How smart is peptide receptor radionuclide therapy of neuroendocrine tumors especially in the salvage setting? The clinician’s perspective

Abstract

In the recent past there has been a substantial growth in the understanding of cancer biology with a consequent opening of a Pandora's box of scientific knowledge and advance in the biological perception of the disease. Paradoxically, this indepth, sun-burst-like knowledge has fogged the several established management protocols rather than clearing the doubts. The 'knowledge' that the hitherto established and proven therapeutics do not only target cancer cells but also 'normal' cells has shifted the attention more onto toxicity.To overcome the toxicity related to the 'generalized' treatment approach medical scientists across the world have gleefully (and possibly gullibly) accepted targeted therapy and the 'theranostic concept'. This evolved approach should eventually, supposedly, tackle the intelligent cancer cells which have successfully challenged 'Darwin's Theory of Evolution' by replacing the normal 'chosen' cells of the best creation and evolved creature of nature. Paradoxically survival of the fittest in this instance leads to extinction of the organism! This has generated a new intellectual theocracy whereby new knowledge has been embraced with almost religious zeal and rigorous assessment diminished in the face of fervor as we seek to reverse a biological Darwinian conundrum. As a consequence a note of caution needs to be placed here because the knowledge of the scientific medical community about neoplasia is juvenile, whereas the cancer cells, by the time they are diagnosed, are evolved and are up to 40 years old [1]. In effect they are the adults in the evolutionary cascade, and thereby not only challenging but also winning the natural selection process which decrees that "growth and spread is to the strongest". In consideration of such (very old) philosophy, direct implementation of the promising but not matured theranostic concept in a patient with aggressive cancer, with a relatively shorter life expectancy, might not have a significant adverse influence on an already poor quality of life. The problem however achieves a different degree of proportionality when the concept is translated to the treatment of an indolent tumor associated with a relatively good overall survival following the initial diagnosis. Neuroendocrine tumors (NETs) are a group of such tumors, whose incidence and prevalence appear to be increasing at an alarming rate, partially due to highly advanced diagnostic methods and raised awareness [2].Nuclear medicine is the first exponent of the theranostic concept dating back to early 1950s. The classical example is the use of radioiodine for diagnosis and therapy of various benign and malignant thyroid diseases targeting the thyroid cell sodium iodine transporters. A similar analogy is the identification of the overexpression of somatostatin receptors on NETs. This has enabled nuclear medicine physicians to deal with the complex and heterogeneous tumor by addressing the neoplastic overexpression of particular subclasses of somatostatin receptor. Thus somatostatin receptor-based molecul...

Peptide Receptor Radionuclide Therapy and the Treatment of Gastroentero-pancreatic Neuroendocrine Tumors: Current Findings and Future Perspectives

“…Another report showed that long PFS after the initial treatment with PRRT predicts a prolonged PFS after salvage therapy [51], and argued that PRRT with 177 Lu-octreotate in the retreatment setting is a safe and effective option in patients with metastatic GEP-NETs. For these reasons, retreatment seems a good option for patients who responded well after the initial cycles of PRRT [52]. This novel and important concept of salvage therapy of NET needs to be tested in large, prospective, and multi-center trials to contribute to evidencebased findings.…”

Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

“…In fact, reported experiences vary widely in terms of number of cycles and injected activity in both treatment and retreatment settings. 26 – 30 …”

High Interobserver Agreement for the Standardized Reporting System SSTR-RADS 1.0 on Somatostatin Receptor PET/CT

“…Of note, the recent Food and Drug Administration approval of the most commonly used theranostic twin 68 Ga-/ 177 Lu-DOTATATE will most likely lead to an increased initiation of SSTR-targeting peptide receptor radionuclide therapies (PRRT) all over the U.S. (6). As such, it is anticipated that endoradiotherapy for NEN will experience an increasing use (7,8). Accurate scan interpretation, however, is of utmost importance to triage patients for theranostic interventions (9), to guide the referring oncologist to handle challenging cases or to recommend appropriate work-up (e.g.…”