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Immunotherapy has a crucial role in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, only a small percentage of patients achieve long-term benefit in terms of overall response and survival. It was shown that HNSCC has an immunosuppressive microenvironment due to high levels of regulatory T cells and immunosuppressive molecules, such as LAG3 and CD73. The aim of our study was to investigate if the expression of CD73 by neoplastic and immune cells could affect the efficacy of anti-PD-1 immunotherapy. We reviewed data from 50 patients with R/M HNSCC receiving first line immunotherapy with or without chemotherapy based on a combined positive score (CPS). CD73 expression by cancer and immune cells was evaluated on pre-treatment and the percentage of stained cells was recorded. We analysed the association between CD73 expression on neoplastic and immune cells and early progression (EP), defined as progression occurring within 3 months. In 88â¯% of patients the primary tumour site was in the oral cavity or larynx. All patients received pembrolizumab associated in 40â¯% of cases to chemotherapy. CD73 was positive in 82â¯% and 96â¯% of cases on neoplastic and immune cells, respectively. The median value of CD73 was 32â¯% for neoplastic cells and 10â¯% for the immune ones. We observed a significant association between the CD73 expression on neoplastic cells over the median value and EP disease. We didn't record a correlation between the expression of CD73 on immune cells and early progression. Our findings suggest that higher expression of CD73 on neoplastic cells could predict resistance to immunotherapy in patients with CPS positive R/M HNSCC. The addition of this biomarker to routine evaluation of CPS could help to select the patients primary resistant to anti-PD-1 immunotherapy.
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5'-Nucleotidasa , Neoplasias de Cabeza y Cuello , Inmunoterapia , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Anciano , Inmunoterapia/métodos , 5'-Nucleotidasa/metabolismo , Adulto , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/análisis , Microambiente Tumoral/inmunología , Anciano de 80 o más Años , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: Adenoid cystic carcinoma of minor salivary glands (AdCCmSG) represents a 'rarity in the rarity,' posing a clinical challenge in lack of standardized, evidence-based recommendations. At present, AdCCmSG management is mostly translated from major salivary gland cancers (MSGCs). Ideally, AdCCmSG diagnostic-therapeutic workup should be discussed and carried out within a multidisciplinary, high-expertise setting, including pathologists, surgeons, radiation oncologists and medical oncologists. AREAS COVERED: The present review provides an overview of epidemiology and pathologic classification. Moreover, the most recent, clinically relevant updates in the treatment of AdCCmSG (Pubmed searches, specific guidelines) are critically discussed, aiming to a better understanding of this rare pathologic entity, potentially optimizing the care process, and offering a starting point for reflection on future therapeutic developments. EXPERT OPINION: The management of rare cancers is often hindered by limited data and clinical trials, lack of evidence-based guidelines, and hardly represented disease heterogeneity, which cannot be successfully tackled with a 'one-size-fits-all' approach. Our goal is to address these potential pitfalls, providing an easy-to-use, updated, multidisciplinary collection of expert opinions concerning AdCCmSG management as of today's clinical practice. We will also cover the most promising future perspectives, based on the potential therapeutic targets highlighted within AdCCmSG's molecular background.
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Carcinoma Adenoide Quístico , Neoplasias de las Glándulas Salivales , Glándulas Salivales Menores , Humanos , Carcinoma Adenoide Quístico/terapia , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/diagnóstico , Neoplasias de las Glándulas Salivales/terapia , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/diagnóstico , Glándulas Salivales Menores/patología , Grupo de Atención al Paciente/organización & administración , Guías de Práctica Clínica como AsuntoAsunto(s)
Quimioradioterapia , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Quimioradioterapia/métodos , Terapia Neoadyuvante/métodos , Terapia Combinada , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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.
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Antineoplásicos Inmunológicos , Cetuximab , Quimioradioterapia , Neoplasias de Cabeza y Cuello , Radioterapia de Intensidad Modulada , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Cetuximab/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Quimioradioterapia/métodos , Antineoplásicos Inmunológicos/administración & dosificación , Radioterapia de Intensidad Modulada/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Italia , Tasa de Supervivencia , Adulto , Resultado del Tratamiento , Estadificación de Neoplasias , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
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.
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Terapia Neoadyuvante , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Terapia Neoadyuvante/métodos , Quimioterapia Adyuvante/métodos , Terapia Combinada , Tasa de SupervivenciaRESUMEN
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.
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Anticuerpos Monoclonales Humanizados , Antineoplásicos Inmunológicos , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Antígeno B7-H1 , Estudios Retrospectivos , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/inducido químicamenteAsunto(s)
Bibliometría , Neoplasias , Humanos , Neoplasias/inmunología , Investigación Biomédica , Dieta de InmunonutriciónRESUMEN
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.
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Oncología por Radiación , Radioterapia Guiada por Imagen , Humanos , Radioterapia Guiada por Imagen/métodos , Inteligencia Artificial , Estudios Retrospectivos , Planificación de la Radioterapia Asistida por Computador/métodos , Oncología por Radiación/métodos , ItaliaRESUMEN
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.
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Dieta de Inmunonutrición , Neoplasias , Humanos , Algoritmos , Bibliometría , Análisis por Conglomerados , Francia , Neoplasias/terapiaAsunto(s)
Neoplasias de la Mama , Mamoplastia , Cirugía Plástica , Humanos , Femenino , Neoplasias de la Mama/cirugía , Mama , Italia , Mastectomía SegmentariaRESUMEN
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.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Cutáneas , Humanos , Anciano , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/cirugía , Hipofraccionamiento de la Dosis de RadiaciónRESUMEN
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.
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Neoplasias de la Mama , Mastectomía Segmentaria , Humanos , Femenino , Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/tratamiento farmacológico , Terapia CombinadaRESUMEN
The aim of this editorial is to focus on the urgent need to improve clinical outcomes in patients with bulky primary anal canal carcinoma.
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Neoplasias del Ano , Humanos , Neoplasias del Ano/terapia , QuimioradioterapiaRESUMEN
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.
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The aim is to support the perception of artificial intelligence in the radiation therapy landscape.
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Inteligencia Artificial , Radioterapia , Humanos , Italia , CulturaRESUMEN
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.