Andrew Hoole

A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome

OBJECTIVE We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushings syndrome. DESIGN Twenty patients with i) de novo Cushings disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushings syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. METHODS All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. RESULTS In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushings syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. CONCLUSIONS (11)C-methionine PET-CT can aid the detection of ACTH-secreting tumours in Cushings syndrome and facilitate targeted therapy.

Post-Operative Radiotherapy for Soft Tissue Sarcoma of the Anterior Compartment of the Thigh: Should the Sartorius Muscle be Included?

Purpose: The clinical target volume (CTV) of post-operative radiotherapy for soft tissue sarcoma of the limbs conventionally includes the whole of the transverse cross-section of the affected anatomical compartment. In the anterior thigh sartorius appears to lie within its own fascial compartment and can be safely excluded. We investigated the potential impact of omitting sartorius from the anterior muscle compartment on patients with soft tissue sarcoma of the thigh. Patients and methods:We used the planning CT data from six patients who had previously received post-operative radiotherapy for soft tissue sarcoma of the thigh. The anterior compartments were outlined twice, initially including and then excluding the sartorius muscle. The volumes of the anterior compartment (i.e., the CTVs), both with and without sartorius, and the corresponding planning target volumes (PTVs) were calculated. Treatment plans were prepared for each PTV. For both volumes the unirradiated normal tissue corridor was outlined on each CT slice. The volume and circumference of the unirradiated corridor were then calculated. Results: For all six patients there was an important improvement in normal tissue sparing by excluding sartorius. The mean reduction in volume of the anterior compartment when sartorius was excluded was 10% (95% Confidence Interval 8–12%), whilst the mean decrease in PTV was 11% (95% CI 7–14%). There was a substantial increase in the volume of the unirradiated normal tissue corridor, with a mean value of 77% (95% CI 41–114%) when sartorius was excluded. In addition, the percentage increase in the size of the unirradiated normal tissue corridor, expressed as a percentage of the whole leg circumference, was 10% (95% CI 8–13%). When sartorius was included in the anterior compartment, the circumference of the unirradiated corridor was less than one-third of the whole leg circumference in four of the six patients. When sartorius was excluded, the circumference of the unirradiated corridor was greater than one-third of the leg circumference over the entire length of the target volume in all patients. Discussion: It is essential to know the anatomy of the sartorius muscle to be able to exclude it from the anterior compartment. The increase in the size of the normal tissue corridor when sartorius is excluded should deliver clinical advantage by decreasing the normal tissue adverse effects.

The anatomy of sartorius muscle and its implications for sarcoma radiotherapy.

Purpose: Controversy exists as to whether sartorius muscle is completely invested in fascia. If it is, then direct tumour involvement from soft tissue sarcoma of the anterior thigh would be unlikely and would justify omitting sartorius from the radiotherapy volume. Subjects and methods: Eight thighs in six cadavers were examined in the dissecting room. Using a previous case, conformal radiotherapy plans were prepared to treat the anterior compartment of the thigh including and excluding sartorius. The corridor of unirradiated normal tissue was outlined separately. Results: In all cases, sartorius was enclosed within a fascial sheath of its own. In four of the six cadavers, there was clear evidence of a fascial envelope surrounding sartorius, fused to the fascia lata and medial intermuscular septum. In two, sartorius was fully ensheathed in the upper half of the thigh; in the lower half the intermuscular septum became thin, and blended with the tendinous aponeurosis on the surface of vastus medialis in an example case. By excluding sartorius, the volume of the anterior compartment was reduced by 8%, but the volume of the unirradiated normal tissue corridor increased by 134%. With sartorius included, the unirradiated corridor became very small inferiorly, only 6% of the circumference of the whole leg, compared to 27% with sartorius excluded. Discussion: The anatomy suggests that sartorius could be safely omitted from the clinical target volume of anterior compartment soft tissue sarcomas. This substantially increases the size of the unirradiated normal tissue corridor, expressed as a volume and a circumference, which could give a clinical advantage by reducing normal tissue complications.

Dose–volume population histogram: a new tool for evaluating plans whilst considering geometrical uncertainties

We present a method to incorporate geometrical uncertainties into dose-volume histogram evaluation: the dose-volume population histogram (DVPH). For each dose-volume point, the probability of the plan DVH meeting the constraint is calculated. The use of DVPH for the target shows that the minimum dose to the PTV might not be representative of the minimum dose to the CTV considering geometrical uncertainties when the PTV extends into the build-up region. For OARs, the DVH obtained from DVPH with 90% confidence level is found to be different to the planning organ at risk volume (PRV) DVH recommended by ICRU 62, especially for parallel organs.

Image guidance protocols: balancing imaging parameters against scan time

OBJECTIVE Optimisation of imaging protocols is essential to maximise the use of image-guided radiotherapy. This article evaluates the time for daily online imaging with TomoTherapy® (Accuray®, Sunnyvale, CA), separating mechanical scan acquisition from radiographer-led image matching, to estimate the time required for a clinical research study (VoxTox). METHODS Over 5 years, 18 533 treatments were recorded for 3 tumour sites of interest (prostate, head and neck and central nervous system). Data were collected for scan length, number of CT slices, slice thickness, scan acquisition time and image matching time. RESULTS The proportion of coarse thickness scans increased over time, with a move of making coarse scans as the default. There was a strong correlation between scan time and scan length. Scan acquisition requires 40 s of processing time. For coarse scans, each additional centimetre requires 8 s for acquisition. Image matching takes approximately 1.5 times as long, so each additional centimetre needs 20 s extra in total. Modest changes to the imaging protocol have minimal impact over the course of the day. CONCLUSION This work quantified the effect of changes to clinical protocols required for research. The results have been found to be reassuring in the busy National Institutes of Health department. ADVANCES IN KNOWLEDGE This novel method of data collection and analysis provides evidence of the minimal impact of research on clinical turnover. Whilst the data relate specifically to TomoTherapy, some aspects may apply to other platforms in the future.

Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI

OBJECTIVE To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHODS Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied. RESULTS Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. CONCLUSIONS In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).

The use of shifted-isocentre techniques for plan evaluation

In radiotherapy treatment planning, the effect of geometric uncertainties is usually taken into account by adding margins, creating the Planning Target Volume (PTV) from the Clinical Target Volume (CTV). The use of the PTV is to ensure that the CTV receives the prescribed dose. Clinically, a plan is acceptable if the 95% isodose surface covers the PTV. For shallow tumors where the PTV extends into the build up region, PTV coverage is normally unacceptable following the above criterion due to the region of low dose near the skin surface. As well as PTV coverage, organ-at-risk (OAR) dose distribution is also used as a criterion to evaluate the plan. The use of OAR endpoints is normally applied for static DVH. An alternative planning technique is to calculate multiple subplans with different isocentres chosen using a probability distribution; in this method, a plan is acceptable if all the subplans give good coverage of the CTV and satisfy OAR endpoints. We describe the use of this method to validate the use of PTV coverage for plan evaluation for shallow tumors and to validate the use of endpoints for rectal dose evaluation in prostate cancer for IMRT and conformal planning. The results show that using PTV coverage as an indicator for plan quality in shallow tumor cases is not adequate. Single rectal DVH is not enough to evaluate the endpoints; an acceptable plan can become an unacceptable plan when patient-beam positioning uncertainties were taken account into.