Use of positron emission tomography/ computed tomography in the initial staging of head and neck squamous cell carcinoma: Accuracy in evaluation of the primary site of the tumor, metastases to cervical lymph nodes, and distant metastases.

AIM: Our study aimed to evaluate the use of positron emission tomography/computed tomography (PET/CT) in the initial staging of head and neck squamous cell carcinoma (HNSCC), including assessment of local and distant spread of the disease. We also aimed to compare the accuracy of PET/CT in the evaluation of human papillomavirus (HPV) positive and HPV-negative oropharyngeal carcinoma. MATERIAL AND METHODS: This single-center, prospective study was conducted between August 2016 and September 2021. A total of 198 patients with HNSCC who underwent PET/CT within the primary staging were included. We compared PET/CT results with histological findings. We calculated the accuracy, sensitivity, specificity, and positive and negative predictive values to assess the primary tumor, cervical lymph nodes, and distant metastases. RESULTS: PET/CT showed a high success rate (32%) in revealing the primary site of carcinoma of unknown primary (CUP). The accuracy of PET/CT in displaying the primary tumor, cervical lymph node metastases, and distant metastases was 89.4%, 85.4%, and 87.4%, respectively. The method provided high sensitivity but lower specificity in all three areas. Specifically, PET/CT showed low specificity in the assessment of small tumors (75%), metastatic involvement of cervical lymph nodes (69.6%), and HPV-positive oropharyngeal carcinoma (55.6%). CONCLUSIONS: The high accuracy of PET/CT to identify distant metastases and whole-body staging in one diagnostic step accelerated primary staging and resulted in earlier commencement of therapy. However, it also led to an overestimation of clinical findings and thus to extensive surgical treatment, especially in patients with small tumors, metastatic involvement of cervical lymph nodes, and HPV- positive oropharyngeal carcinoma. PET/CT is also useful for CUP diagnostics.

Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response.

Breast cancer (BC) is the most frequent malignancy in women accounting for approximately 2 million new cases worldwide annually. Several genetic, epigenetic and environmental factors are known to be involved in BC development and progression, including alterations in post-transcriptional gene regulation mediated by microRNAs (miRNAs). Single nucleotide polymorphisms (SNPs) located in miRNA binding sites (miRSNPs) in 3'-untranslated regions of target genes may affect miRNA-binding affinity and consequently modulate gene expression. We have previously reported a significant association of miRSNPs in the SMUG1 and NEIL2 genes with overall survival in colorectal cancer patients. SMUG1 and NEIL2 are DNA glycosylases involved in base excision DNA repair. Assuming that certain genetic traits are common for solid tumours, we have investigated wherever variations in SMUG1 and NEIL2 genes display an association with BC risk, prognosis, and therapy response in a group of 673 BC patients and 675 healthy female controls. Patients with TC genotype of NEIL2 rs6997097 and receiving only hormonal therapy displayed markedly shorter overall survival (HR = 4.15, 95% CI = 1.7-10.16, P = 0.002) and disease-free survival (HR = 2.56, 95% CI = 1.5-5.7, P = 0.02). Our results suggest that regulation of base excision repair glycosylases operated by miRNAs may modulate the prognosis of hormonally treated BC.

Locally advanced laryngeal cancer: Total laryngectomy or primary non-surgical treatment?

Between January 1997 and December 2013, the Charles University 3rd Medical School and Royal Vinohrady Teaching Hospital Ear, Nose and Throat oncology team treated 185 patients with advanced laryngeal cancer, which, from a surgical perspective, required a total laryngectomy. Overall, ~70% of these patients (n=129) underwent conventional treatment (i.e., total laryngectomy with post-operative radiotherapy), and ~30% (n=56) were treated with larynx preservation protocols (including primary radiotherapy, neoadjuvant chemotherapy followed by radiotherapy or chemoradiotherapy, or primary chemoradiotherapy). Patients treated with laryngeal preservation protocols had a 5-year survival probability of 48%, whereas those treated with total laryngectomy and post-operative radiotherapy had a 5-year survival probability of 63%. This difference was not statistically significant. However, patients who underwent primary surgical treatment survived for a significantly longer period (P<0.010). The sex of the patient did not have a statistically significant impact on patient survival probability. More extensive local disease and more advanced disease stages conferred a lower survival probability, but were not statistically significant; however, a lower survival probability in patients >70 years was identified to be statistically significant (P<0.010). Local disease recurrence and recurrent cervical nodal metastases had a statistically significant impact on the 5-year survival probability (P<0.001). A step wise Cox regression analysis was used to compare the parameters of sex, patient age, tumor extent, disease stage, choice of primary surgery, local recurrence and cervical nodal recurrence. In the first step, local recurrence was selected as the parameter having the greatest effect on survival (P<0.001); patient age >70 years (P<0.001) was selected in the second step; cervical nodal recurrence (P<0.001) in the third step; and disease stage (P<0.010) in the fourth step. Other parameters did not significantly affect survival. The results of the present study confirmed that primary non-surgical treatment is an alternative approach to total laryngectomy, and that an informed patient should determine the treatment approach. The decreased overall survival observed in more extensive tumors suggests that surgical treatment may be a better selection in these cases. Due to increased overall survival, primary non-surgical treatment may be recommended for younger patients. If the patient chooses primary non-surgical treatment, concomitant chemoradiotherapy is recommended. If the patient cannot tolerate cytostatic chemotherapy, radiotherapy alone is recommended.