Standard Target Volume Research Articles

Evaluating AI-generated CBCT-based synthetic CT images for target delineation in palliative treatments of pelvic bone metastasis at conventional C-arm linacs

PurposeOne-table treatments with treatment imaging, preparation and delivery occurring at one treatment couch, could increase patients’ comfort and throughput for palliative treatments. On regular C-arm linacs, however, cone-beam CT (CBCT) imaging quality is currently insufficient. Therefore, our goal was to assess the suitability of AI-generated CBCT based synthetic CT (sCT) images for target delineation and treatment planning for palliative radiotherapy. Materials and methodsCBCTs and planning CT-scans of 22 female patients with pelvic bone metastasis were included. For each CBCT, a corresponding sCT image was generated by a deep learning model in ADMIRE 3.38.0. Radiation oncologists delineated 23 target volumes (TV) on the sCTs (TVsCT) and scored their delineation confidence. The delineations were transferred to planning CTs and manually adjusted if needed to yield gold standard target volumes (TVclin). TVsCT were geometrically compared to TVclin using Dice coefficient (DC) and Hausdorff Distance (HD). The dosimetric impact of TVsCT inaccuracies was evaluated for VMAT plans with different PTV margins. ResultsRadiation oncologists scored the sCT quality as sufficient for 13/23 TVsCT (median: DC = 0.9, HD = 11 mm) and insufficient for 10/23 TVsCT (median: DC = 0.7, HD = 34 mm). For the sufficient category, remaining inaccuracies could be compensated by +1 to +4 mm additional margin to achieve coverage of V95% > 95% and V95% > 98%, respectively in 12/13 TVsCT. ConclusionThe evaluated sCT quality allowed for accurate delineation for most targets. sCTs with insufficient quality could be identified accurately upfront. A moderate PTV margin expansion could address remaining delineation inaccuracies. Therefore, these findings support further exploration of CBCT based one-table treatments on C-arm linacs.

Emerging evidence for adapting radiotherapy to immunotherapy.

Immunotherapy has revolutionized the clinical management of many malignancies but is infrequently associated with durable objective responses when used as a standalone treatment approach, calling for the development of combinatorial regimens with superior efficacy and acceptable toxicity. Radiotherapy, the most commonly used oncological treatment, has attracted considerable attention as a combination partner for immunotherapy owing to its well-known and predictable safety profile, widespread clinical availability, and potential for immunostimulatory effects. However, numerous randomized clinical trials investigating radiotherapy-immunotherapy combinations have failed to demonstrate a therapeutic benefit compared with either modality alone. Such a lack of interaction might reflect suboptimal study design, choice of end points and/or administration of radiotherapy according to standard schedules and target volumes. Indeed, radiotherapy has empirically evolved towards radiation doses and fields that enable maximal cancer cell killing with manageable toxicity to healthy tissues, without much consideration of potential radiation-induced immunostimulatory effects. Herein, we propose the concept that successful radiotherapy-immunotherapy combinations might require modifications of standard radiotherapy regimens and target volumes to optimally sustain immune fitness and enhance the antitumour immune response in support of meaningful clinical benefits.

Evaluation of apical clips placed during axillary dissection demonstrates potential under‐coverage of axillary radiation therapy target volumes during breast cancer regional nodal irradiation

Evidence-based Australian guidelines (eviQ) recommend adjuvant supraclavicular fossa irradiation after axillary lymph node dissection (ALND) in node-positive breast cancer patients. Disparity between surgically determined versus computed tomography (CT) determined nodal volumes may result in discontiguous nodal volumes and untreated nodal tissue. We examine the extent of untreated nodal tissue in women with breast cancer post-level II or III ALND and adjuvant radiation therapy (RT) using ESTRO contouring guidelines. Female breast cancer patients who underwent level II and III ALND with apical clip placement from 2016 to 2020 and CT simulated in supine position were included. CT-defined axillary level II-IV volumes were contoured using ESTRO guidelines. The distance between the apical clip and RT nodal volumes was measured to indicate extent of untreated tissue. Of 34 eligible patients treated by 7 surgeons, 76% had level II ALND and 24% level III ALND. Only 5.9% of clips entirely encompassed the corresponding RT nodal volumes. 55.9% of clips fell within and 44.1% fell inferolaterally outside the corresponding RT nodal volumes. A median 3.6 cm (range 0-7.5 cm) of undissected nodal tissue would not be included within standard RT target volumes following eviQ recommendations. There is a disparity between surgically determined versus CT determined axillary nodal volumes, leading to discontiguous nodal volumes and untreated axillary nodal tissue, despite following standard radiation contouring guidelines. Intraoperatively placed apical axillary clips may assist radiation oncologists to accurately delineate undissected nodal tissues at risk.

NIMG-49. A PROSPECTIVE, MULTI-CENTRE TRIAL OF FET-PET IN GLIOBLASTOMA PATIENTS - THE TROG 18.06 FIG STUDY: KEY ASPECTS OF IMAGING AND RADIATION ONCOLOGY CREDENTIALING

Abstract The FIG study is a prospective non-randomised study now recruiting up to 210 newly diagnosed GBM participants across ten Australian sites. Study outcomes will address the role of [18F] fluoroethyl-L-tyrosine positron emission tomography (FET-PET) in radiotherapy (RT) planning, evaluation of post-treatment changes versus disease progression and prognostication. We describe here the methodology and preliminary outcomes for site credentialing. Eligible participants with GBM undergo FET-PET imaging at three time-points: FET-PET1-post-operative pre-chemo-RT, FET-PET2 acquired one month post-chemo-RT and FET-PET3 (+/-FDG-PET) triggered when clinical and/or radiological (MRI) progression is suspected. Dynamic and static FET-PET images are analysed qualitatively and quantitatively. Radiotherapy is as per standard care with the treating Radiation Oncologist (RO) blinded to FET-PET1. Site nuclear medicine (NM) physicians are required to delineate a biological target volume (BTV) based on FET-PET1 with hybrid RT volumes derived post-hoc. Pre-trial NM quality assurance comprises certification from the Australasian Radiopharmaceutical Trials Network encompassing FET-PET radiochemistry Quality Control and PET camera calibration. Site and central integrated workflows incorporating multi-modality image registration, target volume/region of interest contouring and analysis have been developed. NM benchmarking involves delineation of FET-PET BTVs in 3 cases with another 3 cases addressing response criteria interpretation harmonized across FET-PET, FDG-PET and MRI. Site ROs complete 3 cases involving standard and hybrid target volume delineation based on pre-derived FET-PET volumes. All NM and RO credentialing cases undergo central expert review. To date, of six sites which have submitted full credentialing data, 19/21 RO and 6/6 planning cases were passed. Of 72 NM cases, 18/72 (25%) required resubmission, primarily related to ensuring standardisation of background regions and time activity curve interpretation. The FIG study will be pivotal in establishing the role of FET-PET in GBM management. The robust NM and RO credentialing program will build capacity and expertise in FET-PET production, acquisition and image interpretation.

RTHP-30. DOES THE TEMPORAL LOBECTOMY CAVITY NEED TO BE IRRADIATED? PATTERNS OF RECURRENCE AND IMPLICATIONS FOR POSTOPERATIVE RADIATION TREATMENT FIELD DESIGN FOR TEMPORAL LOBE GLIOMAS.

Abstract BACKGROUND Treatment of temporal lobe glioma (TLG) frequently includes partial or complete temporal lobectomy (TL) followed by radiotherapy (RT). However, there are two approaches for temporal resection cavity RT, 1) standard target volumes (STV) targeting the entire TL resection cavity, dura, and peri-tumoral brain parenchyma or 2) modified target volumes (MTV) targeting only the adjacent peri-tumoral brain parenchyma. We report patterns of failure and a dosimetric comparison of these approaches. MATERIALS AND METHODS This was a retrospective review of 49 patients with WHO grade II-IV TLG who underwent partial or complete TL and post-operative RT between 1998 and 2018. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. RESULTS The median patient age was 56 years (range,21–76). Patients were diagnosed with glioblastoma (n=32,65%), anaplastic glioma (n=10,20%) and low-grade glioma (n=7,14%). Treatment included partial TL with STV (n=33,67%), partial TL with MTV (n=5,10%), complete TL with STV (n=8,16%) and complete TL with MTV (n=3,6%). Mean RT dose was 60 Gy (range,40–76) in 30 fractions (range,15–39). At median follow-up time of 18 months (range, 3–161), 44 patients (90%) experienced recurrence: 34 (77%) in-field, 5 (11%) out-of-field, and 5 (11%) both in- and out-of-field. Among the 39 in-field failures, the location of recurrence included brain parenchyma (n=38,97%), ventricle (n=6,15%), and dura (n=5,13%). No patient experienced isolated dural recurrence regardless of tumor grade, extent of TL, or radiation volume. Median PFS was 20 months (95% confidence interval [CI]: 15–24). RT volume (STV vs. MTV) was not associated with worsened PFS (hazard ratio: 1.1, 95% CI: 0.5–2.6). MTV was associated with significant reductions in mean or max doses to brain stem, optic chiasm, optic nerves, hippocampus, and pituitary compared to STV. CONCLUSION Omitting RT to the entire TL cavity may reduce dose to multiple normal tissues with no detriments in dural recurrence or PFS.

Author Reply

The authors performed a retrospective study on 125 patients who experienced a biochemical relapse following radical prostatectomy (RP) and who were subjected to a PSMA-PET/CT in order to assess if the recurrent cancer foci were located within standard radiation target volumes. 1 Boreta L Gadzinski A Wu S et al. Location of recurrence by Gallium-68 PSMA-11 PET scan in prostate cancer patients eligible for salvage radiotherapy. Urology. 2019; 129: 158-164 Google Scholar According to their data, 53% of the patients demonstrated PSMA-positive foci of which 25 lesions were located outside of the small pelvis. The authors concluded that the use of PSMA-PET/CT would have a dramatic effect on the design and the use of salvage radiation therapy.

Location of Recurrence by Gallium-68 PSMA-11 PET Scan in Prostate Cancer Patients Eligible for Salvage Radiotherapy

ObjectiveTo identify locations of recurrence after radical prostatectomy (RP) with prostate-specific antigen (PSA) <2 by Gallium-68 prostate-specific membrane antigen (PSMA)-11 Positron Emission Tomography (PET) imaging, and to determine whether standard nodal radiation fields would cover the location of prostate cancer recurrence. Materials and MethodsWe performed a retrospective review of patients with PSMA-PET imaging for biochemical recurrence following RP with PSA ≤2.0 ng/mL and assessed if the recurrent disease was within standard radiation target volumes. We compared patient and clinical variables between men with recurrences covered by standard salvage radiation fields and those with recurrences outside of standard fields. ResultsWe identified 125 patients for study inclusion. The median PSA at imaging was 0.40 ng/mL (interquartile range 0.28-0.63). PSMA-avid disease was found in 66 patients (53%). Of these, 25 patients (38%) had PSMA-avid lesions found outside of the pelvis, 33 (50%) had lesions confined to the pelvic lymph nodes and prostate bed, and 8 (12%) men had PSMA-avid recurrence only in the prostate bed. Salvage radiation including standard Intensity Modulated Radiation Therapy (IMRT) pelvic nodal volumes would not cover PSMA-avid nodal disease in 38 men (30%). PSA at the time of imaging was statistically associated with having PSMA-avid disease outside of standard nodal fields (P <.01). ConclusionThe 68Ga-PSMA-11 PET detects disease in a majority of patients with PSA ≤2.0 following RP. Nearly one-third of men had PSMA-avid disease that would be missed by standard radiation fields. This imaging modality may dramatically impact the design and use of post-RP salvage radiotherapy.

68Ga-PSMA-PET/CT imaging of localized primary prostate cancer patients for intensity modulated radiation therapy treatment planning with integrated boost.

The purpose of our study was to show the feasibility and potential benefits of using 68Ga-PSMA-PET/CT imaging for radiation therapy treatment planning of patients with primary prostate cancer using either integrated boost on the PET-positive volume or localized treatment of the PET-positive volume. The potential gain of such an approach, the improvement of tumor control, and reduction of the dose to organs-at-risk at the same time was analyzed using the QUANTEC biological model. Twenty-one prostate cancer patients (70years average) without previous local therapy received 68Ga-PSMA-PET/CT imaging. Organs-at-risk and standard prostate target volumes were manually defined on the obtained datasets. A PET active volume (PTV_PET) was segmented with a 40% of the maximum activity uptake in the lesion as threshold followed by manual adaption. Five different treatment plan variations were calculated for each patient. Analysis of derived treatment plans was done according to QUANTEC with in-house developed software. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was calculated for all plan variations. Comparing the conventional plans to the plans with integrated boost and plans just treating the PET-positive tumor volume, we found that TCP increased to (95.2±0.5%) for an integrated boost with 75.6Gy, (98.1±0.3%) for an integrated boost with 80Gy, (94.7±0.8%) for treatment of PET-positive volume with 75Gy, and to (99.4±0.1%) for treating PET-positive volume with 95Gy (all p < 0.0001). For the integrated boost with 80Gy, a significant increase of the median NTCP of the rectum was found, for all other plans no statistical significant increase in the NTCP neither of the rectum nor the bladder was found. Our study demonstrates that the use of 68Ga-PSMA-PET/CT image information allows for more individualized prostate treatment planning. TCP values of identified active tumor volumes were increased, while rectum and bladder NTCP values either remained the same or were even lower. However, further studies need to clarify the clinical benefit for the patients applying these techniques.

Ovary-Sparing Radiation Planning Techniques Can Achieve Ovarian Dose Reduction for Soft Tissue Sarcoma of the Buttock and Thigh.

Background and Objectives Attention to ovary dose is important for premenopausal women undergoing radiation therapy (RT) and must not be overlooked when treating extremity sarcoma. We assessed whether ovary-sparing RT plans could decrease ovary dose without compromising target coverage. Methods Standard sarcoma target volumes and organs at risk (OAR) were contoured by a sarcoma dedicated radiation oncologist on CT planning scans for 23 women with thigh or buttock sarcoma. IMRT plans (50 Gy) with and without attempted ovary-sparing were created by an expert sarcoma dosimetrist. Results All plans met target coverage goals. Compared to standard plans, ovary-sparing plans had lower mean bilateral ovary doses (MBOD) (652 versus 483 cGy, p = 0.007) but higher bone doses (mean V50: 8.5% versus 6.9%, p = 0.049) and lower conformity indexes (1.12 versus 1.19, p = 0.009). Tumors < 8 cm from the pubic symphysis had significant MBOD reduction with ovary-sparing plans (376 cGy versus 619 cGy, p = 0.0184). On multivariate analysis, distance to pubic symphysis and proximal medial thigh site were associated with MBOD reduction with ovary-sparing plan. Conclusions For preoperative IMRT, ovary-sparing planning significantly reduces ovarian dose in women with sarcoma of the proximal thigh and near the pubic symphysis.

Dosimetry advantages of intraoperatively built custom-linked seeds compared with loose seeds in permanent prostate brachytherapy.

PurposeThe aim of this study was to compare the implant quality between intraoperatively built custom-linked seeds (IBCL) and loose seeds (LS) retrospectively.Material and methodsThis study included 74 prostate cancer patients who were treated with permanent prostate brachytherapy (PPB) using IBCL (n = 37) or LS (n = 37) between July 2014 and June 2016. Dose-volume histogram (DVH) parameters, seed migration, and operation time were compared between the IBCL and LS groups. In addition to the standard target volume of the whole prostate gland, DVH parameters for prostate plus a 3 mm margin (CTV) were evaluated.ResultsIn intraoperative planning, prostate V150 was lower (54.8% vs. 59.6%, p = 0.027), and CTV V100 (88.1% vs. 85.6%, p = 0.019) and D90 (98.5% vs. 92.6%, p = 0.0033) were higher in the IBCL group compared with in the LS group. In post-implant dosimetry, prostate V100 (96.9% vs. 95.2%, p = 0.020), CTV V100 (85.6% vs. 81.7%, p = 0.046), and CTV D90 (94.2% vs. 86.5%, p < 0.001) were higher, and prostate V150 (57.1% vs. 64.5%, p = 0.0051) and CTV V150 (31.5% vs. 35.7%, p = 0.046) were lower in the IBCL group compared with in the LS group. Regarding DVH changes between intraoperative planning and post-implant dosimetry, the decrease in prostate D90 was significantly lower in the IBCL group than in the LS group (–1.16% vs. –4.17%, p < 0.001). For the IBCL group, the operation time was slightly but significantly longer than that for the LS group (50.5 minutes vs. 43.7 minutes, p = 0.011). However, the seed migration rate was significantly lower in the IBCL group than in the LS group (5% vs. 41%, p < 0.001).ConclusionsIntraoperatively built custom-linked is more advantageous than LS in terms of dosimetric parameters and migration.

Defining and assessing an anisotropic delineation margin for modern radiotherapy.

Uncertainty in target volume delineation for modern radiotherapy impacts dosimetry and patient outcomes. Delineation uncertainty is generally overlooked in practice as a source of error, potentially since historically, other uncertainties have been the main focus. This work defined and assessed an anisotropic delineation margin in both polar and spherical coordinate systems in order to account for the spatially varying nature of this uncertainty using a whole breast radiotherapy cohort as a proof of concept. A cohort of 21 whole breast radiotherapy patient datasets with clinical target volumes delineated by eight independent observers was utilized. Patients were divided into categories based on target volume and laterality. An anisotropic delineation margin for each category was determined by multiplying the average standard deviation in observer contours in each category by a factor of two. Standard deviation was determined in both polar and spherical coordinates at angular increments. This anisotropic approach was compared to a conventional clinical approach, where the delineation margin was applied in the cardinal directions only. The assessment of the delineation margin was undertaken by comparing the encompassment of the observer volumes by the target volume with added margin. The extra, presumed healthy tissue included in the margin and the malignant tissue missed by the margin were determined. The proposed delineation margin is effective at accounting for inter-observer variation, producing >95% coverage of all CTVs for polar, spherical, and Cartesian margins in 82%, 79%, and 92% of cases, respectively. Additionally, <1% malignant tissue was missed for 65%, 70%, and 91% of cases and <37% healthy tissue was included in 95%, 89%, and 97% of cases. A conventional delineation margin approach is most appropriate for small and gold standard target volumes. However, for large target volumes, an anisotropic margin is necessary, producing significantly greater coverage of CTVs, including significantly less presumed healthy tissue and missing significantly less malignant tissue. All delineation margin methods that account for target volume and laterality proved to be adequate, with appropriate encompassment of interobserver variation and minimal inclusion of extra excess healthy tissue and exclusion of possible malignant tissue. The anisotropic approach was found to be superior to a conventional approach for target volumes >1400 cm3 only with significantly greater encompassment of interobserver variation, less missed malignant tissue and less included healthy tissue. This methodology has been validated for a whole breast radiotherapy cohort as a proof of concept, however could be applied to other anatomical sites.

Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial Findings From a Randomized Trial

(18)F-Fluciclovine (anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of (18)F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes. We report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the (18)F-fluciclovine arm. All patients underwent (18)F-fluciclovine PET-CT for the detection of metabolic abnormalities and high-resolution CT for treatment planning. The 2 datasets were registered first by use of a rigid registration. If soft tissue displacement was observable, the rigid registration was improved with a deformable registration. Each (18)F-fluciclovine abnormality was segmented as a percentage of the maximum standard uptake value (SUV) within a small region of interest around the lesion. The percentage best describing the SUV falloff was integrated in planning by expanding standard target volumes with the PET abnormality. In 21 of 55 abnormalities, a deformable registration was needed to map the (18)F-fluciclovine activity into the simulation CT. The most selected percentage was 50% of maximum SUV, although values ranging from 15% to 70% were used for specific patients, illustrating the need for a per-patient selection of a threshold SUV value. The inclusion of (18)F-fluciclovine changed the planning volumes for 46 abnormalities (83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only 9 PET abnormalities were fully contained in the standard target volumes based on the CT-based segmentations and did not necessitate expansion. The use of (18)F-fluciclovine in postprostatectomy radiation therapy planning was feasible and led to augmentation of the target volumes in the majority (30 of 41) of the patients studied.

Influence of multileaf collimator leaf width on volumetric modulated arc therapy plans evaluated on AAPM standard phantom

Objective To develop double-arc volumetric modulated arc therapy (VMAT) plans using standard phantom and standard target volume in AAPM119 report, and to investigate the dosimetric parameters of Agility and MLCi2 leafs according to the requirements for target dose in AAPM119 report. Methods The Cshape, Head and Neck, Prostate, and Multitarget structures for standard target volume delineation in AAPM119 report were used. The Elekta Agility multi-leaf collimator was used to develop plans, and then with other parameters remaining unchanged, Elekta MLCi2 was used for plan optimization and dose calculation. The target dose in AAPM119 report was used as the standard to analyze the differences in target volume and dose-volume parameters of organs at risk between the four structures for target volume delineation. Results According to the mean dose in AAPM119 report, in the Cshape, Head and Neck, and Multitarget target volumes, the radiotherapy plans developed with Agility had better dosimetric parameters compared with those developed with MLCi2. In the prostate target volume, the radiotherapy plans developed with MLCi2 had better dosimetric parameters compared with those developed with Agility. Conclusions With the structures for target volume delineation, plan designing personnel, designing parameters, and evaluation criteria remaining the same, Elekta Agility can achieve the dose target better than Elekta MLCi2 in the aspect of strict dose limit. Key words: Multi-leaf collimator; Leaf width; Volumetric modulated arc therapy; Dosimetry

RTRB-17NEURAL PROGENITOR CELL (NPC) SPARING RADIATION THERAPY PLUS TEMOZOLOMIDE IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM) ASSOCIATED WITH COGNITIVE FUNCTION BUT NOT TUMOR OUTCOMES: RESULTS OF A SINGLE ARM PROSPECTIVE CLINICAL TRIAL

BACKGROUND: NPC may be associated with neuro-cognitive sequelae of RT, but may contribute to GBM recurrence. This prospective trial limited RT dose to NPC niches to evaluate the impact on neuro-cognitive function, tumor recurrence, and survival in newly diagnosed GBM. METHODS: 30 adults with newly diagnosed GBM and KPS > 60 enrolled. Each received 60 Gy in 30 fractions with concurrent/adjuvant temozolomide. Standard planning target volumes (PTV) delineated. Subventricular zone (SVZ, 0.5 cm adjacent to lateral wall of lateral ventricle) and hippocampus (expanded 5 mm) defined as NPC niches. IMRT limited RT dose to NPC niches without compromising PTV dose. Tests of global cognitive function, processing speed, verbal learning/memory, and executive function obtained at baseline, 6, 12, 24 months. OS/PFS estimated using Kaplan-Meier method. Cox regression model evaluated relationships between performance on cognitive testing, radiation doses to NPC regions, survival outcomes. RESULTS: 16 men, 14 women; 17 gross total resection, 13 subtotal resection; 8 MGMT methylated, 11 unmethylated, 10 unknown; 6 multifocal. Median OS: 15.9 months (95% CI 12.6-35.4). Median PFS: 7.3 months (95% CI 4.8-9.3 months). Mean dose to ipsilateral and contralateral hippocampus: 43.8 Gy (range 9.0 - 61.4) and 17.3 Gy (range 1.7 - 40.2), respectively. Mean dose to ipsilateral and contralateral SVZ: 38.9 Gy (range 6 - 56.2) and 20.5 Gy (range 4.4 - 48.0), respectively. At a minimum FU of 13 months, 2 patients recurred in spared NPC volume. Higher mean RT dose to bilateral SVZ was associated with greater deterioration in performance between baseline and 6 /12 months on processing speed (Coding, p = 0.03). No relationship between RT dose to NPC niches and PFS, OS, or recurrence patterns. CONCLUSIONS: This prospective trial suggests a relationship between RT dose to NPC niches and neuro-psychological function in newly diagnosed GBM without a detrimental effect on recurrence or survival outcomes.

TH‐A‐BRF‐09: Integration of High‐Resolution MRSI Into Glioblastoma Treatment Planning

Purpose:Identification of a metabolite signature that shows significant tumor cell infiltration into normal brain in regions that do not appear abnormal on standard MRI scans would be extremely useful for radiation oncologists to choose optimal regions of brain to treat, and to quantify response beyond the MacDonald criteria. We report on integration of high‐resolution magnetic resonance spectroscopic imaging (HR‐MRSI) with radiation dose escalation treatment planning to define and target regions at high risk for recurrence.Methods:We propose to supplement standard MRI with a special technique performed on an MRI scanner to measure the metabolite levels within defined volumes. Metabolite imaging was acquired using an advanced MRSI technique combining 3D echo‐planar spectroscopic imaging (EPSI) with parallel acquisition (GRAPPA) using a multichannel head coil that allows acquisition of whole brain metabolite maps with 108 μl resolution in 12 minutes implemented on a 3T MR scanner. Elevation in the ratio of two metabolites, choline (Cho, elevated in proliferating high‐grade gliomas) and N‐acetyl aspartate (NAA, a normal neuronal metabolite), was used to image infiltrating high‐grade glioma cells in vivo.Results:The metabolite images were co‐registered with standard contrast‐enhanced T1‐weighted MR images using in‐house registration software and imported into the treatment‐planning system. Regions with tumor infiltration are identified on the metabolic images and used to create adaptive IMRT plans that deliver a standard dose of 60 Gy to the standard target volume and an escalated dose of 75 Gy (or higher) to the most suspicious regions, identified as areas with elevated Cho/NAA ratio.Conclusion:We have implemented a state‐of‐the‐art HR‐MRSI technology that can generate metabolite maps of the entire brain in a clinically acceptable scan time, coupled with introduction of an imaging co‐registration/ analysis program that combines MRSI data with standard imaging studies in a clinically useful fashion.

Abstract P5-14-17: Post-lumpectomy tumorbed delineation for breast boost or partial breast irradiation: The influence of additional MRI and CT imaging

Abstract Rationale/Purpose In early stage breast cancer patients, most recurrences occur in the vicinity of the original tumor location. Therefore, after initial lumpectomy it is important to accurately delineate the tumorbed (TB) area for breast boost and partial breast irradiation on the planning-CT scan. However, consistency in TB delineation among radiation oncologists is low on standard CT imaging. The purpose of this study was to determine whether additional pre- and postoperative MRI and CT imaging could increase consistency in standard CT-guided target volume delineation among radiation oncologists. Methods Fourteen cT1-2 patients underwent MRI and CT imaging in supine radiotherapy position before and after lumpectomy. TBs were delineated by 4 breast radiation oncologists following delineation guidelines on the standard postoperative planning-CT alone, and planning-CT registered to 1) postoperative MRI (T1 (with and without fat suppression) and T2 weighted sequences) 2) preoperative contrast-enhanced (CE) CT, and 3) preoperative CE-MRI (T1 weighted sequence with fat suppression). Consistency was defined by the conformity index (CI), which was calculated by dividing the encompassing volume of each observer pair, by the volume of overlap for each observer pair. Furthermore, volumes and the distance between centres of mass (dCOM) of the delineated TBs were determined. A Wilcoxon signed-rank test was performed to compare variables between different imaging modalities, with a significance level of a = 0.05. Results Results of the analysis are shown in Table 1. Addition of a postoperative MRI to the standard postoperative planning CT did not influence the CI (p = 0.176) or dCOM (p = 0.110). However, the TB volumes increased significantly with a median increase of 6 cm3 (p&amp;lt;0.001). Addition of a preoperative CT or MRI increased the CI by 0.01 and 0.02 (both p&amp;lt;0.001). Furthermore, preoperative CT and MRI increased dCOM (p = 0.004 and p = 0.001) and volumes (both p&amp;lt;0.001). Table 1 medianrange p-valueVolume (cm3) CT224-934 CT + postoperative MRI283-964&amp;lt;0.001CT + preoperative CT266-933&amp;lt;0.001CT + preoperative MRI257-933&amp;lt;0.001 Conformity index CT0.570.00-0.90 CT + postoperative MRI0.610.00-0.890.176CT + preoperative CT0.580.00-0.90&amp;lt;0.001CT + preoperative MRI0.590.00-0.89&amp;lt;0.001 dCOM (mm) CT50-53 CT + postoperative MRI40-520.110CT + preoperative CT31-420.004CT + preoperative MRI50-480.001 Conclusion Although significant, the addition of postoperative MRI, preoperative CE-CT or preoperative CE-MRI did not result in a clinically relevant improvement of the consistency in postoperative CT-guided TB delineation among radiation oncologists. Furthermore, target volumes increased with all imaging modalities. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-17.

Comparative evaluation of CT-based and respiratory-gated PET/CT-based planning target volume (PTV) in the definition of radiation treatment planning in lung cancer: preliminary results

The aim of this study was to compare planning target volume (PTV) defined on respiratory-gated positron emission tomography (PET)/CT (RG-PET/CT) to PTV based on ungated free-breathing CT and to evaluate if RG-PET/CT can be useful to personalize PTV by tailoring the target volume to the lesion motion in lung cancer patients. Thirteen lung cancer patients (six men, mean age 70.0 years, 1 small cell lung cancer, 12 non-small cell lung cancer) who were candidates for radiation therapy were prospectively enrolled and submitted to RG-PET/CT. Ungated free-breathing CT images obtained during a PET/CT study were visually contoured by the radiation oncologist to define standard clinical target volumes (CTV1). Standard PTV (PTV1) resulted from CTV1 with the addition of 1-cm expansion of margins in all directions. RG-PET/CT images were contoured by the nuclear medicine physician and radiation oncologist according to a standardized institutional protocol for contouring gated images. Each CT and PET image of the patient's respiratory cycle phases was contoured to obtain the RG-CT-based CTV (CTV2) and the RG-PET/CT-based CTV (CTV3), respectively. RG-CT-based and RG-PET/CT-based PTV (PTV2 and PTV3, respectively) were then derived from gated CTVs with a margin expansion of 7-8 mm in head to feet direction and 5 mm in anterior to posterior and left to right direction. The portions of gated PTV2 and PTV3 geometrically not encompassed in PTV1 (PTV2 out PTV1 and PTV3 out PTV1) were also calculated. Mean ± SD CTV1, CTV2 and CTV3 were 30.5 ± 33.2, 43.1 ± 43.2 and 44.8 ± 45.2 ml, respectively. CTV1 was significantly smaller than CTV2 and CTV3 (p = 0.017 and 0.009 with Student's t test, respectively). No significant difference was found between CTV2 and CTV3. Mean ± SD of PTV1, PTV2 and PTV3 were 118.7 ± 94.1, 93.8 ± 80.2 and 97.0 ± 83.9 ml, respectively. PTV1 was significantly larger than PTV2 and PTV3 (p = 0.038 and 0.043 with Student's t test, respectively). No significant difference was found between PTV2 and PTV3. Mean ± SD values of PTV2 out PTV1 and PTV3 out PTV1 were 12.8 ± 25.4 and 14.3 ± 25.9 ml, respectively. The percentage values of PTV2 out PTV1 and PTV3 out PTV1 were not lower than 10 % of PTV1 in 6/13 cases (46.2 %) and than 20 % in 3/13 cases (23.1 %). Our preliminary data showed that RG-PET/CT in lung cancer can affect not only the volume of PTV but also its shape, as demonstrated by the assessment of gated PTVs outside standard PTV. The use of a gating technique is thus crucial for better delineating PTV by tailoring the target volume to the lesion motion in lung cancer patients.

Experimental validation of the van Herk margin formula for lung radiation therapy

To validate the van Herk margin formula for lung radiation therapy using realistic dose calculation algorithms and respiratory motion modeling. The robustness of the margin formula against variations in lesion size, peak-to-peak motion amplitude, tissue density, treatment technique, and plan conformity was assessed, along with the margin formula assumption of a homogeneous dose distribution with perfect plan conformity. 3DCRT and IMRT lung treatment plans were generated within the ORBIT treatment planning platform (RaySearch Laboratories, Sweden) on 4DCT datasets of virtual phantoms. Random and systematic respiratory motion induced errors were simulated using deformable registration and dose accumulation tools available within ORBIT for simulated cases of varying lesion sizes, peak-to-peak motion amplitudes, tissue densities, and plan conformities. A detailed comparison between the margin formula dose profile model, the planned dose profiles, and penumbra widths was also conducted to test the assumptions of the margin formula. Finally, a correction to account for imperfect plan conformity was tested as well as a novel application of the margin formula that accounts for the patient-specific motion trajectory. The van Herk margin formula ensured full clinical target volume coverage for all 3DCRT and IMRT plans of all conformities with the exception of small lesions in soft tissue. No dosimetric trends with respect to plan technique or lesion size were observed for the systematic and random error simulations. However, accumulated plans showed that plan conformity decreased with increasing tumor motion amplitude. When comparing dose profiles assumed in the margin formula model to the treatment plans, discrepancies in the low dose regions were observed for the random and systematic error simulations. However, the margin formula respected, in all experiments, the 95% dose coverage required for planning target volume (PTV) margin derivation, as defined by the ICRU; thus, suitable PTV margins were estimated. The penumbra widths calculated in lung tissue for each plan were found to be very similar to the 6.4 mm value assumed by the margin formula model. The plan conformity correction yielded inconsistent results which were largely affected by image and dose grid resolution while the trajectory modified PTV plans yielded a dosimetric benefit over the standard internal target volumes approach with up to a 5% decrease in the V20 value. The margin formula showed to be robust against variations in tumor size and motion, treatment technique, plan conformity, as well as low tissue density. This was validated by maintaining coverage of all of the derived PTVs by 95% dose level, as required by the formal definition of the PTV. However, the assumption of perfect plan conformity in the margin formula derivation yields conservative margin estimation. Future modifications to the margin formula will require a correction for plan conformity. Plan conformity can also be improved by using the proposed trajectory modified PTV planning approach. This proves especially beneficial for tumors with a large anterior-posterior component of respiratory motion.

Hypoxia-targeted radiotherapy dose painting for head and neck cancer using 18F-FMISO PET: A biological modeling study

Background. This study investigates the use of 18F-fluoromisonidazole (FMISO) PET-guided radiotherapy dose painting for potentially overcoming the radioresistant effects of hypoxia in head and neck squamous cell carcinoma (HNSCC). Material and methods. The study cohort consisted of eight patients with HNSCC who were planned for definitive radiotherapy. Hypoxic subvolumes were automatically generated on pre-radiotherapy FMISO PET scans. Three radiotherapy plans were generated for each patient: a standard (STD) radiotherapy plan to a dose of 70 Gy, a uniform dose escalation (UDE) plan to the standard target volumes to a dose of 84 Gy, and a hypoxia dose-painted (HDP) plan with dose escalation only to the hypoxic subvolume to 84 Gy. Plans were compared based on tumor control probability (TCP), normal tissue complication probability (NTCP), and uncomplicated tumor control probability (UTCP). Results. The mean TCP increased from 73% with STD plans to 95% with the use of UDE plans (p < 0.001) and to 93% with HDP plans (p < 0.001). The mean parotid NTCP increased from 26% to 44% with the use of UDE plans (p = 0.003), and the mean mandible NTCP increased from 2% to 27% with the use of UDE plans (p = 0.001). There were no statistically significant differences between any of the NTCPs between the STD plans and HDP plans. The mean UTCP increased from 48% with STD plans to 66% with HDP plans (p = 0.016) and dropped to 37% with UDE plans (p = 0.138). Conclusion. Hypoxia-targeted radiotherapy dose painting for head and neck cancer using FMISO PET is technically feasible, increases the TCP without increasing the NTCP, and increases the UTCP. This approach is superior to uniform dose escalation.

Dosimetric evaluation of intrafractional tumor motion by means of a robot driven phantom

The aim of the work was to investigate the influence of intrafractional tumor motion to the accumulated (absorbed) dose. The accumulated dose was determined by means of calculations and measurements with a robot driven motion phantom. Different motion scenarios and compensation techniques were realized in a phantom study to investigate the influence of motion on image acquisition, dose calculation, and dose measurement. The influence of motion on the accumulated dose was calculated by employing two methods (a model based and a voxel based method). Tumor motion resulted in a blurring of steep dose gradients and a reduction of dose at the periphery of the target. A systematic variation of motion parameters allowed the determination of the main influence parameters on the accumulated dose. The key parameters with the greatest influence on dose were the mean amplitude and the pattern of motion. Investigations on necessary safety margins to compensate for dose reduction have shown that smaller safety margins are sufficient, if the developed concept with optimized margins (OPT concept) was used instead of the standard internal target volume (ITV) concept. Both calculation methods were a reasonable approximation of the measured dose with the voxel based method being in better agreement with the measurements. Further evaluation of available systems and algorithms for dose accumulation are needed to create guidelines for the verification of the accumulated dose.