Proximal and classic epithelioid sarcomas are distinct molecular entities defined by MYC/GATA3 and SOX17/endothelial markers, respectively.

Epithelioid sarcoma (ES) is a rare tumor hallmarked by the loss of INI1/SMARCB1 expression. Apart from this alteration, little is known about the biology of ES. Despite recent advances in treatment, the prognosis of ES remains unsatisfactory. To elucidate the molecular underpinnings of ES, and to identify diagnostic biomarkers and potential therapeutic vulnerabilities, we performed an integrated omics profiling (RNA sequencing and methylation array) of 24 primary, untreated ESs. Transcriptome and methylome analysis identified two distinct molecular clusters that essentially corresponded to the morphologic variants of ES, classic ES (C-ES) and the more aggressive proximal ES (P-ES). The P-ES group was characterized by hyperactivation of GATA3 and MYC pathways, with extensive epigenetic rewiring associated with EZH2 overexpression. Both DNA methylation and gene expression analysis indicated a striking similarity with the "MYC subgroup" of ATRT, another SMARCB1-deficient tumor, implying a shared molecular background and potential therapeutic vulnerabilities. Conversely, the C-ES group exhibited an endothelial-like molecular profile, with expression of vascular genes and elevated pro-angiogenic SOX17 signaling. Immunohistochemistry validated the overexpression of the chromatin regulators GATA3 (9/12 vs. 0/16) and EZH2 (7/7 vs. 2/6) in P-ESs, and of the vascular factors SOX17 (8/8 vs. 1/10) and N-cadherin (5/9 vs 0/10) in C-ESs. Therefore, these molecules emerge as potential diagnostic tools to fill the gap represented by the lack of ES subtype-specific biomarkers. In summary, our study shows that P-ES and C-ES represent distinct molecular entities defined by MYC/GATA3 and SOX17/endothelial molecular traits, respectively. Besides providing insights into the biology of ES, our study pinpoints subtype-specific biomarkers and potential therapeutic vulnerabilities.

Are IDH1 R132 Mutations Associated With Poor Prognosis in Patients With Chondrosarcoma of the Bone?

BACKGROUND: Because chondrosarcomas vary widely in their behavior, and because anticipating their behavior based on histology alone can be challenging, genetic markers represent an appealing area of inquiry that may help us refine our prognostic approaches. Isocitrate dehydrogenase (IDH) mutations are involved in the pathogenesis of a variety of neoplasms, and recently, IDH1/2 mutations have been found in the tissue of benign cartilage tumors as well as in conventional chondrosarcomas and highly aggressive dedifferentiated chondrosarcomas. However, their association with patient survival is still controversial. QUESTIONS/PURPOSES: (1) What proportion of patients with chondrosarcomas carry IDH mutations, and which IDH mutations can be found? (2) Are any specific IDH mutations associated with poorer overall survival, metastasis-free survival, or local recurrence-free survival? METHODS: Between April 2017 and December 2022, we treated 74 patients for atypical cartilaginous tumors or chondrosarcomas in a musculoskeletal tumor referral center. Patients were considered potentially eligible for the present study if the histologic diagnosis was confirmed by two expert soft tissue and bone pathologists following the current WHO classification, complete preoperative imaging and follow-up data were available, surgical excision was performed by sarcoma orthopaedic surgeons directed by a team leader, and the minimum follow-up was 2 years after surgical treatment unless the patient died. Data including sex, age, diagnosis, grade, type of operation, local recurrence, metastasis, and oncologic follow-up were recorded. Forty-one patients (55%) were eligible for the study. For each patient, DNA was extracted and quantified from paraffin-embedded sections of tumor tissue, and the mutational status of IDH1 (codons 105 and 132) and IDH2 (codons 140 and 172) genes was assessed. Of those, 56% (23 of 41) of patients had adequate DNA for analysis of IDH mutations: 10 male and 13 female patients, with a median age of 59 years (range 15 to 98 years). There were 22 conventional chondrosarcomas (8 atypical cartilaginous tumors, 11 Grade 2, and 3 Grade 3) and 1 dedifferentiated chondrosarcoma. Stage was IA in 3 patients, IB in 5, IIA in 1, IIB in 13, and III in 1, according to the Musculoskeletal Tumor Society classification. At a median follow-up of 3.5 years (range 4 months to 5.6 years), 14 patients were disease-free, 2 were alive with disease, and 7 died (3 within 2 years from surgery). Eight patients had metastases, and 7 developed local recurrence. We determined the proportion of patients who carried IDH mutations, and compared patients with and without those mutations in terms of overall survival, metastasis-free survival, and local recurrence-free survival using Kaplan-Meier curves. RESULTS: Six patients showed wild-type IDH genes, and 17 had IDH mutations (12 had IDH1 R132, 3 had IDH1 G105, and 2 had IDH2 R172). Overall survival at 2 years using the Kaplan-Meier estimator was lower in patients with an IDH mutation than in those with the wild-type gene (75% [95% confidence interval 50% to 99%] versus 100% [95% CI 100% to 100%]; p = 0.002). Two-year metastasis-free survival was also lower in patients with an IDH mutation than in those with the wild-type gene (33% [95% CI 7% to 60%] versus 100% [95% CI 100% to 100%]; p = 0.001), as was 2-year local recurrence-free survival (70% [95% CI 42% to 98%] versus 100% [95% CI 100% to 100%]; p = 0.02). CONCLUSION: We found that IDH1 R132 mutations were negatively associated with the prognosis of patients with bone chondrosarcomas. Nevertheless, more extensive studies (such as multicenter international studies) are needed and advisable to confirm our observations in this preliminary small series. Moreover, evaluating mutational status in fresh samples instead of in paraffin-embedded sections could help to increase the number of patients with adequate DNA for analysis. If our findings will be confirmed, the evaluation of IDH mutational status in biopsy samples or resection specimens could be considered when stratifying patients, highlighting those who may benefit from more aggressive treatment (such as adjuvant chemotherapy) or closer follow-up. LEVEL OF EVIDENCE: Level III, prognostic study.

The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives.

Mesenchymal tumours represent one of the most challenging field of diagnostic pathology and refinement of classification schemes plays a key role in improving the quality of pathologic diagnosis and, as a consequence, of therapeutic options. The recent publication of the new WHO classification of Soft Tissue Tumours and Bone represents a major step toward improved standardization of diagnosis. Importantly, the 2020 WHO classification has been opened to expert clinicians that have further contributed to underline the key value of pathologic diagnosis as a rationale for proper treatment. Several relevant advances have been introduced. In the attempt to improve the prediction of clinical behaviour of solitary fibrous tumour, a risk assessment scheme has been implemented. NTRK-rearranged soft tissue tumours are now listed as an "emerging entity" also in consideration of the recent therapeutic developments in terms of NTRK inhibition. This decision has been source of a passionate debate regarding the definition of "tumour entity" as well as the consequences of a "pathology agnostic" approach to precision oncology. In consideration of their distinct clinicopathologic features, undifferentiated round cell sarcomas are now kept separate from Ewing sarcoma and subclassified, according to the underlying gene rearrangements, into three main subgroups (CIC, BCLR and not ETS fused sarcomas) Importantly, In order to avoid potential confusion, tumour entities such as gastrointestinal stroma tumours are addressed homogenously across the different WHO fascicles. Pathologic diagnosis represents the integration of morphologic, immunohistochemical and molecular characteristics and is a key element of clinical decision making. The WHO classification is as a key instrument to promote multidisciplinarity, stimulating pathologists, geneticists and clinicians to join efforts aimed to translate novel pathologic findings into more effective treatments.

The contribution of Juan Rosai to the pathology of soft tissue tumors.

The conceptual evolution in the field of soft tissue tumor pathology has been mostly driven by a relatively small group of individuals that includes giants of the past and the present such as James Ewing, Raffaele Lattes, Arthur Purdy Stout, Franz Enzinger, Sharon Weiss, Lennart Angervall, Harry Evans, Marku Miettinen, and Christopher Fletcher. Juan Rosai, not only exerted an immense impact on surgical pathology in general, but in consideration of his unique talent in identifying novel clinicopathologic entities, has also contributed remarkably to current understanding of mesenchymal neoplasms. The creation of desmoplastic small round cell tumor certainly ranks among his most relevant efforts, although he actually put his mark on a broad variety of soft tissue lesions, including vascular neoplasms. It would be impossible to include in a single article all the entities that he created or contributed to refine; therefore, this review is limited to a selection of what we believe represent true milestones.

Mesenchymal tumours of the gastrointestinal tract.

Mesenchymal tumours represent a heterogenous group of neoplasms encopassing benign, intermediate malignancy, and malignant entities. Sarcomas account for approximately 1% of human malignancies. In consideration of their rarity as well as of intrinsic complexity, diagnostic accuracy represents a major challenge. Traditionally, mesenchymal tumours are regarded as lesions the occurrence of which is mostly limited to somatic soft tissues. However, the occurrence of soft tissue tumours at visceral sites represent a well recognized event, and the GI-tract ranks among the most frequently involved visceral location. There exist entities such as gastrointestinal stromal tumours (GIST) and malignant gastointestinal neuroectodermal tumors that exhibit exquisite tropism for the GI-tract. This review will focus also on other relevant clinico-pathologic entities in which occurrence at visceral location is not at all negligible.

Primary malignant ossifying fibromyxoid tumour of the bone. A clinicopathologic and molecular report of two cases.

OBJECTIVE: To report the exceptional occurrence of ossifying fibromyxoid tumour (OFMT) as a primary bone lesion. OFMT is a rare soft tissue tumour of uncertain differentiation and variable malignant potential, that occurs in adults with a slight male predominance. It is typically located in the subcutis or in the skeletal muscles of the extremities, followed by trunk or head and neck. METHODS: Two cases of OFMT proven to arise from bone are presented. The first is a 65-year old female with a history of rib "osteosarcoma", presenting with an inferior lobe left lung mass. The second is a man with a lytic lesion of the 5th cervical vertebra that recurred shortly after resection. Following H&E and immunohistochemical examination, tumour samples were analysed by NGS and by break-apart FISH to detect rearrangement of the PHF1 and TFE3 genes. RESULTS: PHF1 gene-rearrangement was identified by FISH on both the primary and the metastatic lesion of first patient. NGS identified a PHF1(intron1) and EPC1 (exon 10) fusion transcript later confirmed by positive PHF1 rearrangement on FISH in the second case. CONCLUSIONS: The demonstration of PHF1 gene rearrangements represents a fundamental ancillary diagnostic test when presented with challenging examples of OFMT.

Primary vascular tumors of bone: A comprehensive literature review on classification, diagnosis and treatment.

Primary vascular tumors of bone are a heterogeneous group of neoplasms, ranging from benign hemangiomas to frankly malignant epithelioid hemangioendotheliomas and angiosarcomas. Over the years, their classification has been a matter of discussion, due to morphologic similarities and uncertainty regarding biologic behavior. Over the past decade, with the development of next-generation sequencing, there has been a significant improvement in the molecular characterization of these lesions. The integration of their morphologic, immunohistochemical and molecular features has led to a better stratification, with important prognostic and therapeutic implications. Nevertheless, primary vascular bone tumors still represent a challenge for medical oncologists. Given their rarity and heterogeneity, in the last few years, there has been no significant progress in medical treatment options, so further research is needed. Here we present a review of the current knowledge regarding primary vascular tumors of the bone, correlating clinicopathologic features with tumor behavior and therapeutic approaches.

Development of a Preclinical Double Model of Mandibular Irradiated Bone and Osteoradionecrosis in New Zealand Rabbits.

PURPOSE: Radiotherapy (RT) plays a crucial role in head and neck (HN) cancer treatment. Nevertheless, it can lead to serious and challenging adverse events such as osteoradionecrosis (ORN). A preclinical rabbit model of irradiated bone and ORN is herein proposed, with the aim to develop a viable model to be exploited for investigating new therapeutic approaches. METHODS: Nine New Zealand white rabbits were irradiated using a single beam positioned to the left of the mandible and directed perpendicular to the left mandible. A 10 × 10 mm2 region of interest (ROI) located below the first molar tooth on the left side was identified and irradiated with 7 Gy each fraction, once every 2 days, for five fractions. Dose distributions demonstrated that the corresponding ROI on the contralateral (right) mandibular side received approximately 5 Gy each fraction, thus bilateral irradiation of the mandible was achieved. ROIs were categorized as ROIH on the left side receiving the high dose and ROIL on the right side receiving the low dose. Rabbits were followed up clinically and imaged monthly. After 4 months, the irradiated bone was excised, and histological examination of ROIs was performed. RESULTS: Radiological signs suggestive for ORN were detected in the entire population (100%) 16 weeks after irradiation on ROIH, which consisted of cortical erosion and loss of trabeculae. ROIL did not show any radiological evidence of bone damage. Histologically, both sides showed comparable signs of injury, with marked reduction in osteocyte count and increase in empty lacunae count. CONCLUSIONS: A preclinical double model was successfully developed. The side receiving the higher dose showed radiological and histological signs of bone damage, resulting in an ORN model. Whereas the contralateral side, receiving the lower dose, presented with histological damage only and a normal radiological appearance. This work describes the creation of a double model, an ORN and irradiated bone model, for further study using this animal species.

Fifteen different 18F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy.

PURPOSE: The aim of this study was to correlate qualitative visual response and various PET quantification factors with the tumour regression grade (TRG) classification of pathological response to neoadjuvant chemoradiotherapy (CRT) proposed by Mandard. METHODS: Included in this retrospective study were 69 consecutive patients with locally advanced rectal cancer (LARC). FDG PET/CT scans were performed at staging and after CRT (mean 6.7 weeks). Tumour SUVmax and its related arithmetic and percentage decrease (response index, RI) were calculated. Qualitative analysis was performed by visual response assessment (VRA), PERCIST 1.0 and response cut-off classification based on a new definition of residual disease. Metabolic tumour volume (MTV) was calculated using a 40 % SUVmax threshold, and the total lesion glycolysis (TLG) both before and after CRT and their arithmetic and percentage change were also calculated. We split the patients into responders (TRG 1 or 2) and nonresponders (TRG 3-5). RESULTS: SUVmax MTV and TLG after CRT, RI, ΔMTV% and ΔTLG% parameters were significantly correlated with pathological treatment response (p < 0.01) with a ROC curve cut-off values of 5.1, 2.1 cm(3), 23.4 cm(3), 61.8 %, 81.4 % and 94.2 %, respectively. SUVmax after CRT had the highest ROC AUC (0.846), with a sensitivity of 86 % and a specificity of 80 %. VRA and response cut-off classification were also significantly predictive of TRG response (VRA with the best accuracy: sensitivity 86 % and specificity 55 %). In contrast, assessment using PERCIST was not significantly correlated with TRG. CONCLUSION: FDG PET/CT can accurately stratify patients with LARC preoperatively, independently of the method chosen to interpret the images. Among many PET parameters, some of which are not immediately obtainable, the most commonly used in clinical practice (SUVmax after CRT and VRA) showed the best accuracy in predicting TRG.

Case report: pseudoendocrine sarcoma, a clinicopathologic report of a newly described soft tissue neoplasm.

Papke et al. recently reported a series of twenty-three soft tissue lesions chiefly arising in older adults featuring distinct morphological and genetic characteristics. Pseudoendocrine sarcoma (PS) is the somewhat descriptive and provisional term adopted for the newly reported mesenchymal neoplasm. Since the publication of the original paper published in January 2022, a single case of PS has been published. Pseudoendocrine sarcoma shows a predilection for the paravertebral deep soft tissues of the trunk, low-grade neuroendocrine-like histological features, and hallmark CTNNB1 activating mutations.Herein, we will discuss a case of a 72-year-old woman presenting with a 4-cm laterocervical mass. Hematoxylin and eosin slides showed a multilobular proliferation of monomorphic epithelioid cells with speckled chromatin arranged in nests and trabeculae. Immunohistochemical staining and molecular analysis were consistent with the newly proposed entity.

"While there is p57, there is hope." The past and the present of diagnosis in first trimester abortions: Diagnostic dilemmas and algorithmic approaches. A review.

Distinction of hydatidiform moles (HM) from non-molar (NM) specimens and subclassification of HM as complete hydatidiform mole (CHM) versus partial hydatidiform mole (PHM) are important for clinical practice and investigational studies. The issue of diagnostic reproducibility is still unsolved, the lack of diagnostic accuracy based on morphology is substantial with an important interobserver variability, even between experienced gynecologic pathologists. Many ancillary techniques have been investigated in the last years to refine HM diagnosis. p57 (a paternally imprinted, maternally expressed gene) immunohistochemistry, based on the unique genetics of CHM (purely androgenetic), PHM (diandric triploid), and NM specimens (biparental, with allelic balance) can identify CHMs, which lack p57 expression because of a lack of maternal DNA. However, although its role in HM diagnosis is pivotal, it does not allow the distinction of PHM from NM specimens, both of which express p57 due to the presence of maternal DNA. Molecular genotyping, which compares villous and decidual DNA patterns to determine the parental source and ratios of polymorphic alleles, distinguishes purely androgenetic CHM from diandric triploid PHM, and both of these from NM specimens. Beyond the claim of establishing a "diagnostic truth", exceptions and peculiar genetic scenarios in the origin of rare CHM and PHM should be kept in mind when approaching any ancillary technique. An algorithmic approach, even in settings with limited resources, can help the pathologists in the diagnostic dilemma of diagnosis of first trimester abortions.

Molecular profiling of appendiceal serrated lesions, polyps and mucinous neoplasms: a single-centre experience.

PURPOSE: Non-neuroendocrine neoplasms of the appendix are a phenotypically heterogeneous group of lesions; a comprehensive molecular characterization of these tumors is still lacking. METHODS: A total of 52 samples taken from 49 patients was evaluated: 18 sessile serrated lesions (SSL; 3 with dysplasia), 2 high-grade tubular adenomas, 1 tubulo-villous adenoma,1 hyperplastic polyp, 18 low-grade appendiceal mucinous neoplasms (LAMN), 3 high-grade appendiceal mucinous neoplasms (HAMN) and 9 mucinous adenocarcinomas. Hotspot mutational profiling of the RNF43, SMAD4, KRAS, NRAS, BRAF and PIK3CA genes was performed. Expression of p53, MLH1, PMS2, MSH2, and MSH6 was evaluated by immunohistochemistry. RESULTS: KRAS was the most frequently mutated gene (53.9% of cases), followed by RNF43 (15.4%), and BRAF (13.5%). In particular: KRAS was mutated in 44.4% of adenocarcinomas, 66.7% of HAMNs, 61.1% of LAMNs, 53.3% of SSL without dysplasia and in 66.7% of SSL with dysplasia; RNF43 was mutated in 33.3% of adenocarcinomas, 66.7% of HAMNs, 11.1% of LAMNs and in 6.7% of SSL without dysplasia; BRAF was mutated in 11.1% of adenocarcinomas, 26.7% of SSL without dysplasia and in 5.6% of LAMNs. Only a case of high-grade tubular adenoma showed mismatch repair deficiency, while immunohistochemical expression of p53 was altered in 21.1% of cases. CONCLUSIONS: The histological phenotypic similarities between appendicular mucinous lesions and serrated colon lesions do not reflect a similar genetic landscape. Mismatch repair deficiency is a rare event during appendiceal mucinous carcinogenesis.

The Pathologic and Molecular Landscape of Esophageal Squamous Cell Carcinogenesis.

Esophageal squamous cell carcinoma represents the most common histotype of epithelial neoplasm occurring within esophageal mucosa worldwide. Despite the comprehensive molecular characterization of this entity, to date no significant targeted therapy has been introduced into clinical practice. In this review, we describe the molecular landscape of esophageal squamous cell carcinoma based on the most recent literature. Moreover, we focus on other rare variants and on the relationship with head and neck squamous cell carcinomas.

Histopathological landscape of rare oesophageal neoplasms.

The landscape of neoplastic pathology of the oesophagus is dominated by malignancies of epithelial origin, in particular by oesophageal adenocarcinoma and oesophageal squamous cell carcinoma. However, several other histopathological variants can be distinguished, some associated with peculiar histopathological profiles and prognostic behaviours and frequently underrecognized in clinical practice. The aim of this review is to provide a comprehensive characterization of the main morphological and clinical features of these rare variants of oesophageal neoplastic lesions.

How to harmonize SUVs obtained by hybrid PET/CT scanners with and without point spread function correction.

State of the art point-spread function (PSF) corrections implemented in positron emission tomography/computed tomography (PET/CT) reconstruction improved image quality and diagnostic performance but caused an increase in the standardized uptake value (SUV) compared to a conventional OSEM reconstruction system. The EANM suggested one produce two reconstructions, one optimised for maximum lesion detection and one for semi-quantitative analysis. In this work we investigated an alternative methodology, using a single reconstruction data set together with a post-reconstruction algorithm for SUV harmonization. Data acquisition was performed on a Siemens Biograph mCT system equipped with lutetium oxyorthosilicat crystals, PSF and time-of-flight algorithms and on a General Electric Discovery STE system equipped with BGO crystals. Both a EANM double reconstruction method and a dedicated post-reconstruction algorithm (marketed as EQ-filter) were tested to harmonize the quantitative values of the two PET/CT scanners. For phantom measurements we used a NEMA IQ phantom and a Jaszczak cylindrical phantom equipped with small spheres (lesion to background ratios of 8:1 and 4:1). Several different reconstruction settings were tested in order to provide a general methodology. Data obtained by phantom measurements were validated on seven oncologic patients who performed a one-bed extra acquisition on a different scanner. The evaluation regarded 39 small lesions (diameters: 0.3-2.6 cm) and was performed by two experienced nuclear medicine physicians. The SUV recoveries measured with the PSF reconstruction exceeded those obtained by the OSEM reconstruction with deviations ranging from 16% to 150%. These discrepancies resulted below 7% applying the optimized value of the EQ.filter or the double-reconstruction methods. For each reconstruction setting the optimal value of the EQ.filter was identified in order to minimize these discrepancies. Patient data, analyzed by Wilcoxon statistical test, confirmed and validated phantom measurements. EQ.filter can harmonize SUV values between different PET/CT scanners using a single reconstruction optimized to maximum lesion detectability. In this way, the second reconstruction proposed by EANM/EARL is avoided.

Thyroid Paraganglioma: Our Experience and Systematic Review of the Literature on a Rare Tumor.

INTRODUCTION: Primary paraganglioma (PG) of the thyroid gland is an extremely rare neuroendocrine tumor with potential for misdiagnosis. We describe 2 cases of thyroid PG, suggest a possible diagnostic and therapeutic management strategy, and present a systematic review of the literature. CASE REPORTS: Two 67-year-old women presented similarly with asymptomatic but rapidly growing thyroid nodules in which malignancy was suspected after fine needle aspiration biopsy, "THY 4" according to the 2014 SIAPEC classification, both undergoing total thyroidectomy. Unexpectedly, immunohistochemistry showed neuroendocrine cellular architecture that was negative for common markers of well-differentiated follicular neoplasms, thyroglobulin, thyroid transcription factor 1, cytokeratins and medullary thyroid cancer, calcitonin, carcinoembryonic antigen, whereas neuron-specific enolase, synaptophysin, chromogranin A, and S-100 protein were highly expressed, confirming the diagnosis of primary thyroid PG. The patients were both discharged on postoperative day 2, without any other therapy and are currently well without evidence of local recurrence of metastatic disease, after 4 years and 3 months of follow-up, respectively. DISCUSSION: These are the only 2 cases of thyroid PG experienced in our center which specializes in thyroid surgery. Thyroid PG is a rare neuroendocrine neoplasm first described by Van Miert in 1964 with just over 50 cases reported in the literature. Our experience is concordant with the literature that the diagnosis of the primary PG of the thyroid is challenging, due to its low prevalence and the cytologic and histopathologic similarities with other more frequently diagnosed benign and malignant thyroid tumors. Immunohistochemistry is required for definitive diagnosis but gross tumor characteristics are also helpful for diagnosis. Surgical resection is the recommended standard treatment.

Biological target volume overlapping segmentation system method for avoiding false-positive PET findings in assessing response to neoadjuvant chemoradiation therapy in rectal cancer.

PURPOSE: FDG PET/CT has a recognized high predictive power to assess the response to neoadjuvant chemoradiation therapy (CRT) in patients affected by locally advanced rectal cancer (LARC), but a relatively high number of false-positive findings decrease its specificity: with the aim to solve this problem, a new method of imaging analysis is here proposed. METHODS: The new method here described, named Biological target volume (BTV) Overlapping Segmentation System (BOSS), has been applied on 24 consecutive patients with LARC that were all previously classified as nonresponders to CRT by means of the response index criterion that is adopted in our center. The BOSS method is based on the quantification of the amount of superimposition between pretreatment and posttreatment BTV. All BTVpre was down using a threshold of 60% of SUVmax in the tumor (BTV60). The results (overlap volumes and percentage of overlap volumes) were then matched up with postoperative pathology classified by the Mandard's tumor regression grade (TRG) system. RESULTS: Eleven patients were classified as responders (TRG1-2) and 13 as nonresponders (TRG 3-5). Among all the results obtained by BOSS method, only the percentage of overlap volume data between BTV60 and BTVpost (%Over_60) was able to correctly distinguish between responders and nonresponders. In our experience, a cutoff of 56% on the %Over_60 provided the best results in terms of true negative (11 cases), true positive (12 cases), false negative (1 case), and false positive (none). CONCLUSIONS: This new method, we developed, appears able to unmask the false-positive cases, improving the specificity of FDG PET/CT to predict the response to CRT patients with LARC.

Phantom study of the impact of reconstruction parameters on the detection of mini- and micro-volume lesions with a low-dose PET/CT acquisition protocol.

PURPOSE: Every PET scanner suffers of the partial volume effect (PVE), that is a loss of contrast in small lesions causing a worsening in standardized uptake value (SUV) accuracy, that is critical if quantitative PET/CT imaging is used for diagnosis and therapy. METHODS: In order to quantify PVE and optimize our clinical protocols to minimize this effect in a last generation PET/CT scanner, we utilized a cylindrical phantom equipped with ten mini- and micro-volume hollow spheres. The lesion detectability and the SUV accuracy were evaluated at a fixed spheres to background intrinsic contrast (activity concentration ratio 8:1) but in different scan conditions: (a) acquisition modality (3D vs. 2D), (b) number of subset per iteration, (c) type of post-reconstruction filter and (d) activity concentration (i.e. total counts). Also the effect of different absorber thickness was evaluated. RESULTS: Small lesion detectability resulted better in images acquired in 3D mode rather than 2D, mainly because of the lower noise produced by the fully-3D algorithm. The number of reconstruction iterations and the post-processing filter used affected both the contrast underestimation and the spatial resolution. Decreasing the (18)F activity injected according to the low-dose protocol, the small lesions could be distinguished from the background down to a diameter of 6.2mm and the SUV accuracy did not deteriorate. Adding absorber thickness around the phantom, the image noise slightly increased while SUV accuracy did not change. CONCLUSIONS: The hybrid PET/CT scanner we evaluated showed good performances, mainly in 3D acquisition modality. The phantom measurements showed that the most appropriate reconstruction protocol derived from a compromise between the contrast accuracy and the noise variance in PET images. The low-dose protocol clinically used demonstrated no loss in SUV accuracy and an adequate lesion detectability for lesions down to 6.2mm in diameter.