| 1. |
- Lamarca, Angela, et al.
(författare)
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Tumour Growth Rate as a validated early radiological biomarker able to reflect treatment-induced changes in Neuroendocrine Tumours : the GREPONET-2 study
- 2019
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 15:25, s. 6692-6699
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: TGR represents the percentage change in tumour volume per month (%/m). Previous results from the GREPONET study showed that TGR measured after 3 months (TGR3m) of starting systemic treatment (ST) or watch and wait (WW) was an early biomarker predicting progression-free survival (PFS) in NETs.EXPERIMENTAL DESIGN: Pts from7 centres with advanced grade(G) 1/2 NETs from the pancreas(P)/small bowel(SB) initiating ST/WW were eligible. Computed tomography (CT) / magnetic resonance imaging (MRI) performed at pre-baseline, baseline and 3(+/-1) months of study entry were retrospectively reviewed. Aim-1: explore treatment-induced changes in TGR (ΔTGR3m-BL) (paired T-test) and Aim-2: validate TGR3m (<0.8%/m vs ≥0.8%/m) as an early biomarker in an independent cohort (Kaplan-Meier/Cox Regression).RESULTS: Out of 785 pts screened, 127 were eligible. Mean (SD) TGR0 and TGR3m were 5.4%/m (14.9) and -1.4%/m (11.8), respectively. Mean(SD) ΔTGR3m-BL paired-difference was -6.8%/m(19.3) (p<0.001). Most marked ΔTGR3m-BL (mean (SD);p) were identified with targeted therapies (-11.3%/m(4.7);0.0237) and chemotherapy (-7.9%/m(3.4);0.0261). Multivariable analysis confirmed the absence of previous treatment (Odds Ratio (OR) 4.65 (95%CI 1.31-16.52); p-value0.018) and low TGR3m (continuous variable; OR 1.09 (95%CI 1.01-1.19); p-value0.042) to be independent predictors of radiological objective response. When the multivariable Cox Regression was adjusted to grade (p-value 0.004) and stage (p-value0.017), TGR3m≥0.8 (vs.<0.8) maintained its significance (p<0.001), while TGR0 and ΔTGR3m-BL did not. TGR3m was confirmed as an independent prognosis factor for PFS (external validation; Aim-2) (multivariable HR 2.21 (95%CI 1.21-3.70); p-value0.003).CONCLUSIONS: TGR has a role as biomarker for monitoring response to therapy for early prediction of PFS and radiological objective response.
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| 2. |
- Dawod, Mohammed, et al.
(författare)
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Antiproliferative Systemic Therapies for Metastatic Small Bowel Neuroendocrine Tumours
- 2021
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Ingår i: Current Treatment Options in Oncology. - : Springer Nature. - 1527-2729 .- 1534-6277. ; 22:8
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Forskningsöversikt (refereegranskat)abstract
- Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies with rising incidence and prevalence. Outcome and therapy of small bowel neuroendocrine tumours (SBNETs) is variable, depending on the grade, differentiation, tumour burden, as well as the site of the tumour origin. Because of this, multidisciplinary approach is essential. Large randomized clinical trials, with somatostatin analogues (PROMID, CLARINET) or with peptide receptor radionuclide therapy (PRRT) with 177-lutetium (NETTER-1 trial) as well as the mammalian target of rapamycin inhibitor (mTOR) everolimus (RADIANT trials), represent milestones for the medical management of unresectable grade 1 and 2 SBNETS over the last decade. Novel therapies, such as tyrosine kinase inhibitors (TKI), are on the cutting edge. However, multiple unsolved questions remain. This review provides a comprehensive review of the main systemic therapeutic options for advanced SBNETs and discusses the latest guideline recommendations for palliative treatment.
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| 3. |
- Dromain, Clarisse, et al.
(författare)
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Tumour Growth Rate to predict the outcome of patients with Neuroendocrine Tumours : Performance and sources of variability
- 2021
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Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 111:9, s. 831-839
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Tidskriftsartikel (refereegranskat)abstract
- 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 tumors (NETs) patients. We assessed the performance and reproducibility of TGR 3 months (TGR3m) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability.METHODS: Baseline and 3-months (±1month) 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 TGR3m to predict PFS was assessed by uni/multivariable Cox regression analysis. Agreement between readers was assessed by the Lin's concordance coefficient (LCC) and Kappa (KC).RESULTS: A total of 790 lesions were measured in 222 patients. Median PFS was 22.9 months. On univariable analysis, number of lesions (DISCUSSION/CONCLUSION: TGR3m is a robust and early radiological biomarker able to predict PFS. It may be used to identify patients with advanced NETs who require closer radiological follow-up.
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| 4. |
- Lamarca, Angela, et al.
(författare)
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Advanced small-bowel well-differentiated neuroendocrine tumours : An international survey of practice on 3(rd)-line treatment
- 2021
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Ingår i: World Journal of Gastroenterology. - : BAISHIDENG PUBLISHING GROUP INC. - 1007-9327 .- 2219-2840. ; 27:10, s. 976-989
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Somatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours (Wd-SBNETs), while and peptide receptor radionuclide therapy (PRRT) is frequently used as a second-line therapy. Adequate treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic sequence. AIM To understand current practice and rationale for decision-making by physicians in the 3(rd)-line setting by building an online survey. METHODS Weighted average (WA) of likelihood of usage between responders (1 very unlikely; 4 very likely) was used to reflect the relevance of factors explored. RESULTS Replies from representatives of 28 centers were received (5/8/2020-21/9/2020); medical oncologist (53.6%), gastroenterologist (17.9%); United Kingdom (21.4%), Spain (17.9%), Italy (14.3%). Majority from European Neuroendocrine Tumor Society (ENETS) Centres of Excellence (57.1%), who followed ENETS guidelines (82.1%). Generally speaking, 3(rd)-line treatment for Wd-SBNETs was: everolimus (EVE) (66.7%), PRRT (18.5%), liver embolization (LE) (7.4%) and interferon-alpha (IFN) (3.7%); chemotherapy (0%); decision was based on clinical trial data (59.3%), or personal experience (22.2%). EVE was most likely used if Ki-67 < 10% (WA 3.27/4) or age < 70 years (WA 3.23/4), in the 3(rd)-line setting (WA 3.23/4); regardless of presence/absence of carcinoid syndrome (CS), rate of progression or extent of disease. Chemotherapy was mainly utilised only if rapid progression (within 6 mo) (WA 3.35/4), Ki-67 10%-20% (WA 2.77/4), negative somatostatin receptor imaging (WA 2.65/4) or high tumour burden (WA 2.77/4); temozolomide or streptozocin was used with capecitabine or 5-fluorouracil (5-FU) (57.7%), FOLFOX (5-FU combined with oxaliplatin) (23.1%). LE was selected if presence of CS (WA 3.24/4) or Ki-67 < 10% (WA 2.8/4), after progression to other treatments (WA 2.8/4). IFN was rarely used (WA 1.3/4). CONCLUSION Everolimus was the most frequently used therapeutic option in the third-line setting. The most important factors for decision-making included Ki-67, rate of progression, functionality and tumour burden; since this decision is based on multiple factors, it highlights the need for a multidisciplinary assessment.
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| 5. |
- Lamarca, Angela, et al.
(författare)
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Value of Tumor Growth Rate (TGR) as an Early Biomarker Predictor of Patients' Outcome in Neuroendocrine Tumors (NET) : The GREPONET Study
- 2019
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1083-7159 .- 1549-490X. ; 24:11, s. E1082-E1090
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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