Mechanisms and protective measures for radiation-induced brachial plexus nerve injury.

Radiation therapy is a common treatment modality for patients with malignant tumors of the head and neck, chest and axilla. However, radiotherapy inevitably causes damage to normal tissues at the irradiated site, among which damage to the brachial plexus nerve(BP) is a serious adverse effect in patients receiving radiation therapy in the scapular or axillary regions, with clinical manifestations including abnormal sensation, neuropathic pain, and dyskinesia, etc. These adverse effects seriously reduce the living quality of patients and pose obstacles to their prognosis. Therefore, it is important to elucidate the mechanism of radiation induced brachial plexus injury (RIBP) which remains unclear. Current studies have shown that the pathways of radiation-induced BP injury can be divided into two categories: direct injury and indirect injury, and the indirect injury is closely related to the inflammatory response, microvascular damage, cytokine production and other factors causing radiation-induced fibrosis. In this review, we summarize the underlying mechanisms of RIBP occurrence and possible effective methods to prevent and treat RIBP.

Predicting Radiation-Induced Lung Injury in Patients With Lung Cancer: Challenges and Opportunities.

Radiation-induced lung injury (RILI) is one of the main dose-limiting toxicities in radiation therapy (RT) for lung cancer. Approximately 10% to 20% of patients show signs of RILI of variable severity. The reason for the wide range of RILI severity and the mechanisms underlying its development are only partially understood. A number of clinical risk factors have been identified that can aid in clinical decision making. Technological advancements in RT and the use of strict organ-at-risk dose constraints have helped to reduce RILI. Predicting patients at risk for RILI may be further improved with a combination of cytokine assessments, γH2AX-assays in leukocytes, or epigenetic markers. A complicating factor is the lack of an objective definition of RILI. Tools such as computed tomography densitometry, fluorodeoxyglucose-positron emission tomography uptake, changes in lung function measurements, and exhaled breath analysis can be implemented to better define and quantify RILI. This can aid in the search for new biomarkers, which can be accelerated by omics techniques, single-cell RNA sequencing, mass cytometry, and advances in patient-specific in vitro cell culture models. An objective quantification of RILI combined with these novel techniques can aid in the development of biomarkers to better predict patients at risk and allow personalized treatment decisions.

Cytokine, chemokine alterations and immune cell infiltration in Radiation-induced lung injury: Implications for prevention and management.

Radiation therapy is one of the primary treatments for thoracic malignancies, with radiation-induced lung injury (RILI) emerging as its most prevalent complication. RILI encompasses early-stage radiation pneumonitis (RP) and the subsequent development of radiation pulmonary fibrosis (RPF). During radiation treatment, not only are tumor cells targeted, but normal tissue cells, including alveolar epithelial cells and vascular endothelial cells, also sustain damage. Within the lungs, ionizing radiation boosts the intracellular levels of reactive oxygen species across various cell types. This elevation precipitates the release of cytokines and chemokines, coupled with the infiltration of inflammatory cells, culminating in the onset of RP. This pulmonary inflammatory response can persist, spanning a duration from several months to years, ultimately progressing to RPF. This review aims to explore the alterations in cytokine and chemokine release and the influx of immune cells post-ionizing radiation exposure in the lungs, offering insights for the prevention and management of RILI.

Predictive factors for severe radiation-induced lung injury in patients with lung cancer and coexisting interstitial lung disease.

BACKGROUND AND PURPOSE: This study aimed to investigate the predictive factors of severe radiation-induced lung injury (RILI) in patients with lung cancer and coexisting interstitial lung disease (ILD) undergoing conventionally fractionated thoracic radiotherapy. MATERIALS AND METHODS: The study includes consecutive patients treated with thoracic radiotherapy for lung cancer at two tertiary centers between 2010 and 2021. RILI severity was graded using the National Cancer Institute Common Terminology Criteria version 5.0, with severe RILI defined as toxicity grade ≥4, and symptomatic RILI as grade ≥2. The absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and C-reactive protein were collected within 4 weeks before starting radiotherapy. Neutrophil-lymphocyte ratios (NLR) were calculated as ANC/ALC. The median follow-up was 9 (range, 6-114) months. RESULTS: Among 54 patients, 22 (40.7 %) had severe RILI. On multivariate logistic regression analysis, high pretreatment ANC (p = 0.030, OR = 4.313), pretreatment NLR (p = 0.007, OR = 5.784), and ILD severity (p = 0.027, OR = 2.416) were significant predictors of severe RILI. Dosimetric factors were not associated with severe RP. Overall survival was significantly worse for patients with severe RILI than those without, with 1-year cumulative overall survival rates of 7.4 % and 62.8 %, respectively. CONCLUSION: Pretreatment blood NLR, ANC, and ILD severity were associated with severe RILI. Overall survival was dismal for patients with severe RILI.

Two Cases of Intractable Radiation-Induced Hemorrhagic Cystitis Treated with Transcatheter Embolization.

Radiation-induced hemorrhagic cystitis is a late complication of radiotherapy, and in rare cases, refractory. Refractory bleeding may not be resolved by transurethral electrocoagulation (TUEC) or hyperbaric oxygen (HBO) therapy and requires transcatheter arterial embolization (TAE) or urinary diversion. Here, we report two cases of radiation-induced hemorrhagic cystitis successfully treated with TAE. Case 1 was a 61-yearold man who underwent total prostatectomy for prostate cancer followed by salvage radiation therapy. The patient developed radiation-induced hemorrhagic cystitis 2 years and 3 months after radiotherapy. After no improvement with TUEC and HBO, TAE was performed. Case 2 was a 78-year-old man who underwent total prostatectomy followed by salvage radiation therapy and developed radiation-induced hemorrhagic cystitis 12 years later. TAE was performed after no improvement with HBO. TAE proved successful in both patients, and there was no relapse. TAE is a potential treatment option for refractory radiation-induced hemorrhagic cystitis.

Intraoperative appearance of radiation enteritis: What should be resected?

Radiation enteritis can appear up to 30 years after radiotherapy. Outside acute complications, it usually manifests itself as chronic intestinal obstruction. If medical treatment (corticosteroid therapy) fails, surgical treatment is indicated, namely resection of the affected bowel, with removal of the ileo-caecal valve.

[Radiation-induced lymphopenia: Lymphocytes as a new organ at risk]. / Lymphopénie radio-induite : les lymphocytes comme nouvel organe à risque.

Taking the immune system into account in the fight against tumors has upset the cancer treatment paradigm in the 21st century. Combination treatment strategies associating radiotherapy with immunotherapy are being increasingly implemented in clinical practice. In this context, lymphocytes, whether lymphocytes infiltrating the tumour, circulating blood lymphocytes or lymphocytes residing within the lymph nodes, are key players in cellular and humoral anti-tumor immunity. The significant radiosensitivity of lymphocytes was demonstrated in the early 1990s. Along with the cells of the digestive mucosa, lymphocytes are thus among the most radiosensitive cell types in the body. Compared to the old practices of external radiotherapy, current intensity modulated treatments have allowed a considerable improvement in acute and late toxicity, at the cost of a significant increase in the volume irradiated at low doses. This is not without consequence on the incidence of radiation-induced lymphopenia, with prognostic implications for many tumor types. Thus, in order not to hinder the action of antitumor immunity and the efficacy of immunotherapy, it is essential to consider lymphocytes as a new organ at risk in its own right. In this development, based on current data from the literature, we will begin by justifying the necessary prevention of radiation-induced lymphopenia, before providing the tools currently known to apprehend lymphocytes as a new multicompartments. Finally, we will broaden the perspective by outlining ways to develop research in this area.

Vitamin E ameliorates oral mucositis in gamma-irradiated rats (an in vivo study).

BACKGROUND: Radiation therapy is the primary treatment for neck and head cancer patients; however, it causes the development of oral mucositis accompanied by tissue structure destruction and functional alteration. This study was conducted to evaluate the effect of different doses of vitamin E as a treatment for radiationinduced oral mucositis in rat model. METHODS: 35 male albino rats were randomly divided into five groups: control, untreated radiation mucositis (single dose of 20 Gy), treated radiation mucositis; radiation (single dose of 20 Gy) then vitamin E at doses of 300, 360 and 500 mg/Kg for seven days started 24 h after irradiation. Body weight and food intake were evaluated for each rat. The mucositis score was assessed every day. Rats were sacrificed once at the end of the experiment, and tongue specimens were stained with hematoxylin and eosin, anti P53 and anti Ki67 antibodies. RESULTS: Results indicated more food intake and less weight reduction in vitamin E treated groups and the contrary for gamma-irradiated group. Additionally, vitamin E delayed the onset and decreased the severity and duration of mucositis. It also restored the histological structure of lingual tongue papillae. Vitamin E treated groups showed a significant higher Ki67 and lower P53 expression as compared to untreated radiation group. The overall improvement increased as vitamin E dose increased. Finally, the amelioration can be attributed to the decreased apoptosis and increased proliferation of cells. CONCLUSIONS: Vitamin E especially at dose of 500 mg/Kg could be an effective treatment for radiation-induced oral mucositis.

Argon plasma coagulation therapy in hemorrhagic radiation proctitis following pelvic radiation in gynecological malignancies.

Introduction: Chronic radiation proctitis is a common chronic complication of malignant pelvic diseases after pelvic radiation therapy. Although, the incidence has decreased after advent of intensity-modulated radiotherapy due to better control of radiation dose to rectum. In the era of conventional two-field radiotherapy to pelvis, this was a common complication usually presenting after 1-2 years of treatment completion. Rectal bleeding caused by radiation proctitis is difficult to manage. Argon plasma coagulation (APC) is an electrocoagulation technique that appears to be an effective and low-cost alternative to the use of lasers in gastrointestinal endoscopy. The aim of this study was to evaluate the efficacy of APC, as well as patients' tolerance of the procedure, in the treatment of bleeding radiation-induced proctitis. Materials and Methods: Between January 2015 and August 2017, 29 patients of cancer cervix treated with definite radiotherapy both external and brachytherapy who suffered from rectal bleeding due to radiation proctitis were included for treatment with argon plasma laser (APC). Twenty-three patients suffered from anemia, 16 of whom required blood transfusion. APC was performed, applying the no-touch spotting technique at an electrical power of 40 Watt and an argon gas flow of 1.5-2.0 l/min. Pulse duration was <0.5 s. Treatment sessions were carried out at intervals of 3 weeks. Subjects received 2-4 treatment sessions. Results: Twenty-eight out of 29 patients were accessible for effects and results. APC led to persistent clinical and endoscopic remission of rectal bleeding after a median of three sessions. No adverse effects were encountered after initial treatment. All the patients were in complete remission. Conclusions: APC is an effective, safe, and well-tolerated treatment for rectal bleeding caused by chronic radiation proctitis. It should be considered as a first-line therapy for radiation proctitis.

Proton therapy and oral mucositis in oral & oropharyngeal cancers: outcomes, dosimetric and NTCP benefit.

INTRODUCTION: Radiation-induced oral mucositis (RIOM), is a common, debilitating, acute side effect of radiotherapy for oral cavity (OC) and oropharyngeal (OPx) cancers; technical innovations for reducing it are seldom discussed. Intensity-modulated-proton-therapy (IMPT) has been reported extensively for treating OPx cancers, and less frequently for OC cancers. We aim to quantify the reduction in the likelihood of RIOM in treating these 2 subsites with IMPT compared to Helical Tomotherapy. MATERIAL AND METHODS: We report acute toxicities and early outcomes of 22 consecutive patients with OC and OPx cancers treated with IMPT, and compare the dosimetry and normal tissue complication probability (NTCP) of ≥ grade 3 mucositis for IMPT and HT. RESULTS: Twenty two patients, 77% males, 41% elderly and 73% OC subsite, were reviewed. With comparable target coverage, IMPT significantly reduced the mean dose and D32, D39, D45, and D50, for both the oral mucosa (OM) and spared oral mucosa (sOM). With IMPT, there was a 7% absolute and 16.5% relative reduction in NTCP for grade 3 mucositis for OM, compared to HT. IMPT further reduced NTCP for sOM, and the benefit was maintained in OC, OPx subsites and elderly subgroup. Acute toxicities, grade III dermatitis and mucositis, were noted in 50% and 45.5% patients, respectively, while 22.7% patients had grade 3 dysphagia. Compared with published data, the hospital admission rate, median weight loss, feeding tube insertion, unplanned treatment gaps were lower with IMPT. At a median follow-up of 15 months, 81.8% were alive; 72.7%, alive without disease and 9%, alive with disease. CONCLUSION: The dosimetric benefit of IMPT translates into NTCP reduction for grade 3 mucositis compared to Helical Tomotherapy for OPx and OC cancers and encourages the use of IMPT in their management.

[Research Progress on the Protective Effect of Intestinal Flora on 
Radiation-induced Lung Injury in Thoracic Tumors].

Radiation therapy is one of the main treatment methods for patients with thoracic malignant tumors, which can effectively improve the survival rate of the patients. However, radiation therapy can also cause damage to normal tissues while treating tumors, leading to radiation-induced lung injury such as radiation pneumonia and pulmonary fibrosis. Radiation-induced lung injury is a complex pathophysiological process involving many factors, and its prevention and treatment is one of the difficult problems in the field of radiation medicine. Therefore, the search for sensitive predictors of radiation-induced lung injury can guide clinical radiotherapy and reduce the incidence of radiation-induced lung injury. With the in-depth study of intestinal flora, it can drive immune cells or metabolites to reach lung tissue through the circulatory system to play a role, and participate in the occurrence, development and treatment of lung diseases. At present, there are few studies on intestinal flora and radiation-induced lung injury. Therefore, this paper will comprehensively elaborate the interaction between intestinal flora and radiation-induced lung injury, so as to provide a new direction and strategy for studying the protective effect of intestinal flora on radiation-induced lung injury.
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Gut microbiota controlling radiation-induced enteritis and intestinal regeneration.

Cancer remains the second leading cause of mortality, with nearly 10 million deaths worldwide in 2020. In many cases, radiotherapy is used for its anticancer effects. However, radiation causes healthy tissue toxicity as a side effect. In intra-abdominal and pelvic malignancies, the healthy bowel is inevitably included in the radiation field, causing radiation-induced enteritis and dramatically affecting the gut microbiome. This condition is associated with significant morbidity and mortality that impairs cancer patients' and survivors' quality of life. This Review provides a critical overview of the main drivers in modulating the gut microenvironment in homeostasis, disease, and injury, focusing on gut microbial metabolites and microorganisms that influence epithelial regeneration upon radiation injury.

The dental management of patients irradiated for head and neck cancer.

Patients undergoing radiotherapy for head and neck cancers are prone to a range of dental complications, including mucositis, trismus, xerostomia, radiation caries and osteoradionecrosis. Specific considerations include the preventive, restorative and rehabilitative management of such patients, and the prevention and treatment of complications. This article aims to highlight the current understanding and management of dental needs for patients who have had or will undergo radiotherapy.

Prediction of Radiation-Induced Parotid Gland-Related Xerostomia in Patients With Head and Neck Cancer: Regeneration-Weighted Dose.

PURPOSE: Despite improvements to treatment, patients with head and neck cancer (HNC) still experience radiation-induced xerostomia due to salivary gland damage. The stem cells of the parotid gland (PG), concentrated in the gland's main ducts (stem cell rich [SCR] region), play a critical role in the PG's response to radiation. Treatment optimization requires a dose metric that properly accounts for the relative contributions of dose to this SCR region and the PG's remainder (non-SCR region) to the risk of xerostomia in normal tissue complication probability (NTCP) models for xerostomia. MATERIALS AND METHODS: Treatment and toxicity data of 1013 prospectively followed patients with HNC treated with definitive radiation therapy (RT) were used. The regeneration-weighted dose, enabling accounting for the hypothesized different effects of dose to the SCR and non-SCR region on the risk of xerostomia, was defined as Dreg PG = Dmean SCR region + r × Dmean non-SCR region, where Dreg is the regeneration-weighted dose, Dmean is the mean dose, and r is the weighting factor. Considering the different volumes of these regions, r > 3.6 in Dreg PG demonstrates an enhanced effect of the SCR region. The most predictive value of r was estimated in 102 patients of a previously published trial testing stem cell sparing RT. For each endpoint, Dreg PG, dose to other organs, and clinical factors were used to develop NTCP models using multivariable logistic regression analysis in 663 patients. The models were validated in 350 patients. RESULTS: Dose to the contralateral PG was associated with daytime, eating-related, and physician-rated grade ≥2 xerostomia. Consequently, r was estimated and found to be smaller than 3.6 for most PG function-related endpoints. Therefore, the contribution of Dmean SCR region to the risk of xerostomia was larger than predicted by Dmean PG. Other frequently selected predictors were pretreatment xerostomia and Dmean oral cavity. The validation showed good discrimination and calibration. CONCLUSIONS: Tools for clinical implementation of stem cell sparing RT were developed: regeneration-weighted dose to the parotid gland that accounted for regional differences in radiosensitivity within the gland and NTCP models that included this new dose metric and other prognostic factors.

Effects of PEG in patients with esophageal squamous cell carcinoma during concurrent chemoradiotherapy: a prospective study.

BACKGROUND AND AIMS: This prospective study aimed to compare the changes in nutritional status and adverse events among patients with esophageal squamous cell carcinoma who received enteral nutrition through oral intake, PEG, and an enteral nasogastric tube (NGT) during concurrent chemoradiotherapy (CCRT). METHODS: Of 141 included patients, 38, 74, and 29 patients were fed through oral intake, PEG, and NGTs, respectively. The clinical characteristics and baseline nutritional status of the 3 groups were recorded and analyzed. The Patient-Generated Subjective Global Assessment score, skeletal muscle index, and quality of life were evaluated before and after CCRT; the incidence of adverse events during feeding using PEG and NGTs was also recorded. The correlations among the different nutritional pathways and the CCRT-related adverse events (eg, radiation esophagitis and myelosuppression) were assessed. RESULTS: At baseline, the oral intake group had a significantly better nutritional status and lower disease stage than those in the PEG and NGT groups. However, during CCRT, the oral intake group exhibited the most significant decreases in weight and skeletal muscle index. The synchronous chemotherapy completion rate was the highest in the PEG group. Multivariate analysis showed that the planning tumor volume and oral intake and NGT feeding pathways were associated with radiation esophagitis of at least grade 2. CONCLUSIONS: We found that PEG effectively maintained the body weight and skeletal muscle index of patients with esophageal cancer during CCRT. PEG also improved the synchronous chemotherapy completion rate and reduced the occurrence of at least grade 2 radiation esophagitis. (Clinical trial registration number: NCT04199832.).

[Limits of dose constraint definition for organs at risk specific to stereotactic radiotherapy]. / Limites de la définition des contraintes de dose pour les organes à risque spécifiques à la radiothérapie stéréotaxique.

Stereotactic radiotherapy is a very hypofractionated radiotherapy (>7.5Gy per fraction), and therefore is more likely to induce late toxicities than conventional normofractionated irradiations. The present study examines four frequent and potentially serious late toxicities: brain radionecrosis, radiation pneumonitis, radiation myelitis, and radiation-induced pelvic toxicities. The critical review focuses on the toxicity scales, the definition of the dose constrained volume, the dosimetric parameters, and the non-dosimetric risk factors. The most commonly used toxicity scales remain: RTOG/EORTC or common terminology criteria for adverse events (CTCAE). The definition of organ-at-risk volume requiring protection is often controversial, which limits the comparability of studies and the possibility of accurate dose constraints. Nevertheless, for the brain, whatever the indication (arteriovenous malformation, benign tumor, metastasis of solid tumors...), the association between the volume of brain receiving 12Gy (V12Gy) and the risk of cerebral radionecrosis is well established for both single and multi-fraction stereotactic irradiation. For the lung, the average dose received by both lungs and the V20 seem to correlate well with the risk of radiation-induced pneumonitis. For the spinal cord, the maximum dose is the most consensual parameter. Clinical trial protocols are useful for nonconsensual dose constraints. Non-dosimetric risk factors should be considered when validating the treatment plan.

Risk of Radiation Dermatitis in Patients With Skin of Color Who Undergo Radiation to the Breast or Chest Wall With and Without Regional Nodal Irradiation.

PURPOSE: Acute radiation dermatitis (ARD) is common after radiation therapy for breast cancer, with data indicating that ARD may disproportionately affect Black or African American (AA) patients. We evaluated the effect of skin of color (SOC) on physician-reported ARD in patients treated with radiation therapy. METHODS AND MATERIALS: We identified patients treated with whole breast or chest wall ± regional nodal irradiation or high tangents using 50 Gy in 25 fractions from 2015 to 2018. Baseline skin pigmentation was assessed using the Fitzpatrick scale (I = light/pale white to VI = black/very dark brown) with SOC defined as Fitzpatrick scale IV to VI. We evaluated associations among SOC, physician-reported ARD, late hyperpigmentation, and use of oral and topical treatments for RD using multivariable models. RESULTS: A total of 325 patients met eligibility, of which 40% had SOC (n = 129). On multivariable analysis, Black/AA race and chest wall irradiation had a lower odds of physician-reported grade 2 or 3 ARD (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.030-0.397; P = .001; OR, 0.377; 95% CI, 0.161-0.883; P = .025), whereas skin bolus (OR, 8.029; 95% CI, 3.655-17.635; P = 0) and planning target volume D0.03cc (OR, 1.001; 95% CI, 1.000-1.001; P = .028) were associated with increased odds. On multivariable analysis, SOC (OR, 3.658; 95% CI, 1.236-10.830; P = .019) and skin bolus (OR, 26.786; 95% CI, 4.235-169.432; P = 0) were associated with increased odds of physician-reported late grade 2 or 3 hyperpigmentation. There was less frequent use of topical steroids to treat ARD and more frequent use of oral analgesics in SOC versus non-SOC patients (43% vs 63%, P < .001; 50% vs 38%, P = .05, respectively). CONCLUSIONS: Black/AA patients exhibited lower odds of physician-reported ARD. However, we found higher odds of late hyperpigmentation in SOC patients, independent of self-reported race. These findings suggest that ARD may be underdiagnosed in SOC when using the physician-rated scale despite this late evidence of radiation-induced skin toxicity.

Advances in the management of radiation-induced cystitis in patients with pelvic malignancies.

OBJECTIVE: Radiotherapy plays a vital role as a treatment for malignant pelvic tumors, in which the bladder represents a significant organ at risk involved during tumor radiotherapy. Exposing the bladder wall to high doses of ionizing radiation is unavoidable and will lead to radiation cystitis (RC) because of its central position in the pelvic cavity. Radiation cystitis will result in several complications (e.g. frequent micturition, urgent urination, and nocturia) that can significantly reduce the patient's quality of life and in very severe cases become life-threatening. METHODS: Existing studies on the pathophysiology, prevention, and management of radiation-induced cystitis from January 1990 to December 2021 were reviewed. PubMed was used as the main search engine. Besides the reviewed studies, citations to those studies were also included. RESULTS AND DISCUSSIONS: In this review, the symptoms of radiation cystitis and the mainstream grading scales employed in clinical situations are presented. Next, preclinical and clinical research on preventing and treating radiation cystitis are summarized, and an overview of currently available prevention and treatment strategies as guidelines for clinicians is provided. Treatment options involve symptomatic treatment, vascular interventional therapy, surgery, hyperbaric oxygen therapy (HBOT), bladder irrigation, and electrocoagulation. Prevention includes filling up the bladder to remove it from the radiation field and delivering radiation based on helical tomotherapy and CT-guided 3D intracavitary brachytherapy techniques.

Effects of radiation on respiratory disease mortality: analysis of the national registry for radiation workers in United Kingdom.

PURPOSE: While some evidence of an effect of radiation exposure on respiratory disease at low dose levels has now emerged, there is heterogeneity in the risks between different studies and countries. In this paper, we aim to show the effect of radiation on three different sub-types of respiratory disease mortality through the analysis of the NRRW cohort in UK. MATERIALS AND METHODS: The NRRW cohort consisted of 174,541 radiation workers. Doses to the surface of the body were monitored using individual film badges. Most of the doses are associated with X-rays and gamma rays and to a less extent of beta and neutron particles. The overall mean 10-year lagged lifetime external dose was 23.2 mSv. Some workers were potentially exposed to alpha particles. However, doses from internal emitters were not available for the NRRW cohort. 25% of male workers and 17% of female workers were identified as being monitored for internal exposure. The Poisson regression methods for grouped survival data with a stratified baseline hazard function were used to describe the dependence of the risk on cumulative external radiation dose. The disease was analyzed by the following subgroups: Pneumonia (1066 cases including 17 cases of influenza), COPD and allied disease (1517 cases) and other remaining respiratory diseases (479 cases). RESULTS: There was very little radiation effect on pneumonia mortality, but evidence of a reduction in mortality risk for COPD and allied disease (ERR/Sv= -0.56, 95%CI: -0.94, -0.06; p = .02) and an increase in risk for other respiratory disease mortality (ERR/Sv = 2.30, 95%CI: 0.67, 4.62; p = .01) with increasing cumulative external dose were observed. The effects of radiation were more prominent amongst workers monitored for internal exposure. The reduction in mortality risk of COPD and allied disease per cumulative external dose was statistically significant for the radiation workers monitored for internal exposure (ERR/Sv= -0.59, 95%CI: -0.99, -0.05; p = .017) but not significant among the workers who were not monitored (ERR/Sv= -0.43, 95%CI: -1.20, 0.74; p = .42). A statistically significant increased risk was observed for other respiratory diseases among monitored radiation workers (ERR/Sv = 2.46, 95%CI: 0.69, 5.08; p = .019), but not among unmonitored workers (ERR/Sv = 1.70, 95%CI: -0.82, 5.65; p = .25). CONCLUSION: The effects of radiation exposure can be different depending on the type of respiratory disease. No effect was seen in pneumonia; a reduction in mortality risk of COPD, and increased mortality risk of other respiratory diseases were observed with cumulative external radiation dose. More studies are needed to verify these findings.