Inferior outcome of neuroendocrine tumor patients negative on somatostatin receptor imaging

2020 ◽  
Vol 27 (11) ◽  
pp. 615-624
Author(s):  
Julie Refardt ◽  
Wouter T Zandee ◽  
Tessa Brabander ◽  
Richard A Feelders ◽  
Gaston J H Franssen ◽  
...  

Sufficient expression of somatostatin receptor (SSTR) in well-differentiated neuroendocrine tumors (NETs) is crucial for treatment with somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) using radiolabeled SSAs. Impaired prognosis has been described for SSTR-negative NET patients; however, studies comparing matched SSTR-positive and -negative subjects who have not received PRRT are missing. This retrospective analysis of two prospectively maintained NET databases aimed to compare matched metastatic grade 1 or 2 SSTR-positive and –negative NET patients. SSTR-negativity was defined as having insufficient tumor uptake on diagnostic SSTR imaging. Patients that underwent PRRT were excluded. Seventy-seven SSTR-negative and 248 SSTR-positive grade 1–2 NET patients were included. Median overall survival rates were significantly lower for SSTR-negative compared to SSTR-positive NET patients (53 months vs 131 months; P < 0.001). To adjust for possible confounding by age, gender, grade and site of origin, 69 SSTR-negative NET patients were propensity score matched to 69 SSTR-positive NET patients. Group characteristics were similar, with the exception of SSTR-negative patients receiving more often chemotherapy and targeted treatment. The inferior survival outcome of SSTR-negative compared to SSTR-positive NET patients persisted with a median overall survival of 38 months vs 131 months (P = 0.012). This relationship upheld when correcting for the main influencing factors of having a higher grade tumor or receiving surgery in a multivariate Cox regression analysis. In conclusion, we showed that propensity score-matched SSTR-negative NET patients continue to have a worse prognosis compared to SSTR-positive NET patients despite receiving more aggressive treatment. Differences in tumor biology likely underlie this survival deficit.

2021 ◽  
Author(s):  
Pei-Min Hsieh ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Gin-Ho Lo ◽  
I-Cheng Lu ◽  
...  

Abstract Background: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.Methods: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.Results: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were 1) SR and cirrhosis; 2) SR, cirrhosis, and Child-Pugh (C-P) class; 3) SR, hepatitis B virus (HBV) infection, and C-P class; and 4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs non-SR were 44.0% vs 28.7%, 72.2% vs 42.6%, 42.6% vs 36.2, 44.6% vs 23.5%, and 41.4% vs 15.3% (all p-values<0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.Conclusion: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yaw-Sen Chen ◽  
Pei-Min Hsieh ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Gin-Ho Lo ◽  
...  

Abstract Background The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages. Methods Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. Results In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0–96) months for the total cohort and was subdivided into 52 (8–96), 32 (1–96), 19 (0–84), and 12 (0–79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child–Pugh (C–P) class; (3) SR, hepatitis B virus (HBV) infection, and C–P class; and (4) SR, HBV infection, and C–P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages. Conclusions SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sami Matrood ◽  
Leonidas Apostolidis ◽  
Jörg Schrader ◽  
Sebastian Krug ◽  
Harald Lahner ◽  
...  

Background and AimsNeuroendocrine neoplasms (NENs) of the presacral space are an extremely rare disease entity with largely unknown outcome and no established standard of care treatment. Therefore, we wanted to analyze clinical presentation, histopathological findings, treatment outcomes, and prognosis in a multicentric patient cohort.MethodsWe searched local databases of six German NEN centers for patients with presacral NEN. Retrospective descriptive analyses of age, sex, stage at diagnosis, symptoms, grade, immunohistochemical investigations, biomarkers, treatment, and treatment outcome were performed. Kaplan–Meier analysis was used to determine median overall survival.ResultsWe identified 17 patients (11 female, 6 male) with a median age of 50 years (range, 35–66) at diagnosis. Twelve cases presented initially with distant metastases including bone metastases in nine cases. On pathological review the majority of patients had well-differentiated G2 tumors. Immunohistochemical profile resembled rectal NENs. All but one patient had non-functioning tumors. Somatostatin receptor imaging was positive in 14 of 15 investigated cases. Eight patients were treated surgically including palliative resections; 14 patients received somatostatin analogs with limited efficacy. With 14 PRRTs completed, 79% showed clinical benefit, whereas only one patient with neuroendocrine carcinoma (NEC) responded to chemotherapy. Treatment with everolimus in three patients was not successful, whereas cabozantinib resulted in a disease stabilization in a heavily pretreated patient. During a median observation period of 44.5 months, 6 patients died. Median overall survival was not reached.ConclusionPresacral NEN are histopathologically similar to rectal NENs. Presacral NEN should be considered as possible primary in NEN of unknown primary. The majority of tumors is non-functioning and somatostatin receptor positive. PRRT demonstrated promising activity; tyrosine kinase inhibitors warrant further investigations. Further molecular characterization and prospective evaluation of this rare tumor entity are needed.


BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuepeng Cao ◽  
Qing Chen ◽  
Zhizhan Ni ◽  
Feng Wu ◽  
Chenshen Huang ◽  
...  

Abstract Background Bridge to elective surgery (BTS) using self-expanding metal stents (SEMSs) is a common alternative to emergency surgery (ES) for acute malignant left-sided colonic obstruction (AMLCO). However, studies regarding the long-term impact of BTS are limited and have reported unclear results. Methods A multicenter observational study was performed at three hospitals from April 2012 to December 2019. Propensity score matching (PSM) was introduced to minimize selection bias. The primary endpoint was overall survival. The secondary endpoints included surgical approaches, primary resection types, total stent-related adverse effects (AEs), surgical AEs, length of hospital stay, 30-day mortality and tumor recurrence. Results Forty-nine patients in both the BTS and ES groups were matched. Patients in the BTS group more often underwent laparoscopic resection [31 (63.3%) vs. 8 (16.3%), p < 0.001], were less likely to have a primary stoma [13 (26.5%) vs. 26 (53.1%), p = 0.007] and more often had perineural invasion [25 (51.0 %) vs. 13 (26.5 %), p = 0.013]. The median overall survival was significantly lower in patients with stent insertion (41 vs. 65 months, p = 0.041). The 3-year overall survival (53.0 vs. 77.2%, p = 0.039) and 5-year overall survival (30.6 vs. 55.0%, p = 0.025) were significantly less favorable in the BTS group. In multivariate Cox regression analysis, stenting (hazard ratio(HR) = 2.309(1.052–5.066), p = 0.037), surgical AEs (HR = 1.394 (1.053–1.845), p = 0.020) and pTNM stage (HR = 1.706 (1.116–2.607), p = 0.014) were positively correlated with overall survival in matched patients. Conclusions Self-expanding metal stents as “a bridge to surgery” are associated with more perineural invasion, a higher recurrence rate and worse overall survival in patients with acute malignant left-sided colonic obstruction compared with emergency surgery.


2021 ◽  
Author(s):  
Zhaolin Yang ◽  
Jiale Zhou ◽  
Yizheng Xue ◽  
Yu Zhang ◽  
Kaijun Zhou ◽  
...  

Abstract Purpose To develop an immunotype-based prognostic model for predicting the overall survival (OS) of patients with clear cell renal carcinoma (ccRCC). We explored novel immunotypes of patients with ccRCC, particularly those associated with overall survival. A risk-metastasis model was constructed by integrating the immunotypes with immune genes and used to test the accuracy of the immunotype model. Patients and Methods Patient cohort data were obtained from The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, Renji database, and Surveillance, Epidemiology, and End Results (SEER) database. We employed the R software to select 3 immune cells and construct an immunotype-based prediction model. Immune genes selected using random Forest Algorithm were validated by immunohistochemistry (IHC). The H&L risk-metastasis model was constructed to assess the accuracy of the immunotype model through Multivariate COX regression analysis. Result Patients with ccRCC were categorized into immunotype H subgroup and immunotype L subgroup based on the overall survival rates. The immunotypes were found to be the independent prognostic index for ccRCC prognosis. As such, we constructed a new immunotypes-based SSIGN model. Three immune genes associated with difference between immunotype H and L were identified. An H&L risk-metastasis model was constructed to evaluate the accuracy of the immunotype model. Compared to the W-Risk-metastasis model which did not incorporate immunotypes, the H&L risk-metastasis model was more precise in predicting the survival of ccRCC patients. Conclusion The established immunotype model can effectively predict the survival of ccRCC patients. Except for mast cells, T cells and macrophages are positively associated with the overall survival of patients. The three immune genes identified, herein, can predict the survival rate of ccRCC patients, and expression of these immune genes is strongly linked to poor survival. The new SSIGN model provides an accurate tool for predicting the survival of ccRCC patients. H&L risk-metastasis model can effectively predict the risk of tumor metastasis.


2020 ◽  
Vol 48 (8) ◽  
pp. 030006052093085
Author(s):  
Jia Han ◽  
Yiyang Yu ◽  
Sujia Wu ◽  
Zhen Wang ◽  
Weibin Zhang ◽  
...  

Objective This study was performed to explore the relationship between various clinical factors and the prognosis of limb osteosarcoma. Methods We retrospectively analyzed the clinical data of 336 patients with limb osteosarcoma treated from June 2000 to August 2016 at 7 Chinese cancer centers. Data on the patients’ clinical condition, treatment method, complications, recurrences, metastasis, and prognosis were collected and analyzed. Kaplan–Meier analysis and Cox regression models were used to analyze the data. Results The patients comprised 204 males and 132 females ranging in age from 6 to 74 years (average, 21.1 years). The overall 3- and 5-year survival rates were 65.0% and 55.0%, respectively. The 5-year overall survival rate was 64.0% with standard chemotherapy and 45.6% with non-standard chemotherapy. Cox regression analysis demonstrated that standard chemotherapy, surgery, recurrence, and metastasis were independent factors associated with the prognosis of limb osteosarcoma. Conclusion The survival of patients with limb osteosarcoma can be significantly improved by combining standard chemotherapy and surgery. The overall survival rate can also be improved by adding methotrexate to doxorubicin–cisplatin–ifosfamide triple chemotherapy.


2020 ◽  
Vol 86 (2) ◽  
pp. 127-133
Author(s):  
Shengxiang Chen ◽  
Wenfeng Tang ◽  
Randong Yang ◽  
Xiaoxiao Hu ◽  
Zhongrong Li

Adrenal neuroblastoma (NB) is a relatively common malignancy in children. The Surveillance, Epidemiology, and End Results database was used to present demographic data and a survival analysis with the aim of making tumor management better. The Surveillance, Epidemiology, and End Results database was used to search pediatric patients (age £16 years) with NB from 2004 to 2013. The Kaplan-Meier method was used to calculate the overall survival. And, we used Cox regression analysis to determine hazard ratios for prognostic variables. Independent prognostic factors were selected into the nomogram to predict individual's three-, five-, and seven-year overall survival. The study included a total of 1870 pediatric patients with NB in our cohort. Overall, three-, five-, and seven-year survival rates for adrenal NB were 0.777, 0.701, and 0.665, respectively, whereas the rates for nonadrenal NB were 0.891, 0.859, and 0.832, respectively. The multivariate analysis identified age >1 year, no complete resection (CR)/CR, radiation, and regional/distant metastasis as independent predictors of mortality for adrenal NB. Concordance index of the nomogram was 0.665 (95% confidence interval, 0.627–0.703). Pediatric patients with adrenal NB have significantly worse survival than those with nonadrenal NB. Adrenal NB with age <1 year, treated with surgery, no radiation, and localized tumor leads to a better survival. There was no survival difference for patients to receive CR and no CR.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 565-565
Author(s):  
Divya Arora ◽  
Salman Hasan ◽  
Deborah Jebakumar ◽  
Yolanda Munoz ◽  
John Ford ◽  
...  

565 Background: While radiation portals are tailored to a patient’s unique anatomy and the selection of systemic agents routinely employs biomarker data, the selection of radiotherapy based on a patient’s tumor biology is not routinely utilized in breast cancer. The purpose of this study was to identify which genetic markers are possible predictors for local recurrence as a surrogate for radiation response. Methods: We identified 200 patients who received radiotherapy for breast cancer. Selected tumor markers included: Androgen receptor (AR), Hypoxia Inducible Factor 1-α (HIF-1), Phosphotidylinosotol-4,5-bisphosphate 3-kinase (PI3K), and Interleukin 13 (IL-13). Biomarkers were analyzed in terms of “extent” and “intensity” on a scale of 0-3 and scored by 2 separate pathologists. The primary endpoint of local recurrence (LR) & secondary endpoint of overall survival were analyzed using Kaplan-Meier survival curves, log-rank test for differences, and Cox regression models. Results: Median follow up was 7.98 years. At 5 years, the rate of LR was 92.6% and overall survival was 89.4%. On multivariate Cox regression analysis, a one unit increase in IL-13 extent increased the hazard of LR by 73%. A one unit decrease in AR extent increased the hazard of LR by 134%. The hazard of death increased 3.2 times for each unit increase in HIF1 extent. The hazard of death increased 1.5 times for each unit increase in PI3K extent. PI3K extent and intensity was increased, and AR extent and intensity was decreased in triple negative breast cancer (TNBC) (n = 68) vs non-TNBC (p < 0.0001). African Americans had a 4.2 times hazard of LR vs Caucasians. Conclusions: Expression of IL-13 was associated with a higher risk of LR; expression of AR was associated with decreased LR. These two markers may be instrumental in predicting radiation response. If this study is validated, cancers that express more IL-13 may require higher doses or targeted therapy. In contrast, those cancers expressing AR may not require as aggressive therapy. Lastly, PI3K and HIF1 α expression were significant predictors of worse overall survival. The clinical implications of these biologic markers are significant as they may help to guide biologically-driven, personalized breast cancer radiotherapy.


2020 ◽  
Author(s):  
Chih-Wen Lin ◽  
Yaw-Sen Chen ◽  
Gin-Ho Lo ◽  
Yao-Chun Hsu ◽  
Chia-Chang Hsu ◽  
...  

Abstract Background: Patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are recommended to undergo transcatheter arterial chemoembolization (TACE). However, TACE in combination with radiofrequency ablation (RFA) is not inferior to surgical resection (SR), and the benefits of surgical resection (SR) for BCLC stage B HCC remain unclear. Hence, this study aims to compare the impact of SR, TACE+RFA, and TACE on analyzing overall survival (OS) in BCLC stage B HCC. Methods: Overall, 428 HCC patients were included in BCLC stage B, and their clinical data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Results: One hundred forty (32.7%) patients received SR, 231 (53.9%) received TACE+RFA, and 57 (13.3%) received TACE. The OS was significantly higher in the SR group than that in the TACE+RFA group [hazard ratio (HR): 1.78; 95% confidence incidence (CI): 1.15-2.75, p=0.009]. The OS was significantly higher in the SR group than that in the TACE group (HR: 3.17; 95% CI: 2.31-4.36, p<0.0001). Moreover, the OS was significantly higher in the TACE+RFA group than that in the TACE group (HR: 1.82; 95% CI: 1.21-2.74, p=0.004). The cumulative OS rates at 1, 3 and 5 years in the SR, TACE+RFA, and TACE groups were 89.2%, 69.4% and 61.2%, 86.0%, 57.9% and 38.2%, and 69.5%, 37.0% and 15.2%, respectively. After propensity score matching, the SR group still had a higher OS than those of the TACE+RFA and TACE groups. The TACE+RFA group had a higher OS than that of the TACE group. Conclusion: The SR group had higher OS than the TACE+RFA and TACE groups in BCLC stage B HCC. Furthermore, the TACE+RFA group had higher OS than the TACE group.


2020 ◽  
Author(s):  
Yuepeng Cao ◽  
Qing Chen ◽  
Zhizhan Ni ◽  
Feng Wu ◽  
Chenshen Huang ◽  
...  

Abstract PurposeBridge to elective surgery (BTS) using self-expanding metal stents (SEMS) is a common alternative to emergency surgery (ES) for acute malignant left-sided colonic obstruction (AMLCO). However, the study regarding long-term impact of BTS is limited and unclear.MethodsA multicenter observational study was performed at three hospitals from April 2012 to December 2019. Propensity score matching (PSM) was introduced to minimize selection bias. The primary endpoint was overall survival. The secondary endpoints included surgical approaches, primary resection types, total stent related adverse effects (AEs), surgical AEs, length of hospital stay, 30-day mortality and tumor recurrence.Results49 patients in both BTS and ES group were matched. Patients in the BTS group more often underwent laparoscopic resection (31 [63.3%] vs 8 [16.3%], p<0.001), less likely to have a primary stoma (13 [26.5%] vs 26 [53.1%], p=0.007) and more often had perineural invasion (25 [51.0%] vs 13 [26.5%], p=0.013). The median overall survival was significantly lower in patients with stent insertion (41 vs 65 months, p=0.041). 3-year overall survival (53.0% vs 77.2%, p=0.039) and 5-year overall survival (30.6% vs 55.0%, p=0.025) were significantly less favorable in the BTS group. In the multivariate Cox regression analysis, stenting (hazard ratio(HR)= 2.309(1.052-5.066), p=0.037), surgical AEs (HR=1.394(1.053-1.845), p=0.020) and pTNM stage (HR=1.706(1.116-2.607), p=0.014) were positively correlated with overall survival in matched patients. ConclusionsSelf-expanding metal stents as “a bridge to surgery” is associated with more perineural invasion, higher recurrence rate and worse overall survival in patients with acute malignant left-sided colonic obstruction compared with emergency surgery.


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