Emergency radiation therapy in modern-day practice: Now or never, or never again ?

Radiation therapy plays a fundamental role in oncological emergencies such as superior vena cava syndrome (SVCS) and metastatic epidural spinal cord compression (MESCC). These are two examples of critical complications of metastatic cancer in terms of pain and functional impact (respiratory and/or neurological). The aim of this review is to explore the current indications, treatment options and outcomes for emergency radiotherapy regarding to these complications.Regarding SVCS, studies are mostly retrospective and unanimously demonstrated a beneficial effect of radiotherapy on symptom relief. Spinal cord compression remains an indication for urgent radiotherapy, and should be combined with surgery when possible. The innovative stereotactic body radiotherapy (SBRT) showed promising results, however this technique requires small volumes and more time preparation and therefore is often unsuitable for SVCS and MESCC emergencies.This review concluded that radiotherapy has a central role to play within a multimodal approach for SVCS and MESCC treatment. Further prospective studies are needed to confirm the effectiveness of radiation and establish the criteria for selecting patients to benefit from this treatment option.

Immunotherapy for head and neck squamous cell carcinoma: current status and perspectives.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several solid cancers, including head and neck squamous cell carcinoma (HNSCC). First approved for second-line settings, ICIs are now used for the first-line treatment of HNSCCs, mainly in combination with standard chemotherapy. This review focuses on the results of the main phase III studies evaluating ICIs in recurrent or metastatic HNSCCs. The efficacy and indications according to the PD-L1 status, the main predictive biomarker, are discussed. The results of trials assessing ICI efficacy for locally advanced disease, including the neoadjuvant setting are also discussed. Finally, therapeutic combinations that are potential treatments for HNSCCs, including ICIs and targeted therapies such as anti-EGFR agents, are presented.

Head and neck (HN) cancer is common and challenging to treat, especially when it relapses locally (recurrence) or in a different organ (metastatic). Immunotherapy, which strengthens the immune system's ability to target tumor cells, has revolutionized the treatment of several cancers, including metastatic HN cancers. Pembrolizumab, an immunotherapy drug, is now combined with chemotherapy as standard treatment for recurrent or metastatic HN cancers; it has a manageable toxicity profile. However, some patients do not respond to treatment, and the disease may relapse after several injections. Efforts are currently underway to improve the efficacies of these immunotherapy treatments by combining them with other therapies, such as anti-EGFR treatment. Current studies seek biomarkers to identify patients likely to benefit from these treatments and those who may require alternative treatments.

Normal Hematopoetic Stem and Progenitor Cells Can Exhibit Metabolic Flexibility Similar to Cancer Cells.

It is known that cancer stem cells (CSCs) with the largest proliferative capacity survive the anoxic and/or ischemic conditions present inside tumorous tissue. In this study we test whether normal stem cells can survive under the same conditions due to cancer cell-like metabolic adaptations. We cultivated a CD34+ population with a majority of hematopoietic progenitors, and a CD34+CD38lowCD133+CD90+CD45RA- population, highly enriched in hematopoietic stem cells (HSCs), under anoxic, anoxic/aglycemic ("ischemia-like"), or physiological conditions (3% O2). Results showed, despite a reduction in total cell fold expansion proportionate to the decrease in O2 concentration; CD34+ cells, aldehyde dehydrogenase-expressing primitive cells, and committed progenitors expanded, even in anoxia. Interestingly, under ischemia-like conditions, stem and CD34+ cell populations are maintained at day-0 level. Cell-cycle analysis further revealed an accumulation of cells in the G0/G1 phase in anoxia or anoxia/aglycemia, with a fraction of cells (~40%) actively cycling (SG2M phases). Also stem cell analysis showed that in these conditions a long-term Scid Repopulating activity was equal to that found with 3% O2. In addition stem cells with the highest proliferative capacity were maintained in anoxia/aglycemia and in anoxia. The estimated ATP profile, active mitochondrial content, and succinate accumulation are indicative of anaerobic mitochondrial respiration in both HSCs and CD34+ progenitors under ischemia-like conditions. We demonstrate here that primitive hematopoietic cells show similar metabolic flexibility to CSCs, allowing them to survive a lack of O2 and O2/glucose. Our study reveals that this feature is not the consequence of malignant transformation, but an attribute of stemness.