Clinical results of carbon-ion radiotherapy for stage I non-small cell lung cancer with concomitant interstitial lung disease: a Japanese national registry study (J-CROS-LUNG).

Anti-cancer treatments for lung cancer patients with interstitial lung disease (ILD) are challenging. The treatment options for ILD are often limited because of concerns that treatments can cause acute exacerbation (AE) of ILD. This study aimed to analyze the outcomes of carbon-ion radiotherapy (CIRT) for stage I non-small cell lung cancer (NSCLC) with ILD, using a multi-institutional registry. Patients with ILD who received CIRT for stage I NSCLC in CIRT institutions in Japan were enrolled. The indication for CIRT was determined by an institutional multidisciplinary tumor board, and CIRT was performed in accordance with institutional protocols. Thirty patients were eligible. The median follow-up duration was 30.3 months (range, 2.5-58 months), and the total dose ranged from 50 Gy (relative biological effectiveness [RBE]) to 69.6 Gy (RBE), and five different patterns of fractionation were used. The beam delivery method was passive beam in 19 patients and scanning beam in 11 patients. The 3-year overall survival (OS), cause-specific survival, disease-free survival (DFS) and local control (LC) rates were 48.2%, 62.2%, 41.2% and 88.1%, respectively. Grade > 2 radiation pneumonitis occurred in one patient (3.3%). In conclusion, CIRT is a safe treatment modality for stage I NSCLC with concomitant ILD. CIRT is a safe and feasible treatment option for early lung cancer in ILD patients.

Is Thoracic Radiotherapy an Absolute Contraindication for Treatment of Lung Cancer Patients With Interstitial Lung Disease? A Systematic Review.

Thoracic radiotherapy decisions in patients with interstitial lung disease (ILD) are complex due to concerns about severe or even fatal radiation pneumonitis. This systematic review analysed the published evidence regarding the incidence of radiation pneumonitis and mortality after thoracic radiotherapy and investigated clinical and dosimetric predictors of radiation pneumonitis in lung cancer patients with ILD. A systematic search was carried out in PubMed, Medline, Embase and the Cochrane database for articles published between January 2000 and April 2021. Two authors independently screened eligible studies that met our predefined criteria. Studies were assessed for design and quality and a qualitative data synthesis was carried out. The search strategy resulted in 1750 articles. After two rounds of screening, 24 publications were included. The median overall incidence of grade ≥3 radiation pneumonitis was 19.7% (range 8-46%). The incidence was greater in conventional radical radiotherapy-treated patients (median 31.8%) compared with particle beam therapy- or stereotactic ablative radiotherapy-treated patients (median 12.5%). The median rate of grade 5 radiation pneumonitis was 11.9% (range 0-60%). The presence of ILD was an independent predictor of severe radiation pneumonitis. Severe radiation pneumonitis was more common in the presence of usual interstitial pneumonia (UIP) pattern or idiopathic pulmonary fibrosis (IPF) than non-UIP or non-IPF subtype. Several other clinical predictors were reported in the literature. V5, V10, V20 and mean lung dose were the most common dosimetric predictors for severe radiation pneumonitis, often with stricter dose constraints than conventionally used. Patients with lung cancer associated with ILD had a poorer overall survival compared with patients without ILD. In conclusion, patients with lung cancer associated with ILD have a poor prognosis. They are at high risk of severe and even fatal radiation pneumonitis. Careful patient selection is necessary, appropriate high-risk consenting and strict lung dose-volume constraints should be used, if these patients are to be treated with thoracic radiotherapy.

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Risk factors for radiation pneumonitis in lung cancer patients with subclinical interstitial lung disease after thoracic radiation therapy.

BACKGROUND: Previous studies have found that patients with subclinical interstitial lung disease (ILD) are highly susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy. In the present study we aimed to evaluate the incidence of and risk factors for RP after thoracic intensity-modulated radiation therapy in lung cancer patients with subclinical ILD. METHODS: We retrospectively analyzed data from lung cancer patients with subclinical ILD who were treated with thoracic intensity-modulated radiation therapy with a prescribed dose of ≥ 50 Gy in our institution between January 2016 and December 2017. RESULTS: Eighty-seven consecutive lung cancer patients with subclinical ILD were selected for the study. The median follow-up period was 14.0 months. The cumulative incidence of grades ≥ 2 and ≥ 3 RP at one year was 51.0% and 20.9%, respectively. In the multivariate analysis, a mean lung dose ≥ 12 Gy was a significant risk factor for grade ≥ 2 RP (p = 0.049). Chemotherapy with gemcitabine in the past, V5 ≥ 50%, and subclinical ILD involving ≥ 25% of the lung volume were significantly associated with grade ≥ 3 RP (p = 0.046, p = 0.040, and p = 0.024, respectively). CONCLUSION: Mean lung dose is a significant risk factor for grade ≥ 2 RP. Lung cancer patients who have received chemotherapy with gemcitabine in the past, V5 ≥ 50%, and those with subclinical ILD involving ≥ 25% of lung volume have an increased risk of grade ≥ 3 RP in lung cancer patients with subclinical ILD.

Nationwide survey of radiation therapy in Japan for lung cancer complicated with interstitial lung disease.

The purpose of this study was to clarify the opinions of radiation oncologists in Japan regarding treatment for lung cancer complicated with interstitial lung disease (ILD) by a questionnaire survey, and the risk of acute exacerbation (AE) after radiotherapy. Questionnaires were sent to all of the facilities in which radiation therapy is performed for lung cancer in Japan by using the mailing list of the Japanese Society for Radiation Oncology (JASTRO). The questionnaire survey was conducted to clarify who judges the existence of ILD, the indications for radiation therapy in cases of ILD-combined lung cancer, and the ratio of ILD-combined lung cancer in lung cancer patients treated with radiation therapy. Patients with ILD-combined lung cancer who received radiotherapy during the period from April 2014 to March 2015 were retrospectively analysed. Any cases of AE without any other obvious cause were included. ILD confirmation was performed by central radiologists using computed tomography images. A total of 47 facilities responded to the questionnaire. Radiation therapy was an option in cases of ILD-combined lung cancer in 39 (83%) of the facilities. The indication for radiation therapy was based on image findings in 35 (90%) of the 39 facilities in which radiation therapy was acceptable or was a choice in some cases of ILD. The final indication was based on the opinion of the pulmonologist in 29 (74%) of those 39 facilities. In fiscal year 2014, a total of 2128 patients in 38 facilities received chest irradiation. Seventy-eight (3.7%) of those 2128 patients had ILD-combined lung cancer. Sixty-seven patients were included in patient analysis. AE occurred in 5 patients (7.5%), and one of those 5 patients (20.0%) died from radiation-induced AE. The median period from radiotherapy to AE was 4 months (range, 2-7 months). The following four independent risk factors for AE were identified in univariate analysis: non-advanced age (<75 years), increased C-reactive protein level (≥0.3 mg/dl), adjuvant chemotherapy and ≥ Grade 2 radiation pneumonitis. Radiotherapy was an option for lung cancer even in cases with ILD in 83% (39/47) of the facilities in Japan. Seventy-eight (3.7%) of 2128 patients who received radiation therapy for lung cancer had ILD. Radiotherapy for ILD-combined lung cancer may induce AE at a substantial rate and AE can be life-threatening. Minimizing the risk of radiation pneumonitis might enable the risk of AE to be reduced.

Assessment of precision irradiation in early non-small cell lung cancer and interstitial lung disease (ASPIRE-ILD): study protocol for a phase II trial.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD. METHODS: ASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1-2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy10 or 217 Gy3), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy10 or 133 Gy3) and 45 Gy in 15 fractions daily (58 Gy10 or 90 Gy3). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR. DISCUSSION: ASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03485378. Date of registration: April 2, 2018.

Biosynthesis of selenium nanoparticles, characterization and X-ray induced radiotherapy for the treatment of lung cancer with interstitial lung disease.

Selinium nanoparticles (SeNPs) with minimal toxicity and efficient antioxidant properties were reported earlier for their anti-carcinogenic influence against various types of cancers, thus elevating its potential. In the present study, the anti-carcinogenic effect of selenium nanoparticles against lung cancer was studied. Selenium nanoparticles were biosynthesized and were characterized using UV- Vis absorption spectroscopy. A decrease in the absorption intensity was recorded with the increase in time, which represented the protein consumption during the reduction of SeO32- to Se0. The calculated average crystalline size from XRD studies of the synthesized selenium nanoparticles was found to be 88.89 nm which was in accordance with the TEM analysis while the SAED pattern has disclosed hexagonal ring structure with diffraction ring pattern.MTT assay was performed to evaluate the radio-sensitizing effect of selenium nanoparticles under the X-ray influence against cancer as well as healthy cell lines. SeNPs showed potent cytotoxicity effect in cancer cells whereas it showed relatively less toxic effect in normal healthy cells. However, caspase-3 activity was even more elevated when subjected to X-ray exposure than in the absence. These findings apparently revealed the cytotoxic potential of SeNPs + X-ray combination in the lung cancer cell lines.

The potential role of brachytherapy in the irradiation of patients with lung cancer: a systematic review

To review the use of brachytherapy as an adjuvant therapy to reduce recurrences after sublobar resections and as a palliation to patients with inoperable disease. Α review of all published studies was performed to identify the recurrence rate after brachytherapy adjuvant to sublobar resection and assess the palliation of symptoms and the complications of brachytherapy as a palliative treatment. Most of the studies that we found about brachytherapy as an adjuvant therapy to sublobar resection due to patient’s poor cardiopulmonary reserve showed that brachytherapy offered low recurrence rate with low toxicity. Ten studies concerning palliative brachytherapy showed improvement of symptoms with good tolerance and good endoscopic response rates. Literature suggests that brachytherapy for inoperable symptomatic disease can be delivered for symptom improvement with acceptable toxicity. Brachytherapy as an alternative treatment option for lung cancer needs more investigation with more prospective trials (AU)

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Severe radiation pneumonitis after lung stereotactic ablative radiation therapy in patients with interstitial lung disease.

PURPOSE: To investigate the incidence and predictive factors of severe radiation pneumonitis (RP) after stereotactic ablative radiation therapy (SABR) in early-stage lung cancer patients with preexisting radiological interstitial lung disease (ILD). METHODS AND MATERIALS: A retrospective analysis of patients with stage I lung cancer treated with SABR from 2009 to 2014 was conducted. Interstitial lung disease diagnosis and grading was based on pretreatment high-resolution computed tomography imaging. A central review of pretreatment computed tomography by a single experienced thoracic radiologist was conducted. Univariate and multivariate analyses were conducted to determine potential predictors of severe RP in patients with ILD. RESULTS: Among 504 patients treated with SABR in this period, 6% were identified as having preexisting ILD. There was a 4% rate of ≥ grade 3 RP in the entire cohort. Interstitial lung disease was associated with increased risk of ≥ grade 3 RP (32% in ILD+ vs 2% in ILD-, P < .001). Five patients (21%) with ILD developed grade 5 RP. Lower forced expiratory volume in 1 second and forced vital capacity, higher V5Gy and mean lung dose, presence of severe radiological ILD, and combined emphysema were significant predictors of ≥ grade 3 RP on univariate analysis; only forced expiratory volume in 1 second remained on multivariate analysis. CONCLUSION: Interstitial lung disease is associated with an increased risk of severe RP after SABR. Chest imaging should be reviewed for ILD before SABR, and the risk of fatal RP should be carefully weighed against the benefits of SABR in this subgroup.

How radiotherapy was historically used to treat pneumonia: could it be useful today?

X-ray therapy was used to treat pneumonia during the first half of the 20th century. Fifteen studies report that approximately 700 cases of bacterial (lobar and bronchopneumonia), sulfanilamide non-responsive, interstitial, and atypical pneumonia were effectively treated by low doses of X-rays, leading to disease resolution, based on clinical symptoms, objective disease biomarkers, and mortality incidence. The capacity of the X-ray treatment to reduce mortality was similar to serum therapy and sulfonamide treatment during the same time period. Studies with four experimental animal models (i.e., mice, guinea pig, cat, and dog) with bacterial and viral pneumonia supported the clinical findings. The mechanism by which the X-ray treatment acts upon pneumonia involves the induction of an anti-inflammatory phenotype that leads to a rapid reversal of clinical symptoms, facilitating disease resolution. The capacity of low doses of X-rays to suppress inflammatory responses is a significant new concept with widespread biomedical and therapeutic applications.

Nitrofurantoína y enfermedad pulmonar intersticial de rápida resolución / Rapid resolution of nitrofurantoin-induced interstitial lung disease

Presentamos el caso de una mujer de 40 años diagnosticada de enfermedad pulmonar intersticial secundaria a la administración crónica de nitrofurantoína. A pesar de la grave desestructuración de la arquitectura bronquiolar y una tomografía computarizada de tórax que confirmó la presencia de panalización, la biopsia transbronquial mostró un patrón de neumonitis intersticial aguda-subaguda y el cuadro clínico y radiológico se resolvió en el plazo de un mes tras la administración de prednisona. Este caso pone de manifiesto que la enfermedad pulmonar inducida por nitrofurantoína puede llegar a ser una entidad benigna con respuesta favorable a los corticoides, incluso en el caso de que haya datos radiológicos de fibrosis pulmonar establecida. La biopsia transbronquial podría ser una prueba útil para evaluar la reversibilidad de las lesiones pulmonares asociadas a la nitrofurantoína(AU)

We report the case of a 40-year-old woman diagnosed with interstitial lung disease due to long-term nitrofurantoin therapy. Despite severely distorted bronchiolar architecture and honeycombing confirmed by computed tomography of the thorax, transbronchial biopsy showed a pattern of acute/subacute interstitial pneumonitis and the symptoms and radiographic findings disappeared within 1 month after administration of prednisone. This case shows that nitrofurantoin-induced lung disease may run a benign course and respond favorably to corticosteroids, even when there is radiographic evidence of established lung fibrosis. Transbronchial biopsy might be useful for assessing the reversibility of pulmonary lesions associated with nitrofurantoin(AU)

Un nuevo caso de neumonía intersticial bronquiolocéntrica idiopática / A New Case of Idiopathic Bronchiolocentric Interstitial Pneumonia

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