Pretreatment Positron Emission Tomography-computed Tomography Research Articles

PET/CT-based radiomics analysis may help to predict neoadjuvant chemotherapy outcomes in breast cancer.

The aim of this study was to evaluate the clinical usefulness of radiomics signature-derived 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) for the early prediction of neoadjuvant chemotherapy (NAC) outcomes in patients with (BC). A total of 124 patients with BC who underwent pretreatment PET-CT scanning and received NAC between December 2016 and August 2019 were studied. The dataset was randomly assigned in a 7:3 ratio to either the training or validation cohort. Primary tumor segmentation was performed, and radiomics signatures were extracted from each PET-derived volume of interest (VOI) and CT-derived VOI. Radiomics signatures associated with pathological treatment response were selected from within a training cohort (n = 85), which were then applied to generate different classifiers to predict the probability of pathological complete response (pCR). Different models were then independently tested in the validation cohort (n = 39) regarding their accuracy, sensitivity, specificity, and area under the curve (AUC). Thirty-five patients (28.2%) had pCR to NAC. Twelve features consisting of five PET-derived signatures, four CT-derived signatures, and three clinicopathological variables were candidates for the model's development. The random forest (RF), k-nearest neighbors (KNN), and decision tree (DT) classifiers were established, which could be utilized to predict pCR to NAC with AUC ranging from 0.819 to 0.849 in the validation cohort. The PET/CT-based radiomics analysis might provide efficient predictors of pCR in patients with BC, which could potentially be applied in clinical practice for individualized treatment strategy formulation.

Could 18-FDG PET-CT Radiomic Features Predict the Locoregional Progression-Free Survival in Inoperable or Unresectable Oesophageal Cancer?

Simple SummaryAlmost 20% of patients with a locally advanced oesophageal cancer presented long-term local control after exclusive chemoradiotherapy (CRT) and could potentially avoid surgery and its morbidity and mortality. With the aim of identifying the patients that would present long-term locoregional control, we analysed in this study the potential of some pre-treatment positron-emission tomography-computed tomography (PET-CT)-based features in predicting long-term responses and local control in patients treated with definitive CRT. Our results show that radiomics allows for the identification of patients with long-term locoregional control. If confirmed on larger populations, our results could allow the identification of patients who are good responders to CRT, and who could potentially avoid surgery.Background: We evaluated the value of pre-treatment positron-emission tomography–computed tomography (PET-CT)-based radiomic features in predicting the locoregional progression-free survival (LR-PFS) of patients with inoperable or unresectable oesophageal cancer. Material and Methods: Forty-six patients were included and 230 radiomic parameters were extracted. After a principal component analysis (PCA), we identified the more robust radiomic parameters, and we used them to develop a heatmap. Finally, we correlated these radiomic features with LR-PFS. Results: The median follow-up time was 17 months. The two-year LR-PFS and PFS rates were 35.9% (95% CI: 18.9–53.3) and 21.6% (95%CI: 10.0–36.2), respectively. After the correlation analysis, we identified 55 radiomic parameters that were included in the heatmap. According to the results of the hierarchical clustering, we identified two groups of patients presenting statistically different median LR-PFSs (22.8 months vs. 9.9 months; HR = 2.64; 95% CI 0.97–7.15; p = 0.0573). We also identified two radiomic features (“F_rlm_rl_entr_per” and “F_rlm_2_5D_rl_entr”) significantly associated with LR-PFS. Patients expressing a “F_rlm_2_5D_rl_entr” of <3.3 had a better median LR- PFS (29.4 months vs. 8.2 months; p = 0.0343). Patients presenting a “F_rlm_rl_entr_per” of <4.7 had a better median LR-PFS (50.4 months vs. 9.9 months; p = 0.0132). Conclusion: We identified two radiomic signatures associated with a lower risk of locoregional relapse after CRT.

Pretreatment 18F-FDG uptake heterogeneity predicts response to pyrotinib in patients with metastatic HER2-positive breast cancer.

e15026 Background: Heterogeneity of 18F-fluorodeoxyglucose (FDG) uptake is a promising marker for predicting response to treatment. This study aimed to evaluate the ability of pretreatment positron emission tomography/computed tomography (PET/CT) 18F-FDG-based heterogeneity to predict the response to pyrotinib in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Methods: Patients with MBC in the Fudan University Shanghai Cancer Center who underwent whole-body 18F-FDG PET/CT before the initiation of pyrotinib was included. The intertumoral and intratumoral heterogeneity indexes (HI-inter and HI-intra, respectively), maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) on the baseline PET/CT were assessed. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared by log-rank test. Time-dependent receiver operating characteristic (ROC) curve analysis was performed, and the predictive accuracies of all markers were evaluated by plotting the cumulative area under the ROC curve (AUC) over time. Results: A total of 22 patients were included in this study. The median PFS of patients with a high HI-intra (&gt; 1.9) was 6.6 months, whereas that of patients with a low HI-intra was 13.4 months (p = 0.044). The HI-inter was able to discriminate patients as well as the coefficient of variance. Univariate analysis showed that patients with a higher HI-inter tended to have worse PFS (10.6 months vs. 13.4 months, p = 0.067). Higher SUVmax and TLG were also associated with worse PFS. ROC curve analysis confirmed the predictive value of the HI-inter and HI-intra. TLG had the highest accuracy in predicting PFS (AUC = 0.87), followed by HI-inter (AUC = 0.86), SUVmax (AUC = 0.85), HI-intra (AUC = 0.80), mean standardized uptake value (AUC = 0.63), and MTV (AUC = 0.60). Conclusions: Intratumoral and intertumoral heterogeneities in metastatic lesions on pretreatment 18F-FDG PET/CT could predict response to pyrotinib treatment in patients with HER2-positive breast cancer, which could provide information to guide treatment decisions.

Prognostic value of bone marrow (18)F-FDG uptake pattern of pretreatment PET-CT in extranodal NK/T cell lymphoma

Objective: To investigate the prognostic value of bone marrow (BM) (18)F-fluorodeoxyglucose ((18)F-FDG) uptake pattern of pretreatment positron emission tomography/computed tomography (PET-CT) in extranodal NK/T cell lymphoma (ENKTL) patients. Methods: We retrospectively collected clinical data from a series of 63 ENKTL patients with stageⅡ~Ⅳ, who have received both (18)F-FDG PET-CT and bone marrow biopsy (BMB) prior to treatment. According the BM (18)F-FDG uptake pattern of PET-CT, the patients were divided into three groups: focal BM FDG uptake higher than liver (fPET+ ), diffuse BM uptake higher than liver (dPET+ ) and normal BM uptake (lower than liver) (nPET). The Kaplan-Meier method and Log-rank test were respectively used for survival analysis and univariate analysis, and COX proportional hazards model for multivariate analysis. Results: Among the 63 patients, 22 patients had nPET, 24 patients showed dPET+ , and 17 patients had fPET+ . BMB positive was found in 8 patients, and negative in 55 patients. Thirty-seven patients had disease progression or relapse, and 31 patients died. The 3-years progression free survival (3y-PFS) rates of fPET+ patients and nPET patients were 14.7% and 63.6% (P=0.006). The 3-years overall survival (3y-OS) rates were 18.8% and 64.8% (P=0.005). The 3y-PFS of dPET+ patients and nPET patients were 35.6% and 63.6% (P=0.161), 3y-OS were 47.9% and 64.8% (P=0.280). Univariate analysis showed that lactate dehydrogenase (LDH) level, Epstein-Barr virus DNA (EBV-DNA), Korean prognostic index (KPI) and BM (18)F-FDG were related with PFS and OS (all P<0.05). Multivariate analysis showed EBV-DNA and BM (18)F-FDG were independent predictors for PFS (P<0.05). EBV-DNA was also an independently predictor for OS (P<0.05). Conclusions: PET/CT-directed BM patterns are meaningful in predicting prognosis of newly diagnosed ENKTL patients. Focal BM (18)F-FDG uptake pattern is an independent predictor for PFS.

Regional Lymph Node Involvement Among Patients With De Novo Metastatic Breast Cancer

Regional nodal irradiation (RNI) for node-positive breast cancer reduces distant metastases and improves survival, albeit with limited reduction in regional nodal recurrences. The mechanism by which RNI robustly reduces distant metastases while modestly influencing nodal recurrences (ie, the presumed target of RNI) remains unclear. To determine whether some distant metastases putatively arise from occult regional nodal disease and whether regional recurrences otherwise remain largely undetected until an advanced cancer presentation. This cohort study examined patients presenting with de novo stage IV breast cancer to the Memorial Sloan Kettering Cancer Center in New York, New York, from 2006 to 2018. Medical records were reviewed to ascertain clinicopathological parameters, including estrogen receptor status and survival. Pretreatment positron emission tomography-computed tomography (PET-CT) imaging was reviewed to ascertain the extent of regional nodal involvement at metastatic diagnosis using standard nodal assessment criteria. A subset underwent regional lymph node biopsy for diagnostic confirmation and served to validate the radiographic nodal assessment. Data analysis was performed from October 2019 to February 2020. Untreated metastatic breast cancer. The primary outcome was the likelihood of regional nodal involvement at the time of metastatic breast cancer presentation and was determined by reviewing pretreatment PET-CT imaging and lymph node biopsy findings. Among 597 women (median [interquartile range] age, 53 [44-65] years) with untreated metastatic breast cancer, 512 (85.8%) exhibited regional lymph node involvement by PET-CT or nodal biopsy, 509 (85%) had involvement of axillary level I, 328 (55%) had involvement in axillary level II, 136 (23%) had involvement in axillary level III, 101 (17%) had involvement in the supraclavicular fossa, and 96 (16%) had involvement in the internal mammary chain. Lymph node involvement was more prevalent among estrogen receptor-negative tumors (92.4%) than estrogen receptor-positive tumors (83.6%). Nodal involvement at the time of metastatic diagnosis was not associated with overall survival. These findings suggest that a majority of patients with de novo metastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence.

Tumor total lesion glycolysis and number of positive pelvic lymph nodes on pretreatment positron emission tomography/computed tomography (PET/CT) predict survival in patients with locally advanced cervical cancer

ObjectiveThe aim of this study was to investigate the prognostic value of metabolic parameters obtained at pretreatment [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in patients with locally advanced cervical...

Prediction of survival outcome based on clinical features and pretreatment 18FDG-PET/CT for HNSCC patients

Background and objectiveIn this study, we have analysed pretreatment positron-emission tomography/ computed tomography (PET/CT) images of head and neck squamous cell carcinoma (HNSCC) patients. We have used a publicly available dataset for our analysis. The clinical features of the patient, PET quantitative parameters, and textural indices from pretreatment PET-CT images are selected for the study. The main objective of the study is to use classifiers to predict the outcome for HNSCC patients and compare the performance of the model with the conventional statistical model (CoxPH). MethodsWe have applied a 40% fixed SUV threshold method for tumour delineation. Clinical features of each patient are provided in the dataset, and other features are calculated using LIFEx software. For predicting the outcome, we have implemented three classifiers - Random Forest classifier, Gradient Boosted Decision tree (GBDT) and Decision tree classifier. We have trained each model using 93 data points and test the model performance using 39 data points. The best model - GBDT is chosen based on the performance metrics. ResultsIt is observed that typically three features: MTV (Metabolic tumour Volume), primary tumour site and GLCM_correlation are significant for prediction of survival outcome. For testing cohort, GBDT achieves a balanced accuracy of 88%, where conventional statistical model reported a balanced accuracy of 81.5%. ConclusionsThe proposed classifier achieves higher accuracy than the state of the art technique. Using this classifier we can estimate the HNSCC patient’s outcome, and depending upon the outcome treatment policy can be selected.

Feasibility of imaging 90 Y microspheres at diagnostic activity levels for hepatic radioembolization treatment planning.

PurposePrior to 90Y hepatic radioembolization, a dosage of 99mTc‐macroaggregated albumin (99mTc‐MAA) is administered to simulate the distribution of the 90Y‐loaded microspheres. This pretreatment procedure enables lung shunt estimation, detection of potential extrahepatic depositions, and estimation of the intrahepatic dose distribution. However, the predictive accuracy of the MAA particle distribution is often limited. Ideally, 90Y microspheres would also be used for the pretreatment procedure. Based on previous research, the pretreatment activity should be limited to the estimated safety threshold of 100 MBq, making imaging challenging. The purpose of this study was to evaluate the quality of intra‐ and extrahepatic imaging of 90Y‐based pretreatment positron emission tomography/computed tomography (PET/CT) and quantitative single photon emission computed tomography (SPECT)/CT scans, by means of phantom experiments and a patient study.MethodsAn anthropomorphic phantom with three extrahepatic depositions was filled with 90Y chloride to simulate a lung shunt fraction (LSF) of 5.3% and a tumor to nontumor ratio (T/N) of 7.9. PET /CT (Siemens Biograph mCT) and Bremsstrahlung SPECT/CT (Siemens Symbia T16) images were acquired at activities ranging from 1999 MBq down to 24 MBq, representing post‐ and pretreatment activities. PET/CT images were reconstructed with the clinical protocol and SPECT/CT images were reconstructed with a quantitative Monte Carlo‐based reconstruction protocol. Estimated LSF, T/N, contrast to noise ratio of all extrahepatic depositions, and liver parenchymal and tumor dose were compared with the phantom ground truth. A clinically reconstructed SPECT/CT of 150 MBq 99mTc represented the current clinical standard. In addition, a 90Y pretreatment scan was simulated for a patient by acquiring posttreatment PET/CT and SPECT/CT data with shortened acquisition times.ResultsAt an activity of 100 MBq 90Y, PET/CT overestimated LSF [+10 percentage point (pp)], underestimated liver parenchymal dose (−3 Gy/GBq), and could not detect the extrahepatic depositions. SPECT/CT more accurately estimated LSF (−0.7 pp), parenchymal dose (−0.3 Gy/GBq) and could detect all three extrahepatic depositions. 99mTc SPECT/CT showed similar accuracy as 90Y SPECT/CT (LSF: +0.2 pp, parenchymal dose: +0.4 Gy/GBq, all extrahepatic depositions visible), although the noise level in the liver compartment was considerably lower for 99mTc SPECT/CT compared to 90Y SPECT/CT. The patient’s SPECT/CT simulating a pretreatment 90Y procedure accurately represented the posttreatment 90Y microsphere distribution.ConclusionsQuantitative SPECT/CT of 100 MBq 90Y could accurately estimate LSF, T/N, parenchymal and tumor dose, and visualize extrahepatic depositions.

Prognostic value of 18F-FDG PET/CT metabolic parameters in small cell lung cancer

ObjectiveTo compare the prognostic values of metabolic parameters from pretreatment PET/CT between limited disease (LD) and extensive disease (ED) small cell lung cancer (SCLC) patients.MethodsData on 118 newly diagnosed SCLC patients (50 LD and 68 ED) who underwent pretreatment positron emission tomography–computed tomography (PET/CT) were reviewed. For PET, metabolic parameters were measured for: (1) primary tumor, maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis; and (2) all tumor lesions, SUVmax of the hottest tumor, whole body metabolic tumor volume (WBMTV), and whole body total lesion glycolysis (WBTLG). Prognostic values of metabolic parameters and other clinical variables were analyzed to predict overall survival (OS).ResultsIn LD, SUVmax of the primary tumor was an independent prognostic factor for OS. Patients with high SUVmax showed significantly worse OS than those with low SUVmax. In ED, WBMTV and WBTLG were independent prognostic factors for OS. Patients with high WBMTV or WBTLG showed significantly worse OS than those with low WBMTV or WBTLG.ConclusionsSUVmax of primary tumor was the only independent prognostic factor for OS in LD SCLC patients. WBMTV and WBTLG were independent prognostic factors in ED SCLC patients.

Treatment Outcomes of Early-Stage Natural-Killer/T-Cell Lymphomas Treated with Chemoradiotherapy: Data from 3 Tertiary Cancer Centres in Singapore

Background: Extranodal natural killer/T cell lymphoma (ENKL) is an aggressive Epstein-Barr virus (EBV) associated lymphoma with a strong geographical predilection for Asia and South America. While treatment outcomes of advanced stage (AS) disease (i.e., stage III and IV) are uniformly poor, early stage (ES) disease treated with concomitant or sequential chemotherapy (ChT) and radiotherapy (RT) can yield good long-term outcomes. Currently there is no standard therapy for ES ENKL. We describe our experience treating patients with ES ENKL in 3 tertiary cancer centres in Singapore. Method: We performed a retrospective analysis using data from Singapore Lymphoma Study Group database which captures patients from 3 largest tertiary cancer centres in Singapore: National Cancer Centre Singapore (NCCS), Singapore General Hospital (SGH) and National University Cancer Institute, Singapore (NCIS). We included patients with stage I or II ENKL that were treated with ChT and RT from 1996 to March 2019. Patients who did not receive treatment or received radiotherapy alone were excluded. We recorded data on patient demographics, chemotherapy regimen, radiotherapy dosage, sequencing of treatment, response and survival outcomes. End of treatment overall response rates (ORR) included those who achieved complete response (CR) and a partial response (PR). Progression free survival (PFS) was defined as date of diagnosis to date of progression, relapse or death. Overall survival (OS) was defined as date of diagnosis to date of death from all causes. Survival distributions were estimated by the Kaplan-Meier method. Assuming cox proportional hazards models, univariate analysis for OS was performed and Wald tests were used to evaluate the statistical significance. All the statistical analysis was performed using R. Results: There were 56 patients who fulfilled the inclusion criteria. Forty (71%) were male, 47 (84%) were Chinese and the median age of this cohort was 50 (range 18-80). Thirty-one (55%) patients had stage I disease and all had nasal involvement. All patients had ECOG performance status of 0 or 1 and most had low or low-intermediate international prognostic index (IPI) score. Ten patients (18%) had B-symptoms and LDH was elevated in 22 (39%). Pre-treatment positron emission tomography-computed tomography (PET/CT) was performed in 36 (64%) patients. Pre-treatment EBV titres were tested in only 23 patients and they were detected in 17 (74%) of patients. Twenty-five patients (45%) had sandwich (ChT, RT then ChT), 25 (45%) had ChT followed by RT, while 6 had RT followed by ChT. None had concurrent ChT/RT. The most commonly used ChT regimen was ICE (ifosfamide, carboplatin, etoposide) in 19 patients and SMILE (steroids, methotrexate, ifosfamide, L-asparaginase, etoposide) was used in 9 patients. Most patients (75%) did not receive L-asparaginase containing regimens. The median RT dose was 50Gy. The ORR for this cohort was 87.5% and 7 patients (12.5%) progressed at the end of treatment. Our median duration of follow up is 3.5 years (range: 0.25 - 21.6 years). The 5-year OS for stage I and II disease were 78.5% (95% CI, 64.2%-96.0%) and 65.6% (95% CI 47.5% to 90.5%) respectively. The 5-year PFS for stage I and II disease was 78.5% (95% CI 64.2%-96.0%) and 58.8% (95% CI 40.9% to 84.5%) respectively. On univariate analysis, only the sequence of therapy i.e., the sandwich ChT-RT-ChT approach when compared to sequential treatment with ChT followed by RT, was associated with better OS with a hazard ratio (HR) of 0.18 (95% CI 0.04 to 0.84 , p = 0.03). When L-asparaginase containing regimens were compared against those without, no statistical significant difference was observed in OS in ES ENKL, with HR of 3.38 (95%CI 0.44-26.15, p=0.243) Conclusion: Survival outcomes for ES ENKL especially that of stage I ENKL, are good with chemoradiotherapy. This contrasts against the treatment outcomes of AS ENKL. It is likely that many patients in this study were under-staged since PET scans were only performed in 64% of patients. Within the limits of this retrospective analysis and the small numbers, the ICE chemotherapy regimen appears to be an effective treatment when "sandwich"-sequenced with radiotherapy. Disclosures Lim: National Cancer Centre Singapore: Employment.

Evaluating Novel PET-CT Functional Parameters TLG and TMTV in Differentiating Low-grade Versus Grade 3A Follicular Lymphoma

BackgroundFollicular lymphoma (FL) grading, low-grade 1-2 (LG) versus grade 3A (3A), informs management. However, accurate grading is challenging owing to disease heterogeneity and inter-reader variability. The [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) parameter maximum standardized uptake value (SUVmax) has utility in differentiating LG from 3A FL, but the utility of novel parameters total lesion glycolysis (TLG) and total metabolic tumor volume (TMTV) is unknown. Patients and MethodsRetrospective review of diagnostic pre-treatment PET-CTs of patients aged > 18 years with FL grades 1-3A from 2009-2017 was performed. PET-CT parameters SUVmax, TLG, and TMTV values were generated using manual (MW) and semi-automated workflows (SW). Poisson regression and receiver operating characteristic curves were used to compare PET-CT parameters between LG and 3A. ResultsA total of 49 patients with FL were identified: 38 LG and 11 3A. PET-CT parameters were significantly higher in 3A as compared with LG in both workflows. The cutoff values, sensitivities, and specificities were as follows: SUVmax: 10.4, 64%, and 74% in MW and 11.9, 73%, and 76% in SW; TLG: 543, 82%, and 74% in MW and 371, 73%, and 74% in SW; and TMTV: 141, 73%, and 76% in MW and 93, 64%, and 76% in SW. SUVmax had identical cutoff, sensitivity, and specificity across all 3 SWs, whereas TLG and TMTV had considerable variance across all 3 SWs. ConclusionsTLG and TMTV are comparable to SUVmax in differentiating LG versus 3A FL. Cutoffs, sensitivities, and specificities varied in MW versus SW. Novel PET-CT parameters serve as reproducible adjuncts but not replacements for biopsy in differentiating grades of FL.

Prospective evaluation of pretreatment and intratreatment FDG PET-CT SUV stability in primary head and neck cancer.

To evaluate standardized uptake value (SUV) stability on pretreatment and intratreatment 18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in patients undergoing definitive CRT for head and neck cancer (HNC). Primary tumor and nodal volumes of interest (VOIs) from HNC patients were contoured on the pretreatment and intratreatment PET-CT by two independent observers. SUV stability was measured with intersection calculations (DICE, overlap fraction, center to center) between the VOIs at threshold levels of 50%, 60%, 70%, 80%, and 90% of the SUV maximum. The mean calculated DICE of the 50%, 60%, 70%, 80%, 90% SUV threshold was 0.53, 0.48, 0.41, 0.28, and 0.12, respectively. The mean calculated overlap fraction was 0.71, 0.65, 0.58, 0.43, and 0.2, respectively. Center-center difference demonstrates spatial variability of 7.8, 8.2, 8.6, 9.5, and 11.2 mm for these SUV subvolumes of interest. HNC subvolumes defined by SUV thresholding technique in FDG PET-CT imaging do not remain physically stable during (chemo)RT. All pretreatment and intratreatment SUV thresholds (50%-90%) overlap indexes are low during the course of (chemo)radiation. Pretreatment and intratreatment center to center variation further corroborates that all FDG threshold volumes do not remain stable during treatment. No difference in SUV threshold stability was seen between p16 positive and negative tumors.

Prognostic Relevance of Medullary Abnormalities in the Appendicular Skeleton Detected By Positron Emission Tomography-Computed Tomography in Patients with Newly Diagnosed Multiple Myeloma

Background: Positron emission tomography-computed tomography (PET-CT) is a valuable tool in the initial evaluation of myeloma and related disorders. However, the prognostic value of PET-CT has not been fully elucidated. We recently reported the prognostic significance of medullary abnormalities in the appendicular skeleton (AS) detected by multidetector computed tomography (MDCT) in patients with multiple myeloma (MM) [Blood Adv, 2018. 2(9): p.1032-39].The study reported that medullary abnormalities in AS detected by MDCT showed different fluourodeoxyglucose-avidity ranging from entirely negative to diffusely positive on concurrently performed PET-CT, despite the presence of unequivocal infiltration of abnormal lesions in AS on MDCT. We further investigate the prognostic relevance of medullary abnormalities in AS by PET-CT in symptomatic MM.Methods: We identified a total of 211 consecutive patients with newly diagnosed, symptomatic MM diagnosed and treated between April 2008 and February 2018 at Kameda Medical Center, Kamogowa-shi, Japan. They were evaluated with pretreatment whole-body PET-CT. We included only patients who had been treated with novel agents. PET-CT imaging was performed as previously reported [Blood, 2011. 118(23): p.5989-95]. PET-CT positivity and negativity were also defined as previously described.Results: Median age of the patients was 73.5 years [interquartile range (IQR): 66.3-80.3 years). There were 129 (61.1%) patients who showed abnormal findings on PET-CT. Consistent with previous reports, known high-risk PET-CT findings including the presence of >3 systemic focal lesions (FLs), maximum standardized uptake value (SUVmax) >4.2, and extramedullary disease were observed in 91 (43.1%), 97 (46.0%), and 11 (5.2%) patients, respectively. Receiver operating characteristic analysis determined the optimal cutoff value of AS focal lesions (AS-FLs) on PET-CT as 3. We then divided patients into two groups with ≤3 or >3 AS-FLs (Fig. 1). There were 35 (16.6%) patients with >3 AS-FLs, and their levels of clonal circulating plasma cells and prevalence of del(17p) and t(14;16) were higher than those in patients without AS-FLs. Patients with >3 AS-FLs showed significantly shorter progression-free survival (PFS) and overall survival (OS) than those without [median PFS: 12.8 and 35.6 months, respectively; P < 0.001, and median OS: 33.4 months and not reached (NR), respectively; P < 0.001]. Patients with 1-3 AS-FLs did not show significant differences in PFS and OS compared to patients with no AS-FL (Fig. 2). In addition, this finding retained its prognostic value for PFS and OS in multivariate analysis [hazard ratio (HR); 2.35, 95% confidence interval (CI); 1.42-3.88; P < 0.001 for PFS, and HR; 2.86, 95% CI; 1.60-5.09; P < 0.001 for OS] (Table 1). As previously described, we observed that the known high-risk PET findings including the presence of >3 systemic FLs and SUVmax> 4.2 had an unfavorable prognostic impact. Patients with >3 AS-FLs showed significantly shorter PFS and OS than those without, even among patients with >3 systemic FLs (Fig. 3) or SUVmax> 4.2 (Fig. 4). Furthermore, we identified 108 and 42 patients with focal/scattered and diffuse marrow pattern on MDCT, respectively. There were 16 (14.8%) and 19 (45.2%) patients with >3 AS-FLs observed on PET-CT with focal/scattered and diffuse marrow pattern on MDCT, respectively. These patients showed shorter PFS and OS than those without AS-FLs among patients with the same AS marrow pattern on MDCT.Conclusions: To the best of our knowledge, ours is the first study to demonstrate that the presence of >3 FLs in AS detected by pretreatment PET-CT was robustly predictive of unfavorable survival independent of known risk factors, including existing high-risk PET-CT findings in patients with newly diagnosed MM. The findings in AS may potentially complement and improve the prognostic performance of PET-CT. Further systematic studies are warranted for the validation of our results and development of more accurate prognostic systems incorporating cross-sectional imaging. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic predictive value of preoperative intratumoral 2-deoxy-2-(18F)fluoro-D-glucose uptake heterogeneity in patients with high-grade serous ovarian cancer.

This study aimed to explore the clinical and prognostic significance of pretreatment positron-emission tomography/computed tomography (PET/CT) parameters, especially 2-deoxy-2-(F)fluoro-D-glucose-based heterogeneity, in high-grade serous ovarian cancer (HGSC). We retrospectively investigated 56 patients with HGSC who underwent PET/CT before primary surgery at our hospital between January 2010 and June 2015. None of these patients received neoadjuvant chemotherapy. PET/CT parameters, including maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and intratumoral heterogeneity index (HI), were measured for all patients. Differences of each PET/CT parameter between primary tumors (-P) and omental metastatic lesions (-M) were compared by paired t tests. Progression-free survival (PFS) and overall survival were analyzed by the Kaplan-Meier method and log-rank tests in univariate analyses. Cox regression analyses were used for multivariate analysis. SUVmean-P was higher than SUVmean-M (P=0.001). However, there were no statistical differences of SUVmax, MTV, TLG, or HI between primary and omental lesions. Chemosensitive patients tended to have higher levels of SUVmax-P (P=0.011), MTV-P (P=0.014), TLG-P (P=0.035), and HI-P (P=0.002), respectively. In univariate analyses, higher HI-P was associated with better PFS (P=0.007). However, in multivariate analysis, HI-P was not an independent predictor of PFS (P=0.581). Neither HI-P nor HI-M was the prognostic predictor for overall survival (P=0.078 and 0.063, respectively). 2-Deoxy-2-(F)fluoro-D-glucose-based heterogeneity appears to be a predictive and prognostic factor for patients with HGSC. Parameters of primary tumors have predominant value compared with omental metastatic lesions.

Predictors of Distant Failure After Stereotactic Body Radiation Therapy for Stages I to IIA Non–Small-Cell Lung Cancer

PurposeThe use of stereotactic body radiation therapy (SBRT) has emerged as an effective treatment modality for patients with early-stage non–small-cell lung cancer (NSCLC), with excellent local control rates. Despite this, there is a predominant pattern of distant failure. We sought to identify factors that help predict which patients with stages I to IIA NSCLC treated with SBRT are at highest risk of distant failure, so that we may utilize these factors in the future to help determine which patients may benefit from the addition of systemic therapies. Patients and MethodsWe retrospectively reviewed 292 patients treated with SBRT for early stage NSCLC from 2006 to 2016 at 2 institutions. Patients were classified by T stage, tumor size, location and histology, pretreatment positron emission tomography/computed tomography (PET/CT) standardized uptake value (SUV), smoking status, and age. The primary endpoint of the study was distant failure. We aimed to analyze if patient characteristics could be identified that predicted for distant failure through the use of competing risk analysis. ResultsThe median follow-up was 21.9 months. The median dose of radiation and fractionation delivered was 50 Gy (range, 45-65 Gy) in 5 fractions (range, 3-13 fractions). The median patient age was 72.8 years (interquartile range, 65.4-79.7 years). The 2-year distant failure was 22.0%, and overall survival at 2 years was found to be 61.0%. For every 1-year increase in patient age, the hazard of distant failure at any given time was 3% lower (hazard ratio, 0.97; 95% confidence interval, 0.94-0.99; P = .04). None of the remaining characteristics emerged as significant risk factors for distant failure on univariable or multivariable analysis. ConclusionsOverall, our cohort had distant failure and survival rates comparable with what has been described in the literature. Although we were unable to identify factors outside of age that correlated to risk of distant failure, this topic warrants further investigation, as distant failure is the primary pattern of failure with SBRT when used as the primary management for early-stage NSCLC. Additional molecular studies are needed to further inform on the role of systemic therapy in patients with early-stage NSCLC to improve clinical outcomes.

Pretreatment 18F-FDG Uptake Heterogeneity Predicts Treatment Outcome of First-Line Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer.

Intratumoral heterogeneity of 18F-fluorodeoxyglucose (18F-FDG) uptake in primary tumor has proven to be a surrogate marker for predicting treatment outcome in various tumors. However, the value of intraindividual heterogeneity in metastatic diseases remains unknown. The aim of this study was to evaluate pretreatment positron emission tomography/computed tomography (PET/CT) 18F-FDG-based heterogeneity for the prediction of first-line treatment outcome in metastatic triple-negative breast cancer (mTNBC). mTNBC patients from three clinical trials (NCT00601159, NCT01287624, and NCT02341911) with whole-body 18F-FDG PET/CT scan before first-line gemcitabine/platinum were included. Heterogeneity index (HI) and the maximum of FDG uptake (MAX) across total metastatic lesions (-T) on baseline PET/CT scans were assessed. HI was measured by MAX divided by the minimum FDG uptake across metastatic lesions. Optimal cutoffs were determined by time-dependent receiver operator characteristics (ROC) analysis. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. A total of 42 mTNBC patients were included in this study. The median PFS of patients with high HI-T (>1.9) and high MAX-T (>10.5) was significantly shorter than patients with low HI-T (<1.9; p = .049) and low MAX-T (<10.5; p = .001). In terms of OS, only high MAX-T was significant for poorer outcome (p = .013). ROC curve analysis confirmed the predictive value of MAX and HI in mTNBC patients. Area under the ROC curve for MAX-T and HI-T was 0.75 and 0.65, indicating a higher predictive accuracy than conventional clinical risk factors. HI and MAX measured among metastatic lesions on pretreatment 18F-FDG PET/CT scans could be potential predicators for first-line treatment outcome in patients with mTNBC. Intratumoral heterogeneity of 18F-fluorodeoxyglucose (FDG) uptake in primary tumor has proven to be a robust surrogate predictive marker. A novel positron emission tomography/computed tomography (PET/CT) parameter-heterogeneity index (HI) to quantify the heterogeneous characteristics of metastatic disease is proposed. Triple-negative breast cancer (TNBC) is a highly heterogeneous disease and remains a clinical challenge. The predictive performance of HI, along with the maximum FDG uptake (MAX), measured on pretreatment PET/CT scans in patients with metastatic TNBC was evaluated. Results indicate that HI and MAX may serve as applicable imaging predicators for treatment outcome of metastatic TNBC in clinical practice.

Utility of PET-CT for Evaluation of Patients With Peripheral T-cell Lymphoma

BackgroundFluorine-18 fluorodeoxyglucose (FDG) avidity varies in peripheral T-cell lymphoma (PTCL). We evaluated FDG avidity of pretreatment positron emission tomography/computed tomography (P-PET/CT), to appraise the prognostic significance of interim PET/CT (I-PET/CT) and end of treatment PET/CT (E-PET/CT) in PTCL. Patients and MethodsWe performed a retrospective cohort study of patients with newly diagnosed or relapsed PTCL who had received any chemotherapy regimen from 2008 to 2015 in a tertiary center. P-PET/CT, I-PET/CT, and E-PET/CT studies were centrally reviewed. The primary outcomes were the prognostic role of I-PET/CT and E-PET/CT on progression-free survival (PFS) and overall survival (OS). The secondary outcomes were P-PET/CT avidity, the prognostic role of other baseline characteristics, and the correlation between the PET/CT and bone marrow biopsy findings. ResultsWe included 40 patients in the present analysis. The median OS and PFS for the whole cohort was 39 and 16 months, respectively. Of the 40 patients, 36 had positive P-PET/CT findings. A total of 23 patients underwent I-PET/CT, with positive findings for 10. Of the 40 patients, 34 underwent E-PET/CT, 26 of which had positive findings. The sensitivity, specificity, and negative predictive value of P-PET/CT for bone marrow involvement was 40%, 83%, and 89%, respectively. The factors significantly associated with PFS and OS on univariate analysis included elevated lactate dehydrogenase, and low lymphocyte, hemoglobin, and albumin levels. On multivariate analysis, only lymphopenia remained prognostic for PFS and OS. The E-PET/CT and I-PET/CT results were not prognostic for PFS or OS. ConclusionOur study has shown that 90% of PTCL cases will be FDG avid. However, PET/CT was not predictive for PFS or OS at any point. The only predictive factor was the presence of lymphopenia.

Reclassifying patients with early-stage Hodgkin lymphoma based on functional radiographic markers at presentation

The presence of bulky disease in Hodgkin lymphoma (HL), traditionally defined with a 1-dimensional measurement, can change a patient's risk grouping and thus the treatment approach. We hypothesized that 3-dimensional measurements of disease burden obtained from baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), would more accurately risk-stratify patients. To test this hypothesis, we reviewed pretreatment PET-CT scans of patients with stage I-II HL treated at our institution between 2003 and 2013. Disease was delineated on prechemotherapy PET-CT scans by 2 methods: (1) manual contouring and (2) subthresholding of these contours to give the tumor volume with standardized uptake value ≥2.5. MTV and TLG were extracted from the threshold volumes (MTVt, TLGt) and from the manually contoured soft-tissue volumes. At a median follow-up of 4.96 years for the 267 patients evaluated, 27 patients were diagnosed with relapsed or refractory disease and 12 died. Both MTVt and TLGt were highly correlated with freedom from progression and were dichotomized with 80th percentile cutoff values of 268 and 1703, respectively. Consideration of MTV and TLG enabled restratification of early unfavorable HL patients as having low- and high-risk disease. We conclude that MTV and TLG provide a potential measure of tumor burden to aid in risk stratification of early unfavorable HL patients.

Complete metabolic response (CMR) in positron emission tomography-computed tomography (PET-CT) scans may have prognostic significance in patients with marginal zone lymphomas (MZL).

Although clinical use of positron emission tomography-computed tomography (PET-CT) scans is well established in aggressive lymphomas, its prognostic value in marginal zone lymphoma (MZL) remains yet unclear. Hence, we investigated potential role of PET-CT in predicting MZL patients' outcomes following systemic chemotherapy. A total of 32 patients with MZL who received first-line chemotherapy were included in the analysis. They all underwent pretreatment, interim, and posttreatment PET-CT scans. The primary objective was to evaluate the role of complete metabolic response (CMR) in posttreatment PET-CT scans in predicting progression-free survival (PFS). Compared with non-CMR group, 5-year PFS rate was significantly higher in patients who achieved CMR in posttreatment PET-CT (54.2% vs 0.0%, P=.003) and also in patients gaining CMR in interim PET-CT scans (62.5% vs 15.6%, P=.026). Interestingly, early CMR group, who achieved and maintained CMR in both interim and posttreatment PET-CT scans, showed significantly higher 5-year PFS than those with delayed or never CMR group (62.5% vs 37.5% vs 0%, P=.008). Therefore, interim and/or posttreatment CMR can be prognostic at least in these subsets of patients with MZL treated with chemotherapy.

Importance of baseline PET/CT imaging on radiation field design and relapse rates in patients with Hodgkin lymphoma

PurposeThis study analyzed the impact of pretreatment positron emission tomography/computed tomography (PET/CT) scans on involved site radiation therapy (ISRT) field design and pattern of relapse among patients with Hodgkin lymphoma (HL). Methods and materialsThirty-seven patients with stage I or II HL who received first-line chemotherapy followed by consolidative ISRT to all initial sites of disease were enrolled in an institutional review board–approved outcomes-tracking protocol between January 2009 and December 2014. Patients underwent standard-of-care follow-up. Relapse-free survival (RFS) was evaluated using a Kaplan-Meier analysis and cohort comparisons using a χ2 test. ResultsThirty-one patients underwent (PET/CT) scans before chemotherapy and 6 did not because of a lack of insurance (n = 2), inpatient chemotherapy administration (n = 2), scheduling conflicts (n = 1), and unknown reasons (n = 1). The median follow-up was 46 months, and the 4-year RFS rate was 92%. Patients without pretreatment PET imaging were more likely to experience disease relapse (4-year RFS, 97% vs. 67%; P = .001). Among the 6 patients who did not receive a baseline PET/CT scan, all 3 recurrences occurred in lymph node regions outside of, but immediately adjacent to, the radiation field. ConclusionsPatients with stage I/II HL who receive ISRT without pretreatment PET/CT scans appear to have an increased risk for relapse in adjacent nodal stations just outside the radiation field. A larger cohort with a longer follow-up is needed to confirm these findings.