Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE; Differences in Tumor Dosimetry, Vascularity and Lesion Metrics in Pancreatic and Small Intestinal Neuroendocrine Neoplasms

Jahn, Ulrika; Ilan, Ezgi; Sandström, Mattias; Lubberink, Mark; Garske-Román, Ulrike; Sundín, Anders

doi:10.3390/cancers13050962

Cited by 29 publications

(25 citation statements)

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“…Thus the study of radiation toxicity is a core component of radiation oncology training, and practices are guided by an extensive and evolving literature on factors associated with toxicity probability 3,4 . The study of radiation toxicity is also pertinent to nuclear medicine and the evolving field of “theranostics,” in which radionuclides linked to targeting agents have both diagnostic and therapeutic utility, although dosimetric studies on efficacy and toxicity have been limited 5,6 …”

Section: Introductionmentioning

confidence: 99%

Radiation therapy‐associated toxicity: Etiology, management, and prevention

Wang

Tepper

2021

CA A Cancer J Clinicians

155

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Radiation therapy (RT) is a curative treatment for many malignancies and provides effective palliation in patients with tumor-related symptoms. However, the biophysical effects of RT are not specific to tumor cells and may produce toxicity due to exposure of surrounding organs and tissues. In this article, the authors review the clinical context, pathophysiology, risk factors, presentation, and management of RT side effects in each human organ system. Ionizing radiation works by producing DNA damage leading to tumor death, but effects on normal tissue may result in acute and/or late toxicity. The manifestation of toxicity depends on both cellular characteristics and affected organs' anatomy and physiology. There is usually a direct relationship between the radiation dose and volume to normal tissues and the risk of toxicity, which has led to guidelines and recommended dose limits for most tissues. Side effects are multifactorial, with contributions from baseline patient characteristics and other oncologic treatments. Technological advances in recent decades have decreased RT toxicity by dramatically improving the ability to deliver RT that maximizes tumor dose and minimizes organ dose. Thus the study of RT-associated toxicity is a complex, core component of radiation oncology training that continues to evolve alongside advances in cancer management. Because RT is used in up to one-half of all patients with cancer, an understanding of its acute and late effects in different organ systems is clinically pertinent to both oncologists and nononcologists.

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Section: Introductionmentioning

confidence: 99%

Radiation therapy‐associated toxicity: Etiology, management, and prevention

Wang

Tepper

2021

CA A Cancer J Clinicians

155

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“…A protocol of 4 cycles of 7.4 GBq administered at an interval of approximately 2 months has been proven safe and effective (1)(2)(3). Since the therapy is based on ionizing radiation, the likelihood of tumor response is expected to be related to the absorbed dose (AD) (4)(5)(6)(7)(8)(9)(10)(11). Current data indicate that the tumor ADs vary considerably between patients, from a few grays to nearly 200 Gy (8, 9,[12][13][14][15].…”

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confidence: 99%

“…Most studies on tumor dosimetry have focused on a single lesion in each patient, and there is currently limited data on the variation in AD between metastases within patients, and variation across treatment cycles. Such information is important to advance the understanding of how the AD delivery is currently fractionated, and to inform the design of alternatives to the standard administration scheme where the activity per cycle, number of cycles, or time between cycles are modified (4,(7)(8)(9)11,16).…”

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confidence: 99%

Dosimetric Quantities in Neuroendocrine Tumors over Treatment Cycles with¹⁷⁷Lu-DOTATATE

et al. 2021

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Tumor dosimetry was performed for 177 Lu-DOTA-TATE with the aims of better understanding i) the range and variation of the tumor absorbed doses (ADs), ii) how different dosimetric quantities evolve over the treatment cycles, and iii) whether this evolution differs depending on the tumor grade. Such information is important for radiobiological interpretation and may inform the design of alternative administration schemes. Methods: Data come from 41 patients with neuroendocrine tumors (NETs) of grade 1 (n=23) or 2 (n=18), that had received between 2 and 9 treatment cycles. Dosimetry was performed for 182 individual lesions, giving in total 880 individual AD assessments across all cycles. Hybrid planar-SPECT/CT imaging was used, including quantitative SPECT reconstruction, voxel-based absorbed-dose-rate calculation, semiautomatic image segmentation, and partial-volume correction. Linear mixed-effect models were used to analyze changes over cycles in tumor ADs, absorbed-dose rates and activity concentrations at day-1, effective half-times, and tumor volumes. Tumors smaller than 8 ml were excluded from analyses. Results:Tumor ADs ranged between 2 and 77 Gy per cycle. On average the AD decreased over the cycles, with significantly different rates (p < 0.05) for grade 1 and 2 NETs of 6% and 14% per cycle, respectively. The absorbed-dose rates and activity concentrations at day-1 decreased by similar amounts. The effective halftimes were less variable but shorter for grade 2 than grade 1 (p < 0.001). For grade 2 NETS the tumor volumes decreased, with a similar tendency in grade 1. Conclusions: The tumor AD, absorbed-dose rate and activity uptake decrease, in parallel with tumor volumes, between 177 Lu-DOTA-TATE treatment cycles, particularly for grade 2 NETs. The effective half-times vary less but are lower for grade 2 than grade 1 NETs. These results may indicate the development of radiation-induced fibrosis and could have implications for the design of future treatment and dosimetry protocols.

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“…PRRT absorbed dose may play a role in predicting the response. Both for small intestine and PanNETs, a dose–response relationship was found between the absorbed dose and tumor shrinkage, which was more pronounced in PanNET ( 48 ). Histological parameters have also been proposed as predictors of treatment response.…”

Section: Resultsmentioning

confidence: 94%

New Insights in PRRT: Lessons From 2021

et al. 2022

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Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs has been used for over two decades for the treatment of well-differentiated neuroendocrine tumors (NETs), and the publication of the NETTER-1 trials has further strengthened its clinical use. However, many aspects of this treatment are still under discussion. The purpose of this review is to collect and discuss the new available evidence, published in 2021, on the use of 177Lu-Oxodotreotide (DOTATATE) or 90Y-Edotreotide (DOTATOC) in adult patients with NETs focusing on the following hot topics: 1) PRRT use in new clinical settings, broaden its indications; 2) the short- and long-term safety; and 3) the identification of prognostic and predictive factors. The review suggests a possible future increase of PRRT applications, using it in other NETs, as a neoadjuvant treatment, or for rechallenge. Regarding safety, available studies, even those with long follow-up, supported the low rates of adverse events, even though 1.8% of treated patients developed a second malignancy. Finally, there is a lack of prognostic and predictive factors for PRRT, with the exception of the crucial role of nuclear imaging for both patient selection and treatment response estimation.

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Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE; Differences in Tumor Dosimetry, Vascularity and Lesion Metrics in Pancreatic and Small Intestinal Neuroendocrine Neoplasms

Cited by 29 publications

References 30 publications

Radiation therapy‐associated toxicity: Etiology, management, and prevention

Radiation therapy‐associated toxicity: Etiology, management, and prevention

Dosimetric Quantities in Neuroendocrine Tumors over Treatment Cycles with¹⁷⁷Lu-DOTATATE

New Insights in PRRT: Lessons From 2021

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Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE; Differences in Tumor Dosimetry, Vascularity and Lesion Metrics in Pancreatic and Small Intestinal Neuroendocrine Neoplasms

Cited by 29 publications

References 30 publications

Radiation therapy‐associated toxicity: Etiology, management, and prevention

Radiation therapy‐associated toxicity: Etiology, management, and prevention

Dosimetric Quantities in Neuroendocrine Tumors over Treatment Cycles with177Lu-DOTATATE

New Insights in PRRT: Lessons From 2021

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Dosimetric Quantities in Neuroendocrine Tumors over Treatment Cycles with¹⁷⁷Lu-DOTATATE