Positron emission tomography (PET) has a potential improvement for staging and radiation treatment planning of various tumor sites. We analyzed the use of 18F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) images for staging and target volume delineation of patients with head and neck carcinoma candidates for radiotherapy.
Twenty-two patients candidates for primary radiotherapy, who did not receive any curative surgery, underwent both CT and PET/CT simulation. Gross Tumor Volume (GTV) was contoured on CT (CT-GTV), PET (PET-GTV), and PET/CT images (PET/CT-GTV). The resulting volumes were analyzed and compared.
Based on PET/CT, changes in TNM categories and clinical stage occurred in 5/22 cases (22%). The difference between CT-GTV and PET-GTV was not statistically significant (p = 0.2) whereas the difference between the composite volume (PET/CT-GTV) and CT-GTV was statistically significant (p < 0.0001).
PET/CT fusion images could have a potential impact on both tumor staging and treatment planning.
To investigate the utilization of PET-CT in target volume delineation for three-dimensional conformal radiotherapy in patients with non-small cell lung cancer (NSCLC) and atelectasis.
Thirty NSCLC patients who underwent radical radiotherapy from August 2010 to March 2012 were included in this study. All patients were pathologically confirmed to have atelectasis by imaging examination. PET-CT scanning was performed in these patients. According to the PET-CT scan results, the gross tumor volume (GTV) and organs at risk (OARs, including the lungs, heart, esophagus and spinal cord) were delineated separately both on CT and PET-CT images. The clinical target volume (CTV) was defined as the GTV plus a margin of 6-8 mm, and the planning target volume (PTV) as the GTV plus a margin of 10-15mm. An experienced physician was responsible for designing treatment plans PlanCT and PlanPET-CT on CT image sets. 95% of the PTV was encompassed by the 90% isodose curve, and the two treatment plans kept the same beam direction, beam number, gantry angle, and position of the multi-leaf collimator as much as possible. The GTV was compared using a target delineation system, and doses distributions to OARs were compared on the basis of dose-volume histogram (DVH) parameters.
The GTVCT and GTVPET-CT had varying degrees of change in all 30 patients, and the changes in the GTVCT and GTVPET-CT exceeded 25% in 12 (40%) patients. The GTVPET-CT decreased in varying degrees compared to the GTVCT in 22 patients. Their median GTVPET-CT and median GTVPET-CT were 111.4 cm3 (range, 37.8 cm3-188.7 cm3) and 155.1 cm3 (range, 76.2 cm3-301.0 cm3), respectively, and the former was 43.7 cm3 (28.2%) less than the latter. The GTVPET-CT increased in varying degrees compared to the GTVCT in 8 patients. Their median GTVPET-CT and median GTVPET-CT were 144.7 cm3 (range, 125.4 cm3-178.7 cm3) and 125.8 cm3 (range, 105.6 cm3-153.5 cm3), respectively, and the former was 18.9 cm3 (15.0%) greater than the latter. Compared to PlanCT parameters, PlanPET-CT parameters showed varying degrees of changes. The changes in lung V20, V30, esophageal V50 and V55 were statistically significant (Ps< 0.05 for all), while the differences in mean lung dose, lung V5, V10, V15, heart V30, mean esophageal dose, esophagus Dmax, and spinal cord Dmax were not significant (Ps> 0.05 for all).
PET-CT allows a better distinction between the collapsed lung tissue and tumor tissue, improving the accuracy of radiotherapy target delineation, and reducing radiation damage to the surrounding OARs in NSCLC patients with atelectasis.
Atelectasis; PET-CT; Non-small cell lung cancer; Target volume; Three-dimensional conformal radiotherapy
To investigate the accuracy of imaging-based gross tumor volume (GTV) compared with pathological volume in cervical cancer.
Ten patients with International Federation of Gynecology and Obstetrics stage I–II cervical cancer were eligible for investigation and underwent surgery in this study. Magnetic resonance imaging (MRI) and fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET)/computed tomography (CT) scans were taken the day before surgery. The GTVs under MRI and 18F-FDG PET/CT (GTV-MRI, GTV-PET, GTV-CT) were calculated automatically by Eclipse treatment-planning systems. Specimens of excised uterine cervix and cervical cancer were consecutively sliced and divided into whole-mount serial sections. The tumor border of hematoxylin and eosin-stained sections was outlined under a microscope by an experienced pathologist. GTV through pathological image (GTV-path) was calculated with Adobe Photoshop.
The GTVs (average ± standard deviation) delineated and calculated under CT, MRI, PET, and histopathological sections were 19.41 ± 11.96 cm3, 12.66 ± 10.53 cm3, 11.07 ± 9.44 cm3, and 10.79 ± 8.71 cm3, respectively. The volume of GTV-CT or GTV-MR was bigger than GTV-path, and the difference was statistically significant (P < 0.05). No significant difference was observed between GTV-PET and GTV-path (P > 0.05). Spearman correlation analysis showed that GTV-CT, GTV-MRI, and GTV-PET were significantly correlated with GTV-path (P < 0.01). There was no significant difference in the lesion coverage factor among the three modalities.
The present study showed that GTV defined under 40% of maximum standardized uptake value in PET images was very similar to the pathological volume of cervical cancer. This result should be replicated in a larger number of patients with cervical cancer in a future study of ours.
MRI; 18F-FDG PET/CT; pathological tumor volume; gross tumor volume; cervical cancer
In this study, four dimensional computed tomography (4DCT) scanning was performed during free breathing on a 16-slice Positron emission tomography PET /computed tomography (CT) for abdomen and thoracic patients. Images were sorted into 10 phases based on the temporal correlation between surface motion and data acquisition with an Advantage Workstation. Gross tumor volume gross tumor volume (GTV) s were manually contoured on all 10 phases of the 4DCT scan. GTVs in the multiple CT phases were called GTV4D. GTV4D plus an isotropic margin of 1.0 cm was called CTV4D. Two sets of planning target volume (PTV) 4D (PTV4D) were derived from the CTV4D, i.e. PTV4D2cm = CTV4D plus 1 cm setup margin (SM) and 1 cm internal margin (IM) and PTV4D1.5cm = CTV4D plus 1 cm SM and 0.5cm IM. PTV3D was derived from a CTV3D of the helical CT scan plus conventional margins of 2 cm. PTVgated was generated only selecting three CT phases, with a total margin of 1.5 cm. All four volumes were compared. To quantify the extent of the motion, we selected the two phases where the tumor exhibited the greatest range of motion. We also studied the effect of different PTV volumes on dose to the surrounding critical structures. Volume of CTV4D was greater than that of CTV3D. We found, on an average, a reduction of 14% volume of PTV4D1.5cm as compared with PTV3D and reduction of 10% volume of PTVgated as compared with PTV4D1.5cm. We found that 2 cm of margin was inadequate if true motion of tumor was not known. We observed greater sparing of critical structures for PTVs drawn taking into account the tumor motion.
four dimensional computed tomography; tumor motion and PTV margin reduction for thoracic and abdomen tumor
We analyzed the data for 53 patients with histologically proven primary squamous cell carcinoma of the head and neck treated with radiotherapy between February 2006 and August 2009. All patients underwent contrast-enhanced (CE)-CT and 18F-fluorodeoxyglucose (FDG)-PET before radiation therapy planning (RTP) to define the gross tumor volume (GTV). The PET-based GTV (PET-GTV) for RTP was defined using both CE-CT images and FDG-PET images. The CE-CT tumor volume corresponding to a FDG-PET image was regarded as the PET-GTV. The CE-CT-based GTV (CT-GTV) for RTP was defined using CE-CT images alone. Additionally, CT-GTV delineation and PET-GTV delineation were performed by four radiation oncologists independently in 19 cases. All four oncologists did both methods. Of these, PET-GTV delineation was successfully performed in all 19 cases, but CT-GTV delineation was not performed in 4 cases. In the other 15 cases, the mean CT-GTV was larger than the PET-GTV in 10 cases, and the standard deviation of the CT-GTV was larger than that of the PET-GTV in 10 cases. Sensitivity of PET-GTV for identifying the primary tumor was 96%, but that of CT-GTV was 81% (P < 0.01). In patients with oropharyngeal cancer and tongue cancer, the sensitivity of CT-GTV was 63% and 71%, respectively. When both the primary lesions and the lymph nodes were evaluated for RTP, PET-GTV differed from CT-GTV in 19 cases (36%). These results suggested that FDG-PET is effective for defining GTV in RTP for squamous cell carcinoma of the head and neck, and PET-GTV evaluated by both CE-CT and FDG-PET images is preferable to CT-GTV by CE-CT alone.
FDG-PET; gross tumor volume; target delineation; head and neck cancer
To report serial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) tumor response following CyberKnife radiosurgery for stage IA non-small cell lung cancer (NSCLC).
Patients with biopsy-proven inoperable stage IA NSCLC were enrolled into this IRB-approved study. Targeting was based on 3-5 gold fiducial markers implanted in or near tumors. Gross tumor volumes (GTVs) were contoured using lung windows; margins were expanded by 5 mm to establish the planning treatment volumes (PTVs). Doses ranged from 42-60 Gy in 3 equal fractions. 18F-FDG PET/CT was performed prior to and at 3-6-month, 9-15 months and 18-24 months following treatment. The tumor maximum standardized uptake value (SUVmax) was recorded for each time point.
Twenty patients with an average maximum tumor diameter of 2.2 cm were treated over a 3-year period. A mean dose of 51 Gy was delivered to the PTV in 3 to 11 days (mean, 7 days). The 30-Gy isodose contour extended an average of 2 cm from the GTV. At a median follow-up of 43 months, the 2-year Kaplan-Meier overall survival estimate was 90% and the local control estimate was 95%. Mean tumor SUVmax before treatment was 6.2 (range, 2.0 to 10.7). During early follow-up the mean tumor SUVmax remained at 2.3 (range, 1.0 to 5.7), despite transient elevations in individual tumor SUVmax levels attributed to peritumoral radiation-induced pneumonitis visible on CT imaging. At 18-24 months the mean tumor SUVmax for controlled tumors was 2.0, with
a narrow range of values (range, 1.5 to 2.8). A single local failure was confirmed at 24 months in a patient with an elevated tumor SUVmax of 8.4.
Local control and survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional. Early transient increases in tumor SUVmax are likely related to radiation-induced pneumonitis. Tumor SUVmaxvalues return to background levels at 18-24 months, enhancing 18F-FDG PET/CT detection of local failure. The value of 18F-FDG PET/CT imaging for surveillance following lung SBRT deserves further study.
To evaluate the impact of 18F-FDG PET/CT on target volume delineation in gynaecological cancer.
F-FDG PET/CT based RT treatment planning was performed in 10 patients with locally recurrent (n = 5) or post-surgical residual gynaecological cancer (n = 5). The gross tumor volume (GTV) was defined by 4 experienced radiation oncologists first using contrast enhanced CT (GTVCT) and secondly using the fused 18F-FDG PET/CT datasets (GTVPET/CT). In addition, the GTV was delineated using the signal-to-background (SBR) ratio-based adaptive thresholding technique (GTVSBR). Overlap analysis were conducted to assess geographic mismatches between the GTVs delineated using the different techniques. Inter- and intra-observer variability were also assessed.
The mean GTVCT (43.65 cm3) was larger than the mean GTVPET/CT (33.06 cm3), p = 0.02. In 6 patients, GTVPET/CT added substantial tumor extension outside the GTVCT even though 90.4% of the GTVPET/CT was included in the GTVCT and 30.2% of the GTVCT was found outside the GTVPET/CT. The inter- and intra-observer variability was not significantly reduced with the inclusion of 18F-FDG PET imaging (p = 0.23 and p = 0.18, respectively). The GTVSBR was smaller than GTVCT p ≤ 0.005 and GTVPET/CT p ≤ 0.005.
The use of 18F-FDG PET/CT images for target volume delineation of recurrent or post-surgical residual gynaecological cancer alters the GTV in the majority of patients compared to standard CT-definition. The use of SBR-based auto-delineation showed significantly smaller GTVs. The use of PET/CT based target volume delineation may improve the accuracy of RT treatment planning in gynaecologic cancer.
Gynaecologic cancer; PET/CT; Radiotherapy; Target volume delineation; Observer variability
To define a suitable threshold setting for gross tumor volume (GTV) when using 18Fluoro-deoxyglucose positron emission tomography and computed tomogram (PET/CT) for radiotherapy planning in head and neck cancer (HNC).
Fifteen HNC patients prospectively received PET/CT simulation for their radiation treatment planning. Biological target volume (BTV) was derived from PET/CT-based GTV of the primary tumor. The BTVs were defined as the isodensity volumes when adjusting different percentage of the maximal standardized uptake value (SUVmax), excluding any artifact from surrounding normal tissues. CT-based primary GTV (C-pGTV) that had been previously defined by radiation oncologists was compared with the BTV. Suitable threshold level (sTL) could be determined when BTV value and its morphology using a certain threshold level was observed to be the best fitness of the C-pGTV. Suitable standardized uptake value (sSUV) was calculated as the sTL multiplied by the SUVmax.
Our result demonstrated no single sTL or sSUV method could achieve an optimized volumetric match with the C-pGTV. The sTL was 13% to 27% (mean, 19%), whereas the sSUV was 1.64 to 3.98 (mean, 2.46). The sTL was inversely correlated with the SUVmax [sTL = -0.1004 Ln (SUVmax) + 0.4464; R2 = 0.81]. The sSUV showed a linear correlation with the SUVmax (sSUV = 0.0842 SUVmax + 1.248; R2 = 0.89). The sTL was not associated with the value of C-pGTVs.
In PET/CT-based BTV for HNC, a suitable threshold or SUV level can be established by correlating with SUVmax rather than using a fixed threshold.
Published data suggests that wedge resection for stage I non-small cell lung cancer (NSCLC) is associated with improved overall survival compared to stereotactic body radiation therapy. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs) were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV). Treatment plans were designed using a mean of 156 pencil beams. Doses delivered to the PTV ranged from 42 to 60 Gy in three fractions. The 30 Gy isodose contour extended at least 1 cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3 month follow-up intervals. Forty patients (median age 76) with a median maximum tumor diameter of 2.6 cm (range, 1.4–5.0 cm) and a mean post-bronchodilator percent predicted forced expiratory volume in 1 s (FEV1) of 57% (range, 21–111%) were treated. A median dose of 48 Gy was delivered to the PTV over 3–13 days (median, 7 days). The 30 Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12–72 months) follow-up, the 3 year Kaplan–Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91 and 75%, respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1–2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.
non-small cell lung cancer; CyberKnife; stereotactic body radiation therapy; wedge resection
To compare morphological gross tumor volumes (GTVs), defined as pre- and postoperative gadolinium enhancement on T1-weighted magnetic resonance imaging to biological tumor volumes (BTVs), defined by the uptake of 18F fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET)-CT scanner equipped with three triangulation lasers for patient positioning.
Nineteen patients with malignant glioma were included into a prospective protocol using FET PET-CT for radiotherapy planning. To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV ∪ BTV) and planning target volume (PTV = CTV + 20 mm). First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed.
Interrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9). Although, BTVs and GTVs were not significantly different (p = 0.9), CTVs (mean 57.8 ± 30.4 cm3) were significantly larger than BTVs (mean 42.1 ± 24.4 cm3; p < 0.01) or GTVs (mean 38.7 ± 25.7 cm3; p < 0.01). In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended ≥ 10 and 20 mm from the margin of the gadolinium enhancement.
Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients.
Respiration-gated radiotherapy can permit the irradiation of smaller target volumes. 4DCT scans performed for routine treatment were retrospectively analyzed to establish the benefits of gating in stage III non-small cell lung cancer (NSCLC).
Materials and methods
Gross tumor volumes (GTVs) were contoured in all 10 respiratory phases of a 4DCT scan in 15 patients with stage III NSCLC. Treatment planning was performed using different planning target volumes (PTVs), namely: (i) PTVroutine, derived from a single GTV plus 'conventional' margins; (ii) PTVall phases incorporating all 3D mobility captured by the 4DCT; (iii) PTVgating, incorporating residual 3D mobility in 3–4 phases at end-expiration. Mixed effect models were constructed in order to estimate the reductions in risk of lung toxicity for the different PTVs.
Individual GTVs ranged from 41.5 – 235.0 cm3. With patient-specific mobility data (PTVall phases), smaller PTVs were derived than when 'standard' conventional margins were used (p < 0.001). The average residual 3D tumor mobility within the gating window was 4.0 ± 3.5 mm, which was 5.5 mm less than non-gated tumor mobility (p < 0.001). The reductions in mean lung dose were 9.7% and 4.9%, respectively, for PTVall phases versus PTVroutine, and PTVgating versus PTVall phases. The corresponding reductions in V20 were 9.8% and 7.0%, respectively. Dosimetric gains were smaller for primary tumors of the upper lobe versus other locations (p = 0.02). Respiratory gating also reduced the risks of radiation-induced esophagitis.
Respiration-gated radiotherapy can reduce the risk of pulmonary toxicity but the benefits are particularly evident for tumors of the middle and lower lobes.
We applied a learning methodology framework to assist in the threshold-based segmentation of non-small-cell lung cancer (nsclc) tumours in positron-emission tomography–computed tomography (pet–ct) imaging for use in radiotherapy planning. Gated and standard free-breathing studies of two patients were independently analysed (four studies in total). Each study had a pet–ct and a treatment-planning ct image. The reference gross tumour volume (gtv) was identified by two experienced radiation oncologists who also determined reference standardized uptake value (suv) thresholds that most closely approximated the gtv contour on each slice. A set of uptake distribution-related attributes was calculated for each pet slice. A machine learning algorithm was trained on a subset of the pet slices to cope with slice-to-slice variation in the optimal suv threshold: that is, to predict the most appropriate suv threshold from the calculated attributes for each slice. The algorithm’s performance was evaluated using the remainder of the pet slices. A high degree of geometric similarity was achieved between the areas outlined by the predicted and the reference suv thresholds (Jaccard index exceeding 0.82). No significant difference was found between the gated and the free-breathing results in the same patient. In this preliminary work, we demonstrated the potential applicability of a machine learning methodology as an auxiliary tool for radiation treatment planning in nsclc.
Positron-emission tomography; pet; radiation treatment; lung cancer; gross tumour volume; gtv; artificial intelligence; machine learning; support vector machine; svm
To evaluate the interobserver variability of gross tumor volume (GTV) - delineation of Dominant Intraprostatic Lesions (DIPL) in patients with prostate cancer using published MRI criteria for multiparametric MRI at 3 Tesla by 6 different observers.
Material and methods
90 GTV-datasets based on 15 multiparametric MRI sequences (T2w, diffusion weighted (DWI) and dynamic contrast enhanced (DCE)) of 5 patients with prostate cancer were generated for GTV-delineation of DIPL by 6 observers. The reference GTV-dataset was contoured by a radiologist with expertise in diagnostic imaging of prostate cancer using MRI. Subsequent GTV-delineation was performed by 5 radiation oncologists who received teaching of MRI-features of primary prostate cancer before starting contouring session. GTV-datasets were contoured using Oncentra Masterplan® and iplan® Net. For purposes of comparison GTV-datasets were imported to the Artiview® platform (Aquilab®), GTV-values and the similarity indices or Kappa indices (KI) were calculated with the postulation that a KI > 0.7 indicates excellent, a KI > 0.6 to < 0.7 substantial and KI > 0.5 to < 0.6 moderate agreement. Additionally all observers rated difficulties of contouring for each MRI-sequence using a 3 point rating scale (1 = easy to delineate, 2 = minor difficulties, 3 = major difficulties).
GTV contouring using T2w (KI-T2w = 0.61) and DCE images (KI-DCE = 0.63) resulted in substantial agreement. GTV contouring using DWI images resulted in moderate agreement (KI-DWI = 0.51). KI-T2w and KI-DCE was significantly higher than KI-DWI (p = 0.01 and p = 0.003). Degree of difficulty in contouring GTV was significantly lower using T2w and DCE compared to DWI-sequences (both p < 0.0001). Analysis of delineation differences revealed inadequate comparison of functional (DWI, DCE) to anatomical sequences (T2w) and lack of awareness of non-specific imaging findings as a source of erroneous delineation.
Using T2w and DCE sequences at 3 Tesla for GTV-definition of DIPL in prostate cancer patients by radiation oncologists with knowledge of MRI features results in substantial agreement compared to an experienced MRI-radiologist, but for radiotherapy purposes higher KI are desirable, strengthen the need for expert surveillance. DWI sequence for GTV delineation was considered as difficult in application.
Prostate cancer; Gross tumor volume; Focal dose escalation; Simultaneous integrated boost; 3 Tesla MRI; Interobserver variability
To assess the pattern of local failure using 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans after radiotherapy (RT) in non–small-cell lung cancer (NSCLC) patients treated with definitive RT whose gross tumor volumes (GTVs) were defined with the aid of pre-RT PET data.
Method and Materials
The data from 26 patients treated with involved-field RT who had local failure and a post-RT PET scan were analyzed. The patterns of failure were visually scored and defined as follows: (1) within the GTV/planning target volume (PTV); (2) within the GTV, PTV, and outward; (3) within the PTV and outward; and (4) outside the PTV. Local failure was also evaluated as originating from nodal areas vs. the primary tumor.
We analyzed 34 lesions. All 26 patients had recurrence originating from their primary tumor. Of the 34 lesions, 8 (24%) were in nodal areas, 5 of which (63%) were marginal or geographic misses compared with only 1 (4%) of the 26 primary recurrences (p = 0.001). Of the eight primary tumors that had received a dose of <60 Gy, six (75%) had failure within the GTVand two (25%) at the GTV margin. At doses of ≥60 Gy, 6 (33%) of 18 had failure within the GTV and 11 (61%) at the GTV margin, and 1 (6%) was a marginal miss (p < 0.05).
At lower doses, the pattern of recurrences was mostly within the GTV, suggesting that the dose might have been a factor for tumor control. At greater doses, the treatment failures were mostly at the margin of the GTV. This suggests that visual incorporation of PET data for GTV delineation might be inadequate, and more sophisticated approaches of PET registration should be evaluated.
Non–small-cell lung cancer; FDG-PET scan; Local failure; Definitive radiotherapy
To compare computed tomography (CT) with co-registered positron emission tomography-computed tomography (PET-CT) as the basis for delineating gross tumor volume (GTV) in unresectable, locally advanced pancreatic carcinoma (LAPC).
Fourteen patients with unresectable LAPC had both CT and PET images acquired. For each patient, two three-dimensional conformal plans were made using the CT and PET-CT fusion data sets. We analyzed differences in treatment plans and doses of radiation to primary tumors and critical organs.
Changes in GTV delineation were necessary in 5 patients based on PET-CT information. In these patients, the average increase in GTV was 29.7%, due to the incorporation of additional lymph node metastases and extension of the primary tumor beyond that defined by CT. For all patients, the GTVCT versus GTVPET-CT was 92.5 ± 32.3 cm3 versus 104.5 ± 32.6 cm3 (p = 0.009). Toxicity analysis revealed no clinically significant differences between two plans with regard to doses to critical organs.
Co-registration of PET and CT information in unresectable LAPC may improve the delineation of GTV and theoretically reduce the likelihood of geographic misses.
Curative surgery is not an option for many patients with clinical stage I non-small-cell lung carcinoma (NSCLC), but radical radiosurgery may be effective.
Inoperable patients with small peripheral clinical stage I NSCLC were enrolled in this study. Three-to-five fiducial markers were implanted in or near tumors under CT guidance. Gross tumor volumes (GTVs) were contoured using lung windows. The GTV margin was expanded by 5 mm to establish the planning treatment volume (PTV). A dose of 42–60 Gy was delivered to the PTV in 3 equal fractions in less than 2 weeks using the CyberKnife radiosurgery system. The 30-Gy isodose contour extended at least 1 cm from the GTV. Physical examination, CT imaging and pulmonary function testing were completed at 6 months intervals for three years following treatment.
Twenty patients with an average maximum tumor diameter of 2.2 cm (range, 1.1 – 3.5 cm) and a mean FEV1 of 1.08 liters (range, 0.53 – 1.71 L) were treated. Pneumothorax requiring tube thoracostomy occurred following CT-guided fiducial placement in 25% of the patients. All patients completed treatment with few acute side effects and no procedure-related mortality. Transient chest wall discomfort developed in 8 of the 12 patients with lesions within 5 mm of the pleura. The mean percentage of the total lung volume receiving a minimum of 15 Gy was 7.3% (range, 2.4% to 11.3%). One patient who received concurrent gefitinib developed short-lived, grade III radiation pneumonitis. The mean percent predicted DLCO decreased by 9% and 11% at 6 and 12 months, respectively. There were no local failures, regional lymph node recurrences or distant metastases. With a median follow-up of 25 months for the surviving patients, Kaplan-Meier overall survival estimate at 2 years was 87%, with deaths due to COPD progression.
Radical CyberKnife radiosurgery is a well-tolerated treatment option for inoperable patients with small, peripheral stage I NSCLC. Effective doses and adequate margins are likely to have contributed to the optimal early local control seen in this study.
We investigated the dosimetric differences among volumetric-modulated arc radiotherapy (RapidArc, RA) plans designed for various target volumes in hepatocellular carcinoma (HCC). Ten HCC patients underwent 3D-CT scanning at free breathing (FB), 3D-CT at end inspiration hold (EIH) assisted by an Active Breathing Coordinator (ABC), and 4D-CT scanning. Gross tumor volumes (GTVs) were manually contoured on CT images. The individualized internal gross target volume (IGTV1) was obtained from 10 GTVs from 4D-CT images. Tumor individual margins were measured from GTVFB to IGTV1. The IGTV2 was obtained from GTVFB by applying individual margins. Four planning target volumes (PTV1-4) were obtained from IGTV1, IGTV2, GTVFB, and GTVEIH, respectively. An RA plan was designed for each of the PTVs (RA1–4). One 358° arc was used for PTVs1–3, while three 135° arcs were used for PTV4. It was found that PTV2 and PTV3 were larger than PTV1 and PTV4. The mean values of PTV3/PTV1 and PTV3/PTV4 were 2.5 and 1.9, respectively. The individual margins in the X, Y and Z axial directions varied greatly among these patients. There were no significant differences in the conformal index or homogeneity index among the four RA plans. RA1 and RA4 significantly reduced the radiation dose of normal liver tissue compared with RA2 and RA3 (P < 0.01). There were no significant differences between the radiation doses of the stomach and duodenum. RapidArc combined with 4D-CT or ABC technology is a promising method in radiotherapy of HCC, and accurately targeted the tumor volume while sparing more normal liver tissue.
hepatocellular carcinoma; radiotherapy; intensity-modulated arc radiotherapy; dosimetry
This study compared manually delineated gross tumour volume (GTV) and automatically generated biological tumour volume (BTV) based on fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT to assess the robustness of predefined PET algorithms for radiotherapy (RT) planning in routine clinical practice.
RT-planning data from 20 consecutive patients (lung- (40%), oesophageal- (25%), gynaecological- (25%) and colorectal (10%) cancer) who had undergone FDG-PET/CT planning between 08/2010 and 09/2011 were retrospectively analysed, five of them underwent neoadjuvant chemotherapy before radiotherapy. In addition to manual GTV contouring, automated segmentation algorithms were applied–among these 38%, 42%, 47% and 50% SUVmax as well as the PERCIST total lesion glycolysis (TLG) algorithm. Different ratios were calculated to assess the overlap of GTV and BTV including the conformity index and the ratio GTV included within the BTV.
Median age of the patients was 66 years and median tumour SUVmax 9.2. Median size of the GTVs defined by the radiation oncologist was 43.7 ml. Median conformity indices were between 30.0–37.8%. The highest amount of BTV within GTV was seen with the 38% SUVmax algorithm (49.0%), the lowest with 50% SUVmax (36.0%). Best agreement was obtained for oesophageal cancer patients with a conformity index of 56.4% and BTV within GTV ratio of 71.1%.
At present there is only low concordance between manually derived GTVs and automatically segmented FDG-PET/CT based BTVs indicating the need for further research in order to achieve higher volumetric conformity and therefore to get access to the full potential of FDG-PET/CT for optimization of radiotherapy planning.
PET/CT; Planning study; BTV; Target delineation
A study was performed comparing volumetric modulated arcs (RA) and intensity modulation (with photons, IMRT, or protons, IMPT) radiation therapy (RT) for patients with recurrent prostate cancer after RT.
Plans for RA, IMRT and IMPT were optimized for 7 patients. Prescribed dose was 56 Gy in 14 fractions. The recurrent gross tumor volume (GTV) was defined on 18F-fluorocholine PET/CT scans. Plans aimed to cover at least 95% of the planning target volume with a dose > 50.4 Gy. A maximum dose (DMax) of 61.6 Gy was allowed to 5% of the GTV. For the urethra, DMax was constrained to 37 Gy. Rectal DMedian was < 17 Gy. Results were analyzed using Dose-Volume Histogram and conformity index (CI90) parameters.
Tumor coverage (GTV and PTV) was improved with RA (V95% 92.6 ± 7.9 and 83.7 ± 3.3%), when compared to IMRT (V95% 88.6 ± 10.8 and 77.2 ± 2.2%). The corresponding values for IMPT were intermediate for the GTV (V95% 88.9 ± 10.5%) and better for the PTV (V95%85.6 ± 5.0%). The percentages of rectal and urethral volumes receiving intermediate doses (35 Gy) were significantly decreased with RA (5.1 ± 3.0 and 38.0 ± 25.3%) and IMPT (3.9 ± 2.7 and 25.1 ± 21.1%), when compared to IMRT (9.8 ± 5.3 and 60.7 ± 41.7%). CI90 was 1.3 ± 0.1 for photons and 1.6 ± 0.2 for protons. Integral Dose was 1.1 ± 0.5 Gy*cm3 *105 for IMPT and about a factor three higher for all photon's techniques.
RA and IMPT showed improvements in conformal avoidance relative to fixed beam IMRT for 7 patients with recurrent prostate cancer. IMPT showed further sparing of organs at risk.
A combination of four-dimensional computed tomography with 18F-fluorodeoxyglucose positron emission tomography (4D CT-FDG PET) was used to delineate gross tumor volume (GTV) in esophageal cancer (EC). Eighteen patients with EC were prospectively enrolled. Using 4D images taken during the respiratory cycle, the average CT image phase was fused with the average FDG PET phase in order to analyze the optimal standardized uptake values (SUV) or threshold. PET-based GTV (GTVPET) was determined with eight different threshold methods using the auto-contouring function on the PET workstation. The difference in volume ratio (VR) and conformality index (CI) between GTVPET and CT-based GTV (GTVCT) was investigated. The image sets via automatic co-registrations of 4D CT-FDG PET were available for 12 patients with 13 GTVCT values. The decision coefficient (R2) of tumor length difference at the threshold levels of SUV 2.5, SUV 20% and SUV 25% were 0.79, 0.65 and 0.54, respectively. The mean volume of GTVCT was 29.41 ± 19.14 ml. The mean VR ranged from 0.30 to 1.48. The optimal VR of 0.98, close to 1, was at SUV 20% or SUV 2.5. The mean CI ranged from 0.28 to 0.58. The best CI was at SUV 20% (0.58) or SUV 2.5 (0.57). The auto-contouring function of the SUV threshold has the potential to assist in contouring the GTV. The SUV threshold setting of SUV 20% or SUV 2.5 achieves the optimal correlation of tumor length, VR, and CI using 4D-PET/CT images.
FDG PET/CT; gross tumor volume; radiotherapy; esophageal cancer
To determine the optimal approach to delineating patient-specific internal gross target volumes (IGTV) from four-dimensional (4-D) computed tomography (CT) image data sets used in the planning of radiation treatment for lung cancers.
We analyzed 4D-CT image data sets of 27 consecutive patients with non-small-cell lung cancer (stage I: 17, stage III: 10). The IGTV, defined to be the envelope of respiratory motion of the gross tumor volume in each 4D-CT data set was delineated manually using four techniques: (1) combining the gross tumor volume (GTV) contours from ten respiratory phases (IGTVAllPhases); (2) combining the GTV contours from two extreme respiratory phases (0% and 50%) (IGTV2Phases); (3) defining the GTV contour using the maximum intensity projection (MIP) (IGTVMIP); and (4) defining the GTV contour using the MIP with modification based on visual verification of contours in individual respiratory phase (IGTVMIP-Modified). Using the IGTVAllPhases as the optimum IGTV, we compared volumes, matching indices, and extent of target missing using the IGTVs based on the other three approaches.
The IGTVMIP and IGTV2Phases were significantly smaller than the IGTVAllPhases (p < 0.006 for stage I and p < 0.002 for stage III). However, the values of the IGTVMIP-Modified were close to those determined from IGTVAllPhases (p = 0.08). IGTVMIP-Modified also matched the best with IGTVAllPhases.
IGTVMIP and IGTV2Phases underestimate IGTVs. IGTVMIP-Modified is recommended to improve IGTV delineation in lung cancer.
Local failure after definitive chemoradiation therapy for unresectable esophageal cancer remains problematic. Little is known about the failure pattern based on modern day radiation treatment volumes. We hypothesized that most local failures would be within the gross tumor volume (GTV), where the bulk of the tumor burden resides.
Methods and Materials
We reviewed treatment volumes for 239 patients who underwent definitive chemoradiation therapy and compared this information with failure patterns on follow-up positron emission (PET). Failures were categorized as within the GTV, the larger clinical target volume (CTV, which encompasses microscopic disease), or the still larger planning target volume (PTV, which encompasses setup variability) or outside the radiation field.
At a median follow-up time of 52.6 months (95% CI: 46.1 – 56.7 months), 119 patients (50%) had experienced local failure, 114 (48%) had distant failure, and 74 (31%) had no evidence of failure. Of all local failures, 107 (90%) were in the GTV, 27 (23%) in the CTV; and 14 (12%) in the PTV. In multivariate analysis, GTV failure was associated with tumor status (T3/T4 vs. T1/T2: OR=6.35, p value =0.002), change in standardized uptake value on PET before and after treatment (decrease >52%: OR=0.368, p value = 0.003) and tumor length (>8 cm: 4.08, p value = 0.009).
Most local failures after definitive chemoradiation for unresectable esophageal cancer occur in the GTV. Future therapeutic strategies should focus on enhancing local control.
Esophageal cancer; dose escalation; failure patterns
The purpose of this study was to validate the dose prescription defined to the gross tumor volume (GTV) 3D and 4D dose distributions of stereotactic radiotherapy for lung cancer. Treatment plans for 94 patients were generated based on computed tomography (CT) under free breathing. A uniform margin of 8 mm was added to the internal target volume (ITV) to generate the planning target volume (PTV). A leaf margin of 2 mm was added to the PTV. The prescription dose was defined such that 99% of the GTV should receive 100% of the dose using the Monte Carlo calculation (iPlan RT DoseTM) for 6-MV photon beams. The 3D dose distribution was determined using CT under free breathing. The 4D dose distribution plan was recalculated to investigate the effect of tumor motion using the same monitor units as those used for the 3D dose distribution plan. D99 (99% of the GTV) in the 4D plan was defined as the average D99 in each of the four breathing phases (0%, 25%, 50% and 75%). The dose difference between maximum and minimum at D99 of the GTV in 4D calculations was 0.6 ± 1.0% (range 0.2–4.6%). The average D99 of the GTV from 4D calculations in most patients was almost 100% (99.8 ± 1.0%). No significant difference was found in dose to the GTV between 3D and 4D dose calculations (P = 0.67). This study supports the clinical acceptability of treatment planning based on the dose prescription defined to the GTV.
four-dimensional computed tomography; gross tumor volume; Monte Carlo calculation; stereotactic body radiotherapy; lung cancer
To report acute toxicity, initial outcome results and planning therapeutic parameters in radiation treatment of advanced lung cancer (stage III) with volumetric modulated arcs using RapidArc (RA).
Twenty-four consecutive patients were treated with RA. All showed locally advanced non-small cell lung cancer with stage IIIA-IIIB and with large volumes (GTV:299 ± 175 cm3, PTV:818 ± 206 cm3). Dose prescription was 66Gy in 33 fractions to mean PTV. Delivery was performed with two partial arcs with a 6 MV photon beam.
From a dosimetric point of view, RA allowed us to respect most planning objectives on target volumes and organs at risk. In particular: for GTV D1% = 105.6 ± 1.7%, D99% = 96.7 ± 1.8%, D5%-D95% = 6.3 ± 1.4%; contra-lateral lung mean dose resulted in 13.7 ± 3.9Gy, for spinal cord D1% = 39.5 ± 4.0Gy, for heart V45Gy = 9.0 ± 7.0Gy, for esophagus D1% = 67.4 ± 2.2Gy. Delivery time was 133 ± 7s. At three months partial remission > 50% was observed in 56% of patients. Acute toxicities at 3 months showed 91% with grade 1 and 9% with grade 2 esophageal toxicity; 18% presented grade 1 and 9% with grade 2 pneumonia; no grade 3 acute toxicity was observed. The short follow-up does not allow assessment of local control and progression free survival.
RA proved to be a safe and advantageous treatment modality for NSCLC with large volumes. Long term observation of patients is needed to assess outcome and late toxicity.
RTOG 0515 is a Phase II prospective trial designed to quantify the impact of PET/CT compared to CT alone on radiation treatment plans (RTPs) and to determine the rate of elective nodal failure for PET/CT derived volumes.
Each enrolled patient underwent definitive radiation therapy for NSCLC (≥60 Gy) and had two RTP datasets generated: gross tumor volume (GTV) derived with CT alone and with PET/CT. Patients received treatment using the PET/CT-derived plan. The primary endpoint, the impact of PET/CT fusion on treatment plans was measured by differences of the following variables for each patient: GTV, number of involved nodes, nodal station, mean lung dose (MLD), volume of lung exceeding 20 Gy (V20), and mean esophageal dose (MED). Regional failure rate was a secondary endpoint. The nonparametric Wilcoxon matched-pairs signed-ranks test was used with Bonferroni adjustment for an overall significance level of 0.05.
RTOG 0515 accrued 52 patients, 47 of whom are evaluable. The follow-up time for all patients is 12.9 months (2.7–22.2). Tumor staging was as follows: II = 6%; IIIA = 40%; and IIIB = 54%. The GTV was statistically significantly smaller for PET/CT-derived volumes (98.7 vs. 86.2 cc; p<0.0001). MLDs for PET/CT plans were slightly lower (19 vs. 17.8 Gy; p=0.06). There was no significant difference in the number of involved nodes (2.1 vs. 2.4), V20 (32% vs. 30.8%), or MED (28.7 vs. 27.1 Gy). Nodal contours were altered by PET/CT for 51% of patients. One patient (2%) has developed an elective nodal failure.
PET/CT-derived tumor volumes were smaller than those derived by CT alone. PET/CT changed nodal GTV contours in 51% of patients. The elective nodal failure rate for GTVs derived by PET/CT is quite low, supporting the RTOG standard of limiting the target volume to the primary tumor and involved nodes.
Lung Cancer; FDG-PET; Mediastinal nodal staging; mediastinum