Spectrum and surgical outcomes of gastrointestinal stromal tumours.

BACKGROUND: Surgery and imatinib are the mainstays of the management of gastrointestinal stromal tumours (GIST). This study aimed to analyse the outcomes in the management of GIST utilising surgery and imatinib. METHODS: Progression-free survival (PFS) and overall survival (OS) were analysed in relation to imatinib therapy, location of tumour, resection margins, type and extent of surgery. Imatinib was administered in the neoadjuvant (maximum 12 months) and adjuvant setting (minimum 36 months) and until disease progression or drug intolerance. Disease response was assessed with the Choi criteria. Survival analysis included calculation of PFS, OS and Kaplan-Meier curves. RESULTS: Sixty-two patients were reviewed and 56 had surgical resection. The median age (range) was 58.5 (8-95) years. The median PFS and OS (IQR) was 24.0 (0-52.0) and 41.0 (15.0-74.0) months, respectively. Thirty-nine (70%) patients were treated with imatinib, with 21 of these in a neoadjuvant setting. In the patients undergoing surgery, surgical margins were R0, R1 and R2 in 41 (75%), eight (15%) and six (11%) respectively. There was an insignificant difference in the overall survival in these three groups. For those having liver metastasectomy and multivisceral resection, the PFS and OS were 32.5 (17.5-60.3) and 28.5 (5.75-49.8) (p = 0.008), and 96.0 (58.5-116) and 80 (50.5-92.3) months (p = 0.033), respectively. CONCLUSION: Whilst the numbers were small, certain trends were observed. Surgery in combination with imatinib offers survival benefit in patients undergoing R0, R1, R2, liver metastases and multivisceral resections.

The Association between Tumour Markers and Meta-iodobenzylguanidine Scans in South African Children with High-risk Neuroblastoma.

AIMS: Diagnostic and post-induction 123I-meta-iodobenzylguanidine (123I-mIBG) scans have prognostic significance in the treatment of neuroblastoma, but data from low- and middle-income countries are limited due to resource constraints. The aim of this study was to determine the association between neuroblastoma-associated tumour markers (lactate dehydrogenase [LDH], ferritin and MYCN amplification) and 123I-mIBG scans (modified Curie scores and metastatic disease patterns) in predicting complete metastatic response rates (mCR) and overall survival. MATERIALS AND METHODS: Two hundred and ninety patients diagnosed with high-risk neuroblastoma in South Africa between January 2000 and May 2018 and a subanalysis of 78 patients with diagnostic 123I-mIBG scans were included. Data collection included LDH, ferritin and MYCN amplification at diagnosis. Two nuclear physicians independently determined the modified Curie scores and pattern of distribution for each diagnostic and post-induction 123I-mIBG scans with high inter-rater agreement (r = 0.952) and reliability (K = 0.805). The cut-off values for the diagnostic and post-induction modified Curie scores of ≥7.0 (P = 0.026) and 3 (P = 0.009), respectively, were generated. The association between the tumour markers and the modified Curie score of the 123I-mIBG scans was determined using post-induction mCR and 2-year overall survival. RESULTS: Diagnostic LDH (P < 0.001), ferritin (P < 0.001) and the diagnostic modified Curie scores (P = 0.019) significantly predicted mCR. Only ferritin correlated with diagnostic modified Curie scores (P = 0.003) but had a low correlation coefficient of 0.353. On multivariable analysis, the only significant covariate for 2-year overall survival at diagnosis was LDH <750 U/l (P = 0.024). A post-induction chemotherapy modified Curie score ≤3.0 had a 2-year overall survival of 46.2% compared with 30.8% for a score >3.0 (P = 0.484). CONCLUSION: LDH, ferritin and the diagnostic 123I-mIBG scans significantly predicted mCR, but only LDH predicted 2-year overall survival. Ferritin and the modified Curie scores correlated with each other. MYCN amplification neither correlated with any aspect of the 123I-mIBG scans nor significantly predicted mCR or 2-year overall survival. LDH and ferritin are therefore appropriate neuroblastoma tumour markers to be used in low- and middle-income countries with limited or no access to mIBG scans and/or MYCN amplification studies.

South African guidelines for receptor radioligand therapy (RLT) with Lu-177-PSMA in prostate cancer.

BACKGROUND: Prostate cancer is an important cause of morbidity and mortality in South Africa, as it is in the rest of the world. In African men, however, prostate cancer tends to follow a more aggressive course when compared to their European counterparts. This is attributed to a plethora of diverse factors of which an underlying genetic component has been shown to be an important aspect. Such differences highlight the need for individualised therapy and for local guidelines. The aim of this guideline is to aid nuclear physicians and other clinicians who manage patients with prostate cancer in the correct identification and treatment of patients who are likely to benefit from receptor radioligand therapy. RECOMMENDATIONS: There are a multitude of treatment modalities available for the treatment of prostate cancer and these therapies may be required at various time points during the course of the disease in any individual patient. A multidisciplinary approach is crucial in deciding which therapy, or combination of therapies, would be most advantageous at particular time points. The multidisciplinary team should include a urologist, oncologist and nuclear medicine physician as a minimum, and should ideally also involve a palliative/pain specialist, a dietician and a psychologist. CONCLUSION: Treatment with 177Lu-PSMA has emerged as a promising systemic modality, which involves the delivery of targeted radiation therapy in the form of ß-particles to sites of tumour tissue. Therapy is provided on an outpatient basis, is well tolerated with relatively few side effects and has a positive effect on overall survival and quality of life. At present, it is used mostly in the setting of advanced, castrate-resistant cancer. Patients are selected (amongst other criteria) based on the prior PSMA-based SPECT/PET/CT imaging (99mTc-,68Ga- or 18F-PSMA), which should demonstrate sufficient receptor expression in order to consider PSMA-based targeted radionuclide therapy. Such imaging of an intended target prior to its therapeutic targeting is known as a theranostic approach.

The College of Nuclear Physicians of South Africa Practice Guidelines on Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumours.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) for metastatic or inoperable neuroendocrine tumours (NETs) is a systemic therapy which targets somatostatin receptors overexpressed by differentiated NETs for endoradiotherapy. This guideline has been compiled by the College of Nuclear Physicians of the Colleges of Medicine of South Africa, with endorsement by the South African Society of Nuclear Medicine and the Association of Nuclear Physicians to guide Nuclear Medicine Physicians in its application during the management of these patients. RECOMMENDATIONS: Patients with well- to moderately-differentiated NETs should be comprehensively worked-up to determine their suitability for PRRT. Treatment should be administered by a Nuclear Medicine Physician in a licensed, appropriately equipped and fully staffed facility. Patient monitoring is mandatory during and after each therapy cycle to identify and treat therapy-related adverse events. Patients should also be followed-up after completion of therapy cycles for monitoring of long-term toxicities and response assessment. CONCLUSION: PRRT is a safe and effective therapy option in patients with differentiated NETs. Its use in appropriate patients is associated with a survival benefit.

Blood-brain barrier integrity in a zolpidem-responder patient.

A 27-year-old neurologically disabled but fully conscious male zolpidem-responder patient was investigated for blood brain barrier (BBB) dysfunction 5 years after a traumatic brain injury. A baseline single-photon emission computed tomography (SPECT) technetium-99m-labelled hexamethylpropylene amine oxime (99mTcHMPAO) brain scan was performed and the patient was administered 10 mg zolpidem daily. The patient was rescanned 2 weeks later when 99mTcHMPAO was injected 1 hour after zolpidem application. SPECT technetium-99m-labelled diethylene-triamine-pentacetic acid (99mTcDTPA) BBB scans were also performed before and after zolpidem treatment. There was decreased uptake of 99mTcHMPAO in the left frontoparietal brain region, left temporal region and left thalamus on baseline scanning; this improved within 1 hour after zolpidem treatment at the follow-up scan. The 99mTcDTPA scan remained within normal limits before and after zolpidem treatment. The patient's neurological disabilities, especially coordination, speech and gait, improved markedly. The Barthel Index remained normal, but the Tinetti falls efficacy scale improved from 21/100 to 15/100. The results implied that the underlying cause for the patient's long-term neurological disability and brain suppression was not due to a long-term dysfunctional BBB.

Radionuclide therapy and integrated protocols for bone metastases.

Bone metastases are responsible for most of the morbidity and mortality associated with solid malignant tumors, occurring in about 65-70% of the patients with advanced breast or prostate cancer. The pathophysiology of skeletal metastasis is a complex process that involves several biologic process leading to cellular invasion, adhesions and stimulation of osteoclasts and osteoblasts with the mediation of several factors including cytokines, serine proteases and tumor-derived factors. The clinical management of pain from bone metastasis, which is mostly due to indirect stimulation of sensory nerve endings by cytokines and other biologically-active compounds released locally in response to the presence of tumor cells in the bone marrow, includes several options that can be used either alone or in varying combinations, such as analgesic drugs, chemo- or hormonal therapy, bisphosponates, external beam radiation therapy, and surgery. Bone-seeking radiopharmaceuticals play an important role in the treatment of pain caused by multiple blastic or mixed-type skeletal lesions; they have in general a favorable toxicity profile and a high rate of overall clinical benefit, although they may differ in terms of duration of pain palliation and suitability for repeat treatments. The palliative effect can be attributed to the radiation targeted to the bone marrow space, and the overall average response ranges between about 45-80%, with complete response in 10-30% of the cases. In selected clinical conditions, radionuclide therapy can also constitute an effective systemic treatment beyond bone pain palliation, and a synergistic anti-tumour effect can be expected by the combination with other agents, such as chemotherapy or bisphosphonates. This review summarizes the current experience with bone-seeking radiopharmaceuticals used for bone pain palliation, focusing on indications, patients' selection, efficacy and toxicity. Finally, the available data on combination therapies showing encouraging results as to potential anti-tumor efficacy are also reviewed.