The growing interest in proton therapy (PT) in recent decades is justified by the evidence that protons dose distribution allows maximal dose release at the tumor depth followed by sharp distal dose ...fall-off. But, in the holistic management of head and neck cancer (HNC), limiting the potential of PT to a mere dosimetric advantage appears reductive. Indeed, the precise targeting of PT may help evaluate the effectiveness of de-escalation strategies, especially for patients with human papillomavirus associated-oropharyngeal cancer (OPC) and nasopharyngeal cancer (NPC). Furthermore, PT could have potentially greater immunogenic effects than conventional photon therapy, possibly enhancing both the radiotherapy (RT) capability to activate anti-tumor immune response and the effectiveness of immunotherapy drugs. Based on these premises, the aim of the present paper is to conduct a narrative review reporting the safety and efficacy of PT compared to photon RT focusing on NPC and OPC. We also provide a snapshot of ongoing clinical trials comparing PT with photon RT for these two clinical scenarios. Finally, we discuss new insights that may further develop clinical research on PT for HNC.
Advanced stage nasopharyngeal cancer (NPC) shows highly variable treatment outcomes, suggesting the need for independent prognostic factors. This study aims at developing a magnetic resonance imaging ...(MRI)-based radiomic signature as a prognostic marker for different clinical endpoints in NPC patients from non-endemic areas. A total 136 patients with advanced NPC and available MRI imaging (T1-weighted and T2-weighted) were selected. For each patient, 2144 radiomic features were extracted from the main tumor and largest lymph node. A multivariate Cox regression model was trained on a subset of features to obtain a radiomic signature for overall survival (OS), which was also applied for the prognosis of other clinical endpoints. Validation was performed using 10-fold cross-validation. The added prognostic value of the radiomic features to clinical features and volume was also evaluated. The radiomics-based signature had good prognostic power for OS and loco-regional recurrence-free survival (LRFS), with C-index of 0.68 and 0.72, respectively. In all the cases, the addition of radiomics to clinical features improved the prognostic performance. Radiomic features can provide independent prognostic information in NPC patients from non-endemic areas.
Background: The standard treatment for skull base chondrosarcoma (SB-CHS) consists of surgery and high-dose radiation therapy. Our aim was to evaluate outcome in terms of local control (LC) and ...toxicity of proton therapy (PT) and carbon ion (CIRT) after surgery. Materials and methods: From September 2011 to July 2020, 48 patients underwent particle therapy (67% PT, 33% CIRT) for SB-CHS. PT and CIRT total dose was 70 GyRBE (relative biological effectiveness) in 35 fractions and 70.4 GyRBE in 16 fractions, respectively. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE v5). Results: After a median follow-up time of 38 months, one local failure (2%) was documented and the patient died for progressive disease. Overall, 3-year LC was 98%. One (2%) and 4 (8%) patients experienced G3 acute and late toxicity, respectively. White-matter brain changes were documented in 22 (46%) patients, but only 7 needed steroids (G2). No patients had G3 brain toxicity. No G4–5 complications were reported. We did not find any correlation between high-grade toxicity or white-matter changes and characteristics of patients, disease and surgery. Conclusions: PT and CIRT appeared to be effective and safe treatments for patients with SB-CHS, resulting in high LC rates and an acceptable toxicity profile.
(1) Background: we proposed an integrated strategy to support clinical allocation of nasopharyngeal patients between proton and photon radiotherapy. (2) Methods: intensity-modulated proton therapy ...(IMPT) plans were optimized for 50 consecutive nasopharyngeal carcinoma (NPC) patients treated with volumetric modulated arc therapy (VMAT), and differences in dose and normal tissue complication probability (ΔNTCPx-p) for 16 models were calculated. Patient eligibility for IMPT was assessed using a model-based selection (MBS) strategy following the results for 7/16 models describing the most clinically relevant endpoints, applying a model-specific ΔNTCPx-p threshold (15% to 5% depending on the severity of the complication) and a composite threshold (35%). In addition, a comprehensive toxicity score (CTS) was defined as the weighted sum of all 16 ΔNTCPx-p, where weights follow a clinical rationale. (3) Results: Dose deviations were in favor of IMPT (ΔD
≥ 14% for cord, esophagus, brainstem, and glottic larynx). The risk of toxicity significantly decreased for xerostomia (-12.5%), brain necrosis (-2.3%), mucositis (-3.2%), tinnitus (-8.6%), hypothyroidism (-9.3%), and trismus (-5.4%). There were 40% of the patients that resulted as eligible for IMPT, with a greater advantage for T3-T4 staging. Significantly different CTS were observed in patients qualifying for IMPT. (4) Conclusions: The MBS strategy successfully drives the clinical identification of NPC patients, who are most likely to benefit from IMPT. CTS summarizes well the expected global gain.
Adenoid cystic carcinoma (ACC) is a rare, basaloid, epithelial tumor, arising mostly from salivary glands. Radiation therapy can be employed as a single modality for unresectable tumors, in an ...adjuvant setting after uncomplete resection, in case of high-risk pathological features, or for recurrent tumors. Due to ACC intrinsic radioresistance, high linear energy transfer (LET) radiotherapy techniques have been evaluated for ACC irradiation: while fast neutron therapy has now been abandoned due to toxicity concerns, charged particle beams such as protons and carbon ions are at present the beams used for hadron therapy. Carbon ion radiation therapy (CIRT) is currently increasingly used for ACC irradiation. The aim of this review is to describe the immunological, molecular and clinicopathological bases that support ACC treatment with CIRT, as well as to expose the current clinical evidence that reveal the advantages of using CIRT for treating ACC.
Objectives
The objective of the paper was to assess real-life experience in the management of head and neck cancer (HNC) patients during the COVID-19 pandemic in radiotherapy departments and to ...evaluate the variability in terms of adherence to American Society of Radiation Oncology (ASTRO) and European Society for Radiotherapy and Oncology (ESTRO) recommendations.
Materials and methods
In May 2020, an anonymous 30-question online survey, comparing acute phase of outbreak and pre-COVID-19 period, was conducted. Two sections exploited changes in general management of HNC patients and different HNC primary tumors, addressing specific statements from ASTRO ESTRO consensus statement as well.
Results
Eighty-eight questionnaires were included in the demographic/clinical workflow analysis, and 64 were analyzed for treatment management. Forty-eight percent of radiotherapy departments became part of oncologic hubs. First consultations reduced, and patients were addressed to other centers in 33.8 and 18.3% of cases, respectively. Telematic consultations were used in 50% of follow-up visits and 73.9% of multidisciplinary tumor board discussions. There were no practical changes in the management of patients affected by different primitive HNCs. Hypofractionation was not favored over conventional schedules.
Conclusions
Compared to pre-COVID era, the clinical workflow was highly re-organized, whereas there were no consistent changes in RT indications and schedules.
Background: Currently, 13 Asian and European facilities deliver carbon ion radiotherapy (CIRT) for preclinical and clinical activity, and, to date, 55 clinical studies including CIRT for adult and ...paediatric solid neoplasms have been registered. The National Center for Oncological Hadrontherapy (CNAO) is the only Italian facility able to accelerate both protons and carbon ions for oncological treatment and research. Methods: To summarise and critically evaluate state-of-the-art knowledge on the application of carbon ion radiotherapy in oncological settings, the authors conducted a literature search till December 2022 in the following electronic databases: PubMed, Web of Science, MEDLINE, Google Scholar, and Cochrane. The results of 68 studies are reported using a narrative approach, highlighting CNAO’s clinical activity over the last 10 years of CIRT. Results: The ballistic and radiobiological hallmarks of CIRT make it an effective option in several rare, radioresistant, and difficult-to-treat tumours. CNAO has made a significant contribution to the advancement of knowledge on CIRT delivery in selected tumour types. Conclusions: After an initial ramp-up period, CNAO has progressively honed its clinical, technical, and dosimetric skills. Growing engagement with national and international networks and research groups for complex cancers has led to increasingly targeted patient selection for CIRT and lowered barriers to facility access.
(1) Background: In this work, we aim to provide selection criteria based on normal tissue complication probability (NTCP) models and additional explanatory dose-volume histogram parameters suitable ...for identifying locally advanced sinonasal cancer patients with orbital invasion benefitting from proton therapy. (2) Methods: Twenty-two patients were enrolled, and two advanced radiation techniques were compared: intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT). Plans were optimized with a simultaneous integrated boost modality: 70 and 56 Gy(RBE) in 35 fractions were prescribed to the high risk/low risk CTV. Several endpoints were investigated, classified for their severity and used as discriminating paradigms. In particular, when NTCP models were already available, a first selection criterion based on the delta-NTCP was adopted. Additionally, an overall analysis in terms of DVH parameters was performed. Furthermore, a second selection criterion based on a weighted sum of the ΔNTCP and ΔDVH was adopted. (3) Results: Four patients out of 22 (18.2%) were suitable for IMPT due to ΔNTCP > 3% for at least one severe toxicity, 4 (18.2%) due to ΔNTCP > 20% for at least three concurrent intermediate toxicities and 16 (72.7%) due to the mixed sum of ΔNTCP and ΔDVH criterion. Since, for some cases, both criteria were contemporary fulfilled, globally 17/22 patients (77.3%) would benefit from IMPT. (4) Conclusions: For this rare clinical scenario, the use of a strategy including DVH parameters and NTCPs when comparing VMAT and IMPT is feasible. We showed that patients affected by sinonasal cancer could profit from IMPT compared to VMAT in terms of optical and central nervous system organs at risk sparing.
The present study aims to evaluate dosimetric and clinical risk factors for the development of maxillary osteoradionecrosis (ORN) in head and neck adenoid cystic carcinoma (ACC) patients treated with ...carbon ion radiotherapy (CIRT).
Clinical data and treatment plans of ACC patients, consecutively treated from January 2013 to September 2016 within the phase II clinical trial CNAO S9/2012/C, were retrospectively reviewed. ORN and other treatment-related toxicity were graded according to the Common Terminology Criteria for Adverse Events (CTACE), version 4.0. The maxillary bone was contoured on the planning CT, and only patients receiving more than 10% of the prescription dose at their maxilla were considered for the analysis (67 patients). The volumes of maxilla receiving doses from 10 Gy (RBE) to 60 Gy (RBE) (V
), with an increment of 10 Gy (RBE), and additional clinical factors were correlated to the incidence of ORN with univariate analysis (Chi-square test). The logistic regression model was subsequently applied for multivariate analysis. Treatment plans calculated with a local effect model (LEM)-based optimization were recalculated with the modified microdosimetric kinetic model (MKM), and compared with literature data from the Japanese experience.
The median time interval from the start of CIRT to ORN appearance was 24 months (range, 8-54 months). Maxillary ORN was observed in 11 patients (16.4%). Grade 1 ORN was observed in 2 patients (18.1%), G2 in 4 (36.3%), G3 in 4 (36.3%) and G4 in 1 (9.3%). From univariate analysis, the site of the tumor, the presence of teeth within the PTV and acute mucositis correlated with the development of maxillary ORN. V
were significantly higher for all the dose levels tested in patients with maxillary ORN than patients without necrosis, according to both radiobiological models. The multivariate analysis showed that V60 significantly correlated with ORN risk.
The volume of maxilla irradiated with high dose values was relevant for ORN development in our cohort of ACC patients. These results are in line with previously published data obtained with a different radiobiological model. Our findings might be helpful to prevent the risk of ORN in patients receiving CIRT.
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