Val Lewington

Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone

The palliative efficacy of strontium-89 chloride has been evaluated in a prospective double-blind crossover study comparing it with stable strontium as placebo in 32 patients with prostate cancer metastatic to bone. Response was assessed 5 weeks after each treatment. 26 patients were evaluable. Complete pain relief was only reported following strontium-89 injection. Statistical comparison between placebo and strontium-89 showed clear evidence of a therapeutic response to strontium-89 compared with only a limited placebo effect (P less than 0.01).

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Towards a Standardized Approach to the Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors and Their Prognostic Stratification

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors : towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Somatostatin receptor imaging with IIIIn-pentetreotide

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors : Somatostatin Receptor Imaging with In-111-Pentetreotide

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Follow-Up and Documentation

Summary of follow-up recommendations in patients with benign and malignant neuroendocrine tumorsFollow-upyes/no endoscopy US/CT/MRI Octreoscan CgABenign insulinoma noType 1 gastric carcinoid yes yearlyRectal carcinoid no (if completely resected)Appendiceal carcinoid T1 noAppendiceal carcinoid T2 ? (see text)Resectable tumor (uncertain behavior)G1 every 6–12 months yes(gastric carc.)yes every 2 years 2 yes 1 Resectable malignant tumor with/without nodal involvementG1 every 6–12 months yes every 2 years 2 yes 1 G2 every 6 months yes yearly 2 yes 1 G3 every 3 months yes yearly 2 yes 3 Non-resectable malignant tumor with/without nodal involvement and/or liver and other metastasesG1 every 6–12 months yes every 2 years 2 yesG2 every 6 months yes yearly 2 yesG3 every 3 months yes yearly 2 yes 31 Only in the presence of a visible tumor. 2 Recommendations regarding the time frames of Octreoscan should be adjusted to the individual situation. 3 In poorly differentiated tumors and negative CgA NSE may act as a suitable marker.

Targeted radionuclide therapy for bone metastases

Recent advances in targeted radiotherapy offer a new approach for the management of metastatic bone pain. This paper will review the scientific basis for radionuclide therapy and will examine the evidence for clinical efficacy. The therapeutic potential of targeted radiotherapy can only be appreciated by comparison with established treatments. Alternative treatment options will, therefore, be discussed, to bring the potential advantages and hazards of targeted radiotherapy into perspective and to define its place in routine management.

18F-fluoride PET changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with 223Ra-chloride (Alpharadin)

BackgroundA qualitative assessment of conventional bone scintigraphy with 99mTc methylene diphosphonate is perceived as an insensitive method for monitoring the treatment response of bone metastases, and we postulated that semi-quantitative 18F-fluoride positron emission tomography (PET) might serve as a suitable alternative biomarker of the treatment response.MethodsFive patients with castrate-resistant prostate cancer and bone metastases with no known soft tissue disease received 100 kBq/kg of radium-223 (223Ra)-chloride (Alpharadin) therapy at 0 and 6 weeks and had whole body 18F-fluoride PET scans at baseline, 6 and 12 weeks with concurrent prostatic-specific antigen (PSA) and alkaline phosphatase (ALP) measurements. A qualitative comparison of the PET scans was performed blinded to the PSA and ALP results. A semi-quantitative comparison was made by measuring the maximum standardised uptake values (SUVmax) in five bone metastases in each patient. The means of the five SUVmax measurements in each subject were used as a quantitative measure of global metastatic activity at each time point.ResultsThree patients showed a PSA decline at 12 weeks (-44%, -31%, -27% reduction) whilst two patients showed PSA increases (+10%, +17%). All five patients showed a reduction in ALP of greater than 25%. The qualitative assessment of the 18F-fluoride scans recorded a stable disease in each case. However, the semi-quantitative assessment showed agreement with the PSA decline in three patients (-52%, -75%, -49%) and minimal change (+12%, -16%) in two patients with increased PSA at 12 weeks. Four patients showed similar reductions in mean SUVmax and ALP at 12 weeks.ConclusionsThe semi-quantitative 18F-fluoride PET is more accurate than the qualitative comparison of scans in assessing response in bone metastases, correlating with the PSA response and ALP activity and offering a potential imaging biomarker for monitoring treatment response in bone metastases following treatment with 223Ra-chloride.

Phase 1/2 study of fractionated (131)I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy.

The effect of induction therapy with multiple doses of rituximab on the subsequent efficacy and toxicity of anti-CD20 radioimmunotherapy is unknown. We evaluated a novel protocol using 4 weekly infusions of 375 mg/m(2) rituximab followed by 2 fractions of (131)I-rituximab, preceded by a 100-mg/m(2) predose of rituximab, in relapsed indolent B-cell lymphoma. Induction therapy with rituximab significantly increased the effective half-life of (131)I-rituximab (P = .003) and high serum levels of rituximab after induction therapy correlated with increased effective half-life of the radioimmunoconjugate (P = .009). Patients with large tumor burdens experienced significant increases in the effective half-life of (131)I-rituximab between delivery of the first and second fractions (P = .007). Induction therapy with multiple doses of rituximab did not appear to compromise the clinical efficacy or increase toxicity of subsequent (131)I-rituximab radioimmunotherapy. The overall response rate was 94%, with complete response rate 50%. The median time to progression was 20 months, significantly longer than for the last qualifying chemotherapy (P = .001). Fractionation of (131)I-rituximab allowed cumulative whole-body doses of more than 120 cGy, approximately 60% greater than those previously achieved with a single administration of a murine radioimmunconjugate, to be delivered without significant hematologic toxicity.

Palliation of bone metastases in prostate cancer. Hemibody irradiation or strontium-89?

The palliation of bone pain is a common clinical problem once metastatic prostate cancer has escaped from hormonal control. This retrospective study compares the results of treatment using hemibody irradiation (HBI) at the Royal Marsden Hospital (27 cases) with isotope therapy using the bone-seeking isotope strontium-89 (89Sr) at Southampton General Hospital (51 cases). Prior to analysis patients were matched for potential prognostic factors (performance status, bone scan extent of disease, age, histology and duration of hormone response) to minimize the effect of treatment selection bias. Pain control assessed at 3 months was similar for HBI and matched 89Sr cases, with 63% and 52% respectively showing some benefit. Median survival was similar for these groups at 20 and 21 weeks respectively. The unmatched 89Sr group, which had more favourable prognostic factors, had a better outcome with 96% showing improvement in pain and with a median survival of 59 weeks. Subsequent univariate analysis demonstrated that performance status and extent of disease on bone scan were of overriding importance in determining outcome. Transfusion requirements were higher for the HBI group than for the matched 89Sr group (50% and 25% respectively) but other bone marrow toxicity was similar. Despite routine anti-emetic therapy 37% of patients treated with HBI had some nausea or vomiting. Although expensive, 89Sr appears as effective a treatment option as HBI. Response is most likely with either approach when patients have a good performance status and a limited extent of disease.

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biotherapy

aDepartment of Internal Medicine, Endocrine Unit, Uppsala University Hospital, Uppsala, Sweden; bDepartments of Internal Medicine and Endocrinological and Metabolic Sciences, University of Genoa, Genoa, Italy; cG. Genimatas Hospital, Athens, Greece; dDepartment of Surgery, Rigshospitalet, Copenhagen, Denmark; eNetherlands Cancer Centre, Amsterdam, The Netherlands; fDepartment of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charite-Universitatsmedizin Berlin, Berlin, Germany