scholarly journals Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

2013 ◽  
Vol 21 (3) ◽  
pp. R105-R120 ◽  
Author(s):  
Louis de Mestier ◽  
Clarisse Dromain ◽  
Gaspard d'Assignies ◽  
Jean-Yves Scoazec ◽  
Nathalie Lassau ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Targeted Therapies ◽  
Current Knowledge ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Tumor Evolution ◽  
Free Survival ◽  
Well Differentiated ◽  
Slow Growing ◽  
Therapeutic Responses

Well-differentiated neuroendocrine tumors (NETs) are a group of heterogeneous rare tumors. They are often slow-growing and patients can have very long survival, even at the metastatic stage. The evaluation of tumor progression and therapeutic responses is currently based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST) criteria. As for other malignancies, RECIST criteria are being reexamined for NETs in the era of targeted therapies because tumor response to targeted therapies is rarely associated with shrinkage, as opposed to prolonged progression-free survival. Therefore, size-based criteria no longer seem to be suitable to the assessment of NET progression and therapeutic responses, especially considering targeted therapies. New imaging criteria, combining morphological and functional techniques, have proven relevant for other malignancies treated with targeted therapies. To date, such studies have rarely been conducted on NETs. Moreover, optimizing the management of NET patients also requires considering clinical, biological, and pathological aspects of tumor evolution. Our objectives herein were to comprehensively review current knowledge on the assessment of tumor progression and early prediction of therapeutic responses and to broaden the outlook on well-differentiated NETs, in the era of targeted therapies.

Response evaluation using RECIST and CHOI criteria in patients with well-differentiated pancreatic neuroendocrine tumors (pNET) treated with sunitinib or everolimus.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14660-e14660 ◽  
Author(s):  
Olivia Hentic ◽  
Chantal Dreyer ◽  
Magaly Zappa ◽  
Pascal Hammel ◽  
Cristian Mateescu ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Phase Iii ◽  
Free Survival ◽  
Kaplan Meier ◽  
Choi Criteria ◽  
Large Phase ◽  
Well Differentiated ◽  
Best Responses

e14660 Background: Despite low response rate by RECIST, sunitinib and everolimus improved the progression-free survival of patients (pts) with well-differentiated pNET in two large phase III controlled trials. RECIST being a poor surrogate endpoint for PFS, this study aimed evaluating the value of CHOI criteria in PNET pts. Methods: Data for this analysis were collected from pts with well-differentiated PNET treated consecutively with sunitinib or everolimus in our center between 10-2006 and 11-2010. All pts had tumor progression within 12 months (m) prior to treatment. Pts were considered evaluable if CT-scans were performed within 6 weeks prior treatment and <3 months following treatment initiation. A radiologist blinded for clinical data evaluated responses according to RECIST and CHOI criteria. Best responses were correlated with Kaplan Meier estimates of time-to-progression (TTP) and overall survival (OS). Results: A total of 25 pts were treated with either sunitinib or everolimus. Among them, three pts were evaluated using MRI and thus were not evaluable in this study. Twelve pts received sunitinib and ten pts were treated with everolimus (Male/female: 8/14, median age: 57, range 38-76). All pts had tumor progression within 12 m prior to sunitinib or everolimus. Pts were either treated in 1st line (n=6), 2nd line (n=9), 3rd line (n=7) or 4th line (n=1) after cytotoxic chemotherapy. At the first CT-scan evaluation, 2 pts presented a partial response (PR), 18 pts had a stable disease (SD), and 2 pts had a progressive disease (PD) by RECIST. Using CHOI criteria, 11 PR, 8 SD, and 3 PD were observed. Nine of 18 pts (50%) with SD according to RECIST were reallocated to the responders (PR) using CHOI criteria. Median TTP and OS for all pts were 14.0 m and 35.8 m, respectively. According to RECIST, TTP was higher in pts with PR+SD compared to PD (14.2m vs 3.3m, p<0.0001). According to CHOI criteria, TTP was 26.1m in pts with PR, 8.7m in pts with SD, and 3.5m in pts with PD (p=0.038). Conclusions: Response byCHOI criteria is a prognostic factor for TTP and may identify among SD pts by RECIST those benefiting the most of targeted therapy.

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

scholarly journals One-Year Progression-Free Survival of Therapy-Naive Patients With Malignant Pheochromocytoma and Paraganglioma

2013 ◽  
Vol 98 (10) ◽  
pp. 4006-4012 ◽  
Author(s):  
Ségolène Hescot ◽  
Sophie Leboulleux ◽  
Laurence Amar ◽  
Delphine Vezzosi ◽  
Isabelle Borget ◽  
...  
Keyword(s):  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Malignant Pheochromocytoma ◽  
Inherited Disease ◽  
High Power Field ◽  
Free Survival ◽  
History Of ◽  
Wait And See ◽  
One Year

Abstract Context: The natural history of malignant pheochromocytoma or paragangliomas (MPP) remain unknown. Objective: The primary aim of this study was to define progression-free survival at 1 year in therapy-naive patients with MPP. Secondary objectives were to characterize MPP and to look for prognostic parameters for progression at 1 year. Design and Setting: The files of MPP followed up between January 2001 and January 2011 in two French Endocrine Networks were retrospectively reviewed. Therapy-naive patients were enrolled. Main Outcome Measures: The main outcome was progression-free survival at 1 year in therapy-naive MPP patients according to Response Evaluation Criteria In Solid Tumors 1.1 criteria. Results: Ninety files (46 men, 44 women, mean age of 47.5 ± 15 years) were reviewed on site by one investigator. MPP characteristics were as follows: presence of an adrenal primary, a mitotic count exceeding 5 per high power field, hypertension, inherited disease, and presence of bone metastases in 50%, 22%, 60%, 49%, and 56% patients, respectively. Fifty-seven of the 90 patients with MPP (63%) were classified as therapy-naive. The median follow-up of these 57 patients was 2.4 years (range, 0.4–5.7). At 1 year, progression-free survival was 46% (CI 95: 33–59). Twenty-six of 30 (87%) patients with progression at 1 year had exhibited progressive disease at the first imaging workup performed after a median of 5.7 months. No prognostic parameter was identified. Conclusions: Half of the therapy-naive patients with MPP achieved stable disease at 1 year. In symptom-free patients with MPP, a wait-and-see antitumor policy seems appropriate as first line. Modality for a prospective follow-up is proposed.

scholarly journals Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board

2017 ◽  
pp. 1-19 ◽  
Author(s):  
W. Brian Dalton ◽  
Patrick M. Forde ◽  
Hyunseok Kang ◽  
Roisin M. Connolly ◽  
Vered Stearns ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Progression Free Survival ◽  
Molecular Profiling ◽  
Tumor Board ◽  
Free Survival ◽  
Off Label ◽  
Tumor Boards ◽  
Molecular Tumor Board

Purpose Tumor genomic profiling for personalized oncology therapy is being widely applied in clinical practice even as it is being evaluated more formally in clinical trials. Given the complexities of genomic data and its application to clinical use, molecular tumor boards with diverse expertise can provide guidance to oncologists and patients seeking to implement personalized genetically targeted therapy in practice. Methods A multidisciplinary molecular tumor board reviewed tumor molecular profiling reports from consecutive referrals at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins over a 3-year period. The tumor board weighed evidence for actionability of genomic alterations identified by molecular profiling and provided recommendations including US Food and Drug Administration–approved drug therapy, clinical trials of matched targeted therapy, off-label use of such therapy, and additional tumor or germline genetic testing. Results One hundred fifty-five patients were reviewed. Actionable genomic alterations were identified in 132 patients (85%). Off-label therapies were recommended in 37 patients (24%). Eleven patients were treated off-label, and 13 patients were enrolled onto clinical trials of matched targeted therapies. Median progression-free survival of patients treated with matched therapies was 5 months ( 95% CI, 2.9 months to not reached), and the progression-free survival probability at 6 months was 43% (95% CI, 26% to 71%). Lack of locally available clinical trials was the major limitation on clinical actionability of tumor profiling reports. Conclusion The molecular tumor board recommended off-label targeted therapies for a quarter of all patients reviewed. Outcomes were heterogeneous, although 43% of patients receiving genomically matched therapy derived clinical benefit lasting at least 6 months. Until more data become available from precision oncology trials, molecular tumor boards can help guide appropriate use of tumor molecular testing to direct therapy.

scholarly journals Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study

2019 ◽  
Vol 37 (28) ◽  
pp. 2571-2580 ◽  
Author(s):  
Alberto Carmona-Bayonas ◽  
Paula Jiménez-Fonseca ◽  
Ángela Lamarca ◽  
Jorge Barriuso ◽  
Ángel Castaño ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Failure Time ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Accelerated Failure Time Model ◽  
Endocrine Tumors ◽  
First Line ◽  
Ki 67 ◽  
Free Survival ◽  
Well Differentiated

PURPOSE Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.

Effectiveness of peptide receptor radionuclide therapy for neuroendocrine neoplasms: A multi-institutional registry study with prospective follow-up.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4033-4033
Author(s):  
Dieter Hörsch ◽  
Keyword(s):  
Small Bowel ◽  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Unknown Primary ◽  
Neuroendocrine Neoplasms ◽  
Registry Study ◽  
Free Survival ◽  
Peptide Receptor ◽  
Well Differentiated

4033 Background: Peptide receptor radionuclide therapy targets somatostatin receptors expressed on well differentiated neuroendocrine neoplasms. Retrospective monocentric studies indicate that peptide receptor radionuclide therapy is an effective treatment for patients with neuroendocrine neoplasms. Methods: We initiated a multi-institutional, prospective and board reviewed registry study for patients treated with peptide receptor radionuclide therapy. 450 patients were included and followed for a mean of 24.4 months. Patients were treated with Lutetium-177 (54%), Yttrium-90 (17%) or both radionuclides (29%). Primary neuroendocrine neoplasms were derived of pancreas (38%), small bowel 30%), unknown primary (19%), lung (4%) and colorectum (3,5%). Most neuroendocrine neoplasms were well differentiated with a proliferation rate below 20% in 54% and were pretreated by 1 or more therapies in 73%. Results: Overall survival of all patients from the beginning of therapy was 59 months in median. Median survival depended on radionuclides used (Yttrium-90: 38 months; Lutetium-177: not reached; both: 58 months), proliferation rate (G1: median not reached; G2: 58 months; G3: 33 months; unknown: 55 months) and origin of primary tumors (pancreas: 53 months; small bowel: not reached; unknown primary: 47 months; lung: 38 months) but not upon number of previous therapies. Median progression-free survival measured from last cycle of therapy accounted to 41 months for all patients. Progression-free survival of pancreatic neuroendocrine neoplasms was 39 months in median. Similar results were obtained for neuroendocrine neoplasms of unknown primary with a median of 38 months whereas neuroendocrine neoplasm of small bowel were progression-free for a median of 51 months. Side effects like G3-G4 nephrotoxicity or hematological function were observed in 0.2% and 2% of patients. Conclusions: Peptide receptor radionuclide therapy is effective for patients with G1-G2 neuroendocrine tumors irrespective of previous therapies with a survival advantage of several years compared to other therapies and only minor side effects.

Impact of baseline and concomitant corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 531-531
Author(s):  
David James Pinato ◽  
Ahmed Omar Kaseb ◽  
Yinghong Wang ◽  
Anwaar Saeed ◽  
David Szafron ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Corticosteroid Treatment ◽  
Free Survival ◽  
Checkpoint Inhibitor Therapy ◽  
The Impact

531 Background: The impact of corticosteroid treatment (CT) on the efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) is undefined. We evaluated whether CT administered at baseline (bCT) or concurrently to ICI (cCT) influences clinical outcomes of HCC patients treated with ICI. Methods: This retrospective, multi-center observational study was conducted across 9 tertiary academic referral centers collected 341 HCC patients who received ICI across 3 continents between January 1, 2016 and April 1, 2019. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of ICI commencement and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1) on 6-8 weekly periodic restaging. Results: Of 331 eligible patients, 254 (76%) had BCLC-C stage HCC and received mostly PD(L)-1 ICI monotherapy (n=250, 85%). Median OS was 12.1 months (95%CI 9.2-15.0 months) and median PFS was 8.1 months (95%CI 6.3-10 months). In total 81 patients (24%) received >10 mg prednisone equivalent daily either as bCT (n=15, 4%) or cCT (n=66, 20%). Indications for CT included procedure/prophylaxis (n=37, 45%), management of irAE (n=31, 37%), cancer-related symptoms (n=5, 2%) or comorbidities (n=8, 3%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in uni- and multi-variable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (2.4 vs. 11.3 months, p=0.01), OS (4.5 vs. 12.8 months, p=0.05) and reduced ORR (p=0.03) compared to cancer-unrelated indications. Conclusions: This is the first study to demonstrate that neither bCT nor cCT appear to influence response and OS following ICI in HCC. Worse survival and ORR in CT recipients for cancer-related indications appears driven by the poor prognosis associated with symptomatic HCC.

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