Outcome analyses in patients with metastatic gastroenteropancreatic neuroendocrine tumors receiving peptide receptor radionuclide therapy with 177Lu-DOTATATE – Impact of treatment order and combination on mortality.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4606-4606
Author(s):  
Alexander Rheinhard Siebenhuener ◽  
Dominique Pretot ◽  
Valerie Treyer
Keyword(s):  
Neuroendocrine Tumors ◽  
Survival Data ◽  
Odds Ratio ◽  
Pancreatic Tumor ◽  
Performance Status ◽  
Blood Parameters ◽  
University Hospital ◽  
Somatostatin Analogue ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Significant Deterioration

4606 Background: Neuroendocrine tumors of the gastroenteropancreatic tract present heterogeneous with several systemic treatment options in the advanced setting. PRRT with 177Lu-DOTATATE targeting the SSTR-2 receptor of these tumors showed effective responses in the NETTER-1 trial in the short as well as long term follow-up of patients. The aim of our study was to determine the HRQoL and outcome of GEP-NET patients. Methods: 41 GEP-NET patients who received 177Lu-DOTATATE (mean: 3 cycles) between 2012 and 2017 at University Hospital Zurich (USZ) were included in this retrospective analysis. HRQoL parameters (fatigue, insomnia, loss of appetite, abdominal pain, nausea, emesis, diarrhea, weight loss) were assessed before and after treatment. At least 3 weeks after the last PRRT cycle, data on blood parameters, HRQoL, and overall survival data were extracted from patient records. To determine factors influencing the success of PRRT therapy and survival, we recorded pre- and post-PRRT treatments (e.g. selective internal radiation therapy/SIRT, somatostatin analogue therapy/SSA, TKI or chemotherapy) and the time-point of PRRT in the therapeutic sequence was analyzed. Results: Baseline rates of HRQoL and ECOG performance status were assessed (baseline mean: ECOG 0). PRRT was well tolerated, with most patients reporting no significant deterioration in HRQoL after treatment. Blood parameters (hemoglobin, leucocyte and platelet counts, creatinine) and glomerular filtration rate were not significantly affected by PRRT therapy. The number of previous treatments did not influence survival after PRRT; neither did the length of the time period between first diagnosis and PRRT. Patients with a SIRT treatment prior to PRRT had an elevated mortality odds ratio of 4.083. If SIRT was applied to patients with a pancreatic tumor, the mortality odds ratio was 1.33 compared to patients without a pancreatic tumor. Post-PRRT SSA increased the odds for survival, with a mortality odds ratio of 2.33 for patients without SSA after PRRT. Conclusions: Patients with advanced GEP-NETs may benefit from PRRT with 177Lu-DOTATATE, as this treatment appears to be well tolerated and does not significantly impair the HRQoL or symptom load. SIRT before PRRT seems to lower the chances of response and reduces survival instead using this sequence vice versa. This trend was also seen if SSA was not used after PRRT. But these trends have to be proven in prospective trials.

Analysis of chemotherapy efficacy according to histology in malignant pleural mesothelioma (MPM) patients (p).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20563-e20563
Author(s):  
Susana Cedres Perez ◽  
Juan David Assaf Pastrana ◽  
Patricia Iranzo ◽  
Ana Callejo ◽  
Nuria Pardo ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Survival Data ◽  
Cox Regression ◽  
Asbestos Exposure ◽  
Performance Status ◽  
University Hospital ◽  
First Line ◽  
Neutrophil Lymphocyte Ratio ◽  
The Impact ◽  
Line Chemotherapy

e20563 Background: MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. Histology is a prognostic factor and recently CheckMate 743 trial demonstrated survival benefit of immunotherapy in first line with some differences in the efficacy of chemotherapy according to histology. However, randomized trials who led to the approval of antifolate in mesothelioma did not include analysis of outcomes by histology. The objective of this study is to characterize the impact of chemotherapy according to histology in p with MPM at our institution. Methods: We review 189 MPM p diagnosed at Vall d´Hebron University Hospital between November 2002 and April 2020. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: Patient’s characteristics: median age 68 years (y) (45-88 y), males: 70%, performance status (PS)1: 69%, asbestos exposure: 75%, epithelioid subtype: 76%. First line chemotherapy was offered to 85% of p (66% cisplatin-pemetrexed and 27% carboplatin-pemetrexed). Median overall survival (OS) in overall population was 21.3 m (95%CI17.2-24.3). Epithelioid histology, PS 0, neutrophil-lymphocyte ratio <5 and treatment with cisplatin vs carboplatin were associated with significant improvements in OS (p<0.001). When we analyzed the survival of patients who received first line chemotherapy according to histology, we found that patients with epithelioid tumors had better PFS and OS. Median PFS for p with epithelioid tumors treated with chemotherapy in first line was 4.8 m versus 3.6 months non-epithelioid (HR1.5 CI95% 1.1-2.3; p=0.03). OS of epithelioid p treated with first line chemotherapy was 26.7 m versus 15.0 m non-epithelioid patients (HR2.25 CI95% 1.4-3.4; p<0.001). We analyzed if the differences in survival according to histology were due to type of systemic treatment received (Table). Conclusions: In our series, p with non-epithelioid tumors presented worse prognosis. We confirmed histology is a prognostic factor with better OS for p with epithelioid tumors. Moreover, we demonstrated better efficacy of chemotherapy in epithelioid tumors, although histology is not a predictive factor for the platinum agent sensitivity (p of interaction PFS=0.09, p of interaction OS= 0.65).[Table: see text]

Analysis of mismatch repair (MMR) proteins expression in a series of malignant pleural mesothelioma (MPM) patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20062-e20062
Author(s):  
Susana Cedres ◽  
Santiago Ponce Aix ◽  
Ana Callejo ◽  
Nuria Pardo ◽  
Alejandro Navarro ◽  
...  
Keyword(s):  
Protein Expression ◽  
Survival Data ◽  
Cox Regression ◽  
Asbestos Exposure ◽  
Performance Status ◽  
Predictive Biomarkers ◽  
University Hospital ◽  
Tumor Biomarker ◽  
Neutrophil Lymphocyte Ratio ◽  
Mmr Proteins

e20062 Background: The increasing incidence and poor outcome associated with MPM demand identification of effective treatment options. Promising results have been reported with immunotherapy (IO) in a small proportion of MPM patients (p). MMR deficiency (dMMR) has been well described in several malignancies and was recently approved as a tumor biomarker for IO with anti-PD-1 checkpoint inhibitor. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM p. Methods: Tumors of 159 MPM p from Vall d´Hebron University Hospital and October 12th University Hospital diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR when any MMR protein expression was negative and MMR intact when all MMR proteins were positively expressed. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: P characteristics: median age: 69 years (29-88 years), males: 71%, performance status (PS) 1:69%, asbestos exposure: 52%, stage III at diagnosis: 42%, epithelial subtype: 65%, systemic treatment 81% (57% chemotherapy with cisplatin plus pemetrexed in first line), 50% received second line and 28% third line. MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8m). In a multivariate model factors associated to improved mOS were PS 0 vs PS2 (13 v 2 m, HR 12.8, p < 0.01), neutrophil-lymphocyte ratio (NLR) < 5 (18 v 9 m in NLR ≥5,HR 1.5, p < 0.05) and epitheliod vs sarcomatoid histology (18 vs 4 m HR 4.7, p < 0.01). Thirteen p received IO with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1m). Conclusions: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate novel predictive biomarkers benefit from IO in MPM.

scholarly journals A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 168
Author(s):  
Gil Awada ◽  
Yanina Jansen ◽  
Julia Katharina Schwarze ◽  
Jens Tijtgat ◽  
Lennert Hellinckx ◽  
...  
Keyword(s):  
Survival Data ◽  
Cox Regression ◽  
Clinical Laboratory ◽  
Performance Status ◽  
Stage Iv ◽  
Absolute Lymphocyte Count ◽  
Comprehensive Analysis ◽  
Advanced Melanoma ◽  
University Hospital ◽  
Cox Regression Analysis

Background: Pembrolizumab improves the survival of patients with advanced melanoma. A comprehensive analysis of baseline variables that predict the benefit of pembrolizumab monotherapy has not been conducted. Methods: Survival data of patients with advanced melanoma who were treated with pembrolizumab in a single university hospital were collected. A multivariate Cox regression analysis was performed to correlate baseline clinical, laboratory, and radiologic characteristics and NanoString IO360 gene expression profiling (GEP) with survival. Results: 183 patients were included (stage IV 85.2%, WHO performance status ≥1 31.1%; pembrolizumab first-line 25.7%), of whom 112 underwent baseline 18F-FDG-PET/CT imaging, 58 had circulating tumor DNA (ctDNA) assessments, and GEP was available in 27 patients. Active brain metastases, a higher number of metastatic sites, lower albumin and absolute lymphocyte count (ALC), higher C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio, higher total metabolic tumor volume (TMTV), and higher ctDNA levels were associated with worse survival. Elevated lactate dehydrogenase (LDH) ≥ 2ULN (upper limit of normal), CRP ≥ 10ULN, or ALC < 750/mm3 delineate a subpopulation where treatment with pembrolizumab is futile. A TMTV ≥ 80 mL encompassed 17/21 patients with LDH ≥ 2ULN, CRP ≥ 10ULN, or ALC < 750/mm3. No significant associations were observed between baseline GEP scores and survival. Conclusion: Multiple baseline variables correlate with survival on pembrolizumab. TMTV is a more comprehensive baseline biomarker than CRP, LDH, or ALC in predicting the futility of pembrolizumab.

Etctn 10388: A phase I trial of triapine and lutetium Lu 177 dotatate in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4660-TPS4660
Author(s):  
Aman Chauhan ◽  
Charles Kunos ◽  
Riham El Khouli ◽  
Jill Kolesar ◽  
Heidi Weiss ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Somatostatin Receptor ◽  
Phase Iii ◽  
Somatostatin Analogue ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Potent Inducer ◽  
Radiation Sensitizer ◽  
Well Differentiated

TPS4660 Background: Radiolabeled somatostatin analogues provide a means of delivering targeted radiation with a high therapeutic index to NETs that express somatostatin receptors (SSTRs). Radiolabeled somatostatin analogue Lutetium Lu 177 Dotatate (Lutathera) is a beta-emitting radionuclide, recently FDA approved for use in SSTR positive gastroenteropancreatic neuroendocrine tumors (GEPNETS) in the US based on the NETTER-1 Phase III trial. Despite favorable PFS and safety profile, the drug has limited cytoreductive capability with a 17% ORR. We hypothesize that addition of an effective radiation sensitizer could help improve antitumor activity of Lutathera. Ribonucleotide reductase (RNR) is the only enzyme responsible for conversion of ribonucleoside diphosphate to deoxyribonucleotide diphosphate (dNDP), the key building blocks for DNA synthesis. Radiation is a potent inducer of DNA double-strand breaks (DSBs), and RNR is the rate-limiting enzyme in the repair of DNA in this setting. Triapine is an inhibitor of RNR. This study will test the hypothesis that radiation sensitizer triapine can be safely combined with peptide receptor radionuclide therapy and ultimately may improve antitumor activity of Lutetium Lu 177 Dotatate. Methods: This study is an investigator initiated, NCI sponsored, multicenter phase 1 trial of triapine and Lutetium Lu 177 Dotatate in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumor (GEP-NETs) after the failure of at least one line of prior systemic cancer treatment. A total of 29 patients will be enrolled in the dose escalation with help of Bayesian optimal interval design (BOIN) and dose expansion cohorts. The study will be open through the NCI ETCTN (National Cancer Institute Experimental Therapeutics Clinical Trials Network) program. Patients will be treated with 177 lutetium dotatate in combination with triapine. Triapine will be administered orally (100 mg once a day starting dose) from D1-14 with each dose of PRRT [200 mCi]. Primary endpoint is to evaluate recommended phase II dose (RP2D). Secondary endpoints are to evaluate safety, pharmacokinetics, and clinical activity (ORR and PFS). We are also evaluating NETEST, a novel blood based test that evaluates levels of 51 neuroendocrine tumor gene transcripts. In addition, the study will correlate clinical outcome with baseline somatostatin receptor density, somatic tumor mutations and germline mutations. Clinical trial information: 04234568 .

scholarly journals Efficacy and Prognostic Factors for Y-90 Radioembolization (Y-90) in Metastatic Neuroendocrine Tumors with Liver Metastases

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Erica S. Tsang ◽  
Jonathan M. Loree ◽  
Janine M. Davies ◽  
Sharlene Gill ◽  
David Liu ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Neuroendocrine Tumors ◽  
Performance Status ◽  
Population Based ◽  
Somatostatin Analogue ◽  
Ecog Performance Status ◽  
Ki 67 ◽  
Well Differentiated ◽  
Grade 3 ◽  
Metastatic Liver

Background. Yttrium-90 (Y-90) can be an effective liver-directed therapy for patients with metastatic neuroendocrine tumors (NETs), but population-based data are limited. We characterized the use of Y-90 in NET patients and identified factors associated with response. Methods. We identified 49 patients with metastatic liver-dominant NETs across BC Cancer’s six regional centres who received Y-90 between June 2011 and January 2017 in British Columbia, Canada. Baseline characteristics, radiographic responses, and outcomes were summarized. Results. Of the 49 patients who received Y-90, the median age was 56 years (range 21–78), 49% were male, and 94% had an ECOG performance status of 0–1. The primary location of the NET included pancreas (31%), small bowel (41%), large bowel (6%), unknown (14%), and others (12%). 69% of these patients had liver metastases alone, and tumors were graded as G1 (61%), G2 (25%), G3 (2%), and unknown (12%). Prior therapies included surgery (63%), local ablative therapy (25%), somatostatin analogue (69%), and systemic therapy (35%). The median Y-90 dose was 2.2 GBq (range 0.8–3.6), as SIR-spheres (69%) or TheraSpheres (29%). Median time to Y-90 from diagnosis of metastases measured 1.54 years. 88% received segmental Y-90, with 1 (69%), 2 (29%), and 3 (2%) treatments. Y-90 resulted in partial response (53%), stable disease (33%), and progressive disease (12%). Y-90 was well-tolerated, with infrequent grade 3-4 biochemical toxicities (2%) and grade 3 abdominal pain (6%). Longer overall survival (OS) was associated with resection of primary tumor, well-differentiated histology, and low Ki-67. Median OS was 27.2 months (95% CI 8.0–46.5).Conclusions. In our population-based cohort, Y-90 was well-tolerated in patients with metastatic liver-dominant NETs. Prior surgical resection was an important predictor of OS.

The occurrence of hyponatriemia in SCLC and the influence on prognosis. A retrospective study of 468 patients treated in single institution in a 10-year period

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7091-7091
Author(s):  
O. Hansen ◽  
P. Sorensen ◽  
K. H. Hansen ◽  
E. Holtved
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Survival Rate ◽  
Odds Ratio ◽  
Poor Prognosis ◽  
Performance Status ◽  
University Hospital ◽  
Significant Prognostic Factor ◽  
Extensive Disease ◽  
Significant Factors

7091 Background: Hyponatriemia is very often seen in SCLC due to the paraneoplastic syndrome SIADH. Hyponatriemia has been found to be associated with poorer outcome in some but not in the majority of published studies. This study was performed to investigate the prognostic value of hyponatriemia in SCLC. Methods: Data from the patient files from 468 patients diagnosed with SCLC and treated at Odense University Hospital 1995 to 2005. In the 444 cases data on the initial S-Na was available. A Cox multivariate analysis was performed including possible prognostic factors. Results: Stage: Extensive disease (ED) 283 (64%), limited disease (LD) 161 (36%). The standard chemotherapy was 6 cycles of carboplatin-etoposide. 70% of the patients with LD received thoracic radiotherapy, usually in a dose of 45 Gy/22–30 F and 49% received PCI usually as 25 Gy/11F. Median survival in ED 7.2 months with a 1 and 2-year survival rate of 21% and 6%. In LD the figures was 15.2 months, 65%, 31% and a 5-year survival rate of 16%. S-Na was <125 mEq/L in 36 patients (8%), between 126–135 mEq/L in 158 (36%). 250 patients (56%) showed normal values of S-Na. In a Cox multivariate analysis, hyponatriemia was associated with poor prognosis. Other independent prognostic factors included LDH, gender, age, performance status and stage. Among non-significant factors were hemoglobin, WBC, and alkaline phosphatase. Conclusions: Hyponatriemia was a significant prognostic factor associated with poor prognosis with an odds ratio of 1.5 (p = 0.0013) if S-Na was 1.25–1.35 mEq/L and an odds ratio of 1.9 (p = 0.0008) if S-Na was <1.25 mEq/L. [Table: see text] No significant financial relationships to disclose.

Gastroenteropancreatic neuroendocrine tumors: descriptive study in a reference Spanish hospital

2013 ◽  
Author(s):  
Zayas Beatriz Leon de ◽  
Olmo Garcia Maria Isabel del ◽  
Agustin Ramos Prol ◽  
Antonia Perez Lazaro ◽  
Susana Tenes Rodrigo ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Descriptive Study ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Spanish Hospital

Evaluation of neurofibromatosis type 1 and gastroenteropancreatic neuroendocrine tumors.

2018 ◽  
Author(s):  
Juan Carlos Percovich ◽  
Jose Atencia ◽  
Rogelio Garcia ◽  
Marcel Sambo ◽  
Montserrat Blanco ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Gastroenteropancreatic Neuroendocrine Tumors

scholarly journals The state of PRRT and its sequencing amongst current therapeutic options for gastroenteropancreatic neuroendocrine tumors

2021 ◽  
Author(s):  
Lauren M Raymond ◽  
Tetiana Korzun ◽  
Adel Kardosh ◽  
Kenneth J. Kolbeck ◽  
Rodney Pommier ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Standard Dose ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Tumor Burden ◽  
Treatment Modalities ◽  
Its Sequencing ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Reduce Tumor Burden ◽  
Spectrum Of Patients

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common form of neuroendocrine neoplasia, but there is no current consensus for the sequencing of approved therapies, particularly with respect to peptide receptor radionuclide therapy (PRRT). This comprehensive review evaluates the data supporting approved therapies for GEP-NETs and recommendations for therapeutic sequencing with a focus on how PRRT currently fits within sequencing algorithms. The current recommendations for PRRT sequencing restrict its use to metastatic, inoperable, progressive midgut NETs, however, this may change with emerging data to suggest PRRT might be beneficial as neoadjuvant therapy for inoperable tumors, is more tolerable than other treatment modalities following first-line standard dose somatostatin analogues, and can be used as salvage therapy after disease relapse following prior successful cycles of PRRT. PRRT has also been shown to reduce tumor burden, improve quality of life, and prolong the time to disease progression in a broad spectrum of patients with GEP-NETs. As the various potential benefits of PRRT in GEP-NET therapy continues to expand, it is necessary to review and critically evaluate our treatment algorithms for GEP-NETs.

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