Issuu Medical Chronicle February 2020: www.issuu.com/newmediamedical/docs/mc_feb_2020_issuu/32
With the World Cancer Day and International Childhood Cancer Day in February this year we focus a little on childhood malignancy and where Nuclear Medicine plays a role in the management of these malignancies and shows future promise in refractory disease.
Background:
Childhood cancer is a completely different subset of oncology and rightly so given that there is very little in common between the malignancies of children versus those found in adults. For starters adult malignancy has a high correlation with lifestyle with lung and respiratory tract cancers accounting for the second leading cause of death after cardiovascular disease (also lifestyle related).
In the US, while childhood malignancy accounts for the 3rd most common cause of death in children, given that first and second place are held by motor vehicle accidents and firearm-related incidents, childhood malignancy takes first place in non-trauma related cause of death and none of the malignancies found in children aged 0-19 years are related to lifestyle, but rather genetic predisposition and aberrant progenitor cell mutations. In a perfect world we would expect similar incidences internationally, but childhood malignancy is far exceeded by largely preventable cause of death with the vast majority of these occurring in developing nations. Overall however leukaemia, lymphoma and brain malignancies account for the most common malignancies of childhood.
| Birth – 14 years | 14-19 years | |||
| % of Cases | % 5-year survival | % of Cases | % 5-year survival | |
| All ICCC groups combined | 83.4 | 84.6 | ||
| Lymphoid leukaemia | 22% | 90.8 | 7% | 73.8 |
| Acute myeloid leukaemia | 4% | 66.4 | 4% | 64.2 |
| Hodgkin lymphoma | 3% | 97.8 | 12% | 96.1 |
| Non‐Hodgkin lymphoma (including Burkitt lymphoma) | 5% | 90.2 | 7% | 89.1 |
| Central nervous system neoplasms | 26% | 72.9 | 21% | 77.9 |
| Neuroblastoma & other peripheral nervous cell tumours | 6% | 80.2 | <1% | 54.1 † |
| Retinoblastoma | 2% | 95.2 | <1% | — |
| Nephroblastoma & other nonepithelial renal tumours | 5% | 92.7 | <1% | — |
| Hepatic tumours | 2% | 80.4 | <1% | 52.4 † |
| Hepatoblastoma | 1% | 84.6 | <1% | — |
| Osteosarcoma | 2% | 69.6 | 3% | 65.7 |
| Ewing tumour & related bone sarcomas | 1% | 77.7 | 2% | 64.3 |
| Rhabdomyosarcoma | 3% | 70.3 | 1% | 46.2 |
| Germ cell & gonadal tumours | 3% | 91.6 | 11% | 92.6 |
| Thyroid carcinoma | 2% | 99.7 | 11% | 99.2 |
| Malignant melanoma | 1% | 94.9 | 4% | 94 |
Siegel, R.L., Miller, K.D. and Jemal, A. (2019), Cancer statistics, 2019. CA A Cancer J Clin, 69: 7-34.
Nuclear Medicine’s role in childhood cancer management – Hybrid-/Molecular Imaging and Theragnostics:
Overall 5-year survival rates in children tend to be relatively high. This is largely due to early detection and increased clinical sensitivity for these conditions. Nuclear Medicine has both an imaging role to play (staging, re-staging and follow-up) and therapeutic role in refractory malignancies.
Hybrid imaging techniques:
F18-FDG PET-CT has largely become the staging imaging modality of choice in children with lymphoma, various sarcomas, certain germ-cell tumours and malignant melanoma, the latter of which is increasing remarkable in incidence in South Africa. F18-FDG being a radio-active glucose-analogue reflects the metabolic activity of these malignancies, oftentimes detected long before conventional diagnostic radiology would detect a change in size. The more aggressive or de-differentiated the malignancy (and the more reliant on first-path anaerobic glucose metabolism a malignancy is) the greater the increased tracer accumulation of F18-FDG. Inversely, due to high cellular turnover, the response to conventional therapy in these malignancies tends to be rather stark and clinical decisions can be made relatively early in the treatment process using F18-FDG PET-CT especially in lymphoma management. The interim PET-CT is of particular benefit here where management can be altered is a suitable initial response to therapy is not demonstrated after 2 cycles of initial chemotherapy. Often there is already little to no metabolic uptake after 2-cycles in lymphomatous patients and they can safely continue to regime completion. On conventional radiology lesions may be seen for months after treatment completion as anatomical resolution lags far behind physiological resolution.
While conventional Nuclear Medicine techniques have been used and are still used in other malignancies e.g. I-123 MIBG and Thyroid scanning for Neuroblastoma, other neuroendocrine and Thyroid malignancies respectively, modern techniques include similar fused-hybridization of whole body tomographic three-dimensional Nuclear Medicine images with CT scan images has greatly improved the overall performance of these studies with better images reconstruction, detection and localization of lesions.
Newer agents e.g. Ga68-DOTATATE PET-CT further improves upon detectability of neuroendocrine tumours expressing somatostatin receptors and certain brain tumours and both MIBG and DOTATATE affords us two opportunities to treat neuroblastoma and neuroendocrine tumours respectively by replacing the gamma-emitting imaging isotope i.e. I-123 and Ga68 with beta-emitters e.g. Lu-177 – coined “Theragnostics”.
Theragnostic medicine:
In a nutshell theragnosis involves seeing a malignancy through use of a specific pharmaceutical agent targeting that cell line (coupled to an imaging isotope) and then treating that condition using the same pharmaceutical but attached to beta- or alpha-emitting isotope—large particles that possess high energy and subsequent killing power but over extremely small distances thus sparing normal body tissue from damage. This targeted radionuclide therapy is rather disease-specific and in turn patient-tailored. This principle of identifying new histology-specific cellular targets to image and then take these killer-isotopes to started with thyroid cancer (I-131 imaging and treatment) and expanded to neuroendocrine imaging (MIBG and octreotide derivatives e.g. DOTATATE). To date, except for thyroid cancer perhaps, these therapies are still mostly used for refractory treatment. But results,
researched in adult populations, have demonstrated remarkable responses especially in the Lu-177 DOTATATE somatostatin receptor targeting, the youngest member of the Theragnostic family.
Radio-immunotherapy offers new and novel ways of delivering radio-isotope beta-emitters to their target using disease-specific antibodies. These are largely still investigational, but the future holds promise as more of these types of duel-purpose disease-specific agents are developed and evidence-advocated, for their earlier use in the disease process.
With the improvement in lesion detection through improved technology and hybridization of imaging and with development of disease-specific tracers and targeted radionuclide therapies the future of treating the previously untreatable and refractory looks promising.
