[Concurrent simultaneous integrated boost radiotherapy and cetuximab in head and neck squamous cell cancer patients: is it feasible in daily clinical practice?] / Radioterapia a intensità modulata con boost simultaneo più cetuximab in pazienti con carcinoma a cellule squamose in stadio localmente avanzato del distretto testa collo: è fattibile nella pratica clinica quotidiana?

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

Pembrolizumab-based first-line treatment for PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis.

BACKGROUND: The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. METHODS: This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. RESULTS: From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. CONCLUSIONS: PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.

The multidisciplinary management of locally advanced rectal cancer.

INTRODUCTION: The classic paradigm for the management of locally advanced rectal cancer (LARC) consists of (chemo)radiotherapy (C)RT), total mesorectal excision, and adjuvant chemotherapy (CHT). At present, due to the high rate of distant metastasis (up to 30%), the total neoadjuvant therapy (TNT) with the administration of systemic CHT in the neoadjuvant setting has gained acceptance as standard of care.Our aim is to critically review the current literature on LARC management and summarize the different approaches recently proposed to improve clinical outcomes. It represents a starting step to develop an effective strategy that ultimately could harmonize the standard of care in daily clinical practice. AREAS COVERED: Studies reporting the impact of TNT approaches were deemed eligible. De-escalation strategies, including non-operative management (NOM) after TNT, as well as RT omission or systemic therapy alone, were also investigated. EXPERT OPINION: The year 2020 has seen promising new data from randomized phase III trials in the field of LARC management. Nowadays, TNT strategy has been accepted as the primary treatment for LARC. The role of de-escalation strategies is still unknown. The goal is to achieve better survival outcomes with improving quality of life. Only selected patients are likely to benefit from NOM or immunotherapy alone.

Omission of radiation therapy after breast-conserving surgery for biologically favourable tumours in younger patients: The wrong answer to the right question.

In this perspective paper, the findings of the recently published LUMINA study are critically evaluated, with an emphasis on the need for careful interpretation and a thoughtful approach in clinical practice. The LUMINA trial, which investigates the role of adjuvant endocrine therapy in low-risk breast cancer patients, is assessed for its limitations, including a highly selective patient cohort and an insufficient follow-up period. The importance of long-term data and further trials to inform clinical decisions effectively is emphasized. While the LUMINA study does not support an immediate change in practice, it is seen as a foundation for generating hypotheses to guide ongoing clinical trials. This important study has served as inspiration to develop this perspective paper, which takes into account ongoing studies and the toxicity profile of postoperative treatments in low-risk recurrence breast cancer. The need for a patient-cantered approach is stressed, considering individual wishes and desires in decision-making, despite the complexity of articulating these aspects in guidelines. A wise interpretation of available findings is essential to ensure sound clinical decision-making before broadly applying omission of radiation therapy.

Definitive weekly hypofractionated radiotherapy in surgery-ineligible older adults with cutaneous squamous cell carcinoma of the head and neck region.

This study intends to address the impact of weekly hypofractionated radiation therapy with curative intent for cutaneous squamous cell carcinoma of the head and neck region in the elderly population.

Mapping the landscape of immunonutrition and cancer research: a comprehensive bibliometric analysis on behalf of NutriOnc Research Group.

The ongoing global health challenge of cancer is driving the pursuit of innovative avenues for prevention, treatment, and enhanced outcomes. The convergence of nutrition and immune modulation, known as immunonutrition, is ready to act as a catalyst for transformative change in cancer research and therapy. Our study employs a bibliometric analysis to uncover the evolving trends within immunonutrition and cancer research across the past 25 years. Bibliometric data, including authors, journals, affiliations, and countries, were analyzed using the Bibliometrix R package. Clustering algorithms were applied to keywords to identify thematic areas and their evolution. A total of 489 documents were analyzed, showing an annual growth rate of 8.7%, with a collaboration index of 5.41, highlighting comprehensive multidisciplinary involvement within this landscape. Core authors demonstrated sustained productivity, while occasional authors indicated widespread interest. The Medical University of Warsaw led in institutional contributions. Country-wise, Italy, France, and the USA emerged as forerunners in fostering research productivity. Key journals like 'Clinical Nutrition' served as beacons, emphasizing the multidimensional nature of this topic. The analysis highlighted growing research output and several collaborations, indicating the importance of immunoenriched nutrition in cancer treatment. The interplay of core authors and diversified engagement harmoniously accentuates the cross-disciplinary nature of this burgeoning field. International collaboration facilitated knowledge exchange. Prominent documents shaped the field, emphasizing the significance of nutritional interventions. Thematic clusters revealed varied focuses, including pharmaconutrients, surgical approaches, inflammation, and specific cancers. The expanding research output suggests further development, particularly in exploring immunoenriched nutrition's impact on cancer types and patient populations. The multidisciplinary nature and international collaborations enhance the field's progress. Gaps in research underscore the need for original studies and personalized approaches. This study guides future research, informing evidence-based nutritional interventions and advancing cancer care practices.

Artificial intelligence applied to image-guided radiation therapy (IGRT): a systematic review by the Young Group of the Italian Association of Radiotherapy and Clinical Oncology (yAIRO).

INTRODUCTION: The advent of image-guided radiation therapy (IGRT) has recently changed the workflow of radiation treatments by ensuring highly collimated treatments. Artificial intelligence (AI) and radiomics are tools that have shown promising results for diagnosis, treatment optimization and outcome prediction. This review aims to assess the impact of AI and radiomics on modern IGRT modalities in RT. METHODS: A PubMed/MEDLINE and Embase systematic review was conducted to investigate the impact of radiomics and AI to modern IGRT modalities. The search strategy was "Radiomics" AND "Cone Beam Computed Tomography"; "Radiomics" AND "Magnetic Resonance guided Radiotherapy"; "Radiomics" AND "on board Magnetic Resonance Radiotherapy"; "Artificial Intelligence" AND "Cone Beam Computed Tomography"; "Artificial Intelligence" AND "Magnetic Resonance guided Radiotherapy"; "Artificial Intelligence" AND "on board Magnetic Resonance Radiotherapy" and only original articles up to 01.11.2022 were considered. RESULTS: A total of 402 studies were obtained using the previously mentioned search strategy on PubMed and Embase. The analysis was performed on a total of 84 papers obtained following the complete selection process. Radiomics application to IGRT was analyzed in 23 papers, while a total 61 papers were focused on the impact of AI on IGRT techniques. DISCUSSION: AI and radiomics seem to significantly impact IGRT in all the phases of RT workflow, even if the evidence in the literature is based on retrospective data. Further studies are needed to confirm these tools' potential and provide a stronger correlation with clinical outcomes and gold-standard treatment strategies.

IAP inhibitor plus chemoradiotherapy for the treatment of bulky anal canal carcinoma.

The aim of this editorial is to focus on the urgent need to improve clinical outcomes in patients with bulky primary anal canal carcinoma.

Radiotherapy and Systemic Therapies: Focus on Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is a complex clinical entity, and its treatment strategy remains a challenge. The best practice management for individual HNSCC patients should be discussed within a multidisciplinary team. In the locally advanced disease, radiation therapy (RT) with or without concomitant cisplatin-based chemotherapy is the current standard of care for most patients treated definitively or adjuvantly after surgery. Intensity-modulated photon therapy (IMRT) is the recommended RT technique due to its ability to offer considerable treatment conformality while sparing surrounding normal critical tissues. At present, the development of novel treatment strategies, as well as alternative systemic agent combinations, is an urgent need to improve the therapeutic ratio in HNSCC patients. Despite the immune landscape suggesting a strong rationale for the use of immunotherapy agents in HNSCC, evidence-based data demonstrate that combining RT with immune checkpoint inhibitors as the primary treatment modality has not been shown to induce significant benefit on survival clinical outcomes. The objective of this article is to review the current literature on the treatment of patients with HNSCC. We initially provided a comprehensive overview of the standard of care. We then focused on the integration of systemic therapies with RT, highlighting the latest published evidence and ongoing trials which investigate different combination strategies in the definitive setting. Our hope is to summarize relevant literature in order to provide a foundation for interpreting emerging data and designing future trials to maximize care, both in disease control and patient quality of life.

Artificial intelligence and Italian culture: an understanding of how artificial intelligence can transform the radiation therapy landscape.

The aim is to support the perception of artificial intelligence in the radiation therapy landscape.

Skin metastases from prostate cancer successfully treated with radiation therapy.

Skin metastases from prostate cancer (PCa) are rare, cause considerable discomfort, and usually indicate advanced disease and a poor prognosis. To date, literature accounts for no more than 88 cases of skin metastasis from PCa, and radiation therapy (RT) is not considered a standard treatment option. Here, we have described a rare case of skin localization of castration-resistant metastatic PCa, which occurred in a 75-year-old male previously treated with RT for PCa, 11 years earlier. The skin lesions, which progressively appeared in different areas of the chest wall, were successfully treated with electron beam RT (900 cGy, for 3 consecutive days). Five months after irradiating skin metastases, the patient showed general fair conditions and no longer developed other skin lesions in the areas already treated or elsewhere. This report describes a scarce case of cutaneous metastases from PCa, underlying the crucial role of RT as a definitive palliative treatment that should be used to limit systemic chemotherapy-related toxicity.

The evolving role of reirradiation in the management of recurrent brain tumors.

Despite aggressive management consisting of surgery, radiation therapy (RT), and systemic therapy given alone or in combination, a significant proportion of patients with brain tumors will experience tumor recurrence. For these patients, no standard of care exists and management of either primary or metastatic recurrent tumors remains challenging.Advances in imaging and RT technology have enabled more precise tumor localization and dose delivery, leading to a reduction in the volume of health brain tissue exposed to high radiation doses. Radiation techniques have evolved from three-dimensional (3-D) conformal RT to the development of sophisticated techniques, including intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and stereotactic techniques, either stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Several studies have suggested that a second course of RT is a feasible treatment option in patients with a recurrent tumor; however, survival benefit and treatment related toxicity of reirradiation, given alone or in combination with other focal or systemic therapies, remain a controversial issue.We provide a critical overview of the current clinical status and technical challenges of reirradiation in patients with both recurrent primary brain tumors, such as gliomas, ependymomas, medulloblastomas, and meningiomas, and brain metastases. Relevant clinical questions such as the appropriate radiation technique and patient selection, the optimal radiation dose and fractionation, tolerance of the brain to a second course of RT, and the risk of adverse radiation effects have been critically discussed.

Surgery-ineligible elderly patients with cutaneous squamous cell carcinoma of the head and neck region gain clinical benefit from definitive weekly hypofractionated radiotherapy.

BACKGROUND: To evaluate the role of definitive weekly hypofractionated radiotherapy (RT) for the treatment of surgery-ineligible elderly patients with cutaneous squamous cell carcinoma of the head and neck region (cHNSCC). METHODS: Eligible elderly patients (aged ≥75 years) with cHNSCC were included. Patients received definitive weekly hypofractionated RT, using megavoltage electrons, to a total dose of 56-64 Gy (8 Gy per fraction). Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), pain response, tolerability, and safety. RESULTS: A total of 19 patients with 27 lesions were included and treated with definitive weekly hypofractionated RT. All patients received the prescribed total dose. ORR was 92.6%, including 70.4% of lesions with a CR and 22.2% with a PR. Median DOR was 12 months. No severe toxicity occurred. CONCLUSIONS: Our study confirmed the satisfying efficacy and acceptable toxicity of definitive weekly hypofractionated RT for cHNSCC in elderly patients. Our results establish weekly hypofractionated scheduleas a promising treatment option for elderly patients with cHNSCC.