Temozolomide and capecitabine (CAPTEM) is effective in metastatic well-differentiated gastrointestinal neuroendocrine tumors.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 366-366
Author(s):  
İzzet Dogan ◽  
Didem Tastekin ◽  
Senem Karabulut ◽  
Burak Sakar

366 Background: The study aimed to evaluate patients' outcomes and prognosis with metastatic gastrointestinal neuroendocrine tumors (mgNET) who treated temozolomide and capecitabine (CAPTEM). Methods: The data of forty-three patients were retrospectively evaluated. Clinicopathological features and treatment approaches were recorded. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS). Prognostic factors were assessed with Cox-regression analysis. Results: Median age was 59 (27-85) years. The number of male and female patients was 23 (%53.5) and 20 (%46.5), respectively. Pancreas (%51.2) was the most common site of the tumor. The number of patients with well- and poorly-differentiated mgNET was 38 (%88.4) and 5 (%11.6), respectively. The most common metastatic sites were liver (%62.8), lymph node (%58.1), and bone (%18.6). Eleven (%25.6) of the patients previously had undergone surgery, and some patients received radiotherapy (%9.5), chemotherapy (%19), and nuclear therapy (%9.3). Also, patients received octreotide (%86) or lanreotide (%14) with CAPTEM. In patients with well-differentiated mgNET, median PFS was 17.4 months, and disease control ratio %79.4 (%3-complete response, %38.2-partial response, and %38.2-stable response). No response observed in patients with poorly differianted mgNET, and the median PFS was calculated as 4.5 months. Grade 1-2 toxicity was observed in 34 (%79.1) of the patients, and grade 3-4 toxicity in 8 (%18.6). Four (%9.5) patients discontinued therapy for the toxicity. The most common toxicities were anemia (%37.2), thrombocytopenia (%25.6), and fatigue (%16.3). At a median follow-up of 33.8 (2.9-172.73) months, the ratio of five-years OS was %61. In multivariate analysis; gender (p=0.008), age (p=0.007), and Ki-67 levels (p=0.011) were a statistically significant for OS. However, the site of the tumor (p=0.186), number of metastatic sites (p=0.255), and type of somatostatin receptor ligand (p=0.903) were not. Conclusions: In the study, we showed that CAPTEM + somatostatin receptor ligands (octreotide or lanreotide) were effective and well-tolerated in patients with well-differentiated mgNET. But, it was not effective in patients with poorly-differentiated mgNET. Male gender, aged over 60 years, and tumor with a high level of Ki-67 were negative prognostic factors.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 373-373
Author(s):  
Samantha M Ruff ◽  
Gary B Deutsch ◽  
Matthew John Weiss ◽  
Danielle Deperalta

373 Background: Ampullary neuroendocrine tumors (NET) make up < 1% of all gastrointestinal NETs. Information about their behavior and prognosis is reliant on small case series. This study set out to describe the population of patients who are diagnosed with ampullary NETs and compare them to patients with duodenal and pancreatic head NETs. Methods: The National Cancer Database (2004 – 2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Clinicopathologic and treatment characteristics were compared. Subset analysis was performed on patients who underwent surgery. Kaplan Meier (KM) analysis and Cox regression were used to analyze the survival of patients with ampullary NETs. Results: Overall, 872 patients were identified with ampullary NET, 9692 with duodenal NET, and 6562 with pancreatic head NET. Patients with ampullary NET had an average age of 60.9 +/- 14.5 years, were evenly split among men and women (N = 437, 50.1% vs N = 435, 49.9%, respectively), and primarily Caucasian (N = 663, 76.0%). 72.1% underwent local tumor destruction or surgery (N = 629). Most did not receive radiation (N = 832, 95.4%), chemotherapy (N = 627, 71.9%), or hormone therapy (N = 788, 90.4%). Patients with ampullary NETs had more poorly differentiated tumors (N = 119, 13.6%) than patients with duodenal (N = 159, 1.6%) or pancreatic head (N = 602, 9.2%) NETs. Patients with ampullary NETs had more positive lymph nodes (N = 288, 33%) than patients with duodenal (N = 915, 9.4%) or pancreatic head (N = 1381, 21%) NETs. At five years, the overall survival for patients with ampullary, duodenal, and pancreatic head NETs was 57%, 68%, and 46%, respectively. Within the surgical population, five-year survival for patients with ampullary (N = 367), duodenal (N = 991), and pancreatic head (N = 1961) NETs was 60%, 74%, and 72%, respectively. When compared, there was a statistically significant difference between the mean overall survival of patients with ampullary (98 +/- 4.7 months), duodenal (112 +/- 2.5 months), and pancreatic head (108 +/- 1.7 months) NETs (p < 0.001). In the cox regression analysis, sex, Charlson-Deyo score, lymph node positivity, lymph-vascular invasion, mitotic rate, chromogranin A level, 5-HIAA level, and tumor size did not correlate with survival. Increasing age (HR 1.04, CI 1.01 – 1.07, p = 0.008) and worse tumor differentiation (poorly differentiated HR 3.33, CI 1.38 – 8.04, p = 0.008 and undifferentiated HR 8.31, CI 2.77 – 24.92, p < 0.001 compared to well differentiated) were associated with increased mortality. Conclusions: This study sheds light on a rare tumor histology. When compared to patients who underwent surgical resection for duodenal or pancreatic head NETs, patients with ampullary NETs had a significantly worse prognosis. Identifying prognostic factors allows us to create more concrete treatment recommendations and provide patients with improved prognostic information.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi152-vi152
Author(s):  
Taylor Perison ◽  
Kayla Wheat ◽  
Salim Gnabode ◽  
Lori Lyn Price ◽  
Suriya Jeyapalan

Abstract INTRODUCTION NM occurs in 5 - 15% of cancer patients and Overall Survival (OS) in treated patients ranges from 2-6 months. The purpose of this study was to analyze the effect of prognostic factors on OS and calculate a graded prognostic assessment (GPA) score based on tissue type, similar to the index score created for cancer patients with brain metastases (BM). METHODS We conducted a single center, retrospective analysis of 118 patients diagnosed between 2006 and 2018 at TMC. The prognostic factors analyzed were: Age (&lt; = 50yo =1pt), Karnofsky Performance Status (KPS &gt; =60 =1 pt), and no extracranial metastases (1pt). The GPA score was calculated from 0.0 - 3.0 by adding the points together. Kaplan Meier curves were used to estimate OS for primary tumors with 10 or more patients (breast, lung, leukemia, lymphoma). Cox regression analysis was used to evaluate the association of the GPA with OS. RESULTS The GPA analysis by tumor type included 76% of the patient population. The median OS was 5 months (breast), 2 months (lung), 7 months (leukemia), and 2 months (lymphoma). We found that leukemia (p =0.008, N = 20) and lung cancer (p =0.002, N = 20) patients showed distinct separation between GPA groups on their Kaplan Meier curves. Higher KPS was associated with increased OS (p &lt; 0.0001) using Cox regression. DISCUSSION: The GPA algorithm was only partially successful in our NM population, which may reflect the smaller number of patients in our study compared to the studies used to create the BM GPA. TMC is a contributing institution to a large, multi-institutional, multi-national registry of patients with NM disease (Neoplastic Meningitis Registry - NeMeRe). We plan to use this larger dataset to validate our GPA score as a useful tool for predicting OS in NM patients.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 368-368
Author(s):  
Kelley Lauren Coffman ◽  
Lisa Bodei ◽  
Tiffany Le ◽  
Ye Choi ◽  
Joanne F. Chou ◽  
...  

368 Background: 177Lu-DOTATATE is an approved therapy for somatostatin receptor (sstr) positive gastroenteropancreatic neuroendocrine tumors (NETs). There are little data available on response and outcomes for well differentiated (WD) high grade (HG) NETs treated with 177Lu-DOTATATE. Methods: Pts with WD HGNETs treated with 177Lu-DOTATATE at MSK from 2018-2020 were identified. Demographics, response to treatment, and progression-free survival (PFS) were determined. In pts with archival tumor tissue, next-generation sequencing (NGS) was performed through an institutional platform (MSK-IMPACT). Results: 19 pts were identified (mean age 54, 63% female). Site of tumor origin included: pancreas (14/19, 74%), small bowel (2/19, 10.5%), rectal (2/19, 10.5%), lung (1/19, 5%). Average tumor Ki-67 was 34.8 (range 22-56). All tumors were sstr avid on pre-treatment Ga68-DOTATATE PET/CT; none of the patients had sstr negative lesions detected. Median number of prior treatments (systemic and/or liver-directed) was 4 (range 2-7). All pts had progressive disease prior to initiation of 177Lu-DOTATATE. 13 pts (68%) completed all four treatment cycles; treatment was incomplete in 6 pts due to treatment-related toxicities (n = 3) and clinical progression (n = 3). Best response by radiographic report was available in 16 patients (84%):10/16 (63%) with partial response, 1/16 (6%) with stable disease, 5/16 (31%) with disease progression. One pt with stable disease as best response received two additional cycles of 177Lu-DOTATATE at progression. Median PFS (from date of first treatment with 177Lu-DOTATATE until progression/death) was 11.1 months (95% CI 10.6 to NA). Five pts (26%) experienced dose modifying toxicity with 177Lu-DOTATATE. The most common treatment-related toxicities were thrombocytopenia (9 pts, 47%; G3/4 in 1 pt, 5%), anemia (7 pts, 37%; G3/4 in 2 pts, 10.5%), leukopenia (6 pts, 32%; G3/4 in 0 pts), and AST/ALT elevation (4 pts, 21%; G3/4 in 0 pts). NGS results were available in the tumor tissue of 13 pts (68%). The most commonly observed alterations were in MEN1 (6/13, 46%) and DAXX (4/13, 31%). No RB1 alterations were identified. Conclusions: We observed a meaningful disease control rate of 69% during treatment of WD HGNETs with 177Lu-DOTATATE. In this heavily pre-treated population, more than half of pts received all four treatment cycles with treatment-related toxicities largely bone-marrow related, as expected, based on historical data. As would be expected in sstr avid tumors, the vast majority had alterations in chromatin remodeling genes (MEN1, DAXX) consistent with WD NETs, with no RB1 alterations identified.


Pituitary ◽  
2021 ◽  
Author(s):  
Liu-Dong Wei ◽  
Chao Li ◽  
Da Li ◽  
Xing-Ju Liu ◽  
Run-Ting Li ◽  
...  

Abstract Purpose Preoperative diagnosis of pituicytomas is difficult, and management and prognostic factors remain ambiguous. The purpose of this study was to elucidate the radiological characteristics of pituicytoma, to assess the risk factors affecting tumor progression, and to propose the optimal treatment regimen based on comprehensive analysis. Methods We reviewed the clinical data of 22 patients with pituicytoma confirmed pathologically in our institution. In addition, 93 cases of pituicytoma in the previous literature were recruited. The individual data of 115 patients were analyzed to evaluate the adverse factors affecting pituicytoma progression. Results In the combined cohort, 3 of 61 patients who underwent gross-total resection (GTR) developed recurrence (4.9%); of the 54 patients who received non-GTR, 19 progressed (35.2%). Univariate and multivariate Cox regression analysis verified male gender (HR 2.855, 95% CI 1.008–8.089; p = 0.048), TS (transsphenoidal surgery; HR 3.559, 95% CI 1.015–12.476; p = 0.047), and non-GTR (HR 4.388, 95%CI 1.240–15.521; p = 0.022) were independent unfavorable factors for pituicytoma progression. A multivariate logistic regression model verified that tumor diameter ≥ 1.85 cm (OR 4.859, 95% CI 1.335–17.691; p = 0.016) was independent adverse factors for GTR. Compared with TS, OT (open transcranial) is more likely to have postoperative complications (OR 3.185, 95% CI 1.020–9.944; p = 0.046), especially vision deterioration (OR 37.267, 95% CI 4.486–309.595; p = 0.001). Conclusion Based on our findings, GTR was advocated as an optimal treatment for pituicytomas. However, in order to avoid damage to important structures, partial resection is acceptable. After that, adjuvant radiotherapy is recommended for male patients with high Ki-67 index, and the remaining patients can be followed up closely. When the tumor recurs or progresses, it is recommended to re-operate and remove the lesion completely as far as possible. If GTR is still not possible, postoperative radiotherapy for the residual tumor is recommended.


2021 ◽  
Vol 11 ◽  
Author(s):  
Waseem Masalha ◽  
Dieter Henrik Heiland ◽  
Christine Steiert ◽  
Marie T. Krüger ◽  
Daniel Schnell ◽  
...  

ObjectiveSpheno-orbital meningiomas (SOM) are rare intracranial tumors that arise at the sphenoid wing. These tumors can invade important neurovascular structures making radical resection difficult, while residual tumors often lead to recurrence. The purpose of this study was to evaluate prognostic factors influencing the recurrence and progression-free survival (PFS) rates of spheno-orbital meningiomas, with a particular focus on the role of surgery and postoperative radiotherapy.MethodsBetween 2000 and March 2020, 65 cases of spheno-orbital meningioma were included, of which 50 cases underwent surgical treatment alone, and 15 cases underwent resection and radiotherapy. A Kaplan-Meier analysis was performed to provide median point estimates and PFS rates; further, Cox regression analysis was used to identify significant factors associated with treatment.ResultsGross total resection significantly reduced the risk of recurrence (p-value = 0.0062). There was no significant benefit for progression-free survival after postoperative radiotherapy (p-value = 0.42). Additionally, spheno-orbital meningiomas with an invasion of the cavernous sinus and intraconal invasion showed significantly worse PFS compared to other locations (p-value = 0.017).ConclusionThe maximal safe resection remains the most important prognostic factor associated with lower recurrence rates and longer PFS in patients with spheno-orbital meningioma. The invasion of the cavernous sinus and intraconal invasion was an independent factor associated with worse PFS. Patients with postoperative high-precision radiotherapy did not show significantly better PFS due to the small number of patients.


2014 ◽  
Vol 465 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Gabriele Carlinfante ◽  
Paola Baccarini ◽  
Debora Berretti ◽  
Tiziana Cassetti ◽  
Maurizio Cavina ◽  
...  

2018 ◽  
Vol 25 (7) ◽  
pp. 1658-1664 ◽  
Author(s):  
Yuksel Urun ◽  
H Arzu Yasar ◽  
Hande Turna ◽  
Ece Esin ◽  
A Murat Sedef ◽  
...  

Purpose Studies in the last decade show survival improvement with checkpoint blocker therapy in patients with metastatic malign melanoma. Our purpose was to define the efficacy of ipilimumab according to the patient's baseline characteristics including absolute lymphocytes count. Methods We collected the data of 97 patients with advanced malign melanoma treated with ipilimumab (3 mg/kg, q3w) retrospectively. Log-rank test was used to analyze the univariate effects of patient's characteristics (age, gender, metastatic sites, ECOG PS, type of melanoma, lactic dehydrogenase levels, anemia, lymphocytes (L), neutrophils (N), N/L ratio), c-kit and BRAF status. Survival analyses were estimated with Kaplan–Meier method. Cox regression analysis was used to assess the possible factors identified with log-rank test. Results The median age was 58, and 58% were male and 90% of patients had at least one prior systemic therapy. The median survival was 9.7 months for all patients; and the 12- and 24-month survival rates were 43% and 19%, respectively. Absolute lymphocytes count, lactic dehydrogenase level, bone metastasis, the number of metastatic sites, and RECIST response were significantly related to survival. After Cox regression analysis, RECIST response (complete or partial response), absolute lymphocytes count (more than 1500/mm3) and the number of metastatic sites (less than three sites) remained as significant independent prognostic factors for longer survival. Conclusion Ipilimumab improved survival of patients with metastatic malign melanoma. However, patients with fewer metastatic sites and higher absolute lymphocytes count have a significantly better benefit. To determine if these markers could be used to direct patient therapy, further validation analysis is needed.


2006 ◽  
Vol 92 (6) ◽  
pp. 531-535 ◽  
Author(s):  
Leonardo Ferrari ◽  
Silvia Della Torre ◽  
Paola Collini ◽  
Antonia Martinetti ◽  
Giuseppe Procopio ◽  
...  

Aims and background Kit protein expression seems to be associated with a poor outcome in cancer patients and may be an important target for new anticancer drugs. We examined by immunohistochemistry the presence of Kit protein in neuroendocrine tumors (NETs) to explore its relationship with histological grade and proliferation index. Patients and methods Thirty-five tumor specimens from patients with 24 well differentiated and 11 poorly differentiated NETs were examined for the presence of Kit protein and the proliferation index marker Ki-67. Results Eleven specimens were positive for Kit protein expression, 8 of which had poorly-differentiated histology and only 3 had well-differentiated histology. Most of the tumors showing immunopositivity for Kit protein were also characterized by a high proliferation index. Conclusions Immunohistochemical positivity for Kit protein is mainly related to poorly differentiated NETs. In our study, the percentage of tumors with immunopositivity for Kit protein was lower than that observed by other authors. This difference could be attributable to the different immunohistochemistry procedures used and to the biological heterogeneity of NETs. The number of Kit protein-positive NETs may justify targeted therapy with a tyrosine kinase receptor-associated inhibitor only in a selected subset of patients, whenever no other therapy is available and an autocrine loop sustained by the Kit receptor and its specific ligand has been demonstrated.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16038-e16038
Author(s):  
A. Tryakin ◽  
M. Fedyanin ◽  
A. Bulanov ◽  
D. Titov ◽  
G. Allakhverdiyeva ◽  
...  

e16038 Background: The commonly used IGCCCG classification probably underestimates other prognostic factors (tumor markers, stage) for advanced seminoma, which was shown later (Fossa S., 1997). Furthermore, in contrast to nonseminoma different cisplatin-based regimens have not been directly compared in this population. We performed an analysis to review the outcome and prognostic factors of patients (pts) with advanced seminoma treated in our center during the last two decades. Methods: From 1983 to 2005, 250 chemotherapy (CT)-naïve pts with advanced seminoma received induction platinum-based CT, which was divided as an “older” (76 pts) and “modern” (174 pts) one. “Older CT” included cyclophosphamide + cisplatin (46 pts), ifosfamide + carboplatin (12 pts), PVB (8 pts) and other regimens (10 pts). “Modern CT” contained BEP (26 pts) and EP (148 pts) regimens. 227 (91%) pts had primary testicular tumor, 241 (96%) pts belonged to IGCCCG good prognostic group. Median follow-up was 57 (range, 3–276) months for the pts who survived. Prognostic factors were analyzed in “modern CT” group. Progression-free survival (PFS) was an end-point for Cox‘ stepwise regression analysis. Results: “Modern CT” significantly improved PFS (5-years, 91% and 74%, p = 0.002) but not OS (5-years, 92% and 89%, p = 0.28), which could be explained by effective salvage CT. Univariate analysis revealed following factors as significant: number of metastatic sites, presence of pulmonary metastases, RPLN size, hCG level, and LDH level. Cox‘ regression analysis showed pre-CT LDH as the only prognostic factor for PFS (HR 7,6, 95% CI 1,6–36.3). Using cut-off 2 x upper limit of normal for LDH level, “modern CT” group can be divided into favorable (105 [60%] pts) and unfavorable (69 (40%) pts) groups with 5-years DFS 98% vs. 78% (HR 11.1, 95% CI 3.2–33.3) and 5-years OS 99% vs. 80% (HR 11.07, 95% CI 3.09–27.92), respectively. Conclusions: Comparing with older cisplatin-based regimens, the new ones (BEP or EP) improved PFS without significant influence on OS in pts with advanced seminoma. Pre-treatment LDH level is an important independent prognostic factor, which could help stratify pts better into risk groups. Further studies with risk-adapted policy in advanced seminoma are warranted. No significant financial relationships to disclose.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Bei Li ◽  
Long Fang ◽  
Baolong Wang ◽  
Zengkun Yang ◽  
Tingbao Zhao

Osteosarcoma often occurs in children and adolescents and causes poor prognosis. The role of RNA-binding proteins (RBPs) in malignant tumors has been elucidated in recent years. Our study aims to identify key RBPs in osteosarcoma that could be prognostic factors and treatment targets. GSE33382 dataset was downloaded from Gene Expression Omnibus (GEO) database. RBPs extraction and differential expression analysis was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to explore the biological function of differential expression RBPs. Moreover, we constructed Protein-protein interaction (PPI) network and obtained key modules. Key RBPs were identified by univariate Cox regression analysis and multiple stepwise Cox regression analysis combined with the clinical information from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Risk score model was generated and validated by GSE16091 dataset. A total of 38 differential expression RBPs was identified. Go and KEGG results indicated these RBPs were significantly involved in ribosome biogenesis and mRNA surveillance pathway. COX regression analysis showed DDX24, DDX21, WARS and IGF2BP2 could be prognostic factors in osteosarcoma. Spearman’s correlation analysis suggested that WARS might be important in osteosarcoma immune infiltration. In conclusion, DDX24, DDX21, WARS and IGF2BP2 might play key role in osteosarcoma, which could be therapuetic targets for osteosarcoma treatment.


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