Change In Total Lesion Glycolysis Research Articles

Comparison of intravoxel incoherent motion and diffusion kurtosis imaging and 18- FDG PET/CT in response assessment in rectosigmoid carcinoma.

To evaluate the performance of intravoxel incoherent motion and diffusion kurtosis imaging (IVIM- DKI) in response assessment of rectosigmoid carcinoma to chemo-radiotherapy (CRT) and compare with 18-FDG PET/CT parameters. A total of 30 patients of recto-sigmoid cancer on CRT underwent baseline staging and follow-up with IVIM - DKI. Out of this cohort, 20 patients underwent 18-FDG PET/CT. IVIM- DKI MRI and PET/CT parameters were noted from both pre and post-chemoradiotherapy (done at 6 weeks after completion) scans. Quantitative IVIM-DKI parameters, viz. apparent (ADC) and molecular (D) diffusion coefficient, perfusion coefficient (f), and kurtosis (K) were measured from non-necrotic areas and semi-quantitative PET parameters including SUV max, SUV ratio, metabolic tumor volume (MTV), total lesion glycolysis (TLG) were also measured. All these parameters correlated with the patient's response keeping RECIST 1.1 criteria as reference standard. A statistically significant increase in D and ADC with a significant decline in K was noted after therapy in the entire cohort. These changes were observed in both responders as well as non-responders. No significant differences were observed in the percentage changes of these parameters post therapy amongst both groups. Among 20 patients with follow-up PET/CT imaging, a significant decline in all parameters of primary lesion was seen post-therapy. Responders (n = 12) showed a significant decline in MTV and TLG from baseline after therapy, whereas non-responders did not show any such decline. Change in TLG (ɗ TLG), followed by ɗ MTV had the strongest correlation with a positive response. A ɗ TLG value of ≥ 54.19 carried a 79% sensitivity and 83% specificity in differentiating responders from non responders. 18-FDG PET/CT is a more accurate single modality for assessing both response and tumor burden post therapy, while ADC and D from IVIM MRI are useful adjuncts to response assessment.

18F-FDG PET/CT metabolism multi-parameter prediction of chemotherapy efficacy in locally progressive gastric cancer

PurposeThis study aimed to use an 18F-FDG PET/CT multiparametric quantitative analysis to determine the efficacy of neoadjuvant chemotherapy in patients with locally progressive gastric cancer.Materials and methodsWe conducted a retrospective analysis of 34 patients with pathologically identified gastric cancer who received neoadjuvant chemotherapy and surgery. Chemotherapy regimens were followed and 18F-FDG PET/CT was conducted. We ascertained multiparamaters of the target lesions pre- and post-treatment and determined the ideal cutoff values for the percentage change in biomarkers. Independent factors were evaluated using binary logistic regression. A response classification system was used to explore the association between metabolic and anatomical responses and the degree of pathological remission.ResultsBinary logistic regression analysis showed that Lauren bowel type and change in total lesion glycolysis >45.2% were risk predictors for the efficacy of neoadjuvant chemotherapy; total lesion glycolysis demonstrated the best predictive efficacy. The categorical variable system of the two-module response (metabolic and anatomical response) group had a higher predictive accuracy than that of the single-module response (metabolic or anatomical response) group.ConclusionsUsing 18F-FDG PET/CT multiparametric quantitative analysis, Lauren bowel type and change in total lesion glycolysis >45.2% were independent predictors of the efficacy of neoadjuvant chemotherapy in patients with gastric adenocarcinoma. Additionally, the dual-module assessment demonstrated high predictive efficacy.

Comparison of 3 Different Therapeutic Particles in Radioembolization of Locally Advanced Intrahepatic Cholangiocarcinoma.

Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90Y-glass, 90Y-resin, and 166Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90Y PET/CT and quantitative 166Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [18F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90Y-glass, 8 90Y-resin, and 7 166Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90Y-glass, 1.5 GBq for 90Y-resin, and 7.0 GBq for 166Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90Y-glass than for 90Y-resin and 166Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90Y-glass vs. 73 Gy for 90Y-resin and 50 Gy for 166Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90Y-glass vs. 37 Gy for 90Y-resin and 31 Gy for 166Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [18F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle.

Risk stratification of oesophageal squamous cell carcinoma using change in total lesion glycolysis and number of PET-positive lymph nodes

BackgroundThe efficacy of neoadjuvant chemotherapy (NACT) correlates with patient survival in oesophageal squamous cell carcinoma (OSCC), but optimal evaluation of the treatment response based on PET-CT parameters has not been established.MethodsWe analysed 226 OSCC patients who underwent PET-CT before and after NACT followed by surgery. We assessed SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for the primary tumour and the number of PET-positive lymph nodes before and after NACT to predict patient survival.ResultsIn a stepwise analysis, we defined 60%, 80%, and 80% as the optimal cut-off values for SUVmax, MTV, and TLG reduction, respectively, to distinguish responders and non-responders to NACT. In the ROC analysis, the TLG reduction rate was the best predictor of recurrence among PET-CT parameters. The TLG responders achieved significantly more favourable prognoses than non-responders (2-year progression-free survival [PFS] rate: 64.1% vs. 38.5%; P = 0.0001). TLG reduction rate (HR 2.58; 95% CI 1.16–5.73) and the number of PET-positive lymph nodes after NACT (HR 1.79; 95% CI 1.04–3.08) were significant independent prognostic factors.ConclusionsTLG reduction is the best predictor of prognosis. Preoperative PET-CT evaluation of both the primary tumour and lymph nodes could accurately stratify risk in OSCC patients.

Dose–Effect Relationships of 166Ho Radioembolization in Colorectal Cancer

Radioembolization is a treatment option for colorectal cancer (CRC) patients with inoperable, chemorefractory hepatic metastases. Personalized treatment requires established dose thresholds. Hence, the aim of this study was to explore the relationship between dose and effect (i.e., response and toxicity) in CRC patients treated with 166Ho radioembolization. Methods: CRC patients treated in the HEPAR II and SIM studies were analyzed. Absorbed doses were estimated using the activity distribution on posttreatment 166Ho SPECT/CT. Metabolic response was assessed using the change in total-lesion glycolysis on 18F-FDG PET/CT between baseline and 3-mo follow-up. Toxicity between treatment and 3 mo was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5, and its relationship with parenchyma-absorbed dose was assessed using linear models. The relationship between tumor-absorbed dose and patient- and tumor-level response was analyzed using linear mixed models. Using a threshold of 100% sensitivity for response, the threshold for a minimal mean tumor-absorbed dose was determined and its impact on survival was assessed. Results: Forty patients were included. The median parenchyma-absorbed dose was 37 Gy (range, 12-55 Gy). New CTCAE grade 3 or higher clinical and laboratory toxicity was present in 8 and 7 patients, respectively. For any clinical toxicity (highest grade per patient), the mean difference in parenchymal dose (Gy) per step increase in CTCAE grade category was 5.75 (95% CI, 1.18-10.32). On a patient level, metabolic response was as follows: complete response, n = 1; partial response, n = 11; stable disease, n = 17; and progressive disease, n = 8. The mean tumor-absorbed dose was 84% higher in patients with complete or partial response than in patients with progressive disease (95% CI, 20%-180%). Survival for patients with a mean tumor-absorbed dose of more than 90 Gy was significantly better than for patients with a mean tumor-absorbed dose of less than 90 Gy (hazard ratio, 0.16; 95% CI, 0.06-0.511). Conclusion: A significant dose-response relationship in CRC patients treated with 166Ho radioembolization was established, and a positive association between toxicity and parenchymal dose was found. For future patients, it is advocated to use a 166Ho scout dose to select patients and yo personalize the administered activity, targeting a mean tumor-absorbed dose of more than 90 Gy and a parenchymal dose of less than 55 Gy.

Concurrent imaging of vascularization and metabolism in a mouse model of paraganglioma under anti-angiogenic treatment.

Rationale: Deregulation of metabolism and induction of vascularization are major hallmarks of cancer. Using a new multimodal preclinical imaging instrument, we explored a sequence of events leading to sunitinib-induced resistance in a murine model of paraganglioma (PGL) invalidated for the expression of succinate dehydrogenase subunit B (Sdhb-/-).Methods: Two groups of Sdhb-/- tumors bearing mice were treated with sunitinib (6 weeks) or vehicle (3 weeks). Concurrent Positron Emission Tomography (PET) with 2′ -deoxy-2′-[18F]fluoro-D-glucose (FDG), Computed Tomography (CT) and Ultrafast Ultrasound Imaging (UUI) imaging sessions were performed once a week and ex vivo samples were analyzed by western blots and histology.Results: PET-CT-UUI enabled to detect a rapid growth of Sdhb-/- tumors with increased glycolysis and vascular development. Sunitinib treatment prevented tumor growth, vessel development and reduced FDG uptake at week 1 and 2 (W1-2). Thereafter, imaging revealed tumor escape from sunitinib treatment: FDG uptake in tumors increased at W3, followed by tumor growth and vessel development at W4-5. Perfused vessels were preferentially distributed in the hypermetabolic regions of the tumors and the perfused volume increased during escape from sunitinib treatment. Finally, initial changes in total lesion glycolysis and maximum vessel length at W1 were predictive of resistance to sunitinib.Conclusion: These results demonstrate an adaptive resistance of Sdhb-/- tumors to six weeks of sunitinib treatment. Early metabolic changes and delayed vessel architecture changes were detectable and predictable in vivo early during anti-angiogenic treatment. Simultaneous metabolic, anatomical and functional imaging can monitor precisely the effects of anti-angiogenic treatment of tumors.

Prognostic Value of the Volumetric Parameters of Dual-Time-Point 18F-FDG PET/CT in Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy.

OBJECTIVE. The purpose of this study is to assess the effectiveness of the volumetric parameters of dual-time-point imaging (DTPI) with 18F-FDG PET (DTPI FDG PET) in predicting the prognosis of patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy (RT). MATERIALS AND METHODS. The records of consecutive patients who received definitive RT for NSCLC from April 2010 to April 2017 were retrospectively reviewed. Pretreatment DTPI FDG PET images were routinely obtained as part of the PET/CT examination. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor (SUVmax-T, MTV-T, and TLG-T, respectively) and those of the primary tumor and lymph nodes (N) combined (SUVmax-TN, MTV-TN, and TLG-TN, respectively) were used as variables, and the percentage change in these parameters (change in SUVmax [ΔSUVmax], change in MTV [ΔMTV], and change in TLG [ΔTLG]) on DTPI FDG PET were analyzed. RESULTS. Of the 118 patients identified and reviewed, 59 met the study eligibility criteria. After a median follow-up of 23.3 months, the 3-year local control rate (LCR) and disease-specific survival rates were 53.5% and 45.0%, respectively. On multivariate analysis, significant predictors of LCR were TLG-T and change in TLG-TN (ΔTLG-TN), and significant predictors of disease-specific survival were adjuvant chemotherapy, treatment response, TLG-T, and change in TLG-T (ΔTLG-T). Low percentage changes in ΔTLG (< 41.0% for ΔTLG-T and < 32.0% for ΔTLG-TN) correlated with poor LCR and disease-specific survival. SUVmax and MTV were not significant predictors of both LCR and disease-specific survival. CONCLUSION. TLG and ΔTLG were significant prognostic factors in patients with NSCLC treated with definitive RT. In particular, a relatively low ΔTLG resulted in poor outcomes in terms of LCR and disease-specific survival.

(P27) Rate of Change in Quantitative PET/CT Metrics Prior to Definitive Chemoradiotherapy for Cervical Cancer Does not Add Prognostic Information Over Single Time Point Metrics

Quantitative metrics from 18-F fluorodeoxyglucose positron emission tomography with computed tomography (PET/CT), such as pre-treatment maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), have been shown to prognosticate recurrence and/or survival from cervical cancer. The change in SUV through treatment and persistent PET avidity on follow-up imaging also predict outcome; however, the prognostic value of temporally changing metrics prior to and early in treatment is unknown. This study aimed to evaluate the prognostic value of the rate of change in quantitative metrics from serial PET/CT scans prior to and through definitive chemoradiotherapy, to identify patients at increased risk of disease recurrence. We identified thirty-three patients with FIGO IB1-IVB cervical cancer treated with definitive chemoradiation and brachytherapy boost and who underwent PET/CT imaging at at least two of the following: diagnosis/staging, simulation, and/or mid-treatment. Patient charts were retrospectively reviewed under Insitutional Review Board approval to collect patient demographics, treatment characteristics, and clinical outcomes. SUVmax, MTV (via gradient-based segmentation), and TLG were measured on PET/CT scans from at least 2 time points. The changes in each metric between each pair of time points was calculated to define the SUV velocity (SUVV), metabolic tumor growth rate (MTGR), and change in TLG (dTLG/dt). Single predictor Cox proportional hazards models were generated with Benjamini-Hochberg false discovery rate adjustment. Generalized linear mixed models evaluated temporally repeated measures (SUVmax, MTV, TLG) and logistic regression evaluated interval rates (SUVV, MTGR, and dTLG/dT) as predictors of recurrence. Median follow up was 12 months (range, 0-39) with 2 local failures (6.1%), 7 distant failures (21.2%), and 3 deaths (9.1%, all after a recurrence). Median (range) time to local failure and distant failure was 21.5 months (15-28) and 3 months (1-10), respectively. Of the 33 patients, 25 (75.8%), 25 (75.8%), and 30 (90.9%) had scans at diagnosis/staging, simulation, and mid-treatment, respectively. For all patients, median (range) SUVmax, MTV, and TLG at simulation were 16.9 U (5.6-41.4), 35.1 ml (1.7-298.2), and 270.2 U*ml (6.9-2979.2). Median (range) SUVV, MTGR, and dTLG/dt between diagnosis and simulation were 0.03 U/d (-1.91-0.18), 0.11 ml/d (-11.32-1.03), and 0.22 U*ml/d (-240.25-8.97), respectively. Single predictor Cox models showed increased hazard of recurrence for larger cervix GTV as measured on PET/CT (HR 1.01, 95% CI 1.00-1.02, p<0.01) and MTV at simulation (HR 1.02, 95% CI 1.00-1.03, p=0.03), however these were not significant after false discovery adjustment. The continuous change in SUV, MTV, and TLG over time and SUVV, MTGR, dTLG/dT between any two time points, were not prognostic/predictive of recurrence. As previously reported, pre-treatment MTV is prognostic of recurrence. The rate of change in SUV, MTV, and TLG prior to treatment or through the initiation of chemoradiotherapy do not add additional prognostic information. However, future studies with larger sample size, more consistent time points, and longer follow-up are warranted. While serial PET/CT may not add to single time point metrics, repeat PET/CT may be important to replicate treatment position, or to plan for lymph node boosts or brachytherapy.

Multimodal Imaging of Pathologic Response to Chemoradiation in Esophageal Cancer

To examine the value of early changes in quantitative diffusion-weighted imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for discriminating complete pathologic response (pCR) to chemoradiation in esophageal cancer. Twenty esophageal cancer patients treated with chemoradiation followed by surgery were prospectively enrolled. Patients underwent magnetic resonance imaging and FDG-PET/CT scans at baseline, interim (2weeks after chemoradiation start), and first follow-up. On the basis of pathologic findings at surgery, patients were categorized into tumor regression groups (TRG1, TRG2, and TRG3+). Distributions of summary statistics in apparent diffusion coefficient (ADC) and FDG-PET at baseline and relative changes at interim and follow-up scans were compared between pCR/TRG1 and non-pCR/TRG2+ groups and across readers. Receiver operating characteristics were evaluated for summary measures to characterize discrimination of pCR from non-pCR. Relative changes in tumor volume ADC (ΔADC) mean and 25th and 10th percentiles from baseline to interim were able to completely discriminate (area under the curve=1, P<.0011) between pCR and non-pCR (thresholds=27.7%, 29.2%, and 32.1%, respectively) and were found to have high interreader reliability (95% limits of agreement of 1.001, 0.944, and 0.940, respectively). Relative change in total lesion glycolysis (TLG) from baseline to interim was significantly different among pCR and non-pCR groups (P=.0117) and yielded an area under the curve of 0.947 (95% confidence interval 0.8505-1.043). An optimal threshold of 59% decrease in TLG provided optimal sensitivity (specificity) of 1.000 (0.867). Changes in ADC summary measures were negatively correlated with that of TLG (Spearman, -0.495, P=.027). Quantitative volume ΔADC and TLG during treatment may serve as early imaging biomarkers for discriminating pathologic response to chemoradiation in esophageal cancer. Validation of these data in larger, prospective, multicenter studies is essential.

Utilization of a hybrid finite-element based registration method to quantify heterogeneous tumor response for adaptive treatment for lung cancer patients

Tumor response to radiation treatment (RT) can be evaluated from changes in metabolic activity between two positron emission tomography (PET) images. Activity changes at individual voxels in pre-treatment PET images (PET1), however, cannot be derived until their associated PET-CT (CT1) images are appropriately registered to during-treatment PET-CT (CT2) images. This study aimed to investigate the feasibility of using deformable image registration (DIR) techniques to quantify radiation-induced metabolic changes on PET images. Five patients with non-small-cell lung cancer (NSCLC) treated with adaptive radiotherapy were considered. PET-CTs were acquired two weeks before RT and 18 fractions after the start of RT. DIR was performed from CT1 to CT2 using B-Spline and diffeomorphic Demons algorithms. The resultant displacements in the tumor region were then corrected using a hybrid finite element method (FEM). Bitmap masks generated from gross tumor volumes (GTVs) in PET1 were deformed using the four different displacement vector fields (DVFs). The conservation of total lesion glycolysis (TLG) in GTVs was used as a criterion to evaluate the quality of these registrations. The deformed masks were united to form a large mask which was then partitioned into multiple layers from center to border. The averages of SUV changes over all the layers were 1.0 ± 1.3, 1.0 ± 1.2, 0.8 ± 1.3, 1.1 ± 1.5 for the B-Spline, B-Spline + FEM, Demons and Demons + FEM algorithms, respectively. TLG changes before and after mapping using B-Spline, Demons, hybrid-B-Spline, and hybrid-Demons registrations were 20.2%, 28.3%, 8.7%, and 2.2% on average, respectively. Compared to image intensity-based DIR algorithms, the hybrid FEM modeling technique is better in preserving TLG and could be useful for evaluation of tumor response for patients with regressing tumors.

Interim FDG-PET Imaging as an Early Response Biomarker for Pathologic Response to Chemoradiation in Esophageal Cancer

To evaluate predictors of complete pathologic response to chemoradiation (CRT) in esophageal cancer (EC) treatment using fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging changes before, during, and after CRT. Previous research shows that change in maximum standardized uptake value (SUVmax) does not predict for response to CRT. We evaluated other PET parameters in this prospective clinical trial. Forty-two EC patients were enrolled in this ongoing prospective imaging study. For this report, we report on the 20 patients who had surgery after neoadjuvant CRT. Outcome was assessed pathologically based on tumor regression grade (TRG, 1 = pathologic complete response, 2 = near complete response, and ≥3 = more than minimal residual). FDG PET imaging was acquired before treatment (baseline, BL), approximately 2 weeks after starting chemoradiation (interim, IM), and at first follow-up (FU) 4-6 weeks after completing CRT. The 3D tumor was contoured on the PET images using gradient edge technique using MIM software (MIM Software Inc. Cleveland, OH). Summary statistics for SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were determined from the contoured volume at each time point. Relative changes in each tumor PET parameter from BL to IM and FU scan were calculated and compared by outcome status defined as TRG1 vs. TRG2/TRG≥3 using Wilcoxon rank-sum test. Multiple logistic regression was used to evaluate receiver operating curve (ROC) characteristics for predicting pathologic response status based on analysis of DSUVmax, DSUVmean, DMTV, and DTLG values. TRG 1, 2, and 3 after CRT and surgery were seen in 5 (29%), 9 (43%), and 6 pts (29%), respectively. Tumors that had a complete pathologic response exhibited significantly greater change in TLG (P = 0.0117) from the baseline to interim scan, with a threshold of 59% decrease. Change in SUVmax (P = 0.232, P = 0.832), SUVmean (P = 0.086, P = 0.550), and MTV from BL to IM or BL to FU scans were not predictive of pathologic CR, respectively. Predicting outcome status based on change in TLG at the IM scan yielded AUROC of 0.888 (95% CI: 0.742-1.000). Youden’s optimal sensitivity (specificity) were 1.000 (0.813) for DTLG at the IM scan. Our results indicate that DTLG on PET imaging after 2 weeks of CRT may predict pathologic complete response in esophageal cancer. Early response assessment with FDG-PET is potentially useful for stratification of EC pts to treatment intensification or non-surgical management.

18F-FDG PET/CT for Very Early Response Evaluation Predicts CT Response in Erlotinib-Treated Non-Small Cell Lung Cancer Patients: A Comparison of Assessment Methods.

The purpose of this study was to determine which method for early response evaluation with 18F-FDG PET/CT performed most optimally for the prediction of response on a later CT scan in erlotinib-treated non-small cell lung cancer patients. Methods:18F-FDG PET/CT scans were obtained before and after 7-10 d of erlotinib treatment in 50 non-small cell lung cancer patients. The scans were evaluated using a qualitative approach and various semiquantitative methods including percentage change in SUVs, lean body mass-corrected (SUL) SULpeak, SULmax, and total lesion glycolysis (TLG). The PET parameters and their corresponding response categories were compared with the percentage change in the sum of the longest diameter in target lesions and the resulting response categories from a CT scan obtained after 9-11 wk of erlotinib treatment using receiver-operating-characteristic analysis, linear regression, and quadratic-weighted κ. Results: TLG delineation according to the PERCIST showed the strongest correlation to sum of the longest diameter (R = 0.564, P < 0.001), compared with SULmax (R = 0.298, P = 0.039) and SULpeak (R = 0.402, P = 0.005). For predicting progression on CT, receiver-operating-characteristic analysis showed area under the curves between 0.79 and 0.92, with the highest area under the curve of 0.92 (95% confidence interval [CI], 0.84-1.00) found for TLG (PERCIST). Furthermore, the use of a cutoff of 25% change in TLG (PERCIST) for both partial metabolic response and progressive metabolic disease, which is the best predictor of the CT response categories, showed a κ-value of 0.53 (95% CI, 0.31-0.75). This method identifies 41% of the later progressive diseases on CT, with no false-positives. Visual evaluation correctly categorized 50%, with a κ-value of 0.47 (95% CI, 0.24-0.70). Conclusion: TLG (PERCIST) was the optimal predictor of response on later CT scans, outperforming both SULpeak and SULmax The use of TLG (PERCIST) with a 25% cutoff after 1-2 wk of treatment allows us to safely identify 41% of the patients who will not benefit from erlotinib and stop the treatment at this time.

FDG-PET parameters as predictors of pathologic response and nodal clearance in patients with stage III non-small cell lung cancer receiving neoadjuvant chemoradiation and surgery

ObjectivePathologic complete response (pCR) following neoadjuvant chemoradiation (CRT) is associated with improved outcomes in stage III non-small cell lung cancer. Conflicting results exist regarding the value of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting pCR. This study evaluated the association between post-CRT FDG-PET and pCR using novel FDG-PET parameters. Methods and materialsThis retrospective study included patients treated with CRT and resection. All underwent pre- and post-CRT FDG-PET imaging. Maximum standard uptake value (SUVmax), standard uptake ratio (SUR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. ResultsIn total, 44 patients were included for review. The majority had cT2 disease (59.0%). Median radiation dose was 60 Gy (45-70.2 Gy). Rate of pCR and near-pCR within the primary lesion was 29.5% and 45.5%, respectively. Average reduction in SUVmax was 9.2, whereas SUR normalized to mediastinum and liver showed mean reductions of 4.7 and 3.5, respectively. No association was found between pCR and either MTV or TLG. Reduction in SUVmax and SUR were significantly associated with increased rate of pCR (P ≤ .02). A threshold of >75% decrease in SUR-liver showed significant association with near-pCR (diagnostic odds ratio [DOR]: 8.3; P = .007). No correlation was found between nodal FDG-PET parameters and nodal pCR. ConclusionsOur results indicate SUV and SUR have utility in predicting pCR after neoadjuvant CRT. SUR parameters trended toward higher DORs, suggesting improved predictive utility compared with SUVmax. Notably, no association was found with nodal pCR. Furthermore, MTV and TLG changes were not predictive, potentially resulting from inflammation after full-dose radiation, but this warrants further investigation.

Serial FDG-PET imaging of metastatic prostate cancers reveals intrapatient intermetastases polyclonality through same patient heterogeneous responses to systemic therapy.

e590 Background: Although intrapatient prostate cancer (PCa) metastasis polyclonality has been recently characterized by genomic and transcriptomic studies, systemic treatment response heterogeneity has yet to be reported or imaged. It remains unknown if polyclonal differentiation leads to heterogeneous treatment responses between metastases in a single patient undergoing therapy. Methods: Between 2010 and 2015, fifteen patients with metastatic PCa were imaged by FDG-PET/CT before and during systemic therapy, and metabolic response was recorded for individual metastatic lesions. Intermetastasis heterogeneity was defined by opposite metabolic responses of at least two metastases from the same compartment (bone or soft tissue) between the two scans. We examined intrapatient intermetastasis heterogeneity of response to systemic therapy based on the assessment of metabolic response in a total of 165 individual lesions (change in SUVmax, complete response, or new lesion). Change in total lesion glycolysis (TLG) was assessed for each patient. Biochemical response and progression-free survival (PFS) were also recorded. Results: Intrapatient intermetastasis response heterogeneity was found in 40% of cases. In univariate statistical analysis, response heterogeneity was associated with a decrease in PFS (p-value= 0.001), but not with age, CRPC status, Gleason score, PSA-DT, TLG, maximum SUVmax, or sum of SUVmax. In two cases, new metastasis and complete metastasis responses were observed in the same patients. Conclusions: Our results suggest that systemic therapies can induce heterogeneous responses among individual metastases in patients with PCa, supporting the polyclonal evolution of PCa in advanced disease. Molecular imaging may thus be useful to identify clinical resistance earlier after therapy initiation and could also enable targeted biopsy of resistant clones for molecular analysis.

The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

PurposeThe purpose of our study was to determine the value of 18F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT).MethodsIn 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, 18F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed.ResultsA poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of −26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18).Conclusions18F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early 18F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders.

Abstract 3972: Total lesion glycolysis (TLG) as an imaging biomarker of regorafenib treatment in metastatic colorectal cancer (mCRC)

Abstract Introduction: Regorafenib is an oral multikinase inhibitor with anti-angiogenic activity. Decrease in tumor density without significant decrease in tumor volume is often observed after treatment with the drug, suggesting the necessity of further means of response evaluation in addition to size criteria. This study was planned to evaluate whether metabolic imaging with 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) could predict outcome in mCRC patient treated with regorafenib. Methods: Patients were enrolled into a main study entitled Identification of Predictive Biomarker of Regorafenib in Refractory Colorectal Cancer: A Prospective Explorative Study (NCT01996969). mCRC patients (N = 117) were treated with regorafenib, 160mg orally once daily, on days 1-21 of a 28-day cycle, and treatment outcome was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1. For this imaging sub-study, the results of 18-FDG PET scans obtained at baseline and after 2 cycles of treatment were analyzed. Total lesion glycolysis (TLG) of each patient was calculated by multiplying the volume exceeding the threshold of 40% of maximum standardized uptake value (SUV) by the mean SUV of the lesion, and the percentage changes of TLG after treatment were calculated. The association between the changes of the metabolic imaging and treatment outcome was analyzed. Results: A total of 44 patients were evaluable for 18-FDG PET scan results. The best overall response in the 44 patients were, partial response in 3 (6.8%), stable disease in 23 (52.3%) and progressive disease in 18 (40.9%). The median progression-free survival (PFS) and the median overall survival (OS) were 5.4 and 14.1 months, respectively. The median of TLG at baseline was 187.4 (range 18.3 to 8893.2). After 2 cycles of regorafenib, 50.0% of patients had a decrease in TLG. Median change in TLG was 1.7% (range, -75.7 to 251.6%). Changes in TLG were modestly associated with size changes (Pearson's r = 0.51, p = 0.001). Patients with lower baseline TLG (&amp;lt; 324.49) showed significantly longer OS (1 year survival rate 75.6 vs. 33.5%, p = 0.008). Moreover, patients showing higher decrease in TLG (change &amp;lt; 1.7%) showed significantly longer PFS (median 8.4 vs. 1.9 months, p&amp;lt;0.001) and trend towards longer OS (1 year survival rate 67.6% vs. 50.9%, p = 0.068). Conclusions: Lower baseline TLG is associated with better OS and higher decrease in TLG after treatment predicted better PFS in mCRC patients treated with regorafenib. Citation Format: Yoojoo Lim, Ji-In Bang, Sae-Won Han, Jin Chul Paeng, Jeong Hee Yoon, Jeong Min Lee, Jae-Kyung Won, Gyeong Hoon Kang, Seung-Yong Jeong, Kyu Joo Park, Kyung-Hun Lee, Jee Hyun Kim, Tae-You Kim. Total lesion glycolysis (TLG) as an imaging biomarker of regorafenib treatment in metastatic colorectal cancer (mCRC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3972.

Changes in Total Lesion Glycolysis Evaluated by Repeated F-18 FDG PET/CT as Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Preoperative Chemoradiotherapy

Aims: The present study was aimed to investigate whether volumetric parameters measured by sequential F-18 fluoro-<smlcap>D</smlcap>-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) could be used as prognostic factors in patients with locally advanced esophageal cancer (LAEC) who received preoperative chemoradiotherapy (CRT). Methods: A total of 61 patients with LAEC were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and after 46 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy. Initial, second, and percent changes (Δ, %) of semiquantitative and volumetric parameters were used to calculate recurrence-free survival (RFS) and overall survival (OS). The median values of each parameter were used as cutoff values. The prognostic significance was assessed using univariate and multivariate Cox proportional hazard regression analyses. Results: Cox proportional hazard regression analyses revealed that change in total lesion glycolysis (ΔTLG) was a potent predictor of RFS and OS. Kaplan-Meier survival curves showed better prognosis in higher ΔTLG. Conclusion: Our data suggest that ΔTLG measured by sequential F-18 FDG PET/CT after preoperative CRT could provide prognostic information in LAEC patients.

Use of PERCIST for Prediction of Progression-Free and Overall Survival After Radioembolization for Liver Metastases from Pancreatic Cancer.

We evaluated the prognostic accuracy of established PET response criteria in patients with liver metastases from pancreatic cancer after treatment with (90)Y microspheres. Seventeen patients underwent (18)F-FDG PET/CT before and 3 mo after radioembolization for liver metastases from pancreatic cancer. Overall survival, progression-free survival, and time to intrahepatic progression were among other factors correlated with metabolic response as revealed by PERCIST 1.0-defined declining SUVpeak and total-lesion glycolysis. Metabolic response by change in SUVpeak (7/17) and change in total-lesion glycolysis (7/17) was a predictor for overall survival (P = 0.039; hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.06-0.93), progression-free survival (P = 0.016; HR, 0.15; 95% CI, 0.03-0.69), and time to intrahepatic progression (P = 0.010; HR, 0.16; 95% CI, 0.04-0.65). A summed baseline CT diameter of less than 8 cm for the 2 largest liver metastases predicted time to intrahepatic progression (P = 0.013; HR, 0.21; 95% CI, 0.06-0.72) but did not predict overall or progression-free survival. Patient outcome was not predicted by other parameters, including baseline SUVpeak, baseline total-lesion glycolysis, or change in serum level of carcinoembryonic antigen or carbohydrate antigen 19-9 from baseline to follow-up (each, P > 0.05). Metabolic response by (18)F-FDG PET/CT predicts overall survival, progression-free survival, and time to intrahepatic progression after radioembolization for liver metastases from pancreatic cancer.

Early Metabolic Response to Neoadjuvant Treatment: FDG PET/CT Criteria according to Breast Cancer Subtype.

To investigate parameters based on fluorine 18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging that are best correlated with pathologic complete response (PCR) in human epidermal growth factor receptor type 2 (HER2)-positive cancer and triple-negative breast cancer (TNBC) and with partial or complete response in ER-positive/HER2-negative breast cancer. This study was approved by institutional review board with waivers of informed written consent and included consecutive patients treated by neoadjuvant chemotherapy. Five PET examination-derived parameters were tested: standard uptake value (SUV) maximum (SUV(max)), peak (SUV(peak)), and mean (SUV(mean)), metabolically active tumor volume, and total lesion glycolysis (TLG). Absolute values at baseline PET, at PET imaging after two cycles of chemotherapy, and variation (ie, change) were measured. Correlations with pathologic response (Wilcoxon rank-sum test) and predictive power assessed (area under the curve [AUC] on the basis of receiver operating characteristic analysis) were examined. Included were 169 consecutive patients (mean age, 50 years). PCR was more frequent in HER2-positive tumors (16 of 33 patients [48.5%]) and TNBCs (20 of 54 patients [37%]) than in ER positive/HER2-negative tumors (four of 82 [4.9%]) (P < .001). Among patients with ER-positive/HER2-negative cancers, 33 patients had partial response. In TNBC, best association with PCR was obtained with change in SUV(max) (AUC, 0.86) or change in TLG (AUC, 0.88). In HER2-positive phenotype, absolute SUV(max) (or SUV(peak)) values at PET imaging after two cycles of chemotherapy (AUC for each cycle, 0.93) were better correlated with PCR than change in SUV(max) (AUC, 0.78; P = .11) or change in TLG (AUC, 0.62; P = .005). Regarding ER-positive/HER2-negative cancers, change in SUV(max) or change in TLG (AUC, 0.75) were parameters best correlated with partial or complete response. Baseline SUV(max) was higher in lymph nodes than in primary tumor in 31 patients. Findings were similar considering the site with highest FDG uptake. Quantitative indexes of tumor glucose use that are best correlated with pathologic response vary by phenotype: change in SUV(max) or TLG are most adequate for TNBCs and ER-positive/ HER2-negative cancers and absolute SUV(max) after two cycles of chemotherapy for HER2-positive breast cancers.

Total lesion glycolysis as an IgG4-related disease activity marker

Objectives. 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) was reported to be useful for monitoring immunoglobulin G4-related disease (IgG4-RD); however, a quantitative FDG-PET/CT analysis such as total lesion glycolysis (TLG) has not yet been conducted. This study aimed to investigate whether TLG would correlate with serum markers in IgG4-RD, and the utility of TLG for disease monitoring.Methods. This retrospective study included 17 patients (12 men; median age, 62 years) who were followed up at Kyoto University Hospital and underwent FDG-PET/CT from April 2009 to November 2013. TLG was calculated for the involved lesions. Correlations between serum markers [IgG4, soluble IL-2 receptor (sIL-2R), lactate dehydrogenase (LDH), and C-reactive protein (CRP)] and TLG concomitant with FDG-PET/CT scans were investigated. Serial changes in TLG were assessed in patients who underwent follow-up FDG-PET/CT (n = 6).Results. The calculated median (IQL) TLG value was 154.8 (63.7–324.4). A significant correlation was found between the sIL-2R level and TLG (P = 0.001, rs = 0.763). In contrast, no correlations were found between the IgG4, LDH, or CRP levels and TLG. Increased or decreased TLG corresponded with clinical disease improvement or worsening.Conclusions. TLG correlated significantly with the serum sIL-2R level and may be useful for disease monitoring in IgG4-RD.