Molecular Markers to Predict Prognosis and Treatment Response in Uterine Cervical Cancer

Uterine cervical cancer is one of the leading causes of cancer-related mortality in women worldwide. Each year, over half a million new cases are estimated, resulting in more than 300,000 deaths. While less-invasive, fertility-preserving surgical procedures can be offered to women in early stages, treatment for locally advanced disease may include radical hysterectomy, primary chemoradiotherapy (CRT) or a combination of these modalities. Concurrent platinum-based chemoradiotherapy regimens remain the first-line treatments for locally advanced cervical cancer. Despite achievements such as the introduction of angiogenesis inhibitors, and more recently immunotherapies, the overall survival of women with persistent, recurrent or metastatic disease has not been extended significantly in the last decades. Furthermore, a broad spectrum of molecular markers to predict therapy response and survival and to identify patients with high- and low-risk constellations is missing. Implementation of these markers, however, may help to further improve treatment and to develop new targeted therapies. This review aims to provide comprehensive insights into the complex mechanisms of cervical cancer pathogenesis within the context of molecular markers for predicting treatment response and prognosis.

Screening Plasma Exosomal RNAs as Diagnostic Markers for Cervical Cancer: An Analysis of Patients Who Underwent Primary Chemoradiotherapy

This preliminary study aimed to screen non-coding RNAs (ncRNAs) from plasma exosomes as a new method for cervical cancer diagnosis. Differentially expressed RNAs were initially selected from among a group of 12 healthy individuals (normal group) and a pretreatment group of 30 patients with cervical cancer (cancer group). Then, we analyzed the association between an ncRNA-mRNA network and cancer using ingenuity pathway analysis after secondary selection according to the number and correlation of mRNAs (or ncRNAs) relative to changes in the expression of primarily selected ncRNAs (or mRNAs) before and after chemoradiotherapy. The number of RNAs selected from the initial RNAs was one from 13 miRNAs, four from 42 piRNAs, four from 28 lncRNAs, nine from 18 snoRNAs, 10 from 76 snRNAs, nine from 474 tRNAs, nine from 64 yRNAs, and five from 67 mRNAs. The combination of miRNA (miR-142-3p), mRNAs (CXCL5, KIF2A, RGS18, APL6IP5, and DAPP1), and snoRNAs (SNORD17, SCARNA12, SNORA6, SNORA12, SCRNA1, SNORD97, SNORD62, and SNORD38A) clearly distinguished the normal samples from the cancer group samples. We present a method for efficiently screening eight classes of RNAs isolated from exosomes for cervical cancer diagnosis using mRNAs (or ncRNAs) altered by chemoradiotherapy.

Could Primary Chemoradiotherapy in T2 Glottic Cancers Yield Results Comparable to Primary Radiotherapy in T1? Considerations from 531 German Early Stage Patients

T1 glottic cancer is a highly treatable disease with local control (LC) rates over 90% by either primary radiotherapy (pRT) or transoral laser microsurgery (TLM). LC of T2 glottic cancers is 15 percent points poorer on average. However, salvage after pRT entails more than 50% total laryngectomy. Therefore, there is a need for enhanced LC. Altered fractionation regimens improved LC in T1 but not in T2. For this reason, for T2, alternative strategies must be considered. In a large observational cohort study including 531 early-stage laryngeal cancers, a small number of patients were treated with primary chemoradiotherapy (pCRT). In multivariable analysis, factors associated with significantly poorer outcomes included age, comorbidities, supraglottic localization, and T category. While there was a significant difference between pRT and surgery (HR 1.79; 95%-CI: 1.15–2.79), there was none between pCRT and surgery (HR 0.70; 95%-CI: 0.33–1.51). There is evidence from the literature that pCRT in early glottic cancers could yield results that surpass the limits so far experienced in radiotherapy alone with acceptable toxicity. Thus, prospective randomized studies with larger numbers of patients are warranted.

Upfront Neck Dissection in Chemoradiotherapy for p16-Negative Oropharyngeal Cancer with Neck Metastases: A Retrospective study

Objective: To determine the role of upfront neck dissection (ND) in patient survival and regional control of p16-negative oropharyngeal squamous cell carcinoma (OPSCC) with neck metastases. Design: Retrospective study. Participants: Patients with p16-negative OPSCC with neck metastases, diagnosed between January 1, 2011 and December 31, 2017, and treated with upfront ND followed by chemoradiotherapy (ND + CCRT) or primary chemoradiotherapy (CCRT). Main outcome measures: Recurrence and survival rates were analysed using the Kaplan-Meier method. Results: Data of 67 patients with p16-negative cN+ OPSCC were analysed. Of them, 23 (34.3%) received ND + CCRT and 44 (65.7%) received primary CCRT. At a median follow-up of 37.9 months, the 3-year neck recurrence rate was significantly lower in the ND + CCRT group than in the CCRT group (0% vs. 19%, p=0.031). This trend was more obvious in patients with neck metastases ≥3 cm (0% vs. 32.1%, p=0.045). Survival outcomes were comparable between the groups; notably, the ND + CCRT group received a significantly lower dose of radiotherapy (3-year disease-specific survival: 77.3% and 75.3%, p=0.968, respectively; 3-year disease-free survival: 77.3% and 70.1%, p=0.457, respectively; 3-year overall survival: 62% and 61.8%, p=0.771, respectively between the ND + CCRT and CCRT groups). Conclusion: Upfront ND was significantly beneficial for regional control and resulted in comparable oncological outcomes with a significantly reduced radiation dose. These results findings can help guide the development of a standardised treatment plan for p16-negative OPSCC. Additional prospective studies with larger sample sizes are warranted.