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The abscopal effect is defined as the systemic regression of distant neoplastic lesions induced by localized treatment. Although the first case reports date back to the beginning of the twentieth century, it remains a very rare event. In recent years, research and reporting on the subject has increased thanks to the development of new immune-checkpoint inhibitors (ICIs) and stereotactic body radiotherapy, as a consequence of molecular and clinical synergism. This work describes an extremely particular presentation of metastatic laryngeal cancer, with mediastinal abdominal nodes and bone progressive disease after PD-1 inhibitor failure, which resulted in reductions of bone pain and abdominal and thoracic lymphadenopathies and an improvement in clinical conditions after treatment with concurrent palliative radiotherapy on the bulky mediastinal node and ICI beyond progression, configuring an important abscopal response.Laryngeal carcinoma is the most common cancer site of the aerodigestive tract and accounts for 25–30% of all head and neck cancer cases. Multimodality treatment (chemotherapy plus surgery and radiotherapy) is pivotal in localized or locally advanced disease, while immunotherapy is reserved for relapsed and metastatic settings. Nivolumab resulted in median overall survival of 7.5 months, progression-free survival of 2.0 months and an estimated 1-year survival rate of 36%; however, the response rate is very poor, at about 14%. Integrating immunotherapy with radiotherapy may prolong the duration of response and enhance efficacy.

Squamous cell carcinoma of the anus (SCCA) is a rising health issue, strongly related to other relevant medical conditions such as (HIV) and human papillomavirus (HPV) infection. Correct assessment of patients with SCCA requires a multidisciplinary evaluation and adequate follow-up. Accurate local and systemic staging, as well as risk evaluation, are essential to optimal treatment planning. Early stage tumours can be definitively treated with a combination of chemotherapy and radiotherapy, while salvage surgery is usually reserved for patients who develop local recurrence. Distant recurrence and de novo metastatic disease are associated with poorer prognosis and require palliative systemic chemotherapy, with different single agent and combination options available. Finally, recent discoveries on the carcinogenesis of SCCA have allowed the development of innovative treatment options, the most promising being immune checkpoint inhibitors. The limited systemic treatments for SCCA and low incidence of the disease, together with insufficient data from clinical research could explain the poor outcomes of these patients, which should therefore be managed in high volume centres and enrolled in clinical trials whenever possible. This article summarises the main strategies for treating patients with SCCA.

Background: Recently, new evidence of the next-generation sequencing (NGS) liquid biopsy utility in clinical practice has been developed. This assay is emerging as a new promising tool to use as a noninvasive biomarker for cancer mutation profiling. Additional data supporting the clinical validity of cell free DNA (cfDNA) based testing is necessary to inform optimal use of these assays in the clinic. Materials and methods: A total of 398 cancer patients were analyzed by FoundationOne Liquid Analysis (F1LA), a genomic profiling assay and by standard NGS diagnostic ThermoFisher platform. The association between diagnostic technique was evaluated using a Poisson regression model. FoundationOne Liquid (F1L) and FoundationOne Liquid CDx (F1LCDx) detect 70 and 324 cancer-related genes alterations, respectively, including genomic signatures tumor fraction, blood tumor mutational burden (only for the 324 genes version), and microsatellite instability high status. Both assays used a single DNA extraction method to obtain cfDNA. The real-life clinical impact and feasibility of F1L and F1LCDx were evaluated across different solid tumors in our department. Results: Between 1 January 2019 and 28 February 2021, 398 samples of different tumor types from 398 patients were analyzed (overall success rate: 92%, in FoundationOne Liquid CDx Analysis success rate: 97%). Most frequent molecular alterations were TP53 (74), APC (40), DNMT3A (39), KRAS (23). The comprehensive clinical impact of F1LA compared with standard diagnostic was 64.7% versus 22.1% [risk ratio (RR) = 2.94; p Conclusions: Although additional studies are needed to better select patients and setting, NGS F1LA is a useful, noninvasive, and repeatable assay to guide therapeutic choice in oncology. It provides a snapshot of cancer heterogeneity profile that could be incorporated in routinely clinical practice.

Immunotherapy has recently become a major treatment modality for several types of solid tumours, achieving remarkable and long-lasting remissions. In metastatic colorectal cancer patients (mCRC), immune checkpoint inhibitors (ICIs) were found to be effective as treatment for deficient mismatch repair (dMMR)/ microsatellite instability high (MSI-H) tumours and received regulatory approval for this indication. However, mCRC is a complex disease and dMMR/MSI-H tumours represent a minority of the cases; therefore, new strategies are needed to extend the benefits of immunotherapy to a larger population of patients. This review explores the immunological differences between dMMR/MSI-H and proficient mismatch repair (pMMR)/ microsatellite instability low (MSI-L) tumours, focuses on new proposed biomarkers to predict response to immunotherapy and illustrates results reported from the main clinical trials with immunotherapeutic agents in CRC, addressing the most promising approaches being currently developed.

A subset of colorectal cancer (CRC) with a mesenchymal phenotype (CMS4) displays an aggressive disease, with an increased risk of recurrence after surgery, reduced survival, and resistance to standard treatments. It has been shown that the AXL and TGFβ signaling pathways are involved in epithelial-to-mesenchymal transition, migration, metastatic spread, and unresponsiveness to targeted therapies. However, the prognostic role of the combination of these biomarkers and the anti-tumor effect of AXL and TGFβ inhibition in CRC still has to be assessed. To evaluate the role of AXL and TGFβ as negative biomarker in CRC, we conducted an in-depth in silico analysis of CRC samples derived from the Gene Expression Omnibus. We found that AXL and TGFβ receptors are upregulated in CMS4 tumors and are correlated with an increased risk of recurrence after surgery in stage II/III CRC and a reduced overall survival. Moreover, we showed that AXL receptor is differently expressed in human CRC cell lines. Dual treatment with the TGFβ galunisertib and the AXL inhibitor, bemcentinib, significantly reduced colony formation and migration capabilities of tumor cells and displayed a strong anti-tumor activity in 3D spheroid cultures derived from patients with advanced CRC. Our work shows that AXL and TGFβ receptors identify a subgroup of CRC with a mesenchymal phenotype and correlate with poor prognosis. Dual inhibition of AXL and TGFβ could represent a novel therapeutic strategy for patients with this aggressive disease. Supplementary Information The online version contains supplementary material available at 10.1007/s12032-021-01464-3.