Impact of baseline and interim quantitative PET parameters on outcomes of classical Hodgkin Lymphoma.

Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUVmax], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (ΔSUVmax, ΔTMTV and ΔTLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4-5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUVmax, TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among ΔSUVmax, ΔTMTV and ΔTLG, only a ΔSUVmax ≥ 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11-0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (ΔSUVmax ≥ 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the ΔSUVmax to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification.

Significance of radiologic extranodal extension in locoregionally advanced nasopharyngeal carcinoma with lymph node metastasis: a comprehensive nomogram.

OBJECTIVE: We aimed to assess the significance of rENE and creat a predictive tool (nomogram) for estimating Overall Survival (OS) in locoregionally advanced Nasopharyngeal Carcinoma (NPC) patients with Lymph Node Metastasis (LNM) based on their clinical characteristics and Radiologic Extranodal Extension (rENE). METHODS: Five hundred and sixty-nine NPC patients with LNM were randomly divided into training and validation groups. Significant factors were identified using univariate and multivariate analyses in the training cohort. Then, the nomogram based on the screening results was established to predict the Overall Survival (OS). Calibration curves and the Concordance index (C-index) gauged predictive accuracy and discrimination. Receiver Operating Characteristic (ROC) analysis assessed risk stratification, and clinical utility was measured using Decision Curve Analysis (DCA). The nomogram's performance was validated for discrimination and calibration in an independent validation cohort. RESULTS: A total of 360 (63.2%) patients were present with radiologic extranodal extension at initial diagnosis. Patients with rENE had significantly lower OS than other patients. Multivariate analysis identified the five factors, including rENE, for the nomogram model. The C-index was 0.75 (0.71-0.78) in the training cohort and 0.76 (0.69-0.83) in the validation cohort. Notably, the nomogram outperformed the 8th TNM staging system, as evident from the higher AUC values (0.77 vs. 0.60 for 2year and 0.75 vs. 0.65 for 3year) and well-calibrated calibration curves. Decision curve analysis indicated improved Net Benefit (NB) with the nomogram for predicting OS. The log-rank test confirmed significant survival distinctions between risk groups in both training and validation cohorts. CONCLUSIONS: We demonstrated the prognostic value of rENE in nasopharyngeal carcinoma and developed a nomogram based on rENE and other factors to provide individual prediction of OS for locoregionally advanced nasopharyngeal carcinoma with lymph node metastasis. LEVEL OF EVIDENCE: III.

Significance of radiologic extranodal extension in locoregionally advanced nasopharyngeal carcinoma with lymph node metastasis: a comprehensive nomogram

Abstract Objective We aimed to assess the significance of rENE and creat a predictive tool (nomogram) for estimating Overall Survival (OS) in locoregionally advanced Nasopharyngeal Carcinoma (NPC) patients with Lymph Node Metastasis (LNM) based on their clinical characteristics and Radiologic Extranodal Extension (rENE). Methods Five hundred and sixty-nine NPC patients with LNM were randomly divided into training and validation groups. Significant factors were identified using univariate and multivariate analyses in the training cohort. Then, the nomogram based on the screening results was established to predict the Overall Survival (OS). Calibration curves and the Concordance index (C-index) gauged predictive accuracy and discrimination. Receiver Operating Characteristic (ROC) analysis assessed risk stratification, and clinical utility was measured using Decision Curve Analysis (DCA). The nomogram's performance was validated for discrimination and calibration in an independent validation cohort. Results A total of 360 (63.2%) patients were present with radiologic extranodal extension at initial diagnosis. Patients with rENE had significantly lower OS than other patients. Multivariate analysis identified the five factors, including rENE, for the nomogram model. The C-index was 0.75 (0.71-0.78) in the training cohort and 0.76 (0.69-0.83) in the validation cohort. Notably, the nomogram outperformed the 8th TNM staging system, as evident from the higher AUC values (0.77 vs. 0.60 for 2 year and 0.75 vs. 0.65 for 3 year) and well-calibrated calibration curves. Decision curve analysis indicated improved Net Benefit (NB) with the nomogram for predicting OS. The log-rank test confirmed significant survival distinctions between risk groups in both training and validation cohorts. Conclusions We demonstrated the prognostic value of rENE in nasopharyngeal carcinoma and developed a nomogram based on rENE and other factors to provide individual prediction of OS for locoregionally advanced nasopharyngeal carcinoma with lymph node metastasis. Level of evidence: III.

Imaging nodal volume and survival in oral tongue cancer with cervical lymph node metastasis.

OBJECTIVES: Oral tongue cancer is the most prevalent type of oral cavity cancer and presents the worst prognosis. With the use of TNM staging system, only the size of primary tumor and lymph node are considered. However, several studies have considered the primary tumor volume as a possible significant prognostic factor. Our study, therefore, aimed to explore the role of nodal volume from imaging as a prognostic implication. METHODS: Medical records and imaging (either from Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan) of 70 patients diagnosed with oral tongue cancer with cervical lymph node metastasis between January 2011 and December 2016 were retrospectively reviewed. The pathological lymph node was identified, and nodal volume was measured using the Eclipse radiotherapy planning system and was further analysed for its prognostic implications, particularly on overall survival, disease-free survival, and distant metastasis-free survival. RESULTS: From A Receiver Operating Characteristic (ROC) curve analysis, the optimal cut-off value of the nodal volume was 3.95 cm3, to predict the disease prognosis, in terms of overall survival and metastatic-free survival (p ≤ 0.001 and p = 0.005, respectively), but not the disease-free survival (p = 0.241). For the multivariable analysis, the nodal volume, but not TNM staging, was a significant prognostic factor for distant metastasis. CONCLUSIONS: In patients with oral tongue cancer and cervical lymph node metastasis, the presence of an imaging nodal volume of ≥3.95 cm3 was a poor prognostic factor for distant metastasis. Therefore, the lymph node volume may have a potential role to adjunct with the current staging system to predict the disease prognosis. LEVEL OF EVIDENCE: 2b.

The effect of primary tumor volume on the prognosis of nasopharyngeal carcinoma in era of volumetric modulated arc therapy: a propensity score matched cohort study

Abstract Objective The role of Primary Tumor Volume (PTV) in Nasopharyngeal Carcinoma (NPC) treated with Volumetric Modulated Arc Therapy (VMAT) is still unclear. The aim of this study was to access the effect of PTV in prognosis prediction of nasopharyngeal carcinoma in era of VMAT. Methods Between January 20 and November 2011, 498 consecutive NPC patients with stage I-IVA disease who received VMAT at a single center were retrospectively analyzed. Receiver Operating Characteristic (ROC) was performed to access the cut-off point of PTV. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate prognostic value for PTV. The Propensity Score Matching (PSM) was used to adjust baseline potential confounders. Results The 5-year Locol-Regional Failure-Free (L-FFR), Distant Failure-Free Survival (D-FFR), Disease-Free Survival (DFS) and Overall Survival (OS) were 90.6%, 83.7%, 71.5% and 79.3%, respectively. Before PSM, the 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with PTV ≤ 38 mL vs. PTV > 38 mL were 94.1% vs. 90.4% (p= 0.063), 87.9% vs. 76.3% (p< 0.001), 78.5% vs. 58.5% (p< 0.001) and 86.3% vs. 66.7% (p< 0.001) respectively. Multivariate analysis showed PTV was an independent prognostic factor for D-FFS (p= 0.034), DFS (p= 0.002) and OS (p= 0.001). PTV classified was still an independent prognostic factor for OS after PSM (HR = 2.034, p= 0.025. Conclusions PTV had a substantial impact on the prognosis of NPC patients treated with VMAT before and after PSM simultaneously. PTV > 38 mL may be considered as an indicator of the clinical stage of nasopharyngeal carcinoma. Level of evidence III.

The effect of primary tumor volume on the prognosis of nasopharyngeal carcinoma in era of volumetric modulated arc therapy: a propensity score matched cohort study.

OBJECTIVE: The role of Primary Tumor Volume (PTV) in Nasopharyngeal Carcinoma (NPC) treated with Volumetric Modulated Arc Therapy (VMAT) is still unclear. The aim of this study was to access the effect of PTV in prognosis prediction of nasopharyngeal carcinoma in era of VMAT. METHODS: Between January 20 and November 2011, 498 consecutive NPC patients with stage I-IVA disease who received VMAT at a single center were retrospectively analyzed. Receiver Operating Characteristic (ROC) was performed to access the cut-off point of PTV. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate prognostic value for PTV. The Propensity Score Matching (PSM) was used to adjust baseline potential confounders. RESULTS: The 5-year Locol-Regional Failure-Free (L-FFR), Distant Failure-Free Survival (D-FFR), Disease-Free Survival (DFS) and Overall Survival (OS) were 90.6%, 83.7%, 71.5% and 79.3%, respectively. Before PSM, the 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with PTV ≤ 38 mL vs. PTV > 38 mL were 94.1% vs. 90.4% (p = 0.063), 87.9% vs. 76.3% (p < 0.001), 78.5% vs. 58.5% (p < 0.001) and 86.3% vs. 66.7% (p < 0.001) respectively. Multivariate analysis showed PTV was an independent prognostic factor for D-FFS (p = 0.034), DFS (p = 0.002) and OS (p = 0.001). PTV classified was still an independent prognostic factor for OS after PSM (HR = 2.034, p = 0.025. CONCLUSIONS: PTV had a substantial impact on the prognosis of NPC patients treated with VMAT before and after PSM simultaneously. PTV > 38 mL may be considered as an indicator of the clinical stage of nasopharyngeal carcinoma. LEVEL OF EVIDENCE: III.

Volumetric measurement of intracranial meningiomas: a comparison between linear, planimetric, and machine learning with multiparametric voxel-based morphometry methods.

PURPOSE: To compare the accuracy of three volumetric methods in the radiological assessment of meningiomas: linear (ABC/2), planimetric, and multiparametric machine learning-based semiautomated voxel-based morphometry (VBM), and to investigate the relevance of tumor shape in volumetric error. METHODS: Retrospective imaging database analysis at the authors' institutions. We included patients with a confirmed diagnosis of meningioma and preoperative cranial magnetic resonance imaging eligible for volumetric analyses. After tumor segmentation, images underwent automated computation of shape properties such as sphericity, roundness, flatness, and elongation. RESULTS: Sixty-nine patients (85 tumors) were included. Tumor volumes were significantly different using linear (13.82 cm3 [range 0.13-163.74 cm3]), planimetric (11.66 cm3 [range 0.17-196.2 cm3]) and VBM methods (10.24 cm3 [range 0.17-190.32 cm3]) (p < 0.001). Median volume and percentage errors between the planimetric and linear methods and the VBM method were 1.08 cm3 and 11.61%, and 0.23 cm3 and 5.5%, respectively. Planimetry and linear methods overestimated the actual volume in 79% and 63% of the patients, respectively. Correlation studies showed excellent reliability and volumetric agreement between manual- and computer-based methods. Larger and flatter tumors had greater accuracy on planimetry, whereas less rounded tumors contributed negatively to the accuracy of the linear method. CONCLUSION: Semiautomated VBM volumetry for meningiomas is not influenced by tumor shape properties, whereas planimetry and linear methods tend to overestimate tumor volume. Furthermore, it is necessary to consider tumor roundness prior to linear measurement so as to choose the most appropriate method for each patient on an individual basis.

Imaging nodal volume and survival in oral tongue cancer with cervical lymph node metastasis

Abstract Objectives Oral tongue cancer is the most prevalent type of oral cavity cancer and presents the worst prognosis. With the use of TNM staging system, only the size of primary tumor and lymph node are considered. However, several studies have considered the primary tumor volume as a possible significant prognostic factor. Our study, therefore, aimed to explore the role of nodal volume from imaging as a prognostic implication. Methods Medical records and imaging (either from Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan) of 70 patients diagnosed with oral tongue cancer with cervical lymph node metastasis between January 2011 and December 2016 were retrospectively reviewed. The pathological lymph node was identified, and nodal volume was measured using the Eclipse radiotherapy planning system and was further analysed for its prognostic implications, particularly on overall survival, disease-free survival, and distant metastasis-free survival. Results From A Receiver Operating Characteristic (ROC) curve analysis, the optimal cut-off value of the nodal volume was 3.95 cm3, to predict the disease prognosis, in terms of overall survival and metastatic-free survival (p≤ 0.001 and p= 0.005, respectively), but not the disease-free survival (p= 0.241). For the multivariable analysis, the nodal volume, but not TNM staging, was a significant prognostic factor for distant metastasis. Conclusions In patients with oral tongue cancer and cervical lymph node metastasis, the presence of an imaging nodal volume of ≥3.95 cm3 was a poor prognostic factor for distant metastasis. Therefore, the lymph node volume may have a potential role to adjunct with the current staging system to predict the disease prognosis. Level of Evidence: 2b.

The effect of size and clinical staging of mammary tumors on blood parameters in bitches

Background: Mammary tumors are the most common type of tumor in female dogs and account for 50% of all tumors in dogs. The clinical prognosis of canine mammary tumors is strongly affected by the size, stages, histological type, and grade of tumor; mitotic index; and nearby and distant metastasis. In canine mammary tumors, it is recommended that prognostic evaluation should also include complete blood count, serum biochemistry, and blood gases in addition to tumor size and stage. This study aimed to investigate the effect of tumor size, volume, and clinical stage on complete blood count, blood gas analysis, and serum biochemical parameters in bitches with mammary tumors and the correlation between them. Materials, Methods & Results: The study included a total of 18 bitches of different breeds, aged 6-15 years, of which 12 had mammary tumors and 6 were healthy. Thoracic X-rays were performed on bitches with mammary tumors in ventrodorsal and laterolateral positions to evaluate lung metastasis. Blood samples were collected from the cephalic vein from bitches in both groups in 2 different tubes (with plastic gel and ethylenediaminetetraacetic acid), 5 mL each, to perform complete blood count and evaluate blood gases and serum biochemical parameters. Blood samples were collected from the animals at the time of initial examination without any intervention. Analysis of the blood showed that bitches with mammary tumors had decreased levels of RBC, HCT, HGB, potassium, TCO2 , base excess, THbc, and ALT enzyme activity and increased levels of lactate, total protein, cholesterol, triglyceride, LDL, uric acid, and ALP and LDH enzyme activities compared with those in the control group. Furthermore, the dogs with a primary tumor of > 5 cm were found to have significantly higher levels of WBC, lactate, total protein, triglyceride, LDL, uric acid, and ALP and LDH enzyme activities and significantly lower levels of RBC and THbc compared with those in the control group. Bitches with tumors in multiple mammary lobes were found to have significantly higher levels of WBC, total protein, triglyceride, LDL, and ALP and LDH enzyme activities and significantly lower levels of RBC, HCT, HGB, TCO2 , THbc, and ALT enzyme activity compared with those in the control group. Based on the laboratory findings and approval of the owners of the dogs, mammary tissues containing the tumor and lymph nodes were surgically removed. After the operation, the removed mammary tissues were evaluated for size and volume. Clinical staging of the tumors was performed based on the size of the primary tumor (T), nearby lymph nodes (N), and metastasis (M) in accordance with the criteria set by WHO. Clinical staging of the tumors was, thus, based on the tumor, nodes, and metastases (TNM) score obtained according to the following system: Stage I: T1 N0 M0 , Stage II: T2 N0 M0 , Stage III: T3 N0 M0 , Stage IV: TanyN1 M0 , Stage V: made as TanyNanyM1 . Discussion: Mammary tumors are the most common type of neoplasm in bitches and, thus, cause serious problems in veterinary medicine. Tumors are significantly correlated with better prognosis compared with larger tumors. Based on this finding, this study investigated the effect of size, volume, and stage of mammary tumors in bitches on some blood parameters and the correlation between them. Therefore, it was concluded that clinical staging and evaluation of blood parameters could be useful in the diagnosis, treatment, and prediction of prognosis in canine mammary tumors. This study found that bitches with mammary tumors exhibited significant changes in their blood parameters (complete blood count, blood gas analysis, and serum biochemistry). The results obtained from this study may contribute to the development of approaches to the diagnosis, prediction of prognosis, and treatment of canine mammary tumors.

Metabolic Volume Measurements in Multiple Myeloma.

Multiple myeloma (MM) accounts for 10-15% of all hematologic malignancies, as well as 20% of deaths related to hematologic malignant tumors, predominantly affecting bone and bone marrow. Positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (FDG-PET/CT) is an important method to assess the tumor burden of these patients. It is often challenging to classify the extent of disease involvement in the PET scans for many of these patients because both focal and diffuse bone lesions may coexist, with varying degrees of FDG uptake. Different metrics involving volumetric parameters and texture features have been proposed to objectively assess these images. Here, we review some metabolic parameters that can be extracted from FDG-PET/CT images of MM patients, including technical aspects and predicting MM outcome impact. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters known to be independent predictors of MM outcome. However, they have not been adopted in clinical practice due to the lack of measuring standards. CT-based segmentation allows automated, and therefore reproducible, calculation of bone metabolic metrics in patients with MM, such as maximum, mean and standard deviation of the standardized uptake values (SUV) for the entire skeleton. Intensity of bone involvement (IBI) is a new parameter that also takes advantage of this approach with promising results. Other indirect parameters obtained from FDG-PET/CT images, such as visceral adipose tissue glucose uptake and subcutaneous adipose tissue radiodensity, may also be useful to evaluate the prognosis of MM patients. Furthermore, the use and quantification of new radiotracers can address different metabolic aspects of MM and may have important prognostic implications.

Effect of tumor and normal lung volumes on the lung volume-dose parameters of IMRT in non-small-cell lung cancer

OBJECTIVES: To explore the effect of tumor and normal lung volumes on lung volume-dose parameters in patients with non-small-cell lung cancer (NSCLC) who had undergone intensity-modulated radiation therapy (IMRT). METHODS: The clinical data of 208 patients with NSCLC who underwent radical IMRT between June 2014 and June 2018 were retrospectively analyzed. A regression model curve was used to evaluate the effect of tumor and normal lung volumes on normal lung relative volumes receiving greater than 5 and 20 Gy (V5, V20), on mean lung dose (MLD), and on absolute volumes spared from greater than 5 and 20 Gy (AVS5, AVS20). RESULTS: The V5, V20, and MLD of the bilateral lung were fitted to a quadratic equation curve with the change in tumor volume, which increased initially and then decreased when the tumor volume increased. The V5, V20, and MLD of the lung reached their apex when the tumor volumes were 288.07, 341.69, and 326.83 cm3, respectively. AVS5 and AVS20 decreased in a logarithmic curve with an increase in tumor volume. The V5, V20, and MLD of the small normal lung volume group were all significantly higher than those of the large normal lung volume group (p<0.001, p=0.004, p=0.002). However, the AVS5 and AVS20 of the small normal lung volume group were all significantly lower than those of the large normal lung volume group (p<0.001). CONCLUSION: The effects of tumor volume and normal lung volume on dose-volume parameters should be considered. AVS5 is an important supplementary dose limitation parameter for patients whose tumor volume exceeds a certain boundary value (approximately 300 cm3).

Radiotherapy for the treatment of pituitary adenomas: A dosimetric comparison of three planning techniques.

AIM: Our goal was to compare conformal 3D (C3D) radiotherapy (RT), modulated intensity RT (IMRT), and volumetric modulated arc therapy (VMAT) planning techniques in treating pituitary adenomas. BACKGROUND: RT is important for managing pituitary adenomas. Treatment planning advances allow for higher radiation dosing with less risk of affecting organs at risk (OAR). MATERIALS AND METHODS: We conducted a 5-year retrospective review of patients with pituitary adenoma treated with external beam radiation therapy (C3D with flattening filter, flattening filter-free [FFF], IMRT, and VMAT). We compared dose-volume histogram data. For OARs, we recorded D2%, maximum, and mean doses. For planning target volume (PTV), we registered V95%, V107%, D95%, D98%, D50%, D2%, minimum dose, conformity index (CI), and homogeneity index (HI). RESULTS: Fifty-eight patients with pituitary adenoma were included. Target-volume coverage was acceptable for all techniques. The HI values were 0.06, IMRT; 0.07, VMAT; 0.08, C3D; and 0.09, C3D FFF (p < 0.0001). VMAT and IMRT provided the best target volume conformity (CI, 0.64 and 0.74, respectively; p < 0.0001). VMAT yielded the lowest doses to the optic pathway, lens, and cochlea. The position of the neck in extreme flexion showed that it helps in planning mainly with VMAT by allowing only one arc to be used and achieving the desired conformity, decreasing the treatment time, while allowing greater protection to the organs of risk using C3D, C3DFFF. CONCLUSIONS: Our results confirmed that EBRT in pituitary adenomas using IMRT, VMAT, C3D, C3FFF provide adequate coverage to the target. VMAT with a single arc or incomplete arc had a better compliance with desired dosimetric goals, such as target coverage and normal structures dose constraints, as well as shorter treatment time. Neck extreme flexion may have benefits in treatment planning for better preservation of organs at risk. C3D with extreme neck flexion is an appropriate treatment option when other treatment techniques are not available.

A New Interpretation of the Standard PSA-Test.

BACKGROUND: In Puerto Rico, prostate cancer (PC) has the highest incidence and level of mortality. PC screening is performed using the standard prostatic-specific antigen (PSA) test with a cut-off value of 4.0 ng/mL. However, the standard PSA test is very controversial because it is subject to false positives and negatives. PURPOSE: To establish a new interpretation of the standard PSA test based on the strong correlation between total serum PSA and tumor volume. PATIENTS AND METHODS: A PSA database of 21,980 Puerto Rican men (2004-2015) with proven PC was provided by the Puerto Rico Cancer Center Register (PRCCR). A statistical analysis was conducted for the entire PC population divided into two categories i) age and PSA ranges and ii) diagnostic year, age ranges, and PSA ranges. The weighted first percentiles of the PSA ranges were used to define three PSA cut-off values related to small, intermediate, and large tumor volumes. Further, three baseline PSA weighted median values were calculated to enable better prognosis of PC. RESULTS: Three PSA cut-off values of 2.1 ng/mL, 6 ng/mL, and 10.5 ng/mL were found related to small (1.0 cc), intermediate (2.8 cc), and large (5.0 cc) PC tumor volumes, respectively. PSA values greater than the weighted median values of 3.1 ng/mL, 7 ng/mL, were associated with increased risks of tumors growing from small to intermediate and from intermediate to large size, respectively. A PSA value greater than 14.1 ng/mL was related to metastasis. CONCLUSION: In this research, we have found a new interpretation of the PSA test based on PSA cut-off values correlated to small, intermediate, and large prostate cancer tumor volumes. The set of these results together with the weighted PSA median values enhance the usefulness of the standard PSA test and provide a tool for a better decision-making and treatment.

Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma.

Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60 mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100 µg/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9 Gy was applied in the tumor area, before (3 days), during (30 min) and after (3 days) the PTX + GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTX + GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTX + GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTX + GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.

Rapamycin Combi with TAE on the Growth, Metastasis, and Prognosis of Hepatocellular Carcinoma in Rat Models.

INTRODUCTION AND AIM: To investigate the effect of mTOR inhibitor Rapamycin combined with transcatheter arterial embolization (TAE) on the growth, metastasis, and prognosis of hepatocellular carcinoma (HCC) in rat model. MATERIAL AND METHOD: McARH7777 cells were used to construct rat models of HCC, which were randomly divided into Model, Rapamycin, TAE, and Rapamycin + TAE groups. Quantitative reverse transcription-PCR (qRT-PCR) and Western Blot were used to detect the expression of Epithelial-Mesenchymal Transition (EMT)-related molecules, and immunohistochemical staining to determine the expression of EMTrelated proteins, angiogenic factors as well as microvessel density (MVD)-CD34. RESULTS: The hepatic tumor volume of rats in the other three groups were all significantly smaller than the Model group on the 7th, 14th, and 21st day after treatment and the combination treatment was apparently more effective than either treatment alone. Besides, both the number and the size of metastatic nodules of HCC rats after combination treatment were remarkably reduced. In addition, compared with rats in the Rapamycin + TAE group, N-cadherin, Vimentin, HIF-1α, VEGF, and MVD-CD34 were obviously enhanced, while E-cadherin was lowered in those TAE group, which were the complete opposite to the Rapamycin group. Besides, the median survival time of rats in the Rapamycin + TAE group was evidently longer than the resting groups. CONCLUSION: Rapamycin combined with TAE may effectively suppress the EMT formation and angiogenesis, thereby inhibiting the growth and lung metastasis of HCC rats, which provides a new idea for countering the recurrence and metastasis of HCC.

Comparison of semi-automated and manual methods to measure the volume of prostate cancer on magnetic resonance imaging.

PURPOSE: The purpose of this study was to determine the accuracy of manual semi-automated and volumetric measurements to assess prostate cancer volume on multiparametric magnetic resonance imaging (MP-MRI) using whole-mount histopathology for validation. MATERIALS AND METHODS: We evaluated 30 consecutive men (median age, 65.7 years; interquartile range [IQR], 61.5-70.9 years) with a median prostatic specific antigen of 8.5ng/dL (IQR, 5.5-10.5ng/dL), who underwent MP-MRI before radical prostatectomy. Index tumor volume was determined prospectively and independently on the basis of MRI and whole-mount section volumetric assessment using the maximum histologic diameter (MHD) and the histologic volume (HV). The MRI index tumor volume was determined by two independent radiologists using a single measurement of the maximum tumor dimension (MTD), a simplified MR ellipsoid volume (MREV) calculation and a MR region of interest volume (MROV) segmentation displayed by a commercially available OsiriX®. MTD was compared to MHD, whereas MREV and MROV were compared to HV. RESULTS: Thirty index lesions (median HV, 1.514 cm3; IQR, 0.05-3.780 cm3) were analyzed. The MREV, MROV and HD were significantly correlated with each other (r>0.5). Inter-observer agreement for measurements was good for each method (r>0.780). The MTD was the best predictor of maximum histologic diameter (r=0.980 and 0.791) and had an excellent inter-variability correlation (P<0.0001). CONCLUSION: Prostate cancer histologic volume can be assessed using MREV or MROV with a good accuracy and low inter-observer variability. MTD has the lowest inter-observer variability and provides best degrees of correlation with MHD. MTD should be used on MRI for selecting and following patients for active surveillance and staging before focal treatment of prostate cancer.

A Kindler syndrome-associated squamous cell carcinoma treated with radiotherapy.

Kindler syndrome1, 2 is a genetic disorder mainly characterized by increased skin fragility and photosensitivity,3, 4 making the use of treatments based on radiation difficult or even prohibited. Thus, cases reporting Kindler syndrome patients treated with radiotherapy are rare. In this study, we report clinical outcomes and care provided for a rare case of a Kindler syndrome patient submitted to radiotherapy. Diagnosed with squamous cell carcinoma involving the buccal mucosa, the patient was exclusively treated with radiotherapy, with 70 Gy delivered on the PTV with the Volumetric Modulated Arc technique. The patient's reaction regarding control of the lesion is relevant compared to patients not affected by the syndrome. We noticed acute reactions of the skin and buccal mucosa after few radiotherapy sessions, followed by a fast reduction in the tumor volume. The efficacy of radiotherapy along with multidisciplinary actions allowed treatment continuity, leading to a complete control of the lesion and life quality improvement and showed that the use of radiotherapy on Kindler syndrome patients is possible.

Tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography: association with N categories

OBJECTIVE: To determine whether the gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict the presence of regional lymph node metastasis and could determine N categories. MATERIALS AND METHODS: A total of 202 consecutive patients with gastric adenocarcinoma who had undergone gastrectomy 1 week after contrast-enhanced multidetector computed tomography were retrospectively identified. The gross tumor volume was evaluated on multidetector computed tomography images. Univariate and multivariate analyses were performed to determine whether the gross tumor volume could predict regional lymph node metastasis, and the Mann-Whitney U test was performed to compare the gross tumor volume among N categories. Additionally, a receiver operating characteristic analysis was performed to identify the accuracy of the gross tumor volume in differentiating N categories. RESULTS: The gross tumor volume could predict regional lymph node metastasis (p<0.0001) in the univariate analysis, and the multivariate analyses indicated that the gross tumor volume was an independent risk factor for regional lymph node metastasis (p=0.005, odds ratio=1.364). The Mann-Whitney U test showed that the gross tumor volume could distinguish N0 from the N1-N3 categories, N0-N1 from N2-N3, and N0-N2 from N3 (all p<0.0001). In the T1-T4a categories, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 12.3 cm3), N0-N1 from N2-N3 (cutoff, 16.6 cm3), and N0-N2 from N3 (cutoff, 24.6 cm3). In the T4a category, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 15.8 cm3), N0-N1 from N2-N3 (cutoff, 17.8 cm3), and N0-N2 from N3 (cutoff, 24 cm3). CONCLUSION: The gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict regional lymph node metastasis and N categories.

Are there differences in zonal distribution and tumor volume of prostate cancer in patients with a positive family history?

PURPOSE: To determine if there are any differences in the zonal distribution and tumor volumes of familial and sporadic prostate cancers (PC) in men undergoing radical prostatectomy. MATERIAL AND METHODS: 839 patients underwent a radical prostatectomy in the absence of prior neoadjuvant therapy between 1987 and 1996. Telephone interviews were conducted to obtain an updated family history. A positive family history was defined as the diagnosis of PC in at least one first degree relative. Prostatectomy specimens were examined to determine the number of tumor foci, zonal origin of the dominant tumor focus, tumor volume of the largest cancer focus, total tumor volume, Gleason score and stage, and the surgical margin status. Results were stratified according to family history and ethnicity. RESULTS: We successfully contacted 437 patients (52 percent). Prostatectomy specimens from 55 patients were excluded from review due to a history of prior transurethral resection of the prostate (n = 26) or uncertain pathological stage (n = 29). Of the remaining 382 patients, 76 (20 percent) reported having a first-degree relative with PC. Statistical analysis revealed no significant differences in the pathologic variables between the two groups of patients with or without a family history of PC. CONCLUSIONS: Familial and sporadic PC share similar characteristics. No histopathological differences account for the increased positive predictive value of PC screening tests among patients with a family history of PC.

Ressonância magnética para avaliação dos limites dos campos clássicos de radioterapia em pacientes portadoras de neoplasia maligna de colo uterino / Magnetic resonance imaging in the evaluation of standard radiotherapy field borders in patients with uterine cervix cancer

OBJETIVO: Avaliar os limites de campo padronizados para radioterapia de neoplasia maligna de colo uterino com o uso de ressonância magnética e verificar a importância deste exame na redução de possíveis erros de planejamento com técnica convencional. MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, exames de ressonância magnética do planejamento de 51 pacientes tratadas devido a neoplasia de colo uterino. Os parâmetros estudados foram limites anterior e posterior no corte sagital. RESULTADOS: Observou-se, no corte sagital das ressonâncias magnéticas, que o limite de campo anterior apresentou-se inadequado em 20 (39,2 por cento) pacientes e que houve perda geográfica em 37,3 por cento dos casos no limite posterior. A inadequação de ambos os limites de campo não se relacionou com parâmetros clínicos como idade das pacientes, estadiamento, tipo e grau histológico. CONCLUSÃO: A avaliação dos limites de campo padronizados pela literatura com o uso de ressonância magnética mostrou altos índices de inadequação dos limites do campo lateral, assim como a importância do uso deste exame no planejamento radioterápico de pacientes portadoras de câncer de colo uterino com a finalidade de reduzir a perda geográfica no volume alvo de tratamento.

OBJECTIVE: To evaluate, by means of magnetic resonance imaging, the standardized field borders in radiotherapy for malignant neoplasm of uterine cervix, and to determine the role of this method in the reduction of possible planning errors related to the conventional technique. MATERIALS AND METHODS: Magnetic resonance imaging studies for planning of treatment of 51 patients with uterine cervix cancer were retrospectively analyzed. The parameters assessed were the anterior and posterior field borders on sagittal section. RESULTS: The anterior field border was inappropriate in 20 (39.2 percent) patients and geographic miss was observed in 37.3 percent of cases in the posterior border. The inappropriateness of both field borders did not correlate with clinical parameters such as patients' age, tumor staging, histological type and degree. CONCLUSION: The evaluation of standardized field borders with the use of magnetic resonance imaging has demonstrated high indices of inappropriateness of the lateral field borders, as well as the relevant role of magnetic resonance imaging in the radiotherapy planning for patients with uterine cervix cancer with a view to reduce the occurrence of geographic miss of the target volume.