Short-course Radiotherapy for Airway Stenting in Malignant Airway Obstruction: A Case Report and Literature Review.

Background: Malignant airway obstruction (MAO) secondary to tumor growth occurs in nearly a third of patients with lung cancer and portends a very poor prognosis if untreated. Treatment options include bronchoscopic intervention with tumor debulking, stent placement, endobronchial brachytherapy, or palliative radiotherapy. Case Report: This is a report of a 74-year-old woman with a medical history of metastatic lung adenocarcinoma, hospitalized for dyspnea, hemoptysis, and chest pain with a radiographic finding of MAO on chest X-ray and computed tomography. Patient underwent radiation with a total dose of 13 Gy in two once-weekly fractions of 6.5 Gy per fraction. Three days after the end of radiation treatment, chest X-ray showed a completely right lung re-expansion without atelectasis. Two weeks after radiotherapy treatment, the patient was discharged from hospital without pulmonary symptoms. Conclusion: A different fractionation with a lower equivalent dose in 2 Gy fraction compared to literature data showed efficacy in resolving MAO with excellent local control in the first three months of follow-up.

Proton and photon radiotherapy in stage III NSCLC: Effects on hematological toxicity and adjuvant immune therapy.

BACKGROUND AND PURPOSE: Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment. MATERIALS AND METHODS: Prospectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients. RESULTS: 271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0-4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9-12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16-0.79, P = 0.01). CONCLUSION: IMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab.

PERSIAN trial (NCT05717660): an ongoing randomized trial testing androgen deprivation therapy, apalutamide and stereotactic body radiotherapy. An alternative "triplet" for oligometastatic hormone sensitive prostate cancer patients.

Earlier treatment intensification with systemic potent androgen receptor inhibition has been shown to improve clinical outcomes in metastatic hormone sensitive prostate cancer. Nonetheless, oligometastatic patients may benefit from local treatment approaches such as stereotactic body radiotherapy (SBRT). Aiming to explore the benefit of SBRT in this scenario, we designed this trial to specifically test the hypothesis that SBRT will improve clinical outcomes in select population affected by metachronous oligometastatic HSPC treated with androgen deprivation therapy + apalutamide. Enrolled patients will be randomized to receive the standard systemic treatment alone or in combination with SBRT on all metastatic sites of disease. Here we report the protocol design and an overview of the ongoing trials testing different integration strategies between RT and systemic therapies.

Fiducial markers in adjuvant setting for a patient affected by endometrial cancer: a case report.

Introduction: Intermediate-high and high-risk endometrial cancer often require adjuvant treatments such as radiotherapy (RT) or brachitherapy (BT) to reduce the risk of loco-regional relapse. Inter- and intra-fraction variability of internal pelvic anatomy are possibly the largest source of error affecting pelvic RT. The implantation of Fiducial Makers (FMs) in the vaginal cuff of patients receiving RT or BT could help patient daily setup, image guidance and intra-fraction detection of the radiation targets. Clinical case: We have evaluated the case of an 80-year-old woman treated with surgery for endometrioid adenocarcinoma G2 (stage pT1b Nx LVSI+) who underwent adjuvant pelvic IMRT after the implantation of vaginal cuff FMs. CT-simulation Treatment Planning and IGRT strategy: Patient underwent planning CT scan 10 days after FMs implantation. RT consisted of 45Gy in 25 daily fractions to pelvic lymph nodes and surgical bed with simultaneous integrated boost up to 52.5Gy to the vaginal cuff and the upper two-thirds of the vagina. Cone beam Computed Tomography (CBCT) was acquired prior to every RT fraction for IGRT. Bladder and rectum were re-contoured on every CBCTs. Bladder and rectal volumes and median shifts were reported on a prospective database to quantify the impact of the pelvic organ variations. Results: The patient reported no discomfort during the FMs implantation, and no complications were seen. No evidence of FMs migration was reported. Bladder and rectal volumes planned contours were 245 and 55.3cc. Median bladder volumes for approved and "not acceptable" CBCTs were 222cc (range: 130-398) and 131cc (range: 65-326), respectively. Median rectal volumes for approved and "not acceptable" CBCTs were 75cc (range: 58-117) and 90cc (range: 54-189), respectively. The median values of the anterior-posterior, superior-inferior, lateral direction shifts were 3.4, 1.8 and 2.11 mm, respectively. Conclusion: In our clinical case, the implantation of FMs in the vaginal cuff of a patient who underwent pelvic adjuvant RT was well tolerated and reported no complications. The use of IGRT procedures based on FMs surrogating the vaginal vault may reduce inter-observer variability and pave the way for adaptive strategies or stereotactic treatments as external beam pelvic boost in gynecological field.

Emerging Role of Immunomonitoring to Predict the Clinical Outcome of Patients With Malignant Pleural Mesothelioma Treated With Radical Radiation Therapy.

PURPOSE: The present study aimed at evaluating the baseline immune profile and the immunomodulating effects of radical hemithoracic radiation therapy (RT) in patients affected by malignant pleural mesothelioma (MPM) to identify potential predictive biomarkers of therapy response, toxicity development, and eligibility for further immunotherapeutic treatments. METHODS AND MATERIALS: Blood samples were collected from 55 patients with MPM, enrolled in a phase 3 trial comparing radical hemithoracic RT (interventional arm, n = 28) with local palliative RT (control arm, n = 27). Immunomonitoring was performed before RT, at the end of treatment, and 1 month after therapy, characterizing natural killer cells, B and T lymphocytes, activated CD4 and CD8 T cells, interferon-γ- and tumor necrosis factor-α-producing T helper (Th) 1 cells, regulatory T cells, and Th17 and Th22 lymphocytes, through flow cytometry. Serum levels of interleukin (IL)-6, -8, -10 and mesothelin were quantified through Enzyme-Linked Immunosorbent Assay (ELISA) assays at the same time points. Variations in the immune parameters were investigated by Friedman test and Wilcoxon signed rank post hoc test with Bonferroni correction for multiple testing, while the prognostic effect of immune biomarkers was evaluated through Kaplan-Meier method and Spearman's correlation analysis. RESULTS: Major immune variations were noticed after radical RT compared with palliative treatment, in particular an improvement in activated T cells and in interferon-γ-producing Th1 cells after RT. In the interventional arm, baseline high levels of Th22 and IL-10 and an increase in T cells were associated with an improved survival, whereas a fold increase in serum mesothelin correlated with the development of severe toxicity. An improvement of immunosuppressive regulatory T cells was observed in both arms of treatment. CONCLUSIONS: The immunomonitoring performed in patients with MPM revealed potential prognostic biomarkers for radical hemithoracic RT treatment and identified specific immune signatures induced by RT immunomodulation, which could suggest a synergistic effect with an immunotherapeutic treatment.

Prostate Cancer Treatment-Related Toxicity: Comparison between 3D-Conformal Radiation Therapy (3D-CRT) and Volumetric Modulated Arc Therapy (VMAT) Techniques.

Objective: This paper illustrates the results of a mono-institutional registry trial, aimed to test whether gastrointestinal (GI) and genitourinary (GU) toxicity rates were lower in localized prostate cancer patients treated with image-guided volumetric modulated arc therapy (IG-VMAT) compared to those treated with IG-3D conformal radiation therapy (IG-3DCRT). Materials and Methods: Histologically proven prostate cancer patients with organ-confined disease, treated between October 2008 and September 2014 with moderately hypofractionated radiotherapy, were reviewed. Fiducial markers were placed in the prostate gland by transrectal ultrasound guide. The prescribed total dose was 70 Gy in 28 fractions. The mean and median dose volume constraints for bladder and rectum as well as total volume of treatment were analyzed as potentially prognostic factors influencing toxicity. The Kaplan−Meier method was applied to calculate survival. Results: Overall, 83 consecutive patients were included. Forty-two (50.6%) patients were treated with 3D-CRT and 41 (49.4%) with the VMAT technique. The median follow-up for toxicity was 77.26 months for the whole cohort. The VMAT allowed for a dose reduction to the rectum and bladder for the large majority of the considered parameters; nonetheless, the only parameter correlated with a clinical outcome was a rectal dose limit V66 > 8.5% for late GI toxicity G ≥ 2 (p = 0.045). Rates of G ≥ 2 toxicities were low among the whole cohort of these patients treated with IGRT. The analysis for rectum dose volume histograms (DVHs) showed that a severe (grade ≥ 2) late GI toxicity was related with the rectal dose limit V66 > 8.5% (p = 0.045). Conclusions: This study shows that moderate hypofractionation is feasible and safe in patients with intermediate and high-risk prostate cancer. Daily IGRT may decrease acute and late toxicity to organs at risk and improve clinical benefit and disease control rate, cutting down the risk of PTV geographical missing. The adoption of VMAT allows for promising results in terms of OAR sparing and a reduction in toxicity that, also given the small sample, did not reach statistical significance.

Human amniotic membrane for myocutaneous dehiscence after a radical surgical treatment of vulvar cancer: A case report.

Background: The application of the amniotic membrane could have a favourable effect on tissue repair and regeneration. We report the first case of implant of an amniotic membrane in a patient affected by myo-cutaneous dehiscence, after a radical surgical treatment for vulvar cancer. Methods: We describe a case of a 74-years-old patient affected by vulvar cancer. After radiotherapy, the patient underwent to an anterior pelvic exenteration with uretero-ileo-cutaneostomy by Wallace, bilateral pelvic lymphadenectomy, omental biopsies, omental flap, bilateral inguinal lymphadenectomy, resection of ulcerated left inguinal lesion, reconstruction with left gracilis muscle flap and locoregional V-Y advancement flap. The patient developed a myo-cutaneous dehiscence. Two months after the surgery, following an accurate curettage of the wound and negative pressure therapy, a patch of human amniotic membrane was implanted. Results: The surgical procedure was easy, feasible and did not require long operating room times. No intraoperative or postoperative complications occurred. The results obtained were encouraging with a marked improvement in the surgical wound. Conclusion: the use of amniotic membranes was safely and easily performed to promote the healing of complicated surgical wounds.

Multidisciplinary Approach to Patients With Metastatic Spinal Cord Compression: A Diagnostic Therapeutic Algorithm to Improve the Neurological Outcome.

Introduction: The morbidity associated with metastatic spinal disease is significant because of spinal cord and/or nerve root compression. The purpose of this paper is to define a diagnostic-therapeutic path for patients with vertebral metastases and from this path to build an algorithm to reduce the devastating consequences of spinal cord compression. Materials and Methods: The algorithm is born from the experience of a primary care center. A spine surgeon, an emergency room (ER) physician, a neuroradiologist, a radiation oncologist, and an oncologist form the multidisciplinary team. The ER physician or the oncologist intercept the patient with symptoms and signs of a metastatic spinal cord compression. Once the suspicion is confirmed, the following steps of the flow-chart must be triggered. The spine surgeon takes charge of the patient and, on the base of the anamnestic data and neurological examination, defines the appropriate timing for magnetic resonance imaging (MRI) in collaboration with the neuroradiologist. From the MRI outcome, the spine surgeon and the radiation oncologist consult each other to define further therapeutic alternatives. If indicated, surgical treatment should precede radiation therapy. The oncologist gets involved after surgery for systemic therapy. Results: In 2021, the Spine and Spinal Cord Surgery department evaluated 257 patients with vertebral metastasis. Fifty-three patients presented with actual or incipient spinal cord compression. Among these, 27 were admitted due to rapid progression of symptoms, neurological deficits and/or spine instability signs. The level was thoracic in 21 cases, lumbar in 4 cases, cervical in 1 case, sacral in 1 case. Fifteen were operated on, 10 of these programmed and 5 in emergency. Discussion: Patients with a history of malignancy can present to the ER or to the oncology department with symptoms that must be correctly framed in the context of a metastatic involvement. Even when there is no previous cancer history, the patient's pain characteristics and clinical signs must be interpreted to yield the correct diagnosis of vertebral metastasis with incipient or current spinal cord compression. The awareness of the alert symptoms and the application of an integrated paradigm consent to frame the patients with spinal cord compression, obtaining the benefits of a homogeneous step-by-step diagnostic and therapeutic path. Early surgical or radiation therapy treatment gives the best hope for preventing the worsening, or even improving, the deficits. Conclusions: Metastatic spinal cord compression can cause neurological deficits compromising quality of life. Treatment strategies should be planned comprehensively. A multidisciplinary approach and the application of the proposed algorithm is of paramount importance to optimize the outcomes of these patients.

Stereotactic Radiotherapy and Androgen Deprivation Therapy for Localized Prostate Cancer: A Retrospective Mono-institutional Experience.

BACKGROUND/AIM: Stereotactic radiotherapy (SRT) is an effective treatment for localized prostate cancer. However, is it not clear whether the addition of androgen deprivation therapy (ADT) to SRT is beneficial. The aim of this study was to analyze the outcomes of a series of patients treated with SRT plus ADT for localized prostate cancer. PATIENTS AND METHODS: Patients were treated with SRT with 42 Gy in 7 fractions with volumetric-modulated arc therapy plus Image Guided Radiotherapy (V-MAT IGRT) technique. ADT was administered to patients with intermediate unfavorable- and high-risk disease. Study endpoints were biochemical disease-free survival (bDFS), overall survival (OS), acute and late toxicity and patient-reported outcomes (PROs) using international prostate cancer symptoms scale (IPSS) and international index of erectile function (IIEF). RESULTS: A total of 170 consecutive patients were identified, of which 49 (28.8%) with low-risk, 15 (8.8%) with favorable intermediate-risk 76 (44.7%) with unfavorable intermediate-risk and 30 (17.6%) with high-risk class. All patients of unfavorable intermediate- and high-risk groups were administered LHRH analogue concurrently to SRT and for at least 6 months. Patients with unfavorable intermediate- and high-risk presented a 5-year bDFS of 81.7% and 76.9%, respectively. CONCLUSION: SRT consisting of 42 Gy in seven fractions with short-term ADT represents a safe and effective treatment for unfavorable intermediate and high risk prostate cancer. Our results support the need of high quality studies to test the efficacy of ADT combined with SRT for unfavorable intermediate- and high-risk localized prostate cancer.

Corrigendum: A Real-World, Multicenter, Observational Retrospective Study of Durvalumab After Concomitant or Sequential Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer.

[This corrects the article DOI: 10.3389/fonc.2021.744956.].

A Real-World, Multicenter, Observational Retrospective Study of Durvalumab After Concomitant or Sequential Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer.

INTRODUCTION: For unresectable stage III non-small cell lung cancer (NSCLC), the standard therapy consists of chemoradiotherapy (CRT) followed by durvalumab maintenance for responding patients. The present study reports on the safety and outcome of durvalumab use after CRT in a real-world, multicenter, retrospective cohort. METHODS: Two hundred thirty-eight patients have been included. We collected data on systemic therapy, radiation therapy, the timing between CRT and durvalumab, number of durvalumab cycles, reasons for non-starting or discontinuation, incidence and grade of adverse events (AEs), and progression-free survival (PFS) and overall survival (OS). RESULTS: One hundred fifty-five patients out of 238 (65.1%) received at least one durvalumab dose: 91 (58.7%) after concomitant CRT (cCRT) and 64 (41.3%) after sequential CRT (sCRT). Programmed-death ligand 1 (PD-L1) status was unknown in 7/155 (4.5%), negative in 14 (9.1%), and positive ≥1% in 134/155 (86.4%). The main reasons for non-starting durvalumab were progression (10.1%), PD-L1 negativity (7.5%), and lung toxicity (4.6%). Median follow-up time was 14 months (range 2­29); 1-year PFS and OS were 65.5% (95%CI: 57.6-74.4) and 87.9% (95%CI: 82.26.6-93.9), respectively. No significant differences in PFS or OS were detected for cCRT vs. sCRT, but the median PFS was 13.5 months for sCRT vs. 23 months for cCRT. Potentially immune-related AEs were recorded in 76/155 patients (49.0%). Pneumonitis was the most frequent, leading to discontinuation in 11/155 patients (7.1%). CONCLUSIONS: Durvalumab maintenenace after concurrent or sequential chemoradiation for unresectable, stage III NSCLC showed very promising short-term survival results in a large, multicenter, restrospective, real-world study. Durvalumab was the first drug obtaining a survival benefit over CRT within the past two decades, and the present study contributes to validating its use in clinical practice.

Sequential chemo-hypofractionated RT versus concurrent standard CRT for locally advanced NSCLC: GRADE recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

INTRODUCTION: Almost 30% of non-small cell lung cancer (NSCLC) patients have locally advanced-stage disease. In this setting, definitive radiotherapy concurrent to chemotherapy plus adjuvant immunotherapy (cCRT + IO) is the standard of care, although only 40% of these patients are eligible for this approach. AIMS: A comparison between cCRT and hypofractionated radiotherapy regimens (hypo-fx RT) with the addition of sequential chemotherapy (sCHT) could be useful for future combinations with immunotherapy. We developed a recommendation about the clinical question of whether CHT and moderately hypo-fx RT are comparable to cCRT for locally advanced NSCLC MATERIALS AND METHODS: The panel used GRADE methodology and the Evidence to Decision (EtD) framework. After a systematic literature search, five studies were eligible. We identified the following outcomes: progression-free survival (PFS), overall survival (OS), freedom from locoregional recurrence (FFLR), deterioration of quality of life (QoL), treatment-related deaths, severe G3-G4 toxicity, late pulmonary toxicity G3-G4, and acute esophageal toxicity G3-G4. RESULTS: The probability of OS and G3-G4 late lung toxicity seems to be worse in patients submitted to sCHT and hypo-fx RT. The panel judged unfavorable the balance benefits/harms. CONCLUSIONS: The final recommendation was that sCHT followed by moderately hypo-fx RT should not be considered as an alternative to cCRT in unresectable stage III NSCLC patients.

Radical Hemithoracic Radiotherapy Induces Systemic Metabolomics Changes That Are Associated with the Clinical Outcome of Malignant Pleural Mesothelioma Patients.

Radical hemithoracic radiotherapy (RHRT) represents an advanced therapeutic option able to improve overall survival of malignant pleural mesothelioma patients. This study aims to investigate the systemic effects of this radiotherapy modality on the serum metabolome and their potential implications in determining the individual clinical outcome. Nineteen patients undergoing RHRT at the dose of 50 Gy in 25 fractions were enrolled. Serum targeted metabolomics profiles were investigated at baseline and the end of radiotherapy by liquid chromatography and tandem mass spectrometry. Univariate and multivariate OPLS-DA analyses were applied to study the serum metabolomics changes induced by RHRT while PLS regression analysis to evaluate the association between such changes and overall survival. RHRT was found to affect almost all investigated metabolites classes, in particular, the amino acids citrulline and taurine, the C14, C18:1 and C18:2 acyl-carnitines as well as the unsaturated long chain phosphatidylcholines PC ae 42:5, PC ae 44:5 and PC ae 44:6 were significantly decreased. The enrichment analysis showed arginine metabolism and the polyamine biosynthesis as the most perturbed pathways. Moreover, specific metabolic changes encompassing the amino acids and acyl-carnitines resulted in association with the clinical outcome accounting for about 60% of the interpatients overall survival variability. This study highlighted that RHRT can induce profound systemic metabolic effects some of which may have a significant prognostic value. The integration of metabolomics in the clinical assessment of the malignant pleural mesothelioma could be useful to better identify the patients who can achieve the best benefit from the RHRT treatment.

Dose prescription in SBRT for early-stage non-small cell lung cancer: are we all speaking the same language?

INTRODUCTION: Stereotactic body radiation therapy is increasingly used in the treatment of early-stage lung cancers. Guidelines provide indications regarding the constraints to the organs at risk (OARs) and the minimum coverage of the planning target volume but do not suggest optimal dose distribution. Data on dose distribution from the different published series are not comparable due to different prescription modalities and reported dose parameters. METHODS: We conducted a review of the published data on dose prescription, focusing on the role of homogeneity on local tumor control, and present suggestions on how to specify and report the prescriptions to permit comparisons between studies or between cases from different centers. CONCLUSIONS: To identify the dose-prescription modality that better correlates with oncologic outcomes, future studies should guarantee a close uniformity of dose distribution between cases and complete dose parameters reporting for treatment volumes and OARs.

Radical Hemithoracic Radiotherapy Versus Palliative Radiotherapy in Non-metastatic Malignant Pleural Mesothelioma: Results from a Phase 3 Randomized Clinical Trial.

PURPOSE: We conducted a phase 3 randomized clinical trial to assess whether radical hemithoracic radiation therapy (RHR) compared with palliative radiation therapy (PR) can achieve overall survival (OS) advantages in patients with malignant pleural mesothelioma (MPM). METHODS AND MATERIALS: From August 2014 to May 2018, patients with histologically diagnosed nonmetastatic MPM, who underwent nonradical lung-sparing surgery and chemotherapy (CHT), were randomly assigned (1:1) to receive RHR or PR. RHR total dose to the involved pleural cavity was 50 Gy in 25 fractions, and the gross residual disease received a simultaneous integrated boost of 60 Gy. The primary endpoint was OS. Secondary endpoints were local control, distant metastasis-free survival, progression-free survival, and acute and late toxicity rates. A sample size of 108 patients considering a type I error (α) of 0.05 and a statistical power of 80% was calculated to prove that RHR could improve the 2-year OS. OS was estimated with the Kaplan-Meier method and the log-rank test (2-sided) tested differences between arms. The univariate and multivariate analyses were performed using Cox proportional hazard model. Possible prognostic factors investigated: age, sex, performance status, lung surgery, gross residual disease, and histology. RESULTS: One hundred eight patients were randomized: 53 to the PR arm and 55 to the RHR arm. Median follow-up was 14.6 months. The 2-year OS rate was 58% in the RHR arm versus 28% in the PR arm (hazard ratio, 0.54; 95% confidence interval, 0.31-0.95; P = .031). In the RHR arm: 11 patients experienced acute toxicity grade ≥3, 17 patients had grade 3 to 4 late toxicity. Nine patients experience a grade ≥2 pneumonitis, including 1 patient with grade 5. CONCLUSIONS: RHR significantly improves survival in patients with MPM treated with nonradical lung-sparing surgery and CHT compared with palliative treatments, although it is associated with a nonnegligible toxicity profile.

Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study.

Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients.

Physician Attitudes and Perceptions of Complementary and Alternative Medicine (CAM): A Multicentre Italian Study.

Purpose: Complementary and Alternative Medicine (CAM) interventions are widely used by patients with chronic disorders, including cancer, and may interact with cancer treatment. Physicians are often unaware of this, probably due to poor patient-physician communication on CAM. The purpose of this study was to evaluate physicians' knowledge, attitudes and practice patterns regarding CAM in a survey conducted in Italy. Methods: A questionnaire was administered to 438 physicians (11 Italian hospitals) who predominantly treat patients with chronic disease, to collect personal and professional data and information on attitudes toward CAM and its possible role in Conventional Medicine (CM). Results: Of the 438 participants, most were specialists in oncology (18%), internal medicine (17%), surgery (15%), and radiotherapy (11%). Most worked at university (44%) or research hospitals (31%). Forty-two percent of participants believed that CAM could have an integrative role within CM. Oncologists were the physicians who were best informed on CAM (58%). Physicians working at research institutes or university hospitals had a greater knowledge of CAM than those employed at general hospitals (p < 0.0001), and those who were also involved in research activity had a greater knowledge of CAM than those who were not (p < 0.003). Length of work experience was significantly related to CAM knowledge. Moreover, 55% of participants suggest CAM interventions to their patients and 44% discuss CAM with them. The best-known interventions were acupuncture, Aloe vera and high-dose vitamin C. Conclusion: CAM use by patients with chronic disease and/or cancer has become a topical issue for the scientific community and for physicians. Knowing the reasons that prompt these patients to use CAM and guiding them in their decisions would improve treatment and outcomes and also benefit healthcare systems. Our findings contribute to a greater understanding of CAM knowledge, attitudes, and practice among Italian physicians. Further research is needed to identify the more effective CAM treatments and to work toward an integrated healthcare model.

Electron Density and Biologically Effective Dose (BED) Radiomics-Based Machine Learning Models to Predict Late Radiation-Induced Subcutaneous Fibrosis.

Purpose: to predict the occurrence of late subcutaneous radiation induced fibrosis (RIF) after partial breast irradiation (PBI) for breast carcinoma by using machine learning (ML) models and radiomic features from 3D Biologically Effective Dose (3D-BED) and Relative Electron Density (3D-RED). Methods: 165 patients underwent external PBI following a hypo-fractionation protocol consisting of 40 Gy/10 fractions, 35 Gy/7 fractions, and 28 Gy/4 fractions, for 73, 60, and 32 patients, respectively. Physicians evaluated toxicity at regular intervals by the Common Terminology Adverse Events (CTAE) version 4.0. RIF was assessed every 3 months after the completion of radiation course and scored prospectively. RIF was experienced by 41 (24.8%) patients after average 5 years of follow up. The Hounsfield Units (HU) of the CT-images were converted into relative electron density (3D-RED) and Dose maps into Biologically Effective Dose (3D-BED), respectively. Shape, first-order and textural features of 3D-RED and 3D-BED were calculated in the planning target volume (PTV) and breast. Clinical and demographic variables were also considered (954 features in total). Imbalance of the dataset was addressed by data augmentation using ADASYN technique. A subset of non-redundant features that best predict the data was identified by sequential feature selection. Support Vector Machines (SVM), ensemble machine learning (EML) using various aggregation algorithms and Naive Bayes (NB) classifiers were trained on patient dataset to predict RIF occurrence. Models were assessed using sensitivity and specificity of the ML classifiers and the area under the receiver operator characteristic curve (AUC) of the score functions in repeated 5-fold cross validation on the augmented dataset. Results: The SVM model with seven features was preferred for RIF prediction and scored sensitivity 0.83 (95% CI 0.80-0.86), specificity 0.75 (95% CI 0.71-0.77) and AUC of the score function 0.86 (0.85-0.88) on cross-validation. The selected features included cluster shade and Run Length Non-uniformity of breast 3D-BED, kurtosis and cluster shade from PTV 3D-RED, and 10th percentile of PTV 3D-BED. Conclusion: Textures extracted from 3D-BED and 3D-RED in the breast and PTV can predict late RIF and may help better select patient candidates to exclusive PBI.

COVID-19 outbreak and cancer radiotherapy disruption in Italy: Survey endorsed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Italy experienced one of the world's deadliest COVID-19 outbreaks and healthcare systems had to instantly reorganise activity. The Italian Radiation Oncology Departments adapted numerous solutions to minimize the disruptions. Information technologies, treatment prioritization and implementation of hypofractionation and protection procedures allowed balancing between cancer patient care and patient/healthcare workers safety.