scholarly journals Hyperprogression After Immunotherapy for Primary Small Cell Neuroendocrine Carcinoma of the Ureter: A Case Report

2021 ◽  
Vol 11 ◽  
Author(s):  
Defeng Qing ◽  
Luxing Peng ◽  
Feng Cen ◽  
Xinjun Huang ◽  
Qiang Wei ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Literature Report ◽  
Free Survival ◽  
Hyperprogressive Disease

BackgroundPrimary small cell neuroendocrine carcinoma (SCNEC) in the ureter is extremely rare and has been sporadically reported in case reports. Its incidence, diagnosis, treatment, and outcomes have not yet been thoroughly understood. Here we present a patient with advanced SCNEC in the ureter who was treated by multimodal strategies. To the best of our knowledge, this is the first literature report about the clinical outcomes of the combination of programmed death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) and radiotherapy in patient with primary ureteral SCNEC.Case PresentationA 71-year old male presented with right flank pain and gross hematuria. A laparoscopic right nephroureterectomy was performed. He was diagnosed with primary ureteral SCNEC, pT3N0M0. Following the surgery, 4 cycles of adjuvant chemotherapy with carboplatin and etoposide (CE) were administered, with disease-free survival (DFS) of 10.1 months. He was then offered 4 cycles of palliative first-line chemotherapy with nedaplatin and irinotecan. The disease was continuously progressed, with progression-free survival (PFS) of 3.7 months. The patient subsequently received second-line treatment with PD-L1 ICI combined with radiotherapy. Unfortunately, hyperprogressive disease was found at the end of treatment. MRI and CT scan showed bilateral pubic bones, right acetabulum, and liver metastases. Without further intervention, the patient died from extensive metastatic disease 2 months after diagnosis, with overall survival (OS) of 18.2 months.ConclusionPhysicians must be aware of this rare and aggressive carcinoma at its initial presentation. Special attention should be paid to the potential likelihood of hyperprogression during the treatment.

Prognostic Factors of Surgically Treated Early-Stage Small Cell Neuroendocrine Carcinoma of the Cervix

2015 ◽  
Vol 25 (7) ◽  
pp. 1315-1321 ◽  
Author(s):  
Lei Yuan ◽  
Hongyuan Jiang ◽  
Yin Lu ◽  
Sun-wei Guo ◽  
Xishi Liu
Keyword(s):  
Risk Factors ◽  
Survival Analysis ◽  
Neuroendocrine Carcinoma ◽  
Early Stage ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Free Survival ◽  
Parametrial Invasion ◽  
Disease Free

ObjectiveSmall cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare malignancy and has a high mortality despite of aggressive surgical treatment. The aims of this study were to determine the prognostic factors associated with the survival of surgically treated patients with early-stage SCNECC and to see whether carboplatin plus paclitaxel (TC) therapy after surgery can improve their survival.MethodsThirty-eight women with FIGO stages IA2 (n = 1), IB1 (n = 31), IB2 (n = 3), and IIA1 (n = 3) were treated with radical hysterectomy, followed by adjuvant TC or non-TC, with or without radiotherapy, in our hospital between 2004 and 2013. Medical charts and clinical data were retrieved and retrospectively reviewed. The Kaplan-Meier method and Cox regression model were used for survival analysis.ResultsThe mean age of patients were 40.4 ± 7.0 years. The preoperative detection rate of SCNECC was only 34.2%. The overall 1-, 2-, and 5-year survival rate was 81.6%, 54.7%, and 43%, respectively, whereas the 1-, 2-, and 5-year cumulative recurrence rate was 37.8%, 44.2%, and 49.3%, respectively. For overall survival (OS), the univariate survival analysis indicated that tumor homology, parametrial invasion, chemotherapy regimens, and chemotherapy courses were risk factors. For disease-free survival, the univariate survival analysis identified lymph node involvement, tumor homology, parametrial invasion, chemotherapy regimens, and chemotherapy courses as risk factors. However, when multivariable Cox regression model was used, only parametrial invasion and postoperative chemotherapy regimen were identified as risk factors for both OS (P = 0.037 and P = 0.016) and disease-free survival (P = 0.044 and P = 0.018).ConclusionsSmall cell neuroendocrine carcinoma of the cervix is a deadly variant of cervical cancer. Postoperative TC chemotherapy may improve the OS and disease-free survival in women with early-stage SCNECC.

scholarly journals Novel Treatment of Small-Cell Neuroendocrine of the Vagina

2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
Kathryn Kostamo ◽  
Mishka Peart ◽  
Nathalie McKenzie ◽  
Conisha Holloman ◽  
S. J. Carlan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Neuroendocrine Carcinoma ◽  
Expression Profile ◽  
Tumor Tissue ◽  
Progression Free Survival ◽  
Small Cell ◽  
Initial Visit ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Free Survival

Background. Primary vaginal small-cell neuroendocrine carcinoma is an extremely rare and highly aggressive malignancy. Eighty-five percent of patients die within one year of diagnosis from metastatic disease despite multimodal therapy. Gene expression profiling of tumor tissue may be useful for treatment options for various malignancies. Case. A 34-year-old nulliparous woman was diagnosed with primary vaginal small-cell neuroendocrine carcinoma. Twenty weeks after the initial visit, she was diagnosed with recurrence and started on chemoradiation based on the results of gene expression profile of tumor tissue. She died 34 months after the initial visit and had a 14-month progression-free survival (PFS). Conclusion. Gene expression profile of tumor tissue in the management of primary vaginal small-cell neuroendocrine carcinoma may be helpful in extending progression-free survival.

Baseline systemic inflammatory immune index may predict overall survival and progression-free survival in patients with non-small cell lung cancer patients on immune checkpoint inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21202-e21202
Author(s):  
John P. Palmer ◽  
Yenong Cao ◽  
Samer Ibrahim ◽  
Natasha Dhawan ◽  
Muhammad Zubair Afzal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
The Mean ◽  
Nsclc Patients

e21202 Background: Increased systemic inflammatory state and increased inflammation within tumor micro-environment (TME) have been associated with a worse prognosis and lower responsiveness to immune checkpoint inhibitors (ICI). Systemic inflammatory immune index (SII) reflects the changes in the systemic inflammatory matrix. Studies have shown the association of SII with cancer survival and treatment outcomes. We aim to study the effect of SII on treatment outcomes in non-small cell lung cancer (NSCLC) patients being treated with ICI. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs (pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab) alone or in combination with chemotherapy. SII is the product of platelets multiplied by neutrophils divided by lymphocytes. Baseline and 8-week SIIs were obtained. Radiographic response, duration of radiographic response (date of best response to radiographic progression), overall survival (OS), and progression-free survival (PFS) were evaluated. A high SII was defined as a value greater than the median SII. Cox regression univariate and multivariate analyses were performed. Logistic regression, t-test, and Chi-square tests were applied. Results: Overall, 81% patients had adenocarcinoma and 19% patients had squamous, adenosquamous or large cell carcinoma. The majority of the patients were female (56.2% vs. 43.8%). Median SII at baseline was 1335. The objective response rate (ORR) was 45.1%. The disease control rate was 75.8%. The ORR was 51% in patients receiving ICI first-line compared to 35% in those who received ICI as a second-line therapy. At baseline, there was no difference in the mean SII between responders and non-responders (2146.2 vs. 1917.5, P = 0.5); however at 8 weeks, the mean SII was significantly lower in responders compared to non-responders (1198.8 vs. 2880.2, P = 0.02). A total of 15 (10.9%) patients were found to have pseudoprogression or mixed response on follow-up imaging. Among these, 11(73.3%) patients had low SII at 8 weeks (P = 0.04). The median OS was significantly higher in patients with low SII at baseline (29.6 months vs. 10.1 months, P = 0.001 95% CI 10.6 – 22.1). Similarly, there was a significant difference in median PFS in patients with low SII (14.6 months vs. 6.7 months, P = 0.002, 95% CI 5.6 – 11.6). There was no correlation between high or low SII on the incidence of immune-related adverse events. Conclusions: SII may have significant impact on OS and PFS and could be serially monitored to assess the response to ICI. A low SII may help to differentiate pseudoprogression vs. true progression. Prospective studies are needed to validate these findings. Further, it will be interesting to see if SII could be incorporated into predictive models to determine the duration of cytotoxic therapy in selected patients.

Successful management of small cell neuroendocrine carcinoma of the ureter with neoadjuvant chemotherapy and adjuvant chemoradiation: case report and literature review

2021 ◽  
Vol 14 (8) ◽  
pp. e240613
Author(s):  
Mudasir Farooq ◽  
Sherin Daniel ◽  
Anjana Joel ◽  
Nirmal Thampi John
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Neuroendocrine Carcinoma ◽  
Locally Advanced ◽  
Complete Response ◽  
Small Cell ◽  
Successful Management ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Free Survival ◽  
Worse Prognosis

Neuroendocrine tumours (NETs) of the urinary tract are rare, and the urinary bladder is the the most common primary site. Primary ureteric NET is rarer with under 80 cases reported in the literature thus far. Most of these tumours are of the high-grade small cell neuroendocrine carcinoma subtype, which has a worse prognosis. Neoadjuvant chemotherapy has a proven role in the management of NET of the bladder as it downstages the tumour, which may add to significant recurrence-free survival and overall survival. We report the successful management of a patient with locally advanced small cell neuroendocrine carcinoma of the ureter, who had a pathological complete response after neoadjuvant chemotherapy with etoposide and cisplatin. He subsequently received adjuvant chemotherapy followed by radiation and is recurrence-free at a follow-up of 1 year.

scholarly journals The efficacy and safety of immune checkpoints inhibitors plus radiotherapy as a combination therapy for advanced non-small cell lung carcinoma: a meta-analysis

2020 ◽  
Author(s):  
Dan Yang ◽  
DaiRong Li ◽  
LuLu Wang ◽  
LuMi Huang ◽  
JianLin Long ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Radiotherapy Group

Abstract BackgroundImmune checkpoint inhibitors have showed good efficacy in advanced non-small-cell lung cancer(NSCLC). This meta-analysis was conducted to explore the therapeutic efficacy and safety of immune checkpoint inhibitors combined with radiotherapy for patients with advanced NSCLC.MethodsWe used many proper keywords to perform a systematic search in databases and performed a meta-analysis of trials that conducted immune checkpoint inhibitors plus radiotherapy as a treatment for advanced non-small-cell lung cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.ResultsTen trials were finally included in this meta-analysis. The combined ORR and DCR was 34% (19%-49%) and 72% (65%-79%). The combined six-month progression-free survival rates (PFSR6m) and one-year overall survival rate(OSR1y) were 50.0% (29.4%-72.8%) and 59.0% (48%-69%). Immune checkpoint inhibitors plus radiotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.64; 95% CI 0.46–0.90; P = 0.01), OS (HR, 0.62; 95% CI 0.46–0.85; P = 0.003). In subgroup analyses, the combined ORR was 31.5% (16.4%-46.6%), combined DCR was 72.1% (63.3%-80.9%), combined PFS6m was 50.0% (20.6%-79.5%) and combined OSR1y was 59.7% (48.1%-71.2%) for anti-PD-1/PD-L1 antibody plus radiotherapy. The combined ORR was 19.5% (9.1%-29.8%) for anti-CTLA4 antibody plus radiotherapy. The combined PFS6m and OSR1y were 58.9% (26.2%-91.7%) and 59.7% (29.7%-89.8%) respectively for the concurrent therapy group. And the combined PFS6m and OS1y were 55.2% (41.6%-68.8%) and 55.7% (42.1%-69.3%) for sequential therapy. For the low-dose radiotherapy group. The combined PFS6m and OS1y were 45.9% (27.0%-64.8%) and 51.6% (37.5%-65.6%). The combined PFS6m and OS1y were 71.1% (37.9%-104.4%) and 67.4% (29.2%-105.6%) separately for high-dose radiotherapy group. When using as first-line therapy. The combined ORR was 53.8% (23.6%-84.1%) and combined ORR was 76.5% (65.0%-88.1%). While as subsequent therapy, the combined ORR and DCR were 25.9% (14.7%-37.2%) and 69.9% (60.9%-78.9%). The combined PFS6m and OS1y were 51.1% (40.3%-61.9%) and 51.8% (40.9%-62.7%).ConclusionsImmune checkpoint inhibitors plus radiotherapy might be an effective and tolerable option as a treatment for advanced NSCLC.

scholarly journals Association of Systemic Steroid Treatment and Outcome in Patients Treated with Immune Checkpoint Inhibitors: A Real-World Analysis

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5789
Author(s):  
Agnese Paderi ◽  
Elisabetta Gambale ◽  
Cristina Botteri ◽  
Roberta Giorgione ◽  
Daniele Lavacchi ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Detrimental Effect ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Steroid Treatment ◽  
Systemic Steroid ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival

Background: Immune-related adverse events (irAEs) are inflammatory side effects, which can occur during immune-checkpoint(s) inhibitors (ICIs) therapy. Steroids are the first-line agents to manage irAEs because of their immunosuppressive properties. However, it is still debated whether or when steroids can be administered without abrogating the therapeutic efforts of immunotherapy. Methods: We retrospectively evaluated 146 patients with metastatic non-small cell lung cancer (NSCLC), melanoma and renal cell carcinoma (RCC) treated with ICIs. We assessed the progression-free survival (PFS) of patients treated with steroids due to an irAE compared to a no-steroid group. Results: The early treatment with steroid (within the first 30 days from the beginning of immunotherapy) was not related to a shorter PFS (p = 0.077). Interestingly, patients who were treated with steroids after 30 days from the start of immunotherapy had significantly longer PFS (p = 0.017). In a multivariate analysis, treatment with steroids after 30 days was an independent prognostic factor for PFS (HR: 0.59 [95% CI 0.36–0.97], p = 0.037). Conclusions: This retrospective study points out that early systemic steroids administration to manage irAEs might not have a detrimental effect on patient clinical outcome in NSCLC, melanoma and RCC patients.

scholarly journals Co-expression of SOX2 and HR-HPV RISH predicts poor prognosis in small cell neuroendocrine carcinoma of the uterine cervix

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shi-Wen Zhang ◽  
Rong-Zhen Luo ◽  
Xiao-Ying Sun ◽  
Xia Yang ◽  
Hai-Xia Yang ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Uterine Cervix ◽  
Poor Prognosis ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Small Cell ◽  
Hazard Ratio ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Specific Subgroup

Abstract Background Small cell neuroendocrine carcinoma of the uterine cervix (SCNEC) is a rare cancer involving the human papilloma virus (HPV), and has few available treatments. The present work aimed to assess the feasibility of SOX2 and HPV statuses as predictive indicators of SCNEC prognosis. Methods The associations of SOX2 and/or high-risk (HR)-HPV RNA in situ hybridization (RISH) levels with clinicopathological characteristics and prognostic outcomes for 88 neuroendocrine carcinoma (NEC) cases were analyzed. Results Among these patients with SCNEC, SOX2, P16INK4A and HR-HPV RISH expression and SOX2/HR-HPV RISH co-expression were detected in 68(77.3%), 76(86.4%), 73(83.0%), and 48(54.5%), respectively. SOX2-positive and HR-HPV RISH-positive SCNEC cases were associated with poorer overall survival (OS, P = 0.0170, P = 0.0451) and disease-free survival (DFS, P = 0.0334, P = 0.0309) compared with those expressing low SOX2 and negative HR-HPV RISH. Alternatively, univariate analysis revealed that SOX2 and HR-HPV RISH expression, either separately or in combination, predicted the poor prognosis of SCNEC patients. Multivariate analysis revealed that the co-expression of SOX2 with HR-HPV RISH may be an independent factor of OS [hazard ratio = 3.597; 95% confidence interval (CI): 1.085–11.928; P = 0.036] and DFS [hazard ratio = 2.880; 95% CI: 1.199–6.919; P = 0.018] prediction in SCNEC. Conclusions Overall, the results of the present study suggest that the co-expression of SOX2 with HR-HPV RISH in SCNEC may represent a specific subgroup exhibiting remarkably poorer prognostic outcomes compared with the expression of any one marker alone.

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