PET-based Tumor Volumes Research Articles

Comparison of Multiple Segmentation Methods for Volumetric Delineation of Primary Prostate Cancer with Prostate-Specific Membrane Antigen-Targeted 18F-DCFPyL PET/CT.

This study aimed to assess the accuracy of intraprostatic tumor volume measurements on prostate-specific membrane antigen-targeted 18F-DCFPyL PET/CT made with various segmentation methods. An accurate understanding of tumor volumes versus segmentation techniques is critical for therapy planning, such as radiation dose volume determination and response assessment. Methods: Twenty-five men with clinically localized, high-risk prostate cancer were imaged with 18F-DCFPyL PET/CT before radical prostatectomy. The tumor volumes and tumor-to-prostate ratios (TPRs) of dominant intraprostatic foci of uptake were determined using semiautomatic segmentation (applying SUVmax percentage [SUV%] thresholds of SUV30%-SUV70%), adaptive segmentation (using adaptive segmentation percentage [A%] thresholds of A30%-A70%), and manual contouring. The histopathologic tumor volume (TV-Histo) served as the reference standard. The significance of differences between TV-Histo and PET-based tumor volume were assessed using the paired-sample Wilcoxon signed-rank test. The Spearman correlation coefficient was used to establish the strength of the association between TV-Histo and PET-derived tumor volume. Results: Median TV-Histo was 2.03 cm3 (interquartile ratio [IQR], 1.16-3.36 cm3), and median TPR was 10.16%. The adaptive method with an A40% threshold most closely determined the tumor volume, with a median difference of +0.19 (IQR, -0.71 to +2.01) and a median relative difference of +7.6%. The paired-sample Wilcoxon test showed no significant difference in PET-derived tumor volume and TV-Histo using A40%, A50%, SUV40%, and SUV50% threshold segmentation algorithms (P > 0.05). For both threshold-based segmentation methods, use of higher thresholds (e.g., SUV60% or SUV70% and A50%-A70%) resulted in underestimation of tumor volumes, and use of lower thresholds (e.g., SUV30% or SUV40% and A30%) resulted in overestimation of tumor volumes relative to TV-Histo and TPR. Manual segmentation overestimated the tumor volume, with a median difference of +2.49 (IQR, 0.42-4.11) and a median relative difference of +130%. Conclusion: Segmentation of intraprostatic tumor volume and TPR with an adaptive segmentation approach most closely approximates TV-Histo. This information might be used to guide the primary treatment of men with clinically localized, high-risk prostate cancer.

68Ga-PSMA PET/CT-Based Atlas for Prostate Bed Recurrence After Radical Prostatectomy: Clinical Implications for Salvage Radiation Therapy Contouring Guidelines.

The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.

1419P Radiobiological parameters for the assessment of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer

The lack of robust radiobiological data hampers the further optimization of emerging 177Lu-PSMA-directed radioligand therapy (RLT). This study aims to explore several conventional radiobiological parameters in the assessment of outcomes in tumor and normal organs at risk (OARs) for castration-resistant prostate cancer (CRPC) patients. 20 patients received a median of 3 (range 1–6, a totally of 86 cycles) 177Lu-PSMA-617 RLT were retrospectively included. Hematological status, renal and liver function, and serum PSA test before and within two weeks post-therapy were documented. Pre-therapy PSMA-PET/CT image dates were collected to establish CT-based organ segmentation. The post-therapy dosimetry of each patient was measured using at least 3-time-points SPECT/CT imaging. PSA was used to determine therapy response, and the related adverse events were documented. Dose parameters including conventional radiobiological such as absorbed dose, integral dose (D10/50/90), biologically effective doses (BED) and cumulated BEDs (cBED) were tested. All patients are well-tolerated and 19/20 patients received a partial response post-therapy. The dosimetry evaluation demonstrated a high absorbed dose in tumors compared to OARs (p<.0001). The Dosemean/max/sum of target organs decreases as the treatment cycle increases. The absorbed dose in non-tumor-bearing bones is significantly correlated with hematological AEs (G2-4) (p<.05). The patients with larger PET-based tumor volumes present higher absorbed doses in tumor and OARs (also when normalized to the administered activity). The highest D10/50/90 was received by tumor-bearing bone, the whole-body tumor and lymph/visceral regions respectively compared to OARs. BED1.5 (AUROC: 0.633) and cBED1.5 (AUROC: 0.714) demonstrated aggregable diagnostic accuracy in detecting better post-treatment PSA outcomes. Despite the limited number of patients in this study, the preliminary results encourage the exploration of radiobiological models in the assessment of PSMA-RLT. In-depth analysis and interpretation of these radiobiological parameters are still ongoing.

Prognostic value of subventricular zone involvement in relation to tumor volumes defined by fused MRI and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET imaging in glioblastoma multiforme

BackgroundSubventricular zone (SVZ) involvement is associated with a dismal prognosis in patients with glioblastoma multiforme (GBM). Dual-time point (dtp) O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET/CT (PET) may be a time- and cost-effective alternative to dynamic FET PET, but its prognostic value, particularly with respect to SVZ involvement, is unknown.MethodsThirty-five patients had two scans 5–15 and 50–60 min after i.v. FET injection to define tumor volumes and SVZ involvement before starting radiotherapy. Associations between clinical progression markers, MRI- and dtp FET PET-based tumor volumes, or SVZ involvement and progression-free (PFS) and overall survival (OS) were assessed in univariable and multivariable analyses.ResultsThe extent of resection was not related to outcomes. Albeit non-significant, dtp FET PET detected more SVZ infiltration than MRI (60% vs. 51%, p = 0.25) and was significantly associated with poor survival (p < 0.03), but PET-T1-Gad volumes were larger in this group (p < 0.002). Survival was shorter in patients with larger MRI tumor volumes, larger PET tumor volumes, and worse Karnofsky performance status (KPS), with fused PET-T1-Gad and KPS significant in multivariable analysis (p < 0.03). Uptake kinetics was not associated with treatment outcomes.ConclusionsFET PET-based tumor volumes may be useful for predicting worse prognosis glioblastoma. Although the presence of SVZ infiltration is linked to higher PET/MRI-based tumor volumes, the independent value of dtp FET PET parameters and SVZ infiltration as prognostic markers pre-irradiation has not been confirmed.

Abstract 3730: Early metabolic response to tumor-treating fields in patients with recurrent glioblastoma

Abstract PURPOSE. Tumor-Treating Fields (TTFields) is an FDA-approved treatment approach for patients with both newly-diagnosed and recurrent glioblastoma. The main purpose of the present study was to explore if amino acid positron emission tomography (PET) is able to detect an early, objective metabolic tumor response during the first months of TTFields therapy. METHODS. Patients with MRI signs of recurrent glioblastoma eligible for TTFields along with maintenance temozolomide were recruited for PET scanning with alpha[C-11]-methyl-L-tryptophan (AMT) at baseline (before start of TTFields application) and up to 3 months later. Serial MRIs were also performed in 1-2 months intervals. AMT accumulation in the MRI-detected tumor mass was measured by standardized uptake values (SUVs), and PET-based tumor volumes were also calculated. Interval changes of these PET variables were compared to changes in areas of MRI enhancement. RESULTS. Out of 7 recruited patients, 5 showed appropriate compliance (&amp;gt;75%) with the device and underwent follow-up PET. Four of the 5 patients showed a clear metabolic response during TTF treatment on PET imaging. Two patients, who received TTFields treatment only (in addition to maintenance temozolomide), showed 25% and 100% decrease of PET-based tumor volumes, respectively. MRI was stable (patient #1) or showed increasing contrast enhancement (#2) during the same period. In this latter patient, TTFields was continued with bevacizumab treatment, leading to decreased contrast enhancement and further decrease of AMT uptake on a second follow-up PET. In two other patients (#3 and #4), TTFields were combined with bevacizumab rescue treatment. Patient #3 showed a markedly decreased tumoral AMT uptake and metabolic volume along with stable MRI enhancement. Patient #4 showed interval decrease of tryptophan PET uptake 2 months after initiation of TTFields therapy. Finally, patient #5 showed an interval expansion of the PET-based tumor volume along with MRI progression during a 2-month follow-up despite TTFields combined with bevacizumab and carboplatin. CONCLUSIONS. This is the first study to demonstrate an objective metabolic response of recurrent glioblastoma within 1.5-3 months after initiation of TTFields. The data suggest that amino acid PET can identify early responders to TTFields therapy. Citation Format: Sandeep Mittal, Geoffrey R. Barger, Edit Bosnyák, Varun B. Shah, Csaba Juhász. Early metabolic response to tumor-treating fields in patients with recurrent glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3730. doi:10.1158/1538-7445.AM2017-3730

NIMG-37. IMAGING THE EARLY METABOLIC RESPONSE DURING TUMOR-TREATING FIELDS THERAPY IN RECURRENT GLIOBLASTOMA

Tumor-treating fields (TTF) therapy is an innovative treatment approach for newly diagnosed and recurrent glioblastoma. In this study we evaluated whether positron emission tomography with alpha[11C]-methyl-L-tryptophan (AMT-PET) would detect early metabolic responses during the first 3 months of TTF therapy. Five patients with MRI-detected recurrent glioblastoma being treated with temozolomide underwent AMT-PET scanning prior to delivery of TTF. Four of the 5 patients had >75% compliance with the device and underwent a repeat PET scan 1.5 to 3 months later. Interval changes of tumoral tryptophan uptake and PET-based tumor volumes (based on a previously defined threshold) were measured and compared to changes in MRI enhancement. Three patients showed an early metabolic response reflected by interval decrease of tumoral tryptophan uptake and PET-based tumor volumes during the follow-up period. Patients #1 and #2 who received TTF therapy in addition to maintenance temozolomide showed a ≥25% decrease of PET-based tumor volumes 1.5 and 3 months later, respectively, followed by a delayed MRI response 2 months after the second PET scan. In the other two patients, TTF therapy was combined with bevacizumab. Patient #3 showed markedly decreased tumoral AMT uptake and reduced PET-based tumor volume, along with stable MRI contrast enhancement after 3 months, which continued for 3 additional months before progression. Patient #4, with a much larger baseline tumor volume than the other three patients, showed an increase in the PET-based tumor volume during a 2-month follow-up. MRI showed a steady increase in the volume of contrast enhancement both during and after the AMT-PET follow-up period. These preliminary data demonstrate an early metabolic response to TTF therapy in 3 out of 4 the patients with recurrent glioblastoma who maintained good compliance with the device. This metabolic response seems to precede a subsequent MRI response.

18F-FDG-PET-based tumor delineation in cervical cancer: Threshold contouring and lesion volumes

ObjectiveTo evaluate a semi-automated PET-image tumor segmentation algorithm for gross tumor volume (GTV) delineation in patients with locally advanced cervical cancer. Material and methodsThirty-two patients with locally advanced cervical cancer were retrospectively evaluated. Semi-automated PET-image-based GTV delineation was applied using a previous established algorithm (GTV2SD) and 2 fixed threshold-based methods (GTV40% and GTV50%). GTV2SD was determined as the pixel with the mean value plus 2-standard deviation of the liver intensity, and GTV40% and GTV50% with 40% and 50% of the maximum tumor intensity (Tmax), respectively. The derived volumes were then compared with the GTVs generated manually using MR (GTVMR). ResultsThe mean value of GTV2SD, GTV40% and GTV50% was 85.3cc, 16.2cc and 24.1cc, respectively. Good agreement was noticed between GTV2SD and GTVMR (ρ=0.88). GTV40% and GTV50% showed weaker correlation with GTVMR (ρ=0.68 and ρ=0.71, respectively). ConclusionsThis study provides preliminary evidence that metabolic tumor volume delineation is feasible using computer-generated measurements in 18F-FDG PET images. Generation of PET-based tumor volumes is affected by the choice of threshold level used. Metabolic tumor bulk calculated using the pixel with the mean value plus 2-standard deviations of the liver intensity (GTV2SD) correlates better with the MR-derived tumor volumes. The method is a simple and clinically applicable approach to generate PET-derived GTV for radiation therapy planning of cervical cancer.

18F-FDG-PET-based tumor delineation in cervical cancer: Threshold contouring and lesion volumes

To evaluate a semi-automated PET-image tumor segmentation algorithm for gross tumor volume (GTV) delineation in patients with locally advanced cervical cancer. Thirty-two patients with locally advanced cervical cancer were retrospectively evaluated. Semi-automated PET-image-based GTV delineation was applied using a previous established algorithm (GTV2SD) and 2 fixed threshold-based methods (GTV40% and GTV50%). GTV2SD was determined as the pixel with the mean value plus 2-standard deviation of the liver intensity, and GTV40% and GTV50% with 40% and 50% of the maximum tumor intensity (Tmax), respectively. The derived volumes were then compared with the GTVs generated manually using MR (GTVMR). The mean value of GTV2SD, GTV40% and GTV50% was 85.3cc, 16.2cc and 24.1cc, respectively. Good agreement was noticed between GTV2SD and GTVMR (ρ=0.88). GTV40% and GTV50% showed weaker correlation with GTVMR (ρ=0.68 and ρ=0.71, respectively). This study provides preliminary evidence that metabolic tumor volume delineation is feasible using computer-generated measurements in (18)F-FDG PET images. Generation of PET-based tumor volumes is affected by the choice of threshold level used. Metabolic tumor bulk calculated using the pixel with the mean value plus 2-standard deviations of the liver intensity (GTV2SD) correlates better with the MR-derived tumor volumes. The method is a simple and clinically applicable approach to generate PET-derived GTV for radiation therapy planning of cervical cancer.

Impact of Tumor Size and Tracer Uptake Heterogeneity in 18F-FDG PET and CT Non–Small Cell Lung Cancer Tumor Delineation

The objectives of this study were to investigate the relationship between CT- and (18)F-FDG PET-based tumor volumes in non-small cell lung cancer (NSCLC) and the impact of tumor size and uptake heterogeneity on various approaches to delineating uptake on PET images. Twenty-five NSCLC cancer patients with (18)F-FDG PET/CT were considered. Seventeen underwent surgical resection of their tumor, and the maximum diameter was measured. Two observers manually delineated the tumors on the CT images and the tumor uptake on the corresponding PET images, using a fixed threshold at 50% of the maximum (T(50)), an adaptive threshold methodology, and the fuzzy locally adaptive Bayesian (FLAB) algorithm. Maximum diameters of the delineated volumes were compared with the histopathology reference when available. The volumes of the tumors were compared, and correlations between the anatomic volume and PET uptake heterogeneity and the differences between delineations were investigated. All maximum diameters measured on PET and CT images significantly correlated with the histopathology reference (r > 0.89, P < 0.0001). Significant differences were observed among the approaches: CT delineation resulted in large overestimation (+32% ± 37%), whereas all delineations on PET images resulted in underestimation (from -15% ± 17% for T(50) to -4% ± 8% for FLAB) except manual delineation (+8% ± 17%). Overall, CT volumes were significantly larger than PET volumes (55 ± 74 cm(3) for CT vs. from 18 ± 25 to 47 ± 76 cm(3) for PET). A significant correlation was found between anatomic tumor size and heterogeneity (larger lesions were more heterogeneous). Finally, the more heterogeneous the tumor uptake, the larger was the underestimation of PET volumes by threshold-based techniques. Volumes based on CT images were larger than those based on PET images. Tumor size and tracer uptake heterogeneity have an impact on threshold-based methods, which should not be used for the delineation of cases of large heterogeneous NSCLC, as these methods tend to largely underestimate the spatial extent of the functional tumor in such cases. For an accurate delineation of PET volumes in NSCLC, advanced image segmentation algorithms able to deal with tracer uptake heterogeneity should be preferred.

Impact of Manual and Automated Interpretation of Fused PET/CT Data on Esophageal Target Definitions in Radiation Planning

We compare CT-only based esophageal tumor definition with two PET/CT based methods: (1) manual contouring and (2) a semiautomated method based on specific thresholds. Patients with esophageal cancer treated at Brigham and Women's Hospital from 2003 to 2006 were identified. CT-based tumor volumes were compared with manual PET/CT-based volumes and semiautomated PET-based tumor volumes. Differences were scored as (1) minor if the superior or inferior extent of the primary tumor (or both) differed by 1-2 cm and (2) major if the difference was > 2 cm or if different noncontiguous nodal regions were identified as being grossly involved. Comparing CT-based gross tumor volumes (GTVs) to manually defined PET/CT-based GTVs, use of PET changed volumes for 21 of 25 (84%) patients: 12 patients (48%) exhibited minor differences, whereas for 9 patients (36%), the differences were major. For 4 (16%) patients, the major difference was due to discrepancy in celiac or distant mediastinal lymph node involvement. Use of automated PET volumes changed the manual PET length in 14 patients (56%): 8 minor and 6 major. The use of PET/CT in treatment planning for esophageal cancer can affect target definition. Two PET-based techniques can also produce significantly different tumor volumes in a large percentage of patients. Further investigations to clarify the optimal use of PET/CT data in treatment planning are warranted.

Evaluation of Different Methods of 18F-FDG-PET Target Volume Delineation in the Radiotherapy of Head and Neck Cancer

To quantify differences between the alternative methods of F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)-based delineation of the gross tumor volume in patients with head and neck cancer. Twelve patients with locally-advanced head and neck carcinomas were studied. The reference gross tumor volume (GTVref) was established by a radiation oncologist, along with a neuroradiologist, using the computed tomography-simulation and diagnostic magnetic resonance imaging data. With the GTVref obscured, a second radiation oncologist and a nuclear medicine physician determined the following contours: (1) high FDG uptake based on visual inspection (GTVvis), (2) the contour derived from the 50% maximum standardized uptake value (SUV) threshold (GTV50), (3) the contour derived from a 2.5 SUV absolute threshold (GTV2.5), and (4) the contours derived from an iterative segmentation algorithm (GTViter). These volumes were compared with the GTVref using a signed-ranks test with the exact reference distribution. The average GTVref was 75.5 mL (median 72.8 mL, range 22.2-138.4 mL). The average GTVvis was 57.6 (median 55.4 mL, range 12-115.8 mL). Overall, a 21% reduction in volume size was observed with GTVvis versus GTVref. When the signed-ranks test with the exact reference distribution was applied, the difference was not statistically significant (P = 0.32). The average GTV2.5 was 60 mL (median 64.5, range 8.8-90.3 mL). The differences between GTV2.5 and GTVref were not statistically significant (P = 0.35). The use of GTV50 and GTViter produced significantly smaller volumes with respect to GTVref (P < 0.005). PET-based tumor volumes are strongly affected by the choice of threshold level. Quantitatively, GTVs derived from visual inspection of the region of high FDG uptake do not significantly differ from GTVref in this cohort of patients. The inclusion of alternative FDG-PET segmentation data, other than visual inspection, may reduce target volumes significantly.

Tumor delineation using PET in head and neck cancers: Threshold contouring and lesion volumes

Tumor boundary delineation using positron emission tomography (PET) is a promising tool for radiation therapy applications. In this study we quantify the uncertainties in tumor boundary delineation as a function of the reconstruction method, smoothing, and lesion size in head and neck cancer patients using FDG-PET images and evaluate the dosimetric impact on radiotherapy plans. FDG-PET images were acquired for eight patients with a GE Advance PET scanner. In addition, a 20 cm diameter cylindrical phantom with six FDG-filled spheres with volumes of 1.2 to 26.5 cm3 was imaged. PET emission scans were reconstructed with the OSEM and FBP algorithms with different smoothing parameters. PET-based tumor regions were delineated using an automatic contouring function set at progressively higher threshold contour levels and the resulting volumes were calculated. CT-based tumor volumes were also contoured by a physician on coregistered PET/CT patient images. The intensity value of the threshold contour level that returns 100% of the actual volume, I(V100), was measured. We generated intensity-modulated radiotherapy (IMRT) plans for an example head and neck patient, treating 66 Gy to CT-based gross disease and 54 Gy to nodal regions at risk, followed by a boost to the FDG-PET-based tumor. The volumes of PET-based tumors are a sensitive function of threshold contour level for all patients and phantom datasets. A 5% change in threshold contour level can translate into a 200% increase in volume. Phantom data indicate that I(V100) can be set as a fraction, f, of the maximum measured uptake. Fractional threshold values in the cylindrical water phantom range from 0.23 to 0.51. Both the fractional threshold and the threshold-volume curve are dependent on lesion size, with lesions smaller than approximately 5 cm3 displaying a more pronounced sensitivity and larger fractional threshold values. The threshold-volume curves and fractional threshold values also depend on the reconstruction algorithm and smoothing filter with more smoothing requiring a higher fractional threshold contour level. The threshold contour level affects the tumor size, and therefore the ultimate boost dose that is achievable with IMRT. In an example head and neck IMRT plan, the D95 of the planning target volume decreased from 7770 to 7230 cGy for 42% vs. 55% contour threshold levels. PET-based tumor volumes are strongly affected by the choice of threshold level. This can have a significant dosimetric impact. The appropriate threshold level depends on lesion size and image reconstruction parameters. These effects should be carefully considered when using PET contour and/or volume information for radiotherapy applications.