tbuckley/cabot-search huggingface dataset:
Surgical outcomes of patients with pancreatic cancer treated with stereotactic body radiation therapy.
Authors: Jin He, Shalini Moningi, Alex B Blair, Ahmed Zaki, Daniel A. Laheru, John L. Cameron, Timothy M. Pawlik, Matthew J. Weiss, Christopher Lee Wolfgang, Joseph M. Herman
Journal: Journal of Clinical Oncology (2015)

341 Background: The surgical outcome of patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BRPC/LAPC) treated with stereotactic body radiation therapy (SBRT) is unclear. Methods: A comparative study was performed to determine if surgical outcomes were different among patients receiving neoadjuvant SBRT vs chemoradiation therapy (CRT) vs chemotherapy only. Results: Between 2011 and 2014, 29 patients with BR/LA-PDAC underwent neoadjuvant chemotherapy and SBRT (6.6 Gy x 5 fractions) followed by pancreatectomy. Eighteen of 29 patients (62%) had LAPC. Their outcomes were compared with 82 patients who received neoadjuvant CRT and 26 patients who received neoadjuvant chemotherapy only (Table). When compared to neoadjuvant CRT and chemo only, the neoadjuvant SBRT group had a higher R0 resection rate (90% vs 84% vs 62%, p=0.02) and vascular resection rate (41% vs 13% vs 31%, p=0.005), respectively. Although the vascular resection and complication rates (Clavien grade 3 or above) were higher in the neoadjuvant SBRT group, no in-hospital mortality was encountered. In the SBRT group, the complete pathological response rate (21%) was higher than that of the other groups (4% and 0% respectively, p&lt;0.001). Survival will be updated later as the current median postoperative follow-up is 6 months in the SBRT group. Conclusions: Neoadjuvant chemotherapy and SBRT is associated with improved surgical outcomes and pathologic complete response rates in selected patients with BRPC/LAPC. Longer follow-up is needed to determine its impact on survival. [Table: see text]
A Multicentre Phase II Study of the Aminopeptidase Inhibitor, CHR- 2797, in the Treatment of Elderly and/or Previously Treated patients with Acute Myeloid Leukemia.
Authors: B. Lowenberg, F. Davies, C. Müller-Tidow, Ulrich Dührsen, A. Burnett, P. Zachée, D. Dierickx, C. Jenkins, P. Sonneveld, M. Jongen-Lavrencic, S. Zweegman, G. Morgan, U. Krug, A. Richardson, L. Hooftman, G. Ossenkoppele
Journal: Blood (2008)
Why some clerkship students are not prepared for the clinical female breast examination.
Authors: C. M. Pugh, D. M. Rooney, A. R. Kaye, J. C. Salud, L. H. Salud, K. Blossfield Iannitelli
Journal: Journal of Clinical Oncology (2011)

e11096 Background: The purpose of this study was to identify and track sources of medical student anxiety towards learning the clinical female breast examination (CBE). Methods: A previously validated survey was used to assess medical student anxiety towards learning the CBE. The survey was administered over three academic school years to first year-M1 (N=504) and second year-M2 (N=331) medical students. To further explore results obtained in the first survey, we administered a more in depth survey to M1 (N=321) and M2 (N=178) students. All surveys were administered at the beginning of class, prior to hands-on training using manikins and after training with standardized patients. Chi-Square analysis was used to assess group differences. Results: When evaluating M1 students, 34.7% (175/504) indicated that their top cause of anxiety towards learning CBEs was “the intimate/personal nature of the exam.” M2 students, 48.3% (160/331) indicated that their top cause of anxiety was “fear of missing a lesion.” Analysis of male and female students in both years revealed male M1 students are more anxious about the intimate nature of the CBE compared to female M1 students [Male= 42.4% (106/250), Female=27.5% (68/247), p < .05]. While this phenomenon continues into the second year, [Male=25.7% (45/175), Female=14.3% (22/153), p < .05], the larger focus for both male and female M2s is “fear of missing a lesion.” In depth exploration of student anxiety using the second survey revealed that 48.6% (156/321) of M1 students who had intimacy issues were most concerned about “expression of nipple discharge.” Conclusions: Our findings confirm that there are differences in the focus of anxiety when comparing first and second year medical students as well as male and female students. While early exposure in the first year of medical school may facilitate a shift in the focus of student anxiety towards the CBE, clerkship directors should be aware that some students continue to be uncomfortable with the intimate nature of the CBE.
First report of outcomes with neoadjuvant chemoradiotherapy (NCR) using weekly intravenous (IV) cisplatin with radiation (NCWR) for treatment of stage II and III extremity soft tissue sarcoma (STS).
Authors: K. K. Curtis, J. B. Ashman, C. P. Beauchamp, M. D. Callister, M. W. Dopp, A. C. Dueck, L. L. Gunderson, T. R. Fitch
Journal: Journal of Clinical Oncology (2010)

10075 Background: NCR prior to resection of STS is used routinely at our institution. Outcomes with NCR are compared to neoadjuvant radiation (NR) or surgery alone (SA). In addition, the initial experience with NCWR as a preoperative regimen is described. Methods: A retrospective chart review was performed. 101 patients (pts) were identified with stage II and III extremity STS treated at Mayo Clinic Arizona between 1998 and 2008. Treatments included SA (34 pts), NCR (31 pts), and NR (36 pts). A variety of chemotherapy regimens were used initially; 15 pts in the NCR group received NCWR. Cisplatin doses were 20-40 mg/m2 IV weekly. Time to failure analyses were calculated from date of first contact. Kaplan-Meier, chi-square, and logistic regression analyses were used. The median overall follow- up time was 24.2 months (mos). Results: Pts treated with NCR and NR were significantly more likely to have tumors > 5 cm compared to pts treated with SA (84% vs. 45%; p<0.001). Nevertheless, rates of margin-negative resection, local-regional relapse free survival, distant metastases free survival and overall survival (OS) were not different among the groups. The rate of limb amputation was significantly decreased for pts treated with NCR compared to SA (10% vs. 38%; p=0.009). For pts with tumors > 5 cm, a trend to improved OS was observed with NCR compared to SA (40.2 mos vs. 29.2 mos; p=0.08). NCR produced higher rates of wound complications compared to SA (53% vs. 9%; p<0.0001) but was not significantly different from NR (43%, p=0.4). Tumor size > 5 cm also was a significant independent risk factor for wound complications (OR 12.37; p=0.035). Acute toxicities such as wet desquamation were not significantly different between NCR and NR. All NCWR-treated pts undergoing surgery had margin-negative resections and no local-regional relapses, and 14/15 pts had limb preservation. Conclusions: NCR is a useful strategy for extremity STS and does not increase complications compared to NR. NCWR is well-tolerated, straightforward to deliver, and has excellent local control results in the initial patient cohort. The NCWR regimen warrants further study. No significant financial relationships to disclose.
Hyperactivated mTOR and JAK2/STAT3 pathways: Crucial molecular drivers and potential therapeutic targets of inflammatory breast cancer (IBC).
Authors: Komal L. Jhaveri, Eleonora Teplinsky, Rezina Arju, Shah Giashuddin, Yasmeen Sarfraz, Melissa Alexander, Farbod Darvishian, Deborah Silvera, Paul H Levine, Salman Hashmi, Heather J. Hoffman, Baljit Singh, Judith D Goldberg, Tsivia Hochman, Amanda Valeta, Robert Schneider
Journal: Journal of Clinical Oncology (2013)

11106 Background: IBC is an aggressive form of breast cancer with poor prognosis. Combined multimodality Rx results in 5 year median OS of 30-50%, underscoring the unmet need for novel targeted strategies. Our preclinical research in cell lines and xenografts suggests a role for activated PI3K/AKT/mTOR pathway in IBC. IBC cells not only express high levels of IL-6 and IL-8 but can recruit tumor activated macrophages (TAMs), which can further induce IL-6, IL-8 and activate JAK2/STAT3 pathway. We therefore investigated independent and combined activity of these pathways. Methods: Archived tissue specimens of 42 IBC pts (1999 - 2009) and 13 controls (normal breast) were analyzed using IHC and scored by 3 independent pathologists. Results were defined as: 0, 1+ = neg; 2+ = pos for activated mTOR (phosphorylatedS6) and 0 = neg; 1+, 2+ = pos for activated nuclear JAK2/STAT3 (pJAK2; pSTAT3), cytokine (IL-6), macrophage infiltration (CD68) and TAMs (CD163). Proportion of IBC cases with pos expression were compared to proportion among controls (Fishers exact test). Clinical and survival data were obtained. Results: Median age at diagnosis - 44.5 yrs (29-64). 22 had HER2 overexpression (8 also ER+) and 9 were ER-/HER2-; ER &amp; HER2 unknown for 1 and 2 pts respectively. Majority were Rxed with neoadjuvant anthracycline and/taxane without adjuvant trastuzumab. There were 24 deaths. Median OS: 67 mths (95% CI: lower 41). Proportions of IBC cases with pos expression when compared to controls are listed in the table (Fishers p value: &lt;0.0001). Of the 31 pts with complete biomarker data who were PS6 pos, 97% had activated JAK2 &amp; 58% had activated STAT3 (McNemar’s chi square, p &lt;0.001). 24/31 (80%) showed strong infiltration of macrophages and TAMs. All cases had widespread IL6 staining. Conclusions: This study validates our preclinical findings and shows hyperactivation of mTOR and JAK2 signaling in vast majority of IBC specimens, with close association between mTOR, TAMs, cytokines and JAK2/STAT3 pathways. These findings support a role for dual blockade of mTOR and JAK/STAT pathways in clinical trials. [Table: see text]
CellScan technology for in vitro prediction of tumor response to chemotherapeutic agents
Authors: S. Chaitchik, O. Soritau, E. Fisher, D. Pelau, L. Lazar, Y. S. Schiffenbauer
Journal: Journal of Clinical Oncology (2005)

2125 Background: Tumor heterogeneity with respect to the response to chemotherapy is a major problem in the field of oncology. In this study we have used the CellScan, a novel static cytometer equipped with a unique cell carrier, for the purpose of monitoring changes in fluorescence intensity and polarization in cancer cells affected by anti neoplastic drugs and correlate it with in vivo clinical outcome. The novelty and advantage of the method presented here is its end-point, which is independent of tumor proliferation, avoiding the complication of tumor culturing and reducing significantly the duration of the assay. Methods: The CellScan assay for testing the drug sensitivity or refractoriness of cancer cells was developed by employing human breast cancer cell lines (T47D and T80) and common anti-cancer drugs. It is based on measuring changes in the degree of fluorescence intensity (FI) and polarization (FP) of various fluorescent probes that occur upon exposure of cancer cells to drugs on a patented CellCarrier. Using this technique, 88 surgically resected tumors were tested for in vitro response to drugs: 67 breast cancers (stages II, III and IV), 8 ovarian carcinomas, 12 digestive cancers and 1 malignant melanoma. Briefly, tumors were mechanically dissociated, exposed to the different drugs for 24 hours and stained with two different markers of apoptosis: FDA (fluorescein di acetate), and Rh123 (rhodamine Rh123). The cells were then scanned using the CellScan and changes in fluorescence intensity and polarization of the fluorescent dyes were measured and compared with untreated control cells. In parallel, the patients were treated with the standard protocol regimens and clinical outcome was followed. Results: In vitro results showed a wide variety of responses even among the same histopathological type or stage of disease. Whenever possible in cases of advanced disease, clinical outcome was compared with CellScan results showing good correlation. Different case reports will be presented. Conclusions: Tumors presented a strong individual sensitivity or resistance to drugs and CellScan test may be used to assist in the prediction of this response to anti-cancer agents. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Medis-El Medis-El
Prior cancer diagnosis in men with nonmetastatic prostate cancer and the risk of prostate cancer specific and all-cause mortality.
Authors: Kristina Mirabeau-Beale, Ming-Hui Chen, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2013)

70 Background: We evaluated the impact of a prior diagnosis of cancer on the risk of prostate cancer specific mortality (PCSM) and all cause mortality (ACM) in men with a diagnosis of non-metastatic prostate cancer (PC). Methods: Using the SEER population data registry, 166,104 men (median age: 66 [Interquartile range (IQR): 60 to 73 years]) diagnosed with prostate cancer (PC) between 2004 and 2007 comprised the study cohort. We used a Fine and Grays competing risks and Cox regression to evaluate the impact a prior cancer diagnosis (excluding non-melanoma skin cancer) had on the risk of PCSM and ACM adjusting for PSA level, Gleason score (GS), tumor (T) category, age at and year of diagnosis, race and whether initial treatment received was curative, non-curative or patients underwent active surveillance (AS) or watchful waiting (WW). Prior to the diagnosis of PC, 1,457 malignancies occurred at a median of 4.8 years. Results: After a median follow up of 2.75 years, 12,453 men died: 3,809 (30.6%) from PC. On multivariable analysis, advancing age in years was associated with an increased risk of PCSM as was Gleason score 8 to 10 PC and the use of WW/AS or non-curative therapy (all p values &lt; 0.001). However, men with a prior cancer were significantly older (median age: 72 vs 66 years, p=0.001) and followed longer (median follow up: 3.0 vs 2.75 years, p &lt; 0.001) and were more likely to have high-risk PC (30.1% vs 26.8%, p=0.01) based on the occurrence of Gleason 8 to 10 PC (19.2% vs 15.1%, P &lt; 0.001) and underwent WW or AS more frequently (30.5% vs 22.5%, p&lt;0.001). Despite these findings which would tend toward an increased risk of PCSM in these men, the adjusted risk of PCSM was significantly decreased in these men (Adjusted Hazard Ratio (AHR): 0.66 [95% Confidence Interval (CI): [0.45, 0.97]; p =0.033) while the risk of ACM was increased (AHR: 2.92 [95% CI: 2.64, 3.23]; p &lt; 0.001) suggesting that competing risks and not curative PC treatment may be accounting for the reduction in the risk of PCSM. Conclusions: In men with a malignancy prior to the diagnosis of PC, a careful assessment of life expectancy is needed to decide on whether curative treatment for PC versus WW or AS is appropriate.
A 10-year age-related survival analysis on cytoreductive surgery in stage IIIC-IV ovarian cancer: Elderly versus younger women.
Authors: Ilary Ruscito, Maria Luisa Gasparri, Stefania Crispino, Chiara La Russa, Claudia Marchetti, Violante Di Donato, Innocenza Palaia, Giorgia Perniola, Angela Musella, Ludovico Muzii, Pierluigi Benedetti Panici
Journal: Journal of Clinical Oncology (2016)

123 Background: Approximately half of women diagnosed with advanced ovarian cancer (AOC) is over 65 years old. According to WHO,65 years is the cut-off age for distinguishing elderly individuals from younger people. Aim of the study was to analyze, in a 10-year retrospective series, the age-related differences in perioperative outcome of cytoreductive surgery for stage IIIC-IV ovarian cancer, identifying in ≥ 65y and &lt; 65y patients(pts)the clinicopathological factors associated with poor prognosis. Methods: 167pts with primary epithelial AOC FIGO stage IIIC-IV underwent cytoreduction and platinum-based chemotherapy from 2005 to 2015 at “Sapienza” University of Rome. Pts ≥ 65 and &lt; 65 years were compared regarding surgical outcome, clinicopathological variables and prognosis. Results: Median age was 56 years(19-87);50 pts (29.9%) were ≥ 65y, whereas 117 pts(70.1%) were younger.42%(21/50) of pts in elderly group and 39%(46/117) in younger group received neoadjuvant chemotherapy followed by interval debulking surgery. No residual tumor was achieved in 82% of elderly pts and in 82.9% of younger pts (p &gt; 0.05).No differences between the two groups were found in terms of mean operative time, mean number of blood units transfused, mean postoperative stay and number of pts requiring intensive care unit stay. The perioperative complications rate was 16% in elderly group and 10.2% in younger pts(p &gt; 0.05).The 60-day postoperative mortality was 2%for elderly and 0.8%for younger pts(p &gt; 0.05).The 10y-PFS was 11.6% vs 15.2%(p = 0.84) and the 10y-OS was 16.9% vs 21.4%(p = 0.60) in elderly and younger pts, respectively. Multivariate analysis showed that age itself was not a prognostic factor for OS but in &lt; 65y pts BMI had an independent prognostic significance (HR:4.97;CI 95%:2.09-11.83),together with residual tumor, which was confirmed to be an independent prognostic factor also in elderly pts(HR = 7.33;CI 95% = 1.30-41.33). Conclusions: Elderly pts with AOC showed a similar perioperative outcome compared to younger pts. In ≥ 65y pts, residual tumor was the only variable impacting significantly survival, while in pts &lt; 65y, BMI was also found to be an independent prognostic factor for OS.
Use of yttrium-90 microspheres (90Y-μS) in pts with advanced hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT)
Authors: A. L. Tsai, C. T. Burke, S. A. Bernard, J. Jorgenson, W. A. Dezarn, D. T. Moore, M. A. Mauro, A. S. Kennedy, B. H. O'Neil
Journal: Journal of Clinical Oncology (2008)

15567 Background: HCC is a large and growing problem, with an incidence of >600,000/yr worldwide. Up to 40% of pts with HCC have PVT. Embolic techniques are commonly used to treat HCC; however pts with PVT run a greater risk of hepatic decompensation following embolic therapy due to diminished collateral blood flow. 90Y-μS exert less of an ischemic effect compared with other methods of embolization and are likely better tolerated in pts with PVT. This study tested this hypothesis by assessing the safety & efficacy of 90Y- μS use in HCC with significant PVT. Methods: Retrospective review of pts with HCC (biopsy proven/AFP >400) & main or first branch PVT treated with 90Y-μS under an IRB approved protocol (n=22) was completed. Exclusion criteria included bili > 2x ULN, uncontrolled ascites, encephalopathy, coagulopathy and hepatopulmonary shunt > 20% by tagged albumin scan. Adverse events were coded via CTC v3.0. Response was determined 6–10wks following treatment using MR/CT and RECIST criteria. The Kaplan-Meier method was used to estimate overall survival. Results: 29 treatments were administered to 22 pts (23 glass, 6 resin spheres). Most patients had CLIP 2 or 3 disease (23%, 36%). Common gr 1–2 toxicities included abdominal pain (38%), nausea (28%), fatigue (21%) and anorexia (21%). Common gr 3–4 toxicities included ascites (14%), encephalopathy (14%) and fatigue (10%). 3 post-tx hospitalizations occurred, all <48hrs, all for signs related to liver failure. 1 death occurred 10d following tx, secondary to liver failure in a pt with bili outside entry criterion. 17/29 tx were evaluable for response (others had non-measurable HCC). Response data reported for treated lobe only. One partial response, progressive disease 53% (95% CI: 28–77%), and stable disease 41% (95% CI: 18–67%) of tx. Median overall survival was 5mo (95% CI: 4–18mo). Conclusions: 90Y-μS may prolong survival beyond the median of 2.7 mo reported for untreated HCC with PVT. Compared with TACE, rates of severe adverse events are low. As in other series, the one death in our series occurred in a pt with elevated bili pre treatment. Comparison between 90Y-μS and systemic therapies is warranted given recent sorafenib data in an overlapping pt population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Sirtex
Dose-modified abiraterone acetate (AA) in men with metastatic castration-resistant prostate cancer (mCRPC): The Princess Margaret Cancer Centre (PM) experience.
Authors: Raya Leibowitz-Amit, Eshetu G. Atenafu, Jo-An Seah, Arnoud J. Templeton, Francisco Emilio Vera-Badillo, Henry L. Solow, Jennifer J. Knox, Srikala S. Sridhar, Ian Tannock, Anthony Michael Joshua
Journal: Journal of Clinical Oncology (2014)

61 Background: AA prolongs survival in mCRPC and is used pre- and post-chemotherapy. In the phase I trial, AA showed anti-tumor activity at 250 or 500 mg daily (‘low doses’). In addition, pharmacokinetic analysis showed that when AA was administered with a high-fat meal vs the fasting state, drug exposure was increased by 4.4-fold [ Attard G et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 2008; 26: 4563-4571.]. Based on this, at our cancer centre low-dose AA is sometimes prescribed with high-fat meals to men who otherwise cannot access the drug due to funding constraints, particularly in the pre-chemotherapy setting. Our aim was to study the association between AA dose, PSA response and progression-free survival (PFS). Methods: All men receiving AA at PM (Nov2009-Mar2013) were reviewed retrospectively. PSA response rate (PSA-RR) was defined according to PCWG2 criteria as a confirmed decrease ≥50% in PSA. PFS was defined from start of AA to PSA progression, clinical progression, drug cessation or death. Associations between dose, PSA-RR and PFS were assessed using chi-square and logrank tests, respectively, for all patients and for the sub-group of chemo-naive patients. Results: 109 men were treated with AA, 89 at a full dose of 1000 mg in the fasting state, 20 at low doses with high-fat meals. There was no significant difference in PFS between the two dose levels for all men. PSA-RR was non-significantly lower in chemo-naive men treated with low doses compared to full dose (p=0.09; table). Conclusions: Administration of low dose AA with high-fat meals is not associated with shorter PFS despite a trend to lower PSA-RR. These results are clinically relevant in resource-limited settings and warrant further prospective clinical research. [Table: see text]