Clinicopathological and genomic features in patients with head and neck neuroendocrine carcinoma

AbstractNeuroendocrine carcinoma (NEC) of the head and neck is a rare type of malignancy, accounting for only 0.3% of all head and neck cancers, and its clinicopathological and genomic features have not been fully characterized. We conducted a retrospective analysis of 27 patients with poorly differentiated NEC of the head and neck seen at our institution over a period of 15 years. Patient characteristics, adopted therapies, and clinical outcomes were reviewed based on the medical records. Pathological analysis and targeted sequencing of 523 cancer-related genes were performed using evaluable biopsied/resected specimens based on the clinical data. The most common tumor locations were the paranasal sinus (33%) and the oropharynx (19%). Eighty-one percent of the patients had locally advanced disease. The 3-year overall survival rates in all patients and in the 17 patients with locally advanced disease who received multimodal curative treatments were 39% and 53%, respectively. Histologically, large cell neuroendocrine carcinoma was the predominant subtype (58% of evaluable cases), and the Ki-67 labeling index ranged from 59 to 99% (median: 85%). Next-generation sequencing in 14 patients identified pathogenic/likely pathogenic variants in TP53, RB1, PIK3CA-related genes (PREX2, PIK3CA, and PTEN), NOTCH1, and SMARCA4 in six (43%), three (21%), two (14%), two (14%), and one (7%) patients, respectively. Sequencing also detected the FGFR3-TACC3 fusion gene in one patient. The median value of the total mutational burden (TMB) was 7.1/Mb, and three patients had TMB ≥ 10. Regardless of the aggressive pathological features, our data revealed favorable clinical characteristics in the patients with locally advanced disease who received curative treatment. The lower TP53 and RB1 mutation prevalence rates compared to those described for small cell lung cancer suggests the biological heterogeneity of NEC in different parts of the body. Furthermore, the FGFR3-TACC3 fusion gene and mutations in genes encoding the components of the NOTCH and PI3K/AKT/mTOR pathways found in our study may be promising targets for NEC of the head and neck.

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Optimizing approaches to head and neck cancer: strengths and weaknesses in multidisciplinary treatments of locally advanced disease

Annals of Oncology ◽

10.1093/annonc/mdn447 ◽

2008 ◽

Vol 19 ◽

pp. vii195-vii199 ◽

Cited By ~ 1

Author(s):

J. Giralt ◽

S. Benavente ◽

M. Arguis

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Advanced Disease ◽

Locally Advanced ◽

Locally Advanced Disease

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Trends in head and neck squamous cell carcinoma (HNSCC) clinical research as reported in the ASCO Proceedings from 1996- 2006

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.6089 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 6089-6089

Author(s):

K. A. David ◽

A. Rademaker ◽

M. Agulnik

Keyword(s):

Overall Survival ◽

Clinical Research ◽

Head And Neck ◽

Survival Benefit ◽

Concurrent Chemoradiotherapy ◽

Advanced Disease ◽

Locally Advanced ◽

Phase Iii ◽

Locally Advanced Disease ◽

Number Of Authors

6089 Background: The results of clinical research can be seen through the review of ASCO Proceedings abstracts. We aimed to identify treatment trends in HNSCC as reported at the ASCO annual meetings from 1996 to 2006 and to see if an improvement in patient survival occurred. Methods: All abstracts in the head and neck section of ASCO Proceedings from 1996 to 2006 were reviewed. Abstracts on locally advanced, recurrent or metastatic HNSCC were further explored. Descriptive summary information was recorded regarding number of authors, randomization, trial phase, presence of novel drug or combination therapies, timing of chemotherapy, and disease-free and overall survival. Results: From 1996 to 2006, there were a total of 1,043 Head and Neck Cancer abstracts. Out of 311 phase 2 and 3 abstracts, 207 were presented. Of these, 78 were presented in the first half of the study period (1996–2000) compared to 129 in the second half (2001–2006). The average number of authors over the 10-year period was 12.7. Randomized controlled study proportions fluctuated, ranging from 11.8% in 2005 to 47.1% in 2001. 60% of studies focused on locally advanced disease; 32% on metastatic or recurrent disease, and 7% on both. Induction chemotherapy accounted for 31% of presented abstracts, while only 4% presented adjuvant data. The majority of abstracts used concurrent chemoradiotherapy (57%); 36% studied drug therapy alone. Abstracts presenting new therapies or new therapy combinations decreased (75% in 1996 vs. 61% in 2006). 12 studies (6% of presented studies) showed a statistically significant survival benefit, with 9/12 presented since 2001. All 12 were of patients with locally advanced disease, with the majority (7/12) showing the survival benefit of radiation administered with chemotherapy or cetuximab. Two trials showed the survival benefit of induction docetaxel, cisplatin, and fluorouracil (TPF) compared to PF. Conclusions: Since 1996, the number of presented clinical trials of HNSCC has increased. Overall survival benefits have been shown in Phase III trials in locally advanced disease. The major therapeutic advance over the last decade has been the overall survival gain with the use of concurrent chemoradiotherapy in locally advanced HNSCC. No significant financial relationships to disclose.

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Faculty Opinions recommendation of Optimizing approaches to head and neck cancer: strengths and weaknesses in multidisciplinary treatments of locally advanced disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1124535.581741 ◽

2008 ◽

Author(s):

Robert Haddad

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Advanced Disease ◽

Locally Advanced ◽

Locally Advanced Disease

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Characteristics and outcomes of head and neck cancer in solid organ transplant recipients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17529 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17529-e17529

Author(s):

Samer Alsidawi ◽

Katharine Andress Rowe Price ◽

Ashish V. Chintakuntlawar ◽

Joaquin J. Garcia ◽

Gustavo Figueiredo Marcondes Westin ◽

...

Keyword(s):

Head And Neck ◽

Median Time ◽

Advanced Disease ◽

Locally Advanced ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Cox Proportional Hazards ◽

Solid Organ ◽

Locally Advanced Disease

e17529 Background: The immune system plays a major role in anti-tumor surveillance in healthy individuals. Immunosuppression after solid organ transplant prevents graft rejection, but leads to increased incidence of various malignancies including head and neck squamous cell carcinoma (HNSCC). Outcomes of patients (pts) with post-transplant HNSCC are unknown. Methods: After Institutional Review Board approval, we retrospectively identified pts who developed HNSCC after solid organ transplant between 1995 and 2010. Adults with pathology-proven HNSCC and good follow up were included. Cutaneous cancers were excluded. Median overall survival (mOS) and progression free survival (mPFS) were analyzed using the Kaplan–Meier method. The prognostic effect of variables was studied with Cox proportional hazards models. Results: 33 pts met study inclusion criteria. The median time to HNSCC after transplant was 5.9 years. The primary site was the oral cavity in 15 pts, the oropharynx in 10, the larynx in 3, the hypopharynx in 2, the parotid in 2 and unknown in 1 pt. 58% of pts presented with locally advanced disease, 39% with localized disease and one pt with metastatic disease. 87% underwent upfront surgical resection. Of those, 66% received adjuvant therapy (38% radiation alone and 28% chemoradiation). 6% of pts had definitive chemoradiation. After a median follow up of 10.5 years, the 5-year OS rate was 45% and 37% for localized and locally advanced disease respectively. 75% of pts with oropharyngeal tumors were HPV-positive and they had better outcomes (5-year OS rate of 67%). The mPFS for the cohort was 22.8 months (95% CI; 11.6-50.1) with a median time to relapse of 15.2 months. The pattern of relapse was local in 69% of pts, distant in 25% and local plus distant in 6%. In a multivariate analysis, age > 60 years was a negative predictor of survival (HR 2.7; 95% CI, 1.1 to 6.5; P = 0.03). Conclusions: This retrospective study evaluated the clinical course and outcomes of pts with non-cutaneous HNSCC after solid organ transplant. Pts had inferior survival compared to historical controls. older pts had poor prognosis. The risk of local and distant recurrence was high. HPV-positive oropharyngeal tumors continue to have better outcomes in this population.

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Locally advanced disease: Treatment choice based on risk factors in head and neck cancer

Annals of Oncology ◽

10.1093/annonc/mds452 ◽

2012 ◽

Vol 23 ◽

pp. x171

Keyword(s):

Risk Factors ◽

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Advanced Disease ◽

Locally Advanced ◽

Treatment Choice ◽

Disease Treatment ◽

Locally Advanced Disease

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Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series

Urologia Journal ◽

10.1177/03915603211035191 ◽

2021 ◽

pp. 039156032110351

Author(s):

Alessandro Uleri ◽

Rodolfo Hurle ◽

Roberto Contieri ◽

Pietro Diana ◽

Nicolòmaria Buffi ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Advanced Disease ◽

Independent Predictor ◽

Small Sample Size ◽

Statistical Significance ◽

Locally Advanced ◽

Small Sample ◽

Locally Advanced Disease ◽

Increased Risk

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

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Can 3T multiparametric magnetic resonance imaging accurately detect prostate cancer extracapsular extension?

Canadian Urological Association Journal ◽

10.5489/cuaj.245 ◽

2013 ◽

Vol 7 (11-12) ◽

pp. 699 ◽

Cited By ~ 25

Author(s):

Yannick Cerantola ◽

Massimo Valerio ◽

Aida Kawkabani Marchini ◽

Jean-Yves Meuwly ◽

Patrice Jichlinski

Keyword(s):

Magnetic Resonance Imaging ◽

Prostate Cancer ◽

Magnetic Resonance ◽

Advanced Disease ◽

Locally Advanced ◽

Resonance Imaging ◽

Extracapsular Extension ◽

Predictive Values ◽

Locally Advanced Disease ◽

Multiparametric Magnetic Resonance Imaging

Background: Accurate staging is essential to determine the correct management of patients diagnosed with prostate cancer. We assess the accuracy of 3T multiparametric magnetic resonance imaging (MRI) with endorectal coil (3TemMRI) in detecting prostate cancer local extension.Methods: We retrospectively reviewed charts from January 2008 to July 2012 from all patients undergoing radical prostatectomy. Patients were only included if 3TemMRI and radical prostatectomywere performed at our institution. Based on the presence of extracapsular extension (ECE) at 3TemMRI, prostate cancer was dichotomized into locally advanced or organ-confined disease. The accuracy of 3TemMRI local staging was then evaluated using definitive pathology as a reference.Results: Overall, 177 radical prostatectomies were performed within the timeframe. After applying exclusion criteria, 60 patients were included in the final analysis. The mean patient age was 67 ± 7 (standard deviation) years. Mean prostate-specific antigen value was 12.7 ± 12.7 ng/L. Based on preoperative characteristics, we considered 38 of the 60 patients (63%) patients high risk. 3TemMRI identified an organ-confined tumour in 46 patients and locally advanced disease in 14 patients. When correlated to final pathology, 3TemMRI specificity, sensitivity, negative and positive predictive values, and accuracy in detecting locally advanced prostate cancer were 90%, 35%, 57%, 79% and 62%, respectively.Interpretation: This study shows that the use of preoperative 3TemMRI can be used to identify organ-confined prostate cancer when locally advanced disease is suspected.

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