tbuckley/cabot-search huggingface dataset:
Angiosarcoma of the breast: A rare clinicopathological entity
Authors: T. Biswas, P. Tang, A. Muhs, M. Ling
Journal: Journal of Clinical Oncology (2008)

21504 Background: Angiosarcoma (AS) of the breast accounts for fewer than 1% of all malignant breast neoplasms and can be primary or secondary. Primary AS usually occurs in younger women, primarily involves the breast parenchyma. Secondary AS in the breast could be as a result of persistent lymph edema following radical mastectomy and lymph node dissection, so called Stewart-Treves syndrome and in more recent years following breast conserving therapy for primary breast cancer. We report our institutional experience of angiosarcomas of the breast that were diagnosed and treated between 1996 and 2007. Methods: This study is a retrospective review of patients with a diagnosis of angiosarcoma of the breast. All female patients with a diagnosis of angiosarcoma of the breast were identified from the pathology data-base. Their hospital records were retrieved to gather information on treatment, tumor response, failure and survival. Results: Of 2,500 breast cancers diagnosed at our institute during the study period, only 8 patients (0.3%) were identified who had a histologically confirmed diagnosis of angiosarcoma of the breast. Median age was 70.3 years at diagnosis (range 35.6–85.7 years). Seven (87%) patients had a history of prior radiation to the breast, whereas 1 (13%) had primary AS. The detail of treatment and the outcome is shown in the Table. All patients received initial surgical resection. No patient received adjuvant radiotherapy. Only one patient was treated with neoadjuvant and adjuvant chemotherapy. 87% patients suffered tumor recurrence. The median overall survival (OS) was 37.4 months (8.7–92.8 months) and relapse-free survival (RFS) was 17.9 months (2.5–69.4 months). Conclusions: Even though AS of the breast is still a rare neoplasm, it is being increasingly recognized most probably as result of more breast-conserving therapy. High clinical suspicion and MRI may help for early diagnosis. These tumors tend to behave aggressively and needs multidisciplinary approach to improve the outcome. Treatment and Clinical Outcome Patient (age in yrs.) Initial Tx Salvage Tx Relapse RFS (months) OS (months) 1 (85.7) Mastectomy Excision & Radiation to chest wall Local recurrence 3.22 8.75 2 (68) Neoadjuvant chemo, Mastectomy, adjuvant chemo Excision, more chemo 4 local recurrences 17.88 28.04 3 (72.5) Mastectomy Not applicable No 32.19 32.19 4 (73.1) Mastectomy Chemotherapy, palliative surgery and radiation Distant failure in liver & stomach 42.67 17.95 5 (57.2) Wide excision Re-excision 2 local recurrences 5.85 56.42 6 (63.6) Wide excision Mastectomy & radiation to chest wall Local recurrence 44.38 67.43 7 (35.6) Mastectomy Chemo, radiation Both local and distant in liver & bones 69.4 92.81 8 (85.2) Mastectomy Excision Local recurrence in the medial quadrant of opposite breast 15.19 2.53 Median 17.9 37.4 No significant financial relationships to disclose.
Whether mCRC patients with other <i>RAS</i> mutations benefit from the addition of bevacizumab as first-line therapy.
Authors: Mingyi Zhou, Ping Yu, Kezuo Hou, Xiujuan Qu, Yunpeng Liu, Ying Chen, Jinglei Qu, Jingdong Zhang
Journal: Journal of Clinical Oncology (2016)

579 Background: It is not clear whether Bevacizumab plus chemotherapy could improve the prognosis of mCRC patients with other RAS mutations beyond KRAS exon 2. Methods: The MEDLINE, EMBASE, Cochrane databases, and Clinical Trials databases were reviewed to September 2015. The data of patients with KRAS exon 2 mutations was only available in FIRE3 study. So we could not perform the meta-analysis by KRAS exon 2 mutations. The data of patients with other RAS mutations beyond KRAS exon 2 were available in PEAK and FIRE3 studies. Hazard ratio (HR) was used to analyze the progressive-free survival (PFS) and overall survival (OS). Relative risk (RR) was used to analyze overall response rate (ORR). Results: Patients with other RAS mutations beyond KRAS exon 2 benefited from the addition of Bevacizumab. Bevacizumab + chemotherapy significantly improved the PFS compared with anti-EGFR moAb + chemotherapy (HR: 1.82, CI: 1.20–2.77, P =.005). The addition of Bevacizumab tended to improve ORR, though there is no significant difference (RR: 0.83, CI: 0.58–1.18, P =.288). But the OS tended to be shorter in Bevacizumab + chemotherapy arm than anti-EGFR moAb + chemotherapy arm without significant difference (HR: 0.72, CI: 0.25–2.05, P =.534). Conclusions: Patients with other RAS mutations beyond KRAS exon 2 could choose Bevacizumab plus chemotherapy as first-line therapy. But there is still no adequate evidence to reject or support the predictive value of RAS status in the effect of the addition of Bevacizumab. Moreover, which is the better primary endpoint, PFS or OS? Which is the better consequence of strategy, anti-EGFR moAb followed by Bevacizumab or Bevacizumab followed by anti-EGFR moAb? RCTs with large sample size comparing the efficacy of anti-VEGF moAb + chemotherapy and chemotherapy alone by RAS status as the first-line therapy in mCRC patients are required in the future.
Reply from Orbis to Watts and other rapid responders
Authors: Richard Hurley
Journal: BMJ (2017)

The two articles about Orbis, this year’s beneficiary of The BMJ ’s charity appeal, say, “Donate to Orbis . . . £150 could buy six intraocular lenses for cataract surgery,” and Watts has questioned this cost.123

Laura Burnell, Orbis UK’s head of communications, told me that this price is given in the International Agency for the Prevention of Blindness’s standard list of recommended equipment and consumables.4

“The lens was also chosen as it is …
ERCC1-associated platinum resistance and PARP inhibition in lung cancers.
Authors: H. Cheng, Z. Zhang, C. A. Powell, B. Halmos
Journal: Journal of Clinical Oncology (2011)

e17533 Background: Platinum-based regimens are standard of care in advanced lung cancer despite low response rates. They damage DNA by forming platinum-DNA adducts. Tumor expression of ERCC1, a key enzyme in nucleotide excision repair, may predict the response to platinum agents with increased expression associated with resistance. We examined if combined impairment of two DNA repair pathways, PARP inhibition and low ERCC1 expression, would increase sensitivity to platinum agents in lung cancers. Methods: Cell viability and cell cycle effects were measured using MTS, clonogenic and BrdU proliferation assays. ERCC1 expression and phosphorylation of P53 and γH2A were determined by Western blots. Knockdown was performed using siRNA pools targeting ERCC1. All data were expressed as means ± SD from at least triplicates. Statistical analysis was performed by one- or two-way ANOVA. Results: A549, H157 lung cancer cells have high ERCC1 expression, whereas HCC827, PC9 have low expression. When different dose-combinations of cisplatin and olaparib (PARP inhibitor) were tested, olaparib selectively augmented cisplatin-induced growth inhibition in ERCC1-low but not in ERCC1-high cells. As a single agent, olaparib conferred selective cytotoxicity against ERCC1-low cells with no effects in ERCC1-high cells. Knockdown of ERCC1 in ERCC1-high A549 significantly increased sensitivities to olaparib and cisplatin. Treatment with cisplatin or olaparib led to an increase in the G2/M population in ERCC1-low cells with an even stronger effect seen with the combination. Cisplatin and olaparib activated DNA damage pathways as evidenced by increased phospho-γH2A levels. Olaparib and cisplatin alone or in combination increased phospho-P53 in ERCC-low HCC827 cells in a dose-dependent fashion. Conclusions: PARP inhibition selectively augments cisplatin sensitivity in ERCC1-low but not high lung cancer cells. Cisplatin sensitivity is enhanced by ERCC1 knockdown in ERCC1-high cells. PARP inhibition alone or in combination with cisplatin leads to G2/M cell cycle arrest, likely by activation of the pathway involving γH2A and P53. Our study may identify novel synergistic approaches based on synthetic lethality for lung cancer based on tumor ERCC1 expression.
The influence of tumor location, histology, and patient ethnicity on the accuracy of EUS in staging gastric and gastroesophageal junction (GEJ) cancers.
Authors: Andy Z. Huang, Yiqing Xu, Yiwu Huang, Vimbai Nyemba, Than Than Aye, Na Liu, Ashrei Y Bayewitz, Peter Homel
Journal: Journal of Clinical Oncology (2016)

39 Background: Endoscopic ultrasound (EUS) is a routine staging test performed in patients with gastric and GEJ cancers and is highly valuable in treatment planning. The reported accuracy varies from 40% to 90%. We aim to investigate the staging performance of EUS at our institution and hypothesize that EUS accuracy can be influenced by tumor location, histology, and patient ethnicity. Methods: We performed a retrospective analysis of patients diagnosed with gastric and GEJ cancer between January 2006 and June 2015 who had EUS proceeded directly by surgery. T and N staging by EUS were analyzed for their sensitivity, specificity, and positive (PPV) and negative predictive values using surgery as the gold standard. The following variables were evaluated: tumor histology (intestinal or diffuse type), location (GEJ, cardia, body, or antrum), and patient ethnicity (Asian versus non-Asian). Results: Over 46 patients who met the inclusion criteria, EUS had T and N accuracy of 47.8% and 58.7%, respectively (p &lt;.05). EUS had high specificity (88%) but low sensitivity (38%) for N staging. In predicting T staging, EUS was most accurate when the tumor was located in the body (72%, n = 7) and least accurate in the cardia (33%, n = 6) with 46% (n = 13) in the GEJ and 45% (n = 20) in the antrum. EUS tended to upstage the T value when a tumor is located in the body or GEJ, and downstage it in the cardia or antrum. The PPV using EUS for T1, T2, T3, and T4 were 89%, 22%, 45%, and 57%, respectively. The PPV using EUS for N staging was 73%. EUS was more accurate for T in Asians (55%, n = 33) than in non-Asians (31%, n = 13), and in intestinal type (56%) than diffuse (36%). For N staging, it was most accurate in the body (86%) and least accurate in the GEJ (50%). It was also more accurate in diffuse tumors (79%) than intestinal (52%) and more accurate in non-Asians (77%) than in Asians (53%). Conclusions: EUS as a common tool in preoperative staging may be inaccurate when performed in community hospitals. The predictive rate appears to vary in Asian vs non-Asian patients and in intestinal vs diffuse tumors. It is most predictive when the tumor is T1 and located in the gastric body. A prospective study is needed to confirm these findings.
Interest of percutaneous renal biopsy for small renal masses.
Authors: Alexandre Ingels, Eric Barret, Francois Audenet, Luca Lunelli, Guilherme Prada Costa, Pierre Validire, Stephane Lenoir, Francois Rozet, Marc Galiano, Rafael Sanchez-Salas, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2014)

539 Background: Assess CT-scan guided renal biopsies relevance in the management of small renal masses. Methods: Retrospective analysis from 01/2007 to 12/2012 of percutaneous CT-scan guided renal biopsies performed at our institution for patients harboring renal tumors. Exclusion criteria were presence of metastasis and/or &gt;4cm tumors. Data analyzed were pathological outcomes, management of the tumors and complications from the procedure during the 30 days post-biopsies. Results: 119 patients underwent a renal biopsy during this period. 79 presented the selection criteria. Renal biopsies lead to a diagnosis in 70 cases (88.6%) and were non contributive in 9 cases (11.4%). Among contributive biopsies, there were 46 (66%) cases of cancer and 24 cases (34%) of benign tumors. During follow-up, 2 (2.5%) patients presented Clavien-Dindo grade I-II complications: 1 acute urinary retention and 1 subfebrile lumbar pain. Conclusions: The yield of CT-scan guided renal biopsies to define pathological features of small renal masses was of 88.6%. Morbidity of the technique is low. We consider renal biopsy as a relevant strategy to diagnose a small renal mass, to define the best treatment and to prevent morbidity from useless invasive surgical procedures. [Table: see text]
LTB4/BLT1シグナル伝達欠失は自然および獲得免疫機構を増強することでマウスGM−CSFが誘導した長期的抗腫瘍免疫記憶の産生を促進する
Authors: 洋介 横田, Yosuke Yokota, ヨウスケ ヨコタ
Journal: Blood (2013)
A phase II trial of cetuximab as therapy for recurrent non-small cell lung cancer (NSCLC): Final results
Authors: R. Lilenbaum, P. Bonomi, R. Ansari, T. Lynch, R. Govindan, P. Janne, N. Hanna
Journal: Journal of Clinical Oncology (2005)

7036 Background: A phase II trial was conducted to evaluate the activity of single agent cetuximab in patients (pts) with recurrent NSCLC. Preliminary data was previously reported (Lynch, et al, abstract 7084, ASCO 2004). Methods: Pts with stage IIIB/IV NSCLC with recurrent or metastatic disease following ≥1 prior regimen, including a prior platinum, were enrolled on the study. Pts had an ECOG PS of 0 or 1 and were stratified based on the presence or absence of the EGF receptor. The EGFR undetectable pt strata was closed due to lack of available pts. Pts received an initial cetuximab dose of 400 mg/m2 on Day 1 of Cycle 1, followed by weekly doses of 250 mg/m2 until disease progression or unacceptable toxicity. A cycle was defined as 4 weeks. Response rate (RR) was determined for the total population. Pts were also assessed for time to disease progression (TTP), survival, and safety. Results: Between May 2003 and March 2004, 66 pts were enrolled: male/female 42/24; median age of 63 years (range, 39–79); EGFR detectable 60; ECOG 0/1 28/37; stage IIIB/IV 10/56. Histology included adenocarcinoma 36; squamous cell 14; large cell 6; and other 10. Smoking history included 13 pts who had never smoked, 45 prior smokers and 8 current smokers, with a median of 45 pack years. Number of prior regimens: 1 (28); 2 (26); 3 (9); >3 (3). The median number of cycles of cetuximab received was 2 (range 1–14). Responses in the 60 evaluable pts included PR 2; SD 15; PD 36; for an overall RR of 3.3% (95% CI 0.41–11.53%) and a disease control rate of 28%. The median TTP was 2.3 months and median survival was 8.1 months. The 6 month survival rate was 63% and the 1-yr survival was 43%. Of the 66 pts enrolled, 33 remain alive. The most commonly reported toxicity was rash 77% (Gr.3 6.1%). Grade 3/4 toxicities included dyspnea 15%, fatigue 13.6%, infections 9%, gastrointestinal 6%, back pain 4.5%, HSRs 3%, and pleural effusions 3%. Mutational analysis was performed on 39/43 available samples. Three pts were found to have mutations (2 del746–750 (both SD) and 1 L861Q (PD). Conclusions: Single agent Cetuximab is well tolerated and its role in the treatment of NSCLC along with chemotherapy is under investigation. The relationship between EGFR mutations and response to cetuximab remains unclear. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Eli Lilly
A phase I trial of oblimersen and gemcitabine in refractory and advanced malignancies
Authors: G. Fisher, R. Advani, H. Wakelee, C. Jacobs, K. Gladysheva, A. M. Fitzgerald, B. Sikic
Journal: Journal of Clinical Oncology (2005)

3174 Background: Over-expression of bcl-2 has been associated with poor clinical response to therapy. Oblimersen (O) is a phosphorothioate oligonucleotide antisense molecule that binds to the first six codons of human bcl-2 mRNA. The aim of this study was to determine the maximum tolerated dose (MTD) and pharmacokinetic (PK) and pharmacodynamic (PD) of O and gemcitabine (G) in combination administered every 2 weeks. Methods: Cohorts of 3–6 patients were treated. O was administered as a 5 day CIV every 2 weeks and G at a fixed dose rate of 10 mg/m2/hr IV on day 5 with every cycle. Results: 16 pts with a variety of tumors have been treated with 2–6 infusions (median 3); Tumor types included; 4 each of hepatobiliary and lung, 3 pancreatic, 2 GI and 3 miscellaneous. All 4 planned cohorts have been treated. Dose escalation for O mg/kg/d and G mg/m2 was as follows; Cohort 1 (5/1000, n = 4), Cohort 2 (7/1000, n = 3), Cohort 3 (7/1200, n = 3) and Cohort 4 (7/1500, n = 6). Hematological toxicities were all grade 1 or 2. Non hematological toxicity was mostly grade 1 or 2 with one grade 3 DLT (edema) in cohort 4. PK and PD analyses are ongoing. Conclusions: O and G at the highest dose level of 7/1500 was well tolerated with no DLT. PK and PD analyses are pending. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly
Trends in Discharge Claims for Acute Myocardial Infarction among Patients on Dialysis
Authors: Gautam R. Shroff, Shuling Li, Charles A. Herzog
Journal: Journal of the American Society of Nephrology (2017)

Analysis of a contemporary cohort of patients on dialysis revealed that mortality from acute myocardial infarction (AMI) has decreased, whereas the prevalence of AMI has increased markedly, particularly among patients with non-ST elevation myocardial infarction (NSTEMI). Using inpatient discharge diagnosis codes (1993–2008), we determined that proportions of AMI claims decreased in the primary position (from 65% to 52%) but increased in the secondary position (from 35% to 48%). Proportions of NSTEMI codes increased remarkably in both the primary and secondary positions. The progressive increase in diagnostic claims for secondary AMI identifies a unique high-risk population and has important clinical, economic, and epidemiologic implications among patients on dialysis.
Long term toxicity of tyrosine kinase inhibitors (TKIs) in patients with metastatic clear cell renal cell carcinoma (RCC)
Authors: B. K. Vakkalanka, P. Elson, L. Wood, R. Dreicer, J. A. Garcia, R. M. Bukowski, B. I. Rini
Journal: Journal of Clinical Oncology (2008)

16045 Background: TKIs are in common use in metastatic RCC, often given chronically. The toxicity related to the long term use of oral TKIs in metastatic RCC is not well described. Methods: Patients (pts) with clear cell metastatic RCC, receiving either sunitinib (SU), sorafenib (SOR) or, axitinib (AG), followed for at least 16 months were retrospectively identified. Data on Karnofsky performance status (KPS), response to treatment, dose modifications and, time to worst grade toxicity, were analyzed. Results: Sixteen pts received an oral TKI (SU=12, SOR=3, AG=1) for a median duration of 24.4 months (range 16.5- 46.1). Median age of pts is 61.5 yrs (range 35–70). Baseline KPS was 90 in 7 pts (44%) and 100 in 9 pts (56%).12 pts (75%) experienced a decline in KPS by 10 points and 2 pts (12.5%) by 20 points. Best response was complete response in 1 pt (6%), partial response in 10 pts (63%) and stable disease in 5 pts (31%). Overall 12% (2/16) of pts had Gr 4 toxicity, 38% (6/16) had Gr 3 toxicity, and 50% (8/16) had grade 1–2 as their worst toxicity. The median time to worst grade toxicity was 5.5 (range 0.6–28.3) months. 77% of worst grade toxicities occurred within 12 months and 23% after 12 months (see table). Two pts discontinued therapy; one due to PD and the other following a myocardial infarction. 50% (8/16) of pts had dose reductions at some point in time. Dose of SU starting at 50mg qd was reduced to 37.5mg qd in 5/12 pts and 25 mg qd in 1/12 pts respectively. Dose of SOR starting at 400 mg bid was reduced to 400 mg qd in 1/3 pts and to 400 mg qod in 1/3 pts. Conclusions: Maximum toxicity from oral TKIs is generally, but not always reached within 12 months after initiating treatment. Hypothyroidism, myelosuppression and fatigue were the most common toxicities in pts receiving treatment for longer than 12 months. Specific maximum toxicities and timing Timing of worst grade toxicity after starting treatment <12 M >12 M Pts N % N % Hypothyroidism 7 44 6 38 Anemia 2 13 3 19 Neutropenia 4 25 5 31 Thrombocytopenia 9 56 4 25 Fatigue 9 56 2 13 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Bristol-Myers Squibb, Genentech™ BioOncology, Genzyme, Onyx, Pfizer Oncology, Wyeth Bayer, Onyx, Pfizer Oncology, Wyeth Pfizer Oncology
A single-dose comparative bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers.
Authors: Christina Cognata Smith, Neha Parikh, William G. Kramer, Varun Khurana, Santosh Vetticaden
Journal: Journal of Clinical Oncology (2016)

198 Background: The capsule formulation of dronabinol, a pharmaceutical tetrahydrocannabinol (THC), is approved for anorexia associated with weight loss in patients with AIDS and for cancer chemotherapy-associated nausea/vomiting in patients with inadequate response to conventional antiemetics. A new oral formulation (i.e., dronabinol solution) was evaluated in a bioequivalence study versus currently marketed dronabinol capsules. Methods: In an open-label, 2-treatment, 2-sequence, 4-period, single-dose crossover study, healthy volunteers were randomized to receive 1 of 2 treatment sequences (T-R-T-R or R-T-R-T; T = dronabinol 4.25 mg oral solution and R = dronabinol 5 mg capsules). Dosing occurred after an overnight fast, with a minimum 7-day washout period between treatment periods. A validated liquid chromatography-tandem mass spectrometry method was used to determine plasma concentrations of dronabinol and the primary metabolite 11-OH-Δ9-THC. Results: Fifty-one of 52 enrollees had pharmacokinetic data for analysis. Mean pharmacokinetics were (oral solution vs capsule): C max (2.0 vs 2.4 ng/mL), median T max (1.0 vs 1.5 h), AUC 0-∞ (3.8 vs 4.1 h∙ng/mL), and t 1/2 (5.6 vs 3.1 h). The 2 formulations were bioequivalent with respect to maximum plasma concentration (C max ; reference-scaled criteria) and area under the plasma concentration-time curve (from time zero to last measurable concentration and from time zero to infinity [AUC 0-∞ ]; average bioequivalence) of dronabinol. The data for the 11-OH-Δ9-THC metabolite provide further support for the bioequivalence of the 2 products. Post hoc analysis demonstrated that all volunteers (100%) had detectable plasma dronabinol concentrations at 15 min with the oral solution compared with &lt; 25% of volunteers for the capsules. Intra-individual variability was lower with oral solution versus capsules (for AUC 0-∞ , 13.5% vs 36.8%, respectively). Conclusions: Dronabinol oral solution 4.25 mg was bioequivalent to dronabinol capsules 5 mg, and exhibited quicker onset of detectable levels and lower intra-individual variability in comparison with dronabinol capsules 5 mg. Clinical trial information: NCT01448772.