Predictor Of Metastasis-free Survival Research Articles

Prediction of prognosis using artificial intelligence-based histopathological image analysis in patients with soft tissue sarcomas.

Prompt histopathological diagnosis with accuracy is required for soft tissue sarcomas (STSs) which are still challenging. In addition, the advances in artificial intelligence (AI) along with the development of pathology slides digitization may empower the demand for the prediction of behavior of STSs. In this article, we explored the application of deep learning for prediction of prognosis from histopathological images in patients with STS. Our retrospective study included a total of 35 histopathological slides from patients with STS. We trained Inception v3 which is proposed method of convolutional neural network based survivability estimation. F1 score which identify the accuracy and area under the receiver operating characteristic curve (AUC) served as main outcome measures from a 4-fold validation. The cohort included 35 patients with a mean age of 64 years, and the mean follow-up period was 34 months (2-66 months). Our deep learning method achieved AUC of 0.974 and an accuracy of 91.9% in predicting overall survival. Concerning with the prediction of metastasis-free survival, the accuracy was 84.2% with the AUC of 0.852. AI might be used to help pathologists with accurate prognosis prediction. This study could substantially improve the clinical management of patients with STS.

Estimated absolute percentage of biopsied tissue positive for Gleason pattern 4 (eAPP4) in low dose rate prostate brachytherapy: Evaluation of prognostic utility in a large cohort

PurposeTo determine whether a system to estimate Absolute Percentage of Biopsied Tissue Positive for Gleason Pattern 4 (eAPP4) is useful as a prognostication tool for patients with intermediate risk prostate cancer (IR-PCa) undergoing low dose rate prostate brachytherapy. Methods497 patients with IR-PCa and known grade group 2 or 3 disease treated with low dose rate seed brachytherapy (LDR-BT) at a quaternary cancer centre were retrospectively reviewed. Prostate biopsies for each patient included Gleason grading with synoptic reporting that did not include percentage of pattern 4 disease found within the sample. Each core was assigned a grade grouping, however, and that was used with optimized estimates of percentage of pattern four disease to estimate eAPP4. Outcomes including cumulative incidence of recurrence (CIR), treatment of recurrent disease (RRX), and metastasis-free survival (MFS) were then reviewed and the prognostic value of eAPP4 evaluated. Results428 (86%) patients had Gleason grade group 2 and 69 (14%) patients had Gleason grade group 3 disease. 230 (46%) patients had National Comprehensive Cancer Network (NCCN) favourable intermediate at baseline, while 267 (54%) of patients had NCCN unfavourable intermediate at baseline. Median follow-up was 7.3 (5.5–9.6) years. eAPP4 was predictive of CIR (p = 0.003), RRX (p = 0.003), or MFS (p = 0.001) events, while Gleason grade grouping alone was not. eAPP4 was strongest as a predictor for MFS when estimates of 30% (grade group 2) and 80% (grade group 3) were used [HR 1.07 (1.03–1.12); p = 0.001]. ConclusionseAPP4 was strongly predictive of recurrence and metastasis-free survival in a large cohort of patients receiving LDR-BT treatment for IR-PCa. Treatment of future patients with IR-PCa could include the use of eAPP4 prognostication.

Validation of baseline health-related quality of life as prognostic indicator for survival outcome in men with intermediate risk prostate cancer undergoing radical prostatectomy.

340 Background: Accurate prediction of cancer outcomes remains a key component of prostate cancer (PC) treatment decision-making. Intermediate-risk PC patients represent a heterogeneous group with highly variable prognoses and it is challenging to provide uniform treatment recommendations for those patients. Previous studies have shown baseline health-related quality of life (HRQOL) to be a robust prognostic indicator for survival outcomes of different cancer entities in the metastatic setting, with scarce evidence on PC. We therefore sought to validate the predictive value of baseline HRQOL for survival outcomes in men with intermediate risk PC undergoing radical prostatectomy (RP). Methods: We identified 4780 patients with intermediate risk PC according to NCCN risk stratification and prospectively assessed baseline HRQOL prior RP. Patients were stratified by global health status (GHS) domain of the QLQ-C30 questionnaire. Oncologic endpoints were metastasis-free survival (MFS) and overall survival (OS). Multivariable Cox regression models were applied to assess the predictive value of baseline GHS on survival outcomes. Harrell's discrimination C-index was applied to calculate the predictive accuracy of the model. Decision curve analysis (DCA) was performed to validate the clinical net benefit associated with adding GHS to our multivariable model ( P < .05). Results: Median follow up was 51mo. In multivariable analysis, GHS was confirmed as an independent predictor for increased MFS (HR .98, 95% CI .97-.99; P = .028) and OS (HR .97, 95% CI .95-.99; P = .008), indicating a relative risk reduction of 1.7% for MFS and 2.8% for OS per 1-point increase of baseline GHS. Adding GHS to our model improved predictive accuracy of prognosis for MFS by 6% (c-index .75 vs .72) and for OS by 8% (c-index .78 vs .74). Validation with DCA revealed a net benefit over all thresholds in prediction of MFS and OS when adding GHS to our model. Conclusions: Our findings highlight that baseline HRQOL is a valuable and robust prognostic factor for patients with intermediate-risk PC prior RP. Baseline HRQOL data improve prognostic accuracy of MFS and OS and can therefore support treatment decision-making. [Table: see text]

EAU patient selection criteria are predictors of metastasis-free survival in a large contemporary salvage radical prostatectomy patients cohort

EAU patient selection criteria are predictors of metastasis-free survival in a large contemporary salvage radical prostatectomy patients cohort

Values of alkaline phosphatase at the diagnosis of castration resistance and response to primary androgen deprivation therapy as predictors of subsequent metastasis in non-metastatic castration-resistant prostate cancer.

Among various therapeutic options available for metastatic castration-resistant prostate cancer (mCRPC), only apalutamide and enzalutamide have shown evidences of improved metastasis-free survival (MFS) for non-metastatic castration-resistant prostate cancer (nmCRPC). However, there is a paucity of evidence to indicate who may be targeted for aggressive therapy among patients with nmCRPC. The objectives of this retrospective study were to explore predictors of metastasis in patients with nmCRPC and to identify a subpopulation of patients with nmCRPC who may benefit from aggressive therapy. A total of 115 patients with CRPC who had no metastasis detected at the time of diagnosis of CRPC were included in this retrospective study. All patients were treated at Jikei University and its affiliated hospitals. The primary outcome measure was MFS from the time of diagnosis of CRPC. Predictors of MFS were also explored with a multivariate Cox hazard model. The median observation period after diagnosis of CRPC was 30months (range 2-143months). Kaplan-Meier analysis revealed a median MFS of 76. Multivariate analysis demonstrated that low alkaline phosphatase (ALP) values at diagnosis of CRPC and favorable response to primary androgen deprivation therapy (ADT) were significant predictors of longer MFS (P = 0.011, and 0.031, respectively). Results of this study suggest that high ALP values at diagnosis of CRPC and poor response to primary ADT may predict the propensity of metastasis in patients with nmCRPC. Further prospective studies will be required enrolling more patients to confirm our findings.

Alkaline phosphatase (ALP) value at diagnosis of CRPC and response to primary androgen deprivation therapy may predict metastasis in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).

294 Background: Numerous therapeutic options are available for metastatic castration-resistant prostate cancer (mCRPC). However, current therapeutic options remain inadequate for non-metastatic CRPC (nmCRPC); furthermore, there is a paucity of clear evidence to show who may be targeted for aggressive therapy among nmCRPC patients. Therefore, the objective of this retrospective study was to explore predictors of metastasis in patients with nmCRPC and to identify a subpopulation of nmCRPC patients who may benefit from aggressive therapy. Methods: A total of 115 patients with CRPC who had no metastasis at the time of diagnosis of CRPC were included in this retrospective study. All patients were treated at Jikei University Hospital. The primary outcome measure was metastasis-free survival (MFS) from the time of diagnosis of CRPC. Predictors of MFS were also explored with a multivariate Cox model. Results: The median observation period after diagnosis of CRPC in these patients was 30 months. Kaplan-Meier analysis revealed a median MFS of 76 months in these patients. Multivariate analysis demonstrated that low ALP values at diagnosis of CRPC and favorable response to primary androgen deprivation therapy (ADT) were significant predictors of longer MFS ( P = 0.011, and 0.031, respectively). Conclusions: Study results suggest that high ALP values at diagnosis of CRPC and poor response to primary ADT may predict metastasis in patients with nmCRPC. Further prospective studies will be required in more patients to confirm our findings. Univariate/multivariate analysis of factors contributing to MFS in nmCRPC patients. [Table: see text]

MRI of Extramural Venous Invasion in Locally Advanced Rectal Cancer: Relationship to Tumor Recurrence and Overall Survival.

Purpose To study the relationship between MRI-defined extramural venous invasion (EMVI) prior to treatment and prognosis in patients with locally advanced rectal cancer treated with neoadjuvant chemotherapy-radiation therapy followed by surgery. Materials and Methods This retrospective study included 517 patients with locally advanced rectal cancer evaluated from August 2008 to December 2014. Baseline and posttherapy MRI and follow-up data were retrieved for all patients. After training by using 328 cases with pathologic evaluation of EMVI after therapy, radiologists evaluated baseline MRI for EMVI status in addition to tumor size and characteristics, nodal status, and invasion of the mesorectal fascia. Reader reproducibility was determined by using κ coefficient. Kaplan-Meier curves and adjusted Cox models were used to determine the relationship of baseline MRI parameters to overall survival, metastasis-free survival, and local relapse-free survival. Results Among 517 patients, 335 (64.8%) were men; the mean age was 55.6 years ± 11.5 (standard deviation). At baseline, radiologists identified 259 of 517 (50%) patients with EMVI by using MRI. In adjusted analysis, EMVI and mesorectal fascial invasion at baseline MRI were predictors of metastasis-free survival (hazard ratio, 0.3 and 0.6; P ˂ .01 and P ˂ .02, respectively) and overall survival (hazard ratio, 0.5 and 0.5; P = .01 and P = .02, respectively). EMVI was the only factor associated with local relapse-free survival (hazard ratio, 0.3; P ˂ .01). The κ coefficient for determination of EMVI was 0.80. Conclusion Extramural venous invasion (EMVI) can be reliably evaluated with MRI. The presence of EMVI was associated with greater risk of local and distant tumor recurrence and overall death in patients with locally advanced rectal cancer treated with neoadjuvant chemotherapy-radiation therapy. © RSNA, 2018 Online supplemental material is available for this article.

Breast Cancer: Radiogenomic Biomarker Reveals Associations among Dynamic Contrast-enhanced MR Imaging, Long Noncoding RNA, and Metastasis.

To perform a radiogenomic analysis of women with breast cancer to study the multiscale relationships among quantitative computer vision-extracted dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging phenotypes, early metastasis, and long noncoding RNA (lncRNA) expression determined by means of high-resolution next-generation RNA sequencing. In this institutional review board-approved study, an automated image analysis platform extracted 47 computational quantitative features from DCE MR imaging data in a training set (n = 19) to screen for MR imaging biomarkers indicative of poor metastasis-free survival (MFS). The lncRNA molecular landscape of the candidate feature was defined by using an RNA sequencing-specific negative binomial distribution differential expression analysis. Then, this radiogenomic biomarker was applied prospectively to a validation set (n = 42) to allow prediction of MFS and lncRNA expression by using quantitative polymerase chain reaction analysis. The quantitative MR imaging feature, enhancing rim fraction score, was predictive of MFS in the training set (P = .007). RNA sequencing analysis yielded an average of 55.7 × 10(6) reads per sample and identified 14 880 lncRNAs from a background of 189 883 transcripts per sample. Radiogenomic analysis allowed identification of three previously uncharacterized and five named lncRNAs significantly associated with high enhancing rim fraction, including Homeobox transcript antisense intergenic RNA (HOTAIR) (P < .05), a known predictor of poor MFS in patients with breast cancer. Independent validation confirmed the association of the enhancing rim fraction phenotype with both MFS (P = .002) and expression of four of the top five differentially expressed lncRNAs (P < .05), including HOTAIR. The enhancing rim fraction score, a quantitative DCE MR imaging lncRNA radiogenomic biomarker, is associated with early metastasis and expression of the known predictor of metastatic progression, HOTAIR.

Abstract 45: MACC1 expression and KRas13 mutation for improved survival prognosis of colorectal cancer patients

Abstract Colorectal cancer (CRC) is the third most common cancer worldwide. The metastatic dissemination of the primary tumor is directly linked to patient survival. We previously discovered the gene metastasis-associated in colon cancer 1 (MACC1). MACC1 has been identified as a new remarkable biomarker for disease prognosis and prediction of therapy response for CRC and for a variety of solid cancers. MACC1 expression in tumor tissues and patient blood correlates with tumor formation and progression, development of metastases and patient survival representing a decisive driver for tumorigenesis and metastasis. Here we aim at the refinement of risk assessment in a retrospective study of 100 CRC patients with tumors staged I, II and III by combinatorial analyses of MACC1 with the KRas and BRaf mutation status. First, we correlated the single parameters, KRas12, KRas13, BRaf600 mutation and MACC1 expression with clinical outcome data, such as metastasis-free survival (MFS). We found correlations of high MACC1 expression with shorter MFS (P&amp;lt;0.001). Likewise, patients with a somatic KRas13 mutation showed decreased MFS (P=0.003). Interestingly, KRas12 or BRaf600 mutations as well as their wild type counterparts had no impact on survival prognosis. Multivariate analyses combining MACC1 expression level with the single parameters KRas12, KRas13 and BRaf600 mutation revealed an improved prognosis exclusively for KRas13 mutated tumors vs. MACC1 expression alone. High MACC1 expressers with KRas13 mutation had the poorest median MFS (17.2 months) compared to MACC1 high/KRas wild type patients (37.2 months; P=0.039). Further, we addressed the impact of KRas13 on regulation of MACC1 expression in vitro. We used RNAi to analyze the impact of KRas signaling on MACC1 in several CRC cell lines with different KRas mutation status. In addition, we employed HCT116 cells harboring the activating G13D KRAS mutation together with the HCT116-derived sublines Hkh-2 and Hke-3 lacking the mutated KRas13 allele by homologous recombination. Disrupting the constitutive active KRas signaling led to increased MACC1 mRNA and protein expression levels in HCT116 cells, either by knock-down of the endogenous G13D mutated KRas expression by RNAi or through gene targeting. In summary, MACC1 expression levels together with KRas13 mutation status was the only combination that improved the identification of CRC patients at high risk for metastasis formation and the prediction of MFS when compared to MACC1 alone Citation Format: Katharina Ilm, Wolfgang Kemmner, Gudrun Koch, Pia Herrmann, Marc Osterland, Senji Shirasawa, Takehiko Sasazuki, Ulrike S. Stein. MACC1 expression and KRas13 mutation for improved survival prognosis of colorectal cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 45. doi:10.1158/1538-7445.AM2014-45

A 19-gene prognostic GEP signature to determine metastatic risk associated with thymomas.

68 Background: Therapeutic decisions for patients with thymomas are made on tumor stage as histologic classification is of limited prognostic value. A molecular prognostic tool may better predict the likelihood of metastasis in thymomas and enable better management of patients. Methods: Reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay for 23 genes (19 test and 4 reference genes) was performed on archival paraffin-embedded primary thymomas (n=36). The gene expression levels were used to compute gene expression profile (GEP) signature and classify tumors into low or high risk. The GEP was validated in an independent test set (n=75) of patients. Results: We developed and validated a 19-gene prognostic GEP signature for predicting metastatic behavior in thymomas. Using radial basis machine (RBM) modeling in the training set, both 5-year and 10-year MFS rates were 85% and 22% for predicted low risk and high risk of metastasis (p&lt;0.0005, log-rank), respectively. For the validation set, 5-year MFS rates were 93% and 35% for predicted low and high risk patients (p&lt;0.0018 log-rank), respectively. The 5-year MFS rates for Masaoka stage in the validation set were 53% and 41% for stage I/II and stage III/IV(p&lt;0.0433 log-rank), respectively. In a multivariate Cox model, the GEP was the only independent predictor of metastasis free survival compared to age at diagnosis and stage (p=0.048). Conclusions: Using archival tissues, we identified and validated a 19-gene signature that predicts likelihood of metastases of thymomas more accurately than traditional staging. The signature provides insights for both patient stratification and targeted therapy.

Comparison of the 2002 and 2010 version of the TNM classification system regarding the prediction of metastasis-free survival in patients with renal cell carcinoma.

448 Background: A new version of the TNM classification system for renal cell carcinoma (RCC) has been introduced in 2010 by the American Joint Committee on Cancer (AJCC). However, data for it’s ability to predict metastasis-free survival in RCC patients from validation studies of independent cohorts are sparse. Therefore, we decided to compare the predictive ability of the 2010 vs. the 2002 version of the TNM classification system. Methods: Pathological reports of 2595 patients with uni- or bilateral synchronous non-metastatic (pT1-4N0M0) RCCs, treated with radical nephrectomy or nephron sparing surgery between 1984 and 2010 at a single tertiary academic center, were re-evaluated. Metastasis-free survival (MFS) was assessed using the Kaplan-Meier method and pairwise log-rank tests. Results: Mean follow up was 95 (0-322) months and 430 (16.6%) patients were found to develop metastatic disease from RCC. Pairwise comparisons revealed statistically significant differences in MFS between adjacent 2002 primary tumor classifications, including pT1a vs. pT1b (p&lt;0.001), pT1b vs. pT2 (p=0.029), pT3a vs. pT3b (p&lt;0.001), and pT3c vs. pT4 (p=0.007) but excluding, pT2 vs. pT3a (p=0.963) and pT3b vs. pT3c (p=0.968). With the changes to the 2010 primary tumor classification different trends in statistical significance were observed in pairwise comparisons, including pT1a vs. pT1b (p&lt;0.001), pT3a vs. pT3b (p=0.001) but excluding pT1b vs. pT2a (p=0.062), pT2a vs. pT2b (p=0.856), pT2b vs. pT3a (p=0.395), pT3b vs. pT3c (p=0.891) and pT3c vs. pT4 (p=0.933). Conclusions: The 2010 version of the TNM classification system remains a robust predictor of MFS compared to the 2002 version. However, the 2010 version showed less discriminative power in higher pT-stages compared to the 2002 version of the TNM classification system.

Clustering-Based Method for Developing a Genomic Copy Number Alteration Signature for Predicting the Metastatic Potential of Prostate Cancer.

The transition of cancer from a localized tumor to a distant metastasis is not well understood for prostate and many other cancers, partly, because of the scarcity of tumor samples, especially metastases, from cancer patients with long-term clinical follow-up. To overcome this limitation, we developed a semi-supervised clustering method using the tumor genomic DNA copy number alterations to classify each patient into inferred clinical outcome groups of metastatic potential. Our data set was comprised of 294 primary tumors and 49 metastases from 5 independent cohorts of prostate cancer patients. The alterations were modeled based on Darwin's evolutionary selection theory and the genes overlapping these altered genomic regions were used to develop a metastatic potential score for a prostate cancer primary tumor. The function of the proteins encoded by some of the predictor genes promote escape from anoikis, a pathway of apoptosis, deregulated in metastases. We evaluated the metastatic potential score with other clinical predictors available at diagnosis using a Cox proportional hazards model and show our proposed score was the only significant predictor of metastasis free survival. The metastasis gene signature and associated score could be applied directly to copy number alteration profiles from patient biopsies positive for prostate cancer.

A new method for predicting metastasis in sarcomas

Treatment decisions for soft-tissue sarcomas are dependent on a number of factors, including tumor size, location, grade, and stage. Histological grading has been considered the best predictor of metastasis-free survival and the Federation Nacionale des Centres de Lutte Contre le Cancer (FNCLCC) grading system—defined over 20 years ago—is the most commonly used method.

Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity

Sarcomas are heterogeneous and aggressive mesenchymal tumors. Histological grading has so far been the best predictor for metastasis-free survival, but it has several limitations, such as moderate reproducibility and poor prognostic value for some histological types. To improve patient grading, we performed genomic and expression profiling in a training set of 183 sarcomas and established a prognostic gene expression signature, complexity index in sarcomas (CINSARC), composed of 67 genes related to mitosis and chromosome management. In a multivariate analysis, CINSARC predicts metastasis outcome in the training set and in an independent 127 sarcomas validation set. It is superior to the Fédération Francaise des Centres de Lutte Contre le Cancer grading system in determining metastatic outcome for sarcoma patients. Furthermore, it also predicts outcome for gastrointestinal stromal tumors (GISTs), breast carcinomas and lymphomas. Application of the signature will permit more selective use of adjuvant therapies for people with sarcomas, leading to decreased iatrogenic morbidity and improved outcomes for such individuals.

Patterns of failure and influence of potential prognostic factors after surgery in transitional cell carcinoma of the upper urinary tract

We investigated the long-term outcome of upper urinary tract transitional cell carcinoma (TCC) after surgery. The study population comprised 114 surgically treated patients with upper urinary tract TCC treated at Jikei University Hospital between March 1990 and December 2004. All these patients underwent radical surgery without any type of neoadjuvant therapy. Patterns of failure and patient survival were compared with clinicopathological parameters. The 5- and 10-year overall survival (OAS) rates for the patients were 85% (95% confidence interval [CI], 81%-89%) and 76% (95% CI, 69%-83%). To date, 19 patients (16.7%) have experienced distant or lymph node metastasis at a mean of 13.3 months following surgery (range, 1 to 50 months). The site of the primary tumor did not affect patient survival (P > 0.05). Both lymphovascular involvement (LVI) and positive lymph nodes were found to have poor prognosis in univariate analysis (P = 0.004 and P < 0.0001). Multivariate analysis indicated pathological stage and bladder recurrence (bladder recurrence being a better prognostic factor) to be independent predictors of metastasis-free survival, but not of OAS or cause-specific survival (CSS). Pathological stage and bladder recurrence were found to be the predictors of metastasis-free survival in this study. Further searching for reliable biomarkers is needed to accurately predict the prognosis of this malignancy.

Expression of cancer-testis antigen CT7 (MAGE-C1) in breast cancer: An immunohistochemical study with emphasis on prognostic utility

High expression of the cancer-testis antigen CT7, also referred to as MAGE-C1, has been recently described in a variety of malignant tumors, including breast carcinoma. To our knowledge, no data concerning the prognostic utility of CT7 expression in breast cancer are available. In this retrospective study, we evaluated the relationship between CT7 immunoreactivity and clinicopathological parameters as well as relapse-free survival (RFS) and metastasis-free survival (MFS) of 124 women with invasive breast cancer. A positive CT7 status, defined as immunoreactivity in more than 50% of tumor cells, was found in 18% of cases and correlated significantly with high tumor grade (p=0.004), but with no other clinicopathological parameter. In a univariate analysis, CT7 status showed an association with RFS by trend (p=0.107; relative risk [RR]: 1.85) and a significant association with MFS (p=0.043; RR: 2.02). In a multivariate analysis, tumor grade, stage, nodal status, angioinvasion, HER2 expression as well as estrogen and progesterone receptor expression were identified as significant independent prognostic factors of RFS and/or MFS. In this respect, CT7 expression showed a weak, statistically not significant trend towards an independent prognostic relevance concerning prediction of MFS (p=0.147; RR: 1.95). Our data suggest that estimation of CT7 immunoreactivity is of limited prognostic usefulness in breast cancer. It may provide additional information concerning assessment of MFS in selected cases.

Extracellular pH and P-31 Magnetic Resonance Spectroscopic Variables are Related to Outcome in Canine Soft Tissue Sarcomas Treated with Thermoradiotherapy

The objective was to test whether tumor pH and (31)P magnetic resonance spectroscopic end points were related to treatment outcome in pet canine patients with spontaneous soft tissue sarcomas treated with thermoradiotherapy. Forty-two dogs with evaluable (31)P magnetic resonance spectroscopic end points and pH data were included in this study. Tumor variables (grade and volume), extracellular pH (pHe), T(2) relaxation times, intracellular pH, and selected phosphometabolite ratios were examined for correlation with clinical outcome. From 39 dogs, pHe was a predictor of metastasis-free survival (MFS), with hazard ratio (HR, 0.29; P = 0.005) and overall survival (OS) with (HR, 0.36; P = 0.013). Tumor volume (>19 cm(3)) was related to MFS (HR, 2.14; P = 0.04), time to local failure (HR, 3.4; P = 0.025), and OS (HR, 2.27; P = 0.03). There was no association between T(2) or intracellular pH and clinical outcome. Tumor grade (high versus low/intermediate) and phosphodiester/betaATP ratio were identified as significant predictors for MFS, with (HR, 2.66; P = 0.009) and (HR, 0.75; P = 0.027), respectively, and as predictors of OS with (HR, 2.66; P = 0.009) and (HR, 0.76; P = 0.03), respectively. The phosphodiester/phosphocreatinine ratio predicted time to local failure (HR, 1.24; P = 0.017). pHe was predictive of metastasis and OS in canine spontaneous sarcomas. To our knowledge, this is the first time that pHe has been shown to be predictive of clinical outcome. The results suggest that additional studies should be considered evaluating the prognostic significance of this variable. Phospholipid resonances, related to membrane metabolism, were related to clinical outcome, confirming recent results reported in human patients with soft tissue sarcomas treated with thermoradiotherapy.

Sarcomes des tissus mous : données anatomopathologiques actuelles

Over the last fifteen years, pathology underwent significant changes in the field of soft tissue tumours. They were related to considerable advances in molecular biology and genetics. New data led to the revision of the WHO classification. Malignant fibrous histiocytoma is no longer considered as an entity. It has split up into several subgroups belonging to liposarcomas, leiomyosarcomas or undifferentiated sarcomas. Haemangiopericytoma underwent reappraisal and was put in the same category as solitary fibrous tumour. Many tools have improved. Immunohistochemistry performed with new antibodies had its specificity increased, and became appropriate for the prediction of therapeutic response in some cases, e.g. CD117 detecting mutations of the c-kit proto-oncogen in gastro-intestinal stromal tumours. Refinement of the techniques allows accurate diagnoses from core needle biopsies. Surgical specimens are collegially examined by surgeons and pathologists with special attention paid to resection margins. Although bound by some limitations, the grading system of the French Federation of Cancer Centers has currently remained the best predictor of metastasis-free survival and overall survival of patients. It is based on an assessment of three parameters: differentiation, amount of necrosis, and mitotic count of tumours. The pathologist sets up a diagnosis, and actively takes part in the prediction of the prognosis and therapeutic response. He is one of the major participants in decision making for multimodal treatment of sarcomas.