PURPOSE/OBJECTIVE: To perform a dosimetric and a normal tissue complication probability (NTCP) comparison between intensity modulated proton therapy and photon volumetric modulated arc therapy in a cohort of patients with parotid gland cancers in a post-operative or radical setting. MATERIALS AND METHODS: From May 2011 to September 2021, 37 parotid gland cancers patients treated at two institutions were eligible. Inclusion criteria were as follows: patients aged ⩾ 18 years, diagnosis of parotid gland cancers candidate for postoperative radiotherapy or definitive radiotherapy, presence of written informed consent for the use of anonymous data for research purposes. Organs at risk (OARs) were retrospectively contoured. Target coverage goal was defined as D95 > 98%. Six NTCP models were selected. NTCP profiles were calculated for each patient using an internally-developed Python script in RayStation TPS. Average differences in NTCP between photon and proton plans were tested for significance with a two-sided Wilcoxon signed-rank test. RESULTS: Seventy-four plans were generated. A lower Dmean to the majority of organs at risk (inner ear, cochlea, oral cavity, pharyngeal constrictor muscles, contralateral parotid and submandibular gland) was obtained with intensity modulated proton therapy vs volumetric modulated arc therapy with statistical significance (p < .05). Ten (27%) patients had a difference in NTCP (photon vs proton plans) greater than 10% for hearing loss and tinnitus: among them, seven qualified for both endpoints, two patients for hearing loss only, and one for tinnitus. CONCLUSIONS: In the current study, nearly one-third of patients resulted eligible for proton therapy and they were the most likely to benefit in terms of prevention of hearing loss and tinnitus.
PURPOSE: To evaluate efficacy and toxicity of carbon ion radiotherapy (CIRT) in locally advanced head and neck mucosal melanoma (HNMM) patients treated at our Institute. MATERIALS AND METHODS: Between June 2013 and June 2020, 40 HNMM patients were treated with CIRT. Prescription dose was 65.6-68.8 Gy relative biological effectiveness [RBE] in 16 fractions. Twelve (30%) patients received only biopsy, 28 (70%) surgical resection before CIRT. Immunotherapy was administered before and/or after CIRT in 45% of patients, mainly for distant progression (89%). RESULTS: Median follow-up was 18 months. 2-year Local Relapse Free Survival (LRFS), Overall Survival (OS), Progression Free Survival (PFS) and Distant Metastasis Free Survival (DMFS) were 84.5%, 58.6%, 33.2% and 37.3%, respectively. At univariate analysis, LRFS was significantly better for non-recurrent status, < 2 surgeries before CIRT and treatment started < 9 months from the initial diagnosis, with no significant differences for operated versus unresected patients. After relapse, immunotherapy provided longer median OS (17 months vs 3.6, p-value<0.001). Late toxicity ≥ G3 (graded with CTCAE 5.0 scale) was reported in 10% of patients. CONCLUSION: CIRT in advanced HNMM patients is safe and locally effective. Prospective trials are warranted to assess the role of targeted/immune- systemic therapy to improve OS.
Head and Neck Neoplasms , Heavy Ion Radiotherapy , Melanoma , Humans , Melanoma/radiotherapy , Melanoma/pathology , Prospective Studies , Neoplasm Recurrence, Local/pathology , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/etiology , Heavy Ion Radiotherapy/adverse effects
Sinonasal cancers (SNCs) are rare and heterogeneous in histology and biological behavior. The prognosis is generally unfavorable, especially in inoperable cases. In recent years, for some histologies, such as undifferentiated sinonasal carcinoma (SNUC), multimodal treatment with a combination of induction chemotherapy, surgery, and chemo/radiotherapy (RT) has improved the prognosis. Nevertheless, still about half of the patients treated incur a recurrence, in most of the cases at the local site. Surgery with and without RT is usually the treatment choice in cases of recurrence after previous RT in combination with systemic therapy or RT in a histology-driven fashion. In the case of inoperable disease or contraindications to surgery, RT is still a valid treatment option. In this context, hadron therapy with protons (PT) or carbon ions (CIRT) is often preferred due to the physical and biological characteristics of charged particles, allowing the administration of high doses to the tumor target while sparing the surrounding healthy tissues and potentially limiting the side effects due to the high cumulative dose. In the absence of a standard of care for the recurrent setting, we aimed to investigate the role of re-RT with PT or CIRT. We retrospectively analysed 15 patients with recurrent, previously irradiated, SNCs treated at our institution between 2013 and 2020. Local control (LC) and overall survival (OS) were estimated by the Kaplan-Meier method. Acute and late toxicities were scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events CTCAE version 5.0. A total of 13 patients received CIRT and 2 patients received PT. The median re-RT dose was 54 GyRBE (range 45-64 GyRBE) delivered in 3 or 4 GyRBE/fr (fraction) for the CIRT, and 2 Gy RBE/fr for the PT schedule. LC was 44% at the 1-year follow-up and 35.2% at the 3-year follow-up. OS at 1 and 3 years were 92.9% and 38.2%, respectively. Fourteen patients developed G1-G2 acute toxicity (dermatitis and mucositis), and no patients developed G3-G5. Regarding late toxicity, 10 patients encountered at maximum G1-2 events, and 4 did not experience any toxicity. Only for one patient G3 late toxicity was reported (dysphagia requiring a percutaneous endoscopic gastrostomy).
BACKGROUND AND PURPOSE: In recent years, there is an emerging interest in the prognostic role of chemistry blood biomarkers in oncological patients but their role in adenoid cystic carcinomas (ACCs) is still unknown. This study aims to assess the prognostic significance of baseline neutrophil-to-lymphocyte ratio (NLR) and blood chemistry in a series of head and neck ACC patients treated with carbon ion radiotherapy (CIRT). MATERIAL AND METHODS: We retrospectively retrieved the data of 49 consecutive head and neck ACC patients treated with CIRT. Univariable and multivariable Cox proportional hazard regression (Cox-ph) analyses were performed to look for a potential association of NLR, and other blood biomarker values, with disease-free survival (DFS), Local Control (LC), Metastasis Free Survival (MFS) and overall survival (OS). RESULTS: No significant association between NLR > 2,5 and DFS, LC, MFS and OS was found with univariable analysis although a trend was reported for DFS (Hazard ratio [HR]: 2,10, 95 % CI: 0,85 - 5,08, p-value = 0,11). Patients with hemoglobin (hb) ≤ 14 g/dL showed significantly better DFS, MFS and OS. Multivariable regression Cox-ph analysis for DFS, adjusted for margin status, clinical target volume and Absolute Number of Monocytes, reported the following statistically significant HRs, for both NLR > 2,5 and hb > 14 g/dL respectively: 4,850 (95 % CI = 1,408 - 16,701, p = 0,012) and 3,032 (95 % CI = 1,095 - 8,393, p = 0,033). Moreover, hb > 14 with HR = 3,69 (95 % CI: 1,23 - 11,07, p-value = 0,02), was a negative independent prognostic predictor for MFS. CONCLUSIONS: Pre-treatment NLR and hb values seem to be independent prognostic predictor for clinical outcomes in head and neck ACC patients. If their role will be validated in a larger prospective cohort, they might be worthwhile for a pre-treatment risk stratification in patients treated with CIRT.
Carcinoma, Adenoid Cystic , Heavy Ion Radiotherapy , Humans , Neutrophils , Lymphocyte Count , Carcinoma, Adenoid Cystic/radiotherapy , Retrospective Studies , Prospective Studies , Lymphocytes , Prognosis
(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.
Undifferentiated carcinoma of the nasopharynx (NPC) is a rare disease, which usually occurs in the Asian population. Due to its anatomic location, it is characterised by rich lymph node drainage and has a high incidence of cervical node metastasis. However, cervical nodal metastasis commonly involves retropharyngeal nodes and level II nodes, followed by level III nodes. In recent years, innovations in terms of systemic treatments and radiotherapy techniques have improved oncological outcome and treatment-related toxicities. Therefore, there is a growing interest in de-intensification strategies of reducing volumes and treatment-related side effects, especially in patients with NPC with N0-N1-stage disease. Proton therapy could represent a valid alternative to Intensity Modulated Radiotherapy (IMRT) in the management of NPC in this setting. With this Commentary, we aim to explore the feasibility of Intensity Modulated Proton Therapy (IMPT) in upper-neck irradiation of NPC N1-stage disease. We selected an NPC patient with N1 disease and compared the original IMRT plan with the IMPT plan in terms of dosimetric parameters. IMPT offers a minimal dosimetric advantage over IMRT in the bilateral lower-neck sparing. Clinical trials are needed to evaluate the significance of these proposed suggestions and their applicability in non-endemic areas.
Aim: The purpose of this study is to collect available evidence on the feasibility and efficacy of stereotactic arrhythmia radio ablation (STAR), including both photon radiotherapy (XRT) and particle beam therapy (PBT), in the treatment of atrial fibrillation (AF), and to provide cardiologists and radiation oncologists with a practical overview on this topic. Methods: Three hundred and thirty-five articles were identified up to November 2021 according to preferred reporting items for systematic reviews and meta-analyses criteria; preclinical and clinical studies were included without data restrictions or language limitations. Selected works were analyzed for comparing target selection, treatment plan details, and the accelerator employed, addressing workup modalities, acute and long-term side-effects, and efficacy, defined either by the presence of scar or by the absence of AF recurrence. Results: Twenty-one works published between 2010 and 2021 were included. Seventeen studies concerned XRT, three PBT, and one involved both. Nine studies (1 in silico and 8 in vivo; doses ranging from 15 to 40 Gy) comprised a total of 59 animals, 12 (8 in silico, 4 in vivo; doses ranging from 16 to 50 Gy) focused on humans, with 9 patients undergoing STAR: average follow-up duration was 5 and 6 months, respectively. Data analysis supported efficacy of the treatment in the preclinical setting, whereas in the context of clinical studies the main favorable finding consisted in the detection of electrical scar in 4/4 patients undergoing specific evaluation; the minimum dose for efficacy was 25 Gy in both humans and animals. No acute complication was recorded; severe side-effects related to the long-term were observed only for very high STAR doses in 2 animals. Significant variability was evidenced among studies in the definition of target volume and doses, and in the management of respiratory and cardiac target motion. Conclusion: STAR is an innovative non-invasive procedure already applied for experimental treatment of ventricular arrhythmias. Particular attention must be paid to safety, rather than efficacy of STAR, given the benign nature of AF. Uncertainties persist, mainly regarding the definition of the treatment plan and the role of the target motion. In this setting, more information about the toxicity profile of this new approach is compulsory before applying STAR to AF in clinical practice.
Background: 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). Methods: 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) (VD), 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. Results: 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. VD 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. Conclusion: 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.
PURPOSE: To critically review available literature on hypofractionated (≥ 3 Gy/fraction) proton therapy (PT) for breast cancer (BCa). METHODS: A systematic screening of the literature was performed in April 2021 in compliance with the preferred reporting items for systematic reviews and meta-analyses recommendations. All full-text publication written in English were considered eligible. Acute and late toxicities, oncological outcomes and dosimetric features were considered for the analysis. RESULTS: Twelve publications met the inclusion criteria; all studies but one focused on accelerated partial breast irradiation (APBI). Eleven works considered post-operative patients, one referred to ABPI as a curative-intent modality. The dosimetric profile of PT compared favorably with both photon-based 3D conformal and intensity-modulated techniques, while a more extended follow-up is warranted to fully assess both the long-term toxicities and the non-inferiority of oncological outcomes. CONCLUSION: Our work shows that results on PT for BCa are currently only available for APBI applications, with dosimetric analyses demonstrating a clear advantage over both 3D conformal and intensity modulated X-rays techniques, especially when ≥ 2 treatment fields were used. However, further evidence is needed to define whether such theoretical benefit translates into clinical improvements, especially in the long-term.
Breast Neoplasms , Proton Therapy , Radiotherapy, Conformal , Radiotherapy, Intensity-Modulated , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Female , Humans , Mastectomy, Segmental , Proton Therapy/adverse effects , Radiometry
OBJECTIVES: The aim of this study is to evaluate feasibility of salvage 4-week hypofractionated whole breast radiotherapy (WBRT) in patients with in-breast recurrence after receiving intraoperative radiotherapy with electrons (IOERT) for primary breast cancer (BC). METHODS: BC patients who had repeated quadrantectomy underwent modified WBRT with intensity-modulated radiotherapy using Helical Tomotherapy to underdose the IOERT region. This approach, called POLO (Partially Omitted Lobe), excluded the IOERT volume from receiving the full prescription dose. RESULTS: Nine patients were treated with this approach, receiving 45 Gy in 20 fractions. A simultaneous integrated boost of 2.5 Gy in 20 fractions was delivered in 6/9 patients. Dose constraints and planning objectives were reported. No severe toxicity was reported while local control and overall survival were 100%. CONCLUSION: The POLO approach is technically feasible and capable to achieve a significant reduction of radiation dose delivered to the previous treated IOERT area. ADVANCES IN KNOWLEDGE: The study demonstrates the technical and dosimetric feasibility of conservative salvage whole breast radiotherapy, while sparing the area already treated with IORT, in patients with in-breast recurrence.
Breast Neoplasms , Radiotherapy, Intensity-Modulated , Breast Neoplasms/etiology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Electrons , Female , Humans , Mastectomy, Segmental , Radiotherapy Dosage , Radiotherapy, Adjuvant/adverse effects
