Viable Tumor Tissue Research Articles

The feasibility of using arterial spin labeling for visualization of non perfused volumes after HIFU treatment in the kidney

MR guidance of High Intensity Focused Ultrasound (MFgHIFU) ablation offers the possibility to determine if complete tumor ablation has been established based on imaging the non-perfused volume (NPV). For thermal therapy, contrast enhanced (CE) imaging with a gadolinium-based contrast agent is currently the golden standard to quantify the NPV. A drawback of this method is that gadolinium based intra-vascular contrast agents interfere with HIFU therapy in two ways. First, ablation can release toxic free gadolinium, by long-term decomposition of the encapsulating chelate. Second, it degrades the quality of MR-thermometry. Therefore, even if residual viable tumor tissue is observed with CE-MRI, the treatment cannot be continued. To address this problem for HIFU interventions on the kidney, this study explores other means of perfusion imaging, such as Arterial Spin Labeling (ASL). Petros Martirosan’s group at the University of Tubingen used Flow-sensitive Alternating Inversion Recovery (FAIR) to image perfusion in the kidneys without the use of contrast agents. This in vivo study on a porcine model investigates if ASL potentially allows to perform NPV measurements during therapy and to continue the intervention if incomplete ablation of the target volume is observed.

Reproducibility of mRECIST in assessing response to transarterial radioembolization therapy in hepatocellular carcinoma.

The purpose of our study was to evaluate the reproducibility of Modified Response Evaluation Criteria in Solid Tumors (mRECIST) in hepatocellular carcinoma (HCC) lesions undergoing transarterial radioembolization (TARE) therapy and to determine whether mRECIST reproducibility is affected by the enhancement pattern of HCC. One hundred and three HCC lesions from 103 patients treated with TARE were evaluated. The single longest diameter of viable tumor tissue was measured by two radiologists at baseline; response to therapy was evaluated according to mRECIST. The enhancement pattern of HCC lesions was correlated with their mRECIST response. The response rate between mRECIST and RECIST 1.1 was compared. Wilcoxon signed-rank test, paired t test, Lin's concordance correlation coefficient (ρc ), Bland-Altman plot, kappa statistics, and Fisher's exact test were used to assess intra- and interobserver reproducibilities and to compare response rates. There were better intra- than interobserver agreements in the measurement of single longest diameter of viable tumor tissue (bias = 0 cm intraobserver versus bias = 0.3 cm interobserver). For mRECIST, good intraobserver (ĸ = 0.70) and moderate interobserver (ĸ = 0.56) agreements were noted. The mRECIST response for HCC lesions with homogeneous enhancement at both baseline and follow-up imaging showed better intra- and interobserver agreements (ĸ = 0.77 and 0.60, respectively) than lesions with heterogeneous enhancement at both scans (ĸ = 0.54 and 0.40, respectively). In the early follow-up period mRECIST showed a significantly higher response rate than RECIST (40.8% versus 3.9%; P = 0.025). In HCC patients treated with TARE, mRECIST captures a significantly higher response rate compared with RECIST; it also demonstrates acceptable intra- and interobserver reproducibilities for HCC lesions treated with TARE, and mRECIST reproducibility may be lower for HCC lesions with heterogeneous distribution of the viable tumor tissue.

PTH-331 Non-operative management of low rectal cancer with complete response to standard neoadjuvant chemoradiotherapy

<h3>Introduction</h3> 20% of low rectal cancers respond extremely well to standard long course radiotherapy and on clinical examination apparently disappear from the rectal lumen after chemoradiotherapy; an apparent complete response. There are two dilemmas which follow this: Can we be sure about the complete response and that there is no viable residual tumour tissue? If we believe there is no tumour tissue left, how do we then manage these patients? Our Trust started to suggest non-operative management to ‘complete responders’ in January 2007, and the results were remarkable. <h3>Method</h3> Ongoing study looking at 14 complete responders. Surveillance has been MRI/EUS/EUA under GA during years 0–2 every three months. MRI/EUS/EUA under GA during years 3–5 every six months. MRI/EUS/EUA under GA after 5 years every year. A CT scan and colonoscopy were performed at the two and five year marks. These are the Trust’s local guidelines. <h3>Results</h3> 14 patients in total. Seven are still disease-free and still under surveillance. Three had recurrence; two underwent APR and one underwent ultra low anterior resection; all had R0 resections and are still disease-free. Four were suspected to have recurrence but were not fit for major resections therefore had transanal procedures; all had tumour-free specimens and are still disease-free and under surveillance. <h3>Conclusion</h3> There are an important cohort of patients who have low rectal cancer who may not need an operation. We are still unsure exactly how to manage these patients and it is therefore important for each unit to follow them up and share experiences. As a Trust, we will continue to manage these patients with the diagnosis of low rectal cancer, who are ‘disease-free’ following long course chemoradiotherapy, non-operatively. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Smith JD, <i>et al</i>. Non-operative management of rectal cancer with complete response to neoadjvant therapy. Ann Surg. 2012;256:965–972 Habr-Gama A, <i>et al</i>. Non-operative management of distal rectal cancer after chemoradiation: experience with the “watch and wait” policy. Dis. Colon Rectum. 2010;52:1137–1143 Habr-Gama A, <i>et al</i>. Operative versus non-operative treatment for stage 0 distal rectal cancer following chemoradiation therapy. Ann Surg. 2004;240(4):711–718 Tennyson MD, <i>et al</i>. Transanal excision with radiation therapy for rectal cancer. Clin Med Res. 2012;10(4):224–229 Schmoll HJ, <i>et al</i>. ESMO concensus guideline for management of patients with colon and rectal cancer: a personalised approach to clinical decision making. Ann Oncol. 2012;23:2479–2516 Deferral of Surgery (Watch And Wait) Study. Royal Marsden Hospital, Pelican Cancer Foundation, Phase II Multicentre Single-Arm Study, Cancer Research Trial Number CRUK/10/006

Assessment of tumour viability in human lung cancer xenografts with texture-based image analysis

AimsTo build and evaluate an automated method for assessing tumour viability in histological tissue samples using texture features and supervised learning.MethodsH&E-stained sections (n=56) of human non-small cell lung adenocarcinoma xenografts...

Assessment of clinical and radiological response to sorafenib in hepatocellular carcinoma patients.

Sorafenib is an effective anti-angiogenic treatment for hepatocellular carcinoma (HCC). The assessment of tumor progression in patients treated with sorafenib is crucial to help identify potentially-resistant patients, avoiding unnecessary toxicities. Traditional methods to assess tumor progression are based on variations in tumor size and provide unreliable results in patients treated with sorafenib. New methods to assess tumor progression such as the modified Response Evaluation Criteria in Solid Tumors or European Association for the Study of Liver criteria are based on imaging to measure the vascularization and tumor volume (viable or necrotic). These however fail especially when the tumor response results in irregular development of necrotic tissue. Newer assessment techniques focus on the evaluation of tumor volume, density or perfusion. Perfusion computed tomography and Dynamic Contrast-Enhanced-UltraSound can measure the vascularization of HCC lesions and help predict tumor response to anti-angiogenic therapies. Mean Transit Time is a possible predictive biomarker to measure tumor response. Volumetric techniques are reliable, reproducible and time-efficient and can help measure minimal changes in viable tumor or necrotic tissue, allowing the prompt identification of non-responders. Volume ratio may be a reproducible biomarker for tumor response. Larger trials are needed to confirm the use of these techniques in the prediction of response to sorafenib.

Randomized Comparison of Selective Internal Radiotherapy (SIRT) Versus Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE) for the Treatment of Hepatocellular Carcinoma

PurposeTo prospectively compare SIRT and DEB-TACE for treating hepatocellular carcinoma (HCC).MethodsFrom 04/2010–07/2012, 24 patients with histologically proven unresectable N0, M0 HCCs were randomized 1:1 to receive SIRT or DEB-TACE. SIRT could be repeated once in case of recurrence; while, TACE was repeated every 6 weeks until no viable tumor tissue was detected by MRI or contraindications prohibited further treatment. Patients were followed-up by MRI every 3 months; the final evaluation was 05/2013.ResultsBoth groups were comparable in demographics (SIRT: 8males/4females, mean age 72 ± 7 years; TACE: 10males/2females, mean age 71 ± 9 years), initial tumor load (1 patient ≥25 % in each group), and BCLC (Barcelona Clinic Liver Cancer) stage (SIRT: 12×B; TACE 1×A, 11×B). Median progression-free survival (PFS) was 180 days for SIRT versus 216 days for TACE patients (p = 0.6193) with a median TTP of 371 days versus 336 days, respectively (p = 0.5764). Median OS was 592 days for SIRT versus 788 days for TACE patients (p = 0.9271). Seven patients died in each group. Causes of death were liver failure (n = 4 SIRT group), tumor progression (n = 4 TACE group), cardiovascular events, and inconclusive (n = 1 in each group).ConclusionsNo significant differences were found in median PFS, OS, and TTP. The lower rate of tumor progression in the SIRT group was nullified by a greater incidence of liver failure. This pilot study is the first prospective randomized trial comparing SIRT and TACE for treating HCC, and results can be used for sample size calculations of future studies.

False-positive fluorodeoxyglucose positron emission tomography results after chemotherapy in patients with metastatic seminoma

IntroductionThe treatment of residual masses after chemotherapy in seminomas remains a controversial topic. Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in all patients would lead to severe overtreatment with a high rate of complications and additional procedures. For this reason, fluorodeoxyglucose positron emission tomography (FDG-PET) was introduced. FDG-PET has an accuracy of 88%. In 15% of cases, FDG-PET findings are false positive (FP) with unclear consequences. Therefore, we retrospectively investigated the rate of unnecessary procedures due to FP results on FDG-PET. Materials and methodsBetween July 2003 and September 2013 we performed 305 PC-RPLNDs in 277 patients, 22 because of metastatic seminoma. Of them, 11 patients had a preoperative FDG-PET at least 6 weeks after chemotherapy. Indication for surgery was a marker-negative progression of the lesion in 7 patients who did not undergo FDG-PET, a marker-negative progression with a negative result on FDG-PET in 2 patients, and a positive result on FDG-PET with normal markers in 9 patients. Furthermore, PC-RPLND was indicated in 3 patients because of ureteral compression/infiltration with ureteral stents or nephrostomies. In 1 patient, there was uncertainty whether the initial retroperitoneal tumor contained choriocarcinoma elements. Standardized uptake values (SUVs) were recorded for all patients undergoing FDG-PET. ResultsThe FDG-PET findings were FP in 7 of 11 (64%) patients. The median age of the patients was 45.4 years (39–49). The median SUV in the patients was 6.6 (3.1–11.6), and the median diameter of the residual mass was 6.8cm (2.9–11). In 4 of 7 patients, intraoperative or postoperative complications occurred (polar artery ligation with functional loss, bilateral non–nerve-sparing technique with retrograde ejaculation, ureteral replacement with an ileal segment, and pulmonary embolism). ConclusionIn patients with metastatic seminoma who received chemotherapy, FDG-PET is a valuable tool to evaluate whether the residual mass contains viable tumor tissue or only necrosis. Nevertheless, because of FP results, a subgroup is overtreated with consecutive mortality or morbidity. We suggest an alternative therapy algorithm. In case of a positive result on FDG-PET studies, at least 8 weeks after the end of the chemotherapy, only a minority require surgery (e.g., patients with ureteral compression, patients with high risk of recurrence, or patients with unclear initial histology). In all other cases, we suggest a repeat FDG-PET study at least 6 weeks after the initial PET scan. Only in cases of increased SUVs or progressive disease histology should be obtained, all others can be on active surveillance.

Pentavalent technetium-99m-dimercaptosuccinic acid [Tc-99m (V) DMSA] brain SPECT: does it have a place in predicting survival in patients with glioblastoma multiforme?

Pentavalent technetium-99m dimercaptosuccinic acid (Tc-99m (V) DMSA) is reported as a useful tool for detection of residual or recurrent gliomas. We aimed to investigate the prognostic value of Tc-99m (V) DMSA brain SPECT in patients with glioblastoma multiforme (GBM). 40 patients [21 males and 19 females; mean age 48.6 ± 12.2 years] with GBM were included. Tc-99m (V) DMSA brain SPECT was done after surgery and before onset of radiation therapy or chemotherapy (Baseline study), at 4-6 weeks and at 6 months as a follow-up after therapy. The end point of the study was clinical follow-up for 2 years and/or death. 4-6 weeks after therapy, 40 and 60 % had negative and positive Tc-99m (V) DMSA for viable tumor tissues respectively (P = 0.09). At 6 months follow-up, 62.5 % of (V) DMSA negative patients and 12.5 % of the positive subjects were responders (P = 0.001). The median over-all survival (OS) of all patients was 12.3 month [range 5-24 month]. Patients with positive (V) DMSA had worse survival (8.87 month) compared to the negative ones (16.67 month) (P = 0.0001). Multivariate Cox regression analysis showed that Tc-99m (V) DMSA brain SPECT studies at 4-6 weeks and 6-months follow-up were independent prognostic factors for survival [OR 1.069; 95 % CI 1.417-2.174; P = 0.03 and OR 1.055; 95 % CI 0.821-1.186; P = 0.01 respectively]. Stratification of tumors into risk groups based on prognostic parameters may improve outcome by altering or intensifying treatment methods. Technetium-99m dimercaptosuccinic acid brain SPECT may have an additional prognostic role in patients with GBM which needs further evaluation in larger future series.

간세포암의 경동맥화학색전술 후 추적검사에서 조영증강초음파와 리피오돌 전산화단층촬영의 일치성 비교

Background/Aims: The aim of this study is to evaluate the concordance of contrast-enhanced ultrasonography (CEUS) and lipiodol computed tomography (L-CT) for the assessment of viable hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE).MethodsWe retrospectively reviewed the post-TACE CEUS and L-CT images of 65 consecutive HCCs in 41 patients to assess the presence of viable tumor tissue. Forty-seven HCCs in 31 patients that underwent post-TACE L-CT within 4 weeks of the CEUS examination were included. The degree of concordance between CEUS and L-CT and factors related to concordance were analyzed.ResultsThe overall concordance of CEUS and LDCT was 78.7% (37/47). The concordance with L-CT for viable tumor and non-viable tumor tissue on CEUS was 95.2%, and 65.4% respectively (P<0.013). Diffuse tumors had a tendency for non-concordance (P=0.066). Although 3 of 4 lesions located in the hepatic dome were non-concordant, the sample size was too small to establish significance. The mean tumor size for concordant and non-concordant tumors was 2.9 and 3.0 cm, with no significant difference.ConclusionsAlthough the concordance of CEUS and L-CT for viable tumor tissue was high, the concordance for non-viable tumor tissue was relatively low. Prospective studies using angiography as a gold standard should be performed in the future. (J Liver Cancer 2014;14:115-119)

O6.02 * ANALYSIS OF PD1 AND PD-L1 EXPRESSION IN GLIOBLASTOMA

BACKGROUND: Immune checkpoint inhibitors targeting programmed cell death (PD)1 and PD-ligand (L)1 show promising clinical activity in various solid extracranial cancers. Expression of PD1 on tumor infiltrating T lymphocytes and PD-L1 expression on tumor cells were postulated to have predictive value for the response to PD1/PD-L1 targeting immune checkpoint inhibitors. METHODS: 135 specimens of 117 patients (median age 60, range 21-80); median KPS 90 (range 10-100) with glioblastoma were included. In 18 patients, resection specimens of the first local recurrence in addition to tumor tissue from the initial resection were available. Analyses of PD1, PD-L1, CD3 and CD8 expression were performed by immunohistochemistry and previously published semiquantitative evaluation criteria. O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was analyzed using pyrosequencing and a cut-off at 8%. RESULTS: Sparse to moderate density of tumor-infiltrating lymphocytes (TILs) in a total of 100/135 (74.1%) cases (CD3+ 92/135, 68.1%; CD8+ 64/135, 47.4%) was observed. PD1 expression was found on scattered TILs, both within the tumor tissue and in the perivascular compartment, in 20/135 (14.8%) cases. PD-L1 expression was evident on tumor cells and macrophages/microglial cells throughout the tumor tissue with occasional focal accentuation in 116/135 (85.9%) specimens, with 44.5% showing PD-L1 staining of more than 50% of the viable tumor tissue. MGMT methylation was found in 37/99 (37.4%) analyzed specimens. No significant correlation of expression of PD1 or PD-L1 with the density of TILs or MGMT methylation status (p > 0.05) was observed. Younger age (p = 0.009), high KPS (p = 0.035) and MGMT hypermethylation (p = 0.008) showed a significant correlation with favorable overall survival, while TIL density or expression of PD1 (p = 0.783) and PD-L1 (p = 0.866) did not associate with patient outcome. CONCLUSION: PD1 and/or PD-L1 are immunohistochemically detectable in a majority of glioblastoma samples. A clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastoma.

Quantitative evaluation of CT-perfusion map as indicator of tumor response to transarterial chemoembolization and radiofrequency ablation in HCC patients

PurposeTo assess if radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may influence the evaluation of perfusion parameters obtained with CT-perfusion (CT-p) in HCC treated patients. Materials and methodsThirty-three consecutive cirrhotic patients with biopsy-proven diagnosis of HCC lesions and candidates to TACE or RFA were included. The CT-p study of hepatic parenchyma and of treated lesions was performed about 1 month after treatment on 16 multidetector CT after injection of 50mL of non ionic contrast agent (350mg I/mL) at a flow rate of 6mL/s acquiring 40 dynamic scans. A dedicated perfusion software which generated a quantitative map of arterial and portal perfusion by means of colour scale was employed.The following perfusion parameters were assessed before and after RFA or TACE treatment: hepatic perfusion (HP), arterial perfusion (AP), blood volume (BV), time to peak (TTP), hepatic perfusion index (HPI). ResultsA complete treatment was obtained in 16 cases and incomplete treatment in the 17 remaining cases. The perfusion data of completely treated lesions were: HP 10.2±6.3; AP 10.4±7; BV 4.05±4.8; TTP 38.9±4.2; HPI 9.9±9.2, whereas in partially treated lesions were: HP 43.2±15.1mL/s/100g; AP 38.7±8.8mL/min; BV 20.7±9.5mL/100mg; TTP 24±3.7s; HPI 61.7±7.5%.In adjacent cirrhotic parenchyma, the parameters of all evaluated patients were: HP 13.2±4; AP 12.3±3.4; BV 11.8±2.8; TTP 43.9±2.9; and HPI 17.1±9.8.A significant difference (P<0.001) was found for all parameters between residual viable tumor tissue (P<0.001) compared to successfully treated lesion due to the presence of residual arterial vascular structure in viable portion of treated HCC. ConclusionAccording to our results, CT-p evaluation is not influenced by TACE or RFA treatments, thus representing a feasible technique that allows a reproducible quantitative evaluation of treatment response in HCC patients.

Comparison of volume perfusion computed tomography (VPCT) and contrast-enhanced ultrasound (CEUS) for assessment of therapeutic effect of transarterial chemoembolisation (TACE)

Zielsetzung: To compare contrast-enhanced ultrasound (CEUS) and volume perfusion computed tomography (VPCT) for response evaluation of hepatocellular carcinoma (HCC) to transarterial chemoembolisation (TACE). Material und Methodik: Twenty consecutive patients with inoperable HCC underwent CEUS and VPCT in the pre- and post-TACE setting (mean, 1 day). Quality of CEUS and VPCT was rated as good/adequate/poor. Good and adequate were rated as diagnostic. We measured hepatic perfusion index (HPI), arterial liver perfusion (ALP), blood flow (BF) and blood volume (BV) at both time points by VPCT, calculated ratios and their sensitivity/specificity/negative (NPV) and positive predictive values (PPV) as well as cut-off values for these parameters as thresholds between responders and non-responders. VPCT and CEUS images were rated also according to mRECIST. Tumor response defined by mRECIST at follow-up (mean, 56 days) was accepted for validation. Ergebnisse: CEUS and VPCT yielded correct diagnosis in 20/20 cases. 10/20 patients showed at follow-up a complete response. There was a significant reduction of viable tumor tissue in all patients according to mRECIST (p 29,6% (all 100%), in BV of > 41,4% (all 100%), or in BF of > 53,1% (90%/100%/90%/100%) was indicative of response. Schlussfolgerungen: CEUS performs equally to VPCT for assessment of response to TACE in HCC. E-Mail: kaufmann.79@web.de

The efficiency of sorafenib as an adjuvant therapy on residual tumor after insufficient thermal ablation of rabbit VX2 liver tumor

Objective To evaluate the viability of residual tumor after insufficient thermal ablation of rabbit VX2 liver tumor and investigated the efficacy of sorafenib as an adjuvant therapy.Methods Twenty-one rabbits were implanted with VX2 tumor to establish orthotopic liver tumor models.They were allocated randomly into 3 groups:control (n =7),ablation (n =7),and combination treatment (n =7).Microwave coagulation therapy was conducted with 20 W for 1 min and viable tumor tissue remained at the periphery.A laparotomy was performed in the control group.Sorafenib was given at 20 mg/kg/d during the following 10 days in the combination treatment group,and saline was given to the control and ablation group.Tumor volume was recorded before and after treatment,immunohistochemistry detected CD31 and proliferating cell nuclear antigen (PCNA) expression,and the micro-vessel density (MVD) and proliferation index (PI) were calculated accordingly.Results Ten days after insufficient ablation,tumor volume of the ablation group was larger than that of the control group (P ＜0.05).The MVD and PI of residual tumor were higher compared with those of the control group (P ＜ 0.05).With adjuvant therapy of sorafenib after insufficient ablation,tumor volume showed a decrease on the 10th day compared with tumors undergoing insurfficient ablation alone (P ＜ 0.05).The MVD and PI of residual tumor were lower than those of the ablation group (P ＜0.05).Conclusion Insufficient thermal ablation promotes residual tumor progression,but adjuvant therapy of sorafenib serves as an effective way to suppress the overgrowth and neovasculation of the residual tumor. Key words: Microwave coagulation therapy; Sorafenib; Liver cancer

Simultaneous assessment of vessel size index, relative blood volume, and vessel permeability in a mouse brain tumor model using a combined spin echo gradient echo echo‐planar imaging sequence and viable tumor analysis

Combining multiple imaging biomarkers in one magnetic resonance imaging (MRI) session would be beneficial to gain more data pertaining to tumor vasculature under therapy. Therefore, simultaneous measurement of perfusion, permeability, and vessel size imaging (VSI) using a gradient echo spin echo (GE-SE) sequence with injection of a clinically approved gadolinium (Gd)-based contrast agent was assessed in an orthotopic glioma model. A combined spin echo gradient echo echo-planar imaging sequence was implemented using a single contrast agent Gd diethylenetriaminepentaacetic acid (Gd-DTPA). This sequence was tested in a mouse brain tumor model (U87_MG), also under treatment with an antiangiogenic agent (bevacizumab). T2 maps and the apparent diffusion coefficient (ADC) were used to differentiate regions of cell death and viable tumor tissue. In viable tumor tissue regional blood volume was 5.7 ± 0.6% in controls and 5.2 ± 0.3% in treated mice. Vessel size was 18.1 ± 2.4 μm in controls and 12.8 ± 2.0 μm in treated mice, which correlated with results from immunohistochemistry. Permeability (K(trans) ) was close to zero in treated viable tumor tissue and 0.062 ± 0.024 min(-1) in controls. Our MRI method allows simultaneous assessment of several physiological and morphological parameters and extraction of MRI biomarkers for vasculature. These could be used for treatment monitoring of novel therapeutic agents such as antiangiogenic drugs.

Infrared imaging as a novel method to evaluate the efficacy of a locoregional treatment in a Vx2 liver tumor model

BACKGROUND: The rabbit Vx2 liver tumor is a fast-growing carcinoma model commonly used to study tumor behaviours under cancer treatments. The reduction of tumor viability and the degree of induced necrosis are the common criteria to evaluate the efficacy of cancer treatments. Currently, it is not easy to perform a rapid and reproducible tissue quantification by histopathological analysis. OBJECTIVE: Our objective was to use infrared-imaging combined with linear-discriminant-analysis model (LDA) to automatically quantify the necrotic effect induced by doxorubicin-eluting-implants (DEI) on a Vx2 liver tumors model. METHODS: Three rabbits were subjected to DEI treatment and compared to a control group (CTRL) of nine rabbits. Tumor bearing livers were resected, fixed in formalin and embedded in paraffin. On two consecutive sections, we performed hematoxylin–eosin–saffron (HES) staining and infrared-imaging. Infrared-images were then subjected to the LDA-model analysis. RESULTS: The LDA and HES images strongly correlated for viable and necrotic tumor tissues. For the DEI group, the model determined that the surface of viable tumor represented 0.24 ± 5% of the tumor (CTRL: 55.71 ± 17%, P< 0.0001) and the necrotic tissue 66.46 ± 20% of the tumor (CTRL: 18.45 ± 12%, P< 0.0001). CONCLUSIONS: Our results showed that infrared-imaging coupled with LDA-model analysis could be a helpful to easily and objectively assess the treatment efficacy.

Combined Injection of 18F-Fluorodeoxyglucose and 3′-Deoxy-3′-[18F]fluorothymidine PET Achieves More Complete Identification of Viable Lung Cancer Cells in Mice and Patients than Individual Radiopharmaceutical: A Proof-of-Concept Study

PURPOSE: The objective is to validate the combination of 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) and 18F-fluorodeoxyglucose (18F-FDG) as a “novel” positron emission tomography (PET) tracer for better visualization of cancer cell components in solid cancers than individual radiopharmaceutical. METHODS: Nude mice with subcutaneous xenografts of human non-small cell lung cancer A549 and HTB177 cells and patients with lung cancer were included. In ex vivo study, intratumoral radioactivity of 18F-FDG, 18F-FLT, and the cocktail of 18F-FDG and 18F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, 18F-FDG PET and 18F-FLT PET were conducted in the same subjects (mice and patients) 10 to 14 hours apart. Second, PET scan was also performed 1 hour after one tracer injection; subsequently, the other was administered and followed the second PET scan in the mouse. Finally, 18F-FDG and 18F-FLT cocktail PET scan was also performed in the mouse. RESULTS: When injected individually, 18F-FDG highly accumulated in hypoxic zones and high 18F-FLT in proliferative cancer cells. In case of cocktail injection, high radioactivity correlated with hypoxic regions and highly proliferative and normoxic regions. PET detected that intratumoral distribution of 18F-FDG and 18F-FLT was generally mismatched in both rodents and patients. Combination of 18F-FLT and 18F-FDG appeared to map more cancer tissue than single-tracer PET. CONCLUSIONS: Combination of 18F-FDG and 18F-FLT PET imaging would give a more accurate representation of total viable tumor tissue than either tracer alone and would be a powerful imaging strategy for cancer management.

Reply to Letter re: General Theory of Predictive Dosimetry for Yttrium-90 Radioembolization to Sites Other Than the Liver

We fully approve the content of this Letter, as it provides a comprehensive roadmap on predictive dosimetry and aims at standardisation and good clinical practice for Yradioembolization to sites other than the liver. The field of application is well defined in the dosimetric assumptions and general points. The formulas are clear and applicable at any site. As stated in the introduction of this Letter, the safety and efficacy of selective internal radiotherapy (SIRT) is a combination of ‘‘technical’’ and ‘‘clinical’’ success. In this Reply, we would like to highlight some technical aspects that need special attention in order to achieve a therapeutic success. Before simulation with digital subtraction angiography and Tc-macroaggregated albumin (MAA), presimulation imaging should be performed by CT(or MRI-) angiography to detect vascular variants and abnormalities, to direct additional embolization of vessels, and to plan the most appropriate positioning of the catheter [1]. It is obvious that the position of the catheter and the flow rate should be similar for simulation and treatment. Therefore, it is important to choose a stable position of the catheter, as far as possible from any arterial bifurcation and to store the position of the tip of the catheter (e.g., by means of a screen capture) during simulation to assure a similar distribution of the Tc-MAA and Ymicrospheres. Posttreatment imaging can assess the distribution of the Y-microspheres and should be used to verify and validate the predictive dosimetry, especially in the setting of radioembolization to sites other than the liver. 3D distribution of the Y-microspheres can be assessed by Y-Bremsstrahlung Emission Computed Tomography (BECT) [2, 3] or Y-Time of Flight Positron emission tomography (TOF-PET) [4, 5]. Although the latter technique provides high-resolution images enabling quantification and real posttreatment dosimetry, its application is restricted to a research setting due to the very long acquisition times (at least the double compared to BECT) to obtain sufficient counts. As tissue mass is an essential component of the equations used for dosimetry, accurate delineation of volumesof-interest (VOI) is another technical challenge. For organs, the most obvious choice for estimation of the tissue mass is the volumes and radiographic densities derived from CT. However, the use of CT for delineation of viable tumour tissue, especially in small or necrotic target lesions often is less obvious. In this setting, functional imaging might be more appropriate for accurate VOI-delineation. Hybrid imaging by SPECT/CT is indeed a minimal technical requirement for optimal tissue delineation in SIRTdosimetry, but also requires standardization of the methodology used for VOI-delineation in order to enhance reproducibility and comparability of published data.

ROLE OF DIFFUSION – WEIGHTED MAGNETIC RESONANCE IMAGING IN CHARACTERIZATION OF VERTEBRAL BONE MARROW PATHOLOGICAL LESIONS

AIM: To evaluate the role of diffusion weighted magnetic resonance imaging in characterization of vertebral bone marrow pathological lesions. MATERIALS AND METHODS: Forty patients with bone marrow abnormal MRI signal intensity were enrolled in the study and upon MRI finding they wear grouped into four groups. DWI was performed with b values of 0and 500 s/ mm2. Results of the histo-pathological evaluation or MRI follow up or isotope were compared with the DWI results. Apparent diffusion coefficient (ADC) values were calculated. RESULTS: All cases of malignant collapse (4 cases 10%) were hyper intense on DWIs and hypo intense on ADC map with mean ADC (0.8 ± 0.33 x 10−3 mm2/s). All benign osteoporotic collapse cases (7 cases 17.5%) were hypo intense (3 cases) or iso to hypo intense (4 cases) on DWIs and all wear hyper intense on ADC with mean ADC (1.64 ± 0.33 x 10−3 mm2/s). Twelve cases with endplate changes, the eight infectious spondylitis recorded mean ADC value (1.03 ±0.33× 10−3mm2/s). The remaining, 4 cases (10 %) with degenerative Modic I end plate changes recorded ADC value (1.76 ±0.33× 10−3mm2/s). Also (3 cases) malignant bone marrow infiltration without collapse were hyperintense on DWIs and hypointense on ADC map with mean ADC (0.8 ± 0.33 x 10−3 mm2/s). The mean ADC in hemangioma was (1.9 ± 0.33 x 10−3 mm2/s) and in ABC (1.93 ± 0.33 x 10−3 mm2/s). DW study of 4 cases respond to therapy recorded mean ADC value (1.64 ±0.33× 10−3mm2/s), however, the 2 cases with residual viable tumor tissue record (0.79 ±0.33× 10−3mm2/s). DWI and ADC values have high sensitivity and specificity in differentiating benign from malignant lesions and in post therapy follow up. CONCLUSIONS: DWI with quantitative ADC measurements Using b value (b=500 s / mm2) can be useful in differentiating benign from malignant bone marrow lesions, differentiated between causes of end plate changes and be used in post therapy follow up. Keywords: Diffusion weighted imaging; Bone marrow; Vertebral compression fractures; Osteomyelitis; Therapy monitoring.

Noninvasive Assessment of Response to Neoadjuvant Chemotherapy in Osteosarcoma of Long Bones with Diffusion-Weighted Imaging: An Initial In Vivo Study

ObjectivesThe purpose of our study is to investigate whether diffusion-weighted imaging (DWI) is useful for monitoring the therapeutic response after neoadjuvant chemotherapy in osteosarcoma of long bones.Materials and methodsConventional magnetic resonance imaging (MRI) and DWI were obtained from 35 patients with histologically proven osteosarcomas. MR examinations were performed in all patients before and after 4 courses of preoperative neoadjuvant chemotherapy. Apparent diffusion coefficients (ADC) were measured. The degree of tumor necrosis was assessed macroscopically and histologically by two experienced pathologists after operation. Student’s t test was performed for testing changes in ADC value. Pearson’s correlation coefficient was used to estimate the correlation between necrosis rate and post- neoadjuvant chemotherapy ADC values. P<0.05 was considered to denote a significant difference.ResultsThe difference of the whole osteosarcoma between pre- neoadjuvant chemotherapy ADC value (1.24±0.17×10−3 mm2/s) and post- (1.93±0.39×10−3 mm2/s) was significant difference (P<0.01). Regarding in patients with good response, the post- neoadjuvant chemotherapy values were significantly higher than the pre- neoadjuvant chemotherapy values (P<0.01). The post- neoadjuvant chemotherapy ADC value in patients with good response was higher than that of poor response (t = 8.995, P<0.01). The differences in post- neoadjuvant chemotherapy ADC between viable (1.03±0.17×10−3 mm2/s) and necrotic (2.38±0.25×10−3 mm2/s) tumor was highly significant (t = 23.905, P<0.01). A positive correlation between necrosis rates and the whole tumor ADC values (r = 0.769, P<0.01) was noted, but necrosis rates were not correlated with the ADC values of necrotic (r = −0.191, P = 0.272) and viable tumor areas (r = 0.292, P = 0.089).ConclusionsDWI can identify residual viable tumor tissues and tumor necrosis induced by neoadjuvant chemotherapy in osteosarcoma. The ADC value can directly reflect the degree of tumor necrosis, and it is useful to evaluate the preoperative neoadjuvant chemotherapy response in patients with osteosarcoma.

Extraocular retinoblastoma in Indian children: clinical, imaging and histopathological features.

TO STUDY EYES WITH EXTRAOCULAR DISSEMINATION (EORB), WITH THE FOLLOWING AIMS: first to establish the mean lag period and to understand various reasons for delayed presentation, second to study their imaging profiles and third to analyze histopathological features of eyes enucleated after neoadjuvant chemotherapy. Prospective study of clinical and imaging features of EORBs (stage III and IV International Retinoblastoma Staging System) presenting to a tertiary eye care centre. Histopathological features of eyes enucleated after receiving neoadjuvant chemotherapy were analyzed. A pictorial illustration of the varied imaging profile of EORB was also presented. Over a period of one year, 97 eyes were diagnosed with retinoblastoma; 32 children (36 eyes) (37.1%) had EORB. Mean age 3.6±1.9 years, 71.9% males, 71.9% unilateral, 3.1% with positive family history and 40.6% with metastasis. On imaging, there was extrascleral involvement in 22.2%, involvement of orbital part of optic nerve in 33.3%, involvement of central nervous system in 27.8% and orbital wall involvement in 2.9% eyes. On histopathological analysis of eyes enucleated after neoadjuvant chemotherapy, 25.0% had no residual viable tumour tissue and rest all tumours were poorly differentiated. There are very few human malignancies where definitive treatment is started without any confirmed histopathological diagnosis and imaging plays an important role in diagnosis and appropriate staging of the disease. Chemotherapy has a variable effect on EORB, 75.0% of eyes with EORB had residual viable tumour tissue when enucleated after receiving neoadjuvant chemotherapy.