Radiotherapy is a pivotal component in the curative treatment of patients with localised cancer and isolated metastasis, as well as being used as a palliative strategy for patients with disseminated disease. The clinical efficacy of radiotherapy has traditionally been attributed to the local effects of ionising radiation, which induces cell death by directly and indirectly inducing DNA damage, but substantial work has uncovered an unexpected and dual relationship between tumour irradiation and the host immune system. In clinical practice, it is, therefore, tempting to tailor immunotherapies with radiotherapy in order to synergise innate and adaptive immunity against cancer cells, as well as to bypass immune tolerance and exhaustion, with the aim of facilitating tumour regression. However, our understanding of how radiation impacts on immune system activation is still in its early stages, and concerns and challenges regarding therapeutic applications still need to be overcome. With the increasing use of immunotherapy and its common combination with ionising radiation, this review briefly delineates current knowledge about the non-targeted effects of radiotherapy, and aims to provide insights, at the preclinical level, into the mechanisms that are involved with the potential to yield clinically relevant combinatorial approaches of radiotherapy and immunotherapy.

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<b><i>Objectives:</i></b> The aim of this study was to identify and compare prognostic factors, management strategies, and outcomes of very locally advanced cervical cancer (CC) (i.e., stage IVA) and metastatic CC (i.e., stage IVB). <b><i>Method:</i></b> A retrospective review was conducted based on all consecutive patients treated<b><i></i></b>for stage IV CC in a comprehensive cancer care centre between 2004 and 2017. <b><i>Results:</i></b> Sixty-eight patients were included. Performance status (PS) was ≥2 for 35.9%. Median age at diagnosis was 60.5. There were 24 stage IVA CC (35.3%) and 44 stage IVB CC (64.7%). Seventeen patients with stage IVB CC had only para-aortic lymph node metastases (38.6%), 13 had only distant metastases (29.5%), and 14 had both (31.8%). Patients with stage IVA CC experienced a radiotherapy with curative intent (<i>n</i> = 14, 58.3%) +/– concomitant chemotherapy, or a palliative treatment (<i>n</i> = 10, 41.7%). Twenty-three patients with stage IVB CC received a prior chemotherapy (52.3%), 11 a primary concomitant chemoradiation (25%), and 10 a palliative treatment (22.7%). The mean follow-up was 18.0 months. The 5-year overall survival was 5.1% for stage IVA (95% CI = 0.7–33.9), and 10.5% for stage IVB (95% CI = 3.7–29.7). In multivariate analysis, PS &#x3e;1 was identified as a poor prognostic factor of disease-specific survival for stage IVA CC. PS &#x3e;1 and pelvic lymph node involvement were identified as poor prognostic factors of overall survival and disease-specific survival for stage IVB CC. <b><i>Conclusions:</i></b> In daily clinical practice, outcomes of stages IV CC are poor. Treatment of advanced and metastatic CC remains challenging. New management strategies are needed, as well as efficient preventive strategies.

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This article is a preliminary investigational study that is aimed at giving hints about the interesting biomarkers involved in the transition process from low-grade cervix lesion to invasive cervical cancer. Our study focuses on the risk factors and tumour molecular changes in one patient. First in 1986, she was diagnosed a preinvasive cervix lesion. Then, 16 years later, she was diagnosed an invasive cervical cancer. The 2002 diagnosis was a squamous cell carcinoma of the cervix, stage IIIB (FIGO), whereas in 1986, she had been diagnosed a high-grade squamous intraepithelial cervical lesion. Retrospectively, the analysis of samples of preneoplastic lesions and invasive cervical cancer confirmed the histopathological diagnoses and detected the presence of HPV type and HPV-16 variants, as well as the overexpression of proteins such as hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1 variations seemed confirmed in the development and progression of cervical cancer. As a result, analyzing the molecular changes in one and same tumour that progresses from a low-grade cervix lesion to invasive cervical cancer could provide valuable information in order to improve detection, diagnosis, and treatment in the future.