Introduction Tumor growth rate (TGR; percent size change per month [%/m]) is postulated to be an early radiological biomarker to overcome limitations of RECIST. This study aimed to assess the impact of TGR in neuroendocrine tumors (NETs) and potential clinical and therapeutic applications. Materials and Methods Patients (pts) with advanced grade (G) 1/2 NETs from the pancreas or small bowel initiating systemic treatment (ST) or watch and wait (WW) were eligible. Baseline and follow‐up scans were retrospectively reviewed to calculate TGR at pretreatment (TGR0), first follow‐up (TGRfirst), and 3(±1) months of study entry (TGR3m). Results Out of 905 pts screened, 222 were eligible. Best TGRfirst (222 pts) cutoff was 0.8 (area under the curve, 0.74). When applied to TGR3m (103 pts), pts with TGR3m <0.8 (66.9%) versus TGR3m ≥ 0.8 (33.1%) had longer median progression‐free survival (PFS; 26.3 m; 95% confidence interval [CI] 19.5–32.4 vs. 9.3 m; 95% CI, 6.1–22.9) and lower progression rate at 12 months (7.3% vs. 56.8%; p = .001). WW (vs. ST) and TGR3m ≥ 0.8 (hazard ratio [HR], 3.75; 95% CI, 2.21–6.34; p < .001) were retained as factors associated with a shorter PFS in multivariable Cox regression. TGR3m (HR, 3.62; 95% CI, 1.97–6.64; p < .001) was also an independent factor related to shorter PFS when analysis was limited to pts with stable disease (81 pts). Out of the 60 pts with TGR0 data available, 60% of pts had TGR0 < 4%/month. TGR0 ≥ 4 %/month (HR, 2.22; 95% CI, 1.15–4.31; p = .018) was also an independent factor related to shorter PFS. Conclusion TGR is an early radiological biomarker able to predict PFS and to identify patients with advanced NETs who may require closer radiological follow‐up. Implications for Practice Tumor growth rate at 3 months (TGR3m) is an early radiological biomarker able to predict progression‐free survival and to identify patients with advanced neuroendocrine tumors who may require closer radiological follow‐up. It is feasible to calculate TGR3m in clinical practice and it could be a useful tool for guiding patient management. This biomarker could also be implemented in future clinical trials to assess response to therapy.

Purpose: Tumor growth rate (TGR) represents the percentage change in tumor volume per month (%/m). Previous results from the GREPONET study showed that TGR measured after 3 months (TGR 3m ) of starting systemic treatment (ST) or watch and wait (WW) was an early biomarker predicting progression-free survival (PFS) in neuroendocrine tumors (NET).Experimental Design: Patients from 7 centers with advanced grade (G) 1/2 NETs from the pancreas (P)/small bowel (SB) initiating ST/WW were eligible. Computed tomography (CT)/MRI performed at prebaseline, baseline, and 3 (AE1) months of study entry were retrospectively reviewed. Aim-1: explore treatment-induced changes in TGR (DTGR 3m-BL ; paired T test), and Aim-2: validate TGR 3m (<0.8%/m vs. !0.8%/m) as an early biomarker in an independent cohort (Kaplan-Meier/Cox regression).Results: Of 785 patients screened, 127 were eligible. Mean (SD) TGR 0 and TGR 3m were 5.4%/m (14.9) and À1.4%/m (11.8), respectively. Mean (SD) DTGR 3m-BL paired-difference was À6.8%/m (19.3; P < 0.001). Most marked DTGR 3m-BL [mean (SD)] were identified with targeted therapies [À11.3%/m (4.7); P ¼ 0.0237] and chemotherapy [À7.9%/m (3.4); P ¼ 0.0261]. Multivariable analysis confirmed the absence of previous treatment (OR ¼ 4.65; 95% CI, 1.31-16.52; P ¼ 0.018) and low TGR 3m (continuous variable; OR 1.09; 95% CI, 1.01-1.19; P ¼ 0.042) to be independent predictors of radiologic objective response. When the multivariable survival analysis for PFS (Cox regression) was adjusted to grade (P ¼ 0.004) and stage (P ¼ 0.017), TGR 3m ! 0.8 (vs. <0.8) maintained its significance as a prognostic factor (P < 0.001), whereas TGR 0 and DTGR 3m-BL did not. TGR 3m ! 0.8%/m was confirmed as an independent prognostic factor for PFS [external validation; Aim-2; multivariable HR 2.21 (95% CI, 1.21-3.70; P ¼ 0.003)].Conclusions: TGR has a role as a biomarker for monitoring response to therapy for early identification of treatmentinduced changes and for early prediction of PFS and radiologic objective response.

IntroductionNeuroendocrine neoplasms including neuroendocrine tumors (NETs) are often diagnosed as primary disseminated or inoperable. In those cases, systemic extensive therapy is necessary, but radical treatment is unlikely. As described in the literature, in some selected cases, peptide receptor radionuclide therapy (PRRT) may be used as a first-line/neoadjuvant therapy that allows further successful surgery. Such treatment may enable a reduction of total tumor burden or allow a radical treatment which improves the final outcomes.AimThis study aims to assess whether neoadjuvant PRRT could be a treatment option for patients with initially unresectable NETs.MethodsAmong the group of 114 patients treated with PRRT between the years 2005 and 2020, in 32 cases, it was the first-line therapy, mainly due to massive disease burden at the time of diagnosis. Among them, nine patients received PRRT as the first-line treatment due to the primary inoperable tumors with the intention of preoperative reduction of the tumor size in order to allow for a surgical treatment.ResultsNeoadjuvant PRRT enabled surgery in four out of nine (45%) patients. Finally, in two out of four cases, the goal (radical surgery) has been achieved.ConclusionPRRT may be considered not only as a palliative but also as a neoadjuvant therapy in advanced, somatostatin-positive NETs that were initially inoperable.

Detection of neuroendocrine neoplasms (NENs) and monitoring of their response to therapy is still challenging due to huge heterogeneity of that group of tumors. Actually, NENs visualization is mainly based on molecular imaging while in the past it was relied on less effective structural imaging including CT and MRI. Molecular imaging techniques in combination with structural imaging (hybrid imaging), especially in patients with well-differentiated NENs, in addition to morphological provide the functional information about tumor which benefits in a more accurate patient management, including more sensitive visualization of primary tumors, more precise staging and better therapy follow-up.Overexpression of somatostatin receptors (SSTR) on NENs' cell membrane was a basis for development of somatostatin receptor scintigraphy (SRS) using single photon emission tomography SPECT, which is today a well-established standard in molecular imaging of NENs, and further imaging improvement in the field of positron emission tomography (PET). Use of hybrid imaging (SPECT/CT, PET/CT) increased sensitivity of examination, mainly resulting in better detection of small lesions.

Introduction: Tumor growth rate (TGR), percentage of change in tumor volume/month, has been previously identified as an early radiological biomarker for treatment monitoring in neuroendocrine tumor (NET) patients. We assessed the performance and reproducibility of TGR at 3 months (TGR 3m ) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability. Methods: Baseline and 3-month (±1 month) CT/ MRI images from patients with advanced, grade 1-2 NETs were retrospectively reviewed by 2 readers. Influence of number of targets, tumor burden, and location of lesion on the performance of TGR 3m to predict PFS was assessed by uni/multivariable Cox regression analysis. Agreement between readers was assessed by Lin's concordance coefficient (LCC) and kappa coefficient (KC). Results: A total of 790 lesions were measured in 222 patients. Median PFS was 22.9 months. On univariable analysis, number of lesions (