Tumor Diameter Measurements Research Articles

Criteria to Evaluate Tumor Enlargement During the Active Surveillance of High-Risk Thyroid Nodules: Which is Better, Diameter or Volume?

Tumor enlargement is the most common parameter identifying disease progression during active surveillance, but the value and significance of the changes in tumor diameter and volume in the evaluation of tumor growth have not been compared. This cohort study included 468 patients with high-risk thyroid nodule, in whom nodule size change was monitored using ultrasound, to compare the changes in tumor diameter and volume in assessing tumor growth. A total of 569 high-risk thyroid nodules were found in the 468 patients. A total of 14 nodules (2.5%) showed a diameter increase ≥ 3mm. The number of nodules with a peak volume change exceeding 50% and 100% was 185 (32.5%) and 86 (15.1%), respectively. Among the 555 stable nodules, the number of nodules with volume fluctuations exceeding 50% and 100% was 171 (30.8%) and 72 (13.0%), respectively. Among 212 stable nodules at the baseline and in the first three follow-up, the percentage of peak volume fluctuations exceeding 50% (48.5% vs. 28.5%, p = 0.004) and 100% (26.5% vs. 8.3%, p < 0.001) in the nodules with the sum of three diameters (SOTDs) ≤ 1cm was significantly higher than that of nodules with SOTDs > 1cm. A statistically significant difference was also found in the range distribution of SOTDs ≤ 1cm and SOTDs > 1cm (p = 0.007). Volume is not an appropriate method for determining tumor growth. Tumor diameter measurement alone serves as a better surrogate for disease progression in sonographically high-risk thyroid nodules than volume.

Reducing Gadolinium Exposure in Patients Undergoing Monitoring for Meningiomas.

Background Due to the non-malignant and slow-growing nature of many meningiomas, surveillance with serial magnetic resonance imaging (MRI) serves as an acceptable management plan. However, repeated imaging with gold-standard contrast-based studies may lead to contrast-associated adverse effects. Non-gadolinium T2 sequences may serve as a suitable alternative without the risk of adverse effects of contrast. Thus, this study sought to investigate the agreement between post-contrast T1 and non-gadolinium T2 MRI sequences in the measurement of meningioma growth. Methodology The Virginia Commonwealth University School of Medicine (VCU SOM) brain tumor database was used to create a cohort of meningioma patients and determine the number of patients who had T1 post-contrast imaging accompanied by readily measurable imaging from either T2 fast spin echo (FSE) or T2 fluid-attenuated inversion recovery (FLAIR) sequences. Measurements of the largest axial and perpendicular diameters of each tumor were conducted by two independent observers using T1 post-contrast, T2 FSE, and T2 FLAIR imaging series.Lin's concordance correlation coefficient (CCC) was calculated to assess inter-rater reliability between observers and agreement between measurements of tumor diameter among the different imaging sequences. Results In total, 33 patients (average age = 72.1 ± 12.9 years, 90% female) with meningiomas were extracted from our database, with 22 (66.7%) undergoing T1 post-contrast imaging accompanied with readily measurable imaging from T2 FSE and/or T2 FLAIR sequences. The inter-rater reliability between the measurements of T1 axial and perpendicular diameters was 0.96 (95% confidence interval (CI) = 0.92-0.98) and 0.92 (95% CI = 0.83-0.97), respectively. The inter-rater reliability between the measurements of T2 axial perpendicular diameters was 0.93 (95% = CI 0.92-0.97) and 0.89 (95% CI = 0.74-0.95), respectively. The agreements between the measurement of T1 and T2 FSE axial diameter by each observer were 0.97 (95% CI = 0.93-0.98) and 0.92 (95% CI = 0.81-0.97). The agreements between the measurements of T1 and T2 FSE perpendicular diameter measurements by each observer were 0.98 (95% CI = 0.95-0.99) and 0.88 (95% CI = 0.73-0.95). Conclusions Two-thirds of our patients had meningiomas that were readily measurable on either T2 FSE or T2 FLAIR sequences. Additionally, there was excellent inter-rater reliability between the observers in our study as well as an agreement between individual measurements of T1 post-contrast and T2 FSE tumor diameters. These findings suggest that T2 FSE may serve as a safe and similarly effective surveillance method for the long-term management of meningioma patients.

PET/MR versus PET/CT for locoregional staging of oropharyngeal squamous cell cancer.

The value of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for TN staging in head and neck cancer (HNC) has been proven in numerous studies. A few studies have investigated the value of FDG-PET/magnetic resonance imaging (MRI) in the staging of HNC; the combined results indicate potential for FDG-PET/MRI, but the scientific evidence remains weak. To compare performance of FDG-PET/CT and FDG-PET/MRI for locoregional staging in patients with oropharyngeal carcinomas. Two radiologists independently of each other retrospectively reviewed primary pre-therapeutic FDG-PET/CT and FDG-PET/MRI examinations from 40 individuals with oropharyngeal carcinomas. TN stage and primary tumor size were noted. The results were compared between observers and modalities and against TN stage set at a multidisciplinary conference. For nodal staging, PET/MRI had slightly higher specificity and accuracy than PET/CT for the most experienced observer. Both methods demonstrated excellent sensitivity (≥ 0.97 and 1.00, respectively), as well as high negative predictive values (≥ 0.95 and 1.00, respectively). No significant differences were found for tumor staging or measurement of maximum tumor diameter. There was a weak agreement (κ = 0.35-0.49) between PET/CT and PET/MRI for T and N stages for both observers. Inter-observer agreement was higher for PET/MRI than for PET/CT, both for tumor staging (κ = 0.57 vs. 0.35) and nodal staging (κ = 0.69 vs. 0.55). The agreement between observers was comparable to the agreement between methods. PET/MRI may be a viable alternative to PET/CT for locoregional staging (TN staging) and assessment of maximal tumor diameter in oropharyngeal squamous cell cancer.

Diagnostic Assessment of Deep Learning Algorithms for Frozen Tissue Section Analysis in Women with Breast Cancer.

Assessing the metastasis status of the sentinel lymph nodes (SLNs) for hematoxylin and eosin-stained frozen tissue sections by pathologists is an essential but tedious and time-consuming task that contributes to accurate breast cancer staging. This study aimed to review a challenge competition (HeLP 2019) for the development of automated solutions for classifying the metastasis status of breast cancer patients. A total of 524 digital slides were obtained from frozen SLN sections: 297 (56.7%) from Asan Medical Center (AMC) and 227 (43.4%) from Seoul National University Bundang Hospital (SNUBH), South Korea. The slides were divided into training, development, and validation sets, where the development set comprised slides from both institutions and training and validation set included slides from only AMC and SNUBH, respectively. The algorithms were assessed for area under the receiver operating characteristic curve (AUC) and measurement of the longest metastatic tumor diameter. The final total scores were calculated as the mean of the two metrics, and the three teams with AUC values greater than 0.500 were selected for review and analysis in this study. The top three teams showed AUC values of 0.891, 0.809, and 0.736 and major axis prediction scores of 0.525, 0.459, and 0.387 for the validation set. The major factor that lowered the diagnostic accuracy was micro-metastasis. In this challenge competition, accurate deep learning algorithms were developed that can be helpful for making a diagnosis on intraoperative SLN biopsy. The clinical utility of this approach was evaluated by including an external validation set from SNUBH.

Functional tumor diameter measurement with molecular breast imaging: development and clinical application

Purpose: Molecular breast imaging (MBI) is used clinically to visualize the uptake of 99mTc-sestamibi in breast cancers. Here, we use Monte Carlo simulations to develop a methodology to estimate tumor diameter in focal lesions and explore a semi-automatic implementation for clinical data. Methods: A validated Monte Carlo simulation of the GE Discovery NM 750b was used to simulate >75,000 unique spherical/ellipsoidal tumor, normal breast, and image acquisition conditions. Subsets of this data were used to 1) characterize the dependence of the full-width at half-maximum (FWHM) of a tumor profile on tumor, normal breast, and acquisition conditions, 2) develop a methodology to estimate tumor diameters, and 3) quantify the diameter accuracy in a broad range of clinical conditions. Finally, the methodology was implemented in patient images and compared to diameter estimates from physician contours on MBI, mammography, and ultrasound imaging. Results: Tumor profile FWHM was determined be linearly dependent on tumor diameter but independent of other factors such as tumor shape, uptake, and distance from the detector. A linear regression was used to calculate tumor diameter from the FWHM estimated from a background-corrected profile across a tumor extracted from a median-filtered single-detector MBI image, i.e., diameter = 1.2 mm + 1.2 × FWHM, for FWHM ≥ 13 mm. Across a variety of simulated clinical conditions, the mean error of the methodology was 0.2 mm (accuracy), with >50% of cases estimated within 1-pixel width of the truth (precision). In patient images, the semi-automatic methodology provided the longest diameter in 94% (60/64) of cases. The estimated true diameters, for oval lesions with homogeneous uptake, differed by ± 5 mm from physician measurements. Conclusion: This work demonstrates the feasibility of accurately quantifying tumor diameter in clinical MBI, and to our knowledge, is the first to explore its implementation and application in patient data.

Tumor Size Measurements for Predicting Hodgkin's and Non-Hodgkin's Lymphoma Response to Treatment.

The purpose of this study was to investigate the value of tumor size measurements as prognostic indicators of treatment outcome of Hodgkin’s and Non-Hodgkin’s lymphomas. 18F-FDG PET/CT exams before and after treatment were analyzed and metabolic and anatomic parameters—tumor maximum diameter, tumor maximum area, tumor volume, and maximum standardized uptake value (SUVmax)—were determined manually by an expert and automatically by a computer algorithm on PET and CT images. Results showed that the computer algorithm measurements did not correlate well with the expert’s standard maximum tumor diameter measurements but yielded better three dimensional metrics that could have clinical value. SUVmax was the strongest prognostic indicator of the clinical outcome after treatment, followed by the automated metabolic tumor volume measurements and the expert’s metabolic maximum diameter measurements. Anatomic tumor measurements had poor prognostic value. Metabolic volume measurements, although promising, did not significantly surpass current standard of practice, but automated measurements offered a significant advantage in terms of time and effort and minimized biases and variances in the PET measurements. Overall, considering the limited value of tumor size in predicting response to treatment, a paradigm shift seems necessary in order to identify robust prognostic markers in PET/CT; radiomics, namely combinations of anatomy, metabolism, and imaging, may be an option.

MRI Volumetrics and Image Texture Analysis in Assessing Systemic Treatment Response in Extra-Abdominal Desmoid Fibromatosis.

Purpose To determine whether MRI volumetric and image texture analysis correlates with treatment-induced biologic changes in desmoid fibromatosis (DF) earlier than conventional response criteria. Materials and Methods This retrospective study included 27 patients with histologically proven extra-abdominal DF who were managed with active surveillance or systemic therapy (from 2004 to 2016). MRI volumetric and image texture parameters were derived from manual tumor segmentations, and tumor signal intensity was normalized to muscle. Results were compared with objective response rates based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, World Health Organization (WHO) lesion response, volumetrics, and MRI-modified Choi criteria. Correlation coefficients (r) between image texture features and maximum tumor diameters were obtained by using a meta-analysis approach. Results The 27 included patients (mean age, 39 years; 74% women) were followed for an average of 4 years, comprising 207 distinct time-point assessments. The mean baseline tumor maximum diameter was 7.9 cm (range, 3.4-15.2 cm). Partial response (PR) rates as best response were 37%, 44%, 70%, and 81% by RECIST, WHO, volumetrics, and MRI-modified Choi criteria, respectively. Among the 10 tumors showing RECIST PR, a preceding MRI-modified Choi PR was observed in 70% (seven of 10), on average 1.3 years earlier. Multiple image texture parameters showed associations with objective measurements of tumor diameter including mean tumor-to-muscle signal ratio (r = 0.51; P = .004), median tumor-to-muscle signal ratio (r = 0.52; P = .003), energy (r = 0.48; P < .001), run entropy (r = 0.32, P = .04), and gray-level nonuniformity (r = 0.54; P ≤ .001). Conclusion Volumetric signal and image texture assessment allows more comprehensive analysis of DF biologic change and may permit early prediction of DF behavior and therapeutic response. Keywords: MR Imaging, Soft Tissues/Skin, Neoplasms-Primary © RSNA, 2021.

468 Is topical remetinostat gel an effective and safe treatment for basal cell carcinoma? Results of a phase 2, open label, single arm trial

Surgical excision remains the gold standard treatment for basal cell carcinoma (BCC). However, it is associated with potential morbidity, particularly for patients with multiple or recurrent tumors. To identify novel treatment option for BCC, we previously used molecular data from human BCCs to conduct a drug repositioning screen. Our results identified histone deacetylase (HDAC) inhibitors as the leading predicted therapeutic, strongly opposing the BCC gene-expression signature. We conducted a phase 2, open label, single arm and institution trial of the topical pan-HDAC inhibitor, remetinostat, as the first proof-of-principle study of this medication class for BCC. Participants with at least one BCC referred for excision at Stanford were recruited and instructed to apply 1% remetinostat gel three times daily for six weeks. Measurements of tumor diameter and photography were conducted at baseline and week 8, and remaining tumor was then excised for histological examination, with a subset also sent for immunohistochemistry (IHC). 25 participants with 33 BCCs were included in the per-protocol analysis. The objective response rate (the proportion of tumors achieving at least a 30% decrease in the longest diameter from baseline to week 8) was 69.7% (90% confidence interval 54-82.5%), and 54.8% of the tumors demonstrated complete resolution on histological examination. IHC staining supported the pharmacodynamic effect of the remetinostat, demonstrating increased acetylated histone H3 in the excised biopsies compared to baseline. No systemic adverse events were reported, and the medication was well tolerated. Remetinostat, a topical pan-HDAC inhibitor, is a safe and effective topical treatment for BCC, reducing disease burden in a clinically significant manner. Our results provide the first in-human validation of HDAC inhibitors as a potential therapeutic.

Liver tumor F-18 FDG-PET before and immediately after microwave ablation enables imaging and quantification of tumor tissue contraction.

Poor liver tumor visibility after microwave ablation (MWA) limits direct tumor ablation margin assessments using contrast-enhanced CT or ultrasound (US). Positron emission tomography (PET) or PET/CT may offer improved intraprocedural assessment of liver tumor ablation margins versus current imaging techniques, as 18F-fluorodeoxyglucose (18F-FDG)-avid tumors remain visible on PET immediately following ablation. The purpose of this study was to assess intraprocedural 18F-FDG PET scans before and immediately after PET/CT-guided MWA for visualization and quantification of metabolic liver tumor tissue contraction resulting from MWA. This retrospective study, conducted at a large academic medical center after Institutional Review Board approval, included 36 patients (20 men; mean age 63 [range 37-85]) who underwent PET/CT-guided MWA of 42 18F-FDG-avid liver tumors from May 2013 to March 2018. Tumor metabolic diameters (short/long axes) were measured for each tumor on pre- and post-ablation PET images. Tumor metabolic volumes were calculated using tumor diameter measurements and compared with automated volumes using an SUV threshold algorithm. A two-tailed paired t test was used for the analyses. Comparing intraprocedural pre- and post-ablation PET images, mean metabolic tumor short- and long-axis diameters decreased from 21.4 to 14.9 mm [- 29%, p < 0.001, standard deviation (SD) 18%] and from 24.0 to 18.0 mm (- 24%, p < 0.001, SD 16%), respectively. The mean calculated tumor metabolic volume decreased from 10.5 to 4.6 mm3 (- 55%, p < 0.001, SD 26%). The mean automated tumor metabolic volume decreased from 10.6 to 5.8 mm3 (- 45%, p < 0.001, SD 30%). Intraprocedural PET images of 18F-FDG-avid liver tumors allow visualization and quantification of MWA-induced metabolic tumor tissue contraction during 18F-FDG PET/CT-guided procedures. The ability to visualize contracted tumor immediately post-MWA may facilitate emerging intraprocedural PET and PET/CT imaging techniques that address a clinical gap in directly assessing the ablation margin.

Evaluation of 20-MHz high-frequency ultrasonography for the diagnosis of choroidal nevi.

Evaluate short-term intraoperator reproducibility of ultrasonographic measurements of choroidal nevi using 10- and 20-MHz probes, and the efficacy of the high-frequency probes for the diagnosis of choroidal nevi. Diameters and thicknesses of choroidal nevi were measured using a 10-MHz probe and a high-frequency long focal length 20-MHz probe (Quantel Medical™). The first part of the study evaluated intraoperator reproducibility of measurements of choroidal nevi with 10- and 20-MHz probes and the second part of the study allowed the comparisons of the measurements of largest tumor diameter (LDT) of choroidal nevi of 40 patients between the 10- and 20-MHz probes. The two-way random average agreement intraclass correlation coefficients (ICC), Bland-Altman plot, and a paired t test were used. The intraoperator reproducibility of choroidal nevi measurements with 10- and 20-MHz probes was excellent (ICC > 0.9, n = 20). Four flat nevi, not detectable at 10MHz, could be located with the high-frequency probe (p = 0.12). There was no significant difference in thickness or LTD measurements between the 10- and 20-MHz probes (n = 31). Both techniques showed an excellent agreement (ICC > 0.8) for thickness and LTD measurements. All the choroidal nevi that were not measurable with the 10-MHz probe (n = 7) were measured with the 20-MHz probe. The high-frequency 20-MHz probe allows additional detection and measurements of flat choroidal nevi. When detectable, the ultrasonographic measurements of thickness and diameter of choroidal nevi are similar with both the 10- and the 20-MHz probes.

Application of Enhanced CT and Enhanced MRI Fusion Image in the Treatment of Primary Liver Cancer

Objective: To provide a decision-making opinion for the clinical selection of treatment options by comparing the preoperative enhanced CT and enhanced MRI scan images of liver transplantation for primary liver cancer with the tumor diameter measurement of postoperative gross specimens. Methods: Nine patients with primary liver cancer who underwent liver transplantation from January 2017 to January 2018 were enrolled. The patients were not treated with local treatment before surgery. Previous imaging studies showed nodular liver cancer. 64-slice spiral CT plain scan+three-stage enhanced scan, 3.0T superconducting MRI scan conventional plain scan, postoperative gross specimen anatomy, record tumor location, number, maximum diameter, compare different imaging techniques and postoperative gross specimens The coincidence rate of the maximum diameter of the same tumor (according to the standard is the maximum diameter difference between the imaging and the gross specimen of the postoperative specimen ≤5 mm), the difference between the groups, and the correlation between the groups. Results: The maximum diameter of the same tumor was measured. The coincidence rate between CT and postoperative gross specimens was 22%. The difference was statistically significant (P = −0.017), the correlation coefficient was 0.928, and the coincidence rate between MRI and postoperative gross specimen was 44%. The difference was statistically significant (P = −0.010) and the correlation coefficient was 0.979. Conclusion: Image fusion technology with enhanced CT and enhanced MRI has changed the treatment decision of some patients with liver cancer, and it has certain value for optimizing treatment.

Lipid-weighted intraoperative photoacoustic tomography of breast tumors: Volumetric comparison to preoperative MRI

With a lifetime risk of 1 in 8, breast cancer continues to be a major concern for women and their physicians. The optimal treatment of the disease depends on the stage of the cancer at diagnosis, which is typically assessed using medical imaging. However, currently employed imaging systems for breast tumor measurement rarely agree perfectly.Our group developed an Intraoperative Photoacoustic Screening (iPAS) soft tissue scanner featuring high bulk tissue sensitivity, a clinically compatible scan-time of 6 min, imaging depths greater than 2 cm and the capability to visualize whole breast tumors based on their lipid, rather than hemoglobin, profile. Here, we report on the first clinical experience with breast cancer patients by comparing tumor-measurement using iPAS, preoperative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and gold-standard pathology. Tumor size was measured volumetrically for iPAS and DCE-MRI, and separately using maximum diameters for pathology, DCE-MRI and iPAS. Comparisons were performed using Pearson’s correlation coefficients, and the non-parametric Wilcoxon signed-rank test.Twelve consecutive patients were included in the study, contingent on pathologically documented invasive carcinoma. iPAS volumetric tumor size was positively correlated to DCE-MRI (Pearson’s r = 0.78, p = 0.003) and not significantly different (Wilcoxon, p = 0.97). In comparison to pathology, tumor diameters given by iPAS were positively correlated (Pearson’s r = 0.87, p = 0.0002) and significantly different (Wilcoxon, p = 0.0015).The results indicated that volumetric-measurement of invasive breast tumors with iPAS is similar to that of DCE-MRI. On the other hand, tumor diameter measurements were less reliable. Beyond enhancing surgical specimen examination, an extension of this technology to diagnostic imaging promises a new perspective on tumor assessment, potentially improving our current understanding and treatment of breast cancer.

Interobserver size measurement variability in part-solid lung adenocarcinoma using pre-operative computed tomography.

In the current lung cancer tumor-node-metastasis classification, solid tumor size is used for tumor diameter measurement as the dense component. However, measuring solid tumor size is sometimes difficult and inter-observer variability may increase, particularly in part-solid nodules with ground-glass opacity (GGO). This study aimed to investigate inter-observer size measurement variability in lung adenocarcinoma. Of 47 patients with part-solid lung adenocarcinoma who had undergone surgery at our department from January to December 2016, five surgeons and one radiologist undertook unidimensional solid and total size tumor measurements using pre-operative axial computed tomography images, and we assessed inter-observer size measurement variability. Variability was then subclassified into five groups, according to computer tomography-identified tumor morphological characteristics, namely: (I) minimally invasive; (II) peribronchovascular; (III) spiculation/atelectasis; (IV) adjacent to cystic lesion, and; (V) diffuse consolidation and GGO. The mean inter-observer variability was 9.7 mm (solid size) and 7.7 mm (total size). Analysis of the maximum and minimum measurement size values for each patient undertaken showed that the most experienced surgeon and the radiologist measured the minimum size more frequently. To correct for differences in mean tumor diameter in each group, a comparison was made using a coefficient of variation (CV) calculated as the ratio of the standard deviation to the mean. Group I characteristics showed the largest coefficient value for variation in solid size measurement. Inter-observer measurement variability for solid size was larger than for total size in lung adenocarcinoma. Large variability in group I indicated the difficulty of size measurement for low-grade malignant potential nodules such as adenocarcinoma in situ, minimally invasive adenocarcinoma, and early-stage invasive adenocarcinoma. The possibility of unavoidable size measurement variability should be recognized when deciding on surgical procedures for these diseases.

Assessment of uveal melanomas using advanced diffusion-weighted imaging techniques: value of reduced field of view DWI ("zoomed DWI") and readout-segmented DWI (RESOLVE).

Background Diffusion-weighted imaging (DWI) has become an important tool for lesion characterization. Advanced techniques of DWI may be used to improve image quality. Purpose To evaluate multi-shot segmented DWI (rs-EPI, RESOLVE) and reduced field-of view DWI (rFOV-EPI, “zoomed” EPI) in patients with ocular melanoma and to compare image quality and diagnostic performance in differentiation of melanoma from retinal detachment. Material and Methods In this prospective and IRB-approved trial, we examined 26 patients using methods including conventional single-shot echo-planar DWI (ss-EPI), rs-EPI, and rFOV-EPI. Subjective image quality was compared using a four-point score and the maximum tumor length was measured in all sequences. Apparent diffusion coefficient (ADC) measurements were performed using a region-of interest analysis. Tumor delineation and differences in ADC values between melanomas and retinal detachments were compared. Results Diffusion restriction was markedly reduced in melanomas in all applied image techniques. Subjective image quality was significantly higher for rFOV-EPI (score = 3.5 ± 0.5) compared with rs-EPI (score = 3.3 ± 0.6) and ss-EPI (score = 2.5 ± 0.9). Regarding tumor diameter measurements, rFOV-EPI showed the best agreement compared with high-resolution conventional sequences. ADC measurements of the tumor and retinal detachment differed significantly ( P &lt; 0.001) with the rFOV-EPI performing best (sensitivities and specificities compared with T1-weighted ss-EPI 61%/82%; rFOV-EPI 86%/92%; rs-EPI 79%/92%, respectively). Conclusion rFOV-EPI showed improved image quality compared with ss-EPI and rs-EPI, the most accurate tumor delineation and the best differentiation from retinal detachments in our patients.

ED05.01 What’s New in Lung Cancer Staging?

The tumor, node and metastasis (TNM) classification for malignant tumors has been periodically revised in the International Union for Cancer Control (UICC) and American Joint Committee on Cancer (AJCC). As for lung cancer, the process of revision is quite unique compared with malignancies of other organs in that the corresponding professional society, the International Association for the Study of Lung Cancer (IASLC), has been playing a principal role in database construction, making revision agenda, simulation, and validation as a proposal to UICC and AJCC. The agenda articles have been already published for T, N, M, and stage grouping in the official journal of IASLC. In brief, the IASLC database included 77,156 evaluable patients diagnosed with lung cancer from 1999 to 2010, originating from 35 different databases in 16 countries of 5 continents. Among these, the data of 3905 patients were given by electric data capturing. In the T descriptors, new tumor-size groups were created: T1a </= 1cm; T1b >1-2 cm; T1c >2-3cm; T2a >3-4cm; T2b >4-5cm; T3 >5-7cm; and T4 >7cm. Endobronchial location <2cm from the carina has better prognosis than any other T3 descriptor and will be classified as T2. Total atelectasis/pneumonitis will be classified as T2 because it has a T2 prognosis. Diaphramatic invasion will be T4. Visceral pleural invasion remains the same, and mediastinal pleura invasion, seldom used, disappears as a T descriptor. The N component remains the same, but the number of involved nodal stations has prognostic impact. Therefore, it was proposed to divide N1 into N1a (single station N1) and N1b (multiple station N1), N2 into N2a1 (single station N2 without pN1 involvement), N2a2 (single station N2 with pN1 involvement) and N2b (multiple station N2) for testing. For the M component, M1a (intrathoracic metastases) remains the same, but extrathoracic metastases are divided into single extrathoracic metastasis (new M1b) and multiple extrathoracic metastases in a single or multiple organs (M1c). Regarding stages, stage IA is divided into IA1, IA2 and IA3 to accommodate T1a, T1b and T1cN0M0 tumors; all N1 disease are stage IIB except for T3-T4N1M0 that are IIIA; a new stage IIIC is created for T3-T4N3M0 tumors; and stage IV is divided into IVA (M1a and M1b) and IVB (M1c). The 8th edition of the TNM classification of lung cancer defines new tumor-size groups, confirms the prognostic relevance of quantifying nodal disease, establishes a new category for single extrathoracic metastasis, and creates new stage groupings. Looking at these, the importance of the accurate measurement of tumor diameter and accurate counting of the swollen nodes and lesions of distant disease has been raised. In this way it improves our understanding of the anatomic extent of the tumor, enhances, our capacity to indicate prognosis at clinical and pathologic staging, and increases the possibilities of research by facilitating tumor stratification for future clinical trials. Prognosis, TNM classification, Staging, lung cancer

A99: The influence of live Streptococcus pyogenes on the growth of solid murine tumors

Ability of Streptococcus pyogenes to fight cancer was discovered and clinically tested more than 100 years ago (Coley, 1897), but the mechanisms of these effects are unknown. Recently several murine models demonstrating the anti-cancer activity of Group A Streptococcus (GAS) M49 were established (Maletzki, 2008). The present study is devoted to investigation of anti-cancer activity of GAS M39 strains. Materials and Methods Tumor cells were injected subcutaneously in concentration of 200,000 cells per animal. Two solid tumor models were used: hepatoma 22a in C3HA mice and sarcoma 37 in Swiss mice. GAS (wild and mutant strains) were injected into the tumor 2 × 104 per animal twice with a 5-day-interval. The influence of GAS on tumor growth was evaluated by measurement of tumor diameter and animal survival. Inactivation of M protein (emm) gene was generated by insertional mutagenesis after cloning the fragment of the emm gene in suicidal plasmid pT7ermB.The plasmid was introduced into GAS by electroporation. Insertion had been proved by DNA sequencing. Results Intratumoral injections of wild GAS M39 strain did not influence on tumor size in mice bearing hepatoma 22a and sarcoma 37. The second injection of GAS enhanced inhibition of the tumor growth, but increased the death rates. The treatment by emm mutant strain caused the inhibition of tumor growth and showed less mortality rate both tumor models. The average number of completely cured animals was 10%. Conclusion Inactivation of emm gene in GAS M39 strain resulted in increased anti-tumor activity and decreased lethality rate. We hypothesized that the absence of anti-phagocytic M protein may increase phagocytosis of GAS by macrophages and thus enhance their antitumor activity.

Value of the preoperative TNM staging and the longest tumor diameter measurement of gastric cancer evaluated by MSCT

To explore the value of MSCT in the preoperative TNM staging and the longest tumor diameter measurement (RESIST standard) of gastric cancer. Clinical data of 153 consecutive patients with biopsy-confirmed gastric carcinoma who were preoperatively evaluated with enhanced MSCT scanning in our hospital from January 2012 to March 2013 were retrospectively analyzed. Consistency comparison was performed between preoperative TNM staging and the longest tumor diameter measurement and histopathological findings. T-staging consistency of Kappa value was 0.566, and accuracy was 71.2%. N-staging consistency of Kappa value was 0.284, and accuracy was 47.7%. The Kappa value of M-staging consistency was 0.893, and accuracy was 98.7%. The overall accuracy of TNM staging consistency was 66.7% (102/153) with a Kappa value of 0.573. Effective measurement of the longest cancer diameter was carried out in 53 patients. There was no significant difference between preoperative longest tumor diameter acquired by MSCT and postoperative tumor measurement [(68.8 ± 40.6) mm vs. (64.2 ± 36.2) mm, P=0.969]. MSCT is accurate in preoperative TNM staging and longest tumor diameter measurement of gastric cancer compared with postoperative pathological examination, and can provide reliable evidence for preoperative staging and neoadjuvant therapy evaluation of gastric cancer, but it is unfavorable to evaluate the lymph node metastasis.

Synthesis, characterization and theranostic evaluation of Indium-111 labeled multifunctional superparamagnetic iron oxide nanoparticles

Indium-111 labeled, Trastuzumab-Doxorubicin Conjugated, and APTES-PEG coated magnetic nanoparticles were designed for tumor targeting, drug delivery, controlled drug release, and dual-modal tumor imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by thermal decomposition method to obtain narrow size particles. To increase SPIONs circulation time in blood and decrease its cytotoxicity in healthy tissues, SPIONs surface was modified with 3-Aminopropyltriethoxy Silane (APTES) and then were functionalized with N-Hydroxysuccinimide (NHS) ester of Polyethylene Glycol Maleimide (NHS-PEG-Mal) to conjugate with thiolated 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid (PCTA) bifunctional chelator (BFC) and Trastuzumab antibody. In order to tumor SPECT/MR imaging, SPIONs were labeled with Indium-111 (T1/2=2.80d). NHS ester of monoethyl malonate (MEM-NHS) was used for conjugation of Doxorubicin (DOX) chemotherapeutic agent onto SPIONs surface. Mono-Ethyl Malonate allows DOX molecules to be attached to SPIONs via pH-sensitive hydrazone bonds which lead to controlled drug release in tumor region. Active and passive tumor targeting were achieved through incorporated anti-HER2 (Trastuzumab) antibody and EPR effect of solid tumors for nanoparticles respectively. In addition to in vitro assessments of modified SPIONs in SKBR3 cell lines, their theranostic effects were evaluated in HER2 + breast tumor bearing BALB/c mice via biodistribution study, dual-modal molecular imaging and tumor diameter measurements.

The observation indicator induced from gastrointestinal stromal tumor under long-term monitoring by endoscopic ultrasonography

We report a case of low-risk stomach gastrointestinal stromal tumor (GIST) which has been under a long-term observation, obtaining from this experience knowledge useful in determining the treatment formula for this disease. During the observation for 6 years, no such change as ulcer formation was observed in the appearance of the tumor. The measurement of tumor diameter, however, showed gradual growth of maximum tumor diameter from 2.7 to 5.0 cm. When the changes in the diameter of tumor during this period is plotted, taking the timeon the horizontal axis and the tumor diameter on the vertical axis, the growth of the tumor can be approximated with a secondary function, making it possible to estimate the developmental period of the GIST concerned from the approximated secondary function. Thus, the developmental period in this case was estimated to go back 19 years before the time when it was discovered for the 1(st) time. Further, it was considered that the coefficient of the secondary function represents the rate of tumor growth, and that comparison with this coefficient contributed to the evaluation of malignancy stage of the GIST concerned. The growth curve predicting the growth of tumor could be depicted by measuring the diameter of the tumor in GIST twice or more at an interval of 6-12 months with EUS, and it was thought that this was utilizable for determining treatment formula for GISTs.

Inter-observer reproducibility of semi-automatic tumor diameter measurement and volumetric analysis in patients with lung cancer

ObjectivesTherapy monitoring in oncologic patient requires precise measurement methods. In order to improve the precision of measurements, we used a semi-automated generic segmentation algorithm to measure the size of large lung cancer tumors. The reproducibility of computer-assisted measurements were assessed and compared with manual measurements. MethodsCT scans of 24 consecutive lung cancer patients who were referred to our hospital over a period of 6 months were analyzed. The tumor sizes were measured manually by 3 independent radiologists, according to World Health Organization (WHO) and the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. At least 10 months later, measurements were repeated semi-automatically on the same scans by the same radiologists. The inter-observer reproducibility of all measurements was assessed and compared between manual and semi-automated measurements. ResultsManual measurements of the tumor longest diameter were significantly (p<0.05) smaller compared with the semi-automated measurements. The intra-rater correlations coefficients were significantly higher for measurements of longest diameter (intra-class correlation coefficients: 0.998 vs. 0.986; p<0.001) and area (0.995 vs. 0.988; p=0.032) using semi-automated compared with manual method. The variation coefficient for manual measurement of the tumor area (WHO guideline, 15.7% vs. 7.3%) and the longest diameter (RECIST guideline, 7.7% vs. 2.7%) was 2–3 times that of semi-automated measurement. ConclusionsBy using computer-assisted size assessment in primary lung tumor, interobserver-variability can be reduced to about half to one-third compared to standard manual measurements. This indicates a high potential value for therapy monitoring in lung cancer patients.