PET-CT Data Research Articles

The impact of BTK knockdown on lung adenocarcinoma growth and immune response.

This study explores the molecular role of the BTK gene in lung adenocarcinoma (LUAD) progression and patient prognosis. Using a radiomics model based on BTK expression and PET-CT data analyzed through DeeplabV3, alongside transcriptomic and clinical data from TCGA, we established a strong predictive relationship between BTK levels and LUAD outcomes. Our findings demonstrate that low BTK expression is linked to poorer prognoses. Experimental models, including cell lines and invivo mouse studies, revealed that BTK deficiency leads to increased LUAD cell proliferation, invasion, and metastasis. Furthermore, invivo models indicated that BTK knockdown results in enhanced tumor growth and diminished CD8+ T cell activity. These results suggest that BTK plays a crucial role in modulating LUAD progression and the tumor immune environment, highlighting its potential as a therapeutic target.

Semi-automatic detection and evaluation of metastases in lymph nodes in diagnostics of the prostate from PET-CT data

Abstract We present a novel tool designed for the semiautomatic detection and assessment of prostate cancer during recurrence diagnostics using PET-CT with prostate-specific membrane antigen (PSMA). The tool automatically generates a structured report, which is enhanced by 3D images and ensures the reproducibility of the findings. Moreover, the area of the findings is automatically determined and can be corrected manually. Image data from 50 patients following radical prostatectomy was used. Our approach and its user interface were qualitatively evaluated by a nuclear medicine specialist. The segmentation analysis revealed a requirement for further automation. The resulting report was deemed highly beneficial, particularly in terms of the resulting reproducibility and the presentation of 3D images depicting the findings. The presented tool has great potential for much-needed support in everyday clinical practice, as it facilitates the communication of the diagnostic results to colleagues and patients and thus prevents misunderstandings.

Treatment Outcomes in Primary Mediastinal Large B-Cell Lymphoma. Experience of the AF Tsyb Medical Radiological Research Center (Obninsk)

AIM. To assess chemotherapy outcomes in patients with primary mediastinal large B-cell lymphoma (PMBCL) treated at the AF Tsyb Medical Radiological Research Center from 2016 to 2023. MATERIALS & METHODS. The analysis focused on the data from 58 patients with the morphologically verified diagnosis of PMBCL. The patients were aged 17–62 years (median 34 years), there were 39 women and 19 men. The median follow-up was 51.2 months (range 0.4–200.9 months). Depending on drug chemotherapy regimens, patients were divided into 3 groups: R-NHL-BFM-90 (n = 9), R-CHOP (n = 17), and R-MACOP-B (n = 32). Most patients (90 %) received mediastinal radiotherapy of total 30–46 Gy. RESULTS. The 5-year overall survival in the therapy groups was 66.7 %, 88.2 %, and 100 %, respectively (p = 0.007), progression-free survival was 66.7 %, 70.6 %, and 96.9 % (p = 0.006), and event-free survival was 66.7 %, 54.7 %, and 90.6 % (p = 0.038). On the whole, the toxicity profile of chemotherapy was quite acceptable. Neither low blood values nor other adverse events essentially affected a complete implementation of chemoradiotherapy program. The intermediate outcomes were based on PET-CT data after 2–4 therapy cycles in 37 (64 %) patients. PET-CT showed that at the stage of drug chemotherapy, complete response (CR) was achieved in 27 (73 %) patients, and partial response (PR) was achieved in 4 (11 %) patients. With respect to the CR and PR criteria, there were 6 (16 %) non-responders. CONCLUSION. PMBCL is one of extranodal lymphomas with thymic B-cells being primary source of tumor growth. PMBCL is characterized by aggressive course and extreme heterogeneity of clinical manifestations. Up to now, the first-line chemotherapy decision making in PMBCL has remained an issue with practical importance. This paper reports immediate and long-term outcomes of the program chemoradiotherapy regimen R-MACOP-B with subsequent consolidation radiotherapy. The results obtained can be termed quite satisfactory and noninferior to the data from national and international sources. Nevertheless, more effective chemoradiotherapy programs for PMBCL continue to be elaborated. In this context, immune checkpoint inhibitors as part of therapy programs seem to hold promise for the treatment of newly diagnosed PMBCL.

SUV max as Predictor of Metastatic Disease on 18 F-FDG PET-CT in Hepatocellular Carcinoma.

To ascertain the utility ofmaximum standardised uptake value (SUVmax) in 18F-FDG PET-CT in predicting metastatic disease burden in hepatocellular carcinoma (HCC) patients. Descriptive study. Place and Duration of the Study: Department of Nuclear Medicine and PET-CT Imaging, Institute of Nuclear Medicine and Oncology (INMOL), Lahore, Pakistan, from April to October 2022. 18F-FDG PET-CT data of 87 patients were analysed prospectively. Patients were considered regardless of resection status. The SUVmax measurements were performed, and their association with metastases was determined. Molecular docking studies were conducted to determine a mechanism behind the higher SUVmax at the metastatic sites. A higher number of patients (49) was found to have metastasis (1 to 5 in numbers) and demonstrated higher SUVmax, especially in cases of pre-surgery and post-transplant state. A positive correlation existed between SUVmax of pre-surgery (r = 0.419, p = 0.001) and post-transplant patients (r = 0.779, p = 0.001). Molecular docking studies revealed a strong binding affinity (-5.18± 0.25 kcal/mol) between the hexokinase (HK-II) and 18F-FDG. SUVmax positively correlated with metastatic tumour burden. The strong binding affinity between the HK-II and 18F-FDG may be the reason. 18F-FDG PET-CT appeared beneficial in providing prognostic information for HCC in a selected group. Hepatocellular carcinoma, 18F-FDG, Positron emission tomography, Maximum standardised uptake value, SUVmax, HK-II binding, PET-CT, Metastases.

Behavioral variant frontotemporal dementia associated with GRN and ErbB4 gene mutations: a case report and literature review

ObjectiveTo report the clinical manifestation and genetic characteristics of a patient having frontotemporal dementia (FTD) with abnormal behavior and unstable walking.MethodsThe clinical and imaging features of a patient who was eventually diagnosed with FTD were analyzed. The patient’s neuropsychological, PET-CT, electromyography, and genetic data were collected. Furthermore, the patient’s blood samples were examined for FTD-related genes.ResultsThe patient was a 52-year-old man with hidden onset. The symptoms progressed gradually, presenting with abnormal behaviors, including repeated shopping, taking away other people’s things, constantly eating snacks, and frequently calling friends at night. The patient also exhibited executive dysfunction, such as the inability to cook and multiple driving problems, e.g., constantly deviates from his lane while driving. In addition, the patient showed personality changes such as irritability, indifference, and withdrawal, as well as motor symptoms, including unstable walking and frequent falls when walking. Brain magnetic resonance imaging revealed hippocampal sclerosis along with widening and deepening of the bilateral temporal lobe sulcus. Brain metabolic imaging via PET-CT demonstrated decreased metabolism in the bilateral prefrontal lobe, with the abnormal energy metabolism indicating FTD. Lastly, blood sample analysis detected mutations in the amyotrophic lateral sclerosis (ALS)-related GRN gene c.1352C > T (p.P451L) and ErbB4 gene c.256 T > C (p.Y86H).ConclusionThis is the first case of heterozygous mutations in the GRN and ErbB4 genes in FTD alone. The GRN and ErbB4 genes are likely to be important in the pathogenesis of FTD, expanding the common genetic profile of ALS and FTD.

Abstract 13946: Predictive Value of FDG-PET/CT Derived Coronary Artery Calcium Scoring in Non-Small Cell Lung Cancer Patients

Introduction/Background: Coronary artery calcium (CAC) scoring on PET-CT has emerged as a potential prognostic tool in patients with cancer. Research Question/Hypothesis: CAC determined using non-ECG gated PET-CT data is a useful predictor of major adverse cardiac events (MACE) and overall survival in non-small cell lung cancer (NSCLC) patients. Goals/Aims: To investigate the association between CAC scores, MACE, and survival outcomes in NSCLC patients. Methods/Approach: We retrospectively analyzed baseline staging PET-CT (n=130) or CT (n=24), clinical history, demographics, and follow-up survival data of NSCLC patients. Patients were divided into four groups based on their CAC scores according to the 2016 SCCT/STR guidelines. Cox regression analysis was performed to assess the association between CAC score and survival, CAC score and MACE, and smoking history and survival. Results/Data: The mean age of the population was 66.3 ± 10.8 years with 42.9% never smokers. Of the 154 patients evaluated, 49.3% died during a mean follow-up period of 3.5 years. Cox regression analysis revealed a trend toward improved survival rates of patients with lower CAC scores (P= 0.081 for No/Minimal risk and P= 0.039 for Mild group). Current or prior smoking was significantly associated with decreased survival (P = .013, HR = 1.8). Logistic regression analysis showed a significant inverse relationship between CAC scores and MACE (n=32) for no risk/minimal (P = .001) and mild risk (P < .001) groups. Additionally, there was an inverse association between CAC and number of observed acute MI for no /minimal risk group (P= .02) and mild risk group (P= .003). Conclusion: Our findings suggest that lower CAC scores, measured at initial staging PET-CT, are associated with decreased MACE and acute MI in NSCLC patients. Further studies are needed to validate these findings and explore the potential of CAC scoring as a routine prognostic tool in NSCLC management.

Real World Outcomes with Idecabtagene Vicleucel (Ide-Cel) CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma

Introduction: Idecabtagene vicleucel (ide-cel) was the first FDA approved BCMA targeted CAR-T cell therapy for the treatment of relapsed/refractory multiple myeloma (RRMM). However, clinical trials are highly selective with stringent eligibility criteria. The objective of this study was to evaluate the safety and efficacy of standard of care ide-cel. Methods: Patients treated with ide-cel were reported to the CIBMTR registry for long-term follow up of safety and efficacy outcomes. The current analysis includes the first 603 adult patients who received infusion with commercial ide-cel for the treatment of RRMM, with at least one follow-up form reported. Patients treated on investigational clinical trials or who received non-conforming products were excluded. Multivariate analysis was done using Cox regression. Results: Median follow-up of the 603 patients is 6.6 months, with updated follow up to be presented at the meeting. As shown in Table 1a median age of patients was 65 years, 26% (n=157) were ≥70 years old and 59% (n=354) were male. Black and Hispanic patients comprised 13% (n=77) and 7% (n=42) of the cohort, respectively; 23% (n=137) had Karnofsky performance status <80%, 75% (n=451) had ≥ 1 significant comorbidity and 13% (n=77) had platelets <50,000/µL. Patients for whom data on prior lines of therapy (LoT) were documented (n=470), the median prior LoT was 7 (4-21), 36% (n=217) had penta-refractory disease and 5% (n=28) had received prior-BCMA directed CAR T cell therapy. Data on the use of other BCMA targeting agents are being gathered. 17% (56/331 with PET-CT data) of patients had extramedullary disease (EMD) and 1.5% (n=9) had plasma cell leukemia. High risk cytogenetics [del17p, t(4;14), t(14;16) and/or t(14;20)] were present in 23% (n=141/523) and 45% (n=269/523) when including abnormalities of 1q (ab1q). 36% (n=101/283) of patients had ISS II and 16% (n=46/283) had ISS stage III disease. Lymphodepletion regimen was fludarabine + cyclophosphamide in 95% (n=574) of patients. All patients received ide-cel dose of 300-460 million CAR-T cells, with dose of > 400 million in 56% of patients. Cytokine release syndrome (CRS) was seen in 81% (n=490) of patients (grade ≥3: 3%), with median time to onset being 2 days. Neurotoxicity was seen in 27% (n=164) of patients (grade ≥3: 4%), with median time to onset being 2 days. Prolonged neutropenia (defined as non-recovery of ANC ≥ 500/uL by day 30) and thrombocytopenia (non-recovery of platelets ≥ 20,000/uL by day 30) was seen in 13% (n=81) and 25% (n=148) of patients, respectively. Hemophagocytic Lymphohistiocytosis-like syndrome was seen in 1% (n=6) and tumor lysis syndrome in 1.5% (n=9) of patients. Clinically significant infections were seen in 42% (n=252) of patients (bacterial: 22%, viral: 23%, fungal: 2%). Second malignancies were seen in 4.5% (n=27) of patients, including AML/MDS in 5 patients. Table 1b shows multivariate analysis for CRS and neurotoxicity. Risk factors associated with higher likelihood of grade >2 CRS were age ≥ 70, female sex and baseline platelets < 50,000/uL. Similarly, higher risk of neurotoxicity was seen with older age, high-risk cytogenetics, lower performance status and platelets < 50,000/uL. Overall response rate was 71% (n=421), ≥ very good partial response rate was 53% (n=319) and ≥ complete response (CR) rate was 27% (n=162). On multivariate analysis for response, presence of EMD, CAR-T cell dose ≤ 400 million, penta-refractory disease and lower performance status were associated with lower likelihood of CR. Estimated progression free survival (PFS) at 6 months was 62% (95% CI: 58-66%) and overall survival (OS) at 6 months was 82% (95% CI, 79-85%). At last follow-up, 26% of patients have died, majority due to disease progression (70%, n=108); causes of death in the remaining 47 patients were infection (n=15), CRS (n=1), neurotoxicity (n=2), tumor lysis (n=1), organ failure (n=7), second cancer (n=5), intracranial hemorrhage (n=3) and other (n=13). Conclusion: This is the largest real-world study of ide-cel CAR-T cell therapy in patients with RRMM. We observed a favorable safety and efficacy profile in this real-world population, despite a very heavily pre-treated population and large proportion of patients having co-morbidities that would have made them ineligible for the KarMMa clinical trial. These results further support ide-cel as a therapeutic option for a broad, real-world population of patients with RRMM.

New Data-Driven Gated (DDG) PET/CT for Radiation Treatment Planning of NSCLC

PET/CT for RT simulation of NSCLC is typically conducted in two separate imaging sessions of gated 4D-CT in radiation oncology and fusion with non-gated PET/CT in diagnostic imaging, making treatment response assessment (TRA) with PET/CT and radiation treatment planning (RTP) challenging. To remedy this short-coming, we designed a new data-driven gated (DDG) PET/CT, based on the self-gated PET and self-gated CT data to derive the gated PET/CT data free of tumor blurring and misregistration artifacts without any respiratory monitoring device (ease of use and cost reduction). The new DDG PET/CT also provides the important 4D-CT information of end-inspiratory (EI), end-expiratory (EE), maximum-intensity-projection (MIP) and average-intensity-projection (AIP) CT's. The total imaging time is < 15 min, which makes DDG PET/CT simulation in a single session without any respiratory monitoring device possible. Acquisition is standard PET/CT imaging protocol followed by a cine CT imaging of the tumor area. We utilized the commercial DDG PET from GE Discovery PET/CT and designed a new DDG CT for attenuation correction of the DDG PET for reduction of tumor motion and mis-registration. The AIP and MIP images were from the average and maximum pixel values of the cine CT images, respectively. The cine CT images with the largest and smallest average CT number in the lung region were identified as the EE and EI CT images, respectively. For the image slices without any lung region present, the largest and smallest expansions of the body outline contour were selected to be the EE and EI CT phases, respectively. The AIP and EE CT images were used for attenuation correction of the PET and DDG PET data, respectively. Both DDG PET/CT and 4D-CT of (EI, EE, AIP and MIP) are for RT simulation of NSCLC. 38 4D-CT patient data sets were compared at the EE and EI phases between our DDG CT and 4D-CT to demonstrate the applicability of the newly designed DDG CT. A prototype software on a Dell PC of i5-6500 CPU has been successfully developed to enable DDG PET/CT and 4D-CT on seven GE Discovery PET/CT scanners. The operating system was Ubuntu and the computer language was Python. In the EE phase, the images selected by DDG CT and 4D CT were identical 62.5±21.6% of the time. In the EI phase, the images selected by DDG CT and 4D CT were identical 68.2±18.9% of the time. Inspection of the EE and EI phases of DDG CT and 50% and 0% of 4D-CT demonstrated both data sets of DDG CT and 4D CT were almost identical. A new DDG PET/CT and 4D-CT in a single imaging session without any hardware gating has been developed for TRA and RTP of NSCLC. The utility is available on the network and it enables all PET/CT scanners on the network for TRA and RTP. The new DDG CT provides the benefits of 4D-CT without any requirement of external hardware gating and make possible DDG PET/CT free of tumor motion and misregistration artifacts.

DFO-Km: A Modular Chelator as a New Chemical Tool for the Construction of Zirconium-89-Based Radiopharmaceuticals.

Zirconium-89-labeled monoclonal antibodies and other large macromolecules such as nanoparticles hold great promise as positron emission tomography imaging agents. In general, zirconium-89 is an ideal radionuclide for long-circulating vectors such as antibodies or nanoparticles. It is also a promising radionuclide for theranostic radiopharmaceuticals due to its suitable match in half-life with actinium-225, thorium-227, lutetium-177, and others. As such, demand for new and optimized bifunctional chelators for zirconium-89 continues to grow. Herein, we present the modular chelator DFO-Km, which is octadentate and features lysine as a modular amino acid linker. The modular amino acid linker can be changed to other natural or unnatural amino acids to access different bioconjugation chemistries, while the chelating portion is unchanged thus retaining identical metal ion coordination properties to DFO-Km. The epsilon-amine in the DFO-Km linker (lysine) was used to complete synthesis of a bifunctional derivative bearing a p-SCN-Ph moiety. The chelator DFO-Km includes a redesigned hydroxamic acid, which provides more flexibility for metal ion coordination relative to the monomer used in the previously published DFO-Em. Moreover, a set of comprehensive DFT calculations were performed to model and evaluate 16 geometric isomers of Zr-(DFO-Km), which suggested the complex would form the optimum cic-cis-trans-trans octadentate Zr(IV) coordination geometry with no aqua or hydroxide ligands present. The bifunctional derivative p-SCN-Ph-DFO-Km was compared directly with the commercially available p-SCN-Ph-DFO, and both underwent efficient conjugation to a nonspecific human serum antibody (IgG) to yield two model immunoconjugates. The behavior of [89Zr]Zr-DFO-Km-IgG was studied in healthy mice for 2 weeks and compared to an equivalent cohort injected with [89Zr]Zr-DFO-IgG as a clinical "gold standard" control. PET-CT and biodistribution results revealed higher stability of [89Zr]Zr-(DFO-Km)-IgG in vivo over [89Zr]Zr-DFO-IgG, as demonstrated by the significant reduction of zirconium-89 in the whole skeleton as visualized and quantified by PET-CT at 1, 3, 7, and 14 days post-injection. Using CT-gated regions of interest over these PET-CT images, the whole skeleton was selected and uptake values were measured at 14 days post-injection of 3.6 ± 0.9 (DFO) vs 1.9 ± 0.1 (DFO-Km) %ID/g (n = 4, * p = 0.02), which represents a ∼48% reduction in bone uptake with DFO-Km relative to DFO. Biodistribution experiments performed on these same mice following the 14 day imaging time point revealed bone (both tibia) uptake values of 3.7 ± 1.3 (DFO) vs 2.0 ± 0.6 (DFO-Km) %ID/g (n = 6, * p < 0.05), with the tibia uptake values in close agreement with whole-skeleton ROI PET-CT data. These results indicate that DFO-Km is an improved chelator for [89Zr]Zr4+ applications relative to DFO. The bifunctional chelator p-SCN-Ph-DFO-Km shows potential as a new chemical tool for creating bioconjugates using targeting vectors such as antibodies, peptides, and nanoparticles.

Post-Treatment Neck Dissection of Tonsillar and Base of Tongue Squamous Cell Carcinoma in the Era of PET-CT, HPV, and p16.

Human-papillomavirus (HPV)-positive tonsillar and base of tongue carcinomas (TSCC/BOTSCC) are rising in incidence and treatments with radiotherapy, chemoradiotherapy (RT/CRT), and neck dissections (NDs) have several side effects. Therefore, an improved selection of patients needing salvage NDs would be beneficial. We examined the prevalence and localisations of viable tumour cells in neck lymph nodes in patients post-RT/CRT, identified by fluorodeoxyglucose positron-emission tomography with computer-tomography (FDG PET-CT), with a focus on HPV-associated tumours. Patients with 217 TSCC/BOTSCC with tumours assessed for HPV-DNA and p16INK4a undergoing FDG PET-CT 12 weeks after treatment and/or an ND were included. The FDG PET-CT data were compared with the findings in the pathology report after the ND. In total, 36/217 (17%) patients were selected for an ND due to positive findings in post-treatment FDG PET-CT. Of these, 35/36 were HPV-associated, 10/36 (28%) had viable tumour cells in the pathology reports of the neck specimen, and 8/10 (80%) were consistent with the FDG PET-CT findings, while 2/36 (5%) were missed by FDG PET-CT. We conclude that FDG PET-CT 12 weeks after RT/CRT is useful, but not completely reliable for finding all the metastases of HPV-associated TSCC/BOTSCC. Nonetheless, our data indicate that an ND could be more selectively guided by FDG PET-CT.

Role of 3'-Deoxy-3'-[18F] Fluorothymidine Positron Emission Tomography-Computed Tomography as a Predictive Biomarker in Argininosuccinate Synthetase 1-Deficient Thoracic Cancers Treated With Pegargiminase

IntroductionPegargiminase (ADI-PEG 20I) degrades arginine in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma (MPM) and NSCLC. Imaging with proliferation biomarker 3'-deoxy-3'-[18F] fluorothymidine (18F-FLT) positron emission tomography (PET)-computed tomography (CT) was performed in a phase 1 study of pegargiminase with pemetrexed and cisplatin (ADIPemCis). The aim was to determine whether FLT PET-CT predicts treatment response earlier than CT. MethodsA total of 18 patients with thoracic malignancies (10 MPM; eight NSCLC) underwent imaging. FLT PET-CT was performed at baseline (PET1), 24 hours post-pegargiminase monotherapy (PET2), post one cycle of ADIPemCis (PET3), and at end of treatment (EOT, PET4). CT was performed at baseline (CT1) and EOT (CT4). CT4 (modified) Response Evaluation Criteria in Solid Tumors (RECIST) response was compared with treatment response on PET (changes in maximum standardized uptake value [SUVmax] on European Organisation for Research and Treatment of Cancer–based criteria). Categorical responses (progression, partial response, and stable disease) for PET2, PET3, and PET4 were compared against CT using Cohen’s kappa. ResultsADIPemCis treatment response resulted in 22% mean decrease in size between CT1 and CT4 and 37% mean decrease in SUVmax between PET1 and PET4. PET2 agreed with CT4 response in 62% (8 of 13) of patients (p = 0.043), although decrease in proliferation (SUVmax) did not precede decrease in size (RECIST). Partial responses on FLT PET-CT were detected in 20% (3 of 15) of participants at PET2 and 69% (9 of 13) at PET4 with good agreement between modalities in MPM at EOT. ConclusionsEarly FLT imaging (PET2) agrees with EOT CT results in nearly two-thirds of patients. Both early and late FLT PET-CT provide evidence of response to ADIPemCis therapy in MPM and NSCLC. We provide first-in-human FLT PET-CT data in MPM, indicating it is comparable with modified RECIST.

The correlation between metabolic parameters in (18)F-FDG PET-CT and solid and micropapillary histological subtypes in lung adenocarcinoma

Objective: Solid and micropapillary pattern are highly invasive histologic subtypes in lung adenocarcinoma and are associated with poor prognosis while the biopsy sample is not enough for the accurate histological diagnosis. This study aims to assess the correlation and predictive efficacy between metabolic parameters in (18)F-fluorodeoxy glucose positron emission tomography/computed tomography ((18)F-FDG PET-CT), including the maximum SUV (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and solid and micropapillary histological subtypes in lung adenocarcinoma. Methods: A total of 145 resected lung adenocarcinomas were included. The clinical data and preoperative (18)F-FDG PET-CT data were retrospectively analyzed. Mann-Whitney U test was used for the comparison of the metabolic parameters between solid and micropapillary subtype group and other subtypes group. Receiver operating characteristic (ROC) curve and areas under curve (AUC) were used for evaluating the prediction efficacy of metabolic parameters for solid or micropapillary patterns. Univariate and multivariate analyses were conducted to determine the prediction factors of the presence of solid or micropapillary subtypes. Results: Median SUV(max) and TLG in solid and papillary predominant subtypes group (15.07 and 34.98, respectively) were significantly higher than those in other subtypes predominant group (6.03 and 10.16, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for prediction of solid and micropapillary predominant subtypes [AUC=0.811(95% CI: 0.715~0.907) and 0.725(95% CI: 0.610~0.840), P<0.05]. Median SUV(max) and TLG in lung adenocarcinoma with the solid or micropapillary patterns (11.58 and 22.81, respectively) were significantly higher than those in tumors without solid and micropapillary patterns (4.27 and 6.33, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for predicting the presence of solid or micropapillary patterns [AUC=0.757(95% CI: 0.679~0.834) and 0.681(95% CI: 0.595~0.768), P<0.005]. Multivariate logistic analysis showed that the clinical stage (Stage Ⅲ-Ⅳ), SUV(max) ≥10.27 and TLG≥7.12 were the independent predictive factors of the presence of solid or micropapillary patterns (P<0.05). Conclusions: Preoperative SUV(max) and TLG of lung adenocarcinoma have good prediction efficacy for the presence of solid or micropapillary patterns, especially for the solid and micropapillary predominant subtypes and are independent factors of the presence of solid or micropapillary patterns.

Application of circulating tumour cells to predict response to treatment in head and neck cancer

BackgroundLocal recurrence and metastasis remain the major causes of death in head and neck cancer (HNC) patients. Circulating tumour cells (CTCs) are shed from primary and metastatic sites into the circulation system and have been reported to play critical roles in the metastasis and recurrence of HNC. Here, we explored the use of CTCs to predict the response to treatment and disease progression in HNC patients.MethodsBlood samples were collected at diagnosis from HNC patients (n = 119). CTCs were isolated using a spiral microfluidic device and were identified using immunofluorescence staining. Correlation of baseline CTC numbers to 13-week PET-CT data and multidisciplinary team consensus data were conducted.ResultsCTCs were detected in 60/119 (50.4%) of treatment naïve HNC patients at diagnosis. Baseline CTC numbers were higher in stage III vs. stage I-II p16-positive oropharyngeal cancers (OPCs) and other HNCs (p = 0.0143 and 0.032, respectively). In addition, we found that baseline CTC numbers may serve as independent predictors of treatment response, even after adjusting for other conventional prognostic factors. CTCs were detected in 10 out of 11 patients exhibiting incomplete treatment responses.ConclusionsWe found that baseline CTC numbers are correlated with treatment response in patients with HNC. The expression level of cell-surface vimentin (CSV) on CTCs was significantly higher in patients with persistent or progressive disease, thus providing additional prognostic information for stratifying the risk at diagnosis in HNC patients. The ability to detect CTCs at diagnosis allows more accurate risk stratification, which in the future may be translated into better patient selection for treatment intensification and/or de-intensification strategies.

Cancer de la prostate de risque intermédiaire traité par irradiation externe exclusive : focus sur les sites anatomiques de récidive dans deux essais français

PurposeRetrospective description of anatomical sites of relapse based on (18F)-choline PET-CT, (68Ga)-prostatic specific-membrane antigen PET-CT, bone scan, and prostate magnetic resonance imaging (MRI) data. Materials and methodsFrom two French prospective cohorts, patients treated with exclusive radiotherapy for an intermediate-risk cancer were identified during their follow-ups. They were included if they presented a rising of the prostate-specific antigen (PSA) associated with the realization of an imaging showing the sites of recurrences. ResultsTwo hundred and sixty-three patients were included. After a median follow-up of 76 months (interquartile range [IQR] 67–95), 65 patients had biochemical recurrence and positive imaging. The median nadir PSA was 0.6ng/mL and the median PSA at recurrence was 3.4ng/mL. A single lesion was found in 48% of cases, 2 to 4 lesions in 43% of cases and more than 4 lesions in 9% of cases. The sites of relapse identified were prostate (37/65), prostate only (19/65), seminal vesicles (9/65) Pelvic nodes (35/65), extrapelvic nodes (15/65) and bone (13/65). ConclusionsThe majority of relapses presented as a single lesion localized in the pelvis.

Thoracic lymphadenopathies in diffuse systemic sclerosis: an observational study on 48 patients using computed tomography

BackgroundThoracic multidetector computed tomography (MDCT) is essential for the detection of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). Thoracic MDCT assessment can reveal the presence of thoracic lymphadenopathies (LAP) whose signification remains uncertain. The purpose of the study was to describe the characteristics and to assess the significance of thoracic LAP in patients with diffuse SSc.MethodsWe conducted a monocentric observational study on adult patients with diffuse SSc, and collected general patient and first thoracic MDCT characteristics, PET-CT and outcome data. Comparisons were made between patients with and without thoracic LAP.ResultsForty-eight patients were included. There were 30 patients (62.5%) with an ILD and 23 (48%) with at least one thoracic LAP on the first MDCT assessment. Median number per patient of thoracic LAP was 3 [1–8], with a mean size of 11.7 ± 1.7 mm, mainly located in right para-tracheal area (22.8% of the total number of LAP), right hilar area (20.3%), left hilar area (6.5%), and sub-carinal area (15.2%). PET-CT showed lymph node hypermetabolism in 11/15 patients (73.3%) with mean SUVmax at 4 ± 1.3. There were significantly more males (p = 0.002) and more patients exposed to silica (p = 0.001) in patients with thoracic LAP. ILD was significantly more extended according to Goh score (p = 0.03), and using semi-quantitative score for mixed ground-glass reticulation (p = 0.01) and global abnormalities (p = 0.03) in patients with thoracic LAP and ILD. Thirteen patients (27.1%) died during follow-up without significant difference according to the presence or not of thoracic LAP (p = 0.15). There was also no significant difference concerning immunosuppressive treatment initiation (p = 0.17).ConclusionsThoracic LAP are common in diffuse SSc and are generally multiple, not bulky, moderately hypermetabolic, and located at the base of the mediastinum lymph node chains. Their presence correlates with the extent of ILD. In absence of ILD, thoracic LAP presence seems to be often explained by silica exposure.Trial Registration: NA.

Oncobox molecular profiling for a patient with recurrent endometrial cancer

Relevance. Endometrial cancer (EC) is the most common gynecological tumor. As a rule, it has a good prognosis, but in case of relapse, it worsens significantly. The effectiveness of cytotoxic chemotherapy for the treatment of such patients remains low.Purpose. To present a clinical case demonstrating the possibilities of therapy performed according to the results of molecular profiling of the tumor by RNA sequencing methods.Methods. Analysis of the anamnesis data, the results of histological and immunohistochemical studies, PET-CT, ultrasound images, and RNA sequencing data was carried out. The results of therapy prescribed in accordance with the rating of targeted drugs obtained after processing the transcriptomic profile by the Oncobox diagnostic platform were evaluated.Results. After experimental second-line therapy, a partial response was recorded.Conclusion. Early molecular profiling and therapy assignment in accordance with its results can change the course of the disease and improve the quality of life of patients.

P14.78 Comparison of progression-free survival after reirradiation of local and distant glioblastoma’s relapses

Abstract BACKGROUND Despite using of modern comprehensive approaches to the treatment of patients with glioblastomas (GB) it invariably recur after a median interval of less than 7 months. Relapses are inevitable and is often the leading cause of death in patients. About 80–90% of recurrences are local, distant relapses are 5–20%. The optimal treatment strategy of recurrent GB have not yet been determined. MATERIAL AND METHODS The analysis included 130 patients with 160 lesions after primary combined treatment. Progression was assessed based on the RANO criteria. All patients have been re-irradiated in various regimens: 26 pts with median dose 60 Gy/30 fr, 20 pts with median dose 45 Gy/15 fr, 74 pts with dose 24-35Gy for 3–7 fr., 10 pts with median dose 22Gy/1fr. The scheme and regimen of fractionation were determined by tumor volume, localization and functional status of patient. Chemotherapy was changed to a regimen with Bevacizumab (BVZ) before the re-irradiation. According to the EORTC criteria lesions were divided as local (n=112) and distant (n=48) progression with median volume 23.6 cc and 14.7 cc respectively. RESULTS The median progression-free survival in the whole group was 8.2 months(95% CI 7–8.7). Progression-free survival at 6; 12 and 24 months was 65.8%; 21.9% and 4% respectively. Progression-free median survival after treatment of local and distant glioblastoma recurrences was different: 7.6 and 9.2 months, respectively (p = 0.048). In 17.4% radiation necrosis was detected according to MRI and 11C-methionine PET-CT data. Steroid and BVZ therapy were effective in these cases, no one of them was reoperated. CONCLUSION Re-irradiation for GB recurrences is effective and safe way for improvement of outcomes in patients with progression. In the group of patients with local relapses, local control is lower than in the group of distant ones. It may associated with the increasing of the radioresistance of tumor cells after the initial combined treatment. Further studies are needed to compare and assess the role of radiobiological and others factors in the development of local and distant recurrence.The research was supported financially by RFBR (Project No. 18-29-01061).

Influence of Baseline Positron Emission Tomography in Metastatic Gastroesophageal Cancer on Survival and Response to Therapy

Background: The value of baseline fluorodeoxyglucose-positron emission tomography-computed tomography (PET-CT) remains uncertain once gastroesophageal cancer is metastatic. We hypothesized that assessment of detailed PET-CT parameters (maximum standardized uptake value [SUVmax] and/or total lesion glycolysis [TLG]), and the extent of metastatic burden could aid prediction of probability of response or prognosticate. Methods: We retrospectively analyzed treatment-naive patients with stage 4 gastroesophageal cancer (December 2002–August 2017) who had initial PET-CT for cancer staging at MD Anderson Cancer Center. SUVmax and TLG were compared with treatment outcomes for the full cohort and subgroups based on metastatic burden (≤2 or >2 metastatic sites). Results: We identified 129 patients with metastatic gastroesophageal cancer who underwent PET-CT before first-line therapy. The median follow-up time was 61 months. The median overall survival (OS) was 18.5 months; the first progression-free survival (PFS) was 5.5 months. SUVmax or TLG of the primary tumor or of all metastases combined had no influence on OS or PFS, whether the number of metastases was ≤2 or >2. Overall response rates (ORRs) to first-line therapy were 48% and 45% for patients with ≤2 and >2 metastases, respectively (nonsignificant). ORR did not differ based on low or high values of SUVmax or TLG. Conclusions: This is the first assessment of a unique set of PET-CT data and its association with outcomes in metastatic gastroesophageal cancer. In our large cohort of patients, detailed analyses of PET-CT (by SUVmax and/or TLG) did not discriminate any parameters examined. Thus, baseline PET-CT in untreated metastatic gastroesophageal cancer patients has limited or no utility.

Prognostic Role of Interim 18-Fluorodeoxyglucose-PET in Diffuse Large B Cell Lymphoma: Experience from a Tertiary Care Centre in North India.

This study was done to investigate the role of Interim 18-FDG-PET/CT (i-PET) in predicting the outcome of Diffuse Large B Cell Lymphoma (DLBCL) patients. The Lymphoma registry data base of the Department of Haematology was reviewed for all newly diagnosed DLBCL patients treated with R-CHOP-21 (n = 63). The PET-CT data of these patients at pre-defined time points (baseline, interim and end of treatment) was systematically collected. The predictive accuracy of i-PET-CT (done after 4 cycles R-CHOP-21 chemotherapy) was analysed to define their prognostic importance. 47 patients were eligible for final analysis in this study. According to Deauville's criteria 15 patients (31%) were positive on i-PET. The positive predictive value (PPV) of i-PET by DS was 73.3%. At a median follow up of 21months, DS based i-PET negative and positive cases showed significant differences in 2-year OS (81.2% vs 46.7%, p = 0.007) and PFS (75% vs 26.7%, p = 0.005). Combined analysis of i-PET (by DS) and IPI showed negative predictive value (NPV) of 92.3% in Low IPI while PPV of 76.9% in high IPI subgroup of DLBCL. On a multivariate analysis of all prognostic variables, i-PET was found to be independent prognostic marker predicting outcome in DLBCL patients. i-PET is an independent prognostic marker for outcome in DLBCL patients. Combined analysis of Interim PET along with IPI score at diagnosis improves the predictive accuracy of i-PET (both PPV & NPV) and may guide tailoring of therapy in these patients.

The Peripheral Blood Transcriptome Is Correlated With PET Measures of Lung Inflammation During Successful Tuberculosis Treatment.

Pulmonary tuberculosis (PTB) is characterized by lung granulomas, inflammation and tissue destruction. Here we used within-subject peripheral blood gene expression over time to correlate with the within-subject lung metabolic activity, as measured by positron emission tomography (PET) to identify biological processes and pathways underlying overall resolution of lung inflammation. We used next-generation RNA sequencing and [18F]FDG PET-CT data, collected at diagnosis, week 4, and week 24, from 75 successfully cured PTB patients, with the [18F]FDG activity as a surrogate for lung inflammation. Our linear mixed-effects models required that for each individual the slope of the line of [18F]FDG data in the outcome and the slope of the peripheral blood transcript expression data correlate, i.e., the slopes of the outcome and explanatory variables had to be similar. Of 10,295 genes that changed as a function of time, we identified 639 genes whose expression profiles correlated with decreasing [18F]FDG uptake levels in the lungs. Gene enrichment over-representation analysis revealed that numerous biological processes were significantly enriched in the 639 genes, including several well known in TB transcriptomics such as platelet degranulation and response to interferon gamma, thus validating our novel approach. Others not previously associated with TB pathobiology included smooth muscle contraction, a set of pathways related to mitochondrial function and cell death, as well as a set of pathways connecting transcription, translation and vesicle formation. We observed up-regulation in genes associated with B cells, and down-regulation in genes associated with platelet activation. We found 254 transcription factor binding sites to be enriched among the 639 gene promoters. In conclusion, we demonstrated that of the 10,295 gene expression changes in peripheral blood, only a subset of 639 genes correlated with inflammation in the lungs, and the enriched pathways provide a description of the biology of resolution of lung inflammation as detectable in peripheral blood. Surprisingly, resolution of PTB inflammation is positively correlated with smooth muscle contraction and, extending our previous observation on mitochondrial genes, shows the presence of mitochondrial stress. We focused on pathway analysis which can enable therapeutic target discovery and potential modulation of the host response to TB.