Standardised quantitative radioiodine SPECT/CT Imaging for multicentre dosimetry trials in molecular radiotherapy.

The SEL-I-METRY trial (EudraCT No 2015-002269-47) is the first multicentre trial to investigate the role of 123I and 131I SPECT/CT-based tumour dosimetry to predict response to radioiodine therapy. Standardised dosimetry methodology is essential to provide a robust evidence-base for absorbed dose-response thresholds for molecular radiotherapy (MRT). In this paper a practical standardised protocol is used to establish the first network of centres with consistent methods of radioiodine activity quantification. Nine SPECT/CT systems at eight centres were set-up for quantitative radioiodine imaging. The dead-time of the systems was characterised for up to 2.8 GBq 131I. Volume dependent calibration factors were measured on centrally reconstructed images of 123I and 131I in six (0.8-196 ml) cylinders. Validation of image quantification using these calibration factors was performed on three systems, by imaging a 3D-printed phantom mimicking a patient's activity distribution. The percentage differences between the activities measured in the SPECT/CT image and those measured by the radionuclide calibrator were calculated. Additionally uncertainties on the SPECT/CT-based activities were calculated to indicate the limit on the quantitative accuracy of this method. For systems set-up to image high 131I count rates, the count rate versus activity did not peak below 2.8 GBq and fit a non-paralysable model. The dead-times and volume-dependent calibration factors were comparable between systems of the same model and crystal thickness. Therefore a global calibration curve could be fitted to each. The errors on the validation phantom activities' were comparable to the measurement uncertainties derived from uncertainty analysis, at 10% and 16% on average for 123I and 131I respectively in a 5 cm sphere. In conclusion, the dead-time and calibration factors varied between centres, with different models of system. However, global calibration factors may be applied to the same system model with the same crystal thickness, to simplify set-up of future multi-centre MRT studies.

Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols.

OBJECTIVE: To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1- and 2-day protocol that can be used as a minimal invasive procedure for staging of penile cancer. PATIENTS AND METHODS: This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ-counts, false-negative rates (FNR), and complication rates (Clavien-Dindo grading system). RESULTS: In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine-needle aspiration cytology. The 1-day protocol was performed in 65 groins and the 2-day protocol in 215. Statistically significantly more nodes were harvested with the 1-day protocol (1.92/groin) compared with the 2-day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1-day protocol, 2-day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1-day and 2-day protocols, respectively. Most of the complications were of Clavien-Dindo Grade 1-2. CONCLUSIONS: DSNB is safe for staging patients with penile cancer. There is a trend towards a 1-day protocol having a lower FNR than a 2-day protocol, albeit at the expense of a slightly higher complication rate.

No adverse affect in clinical outcome using low preablation diagnostic (131)i activity in differentiated thyroid cancer: refuting thyroid-stunning effect.

CONTEXT: Published studies of thyroid stunning due to preablation (131)I scanning in the treatment of differentiated thyroid cancer after thyroidectomy had shown inconsistent clinical impact. OBJECTIVE: The objective of the study was to evaluate the clinical outcome in patients who were given a low diagnostic (131)I activity (1.1 mCi or 40 MBq) 6 days prior to radioiodine ablation (RAI). DESIGN/SETTING: Two cohorts of patients were treated in a cancer referral center in 2004-2011. The eligibility criteria were as follows: 1) diagnosis of differentiated thyroid cancer; 2) total or near total thyroidectomy; 3) no distant metastasis; and 4) receiving 82.4 mCi or greater (3050 MBq) therapeutic (131)I activity. PATIENTS/INTERVENTIONS: Three hundred five consecutive patients treated in 2004-2008 (group A) had a diagnostic activity 1.1 mCi of (131)I prior to RAI. The second cohort treated in 2009-2011 (group B) consisted of 237 patients who did not undergo diagnostic (131)I scanning prior to RAI. MAIN OUTCOME MEASURES: The tumor recurrence rate at 3 years and quantitative assessment using diagnostic whole-body radioiodine scans and TSH-stimulated thyroglobulin levels at 3-12 months after RAI were measured. RESULTS: The 3-year recurrence-free survival rates were 96.4% in both groups, with 4.3% in group A and 3.4% in group B having tumor recurrence (P = .91). The ablation success rates measured by diagnostic whole-body radioiodine scans were 97.6% and 100% and by stimulated thyroglobulin were 85.3% and 85.8% in group A and B, respectively (P = .62). CONCLUSIONS: The use of low diagnostic (131)I activity (1.1 mCi) given 6 days prior to RAI was safe and convenient without adversely affecting the long-term clinical outcome.

Use of Pre-Ablation Radioiodine-131 Scan to Assess the Impact of Surgical Volume and Specialisation following Thyroidectomy for Differentiated Thyroid Carcinoma.

BACKGROUND: We evaluated the relationship between thyroid remnant size following thyroidectomy for differentiated thyroid carcinoma and surgical volume and specialisation by assessing pre-ablation radioiodine-131 ((131)I) thyroid bed uptake (TBU) scanning as a surrogate for residual thyroid tissue. METHODS: We analysed data of 651 patients in our thyroid cancer database. Patients' data were included if the following criteria were met: (1) diagnosis of differentiated thyroid carcinoma, (2) total or near-total thyroidectomy, (3) pre-ablation (131)I scan prior to radioiodine ablation (RAI), (4) no distant metastasis, and (5) >3,000 MBq ablative dose of (131)I. (131)I diagnostic whole-body scans and measurement of thyroglobulin levels were carried out 3-9 months after RAI. 305 patients were included in the final analysis. RESULTS: Four endocrine, 19 otolaryngology and 25 general surgeons performed thyroidectomies with median pre-ablation (131)I TBU values of 1.0, 1.8 and 2.9%, respectively (p = 0.0031). There was a statistically significant relationship between number of thyroidectomies performed and median pre-ablation (131)I TBU values up to the optimal number of 11 operations beyond which there was no further significant difference between surgeons. There were differences in remnant size between endocrine and general surgeons (p = 0.001), otolaryngology and general surgeons (p = 0.023) but not between endocrine and otolaryngology surgeons (p = 0.167). CONCLUSION: Using the pre-ablation (131)I uptake scan as a surrogate for thyroid remnant quantification following thyroidectomy demonstrates the relationship between the surgical volume and size of thyroid remnant. The study also demonstrated beneficial effects of specialisation with specialist surgeons achieving the smallest thyroid remnant.

The accuracy of the sentinel node procedure after excision biopsy in squamous cell carcinoma of the vulva.

INTRODUCTION: Restricting inguinofemoral lymphadenectomy to patients with malignant nodes would reduce treatment-related morbidity in vulval cancer patients. A prospective study was conducted to determine the diagnostic accuracy of the Sentinel Lymph Node (SLN) procedure in vulval cancer patients referred following either diagnostic or excision biopsy. METHODS: Patients with clinical stage I and II squamous cell carcinoma of the vulva underwent SLN identification with peri-scar/lesional injection of (99m)Technetium-labelled nanocolloid (pre-operative lymphoscintigraphy and intra-operative use of a hand-held probe) and intra-operative blue dye. Radical excision of the vulval tumour or scar and formal inguinofemoral lymphadenectomy was then performed as necessary. SLN were processed separately and further examined at multiple levels to exclude micrometastases (H&E/cytokeratin staining) if negative on routine analysis. Clinical follow-up was carried out to identify and treat recurrences or treatment-related morbidity. RESULTS: Thirty-two women took part. Fifteen were referred following excision biopsy and seventeen following diagnostic biopsy of their primary vulval tumour. One or more SLN was successfully detected intra-operatively in 31 patients (97%) and 45 groins. An SLN could not be identified intra-operatively in one case (re-excision of scar). On average, more SLN were identified in patients with their primary vulval lesion in situ compared with those whose tumour had previously been excised (2.6 vs. 1.8, p = 0.03). Midline tumours were more likely (15/17) than lateral tumours (1/15) to have bilateral SLN identified pre-operatively. Two patients with midline tumours previously excised had unilateral SLN. Seven patients (23%) and ten groins had inguinofemoral lymph node metastases. The SLN procedure correctly identified inguinofemoral metastases in six patients (nine groins). In one case (midline tumour, re-excision of scar) the sentinel node was positive on one side but false negative on the other. CONCLUSIONS: The SLN procedure may be used to identify malignant groins in selected patients with vulval cancer. The extent to which previous vulval surgery might influence the accuracy of the SLN procedure deserves further investigation.

Autologous lymphocytes as vectors to target therapeutic radiation, using indium-114m, in patients with lymphoid cell malignancy.

Autologous lymphocytes provide a potential vector for the delivery of a cytotoxic agent in patients with lymphoid cell malignancy. This report describes a phase I-II study using autologous lymphocytes to target the radionuclide indium-114m ((114m)In) in patients with refractory chronic lymphocytic leukaemia or small lymphocytic non-Hodgkin's lymphoma. Nineteen patients, the majority of whom had been heavily pretreated with conventional chemotherapy and radiotherapy, received between 69 and 211 MBq (114m)In-labelled autologous lymphocytes. Approximately 80% of the administered activity was localized in the liver and spleen, with around 5% accumulating in the bone marrow. Ten patients (53%) responded (one complete response and nine partial responses). The median duration of response was 7 months. The median survival for the responders was 14 months and for the non-responders was 3 months. The first notable response in every patient was a fall in peripheral lymphocyte count. The indium treatment was not associated with any subjective toxicity, although all patients suffered from myelosuppression, with thrombocytopenia being the dose-limiting factor. This study has demonstrated a significant anti-tumour effect in a group of patients with late-stage highly resistant disease.