tbuckley/cabot-search huggingface dataset:
A cross-sectional study of angiopoietin-1 (Ang-1) in early and advanced prostate cancer
Authors: D. M. Sahasrabudhe, E. Messing, S. R. Schoen, C. Feng, J. Joseph, A. Constantino, S. VidyaRao, M. Kohli
Journal: Journal of Clinical Oncology (2008)

5137 Background: Ang-1, a prostate cancer associated angiogenesis growth factor was measured in serum of an age-matched non-cancer cohort and in prostate cancer patients at different stages of tumor progression. Methods: An IRB approved collection of blood specimens in patients with prostate disease was performed in 188 subjects (cancer and non cancer patients). Based on stage of tumor, cancer patients were grouped in four cohorts. Ang-1 levels were measured in serum using commercially available ELISA kits (R & D systems, MN). Results: Hundred and sixty two cancer patients and 26 non-cancer subjects were enrolled. Cancer cohort included Group 1: 51 patients with localized stage cancer prior to radical prostatectomy were enrolled in this group, of which 27 patients had post prostatectomy serum specimens available for serial evaluation of Ang-1 levels; Group 2: patients with early biochemical failure post primary therapy, and prior to initiation of androgen deprivation therapy (ADT) (n=56); Group 3: patients with gross metastasis prior to ADT (n=12); and Group 4: patients with tumor progression during ADT (n=23). Table 1 summarizes PSA and Ang-1 results and comparisons between groups. Conclusions: A significant decrease of serum Ang-1 was observed after prostatectomy in the localized cancer group, even as significant elevation in serum Ang-1 was observed in the pre-prostatectomy stage compared to non-cancer controls. This suggests a role for Ang-1 associated angiogenesis in early stage prostate cancer. Interestingly, lower (than pre-prostatectomy localized stage disease) serum Ang-1 in advanced, grossly metastatic disease may indicate a silencing of the Ang-1-tie2 receptor axis in advanced stage disease possibly secondary to a competitive switching from Ang-1 to Ang-2 with development of metastasis. These findings should be explored further as they have implications in developing therapeutic strategies for targeting angiopoietin nediated angiogenesis in different stages of tumor progression. Serum Ang-1 levels in cancer cohorts and controls Groups (N) Median PSA (ng/ml) (range) P-value Median Ang-1 (ng/ml) (range) P-value Non-cancer (26) vs. pre-treatment Group 1 (51) 5.6 vs. 6.1 (0.8–31.1) vs. (0.08–18.9) 0.31 27.9 vs. 33.5 0.04 Group 1 pre (51) vs. post-treatment (27) 6.1 vs. 0.05 (0.08–18.9) vs. (0–14.6) <0.0001* 30.7 vs. 28.3 0.04* Group 1 post- treatment (27) vs. Group 2 (56) 0.04 vs. 0.79 (0–14.6) vs. (0.01–20.9) 0.0001 28.3 vs. 27.2 0.41 Group 1 pre- treatment (51) vs. Group 3 (12) 6.1 vs. 8.3 (0.08–18.9) vs. (0.01–20.9) 0.52 33.5 vs. 21.5 0.0002 Group 1 pre- treatment (51) vs. Group 4 (23) 6.1 vs. 10.2 (0.08–18.9) vs. (0.7–1352) 0.04 33.5 vs. 23.6 0.002 p-values-Wilcoxon two-sample test; * signed rank test No significant financial relationships to disclose.
Phase II study of capecitabine in substitution of 5-FU in the chemoradiotherapy regimen for patients with squamous cell carcinoma of the anal canal.
Authors: Suilane Coelho Ribeiro, Camila Venchiarutti, Rachel Riechelmann, Erlon Gil, Caio Nahas, Renata Coudry, Daniela Freitas, Daniel F. Saragiotto, Fernando Arruda, Rodrigo Azambuja, Paulo Hoff
Journal: Journal of Clinical Oncology (2012)

659 Background: Squamous cell carcinoma (SCC) of the anal canal is an uncommon malignancy accounting for 1-5% of intestinal tumors; however, its incidence has been increasing. The standard treatment of anal canal SCC stage II-III consists of infusional 5-fluorouracil associated with mitomycin and radiotherapy. This scheme was proposed by Nigro in 1974, and since then no other effective treatment was developed. Methods: Patients with SCC of anal cancer T2-4N0M0 or T (any) N1-3M0, with good performance status, normal blood and renal function were treated with capecitabine 825 mg/m2 12/12hs during radiotherapy associated with a single dose of mitomycin 15 mg/m2 on Day 1. Primary objective is determine local control rate in 6 months with capecitabine, mitomycin and radiotherapy in patients with SCC of the anal canal. After the end of the treatment patients were reassessed for clinical and radiological response. Sample size was calculated using Fleming's single stage. Considering 85% of expected events (rate of local control in 6 months), standard deviation and a 5% error, sample size calculated was 51 patients. Results: 13 patients have been included, 9 patients have finished, 3 patients are still in treatment and 1 patient was excluded because of poor compliance with oral medications. Regarding the staging, 5 patients (38,4%) with stage II, 4 patients ( 30,8%) with stage IIIA and 4 patients (30,8%) with stage IIIB. Among patients who finished the treatment and were reevaluated 1 patient ( 16,7%) presented partial clinical response, 6 patients (83,3%) had clinical complete response. Three patients are waiting for clinical and radiologic reassessement. The main toxicities observed were grade I diarrhea ( 30,7%), grade II (38,5%) and III (30,7%) radiodermitis, nausea ( 38,5%), grade I-II plaquetopenia( 30,7%). Grade I hand–foot syndrome was observed in 1 patient and hemorrhagic cystitis related to radiotherapy was observed in 1 patient. No serious adverse event was observed. Colostomy was required in 1 patient before the beginning of the treatment. Conclusions: The study is ongoing but capecitabine and mytomicin with radiotherapy seem to be a safe treatment for SCC of the anal cancer.
Single-fraction radiosurgery for the treatment of renal cell carcinoma.
Authors: Michael D. Staehler, Boris Schlenker, Alexander Karl, Annabel Spek, Alexander Muacevic
Journal: Journal of Clinical Oncology (2016)

590 Background: We report on patients with renal cell carcinoma (RCC) who were treated with single fraction high-dose local stereotactic radiosurgery (SRS) using the robotic Cyberknife system to avoid nephrectomy and consecutive hemodialysis. Methods: Fifty-two patients with histologically confirmed RCC and median age of 63.6 years (43.6-86.5) with the indication for renal surgery and highest risk for consecutive hemodialysis were entered into a prospective case control study of single fraction SRS with 25Gy. Tumor response, renal function, survival, and adverse events were estimated every three months with a follow-up of at least six months. Results: R.E.N.A.L. score was low in 1, moderate in 30 and high in 21 patients. 28 patients had singular renal units. Median follow-up was 26.9 months (1.8 - 52.6). Local tumor control nine months after SRS was 98% (95% CI: 89-99%). 43 lesions showed a measurable tumor size reduction including six complete remissions and 33 partial remissions. Renal function remained stable with a median serum creatinine at baseline of 1.10 mg/dl (0.4 -2.0) and 1.11 mg/dl (0.8-2.2) at follow-up. In one patient grade I erythrodermia, in three patients grade I fatigue and in two patients grade I nausea occurred. In all patients nephrectomy was avoided. Conclusions: Single-fraction SRS as an outpatient procedure is a treatment modality with short-term safety and efficacy to avoid treatment-related loss of renal function and hemodialysis in selected patients with RCC. Short term follow up of oncological and functional results so far is excellent. Further studies are needed to determine the limits of SRS in this setting and long term results.
Long-term outcome of patients with hepatocellular carcinoma treated with hypofractionated stereotactic radiation therapy as a bridge to liver transplantation.
Authors: Alan W. Katz, Douglas P Rosenzweig
Journal: Journal of Clinical Oncology (2014)

368 Background: Stereotactic hypofractionated radiation therapy (SHORT) is a safe, non-invasive, treatment modality for patients with hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the long-term outcome of patients with HCC receiving SHORT as a bridge therapy to LT. Methods: We reviewed 9 consecutive patients who underwent LT between 2008 and 2010 after receiving SHORT as bridge therapy. Radiation therapy was delivered using a 6 MV linear accelerator and an infrared based patient posititiong system. Total dose was 50 Gy in 10 fractions. Doses were prescribed to the 100% isodose line (IDL), with the 80% IDL covering the gross tumor plus a minimum margin of 7 mm. Survival was measured from the date of LT. Results: Median time from completion of SHORT to LT was 5.9 months (range; 0.9-15.7 months). After a median follow up of 48.6 months (range; 17.8-65.3 months) all patients were still alive. No significant surgical complications were seen in any of the patients. 8 patients demonstrated necrosis in the treated tumors, ranging from 8-100%. Only 1 patient did not show any treatment effect on pathological examination. One patient developed recurrent disease in a lymph node and in the transplanted liver, both treated by SHORT with complete response. Conclusions: SHORT is a safe and effective bridging therapy with patients experiencing excellent disease-free and overall survival following LT.
The effect of curative surgery in Borrmann type IV advanced gastric cancer.
Authors: Kyo Young Song, Eun Young Kim
Journal: Journal of Clinical Oncology (2015)

176 Background: The aims of the present study are to know the significance of curative surgery in Borrmann type IV and prove the causes related with poor prognosis by analyzing the recurrence patterns and unique diagnostic characteristics. Methods: We analyzed 168 patients with Borrmann type IV undergoing surgery at Seoul St. Mary Hospital from 1989 to 2010. We categorized the patients into curative (R0) and non-curative (R1, R2 and no-resection) group. Results: The numbers of curative and non-curative group were 91 and 77. The 3- and 5-yr OSRs of patients in curative group were significantly higher than those in non-curative group (curative: 52.4% and 33.0%, non-curative: 18.6% and 7.0%; p&lt;0.001). In multivariate analysis, the curability was not a significant prognostic factor for survival (p=0.527). The most frequent recurrence site was peritoneum (64.7%). Most of recurrences were presented within early 2 years. The preoperative diagnostic rate of Borrmann type IV was only 50.5%. The reasons for non-curative surgery were unexpected peritoneal seeding (28.4%) and resection margin involvement (6.4%). Conclusions: The role of surgery for Borrmann type IV is quite limited. It has poor prognosis even after curative surgery, because it is very difficult to diagnose preoperatively and make curative surgery. [Table: see text]
Validation of p95 as a predictive marker for trastuzumab-based therapy in primary HER2-positive breast cancer: A translational investigation from the neoadjuvant GeparQuattro study.
Authors: S. Loibl, J. Bruey, G. Von Minckwitz, J. B. Huober, M. F. Press, S. Darb-Esfahani, C. Solbach, C. Denkert, H. Tesch, F. Holms, T. N. Fehm, K. Mehta, M. Untch
Journal: Journal of Clinical Oncology (2011)

530 Background: p95 might indicate resistance to trastuzumab (T) (Scaltriti et al. 2007). An immunohistochemical assay has been developed to detect p95, a C-terminal fragment (CTF) of the full-length HER2, by using a monoclonal antibody that specifically recognizes the 611 CTF, the truncated form of HER2 by immunohistochemistry (IHC), and does not recognize total HER2. We investigated p95 as validation in a trial cohort of HER2 positive patients. Methods: 445 patients with HER2+ (locally tested) primary breast cancer received neoadjuvant EC-docetaxel +/-capecitabine concomitant to T in the GeparQuattro study. Tissue microarrays (TMA) from pre-therapeutic core biopsies of 153 patients were available with sufficient tumor tissue on the TMA (>30%) and positive HER2 status centrally confirmed. p95 expression could be assessed with % of positive cells by 3 independent pathologists with a cut-off at 10 (primary analysis), 20 and 30% positive cells on 134 samples. We assessed the pCR rate defined as non invasive residuals in breast and lymph nodes. Resistance was defined as minimal or no microscopic changes in surgically excised tumor tissue (regression grade, RG 0-1 according to Sinn et al). Results: The median age was 49 years (22-78). Clinical T stadium was T1,2,3,4a-c/4d in 3%/70%/11%/8%/8% respectively, 59%/ 41% of these tumors were G2/G3; 51% were hormone receptor (HR) positive. The overall pCR rate was 51% and resistance rate was 32.8%. The pCR rate in the p95 positive tumors (10% cutoff) was 58.2% vs 32.6% in the p95negative group (p=0.009). The resistance rate in the p95 positive group was 25.8% vs 48.7% in the p95 negative group (p=0.014). Results were similar when the cutoff was set at 20% and 30% as well as for clinical response. Conclusions: In contrast to our expectations p95 expression measured by IHC indicates response to neoadjuvant trastuzumab containing treatment in primary HER2 positive breast cancer but not resistance. p95 will be evaluated in whole sections for each patient and data will also be reported. The marker needs to be further validated especially also in the neoadjuvant trials using lapatinib.
Impact of altered Wnt1/ß-catenin expression on clinicopathology and prognosis in renal cell carcinoma.
Authors: Stephan Kruck, Christian Eyrich, Marcus Scharpf, Falko Fend, Arnulf Stenzl, Jens Bedke
Journal: Journal of Clinical Oncology (2014)

465 Background: Members of the Wnt/ß-catenin signaling pathway are abnormally expressed in renal cell carcinoma (RCC). This study analyzed the role of Wnt1/ß-catenin alterations in clear cell RCC (ccRCC) with regard to clinicopathology, overall survival (OS) and cancer specific survival (CSS) to prove the options of a Wnt targeted therapy. Methods: Corresponding ccRCCs and benign renal tissue were analyzed in 278 patients for Wnt1 and ß-catenin by immunohistochemistry in tissue microarrays. Expression scores including intensity and percentage of stained cells were compared between normal kidney and ccRCCs. Data was categorized according to the mean expressions core and correlated to tumor and patients’ characteristics and analyzed for OS and CSS according to the Kaplan-Meier and log-rank test. To identify prognostics value of wnt1 and ß-catenin, univariable and multivariable Cox proportional hazard regression models were used. Results: High Wnt1 tumor expression was associated with increased tumor diameter (p=0.01), stage (p=0.004) and vascular invasion (p=0.02). Positive membranous ß-catenin was associated with advanced stage (p=0.003), vascular invasion (p=0.01) and tumor necrosis (p=0.004). Increased tumor diameter (p=0.01), stage (p=0.003), node involvement (0.04), grade (p=0.001), vascular invasion (p=0.002), and sarcomatoid differentiation (p=0.01) were found in patients with high cytoplasmic ß-catenin. Furthermore, this patient subgroup showed reduced OS (p=0.03) and CSS (p=0.009). Conclusions: Significant clinicopathological associations underline the oncogenic potential of Wnt1/ß-catenin pathway parameters. Whereas, cytoplasmic ß-catenin was identified as the most valuable parameter with regard to clinico-prognostic implications for future targeted therapies.
Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete remission: Phase III clinical trial results
Authors: S. J. Schuster, S. S. Neelapu, B. L. Gause, F. M. Muggia, J. P. Gockerman, E. M. Sotomayor, J. N. Winter, C. R. Flowers, A. M. Stergiou, L. W. Kwak
Journal: Journal of Clinical Oncology (2009)

2 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]
Weekly paclitaxel versus ADT alone in localized high-risk prostate cancer: Results of a single-institution phase II trial.
Authors: Carolina Saldana, Laurent Salomon, Benoit Rousseau, Marie Chaubet-Houdu, Charlotte Joly, Guillaume Ploussard, Yves Allory, Christophe Tournigand, Alexandre de la Taille
Journal: Journal of Clinical Oncology (2015)

37 Background: Adjuvant chemotherapy’s role after radical prostatectomy (RP) remains controversial in localized high-risk prostate cancer (HRPC). This phase II trial assessed the combination of weekly paclitaxel (WP) with androgen deprivation therapy (ADT) in this population. Methods: All eligible patients (pts) had undergone a laparoscopic RP with pelvic lymph node dissection for a localized HRPC defined with ≥1 of the following criteria: T3b-T4 post-operated Gleason score (GS) ≥8, PSA≥ 20 ng/mL, pN+, in Henri Mondor Hospital. Pts were randomly assigned to either triptoreline 11.25mg every 3 months during 3 years and 8 cycles of WP 100 mg/ m2 (WP arm, n=21) or triptoreline alone (ADT arm, n=26). The primary endpoint is disease free survival (DFS); events=PSA relapse, clinical and radiographic relapse, death. The planned number of pts was 152. Toxicity results indicated a good tolerability with neutropenic fever in 4.3% (n=1), and no negative impact on QoL in the WP arm (Ploussard, Prostate Cancer Prostatic Dis. 2010). Here we report 8-year DFS and overall survival (OS) results. Results: Between February 2005 and October 2007, 47 pts were enrolled. This trial was terminated prematurely because of slow accrual. After a mean follow-up of 8.4 y, we identified a PSA relapse in 25 pts (53%) and castrate-resistant prostate cancer occurred in 6 pts. No statistically difference was found in terms of either biochemical or clinical DFS (bDFS, cDFS) and OS: 8-year bDFS rate: 50% [n=11/22] in the WP arm vs 46% [n=12/26] in the ADT arm (p=0.79); 8-year cDFS rate: 95.4% [n=21/22] in the WP arm vs 88.5% [n=23/26] in the ADT arm (p=0.38). The 8-year OS rate is 90.9% (n=20/22) and 84.6% (n=22/26) respectively with no difference between treatment arms (p=0.51). No clinical, histological or biological variable demonstrated a difference in either 8-year bDFS, cDFS or OS rate. Conclusions: Provided that this trial is probably underpowered to detect a DFS benefit, adjuvant weekly paclitaxel after RP was not associated with any significant reduction in the risk of biological relapse or death compared to ADT alone in patients with localized HRPC. Chemotherapy should be only proposed in dedicated clinical trial for localized HRPC.
Clinicopathological characters and prognostic significance of cytokeratins expression in intrahepatic cholangiocarcinoma.
Authors: Q. Zhu, X. Yang, Y. Xu, J. Fan
Journal: Journal of Clinical Oncology (2011)

e14667 Background: The prognosis is unsatisfactory and can hardly be predicted for those patients with intrahepatic cholangiocarcinoma (ICC) underwent hepatectomy. The aim of this study is to investigate the prognostic values of glandular epithelia related cytokeratin 7 (CK7), cytokeratin 8 (CK8), cytokeratin 18 (CK18), and cytokeratin 19 (CK19) and their relations with clinicopathological characteristics in ICC patients. Methods: Tumor tissue microarrays (TMAs) of 162 ICC patients who underwent curative resection between 2001 and 2006 were used to detect the expressions of CK7, CK8, CK18 and CK19. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Clinicopathologic data for these patients were evaluated. Results: The strong expression percentage for these four cytokeratins in 162 ICC patients was 79.0% (CK7), 51.2% (CK8), 76.5% (CK18), and 68.5% (CK19). The expression of CK7 was found to be associated with hepatitis B surface antigen (HBsAg) and alpha-fetoprotein (AFP) while CK19 was associated with HBsAg, carcinoembryonic antigen (CEA), gammaglutamyl transferase (GGT), carbohydrate antigen 19-9 (CA19-9) and tumor size. Tumor staging was linked with the expression of CK7, CK8 and CK18 except CK19. Both univariate and multivariate analyses revealed that CK18 and CK19 were significant predictors for overall survival (OS). CK19 strong expression and CK18 weak expression were correlated with poor prognosis regardless of tumor size, tumor encapsulation and perihila lymph node involvement. The OS rate in CK19strong and CK19weak patients were 16.2% and 39.2 % (P<0.005). The OS rate in CK18strong and CK18weak patients were 28.2% and 7.9% (P<0.001). CK19 combined with CK18 still related with OS. The OS rate in CK19strongCK18weak patients was 7.1%, which was significantly lower than that of CK19weakCK18strong patients (46.3%, P<0.001). Conclusions: CK18 and CK19 can be used as novel predictors for the prognosis of ICC.
Preclinical Melanoma Imaging with <sup>68</sup>Ga-Labeled α-Melanocyte-Stimulating Hormone Derivatives Using PET
Authors: Chengcheng Zhang, Zhengxing Zhang, Kuo-Shyan Lin, Jinhe Pan, Iulia Dude, Navjit Hundal-Jabal, Nadine Colpo, François Bénard
Journal: Theranostics (2017)

It is estimated that melanoma accounted for 76,380 new cases and 10,130 deaths in the United States in 2016.The melanocortin 1 receptor (MC1R) is highly expressed in the vast majority of melanomas, which makes it an attractive target for molecular imaging and radionuclide therapy.Lactam bridge-cyclized α-melanocyte-stimulating hormone (Ac-Nle 4 -cyclo[Asp 5 -His-D-Phe 7 -Arg-Trp-Lys 10 ]-NH2, or Nle-CycMSHhex) analogues have been successfully developed and studied for MC1R-targeted imaging, predominantly with single-photon emission computed tomography (SPECT).The goal of this study was to design and evaluate novel peptides for melanoma imaging with positron emission tomography (PET).We designed and synthesized three peptides, DOTA-PEG2-Nle-CycMSHhex (CCZ01047), DOTA-4-amino-(1-carboxymethyl) piperidine (Pip)-Nle-CycMSHhex (CCZ01048), and DOTA-Pip-Pip-Nle-CycMSHhex (CCZ01056).All three peptides exhibited high binding affinity to MC1R with sub-nanomolar Ki values, rapid internalization into B16F10 melanoma cells and high in vivo stability with more than 93% remaining intact at 15 min post-injection (p.i.) in blood plasma.All three 68 Ga-labeled tracers produced high contrast PET images in C57BL/6J mice bearing B16F10 tumors, and their respective tumor uptakes were 8.0 ± 3.0, 12.3 ± 3.3, and 6.5 ± 1.4 %ID/g at 1 h p.i. Minimal normal organ activity was observed at 1 h p.i., except for kidneys (5.1 ± 1.4, 4.7 ± 0.5, and 6.2 ± 2.0 %ID/g, respectively), and thyroid (4.1 ± 0.6 %ID/g for CCZ01047 and 2.4 ± 0.6 %ID/g for CCZ01048).Due to high accumulation at tumor sites and rapid background clearance of 68 Ga-CCZ01048, we further evaluated it at 2 h p.i., and a tumor uptake of 21.9 ± 4.6 %ID/g was observed, with background activity further decreased.Exceptional image contrast was also achieved, i.e. tumor-to-blood, tumor-to-muscle, tumor-to-bone and tumor-to-kidney ratios were 96.4 ± 13.9, 210.9 ± 20.9, 39.6 ± 11.9 and 4.0 ± 0.9, respectively.A blocking study was also performed by co-injection of excess amount of non-radioactive Ga-coupled of CCZ01048, which confirmed that the tumor uptake was MC1R mediated.In conclusion, the introduction of a cationic Pip linker to Nle-CycMSHhex, CCZ01048, not only improved tumor uptake, but also generated high tumor-to-normal tissue contrast with PET imaging in a preclinical melanoma model.Therefore, CCZ01048 is a promising candidate for PET imaging of melanoma, and potentially as a theranostic agent for radionuclide therapy of melanoma when labeled with α or β emitters.