68Ga-DOTATATE PET/CT parameters predict response to peptide receptor radionuclide therapy in neuroendocrine tumours

Sharma, Rohini; Wang, Wai Meng; Yusuf, Salim; Evans, Joanne; Ramaswami, Ramya; Wernig, Florian; Frilling, Andrea; Mauri, Francesco; Al‐Nahhas, Adil; Aboagye, Eric O.; Barwick, Tara

doi:10.1016/j.radonc.2019.09.003

Cited by 79 publications

(85 citation statements)

References 26 publications

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“…Synergetic mechanism of action on PI3K/AKT/mTOR pathway [142] is one probable reason of combing SSAs and everolimus that could be seen in the result from RADIANT-1 confirmed in phase II EVERLAR study [22,143]. There were some promising results regarding RR especially in PanNETs from couple of trials exploring the combination of metronomic chemotherapy (cepecitabine or temozolomide) with Bevacizumab and SSAs [144,145]. In the study with Temozolomide induced depletion of MGMT by prolonged administration of the cytotoxic drug is discussed to be potential reason for the observed responses, but this needs to be further explored [144].…”

Section: Challenges In the Sequencing Of Therapymentioning

confidence: 96%

“…There were some promising results regarding RR especially in PanNETs from couple of trials exploring the combination of metronomic chemotherapy (cepecitabine or temozolomide) with Bevacizumab and SSAs [144,145]. In the study with Temozolomide induced depletion of MGMT by prolonged administration of the cytotoxic drug is discussed to be potential reason for the observed responses, but this needs to be further explored [144].…”

Section: Challenges In the Sequencing Of Therapymentioning

confidence: 99%

“…In addition, more sensitive and specific nuclear imaging techniques visualising SSTR expression (111In-SPECT, 68-GaPET/CT) may be used for the diagnosis and assessing response to therapy beyond RECIST. Combining different imaging technologies and assessment of disease with cross-sectional and molecular imaging is increasingly relevant for patients with PanNETs, not only for treatment selection following a theranostic approach, but also for assessment of response to therapy [143,144]. The development of novel radiological assessment strategies may also be of help (i.e., alternative cut-off definitions for assessment of response [145] or assessment of Tumour Growth Rate (TGR) [123,146,147].…”

Section: Ongoing Challengesmentioning

confidence: 99%

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Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

Megdanova-Chipeva

Lamarca

Backen

et al. 2020

Cancers

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Pancreatic neuroendocrine tumours (PanNETs) are rare diseases and a good example of how research is not only feasible, but also of crucial importance in the scenario of rare tumours. Many clinical trials have been performed over the past two decades expanding therapeutic options for patients with advanced PanNETs. Adequate management relies on optimal selection of treatment, which may be challenging for clinicians due to the fact that multiple options of therapy are currently available. A number of therapies already exist, which are supported by data from phase III studies, including somatostatin analogues and targeted therapies (sunitinib and everolimus). In addition, chemotherapy remains an option, with temozolomide and capecitabine being one of the most popular doublets to use. Peptide receptor radionuclide therapy was successfully implemented in patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumours, but with certain questions waiting to be solved for the management of PanNETs. Finally, the role of immunotherapy is still poorly understood. In this review, the data supporting current systemic treatment options for locally advanced or metastatic PanNETs are summarized. Strategies for treatment selection in patients with PanNETs based on patient, disease, or drug characteristics is provided, as well as a summary of current evidence on prognostic and predictive biomarkers. Future perspectives are discussed, focusing on current and forthcoming challenges and unmet needs of patients with these rare tumours.

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Section: Challenges In the Sequencing Of Therapymentioning

confidence: 96%

Section: Challenges In the Sequencing Of Therapymentioning

confidence: 99%

Section: Ongoing Challengesmentioning

confidence: 99%

See 1 more Smart Citation

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

Megdanova-Chipeva

Lamarca

Backen

et al. 2020

Cancers

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“…Concerning 68 Ga-DOTA-peptide PET, all studies assessed tumor standardized uptake value (SUV) as a quantitative parameter, to predict response to PRRT (see Table 2). Among eleven papers that analyze 68 Ga-PET, three papers did not find any significant result that attributes a predictive role to maximum SUV (SUV max ) during 68 Ga-PET ( [26,27,73]), two papers from the same group [80,81] identified other parameters besides SUV max , able to predict outcome of PRRT treatment, and six identified SUV max as a predictor of response to therapy [25,31,38,53,54,71]. All studies were performed on rather small NET series.…”

Section: Petmentioning

confidence: 99%

“…The authors also indicated a cut-off of 13.0, when considering single lesion SUV max , to give high sensitivity and specificity in prognosticating a favorable treatment response. Tumor to liver SUV ratio (SUV T/H ) and tumor to spleen SUV ratio SUV T/S were investigated as well, but neither SUV T/S or SUV T/H were predictive of response to PRRT [71]. A significant correlation between the ORR to PRRT and the 6 8 Ga-DOTANOC PET baseline SUV max was also found in the prospective trial conducted from [53], but p value was not reported.…”

Section: "Positive Studies"mentioning

confidence: 99%

PRRT: identikit of the perfect patient

Albertelli

Dotto

Dato

et al. 2020

Rev Endocr Metab Disord

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Peptide receptor radionuclide therapy (PRRT) has been strengthened since the publication of NETTER-1. Nevertheless, the correct positioning in the therapeutic algorithm is debated, and no optimal sequence has yet been standardized. Possible criteria to predict the response to PRRT in neuroendocrine tumors (NET) have been proposed. The aim of this review is to define the perfect identity of the eligible patient who can mostly benefit from this therapy. Possible predictive criteria which have been analysed were: primary tumor site, grading, tumor burden, FDG PET and 68Ga-PET uptake. Primary tumor site and 68Ga-PET uptake do not play a pivotal role in predicting the response, while tumor burden, FDG PET uptake and grading seem to represent predictive/prognostic factors for response to PRRT. The heterogeneity in trial designs, patient populations, type of radionuclides, previous therapies and measurement of outcomes, inevitably limits the strength of our conclusions, therefore care must be taken in applying these results to clinical practice. In conclusion, the perfect patient, selected by 68Ga-PET uptake, will likely have a relatively limited liver tumor burden, a ki67 index <20% and will respond to PRRT irrespective to primary tumor. Nevertheless, we have mostly prognostic than predictive factors to predict the efficacy of PRRT in individual patients, while a promising tool could be the NETest. However, to date, the identikit of the perfect patient for PRRT is a puzzle without some pieces and still we cannot disregard a multidisciplinary discussion of the individual case to select the patients who will mostly benefit from PRRT.

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Comparison of maximum likelihood and conventional PET scatter scaling methods for ¹⁸F‐FDG and ⁶⁸Ga‐DOTATATE PET/CT

et al. 2021

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Purpose We aim to quantify differences between a new maximum likelihood (ML) background scaling (MLBS) algorithm and two conventional scatter scaling methods for clinical PET/CT. A common source of reduced image quantification with conventional scatter corrections is attributed to erroneous scaling of the initial scatter estimate to match acquired scattered events in the sinogram. MLBS may have performance advantages over conventional methods by using all available data intersecting the subject. Methods A retrospective analysis was performed on subjects injected with 18F‐FDG (N = 71) and 68Ga‐DOTATATE (N = 11) and imaged using time‐of‐flight (TOF) PET/CT. The scatter distribution was estimated with single scatter simulation approaches. Conventional scaling algorithms included (a) tail fitted background scaling (TFBS), which scales the scatter to “tails” outside the emission support, and (b) absolute scatter correction (ABS), which utilizes the simulated scatter distribution with no scaling applied. MLBS consisted of an alternating iterative reconstruction with a TOF‐based ML activity image update allowing negative values (NEG‐ML) and nested loop ML scatter scaling estimation. Scatter corrections were compared using reconstructed images as follows: (a) normalized relative difference images were generated and used for voxel‐wise analysis, (b) liver and suspected lesion ROIs were drawn to compute mean SUVs, and (c) a qualitative analysis of overall diagnostic image quality, impact of artifacts, and lesion conspicuity was performed. Absolute quantification and normalized relative differences were also assessed with an 18F‐FDG phantom study. Results For human subjects 18F‐FDG data, Bland‐Altman plots demonstrated that the largest normalized voxel‐wise differences were observed close to the lower limit (SUV = 1.0). MLBS reconstructions trended towards higher scatter fractions compared to TFBS and ABS images, with median voxel differences across all subjects for TFBS‐MLBS measured at 1.7% and 7.6% for 18F‐FDG and 68Ga‐DOTATATE, respectively. For mean SUV analysis, there was a high degree of correlation between the scatter corrections. For 18F‐FDG, ABS scatter correction reconstructions trended towards higher liver mean SUVs relative to MLBS. The qualitative image analysis revealed no significant differences between TFBS and MLBS image reconstructions. For a uniformly filled relatively large 37 cm diameter phantom, MLBS produced the lowest bias in absolute quantification, while normalized voxel‐wise differences showed a trend in scatter correction performance consistent with the human subjects study. Conclusions For 18F‐FDG, MLBS is at least a valid substitute to TFBS, providing reconstructed image performance comparable to TFBS in most subjects but exhibiting quantitative differences in cases where TFBS is typically prone to inaccuracies (e.g., due to patient motion and CT‐based attenuation map truncation). Particularly for low contrast regions, quantification differs for ABS compared to MLBS and TFBS, and caution shoul...

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68Ga-DOTATATE PET/CT parameters predict response to peptide receptor radionuclide therapy in neuroendocrine tumours

Cited by 79 publications

References 26 publications

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

PRRT: identikit of the perfect patient

Comparison of maximum likelihood and conventional PET scatter scaling methods for ¹⁸F‐FDG and ⁶⁸Ga‐DOTATATE PET/CT

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68Ga-DOTATATE PET/CT parameters predict response to peptide receptor radionuclide therapy in neuroendocrine tumours

Cited by 79 publications

References 26 publications

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs)

PRRT: identikit of the perfect patient

Comparison of maximum likelihood and conventional PET scatter scaling methods for 18F‐FDG and 68Ga‐DOTATATE PET/CT

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Comparison of maximum likelihood and conventional PET scatter scaling methods for ¹⁸F‐FDG and ⁶⁸Ga‐DOTATATE PET/CT