Giammaria Fiorentini

Over the past two decades, interest in prone-position whole breast irradiation (WBI) as an effective and practical alternative to supine treatment has been growing a lot. Although solid scientific data has provided evidence of substantial dosimetric benefit with decreased toxicity, there is still conflict in the radiotherapy community over whether to adopt prone-position WBI as a valid alternative to supine radiotherapy (RT) in routine clinical practice. A large number of prone trials have been conducted to assess and address concerns related to prone treatment in large and pendulous breasts and in left and right breast cancer (BC), nodal irradiation, and its reproducibility with deep inspiration breath hold (DIBH) delivery with photons or protons. Appropriate atlases have been defined to improve prone nodal irradiation. Additionally, more comfortable customized immobilization couches have been constructed to permit IMRT beams and VMAT arrangements with modern LINACs. Although our search in literature databases shows a growing body of evidence from the past two decades on this issue, prone WBI is still underused. Given the paradox of the advances and benefits of this positioning and the lack of drive in the radiotherapy community towards its clinical implementation, the purpose of this comprehensive review is to evaluate the true advantages of this position in real life and contextualize it in scenarios like large breasts, left-sided breast cancer, and nodal irradiation to encourage its implementation in clinical practice.

In the past two decades, the interest in prone position whole breast irradiation (WBI) as an effective and practical alternative to supine treatment has been growing a lot. Although solid scientific evidence have provided data of substantial dosimetric benefit and decreased toxicity, there is still a paradox in the radiotherapy community to adopt prone position WBI as valid alternative to supine radiotherapy (RT) in routinary clinical practice. A large number of prone trials have been conducted to assess and address concerns related to treatment in large and pendulous breasts and in left and right BC, nodal irradiation, and its reproducibility with Deep Inspiration Breath Hold (DIBH) delivery with photons or protons. Appropriate atlases have been defined to improve prone nodal irradiation. Additionally, more comfortable customised immobilisation couches have been constructed to permit IMRT beams arrangements. A search in literature databases with the keywords ‘prone positioning radiotherapy’, ‘prone set up’, ‘prone breast radiation’, ‘prone breast and lymph node irradiation’, ‘prone position versus supine position’, and ‘prone DIBH’ revealed a growing body of evidence from the past two decades. However, prone WBI is still underused. Given the paradox of advances and benefits of this positioning and the lack of drive in the radiotherapy community for its clinical implementation, the aim of this paper is to provide a comprehensive summary of innovations in this field to overcome this paradox and implement prone positioning in real life breast cancer radiotherapy.

The applicability of RHT in the treatment and supportive care of tumors has been discussed for years in many publications. There are hundreds of articles that have reported on the good acceptance and feasibility of HT, as well as its value in terms of controlling malignant diseases, enhancing response and, in some randomized controlled trials (RCTs), clear improvements in OS. Despite this, HT has never fully been accepted as a standard treatment among radiation and medical oncologists. The increased activity that HT offers in the context of chemotherapy (CHT), radiotherapy (RT), chemoradiotherapy (CRT), and immunotherapy, thus facilitating programmed cell death (PCD), has been documented in many studies. This aspect has been demonstrated in many tumors, including soft tissue sarcoma, cancers of the cervix, esophagus, stomach, colon/rectum, pancreas, breast, head and neck, and prostate, and bone metastases. HT improves cancer cell death through many modalities, targeting both the tumor microenvironment (TME) and the cancer cells directly. Targeted HT increases the temperature of the primary tumor and surrounding tissues to 39–43 °C, causing the tumor cells to become more immune-responsive. HT can also activate the immune response of the TME through inducing heat shock proteins (HSPs), which also promote an immunological response and PCD. HT can oxygenate hypoxic tumors, facilitating RT-induced DNA damage in cancer cells. At present, it seems that the combination of HT and RT, CHT, and immunotherapy might lead to immune enhancement effects in the TME, making cancer cells more responsive to immunotherapies. This narrative review presents the novel aspects of HT reported in recent years.

Hyperthermia combined with chemotherapy vs chemotherapy in patients with advanced pancreatic cancer: A multicenter retrospective observational comparative study

Aim: Pseudomyxoma peritonei (PMP) is an uncommon pathology, and its rarity causes a lack of scientific evidence, precluding the design of a prospective trial. A diagnostic and therapeutic algorithm (DTA) is necessary in order to standardize the disease treatment while balancing optimal patient management and the correct use of resources. The Consensus of the Italian Society of Surgical Oncology (SICO) Oncoteam aims at defining a diagnostic and therapeutic pathway for PMP and appendiceal primary tumors applicable in Italian healthcare. Method: The consensus panel included 10 delegated representatives of oncological referral centers for Peritoneal Surface Malignancies (PSM) affiliated to the SICO PSM Oncoteam. A list of statements regarding the DTA of patients with PMP was prepared according to recommendations based on the review of the literature and expert opinion. Results: A consensus was obtained on 33 of the 34 statements linked to the DTA; two flowcharts regarding the management of primary appendiceal cancer and peritoneal disease were approved. Conclusion: Currently, consensus has been reached on pathological classification, preoperative evaluation, cytoreductive surgery technical detail, and systemic treatment; some controversies still exist regarding the exclusion criteria for HIPEC treatment. A shared Italian model of DTA is an essential tool to ensure the appropriateness and equity of treatment for these patients.

Modulated electro-hyperthermia in stage III and IV pancreatic cancer: Results of an observational study on 158 patients

Aims: Bevacizumab (B) in association with systemic chemotherapy is commonly used for the treatment of colorectal cancer liver metastases. The aim of this study was to monitor tumor response, overal...

Merkel cell carcinomas (MCCs) are rare, aggressive, cutaneous neuroendocrine tumours, approximately 80% of which are caused by the genomic integration of Merkel cell polyomavirus (MCPyV). MCPyV-positive MCCs carry poor prognosis in approximately 70% of cases, highlighting the need for greater understanding of the oncogenic mechanisms involved in pathogenesis, progression and post-therapeutic relapse, and translation into novel therapeutic strategies. In a previous pilot study, we reported a potential relationship between MCPyV gene expression and oncogenic alternative Δ exon 6–7 TrkAIII splicing in formalin-fixed paraffin-embedded (FFPE) MCC tissues from a 12-patient cohort of >90% MCPyV-positive MCCs, diagnosed at San Salvatore Hospital, L’Aquila, Italy, characterising a new MCC subgroup and unveiling a novel potential MCPyV oncogenic mechanism and therapeutic target. This, however, could not be fully verified due to poor RNA quality and difficulty in protein extraction from FFPE tissues. Here, therefore, we extend our previous observations to confirm the relationship between MCPyV and oncogenic alternative Δ exon 6–7 TrkAIII splicing in fresh, nonfixed, MCPyV-positive MCC metastasis by detecting sequence-verified RT-PCR products, including full-length Δ exon 6–7 TrkAIII, and by Western blot detection of a 100 kDa TrkA protein isoform of identical size to 100 kDa Δ exon 6–7 TrkAIII expressed by stable transfected SH-SY5Y cells. We also report that in three MCC patients submitted for multidisciplinary treatment, including locoregional chemotherapy, MCPyV large T-antigen mRNA expression, Δ exon 6–7 TrkAIII mRNA expression and intracellular indirect immunofluorescence (IF) TrkA and phosphorylation protein isoform(s) immunoreactivity in FFPE tissues were not reduced in postchemotherapeutic-relapsed MCCs compared to pretherapeutic MCCs, extending the possible roles of this novel potential MCPyV oncogenic mechanism from MCC pathogenesis to post-therapeutic relapse and progression. Detection of alternative Δ exon 6–7 TrkAIII splicing in MCC, therefore, not only characterises a new MCPyV-positive MCC subgroup and unveils a novel potential MCPyV oncogenic mechanism but also identifies patients who may benefit from inhibitors of MCPyV T-antigen and/or TrkAIII expression or clinically approved Trk kinase inhibitors such as larotrectinib or entrectinib, which are known to inhibit activated TrkA oncogenes and to elicit durable responses in TrkA-fusion oncogene-driven cancers, supporting the call for a large-scale multicentre clinical study.