four patients were <50 years of age. B symptoms occurred in 14 (46%), ECOG >2 was seen in 19 (61%), and advanced stage in 16 patients (57%). The IPI score was high intermediate and high in 19 patients (61%). Extranodal disease occurred in 15 patients (48%); GI tract (n=6), oral cavity (n=3), soft tissue (n=2), CNS (n=2), lung (n=2), adrenal gland (n=1), peritoneum (n=1), and bone marrow (n=1). Interestingly, three patients (9%) were HTLV-1 carriers. By IHC, 21 patients (72%) had a non-germinal center (NGC) profile and nine cases (27%) were CD30+. Eight patients did not receive chemotherapy because of a poor performance status. From the 23 patients who received chemotherapy, 9 received R-chemotherapy with an ORR of 67% (5 complete responses and 1 partial response), and 14 received chemotherapy with an ORR of 29% (4 complete responses). Median overall survival (OS) for the whole group was 6 months. The median OS for patients who did not receive therapy was 1.5 months, 12 months for patients who received chemotherapy and 20 months for R-chemotherapy (p=0.001). Conclusions: EBV+ DLBCL of the elderly was associated with high IPI scores, poor performance status, frequent extranodal involvement, NGC profile, poor response to treatment and short survival rate. The role of rituximab-containing regimens in EBV+ DLBCL of the elderly needs further evaluation.
Comparison of health care resource use before and after docetaxel treatment among prostate cancer patients.
Authors: M. Mehra, Y. Wu, R. Dhawan
Journal: Journal of Clinical Oncology (2011)

215 Background: Docetaxel is standard of care among late-stage prostate cancer patients. We analyzed patterns of health care resource utilization (RU) among patients before and after exposure to docetaxel using a large commercial claims database. Methods: A random sample of patients (N = 336) with a diagnosis of prostate cancer (ICD 9 code: 185.X) and a claim for docetaxel (2003–2009) was identified from the PharMetrics database, a nationally representative, non-payer-owned integrated commercial U.S. claims database. All patients had ≥ 12 months of enrollment prior to initiation of docetaxel. Patients were followed from their first docetaxel claim until lost to follow-up or June 30, 2009 (censored). RU was defined as all-cause hospitalization, ER, physician, and ambulatory visits. Incidence rates were derived. Results: Mean age of patients was 67.9 years (SD 10.6); mean number of docetaxel prescriptions was 9.9 (SD 10.3). Mean time to study end/lost to follow-up was 15.41 (SD 12.49) months from the index date. The table shows health care RU for the 12 months before, and over the follow-up period after docetaxel initiation. Hospitalizations, ER, physician, and ambulatory visits were significantly higher in the follow-up period. The average length of hospital stay was significantly longer after docetaxel treatment (8.2 vs 5.5 days). Prior to docetaxel, two-thirds of the patients were on hormonal therapy; 51% on analgesics, and 31% on bisphosphonates. After docetaxel, the proportions were 62%, 58%, and 54%, respectively. Conclusions: The significantly higher RU with disease progression in prostate cancer patients suggests a need for new treatment options that can effectively manage and improve patient outcomes. [Table: see text] [Table: see text]
Risk of high-grade skin rash in cancer patients treated with panitumumab—A meta-analysis.
Authors: A. Shaker, M. E. Lacouture, S. Wu
Journal: Journal of Clinical Oncology (2010)

e14079 Background: Panitumumab, a fully human monoclonal antibody targeting epidermal growth factor receptor has emerged as an effective therapy for metastatic colorectal cancer (CRC). Its efficacy in the treatment of other cancers is also undergoing extensive investigation. Its association with skin toxicity has been reported by several individual studies, but the overall risk has not been defined. We performed a systemic review and meta-analysis of published clinical trials to quantify its overall risk of skin rash in cancer patients. Methods: Databases including PubMed, abstracts presented at the American Society of Clinical Oncology conferences and the European Society of Medical Oncology until December, 2009 were searched to identify relevant studies. Eligible studies included phase II and III clinical trials in which cancer patients were treated with panitumumab as a monotherapy or in combination with chemotherapy. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using a fixed-effects or random effects model based on the heterogeneity of included studies. Results: A total of 2,503 patients with mainly CRC from 11 trials were included for analysis. The overall incidence of all-grade skin rash was 80.3% (95% CI: 68.0%–88.7%), with 8.6% (95% CI: 3.8%–18.6%) being high-grade (grade 3 or above). The overall incidence of all-grade acne-like skin rash was 57.6% (95% CI: 37.0%–75.8%), with 6.2% (95% CI: 4.5%–8.5%) being high-grade. In comparison with panitumumab monotherapy, combination with chemotherapeutic agents significantly increased the risk of high-grade skin rash (RR 2.51, 95% CI: 1.75-3.60, p < 0.001), but not all-grade skin rash (RR 1.02, 95% CI 0.98-1.07, p = 0.35). From randomized controlled studies, panitumumab significantly increased the risk of developing all-grade skin rash (RR 5.51, 95% CI: 2.79-10.90, p < 0.001) and high-grade skin rash (RR 49.2, 95% CI: 18.4–131.5, p < 0.001) in comparison with controls. Conclusions: Panitumumab was associated with a substantial risk of high-grade skin rash, particularly when combined with chemotherapy. Further studies are strongly recommended for the prevention and treatment of high-grade skin rash. No significant financial relationships to disclose.
Neoadjuvant DCF in resectable esophageal cancer: Single-center experience.
Authors: Vanita Noronha, Seema Gulia, Amit Joshi, Kumar Prabhash
Journal: Journal of Clinical Oncology (2013)

124 Background: Despite improvement in surgical techniques and peri-operative care, the 5 yr OS in esophageal cancer is 10%. RCTs comparing NACT to surgery alone have demonstrated a significant increase in median survival from 13 months to 17 months. We aimed at studying impact of DCF NACT. Methods: Retrospective analysis of prospective database of patients with locally advanced esophageal cancer. All patients had ECOG performance status of 0 to 1, with no uncontrolled comorbidities. Chemotherapy consisted of 3 cycles of standard DCF (Docetaxel 75 mg/m2 on day1, Cisplatin 75 mg/m2 on day 1 and 5 fluorouracil 750mg/m2 as a continuous intravenous infusion for 5 days) with growth factors and prophylactic antibiotics were administered. Following chemotherapy, a restaging scan was performed. If disease was deemed resectable, surgery was performed. Patients were followed up after surgery and then 3-monthly. Toxicity was graded according to CTCAE v.4.03, response was calculated as per RECIST 1.1 and statistics were by simple percentages. OS and PFS calculated by Kaplan–Meier method. Results: Between February 2010 and April 2012, there were 22 patients who received neoadjuvant DCF chemotherapy. Male to female ratio 1.2. Median age 44.5 years (range: 32- 63 yrs). 20 patients had squamous histology and 2 had adenocarcinoma. Middle one third of esophagus was the primary site in 54.5%. Response rate: CR-32%, PR-55%, SD-9% and PD-4.5%. 16 (73%) patients underwent R0 resections, 1-R1 resection, 3-R2 resection, 1 was deemed unresectable preoperatively and treated with chemo-radiotherapy and 1 had CR but surgery was postponed due to hyperthyroidism. 7 patients (31.8%) had pathologic complete remission. Toxicities grade (3/ 4) included neutropenia (77.3%), febrile neutropenia (86.4%), diarrhea (45.5%), hyponatremia (45.5%), fatigue (18.2%), and mucositis (13.5%). Dose reduction due to toxicities was done in 50% patients. At a median follow up period of 13 months (range 4-31 months), the PFS is 81.8% and OS is 90.9%. Conclusions: Response rate to DCF is 87%, with a pathologic CR rate of 32%. The complete responders appear to have a durable benefit; all remain disease free at the last date of follow up. Our initial data looks promising but follow up period is short.
Overexpression of EVI1 Causes Genomic Instability and Cell Cycle Arrest in Hematopoietic Cells.
Authors: Friederike Herbst, Claudia R Ball, Oksana Zavidij, Annika Mengering, Sylvia Fessler, Manfred Schmidt, Christof von Kalle, Hanno Glimm
Journal: Blood (2012)