tbuckley/cabot-search huggingface dataset:
PET-positive thyroid incidentalomas: Characteristics and risk of malignancy observed in a tertiary referral center
Authors: M. S. Connor, B. D. L. Li, M. R. Ramaswamy, R. H. Turnage, Q. D. Chu
Journal: Journal of Clinical Oncology (2004)

5535 Background: As positron emission tomography (PET) becomes more utilized in the clinical setting, the finding of an incidental focal thyroid uptake (thyroid incidentaloma) presents a diagnostic challenge. We evaluated the incidence of thyroid malignancies in the setting of a PET-positive thyroid incidentaloma. Methods: We reviewed our database for all patients who underwent a 18fluorodeoxyglucose positron emission tomography (FDG-PET) at our institution from January 1, 2000 to November 30, 2003. From this database, information on all patients who had focal thyroid uptake without any history of thyroid disease were culled. Available follow-up data were documented. Results: There were 6,241 PET scans performed during the study period, of which 76 patients (1.2%) had focal thyroid uptake. Records of sixty-two patients (82%) were not available because of incomplete follow-up data or because the patients had other prevailing medical conditions that precluded further work-up. Of the remaining 14 patients (18%) who had further work-up for their incidentalomas, a fine needle aspiration of the abnormal thyroid was performed in 13 patients and a thyroid lobectomy was done in one patient. The following pathology was identified (Table 1). Table 1 * Patient refused surgery Conclusions: FDG-PET thyroid incidentalomas occurred with an incidence of 1.2% at our major referral institution. The incidence of malignancy was 28.6% for those individuals who underwent further evaluation for their incidentalomas. Given the relatively high frequency of malignant pathology in these patients, we recommend that further work-up for these incidentalomas is warranted. No significant financial relationships to disclose.
Soundings: Let the hair sit
Authors: Liam Farrell
Journal: BMJ (2001)

Any time that I hear the word “tradition,” I want to throw up. Traditional is another word for outmoded, narrow minded, tacky, obsolete, kitsch. As living proof, walk into any Olde Tyme shop which sells Traditional Arts and Crafts and have a look around: baskets made out of reeds marinated in dead otter phlegm; useless ornaments sculpted in irritating tweed; pathetically unfashionable and impractical Aran sweaters. It's all shite, isn't it? No one but the most gullible idiot would actually buy anything.

But there is one traditional saying that still has much relevance, particularly to doctors. I think it is an ancient Irish idiom, because I heard it from an ancient Irishman, a man so old he had hairs a foot long growing out of his nose.

We were out herding sheep before the lambing and one old ewe was being skittish, as sheep often are around me (I think they recognise a predator when they see one). No matter how I chased her, she always managed to dodge away just as I thought I had her cornered. Exhausted and red faced and perspiring in my Aran sweater, I swore I would feed her spinal cord to the cows if she didn't behave, but my companion remained serene and unmoved.

“Don't get all hot and bothered, young fella,” he said placidly, drawing noisily and offensively on his pipe, his nasal hairs waving gracefully in the mountain breeze, like fronds of kelp on the Atlantic swell. He leaned back grandly against the gate between the dry stone walls, like an unhygienic White Knight.

“Wait and see,” he continued, “she'll follow the others in a minute. Just take it easy and let the hare sit.”

I sat down beside him for a few minutes, bitter experience leading me to sit upwind to avoid being drenched by the inevitable tobacco-stained spittle and being stroked unpleasantly by the more wayward nasal hairs. Sure enough, after being left alone for a while, the old ewe slowly drifted into the enclosure after the rest of the flock.

I learned much from that little morality play and now, during many a consultation about a troublesome rash or a bad dose of flu, I will sit back thoughtfully in my chair and say sagely, “Ah sure, maybe the best thing would be just to let the hare sit.” Patients understand this (I think).

I also make sure my nasal hairs remain well clipped.
Pharmacokinetics of lenalidomide in subjects with various degrees of renal function
Authors: N. Chen, H. Lau, L. Kong, J. Zeldis, R. Knight, O. Laskin
Journal: Journal of Clinical Oncology (2007)

2520 Background: Lenalidomide is a novel oral immunomodulatory drug approved for treating myelodysplastic syndrome (MDS) and multiple myeloma (MM). As unchanged lenalidomide is eliminated predominantly by urinary excretion, the present study investigated the effect of renal impairment (RI) on pharmacokinetics (PK) of lenalidomide. Results were used to refine initial dosing recommendations based on a subject’s estimated creatinine clearance. Methods: The study was conducted at 3 clinical centers. Thirty male and female subjects aged 39–76 years were stratified into 5 groups based on their creatinine clearance (CLCr) values: normal renal function (NRF) (CLCr &gt; 80 mL/min; N = 7), mild RI (50 = CLCr = 80 mL/min; N = 5), moderate RI (30 = CLCr &lt; 50 mL/min; N = 6), severe RI (CLCr &lt; 30 mL/min, but not on dialysis; N = 6), and end stage renal disease (ESRD, requiring dialysis; N = 6). Subjects with NRF, mild, moderate or severe RI received a single 25-mg oral dose of lenalidomide. Subjects with ESRD received 2 single 25 mg doses which were separated by 7–10 days: one dose on a non-dialysis day and the other dose 3 hours before a 4-hour haemodialysis. Assessments included PK and safety parameters. Results: All subjects completed the study. Total and renal clearance of lenalidomide were strongly correlated with CLCr (R &gt; 0.9, p &lt; 0.01). As a result, AUC 8 increased with decreasing CLCr. The mean difference in AUC 8 between NRF and mild RI was &lt; 20%. Compared with the pooled data from NRF and mild RI groups, mean AUC 8 increased approximately 140% in moderate RI, 240% in severe RI, and 360% in ESRD (off dialysis). There was no correlation between C max or T max and CLCr. Approximately 10% of the dose was recovered in the dialysate of subjects with ESRD. Protein binding of lenalidomide was not markedly affected by RI (∼35 - 44%). The drug was well tolerated. On the basis of these data, recommendations for initial starting doses were made ( Table below). Conclusions: Lenalidomide dosage adjustment should be considered for patients with CLCr &lt; 50 mL/min. [Table: see text] No significant financial relationships to disclose.
An indirect comparison analysis of pazopanib versus other agents in metastatic renal cell carcinoma (mRCC).
Authors: L. McCann, O. Amit, L. Pandite, R. G. Amado
Journal: Journal of Clinical Oncology (2010)

e15128 Background: Treatment for mRCC has changed dramatically since 2005. The phase III trials of sorafenib, sunitinib, pazopanib, and bevacizumab + interferon (IFN) were all best supportive care (BSC) or IFN controlled. In the absence of data from a large-scale head-to-head trial comparing these agents, we conducted an indirect comparison analysis to determine the relative effectiveness of pazopanib versus the other agents. Methods: Adjusted indirect comparison (AIC) was used to compare progression-free survival (PFS) between these agents using data from phase III trials. Data estimating the efficacy of IFN relative to BSC came from the MRCRCC trial (1999) comparison of IFN to hormone therapy. Safety of pazopanib was estimated using integrated data from all pazopanib RCC trials and compared to the other agents using 95% confidence intervals (CI) of event rates from the phase III trials. Results: Patient characteristics were similar across all trials. AIC suggests that pazopanib is superior to IFN with a PFS HR (95% CI) of 0.50 (0.31, 0.81). In treatment-naive patients, the indirect PFS HR (95% CI) suggests that pazopanib is not statistically different from sunitinib (0.93 [0.56, 1.56]) or bevacizumab + IFN (0.79 [0.48, 1.32]). In cytokine-pretreated patients, the indirect PFS HR (95% CI) suggests that pazopanib is not statistically different from sorafenib (0.98 [0.61, 1.58]). Safety comparisons must be interpreted based on the length of exposure to drug for the reported data, which varied across trials. AEs were common with all agents (92% - 99%). Rates of SAEs were similar across agents (27% - 34%). The rate (95% CI) of grade 3/4 AEs was lower with pazopanib (44% [40, 48]) compared to sunitinib (67% [62, 71]) or bevacizumab + IFN (60% [55, 66]). Conclusions: While head-to-head trials remain the gold standard, this indirect comparison suggests comparable efficacy between pazopanib and other approved agents. Indirect safety comparisons suggest that each agent has a unique safety profile even in the presence of some shared class effects. These hypothesis-generating results highlight the need for clinical trials directly comparing these agents. A head-to-head phase III study is ongoing between pazopanib and sunitinib. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Salvage photodynamic therapy (PDT) for locoregional failure after definitive chemoradiotherapy (CRT) for esophageal cancer (EC)
Authors: M. Muto, T. Yano, C. Katada, K. Mera, T. Doi, S. Ishikura, A. Ohtsu, S. Yoshida
Journal: Journal of Clinical Oncology (2004)

4171 Background: Locoregional failure after definitive CRT for EC still remains the major issue. Although salvage surgical resection has curative potential, this approach is associated with high mortality and morbidity rates. PDT is an effective treatment option for EC and then we have been indicated this treatment for the locoregional failure after definitive CRT. The aim of this analysis was to evaluate the feasibility and preliminary efficacy of salvage PDT after definitive CRT. Methods: Salvage PDT was indicated if patients (pts) fulfilled the followings: clinically defined N0M0 by CT and EUS, estimated depth of the recurrent or residual lesions within the muscularis propria layer by EUS, refusal of salvage surgery, and written informed consent. The CRT consisted of 60 Gy of external beam irradiation in 30 fractions and concurrent with chemotherapy (cisplatin or nedaplatin+5FU). Procedures of PDT were as follows: 2mg/kg of Photofrin was administered intravenously followed by photoradiation with excimer dye laser (wavelength:630nm, light dose :75J/cm2) 48 and 72 hrs after the injection. Results: From Dec. 2002 to Sep. 2003, 10 pts underwent salvage PDT: 4 for local recurrence and 6 for residual tumor after definitive CRT. Median age was 66 (51–75) with a male/female ratio of 9/1. Baseline clinical stages before CRT were: I/IIA/IIB/III/IV in 0/4/1/4/1 pts. Median hospital stay during the PDT procedures was 10 (6–20) days. Fever (>38.5°C) and chest pain was observed in 3 and 4 pts, respectively, though they were controlled by conservative treatments. No pt showed cutaneous phototoxicity or treatment-related death. With a median follow-up of 7 (3–9) months after salvage PDT, complete response (CR) was achieved in 7 (70%) pts. Median duration to confirm CR was 63 (35–112) days. Two pts developed local recurrence. The 6-months progression-free and overall survival rates were 44% and 76%, respectively. Conclusion: Salvage PDT appears to be feasible with a high CR rate to locoregional failure after definitive CRT. This treatment may improve local control with low mortality and morbidity, although further follow-up is necessary. No significant financial relationships to disclose.
Apoptosis signal ceramide c6 synergizes anti-tumor effects of paclitaxel oxaliplatin &amp; cisplatin on growth of pancreatic cancer in SCID mice
Authors: D. Shrayer, H. J. Wanebo, M. Resnick
Journal: Journal of Clinical Oncology (2006)

13135 Background: Ceramide (C6) is an analog of endogenous ceramides, which are a major signaling pathway for apoptosis in cells undergoing stress, exposure to chemotherapy. Current report documents in vivo anti tumor effects combining C 6 with oxaliplatin &amp; cisplatin on L3.6 human pancreatic adenocarcinoma implanted in the SCID mouse. Correlative histologic studies provide additional mechanistic insights. Methods: SCID/Beige/ Taconicmale mice were inoculated subcutaneously (S.C.) w/2×10 6 L3.6 pancreatic cells. Chemotherapy doses were based on clinical &amp; in vitro data. Treatment began 4 days post tumor implant with 3 weekly 3×/wk) intraperitoneal (IP) injections of Paclitaxel (P) 3.0 m/kg, oxaliplatin (OX) 2.5 mg/kg, cisplatin (CP) 2.5 mg/kg, with/without ceramide 10 mg/kg. Mice were observed for 6 weeks &amp; were autopsied when near death, or at 6 week level. (All controls died by 3 rd week). Data recovered included maximum tumor volume, tumor weight, body weight &amp; survival. Histopathology studies were carried out in a separate group of 40 mice treated by the same drug dose levels &amp; autopsied at 4 hours &amp; 24 hours. Tumors were bi-valved &amp; fixed in buffered formalin or frozen in hexane/acetone bath. Major focus was effects on tumor necrosis, apoptosis, mitotic index &amp; Apoptosis (caspase 3 expression) index. Results: Combination w/C 6 ceramide augmented the tumor reduction obtained by chemotherapy alone by 57% (while preserving body weight), &amp; increased 6 wk survival from 0% (Chemotherapy alone) to 60% w/combined therapy. Mean survival was increased from 25 to 37 days. Preliminary short term immunohisto chemical studies showed enhancement of apoptotic index by increased and caspase 3 expression at 4 &amp; 24 hr by ceramide combinations. Conclusion: Combination therapy w/C 6 Ceramide significantly enhanced anti tumor response to Paclitaxel, Oxaliplatin &amp; Cisplatin in SCID Mice bearing L3.6 pancreatic tumor implants. Early development of enhanced apoptosis by caspase 3 expressions was shown in preliminary short term exposure experiments. No significant financial relationships to disclose.
A phase II study of radiation with concomitant and then sequential temozolomide (TMZ) in patients (pts) with newly diagnosed supratentorial high grade malignant glioma (MG) who have undergone surgery with carmustine (BCNU) wafer insertion
Authors: R. V. Larocca, T. W. Vitaz, D. J. Morassutti, M. J. Doyle, S. D. Glisson, J. B. Hargis, G. H. Goldsmith, A. Cervera, L. Stribinskiene, P. New
Journal: Journal of Clinical Oncology (2005)

1547 Background: Prior studies demonstrated the effectiveness of both BCNU wafer (Gliadel) and TMZ (Temodar) as adjunctive therapies to resection and radiation therapy (RT) in pts with initial high grade MG. (Westphal et al. Neuro-Onco 2003; Stupp et al. JCO 2002) This study assessed the safety and efficacy of BCNU wafer and TMZ in combination. Methods: This is a phase II, multicenter, trial. Eligible pts were 18–72 years (yrs) of age with surgically operable, initial high grade MG. Enrollment began in July 2003 and continues. After resection and BCNU wafer insertion, pts received concomitant treatment with daily RT 2 Gy (≤total 60 Gy) + TMZ 75 mg/m2 (≤45 days) followed by monthly TMZ (200 mg/m2 daily x 5 every 28 days, ≤18 cycles). Endpoints include survival and progression-free survival (PFS), which were estimated with the Kaplan-Meier Method: Results: As of November 2004, 16 pts have been enrolled at 2 centers. Glioblastoma multiforme was diagnosed in 15 pts. Median (range) age is 59 (29–71) yrs and median Karnofsky Performance Status is 95 (70–100). After a median follow-up of 7 (1–17) months, 7 pts have had a recurrence and 3 pts have died; 8 pts remain on active treatment and one patient withdrew consent. Median survival and PFS have not been reached. The 1-yr survival rate is 63%, and the 1-year PFS rate is 51%. Adverse events include deep vein thrombosis (3 pts), pulmonary embolism (4 pts), sterile brain abscess (1 pt) and bacterial pneumonia (1 pt). Conclusions: These data suggest combination therapy with BCNU wafers followed by RT/ TMZ may be an effective regimen in pts with initial high-grade resectable MG. Randomized trials will be needed to ultimately assess efficacy. The incidence of DVT and PE within 60 days of surgery in this pt population, despite the standard use of postoperative compression stockings and sequential compression devices, merits further evaluation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Guilford Guilford, Schering-Plough Guilford
The use of FDG-PET for axillary lymph node staging in breast cancer
Authors: J. Jeong, I.-K. Lee, S.-A. Lee, B. W. Park, W. H. Jung, Y. H. Ryu, K. K. Oh, H.-D. Lee
Journal: Journal of Clinical Oncology (2005)

760 Background: Axillary lymph node dissection is known as a standard method for evaluation of metastatic axillary lymph node in breast cancer. But recently, sentinel lymph node biopsy is also accepted as a new standard Method: PET is a non invasive imaging study used for positive metastatic lymph node inspection. In this study, we determined the specificity, sensitivity, accuracy, negative predictive value and positive predictive value of PET in evaluation of axillary lymph node status. Methods: 34 subjects were recruited who had invasive breast cancer with clinically negative axillary lymph node (2 patients received neo-adjuvant chemotherapy).The median size of primary tumor was 1.95cm (range 0.7∼7.0cm), and PET was performed within 3 days before surgery. 9 subjects received sentinel lymph node biopsy alone, while additional lymph node dissection was performed in 25 subjects. Dissected lymph nodes were sent for H&E (hematoxylin and eosin) and immmunohistochemistry staining to investigate the presence of metastasis. Results: 4 of 34 subjects showed false-negative result in PET and these included 1 case where the primary tumor was missed for diagnosis. 8 subjects revealed positive metastasis on PET. 2 of theme received sentinel lymph node dissection and they both confirmed positive for metastasis. For those two subjects who received neo-adjuvant chemotherapy, it was possible to evaluate its sensitivity. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET staging were 71.43%, 100%, 88.24%, 100% and 83.33% respectively. Conclusions: The sensitivity of PET for evaluation of metastatic axillary lymph node in breast cancer was low but the specificity and positive predictive value were considerably high. PET staging was proved to be a helpful method in patient selection of axillary lymph node metastasis among the clinically axillary node negative breast cancer patients. In these patients we may omit sentinel lymph node biopsy and do the axillary lymph node dissection directly. Also, it may be clinically used to check the sensitivity of neo-adjuvant chemotherapy. No significant financial relationships to disclose.
A randomized, phase Ib/II trial of rilotumumab (AMG 102; ril) or ganitumab (AMG 479; gan) with panitumumab (pmab) versus pmab alone in patients (pts) with wild-type (WT) <i>KRAS</i> metastatic colorectal cancer (mCRC): Primary and biomarker analyses.
Authors: C. Eng, E. Van Cutsem, E. Nowara, A. Swieboda-Sadlej, N. C. Tebbutt, E. P. Mitchell, I. Davidenko, K. Oliner, L. Chen, J. Huang, I. McCaffery, E. Loh, D. Smethurst, J. Tabernero
Journal: Journal of Clinical Oncology (2011)

3500 Background: Pmab, ril, and gan are fully human monoclonal antibodies against epidermal growth factor receptor, hepatocyte growth factor, and insulin-like growth factor receptor 1, respectively. This 3-part study examined the safety and efficacy of ril or gan with pmab in pts with mCRC expressing WT KRAS. Methods: Part 2 was a phase II, randomized, double-blinded, placebo-controlled trial of pmab (6 mg/kg) + placebo (Arm 1) vs pmab + ril (10 mg/kg, Arm 2) vs pmab + gan (12 mg/kg, Arm 3), all administered Q2W until disease progression or intolerance. Pts were ≥ 18 yrs old, had ECOG PS 0/1, and prior irinotecan and/or oxaliplatin. The primary endpoint for Part 2 was objective response rate (ORR). A Bayesian approach was undertaken to determine a meaningful improvement in ORR in the combination arms. Secondary endpoints included progression-free survival (PFS) and safety (adverse events [AEs]). Biomarker analyses including c-Met expression by immunohistochemistry (IHC) on archival tumor samples were completed. Correlation of c-Met expression with outcomes for the pmab + ril combination is ongoing. Results: 142 pts were enrolled; 58% were men; mean age was 59.7 yrs; 40%/59% had ECOG PS of 0/1, respectively. ORRs are shown (table). Median PFS (95% CI) was 3.7 (2.5-5.3), 5.2 (3.6-5.4), and 5.3 (2.7-5.7) months for Arms 1, 2, and 3, respectively. Grade ≥ 3 AEs were reported in 54%, 79%, and 72% of pts in Arms 1, 2, and 3, respectively and commonly included rash, dermatitis, and hypomagnesemia. c-Met IHC results were obtained for 134 of the142 pts (94%). Conclusions: Pmab + ril met the prespecified criterion for improvement in ORR (greater than Arm 1). Pmab in combination with ril or gan was well tolerated. Results of biomarker analyses of pmab/ril including c-Met staining will be presented. Arm 1 Arm 2 Arm 3 Best response, n (%) Pmab +placebo N = 48 Pmab +ril N = 48 Pmab +gan N = 46 Partial response 10 (21) 15 (31) 10 (22) Stable disease 17 (35) 19 (40) 18 (39) Progressive disease 16 (33) 11 (23) 15 (33) Unevaluable/not done 5 (10) 3 (6) 3 (6) Posterior probability of OR>1* 0.93 0.63 *Odds ratio relative to Arm 1 for ORR.
Circulating endothelial cells (CEC) and circulating tumor cells (CTC) in patients (pts) with metastatic colorectal cancer (mCRC)
Authors: S. J. Cohen, L. W. Terstappen, C. J. Punt, E. P. Mitchell, T. M. Fynan, T. Li, J. Matera, G. V. Doyle, N. J. Meropol
Journal: Journal of Clinical Oncology (2006)

3531 Background: Lack of validated surrogate endpoints is an impediment to developing new cancer therapy. We hypothesized that CTC and CEC could predict outcome in pts undergoing treatment for mCRC. Methods: Eligible pts for this multicenter study had mCRC, and were initiating 1 st , 2 nd , or 3 rd -line systemic therapy. Blood was obtained at baseline and 3–4 weeks after treatment initiation for enumeration of CTC/CEC. CTC/7.5ml and CEC/4ml of blood were measured with the CellSearch System. CTC were immunomagnetically enriched targeting CD326 (EpCAM), stained with DAPI, cytokeratin 8,18,19, and CD45. CEC expressing CD146 were immunomagnetically enriched and stained with DAPI, CD105, and counterstained with CD45. Cell morphology was confirmed in all cases. Results: In 139 controlsCTC were virtually absent (0 CTC in 135 and 1 CTC in 4). For 131 pts with mCRC, &gt;1CTC was detected before therapy in 40/131(31%) (range 0–73) and 3–4 weeks after starting therapy in 12/131 (9%) (range 0–100) (p&lt;0.0001, McNemar’s test). Pts with &gt;1 CTC at baseline and 3–4 weeks did not differ by line of therapy (1st line: 28/93 [30.1%] at baseline, 7/93 [7.5%] at 3–4 weeks; second/third-line: 6/24 [25%] at baseline, 3/24 [12.5%] at 3–4 weeks, p=0.57, Breslow-Day test). For 15/131 (11.5%) a 2-fold increase and for 53/131 (40.5%) a 2-fold decrease in CTC was found after treatment. Using 249 controls, a normal reference range of 4–80 CEC/4 ml of blood was established. In 16/131 (12.2%) pts &gt;80 CEC were detected before (range 1–1342) and in 18/131(13.7%) after start of therapy (range 2–519) (p=0.71, McNemar’s test). Pts with &gt;80 CEC at baseline and 3–4 weeks did not differ by line of therapy (1 st line: 9/93 [9.7%] at baseline, 13/93 [14%] at 3–4 weeks; 2 nd /3 rd line: 5/24 [20.8%] at baseline, 2/24 [8.3%] at 3–4 weeks, p=0.16, Breslow-Day test). In 37/131 (28.2%) a 2-fold increase and in 35/131 (26.7%) a 2-fold decrease in CEC was found after initiation of therapy. Conclusions: Isolating and enumerating CTC/CEC in pts receiving therapy for mCRC is feasible. CTC generally decrease with therapy, while change in CEC has greater variability. Enrollment in this 400 patient multicenter study is nearing completion, and definitive analysis of relationship of CTC/CEC change to clinical outcome is planned. [Table: see text]