tbuckley/cabot-search huggingface dataset:
Soluble CD95 (APO-1/Fas) level in infancy and childhood acute lymphoblastic leukemia
Authors: E. N. Ebeid, A. Khairy, M. Amin, I. Sidhom, H. Hussein
Journal: Journal of Clinical Oncology (2005)

8540 Background: Acute lymphoblastic leukemia is the most common form of childhood cancer. In order for neoplastic cells to expand their population and subsequently form leukemia, they must escape surveillance by the host defence system. A major mechanism of such escape from growth control, at least in lymphoid cells is thought to be mediated via apoptosis triggered by Fas receptor (CD95/APO-1).The objective of this study is to measure the serum level of soluble (Fas/APO-1/CD95) in infants and children with acute lymphoblastic leukemia at presentation, and after end of induction therapy and correlate its level with prognostic parameters. Methods: This study included 30 pediatric patients with newly diagnosed ALL as well as 10 healthy children age-matched as control groups during the period of December 1999 to October 2000.All patients were treated at the NCI ,Cairo,Egpt.All patients were subjected to clinical examination, laboratory investigations, CSF, bone marrow and immunophenotyping and chest x ray.sFAs (CD95/APO-1)level was measured by ELISA technique at presentation, and after 4 weeks of induction. Results: The age ranged between 6months and 14 years, their mean age was 5,male to female ratio was 1.7:1.After induction therapy, 26 cases achieved complete remission. Two patients died during induction and another two patients were resistant to induction therapy. sFas level was high at presentation and dropped after achieving complete remission,the difference was statistically significant (p<0.01) The 2 patients who were resistant to induction therapy, their mean level of sFas remained high. Significant correlation between mean serum level of sFas was recorded before therapy in patients with ALL and control group (p<0.01).There was significant correlation between sFas level and white cell count (≤50,000/cmm vs ≥50,000cmm) (p<0.05), Immunophenotyping (matureB and Tcell vs early preB and preB) (p<0.05)and LDH level(5000u/L vs 5000u/L) (p<0.001). Conclusion: sFas can serve as a prognostic marker for pediatric ALL. No significant financial relationships to disclose.
Scientific evidence underlying National Comprehensive Cancer Network Clinical Practice Guidelines.
Authors: T. K. Poonacha, R. S. Go
Journal: Journal of Clinical Oncology (2010)

6020 Background: The National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive, recognized, and widely used standard for clinical policy in oncology by clinicians and payors in the United States. However, the level of scientific evidence on which these guidelines are based, has not been systematically investigated. Objectives: We performed this study to describe the distribution of categories of evidence and consensus (EC) among the 10 most common cancers in the US with regards to recommendations for staging, initial and salvage therapy, and surveillance practice. Methods: We obtained the latest versions (September 1, 2009) of relevant guidelines from the NCCN. The definitions for various categories of EC used by NCCN panel members were as follows: Category 1 (high level evidence such as randomised controlled trials with uniform consensus), Category 2A (lower level of evidence with uniform consensus), Category 2B (lower level of evidence without a uniform consensus but with no major disagreement) and Category 3 (any level of evidence but with major disagreement). Results: Of the 983 recommendations found in the 10 sets of guidelines, the proportions of Category 1, 2A, 2B and 3 EC were 5%, 85%, 9% and 1%, respectively. Recommendations with any Category 1 EC were found in breast (19%), non-Hodgkin lymphoma (8%), kidney (7%), melanoma (6%), and lung (6%) guidelines. Colorectal, pancreatic, urinary bladder, and uterine guidelines did not have any recommendations with category 1 EC. 8% of all therapeutic recommendations were derived from category 1 EC with the majority (83%) of these pertaining to initial therapy. Guidelines with the highest proportions of therapeutic recommendations based on category 1 EC were breast (30%), lung (10%), and kidney (10%) cancers. No category 1 EC formed basis for any recommendations on screening or surveillance. Conclusions: Recommendations issued in the current NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. Our study underscores both the urgent need and available opportunities to expand evidence base in oncology which forms the platform for clinical practice guidelines. No significant financial relationships to disclose.
Detection of sentinel lymph node micrometastases of breast carcinoma by molecular biology
Authors: F. Perazzo, V. Denninghoff, D. Allende, F. Paesani, A. Garcia, A. Avagnina, E. Abalo, G. Crimi, B. Elsner
Journal: Journal of Clinical Oncology (2008)

22079 Background: The prognosis in individuals with breast carcinoma depends on optimal tumor resection margins and axillary lymph node status. The aim of the present study is to evaluate by molecular biology, the presence of Mammaglobin (MAG) A and B messenger RNA, in breast sentinel lymph node (SNL) and to correlate these findings with the characteristics of the primary breast tumor. This correlation would allow us to identify a subset of patients at higher risk of developing axillary nodes metastases. Methods: Between June 2004 and June 2007, 45 SLN from patients with breast carcinoma (less and/or equal to 3cm, without palpable axillary lymphadenopathies) were prospectively studied. Intraoperative evaluation was performed. Defer studies included HE, IHC and molecular biology (MB). Clinical follow-up was also obtained from chart review. Results: The defer study with routine HE sections showed evidence of metastases in 4 cases. Neoplastic cells were detected in 8 cases by IHC. Twenty-one SLN were detected with MB. The rest of the SLN studied (22/45) failed to show evidence of metastases. No significant differences were seen among women with positive and negative SLN byHE-IHC-MB, regarding the age at diagnosis, age of menarche, hormonal status (pre o postmenopause), family or personal medical history, pregnancy and delivery, carcinoma in the contralateral breast, months of follow-up, tumor subtype and histologic grade, tumor size, surgical margins, hormonal receptors and HER2-neu status, vascular invasion and low, intermediate and high risk classification according to Saint Gallen Consensus. Conclusions: The study of SLN with routine HE stained sections is insufficientfor identifying all the cases with micrometastases. Additional IHC and MB studies increase the sensitivity in micrometastases detection. MAG could be a possible independent prognostic factor. If our findings are verified in the future, MB results would modify the staging and treatment of patients with breast cancer. No significant financial relationships to disclose.
Phase I study of concurrent chemoradiotherapy (CRT) with S-1 and cisplatin (CDDP) in patients (pts) with unresectable locally advanced squamous cell carcinoma of head and neck (SCCHN)
Authors: M. Tahara, H. Minami, H. Mukai, K. Kawada, M. Kawashima, T. Ogino, M. Yamazaki, K. Matsuura, R. Hayashi
Journal: Journal of Clinical Oncology (2005)

5575 Background: An oral drug, S-1, composed of tegafur, 5-chloro-2, 4-dihydroxypyrimidine, and oxonic acid in a 1:0.4:1 molar ratio has shown high activity for head and neck cancer with a response rate of 34%. The aim of this study was to determine the maximum tolerated dose (MTD) of S-1 in combination with CDDP and radiotherapy. Methods: Eligibility: histologically proven SCCHN with unresectable locally advanced lesions, PS 0–1, age ≤ 75, adequate organ functions, and no prior chemotherapy. Chemotherapy consisted of administration of S-1 twice daily on days 1–14 at escalating doses of 40, 60, and 80 mg/m2/day, and 2-hour infusions of CDDP at 20 mg/m2/day on days 8–11, repeated twice with a 5-week interval. Once daily radiotherapy of 70 Gy in 35 fractions was given concurrently starting on day 1. Two additional cycles of S-1 and CDDP were planned 4 weeks after the completion of CRT. Dose-limiting toxicities were defined as neutropenic fever lasting for 4 days, grade (gr) 4 thrombocytopenia, and gr 3 non-hematological toxicities except mucositis, dysphagia, anorexia, nausea, vomiting, and infection due to mucositis. Results: Seventeen pts were enrolled. One pt did not receive CRT because of disease progression. Gr 2–3 stomatitis, dysphagia, neutropenia, dermatitis and xerostomia were the most frequently observed adverse events. The MTD was reached at 80 mg/m2/day of S-1, with 2 of 6 pts experiencing neutropenic fever lasting for 4 days. Of 7 pts treated at 60 mg/m2/day of S-1, one pt developed gr 3 diarrhea, and another developed neutropenic fever lasting for 2 weeks. For the latter, a diagnosis of myelodysplastic syndrome was made based on bone marrow analyses. Of the 16 pts treated with CRT, 12 experienced a complete response (CR) according to RECIST. Two additional pts who had residual neck lymph node metastasis underwent salvage neck dissection and pathological CR was confirmed. Conclusions: S-1 at 60 mg/m2/day for 14 days and CDDP at 20 mg/m2/day for 4 days are recommended for CRT. Although data are preliminary, the CR rate was very promising, and this approach warrants further investigation. No significant financial relationships to disclose.
Estrogen receptor β expression in high-grade breast cancer patients may predict metastases and mortality
Authors: A. Fuentes Alburo, E. Dubon, I. Aguirre, V. Pérez, T. A. Vela, A. Mora, N. A. Hernandez-Rodriguez
Journal: Journal of Clinical Oncology (2005)

671 Background: The two isoforms of Estrogen receptor α and β (ERα and ERβ) are involved in breast tumorigenesis and progression. ERα is a well established prognostic and predictive factor for anti-estrogen therapies in breast cancer, and predicts a favorable disease outcome, ERβ potential as a clinical prognostic marker remains to be defined. The aim of this study was to identify the potential of ERβ as a predictor of metastases and mortality in high grade breast cancer patients. Methods: In a group of 50 patients with confirmed diagnostic of ductal carcinoma and a SBR of 8–9, we assessed by immunoblotting and IHC (using specific monoclonal antibodies directed against ERα and ERβ) the distinct expression pattern of this ER isoforms in primary tumor samples. Chi-square and log rank tests were used to determine differences between proportions of each ER isoform and mortality and survival distributions respectively. A P value ≤ 0.05 were considered significant. Results: The median follow up of this case series was 80 months (2–107 months). Twenty-three (46%) of 50 patients developed metastases, and 25 of 50 (50%) were positive for expression of ERα and ERβ respectively. We found a high frequency of metastasis (13 of 25; 52%) among those cases that express ERβ. Similar to 17 of 25 (68%) observed in ERα negative samples. This relationship was very significant (P = 0.0000) when compared to the rest of the group. We also found a statistically significant correlation between patients with positive ERβ and negative ERα and a higher mortality (P=0.03 and P=0.0038 respectively). Conclusions: These findings suggest that ERβ expression in high grade samples from ductal carcinoma histologic subtype may be used as a poor prognostic marker in breast cancer patients. No significant financial relationships to disclose.
Breast oncology precision medicine: Genomic testing and treatment at the population level.
Authors: Christopher Ryan Friese, Yun Li, Allison W. Kurian, Steven J. Katz
Journal: Journal of Clinical Oncology (2016)

288 Background: The 21-gene assay used to estimate breast cancer recurrence and tailor chemotherapy (chemo) receipt has demonstrated predictive validity and clinical utility. Yet it is unclear how involved patients are in the decision to perform the test, or how oncologists use results to recommend systemic chemo. We examined the patient experience with assay testing, physician recommendations, and chemo receipt based on test results. Methods: The iCanCare study surveyed a weighted random sample of newly diagnosed patients with early-stage breast cancer who were treated in 2013-14, identified through the population-based SEER registries of Los Angeles and Georgia about 3 months after surgical treatment, and merged with SEER data (N=2632, RR=70%). Registries partnered with Genomic Health, Inc. to link assay results to patients. We examined validated results against patient self report; patient satisfaction with testing and chemo decisions (1= not at all satisfied; 5= very satisfied); physician chemo recommendations, and; chemo receipt based on test scores (0-10= low risk; 30-100= high risk for recurrence). Results: Of the 1,908 women with invasive disease, 1,307 (68.5%) women had lower-risk features (Stage 1a/b, 2a, ER-positive, HER-2 negative) and 695 (53.2%) of them had tests performed. Of those tested, 60% recalled scores accurately. Most women were satisfied with their communication with doctors about testing (93%) and the chemo decision (90%). Testing varied slightly across risk groups: Grade 1 or 2 disease (54%), Grade 3 disease (61%), and any node-positive disease (62%). Most (91%) women with high-risk scores (&gt;30) reported their oncologist recommended chemo. Fewer (65%) women with low-risk scores (&lt;10) reported recommendations against chemo. Chemo receipt rates varied by risk scores: 2% for low-risk scores and 66% for high-risk scores. Conclusions: Most women were satisfied with testing and chemo decisions, yet many patients do not accurately recall test scores. Testing is higher in uncertain clinical groups. Physician recommendations and chemo receipt are tightly linked to test scores, suggesting that precision medicine has tailored treatment effectively to women with breast cancer. Funding: P01CA163233
Outcomes of patients with sarcomatoid renal cell carcinoma: The Mayo Clinic experience.
Authors: Brian Addis Costello, Ben Zhang, Christine M. Lohse, Stephen A. Boorjian, John Cheville, Bradley C. Leibovich, Robert Houston Thompson
Journal: Journal of Clinical Oncology (2013)

359 Background: Sarcomatoid renal cell carcinoma (RCC) is an aggressive form of RCC and is associated with a poor prognosis. Standard therapies tend to be less effective in this subset of patients. Methods: Using the Mayo Clinic Nephrectomy Registry, 206 patients with sarcomatoid RCC treated with partial or radical nephrectomy were identified. These patients were characterized based on extent of disease, treatment response and survival. Results: Of these 206, there was no evidence of distant metastases in 110 patients at the time of surgery and the estimated distant metastases-free survival at one year was 44%. The estimated cancer-specific survival rate at one and five years was 56% and 20%, respectively. Compared to patients with grade 4 RCC without sarcomatoid features, those with sarcomatoid RCC were more likely to develop distant metastases following surgery (hazard ratio 1.49). Considering those with metastatic sarcomatoid RCC, 96 patients had metastases at the time of surgery and 77 with no metastases at the time of surgery subsequently developed distant metastases (n=173). Of these, 156 died at a mean of 1.0 years from time of first evidence of distant metastases with a median cancer-specific survival of 0.6 years. Estimated cancer-specific survival rates from time of first metastases at one year and five years were 34% and 4%, respectively. The most common metastatic sites: lung (46%), bone (15%), liver (13%), non-regional lymph nodes (9%), and brain (5%). Patients who received targeted systemic therapy (10%) with either sunitinib (n=14), sorafenib (2) or pazopanib (1) for their first occurrence of distant metastases had an estimated cancer-specific survival rate at one year of 69%, compared to 30% for patients who did not. Median cancer-specific survival for those receiving targeted therapy as first-line was 2.2 years compared to 0.6 years for those patients who did not. Conclusions: Sarcomatoid RCC is an aggressive subtype of kidney cancer as evidenced by poor survival rates. The patients in this registry with metastatic sarcomatoid RCC who received targeted therapy as first-line treatment had improved cancer-specific survival rates.
Evaluation of relative thrombocytopenia, identification of neuropathy, and bleeding risk secondary to utilization of neuromodulating agents in multiple myeloma patients receiving autologous stem cell transplant treated with melphalan, bortezomib, and lenalidomide.
Authors: Doron Feinsilber, Joel Marcus, Robyn Jackson, Marco A. Ruiz, Ryan Patrick Griffin, Rubina Hafeez Khan
Journal: Journal of Clinical Oncology (2016)

212 Background: Chemotherapy–induced polyneuropathy (CIPN) is a crippling manifestation in multiple myeloma (MM) patients that requires attentiveness to safety and quality of life. 2 Bortezomib, lenalidomide, and melphalan are commonly utilized chemotherapy agents that can cause both CIPN 3,4 and significant myelosuppression. Within this subset of patients we wish to insure efficacy and minimization of neuropathic pain while being mindful of bleeding risks. Methods: IRB approval was obtained for a retrospective study of patients with MM who received a bone marrow transplant (BMT). Criteria included those who have undergone treatment with melphalan, bortezomib, and lenalidomide who experienced CIPN and placed on gabapentin, pregabalin, or duloxetine with thrombocytopenia defined by a platelet count less than 100,000 K/ul. We identified all patients seen on the BMT service at Ochsner Medical Center who received an autologous BMT for MM and treated with melphalan, bortezumib, and lenalidomide. Demographic data included age at diagnosis, gender, height, and weight. We examined characteristics including date of diagnosis and progression free survival. Endpoints included signs of peripheral neuropathy, onset of thrombocytopenia, initiation of therapy with gabapentin, pregabalin, or duloxetine. Results: 62 patients were selected with data capture. A preliminary chart review shows of patients meeting selection criteria, 53% of patients identified had shown undocumented or undertreated neuropathy, significant bleeding risk, or low platelet function assays. Complete breakdown of individual factors to be provided graphically. Conclusions: The standard treatment practices for MM patients with CIPN has placed patients at higher risk for development of thrombocytopenia and adverse bleeding risks, requiring more stringent institutional documentation practices.
Primary focal cryosurgery of the prostate: Long-term clinical and biochemical outcomes in a large cohort at a tertiary referral center.
Authors: Jamie Sungmin Pak, Philippa J. Cheetham, Aaron Katz, Sven Wenske
Journal: Journal of Clinical Oncology (2015)

114 Background: Modern primary focal cryosurgery (PFC) has emerged as a primary therapy option for localized and minimal low-risk prostate cancer (PCa), achieving good local cancer control and survival outcome. The aim of this analysis was to report on the experience of PFC in our tertiary referral center in the management of localized PCa. Methods: We identified a consecutive series of patients that underwent PFC for localized PCa at our institution between 8/2000 and 1/2014. Demographics, PSA levels and Gleason scores before primary treatment and at time of recurrence were assessed; BDFS, OS, and DSS were assessed. BCR was defined by the Phoenix (PD) and Stuttgart Definitions (SD). Results: A total of 126 patients were included in the analysis, with a median follow-up of 40.3 (0.8-116, IQR 41) months. Median age was 73.5 (range 45-92, IQR 9) years. Median initial serum PSA level was 6.0 (1-44.5, IQR 3) ng/ml. Median primary and secondary Gleason score on initial biopsy was 3 (3-5, IQR 1) with a median sum of 6 (6-10, 1), and 15% (2-95%, IQR 0) of biopsy tissue involved with cancer. Median number of biopsy cores was 12 (2-32), with a median of 1 (1-12, IQR 1) core affected by cancer. Median PSA nadir post-treatment was 1.3 (0.1-13.1, IQR 2) ng/ml. According to PD and SD, 24 and 37 patients had BCR after a median of 14.9 (3.4-91.3, IQR 17) and 13.0 (2.9-90.3, IQR 11) months. Overall 4-year-BDFS was 83% and 73% by PD and SD, respectively. 5-year OS and DSS was 95%, and 99.2%. Of patients that met BCR criteria, almost 25% were proven to be negative on biopsy, confirming over-estimation of failures. Patients that recurred had significantly higher initial median PSA levels (8.5 vs. 5.8 ng/ml; p&lt;0.01) and PSA-nadir (2.1 vs. 1.0 ng/ml; p&lt;0.05). Conclusions: Our analysis confirms PFC being a good option with low rate of morbidities for patients with localized PCa, with excellent BDFS and DSS at a long follow-up of 40 months. Controversy exists regarding criteria of BCR-definitions after focal therapies. More stringent definitions, such as the SD, especially in a focal cryosurgery setting, significantly over-estimate failure rates, and prostate biopsy seems to be the only reliable means to assess for recurrence at this point.
Cixutumumab combined with temsirolimus in patients with refractory Ewing’s sarcoma.
Authors: A. Naing, P. LoRusso, S. Fu, D. S. Hong, P. M. Anderson, R. S. Benjamin, J. A. Ludwig, H. X. Chen, L. A. Doyle, R. Kurzrock
Journal: Journal of Clinical Oncology (2011)

10031 Background: In this multicenter NCI CTEP-sponsored trial [funded by R21CA13763301A1 (AN), U01CA62461 (RK), and U01CA62487 (PL)], we combined the mTOR inhibitor temsirolimus with cixutumumab, a fully humanized IgG1 monoclonal antibody directed at insulin growth factor-1 receptor (IGF-1R), on the basis of preclinical data suggesting that the combination could putatively overcome the resistance observed when the individual agents were used as monotherapy in Ewing's sarcoma. Methods: Patients received cixutumumab 6 mg/kg IV weekly and temsirolimus 25 mg IV weekly (four week cycles) with restaging after eight weeks. Results: Seventeen Ewing's sarcoma patients were enrolled. Ten patients (59%) were men and the median age was 27.5 years (range, 14 to 41 years). The median number of prior therapies was 6. Six patients had previously received an IGFR inhibitor and two had previously received temsirolimus. The most frequent drug-related toxicities were thrombocytopenia (82%), mucositis (76%), hypertriglyceridemia (71%), hypercholesterolemia (65%), and hyperglycemia (65%). Only 3/17 patients experienced a dose-limiting toxicity, which was grade 3 mucositis. Patients with well-controlled diabetes were not excluded. With early referral to an endocrinologist, hyperglycemia was controlled in one patient with metformin and in another patient with metformin and insulin. One of 17 (6%) patients, who had previously developed resistance to a different IGFR inhibitor, achieved a complete response (CR) of 14+ months in this study.Tumor regression was seen in 4/17 (24%) patients, who had 50%, 23%, 23%, and 27% regressions lasting 6+, 10+, 8 and 15 months, respectively. Conclusions: The combination ofcixutumumab and temsirolimus was well tolerated. Prolonged objective tumor reduction (>6 months) and one CR were seen in 29% of heavily pretreated Ewing's sarcoma patients, suggesting that anti-IGF1R inhibitor and mTOR inhibitor combinations merit further study.
Early Blast Clearance Evaluation after Induction Chemotherapy for Acute Myeloid Leukemia By Multiparameter Flow Cytometry and WT1-RNA Quantification: A Single Center Experience
Authors: Carlo Messina, Matteo G Carrabba, Elisa Sala, Michela Tassara, Raffaella Milani, Paola Ronchi, Cristina Tresoldi, Francesca Pavesi, Jacopo Peccatori, Consuelo Corti, Claudio Bordignon, Fabio Ciceri, Massimo Bernardi
Journal: Blood (2014)