bims-mesote Biomed News
on Mesothelioma
Issue of 2023–10–08
four papers selected by
Laura Mannarino, Humanitas Research



  1. Int J Radiat Oncol Biol Phys. 2023 Oct 01. pii: S0360-3016(23)05183-0. [Epub ahead of print]117(2S): e46
       PURPOSE/OBJECTIVE(S): Malignant Pleural Mesothelioma (MPM) is a rare but aggressive intrathoracic malignancy with an overall poor prognosis. Neoadjuvant chemotherapy, surgery and then radiotherapy is the standard of care in early-stage disease. Our study aim is to evaluate the feasibility and toxicity of the novel adjuvant RT in accelerated hypofractionation. We report the lung toxicity preliminary results of the first patients entreated.
    MATERIALS/METHODS: Starting in 2017, 29 MPM patients were enrolled in the trial (IRST trial 163). All patients were treated with accelerated hypofractionated radiotherapy using a helical 3-D CRT and IMRT system and intensity-modulated arc therapy. We conducted a prospective mono-institutional clinical trial enrolling cyto-histological proven, MPM patients. The major exclusion criteria were: previous thorax radiotherapy, contralateral mediastinum involvement (N3) and/or M1, interstitial pneumopathy, active pneumonitis, and fissural disease. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. All patients were treated in a 3-D CRT and IMRT system. Patients underwent functional lung study before to start radiotherapy treatment, 2 months and 6 months after the end of the treatment. The organs at risk dose-volume histograms were converted to a 2-Gy equivalent dose, and we closely adhered to the dose constraints of the literature data. We in particular analyzed lung toxicity of the first 20 patients.
    RESULTS: No G3/G4 lung toxicity was found. We reported 65.0% G1 pneumonitis and 10% G2 as acute lung toxicity. The majority of the G1 patients had only mild symptoms and pneumonitis was described only for radiologic features with no need for medical therapy. Other respiratory toxicities were G1-G2 cough in 50% of the patients; G1 dyspnea occurred in 65% of the patients and G2 in the 15%. The total lung mean dose was 18 Gy (range 13 Gy-23 Gy), and the contralateral lung mean dose was 2 Gy (range 1 Gy-2 Gy). The median value of Forced Expired Volume in one second (FEV1) recorded was 75.5% (range: 46%-137%) before the treatment was started, the median value of Forced Vital Capacity (FVC) at baseline was 74 (range 46-123) with progressive decreasing values through time. DLCO has also been reported with a progressive decrease over time after radiotherapy treatment. No case of respiratory failure was reported after treatment.
    CONCLUSION: Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. More investigations are mandatory. The protocol is ongoing.
    DOI:  https://doi.org/10.1016/j.ijrobp.2023.06.749
  2. Int J Radiat Oncol Biol Phys. 2023 Oct 01. pii: S0360-3016(23)05205-7. [Epub ahead of print]117(2S): e56-e57
       PURPOSE/OBJECTIVE(S): Pleural metastases are common sites for recurrence and progression in patients with thymic malignancies. The management of pleural metastases typically involves surgical resection with or without neoadjuvant or adjuvant systemic therapy. After surgical resection of pleural metastases, the 5-year progression-free survival (PFS) rate is about 29-45%. While radiation therapy (RT) is standardly used in the management of locally-advanced thymic malignancies, the role of RT in patients with pleural metastases in unclear. Intensity-modulated pleural radiation therapy (IMPRINT) is a RT technique currently being used to treat malignant pleural mesothelioma (MPM) patients with 2 intact lungs at centers that specialize in MPM treatment. This IMPRINT technique can potentially be extrapolated to thymic patients with pleural metastases. Because the risk of toxicity is of greater concern for thymic patients given their overall relatively favorable prognosis, the rate of toxicity, particularly radiation pneumonitis, needs to be established in the thymic patient population.
    MATERIALS/METHODS: This is a single-arm, single institution Phase II study of hemithoracic IMPRINT for patients with pleural metastases from thymic malignancies. The primary endpoint of this study is grade 3 or higher radiation pneumonitis within 4 months of completing RT. Secondary endpoints include any toxicity, progression-free survival, patterns of failure and overall survival. Patients must have a pathologically confirmed diagnosis of a thymic malignancy with radiologic or pathologic evidence of pleural metastases. Thymoma or thymic carcinoma are allowed. Patients may have de novo stage IVA disease or recurrent disease in the pleura. There must be no evidence of extrathoracic metastatic disease or contralateral pleural/pericardial disease. Surgical resection of the pleural nodules (ex: pleurectomy/decortication, debulking/metastasectomy) are allowed. Extrapleural pneumonectomy is not allowed. Patients are excluded if they have undergone prior thoracic radiation therapy preventing hemithoracic pleural IMRT, whereas prior thymic bed radiation and/or prior pleural SBRT are allowed. RT will be administered to the ipsilateral pleura to 50.4 Gy in 28 fractions. An optional dose-painting boost to gross disease up to 60 Gy while respecting normal tissue constraints is allowed. Patients can be treated with photon or proton therapy. Simulation, contouring and RT planning guidelines have been developed. Patients will be followed per protocol at regular intervals for at least 12 months following RT. The expected accrual is 36 patients over 4 years. Further information can be found on clinicaltrials.gov (NCT05354570).
    RESULTS: To be determined.
    CONCLUSION: To be determined.
    DOI:  https://doi.org/10.1016/j.ijrobp.2023.06.771
  3. Int J Radiat Oncol Biol Phys. 2023 Oct 01. pii: S0360-3016(23)06534-3. [Epub ahead of print]117(2S): e662-e663
       PURPOSE/OBJECTIVE(S): Treatment planning for malignant pleural mesothelioma is complex and time-consuming owing to the large volume of the target as well as its overlap and proximity to critical organs. Knowledge-based planning (KBP) model using RapidPlan (RP) was previously developed and clinically tested at our institution for treatment planning of these cases that had undergone pleurectomy-decortication, and therefore had two intact-lungs. The aim of this work is to investigate if multi-criteria optimization (MCO) can further improve the RP model with respect to organ at risk (OAR) sparing without compromising target coverage.
    MATERIALS/METHODS: The RP model was trained with clinically accepted plans of 57 patients that used Volumetric Modulated Arc Therapy (VMAT) with 2 partial arcs and 6 MV photons. The dose volume histogram (DVH) estimation model was trained to estimate doses to the heart, ipsilateral lung, total lung, contralateral lung, stomach, esophagus, kidneys and liver. Clinical treatment plans for 12 patients were re-planned using RP as well as a combination of RP and MCO. Application of MCO was after RP and used tradeoff exploration to navigate to the improved dose distribution on a Pareto surface. Selection of a plan that further improved OAR sparing while maintaining coverage constraints of PTV D95 and V95 ≥ 94% was made. Dosimetric parameters for clinical plans (CP), plans using RP as well as plans generated with RP and MCO were all compared for 12 new validation cases. Wilcoxon sign-rank test was used for statistical significance testing.
    RESULTS: The mean heart dose was reduced from 20.9 Gy ± 3.2 Gy for CP to 17.1 Gy ± 4.2 Gy with RP and further to 13.8 Gy ± 3.3 Gy with RP and MCO. The heart V30 Gy was reduced from 23.7% ± 8% to 18.2% ± 9.4% with RP and further to 13.6% ± 5.7% with RP and MCO. The corresponding results for contralateral lung V5 Gy were 68.6% ± 14.1% with CP, 50% ± 26.3% with RP and 45.3% ± 22.8% with RP and MCO, while the mean esophagus dose was reduced from 26.5 Gy ± 3.1 Gy to 21.5 Gy ± 4.7 Gy with RP and further to 19.1 Gy ± 4.2 Gy with RP and MCO. All these dosimetric improvements were statistically significant (p<0.001). However, improvements with RP and MCO for the total lung mean and V20 Gy, liver mean, stomach mean and kidney V18 Gy were marginal over the RP. Sparing of ipsilateral lung V20 Gy was maintained at ≥ 50 cc on average for all plans. PTV D95 and V95 were both normalized at 94%.
    CONCLUSION: Combination of RP and MCO significantly improved sparing of the OARs, especially the heart, contralateral lung and esophagus without compromising coverage or doses to other structures. Since doses to the heart, and contralateral lung are known to correlate with incidence of radiation pneumonitis, it would be prudent to consider planning with both RP and MCO to help determine the optimal treatment plan for the individual patient's anatomy.
    DOI:  https://doi.org/10.1016/j.ijrobp.2023.06.2100
  4. Arch Environ Occup Health. 2023 Oct 06. 1-10
      Asbestos is a mineral with unique physical and chemical properties that make it highly resistant to heat, fire, and corrosion. Nevertheless, exposure to asbestos fibers has been linked to serious health problems, including lung cancer, mesothelioma, and asbestosis. Despite the ban on asbestos usage, asbestos-related diseases are still a major cause of morbidity and mortality worldwide. Analyzing the mineralogical features and fiber analysis of asbestos in biological materials is critical for scenarios where an asbestos exposure history cannot be obtained, a clinical diagnosis cannot be made, or legal aspects necessitate further investigation. This review outlines the mineralogical features and fiber analysis techniques of asbestos in biological materials.
    Keywords:  Asbestos; asbestos-related diseases; fiber analysis; mineralogy
    DOI:  https://doi.org/10.1080/19338244.2023.2264764