tbuckley/cabot-search huggingface dataset:
How to reduce Ki67 variability jointly evaluating histological grade.
Authors: Maxim Izquierdo, Ignacio Rodriguez, Fransec Tresserra, Rafael Fabregas
Journal: Journal of Clinical Oncology (2015)

127 Background: Proliferative tumor activity measured immunohistochemically by Ki67 has high variability. Clinical use can be improved if it is considered together with the histological grade. Methods: Ki67 value has been studied in 566 breast cancers between 2007 and 2013 at our Institution using MIBI monoclonal antibody. The histological grade and hormonal receptor status were also evaluated. Results: Histological grade was I in 293 (51.7%) tumors, II in 219 (38.7%) and III in 54 (16.8%) tumors. Estrogen receptor was positive in 166 (29.5%) tumors and progesterone receptor was positive in 95 (16.8%) tumors. None of the tumors with Ki 67 value lower than 10% had histological grade III. Only 7% of tumors with histological grade I had a Ki 67 higher than 25%. Conclusions: It has to be considered to repeat or confirm the values of Ki67 higher than 25% with histological grade I, and Ki67 values lower than 10% in tumors with histological grade III.
Prognostic impact of tumor-associated B cells and plasma cells in colorectal cancer.
Authors: Jonna Berntsson, Bjorn Nodin, Jakob Eberhard, Karin Jirstrom
Journal: Journal of Clinical Oncology (2016)

587 Background: Multiple studies have described associations between infiltrating immune cells, prognosis and treatment response in cancer. However, the clinical relevance has most often been attributed to the T-cell linage, whereas the humoral immune response is less investigated. In colorectal cancer (CRC), accumulation of CD20-positive B lymphocytes at the advancing margin of metastatic CRC has been demonstrated to correlate with prolonged survival. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in colorectal cancer (CRC). Methods: Immunohistochemical expression of CD20 and CD138 in was analyzed in tissue microarrays with tumors from 557 incident cases of CRC from the Malmö Diet and Cancer Study, a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20 and CD138 expression on 5-year overall survival (OS). Results: CD20 expression could be evaluated in 549 (98.6 %) cases and CD38 in 534 (95.9 %) cases. CD20 expression correlated significantly with both immune cell-specific and tumor-specific expression of CD138 (p &lt; 0.001 and p = 0.001, respectively). Furthermore, immune cell-specific CD20 and CD138 expression as well as tumor-specific CD138 expression correlated significantly with lower T-stage (p &lt; 0.001, p &lt; 0.001 and p = 0.002, respectively). A higher density of CD20+ cells correlated significantly with an improved OS (HR = 0.66, 95 % CI 0.50-0.86), remaining significant in multivariable analysis adjusted for age, TNM stage, differentiation grade and vascular invasion (HR = 0.65; 95% CI 0.48-0.90). Neither immune cell nor tumor cell-specific CD138 expression was significantly associated with prognosis. Conclusions: Our results demonstrate that increased B cell infiltration in CRC is an independent factor of improved prognosis. Moreover, the study provides a first demonstration of the expression and clinicopathological correlates of immune cell-specific CD138 expression in CRC, thus providing a further characterization of the immune landscape in this type of cancer.
Detection of metastatic disease as a leading cause of screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic castration-resistant prostate cancer (CRPC).
Authors: E. Y. Yu, F. E. Nathan, C. S. Higano
Journal: Journal of Clinical Oncology (2011)

4655 Background: Many patients with biochemical relapse after definitive therapy for prostate cancer receive androgen deprivation therapy. PSA levels eventually will rise despite castrate levels of testosterone. Many of these patients have nonmetastatic disease and do not develop metastases for a median of 30 mos (Smith MR JCO, 2005). However, there is no standard therapy for patients with nonmetastatic CRPC. ENTHUSE M0 (Study 15) is a global phase III study, now closed to enrollment, comparing zibotentan 10 mg vs placebo in nonmetastatic CRPC patients. Coprimary endpoints are overall survival and radiographic progression or death. Patients are screened for metastases by bone and CT/MRI scans. An unexpectedly high number of patients failed screening, prompting this analysis. Methods: All screened patients were included. For each investigator, the number of patients who enrolled and who failed screening were recorded. Screen fail reasons were recorded. Screen failure rates were computed by clinical specialty (oncology or urology) and geographic region by dividing the number of screen failures by the number of enrolled patients in each category. Results: As of January 14, 2011, 2583 patients completed screening, and 1169 (45%) failed screening. Screen failure rates were not different by clinical specialty or by geographic region. The leading causes of screen failures by clinical specialty are listed in the table. Conclusions: These data suggest that detectable asymptomatic metastatic disease may exist in about 30% of presumed nonmetastatic CRPC. These findings stress the value of periodic staging studies in men with CRPC, as those with detectable metastatic CRPC may benefit from emerging therapies. Screen failure criteria, n (%) Oncology (631 patients enrolled) Urology (1,885 patients enrolled) Detection of metastatic disease 184 (29) 566 (30) Creatinine clearance of <50 mL/min 45 (7) 156 (8) Long QTc interval 24 (4) 82 (4) Absence of biochemical progression 27 (4) 76 (4) Testosterone level >70 ng/dL (noncastrate) 15 (2) 71 (4) Total screen failures, n 283* 873* * Some patients had >1 reason for screening failure.
Advanced malignancies in breast cancer survivors.
Authors: I. Shaukat, C. Sahebi, A. J. Cohen
Journal: Journal of Clinical Oncology (2010)

e19621 Background: Survivors of breast cancer (BC) are at risk for second malignancies (2-M). SEER data collected from 1973-2000 reveal the risk of 2-M in patients (pts) with a primary (P) BC has increased to 18%, of which 6.9% were PBC. 2-M may be due to treatment effects, environmental causes and host determinants. The treatment of BC has evolved over the past decade with greater use of hormone, radiation and chemotherapy. We reviewed the pattern of 2-M in PBC survivors treated at a large urban hospital. Methods: A retrospective review of the tumor registry included women with PBC from 1973-2009. Results: 170 women with PBC were identified with 2-M: 20 pts had synchronous cancers (<180 days) and 150 pts were evaluable. The mean age of diagnosis of PBC was 60 yrs (range 29-93 yrs) and 2-M 67 yrs (range 31-94 yrs). 67(45%) were white non hispanic, 79 (53%) were black and 4 (3%) white hispanic. The most common histology of PBC was ductal ca 71%, lobular ca 10%and DCIS 10%. 41/150 (27%) and 45/150 (30%) received hormone and chemotherapy respectively. 62/150 (41%) had lumpectomy and 79/150 (53%) had mastectomy. Time to development of 2-M was 6.4 yrs( range 6 mos to 22 yrs). The most common 2-M were: 78 pts (52%) BC, 21 pts (14%) colorectal ca, 16 pts (11%) lung ca, 4 pts (2.6%) sarcoma, 3 pts (2%) endometrial ca, 2 pts (1.3%) ovarian ca, 1 pt (0.6%) leukemia. 9/20 (45%) pts with colorectal ca and 10/16 (62%) with lung ca had stage III-IV disease, in comparison to 63/78 (81%) of BC with stage I-II disease. Of the second PBC, 62/78 (79%) had contralateral BC while 16/78 (20%) had ipsilateral BC; 67/78 (86%) were invasive and 11/78 (14%) were noninvasive. 15/16 (94%) of lung ca pts were smokers and 4/16 (25%) had received prior radiation. Conclusions: The most common 2-M in BC survivors were breast, colorectal and lung cancers. Consistent with previous studies, second BC usually occurred in the contralateral breast. Of concern, the majority of lung and colorectal ca were diagnosed at advanced stage. Aggressive surveillance and age appropriate screening for second ca should be part of regular followup for earlier diagnosis in PBC survivors. No significant financial relationships to disclose.
The use of octreotide scans in the diagnosis and follow-up of neuroendocrine tumors (NETs).
Authors: T. Di Valentin, M. Febbraro, T. R. Asmis
Journal: Journal of Clinical Oncology (2011)

e14631 Background: NETs are usually diagnosed and followed via a variety of imaging modalities, including MRI, CT scans and somatostatin scintigraphy (OctreoScan, SRS). SRS works by detecting somatostatin receptors found on NETs. There is ongoing debate as to which imaging modality should routinely be used to diagnose and follow patients affected with NETs. This project aims to determine if the information gathered from SRS corresponds or adds to results obtained from modern CT or MRI. Methods: We conducted a retrospective chart review by identifying all patients diagnosed with a NET who were seen at TOHCC between 2003-01-01 and 2009-03-31. We then identified all patients who underwent an SRS within 30 days of a CT or MRI. Results of the SRS were then compared against those of the latter imaging modalities. Results: 70 patients with a diagnosis of NET were identified. Of these, 28 had an SRS within 30 days of a CT or MRI. 5 patients had serial SRS plus either a CT or MRI within the defined time window. In total, 33 SRS results were allowed in the study. When compared to the results of the CT or MRI, 13 (39.4%) were true negatives (TN) SRS, 9 (33.3%) were true positives (TP), and 8 (24.3%) were false negatives (FN) in the setting of metastatic disease. The liver was the most common site missed. One patient had a false positive (FP) SRS (3.0%) with the location of the supposed lesion thought to be in the small bowel. Conclusions: The sensitivity of CT scans and MRIs is superior to that of SRS when investigating NET. There were no cases were an SRS identified lesions that were truly present but not seen on CT or MRI. The most common site missed by the SRS was the liver. This data suggest that SRS does not provide additional information and does not appear to be useful in the diagnosis and follow up of patients with NET, however, further research is needed.
Taking control of cancer: Women’s choice for mastectomy.
Authors: Andrea Marie Covelli, Nancy Baxter, Margaret Fitch, Frances Catriona Wright
Journal: Journal of Clinical Oncology (2013)

11 Background: Rates of both unilateral (UM) and contralateral prophylactic mastectomy (CPM) for early stage breast cancer (ESBC) have been increasing since 2003. Studies suggest that the increase is due to women playing an active role in decision-making. We do not know what factors are influencing the choice for more extensive surgery. Methods: To identify these factors we completed a multi-method study; conducting a systematic review of quantitative literature and qualitative interviews. Decision-making literature was identified from 5 databases and underwent thematic analysis. Purposive sampling identified women across the Toronto Area (Ontario, Canada), who were suitable candidates for breast conserving surgery (BCS) but underwent UM or CPM. Data saturation was achieved after 29 in-person interviews. Constant comparative analysis identified key concepts and themes. Results: ‘Taking control of cancer’ was the dominant theme. Literature illustrated that patients markedly overestimate risk of local recurrence, contralateral cancer and particularly, mortality. Similarly, interviews revealed that fear of breast cancer was expressed at diagnosis and drives the decision-making process. Despite surgeons discussing survival equivalence of BCS and UM, patients chose UM due to fear of recurrence and an overestimated survival advantage. Similarly, patients chose CPM to eliminate contralateral cancer and a misperceived survival benefit. Women were actively trying to Control Outcomes, as more surgery was believed to offer greater survival and therefore greater control. Conclusions: Both the literature and our interviews have illustrated that women seek UM and CPM for treatment of their ESBC to manage their fear of cancer mortality by undergoing more extensive surgery; this in turn drives mastectomy rates. It is important to understand this process so that we may improve our ability to communicate issues of importance to women and facilitate informed decision-making.
Use of the Internet to connect radiation oncologists and medical oncologists with disease site-specific experts: 3-year outcomes of chartrounds.com.
Authors: Patricia H. Hardenbergh, Brigitta Gehl, Kimberly Anne Lyons-Mitchell
Journal: Journal of Clinical Oncology (2013)

241 Background: The purpose of this project is to improve the quality of cancer care by connecting disease site-specific experts with community oncologists through web-based technology. Methods: Chartrounds.com is a conferencing web-site developed to allow community oncologists to present real cases to disease site specialists in oncology on a scheduled basis. Chartrounds was developed initially for radiation oncologists and subsequently has expanded to include multidisciplinary tumor boards and medical oncology specific sessions. Presently 43 disease site expert oncologists including surgeons, medical oncologists and radiation oncologists from 38 academic institutions in the US host sessions. Feedback reports following the completion of each session were designed to assess the impact of the project. Results: Since its inception in December 2010, 43 disease site-specialists have lead 366 sessions, connecting 3,793 participating oncologists from all 50 US states and 24 countries.Broken down by specialty, 348 radiation oncology sessions have linked 3,632 participants, 14 medical oncology specific and multidisciplinary tumor board sessions have included 161 participants. On a 5 point Likert scale with 5 representing the greatest possible impact, the mean response to feedback questions is as follows: session quality: 4.7 for radiation oncology, 4.6 for multidisciplinary; time used effectively: 4.6 for radiation oncology, 4.5 for multidisciplinary; discussions relevant to daily practice: 4.6 for radiation oncology, 4.6 for multidisciplinary; session is likely to result in a change of practice: 4.0 for radiation oncology, 4.0 for multidisciplinary. Chartrounds sessions qualify for 1 CME credit and is approved for a practice quality improvement project by the American Board of Radiology. Conclusions: Chartrounds.com is impacting oncology practices which results in changes in community practice. Future directions of this project include providing chartrounds sessions for oncology nurses and providing a library of video recorded archived sessions. This work has been funded by the Improving Cancer Care Grant of the ASCO Conquer Cancer Foundation.
The Clinical Features and Prognosis of Lymphoplasmacytic Lymphoma/ Waldenström Macroglobulinemia: A Large Series Analysis from a Single Center
Authors: Wenjie Xiong, Shuhua Yi, Heng Li, Zengjun Li, Rui Lv, Wei Liu, Yan Xu, Dehui Zou, Mu Hao, Lugui Qiu
Journal: Blood (2016)
Final analysis of a randomized phase II study of bevacizumab (B) and gemcitabine (G) plus cetuximab (C) or erlotinib (E) in patients (pts) with advanced pancreatic cancer (PC)
Authors: H. L. Kindler, T. Gangadhar, T. Karrison, H. S. Hochster, M. J. Moore, K. Micetich, W. Sun, D. V. Catenacci, W. M. Stadler, E. E. Vokes
Journal: Journal of Clinical Oncology (2008)

4502 Background: Targeting several critical pathways may be more effective than single pathway blockade in a resistant cancer like PC. In preclinical PC models, combining EGFR + VEGF targeted agents is synergistic. Methods: We conducted a multicenter, randomized phase II trial of dual targeted therapy, GBC or GBE, in advanced PC pts who had: no prior therapy for metastatic disease, PS 0–2, measurable disease, no bleeding risk or duodenal invasion. Primary endpoint: response; 2 parallel, Simon 2-stage designs. Baseline correlatives: plasma VEGF, serum VEGFR2. All pts received G 1000 mg/m2 over 30' days (D) 1, 8, 15 Q28D; B 10 mg/kg D 1, 15 Q28D. Pts, stratified by PS and site, were randomized to C 400 mg/m2 D1 then 250 mg/m2 Q7D, or E 150 mg D1–5, 8- 12, 15–26 Q28D. Results: 139 evaluable pts (GBC/GBE 68/71) enrolled at 16 sites 9/04–2/07. Pt characteristics: median age 63/63 (range 36–83/39–86); male 49%/70%; PS 0 35%/48%, 1 59%/46%, 2 6%/6%. Cycles: 343/373 (median 4/4; range 1–18/1–18). Grade 3/4 toxicity (%pts): neutropenia 25%/31%; thrombocytopenia 13%/21%; thrombosis 16%/8%; HTN 15%/11%; rash 10%/6%; diarrhea 3%/11%; GI bleed 3%/6%; proteinuria 1%/6%. Response: complete 1%/3%, partial 22%/15%, stable disease 49%/45%. Median overall survival (OS) 7.8/7.2 mo (95% CI: 5.3, 10.9/5.9, 10.5). Median progression-free survival (PFS) 5.0/5.1 mo (95% CI: 3.6, 5.5/3.4, 5.9). 1-year survival: 35%/30%. Baseline VEGF, VEGFR2 did not correlate with PFS, OS. Early HTN (≥grade 2 in 1st 2 cycles) correlated with response (44% vs. 18%, p=0.04), not OS. There was trend for improved OS in GBE pts with rash ≥grade 2 (10.5 vs. 6.5 mo, p=0.19). Conclusion: Although RR, PFS, and OS are superior to historical controls of G alone, GBC and GBE have insufficient activity to merit phase III evaluation in PC pts. Early HTN and rash may be pharmacodynamic markers. Supported by NCI N01-CM-17102 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech, ImClone, Lilly, OSI, Roche Bristol-Myers Squibb, Genentech, ImClone, Lilly, OSI, Roche Bristol-Myers Squibb, Genentech, ImClone, Lilly, OSI OSI
Hypofractionated stereotactic body radiotherapy for localized prostate cancer.
Authors: M. Ali, B. Collett, D. Stacy, K. Hill, L. Howard, C. Turner, V. Chalian, S. Grampsas
Journal: Journal of Clinical Oncology (2011)

e15012 Background: Convtnl tx of organ-confined malig tumors of the prostate include: surgery, 25-45 XRT tx over 5-9 wks, HDR or LDR brachy, horm tx, or a combo. Optimal tx has never been defined in a randomized trial. The low α/β ratio for prostate cancer(PC) sug a fav response to hypofx dosing. The high degree of accuracy and real time tracking prov by a robotic system allows this schedule. The use of stereotactic body radiotherapy (SBRT) for PC w/this system has been studied at several inst w/good results. This study builds on data and assesses effects of hypofx SBRT on long-term LC of PC and morbidity to rectum, bladder, urethra, penile bulb, and bowel. Methods: 2 level stratification: LR=“Low and Low-Int Risk” or HR=“High-Int and High-Risk”(per NCCN def). LR Mono: 3625 cGy in 5 tx (725 cGy x 5). HR Boost: 2100 cGy in 3 tx (700 cGy x 3). HR Boost foll by IMRT (4500 cGy x 25). PTV=prostate (may/may not include the sem vesicles) w/5mm margin in all dir except post, where margin=3mm. Dose constraints applied to rectum and bladder. Per tx plan 95% of the PTV recv ≥95% of Rx dose. Results: 9 pts w/clin stage T1c-T2a were tx on this study in 2008. LR=#8 and HR=#1. Post tx: 2 cases Grade 2 rectal comp (bleeding). 1 of the 2 pts had res of sx prior to 3 mo and 2nd pt (w/ hx of ulc colitis) had res at 11 mos. 1 pt exp Grade 3 anemia 2 ° to hematuria from bleeding prostate varices and rad cystitis. Grade 1 urinary sx occur in all pts; all managed w/ α blockers. The most sig inc in urinary sx was at 1 mo fu: noct, urg, and freq. Stats for 9 pts (post stats = 24 mo fu): mean pre-tx PSA: 5.8 (SD=3.5); post PSA: 0.6 (SD=0.50); mean pre-tx IPSS: 7.6 (SD=4.4); post IPSS: 9.2 (SD=4.4); mean pre-tx IIEF-5: 13.2 (SD=7.0); post IIEF-5: 7.8 (SD=8.2). An addl 16 pts were tx in 2010. Of these, 5 have comp 3 mo eval. Stats for these 5: Mean pre-tx PSA: 6.4 (SD=1.2); post PSA: 2.6 (SD=1.0); mean pre-tx IPSS: 12.4 (SD=4.3); post IPSS: 8.6 (SD 2.3); mean pre-tx IIEF-5: 10.0 (SD=8.4); post IIEF-5: 8.4 (SD=8.9). Due to ltd sample size, stats for pt tx in 2010 warrant addl fu. Conclusions: Early evidence shows that hypofx SBRT appears to deliver tumor ablating doses of RT to prostate tumors safely and effectively while sparing adjacent tissues. Convenient tx schedules add to the pt QOL. Larger multi-institutional trials currently ongoing will help add to the body of knowledge.
Fish oil, green tea, and prostate cancer prevention.
Authors: J. Shannon, S. Lieberman, C. Maxcy, P. Thuillier, L. Peters, M. Garzotto
Journal: Journal of Clinical Oncology (2010)

TPS140 Background: Fatty acid synthase (FAS) is a lipogenic multienzyme that catalyzes the final step in de novo fatty acid synthesis. FAS more recently has been characterized as an oncogene and is reported to be overexpressed in several tumor types including prostate. While FAS expression in cancer cells does not appear to be normally regulated by nutritional controls, addition of omega-3 fatty acid (w-3 FA), docosahexanoic acid (DHA) has been shown to inhibit FAS expression and fatty acid production in FAS expressing SK-Br3 human breast cancer cells. Once transcribed, FAS activity is dependent upon the appropriate function of each of its component enzymes. Epigallocatechin- 3-gallate (EGCG), a bioactive compound found in green tea, has been demonstrated to inhibit activity of transcribed FAS in prostate cancer cell lines. The primary objective of our clinical trial is to elucidate, in men at high risk for prostate cancer, a potential biologic mechanism whereby EGCG, alone or in combination with w-3 FA, may alter cellular composition and growth, thereby reducing overall risk of prostate cancer. Methods: In this randomized, placebo-controlled intervention study, subjects are men with an initial negative biopsy considered to be at elevated risk of prostate cancer and scheduled for a repeat biopsy. The primary endpoints of this trial are FAS protein and mRNA expression, as measured by immunohistochemistry (IHC) and real-time (RT)-PCR, FAS activity and cell proliferation (Ki-67 expression) in pre and post- intervention benign, pre-neoplastic and neoplastic prostate tissue. Plasma EGCG and red cell fatty acid concentrations are also measured. Subjects are randomized to green tea, fish oil, green tea+fish oil or double placebo for 12 weeks. Green tea supplements consist of extracted green tea polyphenols (75%) and no less than 30% EGCG (approximately 300 mg) per 1,000 mg capsule. Fish oil capsules (1,000 mg) consist of ethyl esters of eicosapentaenoic acid (20:5n-3) and DHA (22:6 n-3). Men take 2 green tea and 3 fish oil capsules daily for a dose of 1.9g of EPA + DHA and 600 mg EGCG. To date, 67 men have completed the trial and 4 are currently enrolled. Our anticipated sample size is 120 men or 30 men per arm. No significant financial relationships to disclose.