Enhanced pulmonary toxicity with bleomycin and radiotherapy in oat cell lung cancer.

In a recently completed study, combination chemotherapy consisting of bleomycin, adriamycin, cyclophosphamide, and vincristine was given to 29 patients with oat cell lung cancer. There were no cases of pulmonary fibrosis in these 29 patients. Although several of these patients had prior radiotherapy, none had concomitant radiotherapy and chemotherapy. This same four-drug chemotherapy regimen was combined with concomitant radiotherapy in 13 patients with oat cell lung cancer. There were three cases of fatal pulmonary fibrosis and two other cases of clinically significant pulmonary fibrosis. All five cases of pulmonary fibrosis occurred several weeks after completion of a six-week course of bleomycin (total dosage 90 units). It is concluded that bleomycin cannot be safely administered while patients are receiving radiotherapy to the lung.     

Erythropoietin ameliorates chemotherapy-induced fibrosis of the lungs in a preclinical murine model

Organ toxicity induced by chemotherapeutic drugs is a serious obstacle in the effective treatment of patients suffering from cancer and autoimmune disease. A strong association exists between pulmonary toxicity, particularly fibrosis, and chemotherapeutic drugs. Attempts have been made to identify compounds capable of suppressing fibrosis. In addition to its erythropoietic activity, erythropoietin (EPO) has been shown to have effects on nonhemopoietic cells. Therefore, we postulated that EPO may exert beneficial effects on lung tissue during chemotherapy. To test our hypothesis, we investigated pulmonary changes caused by bleomycin, a fibrosis-inducing agent, in animals treated with the drug alone and in combination with EPO. Fibrosis, cellular alterations and structural changes were assayed by blind analysis of the lung sections. A 6-fold decrease in the number of prominent endothelial cells--suspected to be indicative of cellular activation and inflammatory response--was observed in lung sections derived from mice treated with bleomycin and EPO compared to animals injected with bleomycin alone (p < 0.008). Additionally, there was twice the number of ICAM1-positive endothelial cells in animals treated with bleomycin alone compared with the number in the bleomycin and EPO-treated group (p < 0.05). Alveolar mononuclear phagocytic hyperplasia was reduced by as much as 100% in animals treated with bleomycin and EPO compared to animals treated with bleomycin alone (p < 0.03). Finally, a 5-fold decrease in interstitial fibrosis was observed in lung sections obtained from animals treated with bleomycin and EPO (p < 0.02). We conclude that EPO can ameliorate drug-induced fibrosis and endothelial damage caused by chemotherapeutic agents.     

Pulmonary toxicity of bischloronitrosourea: report of a case with transient response to corticosteroid therapy.

A case of interstitial pulmonary fibrosis secondary to bischloronitrosourea (BCNU) in a 49-year-old man with carcinoma of the pancreas is reported. The diagnosis was suggested by deteriorating oxygenation, restrictive changes on pulmonary function studies, and increased interstitial markings radiographically in the lower lung fields. Transbronchial biopsy excluded infectious etiologies and confirmed a bland nonspecific interstitial pulmonary fibrosis of recent origin. The patient responded dramatically to high dose corticosteroids, but relapsed when the corticosteroids were decreased. We believe there is now convincing evidence that prolonged use of BCNU can cause potentially fatal interstitial pulmonary fibrosis. Patients should be followed with serial chest radiographs and pulmonary function studies. If diagnosed early, this process may respond to high dose corticosteroid therapy.     

Interstitial shadow on chest CT is associated with the onset of interstitial lung disease caused by chemotherapeutic drugs

Objective: Pretreatment computerized tomography (CT) films ofthe chest was studied to clarify the influence of interstitialshadow on developing interstitial lung disease (ILD). Methods: Eligible patients were those lung cancer patients whostarted to receive first-line chemotherapy between October 2001and March 2004. Patients who received thoracic radiotherapyto the primary lesion, mediastinum, spinal or rib metastaseswere excluded. We reviewed pretreatment conventional CT andplain X-ray films of the chest. Ground-glass opacity, consolidationor reticular shadow without segmental distribution was definedas interstitial shadow, with this event being graded as mild,moderate or severe. If interstitial shadow was detected on CTfilms of the chest, but not via plain chest X-ray, it was gradedas mild. Patients developing ILD were identified from medialrecords. Results: A total of 502 patients were eligible. Mild, moderateand severe interstitial shadow was identified in 7, 8 and 5%of patients, respectively. A total of 188 patients (37%) receivedtyrosine kinase inhibitor (TKI) treatment, namely gefitinibor erlotinib. Twenty-six patients (5.2%) developed ILD eitherduring or after chemotherapy. Multivariate analyses revealedthat interstitial shadow on CT films of the chest and treatmenthistory with TKI were associated with the onset of ILD. Conclusions: It is recommended that patients with interstitialshadow on chest CT are excluded from future clinical trialsuntil this issue is further clarified, as it is anticipatedthat use of chemotherapeutic agents frequently mediate onsetof ILD in this context.     

胸部恶性肿瘤放化疗后肺内癌性淋巴管炎临床及影像学诊断分析

目的：探讨胸部恶性肿瘤在放化疗后出现癌性淋巴管炎的临床及影像学特点。方法：回顾性分析23例经临床证实的胸部恶性肿瘤放化疗后出现癌性淋巴管炎的临床及影像学资料。结果：PLC主要表现为咳嗽、干咳为主,气短进行性加重抗炎治疗无效,肺功为限制性通气障碍。X线片：双肺弥漫性网状,结节状等间质纤维样变,可见胸腔积液。CT见：小叶间隔不均一增厚,结节状,胸膜不规则增厚,肺门纵隔淋巴结增大。放疗后的病人改变多出现在放射野外。结论：对治疗后病人的当影像学检查提示肺呈类间质纤维化改变时,尤其合并肺门纵隔淋巴结肿大、胸水者,应进一步检查必要时病理确诊,早期诊断早期治疗。     

抗纤方中药制剂防治肺辐射损伤的临床研究

目的探讨抗纤方中药制剂对胸部肿瘤放疗所致肺辐射损伤的预防作用。方法148例胸部肿瘤患者随机分为试验组70例，对照组78例，均接受胸部肿瘤常规放疗。试验组病例在放疗同时应用抗纤方中药制剂治疗至放疗结束，对照组患者则接受安慰剂治疗。结果两组放疗后放射性肺炎及放射性肺纤维化的发生率分别为38．4％，12．8％和29．4％，8．5％，两组比较差异有统计学意义（P〈0．05）。结论抗纤方中药制剂能够降低胸部肿瘤放疗所致放射性肺炎及肺纤维化的发生率，对肺辐射损伤有明显的预防作用。     

生脉注射液减轻放射性肺损伤的临床观察

目的 :观察胸部放射治疗的各种恶性肿瘤在放射治疗后应用生脉注射液减轻放射性肺炎、肺纤维化的疗效等临床指标。方法 :15 2例患者随机分为 2组 :治疗组与对照组 ,每组各 76例。对各种恶性肿瘤均行根治放疗。放射源为 6MVX射线 ,常规分割照射 ,照射剂量为 4 0～ 6 0Gy。对照组完成常规的放射治疗 ,治疗组常规放疗的同时应用生脉注射液 2 5～ 4 0mL静脉滴入 ,1次 /d ,10～ 15d为 1个疗程 ,共给 3～ 5个疗程。结果 :治疗组放射性肺炎、肺纤维化的发生率分别为 19.7%、2 3.7% ,对照组放射性肺炎、肺纤维化的发生率分别为 36 8%、4 7 4 %。治疗组与对照组相比 ,放射性肺炎、放射性肺纤维化的发生率差异均有显著性 (P <0 0 5 )。结论 :放射性肺炎、肺纤维化是恶性肿瘤的胸部放射治疗中及放射治疗后常见的并发症 ,纯中药制剂生脉注射液能明显降低其发生率     

Acute interstitial pneumonitis during chemotherapy for haematological malignancy

Fourteen adult patients with haematological malignancies (eight non-Hodgkin's lymphoma, one multiple myeloma, one chronic lymphocytic leukaemia, two acute lymphoblastic leukaemia and two acute myeloid leukaemia) developed acute interstitial pneumonitis (IP) during the course of chemotherapy. All patients manifested high fever over 38 degrees C, bilateral diffuse pulmonary interstitial infiltrates in the chest radiograph and severe hypoxia without hypercapnia in the arterial blood gas analysis. Pathogenic microorganisms were not detected in repeated examinations in any patient. Chemotherapy given included various anti-neoplastic drugs. Five patients had received granulocyte colony-stimulating factor (G-CSF) for chemotherapy-induced leucopenia. The onset was associated with an increase of leucocytes in 10 patients. All patients were treated with high dose steroid hormone and broad spectrum antibiotics with or without anti-fungal agents, and three required mechanical ventilation. Eleven patients quickly recovered from these situations, whereas three died. Autopsies were done in two patients and disclosed pneumocystis carinii (PC) pneumonitis in one and non-specific pulmonary congestive oedema and fibrosis in the other. In conclusion, IP of unknown cause could develop in patients with various haematological malignancies especially at the recovery phase of chemotherapy-induced leucopenia irrespective of the previous G-CSF administration. High dose steroid hormone should be used as therapy for such patients as soon as possible after exclusion of an infective aetiology.     

放射性肺损伤药物防护的研究进展

放射性肺损伤是胸部肿瘤放疗后的最常见并发症,表现为早期放射性肺炎及晚期放射性肺纤维化。放射性肺损伤与肺受照体积和剂量密切相关,也与多种细胞因子的表达及信号传导有关。本文综述不同药物防护放射性肺损伤的研究进展。     

Phase I trial of combined therapy with bleomycin and the calmodulin antagonist,trifluoperazine

Summary Calmodulin antagonists, such as trifluoperazine, can enhance the cytotoxic effects of bleomycin both in tissue culture and in vivo. Therefore, we evaluated the effects of combination treatment with these drugs in a phase I clinical trial. Patients with objectively measurable or evaluable cancer refractory to conventional treatment who had an acceptable performance status (ECOG 0-2) and acceptable laboratory studies were eligible. All patients gave written informed consent. A cycle of therapy consisted of three weekly treatments with trifluoperazine (days 1–4) and 30 IU bleomycin (day 3). After three patients completed a cycle of therapy without experiencing dose-limiting toxicity, new patients were entered in the study and received a higher dose of trifluoperazine. The dose of bleomycin remained constant. Evaluable patients received at least 2 weeks of treatment and survived for 6 weeks; of 19 patients, 2 were unevaluable. The major toxicities were neurological and pulmonary and included one case of fatal pneumonia with interstitial pulmonary fibrosis. There was no hematologic toxicity. Two patients underwent partial responses (PRs) and two had complete responses (CRs). We conclude that trifluoperazine can safely by given with bleomycin and that further study of the potential efficacy of this treatment is indicated.This work was supported by grants from Bristol-Meyers, the National Cancer Institute (CAO8341, CA-4388), and the American Cancer Society (CH302A)Presented in part at the American Association of Cancer Research Meeting, Houston, Texas, 1985Dr. Hait is a Burroughs Wellcome Scholar in Clinical Pharmacology     

Radiotherapy does not influence the severe pulmonary toxicity observed with the administration of gemcitabine and bleomycin in patients with advanced-stage Hodgkin's lymphoma treated with the BAGCOPP regimen: a report by the German Hodgkin's Lymphoma Study Group

PURPOSE: To evaluate the effect of radiotherapy on the severe pulmonary toxicity observed in the pilot study of BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine) for advanced-stage Hodgkin's lymphoma. METHODS AND MATERIALS: Patients with Stage III or IV Hodgkin's lymphoma or Stage IIB with risk factors participated in this single-arm, multicenter pilot study. RESULTS: Twenty-seven patients were enrolled on the study before its premature closure as a result of the development of serious pulmonary toxicity in 8 patients. The pulmonary toxicity occurred either during or immediately after the BAGCOPP chemotherapy course. Pulmonary toxicity contributed to one early fatality but resolved in the other 7 patients after cessation of gemcitabine and bleomycin, allowing continuation of therapy. Fifteen patients received consolidative radiotherapy, including 4 who previously had pulmonary toxicity. There were no reported cases of radiation pneumonitis and no exacerbation of pulmonary symptoms in the 4 patients who had had previous pulmonary toxicity. CONCLUSIONS: The severe pulmonary toxicity observed in this study has been attributed to an interaction between gemcitabine and bleomycin. Gemcitabine (when administered without bleomycin) remains of interest in Hodgkin's lymphoma and is being incorporated into a new German Hodgkin's Lymphoma Study Group protocol that also includes consolidative radiotherapy. This study supports the concept of the integration of radiotherapy in gemcitabine-containing regimens in Hodgkin's lymphoma if there is an interval of at least 4 weeks between the two modalities and with a schedule whereby radiotherapy follows the chemotherapy.     

Fatal bleomycin pulmonary toxicity in the west of Scotland 1991-95: a review of patients with germ cell tumours.

We conducted a retrospective review of fatal bleomycin pulmonary toxicity in patients treated for germ cell tumours during 1991-95 at the Beatson Oncology Centre, Glasgow. Case notes of patients treated with bleomycin were reviewed with respect to cumulative bleomycin dose, renal impairment, exposure to supplemental oxygen, thoracic radiotherapy and age. A total of 194 patients underwent chemotherapy, of whom 180 received bleomycin-containing regimens. Five fatal cases of pulmonary toxicity were identified, an incidence of 2.8%. These cases were older than the remaining patients (P < 0.001), with a median age at diagnosis of 55 vs 33 years. The incidence of fatal pulmonary toxicity increased with each decade of life above age 30. Renal function also differed between the two groups, with the worst glomerular filtration rate recorded at the time of bleomycin administration for each patient, lower in the fatal group, median 69 vs 107 ml min(-1) (P < 0.001). There was no difference with respect to cumulative bleomycin dose or exposure to supplemental oxygen. For patients aged over 40 years, especially those with renal function in the lower range of normal, the risk of developing fatal toxicity may exceed 10%. The benefits of bleomycin could be questioned for this age group.     

Pulmonary complications after bleomycin, irradiation and surgery for esophageal cancer.

Eight patients with epidermoid carcinoma of the esophagus were given radiotherapy of 3000 rads and 120 mg of bleomycin. Esophageal resection was performed five to six weeks later. Four of these patients died within six weeks, three from respiratory failure, and one from complications secondary to an anastomotic fistula. Of the remaining four patients, three showed varying degrees of pulmonary infiltration for several weeks. Interstitial pneumonitis was demonstrated in all the fatal cases. Four patients given the same irradiation and bleomycin doses were only subjected to exploratory surgery. They had no postoperative pulmonary complications. Ten patients given the same irradiation and bleomycin treatment without surgery also showed no pulmonary complications. Sixteen patients received higher doses of radiotherapy and bleomycin. Seven of these developed lung infiltrations terminating fatally in four. The likely mechanism of the observed postoperative pulmonary complications is that the preoperative treatment sensitized the lungs, while the subsequent surgical trauma triggered a reaction in the lungs leading to respiratory failure.     

Fatal bleomycin toxicity from a low cumulative dose in a patient with renal insufficiency

A 54-year-old man with advanced non-Hodgkin's lymphoma and chronic renal insufficiency was treated with combination chemotherapy which included bleomycin. Fatal pulmonary toxicity developed after administration of a total bleomycin dose of only 60 U. Transbronchial biopsy and autopsy demonstrated pathologic findings consistent with bleomycin-induced pulmonary fibrosis. High-dose corticosteroid therapy did not appear to alter the clinical course. Extreme caution should be exercised when administering bleomycin to patients with renal insufficiency.     

乳腺癌术后放疗晚期放射性肺损伤的临床分析

目的:了解乳腺癌根治性手术后放射治疗患者晚期放射性肺损伤的发病情况并探讨其影响因素.方法:分析74例根治/改良根治术后放疗的乳腺癌患者的临床资料,其放疗后随访时间为12～84个月(中位数33.6个月).采用LENT-SOMA标准,从主观症状和客观体征(X线胸片)两方面研究晚期放射性肺损伤的发生情况,并采用Logistic回归分析其相关的发病因素.结果:晚期放射性肺损伤在主观症状和客观体征方面的发生率分别为16.2%和37.8%.多因素分析表明:患者年龄(＞47岁≤)、吸烟史(有和无)、接受化疗周期数(3～6周期和＞6周期)晚期放射性肺损伤的发生率分别为23.3%和47.7%(P=0.034)、0和41.2%(P=0.046)、31.0%和62.5%(P=0.022).结论:晚期放射性肺损伤是乳腺癌术后放疗患者较常见的并发症之一,有一些临床因素会增加该病的发生率.     

Pulmonary complications in survivors of childhood and adolescent cancer. A report from the Childhood Cancer Survivor Study

BACKGROUND: The Childhood Cancer Survivor Study is a resource that was designed to investigate long-term effects among 5-year survivors of childhood and adolescent malignancies. Previous studies have shown that exposure to chemotherapy and/or radiation can compromise pulmonary function in these survivors of childhood cancer. METHODS: Using information obtained from questionnaires from 12,390 childhood cancer survivors and 3546 randomly selected siblings, the authors evaluated the rate of first occurrence of 15 selected pulmonary conditions in three periods: during therapy, from the end of therapy to 5 years postdiagnosis, and >/= 5 years postdiagnosis. Multivariate analyses were used to determine the relative risks with 95% confidence intervals of reported pulmonary conditions by exposure to the following treatment variables: radiation therapy to the chest, bleomycin, cyclophosphamide, busulfan, lomustine (CCNU), and/or carmustine (BCNU). RESULTS: Compared with siblings, survivors had a statistically significant increased relative risk (RR) of lung fibrosis, recurrent pneumonia, chronic cough, pleurisy, use of supplemental oxygen, abnormal chest wall, exercise-induced shortness of breath, bronchitis, recurrent sinus infection, and tonsillitis for all three periods. During the period of >or= 5 years postdiagnosis, statistically significant associations were present for lung fibrosis and chest radiation (RR, 4.3; P = 0 001); for supplemental oxygen use and chest radiation (RR, 1.8; P < 0.001), BCNU (RR, 1.4; P = 0.05), bleomycin (RR, 1.7; P = 0.001), busulfan (RR, 3.2; P = 0.002), CCNU (RR, 2.1; P < 0.001), and cyclophosphamide (RR, 1.5; P = 0.01); for recurrent pneumonia and chest radiation (RR, 2.2; P = 0.001) and cyclophosphamide (RR, 1.6; P = 0.04); for chronic cough and chest radiation (RR, 2.0; P < 0.001), bleomycin (RR, 1.9; P < 0.001), and cyclophosphamide (RR, 1.3; P = 0.004); and for pleurisy and chest radiation (RR, 1.4; P = 0.02) and busulfan (RR, 5.1; P = 0.02). Chest radiation was associated with a 3.5% cumulative incidence of lung fibrosis at 20 years after diagnosis. CONCLUSIONS: For self-report of pulmonary conditions, treatment-related factors that continue to manifest > 5 years after diagnosis and treatment are important determinants of risk. Continued follow-up of childhood cancer survivors is needed to evaluate the impact of pulmonary conditions on quality of life.     

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.     

Idiopathic Systemic Amyloidosis Primarily Affecting the Lungs with Fatal Pulmonary Haemorrhage due to Vascular Involvement

A patient who presented with dyspnea and suspected interstitial pulmonary fibrosis suffered a fatal pulmonary haemorrhage with no feasible cause for bleeding. Autopsy revealed abundant amyloid deposits in both lungs with a diffuse alveolar septal distribution pattern. Amyloid was also found in the cardiac interstitium and in many vessel walls. Considering the affected organs and the histological characteristics, the deposits were regarded as light chain-type. Amyloidosis, which is generally an uncommon disease, very rarely affects the lung predominantly. Haemorrhagic diathesis is a known complication in amyloidosis patients, although fatal haemorrhage is rare and has not yet been reported solely of pulmonary origin. This report describes an uncommon case of idiopathic systemic amyloidosis mainly manifesting in the lungs. The diagnosis was established after fatal pulmonary haemorrhage caused by vessel impairment due to additional vascular amyloid deposits.     

The effect of corticosteroid administration on bleomycin lung toxicity.

Bleomycin is well recognized as an active antineoplastic agent in the treatment of germ cell tumors. Pulmonary toxicity is the most significant complication of bleomycin administration. In this report, an attempt is made to modify both the incidence and severity of this side effect. One hundred eleven patients with advanced germ cell tumors were treated with a combination chemotherapy program that included the administration of 30 units (U) of bleomycin as a continuous infusion daily for 3 days every 3 weeks rather than a weekly bolus injection of a total of 360 U (mean dose received, 307 U). Also, 31 patients received high-dose steroids, which have been shown to modify bleomycin-induced pulmonary toxicity, for the treatment of chemotherapy-induced emesis. Changes in carbon monoxide diffusion capacity (DLCO) prompting cessation of bleomycin therapy occurred in 15 cases (bleomycin was stopped in one case due to dyspnea and lung infiltrates, and one patient suffered fatal respiratory failure probably due to bleomycin lung toxicity). Thus, probable bleomycin pulmonary toxicity changed the clinical treatment in 15.3% of the cases. On long-term follow-up, only two patients have demonstrated a residual decrease in DLCO. The incidence of a greater than 25% decrease in DLCO was 34% and was not significantly altered by the administration of steroids (P = 0.96). It is possible, however, that the low incidence of clinically significant and fatal pulmonary toxicity, as experienced in this group of patients, may be related to the infusion of bleomycin. It also is possible that the reversibility of the decrease in DLCO in 95% of the patients may be related to the duration and schedule of bleomycin administration. As bleomycin continues to be an important drug in the treatment of advanced germ cell tumors, further studies are warranted to evaluate the role of the continuous infusion of bleomycin as opposed to bolus therapy.     

Trends and Correlates of Mean Lung Dose in Patients Receiving Breast Radiotherapy in a Single Institution from 2014 to 2018

AimsHigher mean lung dose (MLD) in breast cancer patients has been associated with pneumonitis, pulmonary fibrosis and secondary lung cancer primaries. This study examined MLD in a single institution from 2014 to 18 to assess trends in median MLD (Gy) over time and factors associated with higher MLD to determine best practices for limiting lung toxicity.Materials and methodsGeneral linear regressions were analysed to determine significant change in median MLD over time in patients receiving conventional or hypofractionated schedules for whole breast/chest wall (WB) radiotherapy with or without sequential boost or simultaneous integrated boost, WB tangential radiotherapy only and WB locoregional radiotherapy. Univariate and multivariable linear regression analysed identified factors associated with MLD.ResultsIn total, 3894 patients were included in the analysis. The total median MLD across all years was 6.8 Gy in patients treated with conventional fractionation and 3.4 Gy in patients treated with hypofractionation. A significant increase in MLD was observed between 2014 and 2018 in patients receiving conventional or hypofractionation, conventional WB treatment with locoregional radiotherapy, conventional WB radiotherapy with simultaneous integrated boost and hypofractionated WB radiotherapy with sequential boost. Increased MLD was significantly correlated with lower lung volume and larger treatment volume due to locoregional radiotherapy, inclusion of a boost, chest wall treatment and reverse decubitus or supine positioning (P < 0.0001).ConclusionA significant increase in MLD was observed over the years in patients receiving conventional and hypofractionated radiotherapy. Techniques such as prone positioning should be considered to lower MLD, particularly for patients with predisposing pulmonary risk.