Percentage Of Tumor Necrosis Research Articles

Elevated Expression of Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3) Is Associated With a Poor Prognosis in Osteosarcoma.

Transforming acidic coiled-coil containing protein 3 (TACC3) is expressed during the mitotic phase of nuclear division and regulates microtubules. Recently, high TACC3 expression in tumor cells of various cancers including soft tissue sarcoma has been reported. However, its role in osteosarcoma remains unknown. Because we have few prognostic markers for survival in osteosarcoma, we wanted to investigate the potential role of TACC3 in human osteosarcoma and determine if it is associated with survival. (1) Is there a relationship between TACC3 expression and clinicopathologic characteristics such as sex, age (< 20 or ≥ 20 years), histologic type (osteoblastic or others), tumor location (femur or others), American Joint Committee on Cancer staging system (AJCC stage IIA or IIB), tumor necrosis percentage after chemotherapy (< 90% or ≥ 90%), p53 expression (low or high), and Ki-67 expression (low or high)? (2) Is TACC3 expression associated with event-free and overall survival in patients with osteosarcoma? Forty-six conventional patients with osteosarcoma were treated at our institution from 1989 to 2013. Patients were excluded because of unresectable primary site (two patients) and no chemotherapy (two patients). Patients with metastasis at the initial visit (five patients), without pretreatment biopsy samples (two patients), or clinical charts (two patients) were also excluded. The left 33 patients who received neoadjuvant and adjuvant chemotherapy, which consisted of cisplatin/doxorubicin/methotrexate or cisplatin/doxorubicin/methotrexate/ifosfamide, and completed surgical resection with histologic wide tumor margins. Primary tumor samples before chemotherapy were used in this study. We investigated TACC3 expression using immunohistochemical staining and statistically analyzed the TACC3 expression, clinicopathologic characteristics, and event-free and overall survival in patients with osteosarcoma. High TACC3 expression was observed in 19 of 33 osteosarcoma specimens (58%), and this was associated with larger tumor size (ie, AJCC stage IIB in this study; p = 0.002), higher p53 expression (p = 0.007), and higher Ki-67 expression (p = 0.002). The estimated metastasis-free survival at 5 years was 21% (95% confidence interval [CI], 7%-41%) in patients with high TACC3 expression and 79% (95% CI, 47%-93%) in patients with low TACC3 expression (p < 0.001), and the estimated overall survival at 5 years was 34% (95% CI, 13%-56%) in patients with high TACC3 expression and 86% (95% CI, 54%-96%) in patients with low TACC3 expression (p < 0.001). Furthermore, high TACC3 expression was an independent poor prognostic factor for metastasis-free survival with a hazard ratio of 3.89 (95% CI, 1.07-19.78; p = 0.039) as well as overall survival with 4.41 (95% CI, 1.01-32.97; p = 0.049). High TACC3 expression was associated with aggressive clinicopathologic features and unfavorable prognosis in these patients with osteosarcoma. Our preliminary results suggest that further analysis about mutation or an inactive form of TACC3 would be useful to understand the mechanism of abnormal TACC3 expression in patients with osteosarcoma. If these findings are substantiated in larger studies, TACC3 might be useful for predicting survival and a potential therapeutic target for osteosarcoma. Level III, therapeutic study.

MP28-03 CONTRAST MEDIA ENHANCEMENT REDUCTION PREDICTS TUMOR RESPONSE TO PRESURGICAL MOLECULAR-TARGETING THERAPY IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging I1 Apr 2018MP28-03 CONTRAST MEDIA ENHANCEMENT REDUCTION PREDICTS TUMOR RESPONSE TO PRESURGICAL MOLECULAR-TARGETING THERAPY IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA Shogo Hosogoe, Shingo Hatakeyama, Hirotake Kodama, Ayumu Kusaka, Noriko Tokui, Hayato Yamamoto, Tohru Yoneyama, Atsushi Imai, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, and Chikara Ohyama Shogo HosogoeShogo Hosogoe More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Hirotake KodamaHirotake Kodama More articles by this author , Ayumu KusakaAyumu Kusaka More articles by this author , Noriko TokuiNoriko Tokui More articles by this author , Hayato YamamotoHayato Yamamoto More articles by this author , Tohru YoneyamaTohru Yoneyama More articles by this author , Atsushi ImaiAtsushi Imai More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Takuya KoieTakuya Koie More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.903AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy. METHODS Between March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis. RESULTS f 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were -19%, -24%, and -49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST. CONCLUSIONS CMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e357 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Shogo Hosogoe More articles by this author Shingo Hatakeyama More articles by this author Hirotake Kodama More articles by this author Ayumu Kusaka More articles by this author Noriko Tokui More articles by this author Hayato Yamamoto More articles by this author Tohru Yoneyama More articles by this author Atsushi Imai More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto More articles by this author Takuya Koie More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Perfusion MR imaging at 3-Tesla: Can it predict tumor grade and histologic necrosis rate of musculoskeletal sarcoma?

To identify quantitative perfusion parameters that are best associated with tumor grade and tumor necrosis at magnetic resonance (MR) imaging at 3-Tesla. MR perfusion studies of 31 patients with a musculoskeletal sarcoma were retrospectively evaluated by two readers. There were 18 men and 13 women with a mean age of 34.9±24.4 (standard deviation [SD] years) (range: 6-87 years). All patients underwent carcinologic tumor resection less than 3 months after MR imaging. For all patients six perfusion parameters (three semi-quantitative and three permeability parameters) were analyzed. The percentage of tumor necrosis was estimated using MR imaging. Perfusion data were compared between groups of tumors with different grades and necrosis ratios. Interobserver variability was calculated using intraclass correlation coefficient (ICC). Interobserver variability among the perfusion parameters was good to excellent (ICC: 0.72-0.9). The area under the curve and maximum slope values showed a significant association with the degree of tumor necrosis (P=0.02-0.04). When tumors with low necrosis ratios were compared to those with high ratios the former parameter was 80% lower. In the same groups, the imaging necrosis index was 56.9-59.8% higher in patients with grade 2 necrosis (P=0.01). Extracellular space volume (Ve) was 31.4% to 55.8% lower in tumors with high grade while the backflow constant (Kep) was 33.6% to 40.1%% higher in tumors with high grade. Semi-quantitative MR perfusion parameters have an excellent reproducibility and are associated with the degree of histologic tumor necrosis in musculoskeletal sarcomas. The utility of permeability parameters for determining tumor grade needs further investigations.

Prediction of post-TACE necrosis of hepatocellular carcinoma usingvolumetric enhancement on MRI and volumetric oil deposition on CT, with pathological correlation.

To investigate whether volumetric enhancement on baseline MRI and volumetric oil deposition on unenhanced CT would predict HCC necrosis and response post-TACE. Of 115 retrospective HCC patients (173 lesions) who underwent cTACE, a subset of 53 HCC patients underwent liver transplant (LT). Semiautomatic volumetric segmentation of target lesions was performed on dual imaging to assess the accuracy of predicting tumour necrosis after TACE in the whole cohort and at pathology in the LT group. Predicted percentage tumour necrosis is defined as 100 % - (%baseline MRI enhancement - %CT oil deposition). Mean predicted tumour necrosis by dual imaging modalities was 61.5 % ± 31.6%; mean percentage tumour necrosis on follow-up MRI was 63.8 % ± 31.5 %. In the LT group, mean predicted tumour necrosis by dual imaging modalities was 77.6 % ± 27.2 %; mean percentage necrosis at pathology was 78.7 % ± 31.5 %. There was a strong significant correlation between predicted tumour necrosis and volumetric necrosis on MRI follow-up (r = 0.889, p<0.001) and between predicted tumour necrosis and pathological necrosis (r = 0.871, p<0.001). Volumetric pre-TACE enhancement on MRI and post-TACE oil deposition in CT may accurately predict necrosis in treated HCC lesions. • Imaging-based tumour response can assist in therapeutic decisions. • Lipiodol retention as carrier agent in cTACE is a tumour necrosis biomarker. • Predicting tumour necrosis with dual imaging potentially obviates immediate post-treatment MRI. • Predicting tumour necrosis would facilitate further therapeutic decisions in HCC post-cTACE. • Pre-TACE MRI and post-TACE CT predict necrosis in treated HCC.

Transhepatic arterial embolization with superparamagnetic iron oxide and lipiodol for the treatment of VX2 tumor in rabbits

To evaluate the feasibility and therapeutic efficacy of transhepatic arterial embolization with superparamagnetic iron oxide (SPIO) and lipiodol (LIP) for the treatment of VX2 tumor in rabbits. Methods: Twenty-four rabbits with hepatic VX2 tumors by surgical implantation were randomly divided into 4 groups and treated with transhepatic arterial embolization of 4 different agents as follows (n=6 each): doxorubicin (DOX) group, DOX-LIP group, SPIO-DOX group, and SPIO-DOX-LIP group. Liver function (AST and ALT) was measured at 0, 1, 3, 5 and 7 d after transhepatic arterial embolization. The serum DOX level was measured at 0, 5, 15, 30, 60, and 120 minutes after transhepatic arterial embolization. MRI was performed at 7 d after the treatment to assess the distribution of SPIO in the SPIO-DOX group and SPIO-DOX-LIP group, while CT was performed to assess the distribution of LIP in the DOX-LIP group and SPIO-DOX-LIP group. All the rabbits were sacrificed and their livers were removed at 7 d after treatment for the detection of tissue DOX level. The histopathologic examinations were performed including HE staining, Prussian blue staining and TUNEL assay, and then the tumor necrosis percentage and apoptosis index were calculated. Results: Compared to the DOX group, the levels of AST and ALT in other 3 groups were significantly elevated at 1 and 3 d after embolization (P<0.05). The levels of ALT and AST in the DOX group, DOX-LIP group or SPIO-DOX-LIP group returned to the baseline at day 7, there were no significant differences (P>0.05). The SPIO-DOX-LIP group exhibited the lowest serum DOX level at all time points up to 120 minutes after embolization (P<0.05). However, the tissue DOX level in the SPIO-DOX-LIP group was the highest among all groups at day 7 (P<0.05). The SPIO-DOX group and SPIO-DOX-LIP group showed significantly lower MRI signal intensity of tumors in T2 weighted imaging (T2WI) at day 7. Meanwhile DOX-LIP group and SPIO-DOX-LIP group showed that high-density lipiodol was deposited in the tumors in CT images. Histopathologic findings showed an almost complete central necrosis coagulation of tumors in the SPIO-DOX-LIP group, and the tumor necrosis percentage and tumor apoptosis index were significantly increased in the SPIO-DOX-LIP group compared to those in other 3 groups (P<0.05). Conclusion: This novel drug-delivery system of SPIO nano-drug carrier together with LIP is safe and feasible when it is used for transhepatic arterial embolization for liver tumor. It provides an excellent MR and CT visualization and improves the therapeutic efficacy for the treatment of rabbit VX2 liver tumor.

Angiosomal radiopathologic analysis of transarterial radioembolizationfor the treatment of hepatocellular carcinoma.

To assess the radiopathologic correlation following Yttrium-90 transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) using variable radiodosimetry to identify imaging surrogates of histologic response. Twelve patients with HCC underwent ablative (≥190Gy) and/or non-ablative (<190Gy) TARE delivered in a segmental, lobar, or combined fashion as a surgical neoadjuvant or bridge to transplantation. Both targeted tumor and treatment angiosome were analyzed before and after TARE utilizing hepatocyte-specific contrast-enhanced MRI or contrast-enhanced CT. Responses were graded using EASL and mRECIST criteria. Histologic findings including percent tumor necrosis and adjacent hepatic substrate effects were correlated with imaging features. Complete pathologic necrosis (CPN) was observed in 7/12 tumors post-TARE. Ablative and non-ablative dosing resulted in CPN in 5/6 and 2/6 tumors, respectively. Hyperintensity on T2-weighted imaging, the absence of hepatocyte-specific gadolinium contrast uptake, and plateau or persistent enhancement kinetics in the angiosome correlated with CPN and performed similarly to EASL and mRECIST criteria in predicting CPN. The absence of hepatocyte-specific contrast uptake, increased signal on T2-weighted sequences, and plateau or persistent enhancement in the angiosome may represent MRI surrogates of CPN following TARE of HCC. These findings correlated with EASL and mRECIST response criteria. Further investigation is needed to determine the role of these findings as possible adjuncts to conventional imaging criteria.

Utility of VS38c in the diagnostic and prognostic assessment of osteosarcoma and other bone tumours/tumour-like lesions

BackgroundVS38c is a monoclonal antibody that recognises a rough endoplasmic reticulum (rER) intracellular antigen termed cytoskeleton-linking membrane protein 63. rER is typically found in viable tumour cells and is abundant in osteosarcoma cells. The aim of this study was to determine the diagnostic and prognostic utility of VS38c in the histological assessment of osteosarcoma and other bone tumours/tumour-like leisons.MethodsImmunohistochemical staining with VS38c was carried out on formalin-fixed specimens of osteosarcoma (pre/post-chemotherapy) and a wide range of benign and malignant bone lesions. In addition, VS38c staining of cultures of MG63 and Sa0S2 osteosarcoma cell cultures. (±cisplatin and actinomycin D-treatment) was analysed.ResultsVS38c strongly stained tumour cells in all low-grade and high-grade osteosarcomas and in undifferentiated sarcomas and high-grade chondrosarcomas. There was little or no VS38c staining of low-grade chondrosarcomas or chordomas and variable staining of Ewing sarcomas. Osteoblasts in benign bone-forming tumours and mononuclear stromal cells in chondroblastomas, giant cell tumours and non-ossifying fibromas strongly stained for VS38c. VS38c staining was absent in cisplatin and actinomycin D treated Sa0S2 and MG63 cells. In specimens of osteosarcoma post-neoadjuvant therapy, VS38c staining was absent in most morphologically necrotic areas of tumor although some cells with pyknotic nuclei stained for VS38c in these areas. Most tumour cells exhibiting atypical nuclear forms were not stained by VS38c.ConclusionsOur findings show that VS38c is a sensitive but not specific diagnostic marker of osteosarcoma. Staining with VS38c identifies viable osteosarcoma cells, a feature which may be useful in the assessment of percentage tumour necrosis post-neoadjuvant chemotherapy.

Contrast media enhancement reduction predicts tumor response to presurgical molecular-targeting therapy in patients with advanced renal cell carcinoma.

Background and ObjectiveA quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy.ResultsOf 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were −19%, −24%, and −49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST.Materials and MethodsBetween March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis.ConclusionsCMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy.

Surrogates of Progression-Free Survival in Endometrial Cancer Patients: An Evaluation of Tissue Composition [19J

INTRODUCTION: Endometrial cancer (EC) is a heterogeneous disease that varies in tumor composition. The goal of this study was to determine if the composition of endometrial tumors have potential prognostic value. METHODS: Tissue composition of frozen tumors and clinical outcome data were downloaded from the Cancer Genome Atlas (TCGA) Uterine Corpus Endometrial Carcinoma project. Tumors were scored by TCGA pathologists for percent tumor cellularity, necrosis, stromal cells, lymphocytes, monocytes, and neutrophils. The relationship between these measures of tissue composition and clinical outcome were evaluated using log-rank test and Cox modeling. Relationships with clinical characteristics were evaluated using Fisher exact testing. RESULTS: There were 547 evaluable EC patients, including 28% with advanced stage, 75% with endometrioid histology and 21% with serous cancers. Presence versus absence of necrosis, stromal cells, or neutrophils in the tumor samples was associated with worse progression-free survival (PFS) and an increased risk of disease progression (P &lt; .05). The presence of necrosis in the research sample was also an independent surrogate of poor PFS in EC patients after adjustments for stage, cell type, grade and myometrial invasion (hazard ratio=1.56, P=.044). Necrosis was more common in patients with advanced stage (P=.012), higher grade (P &lt; .0001), and deeper myometrial invasion (P &lt; .0001). CONCLUSION: The presence versus absence of necrosis in EC tumors is a promising surrogate of poor versus good prognosis for EC patients with independent prognostic value after adjustment for stage, cell type and tumor grade.

Treatment of glomus tympanicum tumors by preoperative embolization and total surgical resection

PurposeThe purpose of this study was to evaluate the effectiveness on function preservation and tumor control of the treatment of glomus tympanicum tumors with pre-operative embolization followed by total surgical resection. Material and methodsWe describe a series of 6 patients with a glomus tympanicum tumor who were treated in our hospital using the same technique: the day before surgery selective tumor embolization due to denaturation with 96% ethanol. Following parameters were considered: tumor classification, tumor control, clinical and audiological outcome, effectiveness of embolization, percentage of tumor necrosis and treatment complications. ResultsThere were no severe complications due to embolization or surgery. Tumor blush disappeared completely in 5 patients on DSA post embolization and histologic evaluation of the resected tissue showed a median of 69.2% of tumor necrosis. Pulsatile tinnitus disappeared in all patients and 3 patients had no symptoms at all. Hearing ameliorated in 4 patients, 1 patient without hearing loss pre- treatment still had normal hearing after treatment and 1 patient's hearing was worse after treatment. Average follow-up was 21.3months. ConclusionsTreatment of glomus tympanicum tumors by pre-operative embolization with ethanol and surgical resection has not been described before. Our results show that it is a safe procedure with a good long term tumor control, good clinical and audiological outcome.

SERUM VALUES OF ALKALINE PHOSPHATASE AND LACTATE DEHYDROGENASE IN EWING'S SARCOMA.

ABSTRACTObjective: To study the relationship between the serum levels of alkaline phosphatase (AP) and lactate dehydrogenase (LDH), and the percentage of tumor necrosis (TN) in patients with Ewing´s Sarcoma (ES). Methods: This is a case series with retrospective evaluation of patients with diagnosis of ES divided into 2 groups: Group 1, patients whose serum levels of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were obtained in the staging phase before preoperative chemotherapy (CT), and Group 2, patients whose values were measured after completion of the preoperative CT. The percentage of tumor necrosis (TN) of surgical specimens extracted in surgery was also evaluated. Results:Eighty four medical records from 1995 to 2015 were included. Both AP as LDH decreased in the patients studied, the pre CT value being higher than the post CT value. The average decrease of LHD was 272.95 U/L and AP was 10.17 U/L. The average tumor necrosis was 65.12 %. There was no statistical correlation between serums levels and the tumor necrosis percentage. Conclusion: The serum levels values of AP and LDH are not predictors for chemotherapy-induced necrosis in patients with ES. Level of Evidence IV, Case Series.

Pamidronate functionalized nanoconjugates for targeted therapy of focal skeletal malignant osteolysis

Malignant osteolysis associated with inoperable primary bone tumors and multifocal skeletal metastases remains a challenging clinical problem in cancer patients. Nanomedicine that is able to target and deliver therapeutic agents to diseased bone sites could potentially provide an effective treatment option for different types of skeletal cancers. Here, we report the development of polylactide nanoparticles (NPs) loaded with doxorubicin (Doxo) and coated with bone-seeking pamidronate (Pam) for the targeted treatment of malignant skeletal tumors. In vivo biodistribution of radiolabeled targeted Pam-NPs demonstrated enhanced bone tumor accumulation and prolonged retention compared with nontargeted NPs. In a murine model of focal malignant osteolysis, Pam-functionalized, Doxo-loaded NPs (Pam-Doxo-NPs) significantly attenuated localized osteosarcoma (OS) progression compared with nontargeted Doxo-NPs. Importantly, we report on the first evaluation to our knowlege of Pam-Doxo-NPs in dogs with OS, which possess tumors of anatomic size and physiology comparable to those in humans. The repeat dosing of Pam-Doxo-NPs in dogs with naturally occurring OS indicated the therapeutic was well tolerated without hematologic, nonhematologic, and cardiac toxicities. By nuclear scintigraphy, the biodistribution of Pam-Doxo-NPs demonstrated malignant bone-targeting capability and exerted measurable anticancer activities as confirmed with percent tumor necrosis histopathology assessment.

SERUM VALUES OF ALKALINE PHOSPHATASE AND LACTATE DEHYDROGENASE IN OSTEOSARCOMA.

ABSTRACTObjective: To study the relationship between the pre and post chemotherapy (CT) serum levels of alkaline phosphatase (AP) and lactate dehydrogenase (LDH), and the percentage of tumor necrosis (TN) found in specimens after the pre surgical CT in patients with osteosarcoma.Methods: Series of cases with retrospective evaluation of patients diagnosed with osteosarcoma. Participants were divided into two groups according to serum values of both enzymes. The values of AP and LDH were obtained before and after preoperative CT. The percentage of tumor necrosis (TN) of surgical specimens of each patient was also included.Results: One hundred and thirty seven medical records were included from 1990 to 2013. Both the AP as LDH decreased in the patients studied, being the higher in pre CT than post CT. The average LHD decrease was 795.12U/L and AP decrease was 437.40 U/L. The average TN was 34.10 %. There was no statistically significant correlation between the serums values and the percentage of tumoral necrosis.Conclusion: The serum levels values of AP and LDH are not good predictors for the chemotherapy-induced necrosis in patients with osteosarcoma. Level of Evidence IV, Case Series.

Correlation of Doxorubicin Delivery and Tumor Necrosis after Drug-eluting Bead Transarterial Chemoembolization of Rabbit VX2 Liver Tumors.

Purpose To quantify the correlation between doxorubicin (DOX) delivery and tumor necrosis after drug-eluting bead (DEB) transarterial chemoembolization (TACE). Materials and Methods In this animal care committee-approved study, New Zealand white rabbit VX2 liver tumors were treated transarterially with DOX-loaded 70-150-μm DEBs in five treatment groups with varying drug doses: sham (saline), 0 mg, 12.5 mg, 25 mg, and 37.5 mg. DEB TACE was followed by 3- and 7-day sacrifice, tumor harvest, and sectioning. Drug delivery was assessed by using fluorescence imaging, and tumor necrosis was quantified by means of histologic analysis. Statistical correlation of DOX delivery and tumor necrosis was performed by using the Spearman rank correlation coefficient (ρ). Results Thirty-six VX2 tumors (median diameter, 1.3 cm) in 20 rabbits (median weight, 2.8 kg) underwent successful DEB TACE. Treatment groups included eight, seven, eight, five, and eight tumors of similar size (P > .05). Tumors showed progressively greater DOX extent (sham, 0%; 0 mg, 0%; 12.5 mg, 3%; 25 mg, 20%; and 37.5 mg, 27%) and intensity (sham, 0.4; 0 mg, 1.9; 12.5 mg, 8.5; 25 mg, 9.6; and 37.5 mg, 18.3) and higher median percentage necrosis (sham, 68%; 0 mg, 64%; 12.5 mg, 76%; 25 mg, 78%; and 37.5 mg, 83%) across DOX treatment groups. Correlation of DOX extent (ρ = 0.975, P = .005) and intensity (ρ = 0.900, P = .037) with percentage tumor necrosis was statistically significant. Conclusion Incremental increases in DOX correlate with greater necrosis in rabbit VX2 liver tumors after DEB TACE. This result indicates an essential role for chemotherapy-induced cytotoxicity in TACE effectiveness and supports the use of chemotherapeutic drugs in transarterial therapy. (©) RSNA, 2016 Online supplemental material is available for this article.

«Factores pronósticos de sobrevida de pacientes con osteosarcoma»

ObjectiveTo identify prognostic factors of survival in patients with osteosarcoma, using a parametric survival model. Material and methodsA retrospective cohort study was carried out on 68 patients diagnosed with osteosarcoma and who were treated at Traumatology Institute from January 1 2002 to December 31 2012.In order to calculate the mean incidence of osteosarcoma, the population greater than or equal to 15 years old during the study period was considered as a denominator. The following were inclusion criteria: patients of either sex, age greater than or equal to 15 years, and positive biopsy for any kind of osteosarcoma.The following predictor variables were considered: sex, tumour site, lung metastasis, relapse, kind of osteosarcoma, histological grade, treatment, and percentage of tumour necrosis. ResultsThe mean incidence rate of osteosarcoma in the population studied was 0.98 cases per 1 million people per year. As a poor prognosis, the multivariate model showed: masculine gender, lung metastasis during the first year, relapse, and less than 90% of tumour necrosis. DiscussionThe predictor variables of survival in patients with osteosarcoma that agree with other multivariate models are: masculine gender, lung metastasis, and less than 90% of tumour necrosis. On the other hand, the discrepancy with other authors can be explained by the wide variation in the methodology used, as well as the variability of the prognostic factors considered, rather than tangible differences in patient management in the various medical centres.

P16 expression predicts neoadjuvant tumor necrosis in osteosarcomas: reappraisal with a larger series using whole sections

The presence of greater than or equal to 90% necrosis after neoadjuvant chemotherapy is a favorable prognostic factor in osteosarcomas. A recent study using tissue microarrays of 40 conventional osteosarcomas showed that p16 expression independently predicted the necrotic response to neoadjuvant chemotherapy. In this study, we investigated this finding using whole sections in a larger group of osteosarcomas. Cases of 83 patients who had pretreatment biopsies and received neoadjuvant chemotherapy and surgical resection were collected from 3 reference hospital archives. Age, sex, tumor size, tumor subtype, location, and percentage of tumor necrosis were recorded; 4-μm sections from pretreatment biopsies were stained for p16. More than 30% strong nuclear staining was regarded as positive. The median age was 17 years (5-68 years), and male/female ratio was 2.3. The mean tumor diameter was 9.9 cm (2-30 cm). Tumors were most commonly of the osteoblastic type (60%) and located at the femur (47%). p16 positivity was seen in 66% of the patients. The median pathologic necrosis was 65%, and 39% of the patients responded favorably (≥%90 necrosis) to neoadjuvant therapy. In univariate analysis, p16 expression significantly correlated with greater than or equal to 90% response (P = .022). On multivariate analysis, p16 expression (odds ratio [OR], 7.71; P = .008), female sex (OR, 8.62; P = .006), and smaller tumor size (OR, 0.86; P = .023) were independent predictors of favorable response to neoadjuvant chemotherapy. We confirmed the finding that p16 expression predicts postchemotherapy necrotic response in conventional osteosarcomas.

Abstract B11: Adaptive therapy modifies tumor vascularity

Abstract Introduction: Disseminated cancers are typically treated with the highest possible dose of drug (i.e. maximum tolerated dose) to achieve the goal of killing as many tumor cells as possible. However, these therapies eventually fail due to emergence of resistant clones. We have predicted, using mathematical models of Darwinian dynamics, that treatment regimens that adapt the dosing to the tumor spatial variability and tumor microenvironment, can retard the emergence of chemoresistance. Here we present an evolutionary-guided treatment strategy (Adaptive Therapy, AT) designed to maintain stable chemosensitive populations while limiting the proliferation of chemoresistant clones by exploiting the fitness cost of the resistant phenotype. We also evaluated how this novel treatment strategy modifies tumor vascularity. Methods: Four cohorts (composed by 12, 11, 13, and 10 mice, respectively) of nude mice were injected with 10x106 MDA-MB-231 (triple-negative breast cancer) cells in the mammary fat pad. Control animals didn't receive any treatment. Mice under standard therapy received 20mg/kg of Tamoxifen twice per week for a total of 5 times. We defined two different Tamoxifen AT algorithms (Table 1), under which AT mice were treated. Table 1.Adaptive Therapy treatment algorithmsAT-1Initial Dose = 20 mg/kg (highest dose)&amp;gt; If VT(n)≤ .8*VT(n-1) -&amp;gt;Dose decreased by 50%&amp;gt; If VT(n)≥ 1.2*VT(n-1) -&amp;gt;Dose increased by 50%&amp;gt; If the tumor volume is within 20% range, we will apply same dose as previous dose.Lower Limit: 150mm3 and skip the doseAT-2Starting dose = 15 mg/kg&amp;gt; If VT(n)≥ 1.25*VT(n-2) -&amp;gt;Dose = 15 mg/kg&amp;gt; If VT(n) &amp;lt; 1.25*VT(n-2) -&amp;gt;Skip Dose When the tumors achieve the volume of, approximately 300 mm3, MRI T2 and Diffusion Weighted acquisitions were performed on a horizontal Agilent ASR 310 7T scanner, with 205/120/HDS gradients and 310 mm bore to determine volume and cellularity, respectively. Thereafter, dynamic contrast enhanced (DCE-) MRI was preformed following bolus of 0.1mmol/kg Magnevist to assess distribution of blood flow. Images were processed with different in-house developed MATLAB scripts to obtain reliable information from these images. At the end of the monitoring time, tumors were collected and processed for H&amp;E and CD31 immunohistochemistry staining to study the viable and necrotic tissue, and vessel presence, respectively. The slides were examined using the Aperio ScanScope XT microscope. Using different selected slides, an algorithm was built in order to analyze all tissue samples (software Spectrum Version 10.2.5.2352, Aperio Technologies with a pixel-wise resolution. Results and Discussion: Tumor growth was monitored during the treatment period using the MRI techniques previously described. The AT treatment algorithm has been modified to fine tune the dose and scheduling based on tumor volume. Among these three protocols (2 AT and one ST), AT-1 resulted in the most significant cancer control. AT-1 protocol was able to maintain tumors at a small size for &amp;gt;120 days. Also, AT-1 has demonstrated to decrease the percent tumor necrosis (data not shown), and increase vascular density. New experiments and data analysis are currently undergoing in order to get more information and a deeper insight on how the AT can benefit the in-vivo cancer treatment. Conclusion: In summary, initial results demonstrate that AT, guided by MRI measurement of tumor volume, can maintain a stable small tumor burden with prolonged progression free survival compared to standard high dose therapy. Also, AT is able to maintain the lower necrotic volume and the higher vessel density, which, in addition with the tumor volume, was correlated with tumor stabilization. Citation Format: Pedro M. Enriquez-Navas, Jonathan Wojtkowiak, Epi Ruiz, Sabrina Hassan, Robert J. Gillies, Robert A. Gatenby. Adaptive therapy modifies tumor vascularity. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B11.

Segmental Transarterial Embolization in a Translational Rat Model of Hepatocellular Carcinoma

PurposeTo develop a clinically relevant, minimally invasive technique for transarterial embolization in a translational rat model of hepatocellular carcinoma (HCC). Materials and MethodsOral diethylnitrosamine was administered to 53 male Wistar rats ad libitum for 12 weeks. Tumor induction was monitored using magnetic resonance imaging. Minimally invasive lobar or segmental transarterial embolization was performed through a left common carotid artery approach. Necropsy was performed to evaluate periprocedural mortality. Histologic analysis of tumors that received embolization was performed to assess percent tumor necrosis. ResultsSevere cirrhosis and autochthonous HCCs were characterized in a cohort of rats composed of two groups of rats identically treated with diethylnitrosamine with median survival times of 101 days and 105 days (n = 10/group). A second cohort was used to develop minimally invasive transarterial embolization of HCCs (n = 10). In a third cohort, lobar embolization was successfully performed in 9 of 10 rats and demonstrated a high rate of periprocedural mortality (n = 5). Necropsy performed for periprocedural mortality after lobar embolization demonstrated extensive tissue necrosis within the liver (n = 3) and lungs (n = 2), indicating nontarget embolization as the likely cause of mortality. In a fourth cohort of rats, a segmental embolization technique was successfully applied in 10 of 13 rats. Segmental embolization resulted in a reduction in periprocedural mortality (P = .06) relative to selective embolization and a 19% increase in average tumor necrosis (P = .04). ConclusionsMinimally invasive, segmental embolization mimicking the currently applied clinical approach is feasible in a translational rat model of HCC and offers the critical advantage of reduced nontarget embolization relative to lobar embolization.

8:45 AM Abstract No. 26 - Effects of doxorubicin (DOX) delivery on tumor necrosis after drug-eluting bead transarterial chemoembolization (DEB-TACE)

Transarterial chemoembolization (TACE) induced tumor necrosis is thought to represent additive results of chemotherapeutic cytotoxic insults and embolic ischemic effects. The benefit of chemotherapy as a constituent of transarterial therapy has been questioned, however, based on studies showing no tumor response differences between bland embolization and TACE. An established relationship between drug delivery and cellular necrosis following TACE is presently unproven. This study aimed to define the incremental tumor necrosis afforded by doxorubicin (DOX) during drug-eluting bead (DEB) TACE. In this IRB-approved study, VX2 liver tumors in New Zealand white rabbits were treated with DOX-loaded 70-150 micron DEBs (LC Bead M1; BTG). Rabbits were divided into 5 treatment groups with varying DOX doses: sham (saline, no beads), 0 mg (bland beads), 12.5 mg, 25 mg, and 37.5 mg. 130,000 beads (10% vial) were administered per procedure. DEB-TACE was followed by sacrifice at 3 and 5 days. Histologic analysis of harvested tumors was used to quantify percent tumor necrosis using the NanoZoomer Digital Pathology System (Hamamatsu). Statistical comparison of quantitative tumor necrosis was performed using one-way ANOVA and the Student’s t-test. 35 VX2 tumors (mean diameter 1.3 cm) in 21 rabbits (mean weight 2.8 kg) were successfully treated with selective DEB-TACE. Treatment groups included 8, 7, 7, 5, and 8 tumors, respectively. Mean tumor size was similar between treatment groups (P=0.311). Tumors showed progressively higher mean percent necrosis across treatment groups with increasing DOX dose (sham: 55%, 0 mg: 55%, 12.5 mg: 64%, 25 mg: 67%, 37.5 mg: 69%). Differences between sham and 0, 12.5, and 25 mg groups were not statistically significant. However, the increase in percent necrosis afforded by 37.5 mg DOX-loaded DEBs achieved statistical significance compared to sham (P=0.041). Incremental increases in DOX dose result in higher percent necrosis of rabbit VX2 liver tumors after DEB-TACE. This result indicates an essential role for chemotherapy-induced cytotoxicity in TACE efficacy, and supports the use of chemotherapeutic drugs as a component of transarterial therapy.

Tumor necrosis is a strong predictor for recurrence in patients with pathological T1a renal cell carcinoma.

Patients with pT1aN0M0 renal cell carcinoma (RCC) generally have good prognosis, and recurrence is rare. However, metastasis develops postoperatively in a small number of patients with pT1aN0M0 RCC. The present study was undertaken to identify predictors for recurrence in patients with pT1aN0M0 RCC. We reviewed the clinicopathological factors of 133 patients with pT1aN0M0 RCC who underwent radical or partial nephrectomy at the Department of Urology, National Defense Medical College (Saitama, Japan). Clinicopathological factors, including age, gender, tumor size, histological subtype, tumor grade, microvascular invasion, histological tumor necrosis, C-reactive protein levels and performance status were reviewed. These factors were compared between patients with and without postoperative recurrence. Recurrence-free survival (RFS) and cause-specific survival (CSS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to determine independent factors predicting recurrence in patients with pT1aN0M0 RCC. The 5-year RFS and CSS rates were 97.2 and 99.1%, respectively. When clinicopathological factors were compared between patients with and without recurrence, tumor size (P=0.0390) and percentage of tumor necrosis (P<0.0001) were significantly different between groups. All patients with recurrence had primary lesions ≥3 cm. By univariate analysis, tumor size (P=0.0379) and the presence of tumor necrosis (P=0.0319) were significant predictors for recurrence; tumor necrosis was also an independent predictor for recurrence (P=0.0143). In patients with pT1b tumors ≤5 cm (recurrence rate, 16.8%; n=48), the percentage of tumor necrosis was significantly higher in patients with recurrence compared with those without (P=0.0261). This suggests that tumor necrosis may be an important predictor for recurrence in small RCCs. Although recurrence is rare in pT1a RCC, the presence of tumor necrosis may be an important predictor for recurrence. Particularly, patients presenting with pT1a RCC with histological tumor necrosis should undergo careful follow-up.