Bronchiolitis obliterans organizing pneumonia syndrome in breast-conserving therapy for early breast cancer: radiation-induced lung toxicity

PURPOSE: Breast-conserving surgery and postoperative radiotherapy have played important roles in the treatment of early breast cancer. Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome has recently been reported to be one of the complications of adjuvant radiotherapy. The purpose of this study was to determine the incidence of and risk factors for BOOP syndrome in breast cancer patients. METHODS AND MATERIALS: Between January 1996 and December 1998, 157 patients with breast cancer underwent radiotherapy after breast-conserving surgery. The criteria used for the diagnosis of BOOP syndrome were as follows: 1) radiation therapy to the breast within 12 months, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lung infiltrates outside the radiation port, and 4) no evidence of a specific cause. RESULTS: BOOP syndrome developed in 4 (2.5%) patients, who had fever and nonproductive cough, with patchy infiltrative shadows on chest roentgenograms which emerged between 5 and 6 months after radiotherapy. The symptoms and pulmonary infiltrates were rapidly improved by treatment with prednisone (40 mg/day), which was tapered over 2- to 5-month periods. However, BOOP syndrome relapsed in all cases during the tapering period or after withdrawal of prednisone. The eosinophil and neutrophil counts were increased and the ratios of CD4+ to CD8+ lymphocytes were elevated in bronchoalveolar lavage fluid in all four cases. There were no differences in proportions of patients by age, irradiated breast site, use of tamoxifen and/or chemotherapy, or radiation dose between those with and without BOOP syndrome. CONCLUSIONS: BOOP syndrome is considered an intractable form of lung toxicity after radiotherapy to the breast. An immunologic reaction mediated by eosinophils, neutrophils, and lymphocytes may be responsible for the development of this syndrome. Methods of prevention of BOOP syndrome should be established.     

A survey of radiation-induced bronchiolitis obliterans organizing pneumonia syndrome after breast-conserving therapy in Japan

PURPOSE: We observed a rare and unique occurrence of radiation-induced pulmonary injury outside the tangential field for early breast cancer treatment. The findings appeared to be idiopathic and were called radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome. We surveyed major hospitals in Japan to review their findings of radiation-induced BOOP, in particular the clinical and pictorial characteristics of the entity. METHODS AND MATERIALS: We reviewed surveys completed and returned by 20 institutions. The survey responses were based on a total of 37 cases of BOOP syndrome. We also reviewed X-ray and computed tomography scans provided by these institutions. We discussed the information derived from the questionnaire and analyzed patients' characteristics, methods used in the treatment of BOOP syndrome, and prognosis. RESULTS: The incidence of the radiation-induced BOOP syndrome was about 1.8% (37 of 2,056). We did not find a relationship between the characteristics of patients and the occurrence of radiation-induced BOOP syndrome. The pulmonary findings were classified into four patterns on chest computed tomography scans. Progression of the pulmonary lesions observed on chest X-ray was classified into three patterns. Pneumonitis appeared within 6 months after radiotherapy was completed and disappeared within 6-12 months after its onset. At 5-year follow-up, 2 patients had died, 1 of breast cancer and the other of interstitial pneumonitis, which seemed to be idiopathic and unrelated to the radiation-induced BOOP syndrome. CONCLUSIONS: Although the incidence of BOOP syndrome and its associated prognosis are not significant, the patients' clinical condition must be carefully followed.     

Two cases of bronchiolitis obliterans organizing pneumonia (BOOP) induced radiotherapy after surgery of breast cancer

We report two cases of bronchiolitis obliterans organizing pneumonia (BOOP) induced radiotherapy after surgery of breast cancer. One of the patients was a 58-year-old woman. She underwent a conserving surgery for bilateral breast cancers, and received radiation therapy to the remaining part of bilateral breasts. Two months after the termination of irradiation, cough, fever and general fatigue developed. We clinically diagnosed this case as BOOP after radiation therapy. After initiation of oral steroid therapy, the clinical symptoms and radiographic findings disappeared. Another patient was a 57-year-old woman. She underwent radical mastectomy for right breast cancer. A month after the operation, she suffered from local recurrence, so radiation therapy to the thoracic wall was performed. After irradiation, resection of the thoracic wall lesion was performed because of malignancy from local skin biopsy specimen. Two months after the termination of irradiation, cough, dyspnea and fever developed. We clinically diagnosed this case as radiation-induced BOOP by BAL and TBLB findings. After an initiation of steroid therapy, the clinical symptoms and radiographic findings disappeared. It is important to be aware of BOOP as a complication in the patient who was given radiation after surgery of breast cancer.     

Bronquiolitis obliterante con neumonía organizada: forma poco frecuente de toxicidad pulmonar en el tratamiento radioterápico del cáncer de mama

The incidence of symptomatic pneumonitis in patients who had received radiation therapy for breast cancer is low (<1%). Recently, bronchiolitis obliterans organizing pneumonia (BOOP) syndrome has been described as a secondary lung toxicity due to the radiation therapy, which appears beyond the radiation field (migratory pneumonitis) and is triggered by hypersensitivity reactions mediated by eosinophils, neutrophils and lymphocytes. We present a patient who, two months after concluding the scheduled radiotherapy, developed a set of clinical, pathological and radiological symptoms compatible with BOOP syndrome. The patient responded well to steroid treatment.

     

Unusual complication after radiotherapy for breast cancer bronchiolitis obliterans organizing pneumonia case report and review of the literature

Breast-conserving surgery and postoperative radiotherapy play an important role in the treatment of early breast cancer. Bronchiolitis obliterans with organizing pneumonia (BOOP) is an uncommon syndrome reported to be one of the complications of adjuvant radiotherapy. We report the case of a 71-year-old woman who developed cough, dyspnea and fever three weeks after radiation therapy to the left breast for breast carcinoma. Chest X-ray and computed tomography scan demonstrated alveolar opacities within both lungs. Antibiotic therapy against any probable septic pathology did not improve the symptoms, while corticosteroid treatment resulted in rapid clinical improvement together with regression of the pulmonary opacities. Irradiation was thought to be the cause of the migratory pneumonitis, hence this case was clinically diagnosed as radiation-induced migratory pneumonitis similar to BOOP, without lung biopsy. The present case suggests that one should be mindful of this disease when treating patients with a history of irradiation to the breast. BOOP promptly responds to systemic corticosteroid therapy with rapid improvement of symptoms and regression of the pulmonary opacities.     

The clinical characteristics and non-steroidal treatment for radiation-induced bronchiolitis obliterans organizing pneumonia syndrome after breast-conserving therapy

Purpose

A rare and unique occurrence of radiation-induced pulmonary injury was observed outside the tangential field for early breast cancer treatment. The findings appeared to be idiopathic and were termed radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome. The goal of this study was to report and determine the incidence, analyze the characteristics of the pulmonary lesions on the images and also investigate the treatment methods.

Materials and methods

A retrospective analysis was conducted of 616 consecutive patients that underwent breast-conserving therapy (BCT) from January 1992 to December 2008. The patients were observed at least one year after radiotherapy for BCT. Radiotherapy was administered by 4 MV photons in all patients. The patients underwent chest X-rays periodically. If the BOOP syndrome was found, chest computed tomography (CT) were conducted to identify the characteristics of the pulmonary lesion outside the radiation field.

Results

The incidence of the radiation-induced BOOP syndrome was 12 patients (1.9%). Six of them had fever and cough, 6 had no symptoms. The pulmonary lesions were classified into four patterns on chest CT. Progression of the pulmonary lesions observed on chest X-ray were classified into three patterns. BOOP syndrome appeared within 5.6 months after radiotherapy and completely disappeared within 12 months after its onset. Their clinical conditions were not severe and these pulmonary lesions disappeared gradually without use of steroids in our institution. There was no death caused by BOOP syndrome.

Conclusions

Although the incidence of BOOP syndrome and its associated prognosis are not significant, this clinical condition must be carefully followed using diagnositic imaging in order to not over administer steroids.     

Bronchiolitis obliterans organizing pneumonia (BOOP) after thoracic radiotherapy for breast carcinoma

Common complications of thoracic radiotherapy include esophagitis and radiation pneumonitis. However, it is important to be aware of uncommon post-radiotherapy complications such as bronchiolitis obliterans organizing pneumonia (BOOP). We report on two patients with carcinoma of the breast who developed an interstitial lung disease consistent with BOOP. BOOP responds to treatment with corticosteroids and the prognosis is generally good despite of the need for long-term administration of corticosteroids as relapses can occur during tapering of steroids. This report provides guidelines for the evaluation and treatment of patients with pulmonary infiltrates after radiotherapy.     

A case of bronchiolitis obliterans organizing pneumonia syndrome with preceding radiation pneumonitis after breast-conserving therapy

Recent case series have demonstrated that bronchiolitis obliterans organizing pneumonia (BOOP) after radiation therapy to the breast is a distinct clinicopathological entity. Most of the investigators speculated that radiation may prime the development of BOOP through an unidentified immunological process; however, none of them showed the relationship between direct radiation injury and BOOP. We report herein a case of a 67-year-old female with BOOP following direct radiation damage confined to the irradiated area after breast-conserving therapy. This is the first case demonstrating that BOOP after breast-conserving therapy arises from direct radiation injury.     

Systematic Review of Postradiotherapy Bronchiolitis Obliterans Organizing Pneumonia in Women With Breast Cancer

Background.

Radiation therapy for breast cancer has been implicated in the development of bronchiolitis obliterans organizing pneumonia (BOOP). This inflammatory lung disorder was first noted in 1983, and there have been numerous reports of BOOP occurring in women who have had radiation therapy for breast cancer since 1995. This study was undertaken to perform a systematic review of postradiotherapy BOOP to determine the occurrence, presentation, treatment, and outcome.

Materials and Methods.

A systematic literature review was conducted according to the guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses report.

Results.

The literature search yielded 10 Japanese epidemiological reports with 129 women, 4 case series reports with 36 women, and 24 case reports with 34 women. Common symptoms included fever, cough, and shortness of breath. Most patients received corticosteroid therapy, and duration of treatment ranged from 6 months to 1 year, although some patients received steroids for longer than 1 year because of relapse, which occurred in approximately one half of patients. No deaths have been reported.

Conclusion.

BOOP is a rare but significant complication from radiation therapy for breast cancer. Chest radiographic studies for women who report new respiratory symptoms during the postradiation period can be beneficial for early diagnosis and for guiding appropriate management.     

Bronchiolitis obliterans organizing pneumonia simulating progression in bronquioloalveolar carcinoma

Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathologic syndrome with characteristic features. The diagnosis of BOOP requires the presence of a combination of pathological, clinical, and radiological features. We report the case of a lung cancer patient with bronquiloalveolar carcinoma (BAC) presenting with BOOP after chemotherapy with docetaxel and gemcitabine producing severe respiratory insufficiency, and simulating a progression of the tumor.     

Bronchiolitis obliterans organizing pneumonia after stereotactic ablative radiation therapy for lung cancer: A case report

Bronchiolitis obliterans organizing pneumonia is an interstitial lung disease rarely occurring after radiotherapy probably due to an activation of autoimmune processes. Most cases have been described after postoperative radiotherapy for breast cancer. Corticosteroids represent the main treatment, prognosis is generally favorable. We described a case of bronchiolitis obliterans organizing pneumonia after stereotactic ablative radiation therapy for a recurrent lung cancer. Antibiotics and steroids were administered to solve the clinical picture. After three years, a new lesion at the right lung was found and treated with stereotactic ablative radiation therapy and concomitant long course of steroids with no recurrence of bronchiolitis obliterans organizing pneumonia. Bronchiolitis obliterans organizing pneumonia is a rare event after radiotherapy with undefined risk factors. In our case, steroids played an important role in management and, maybe, in preventing bronchiolitis obliterans organizing pneumonia recurrence after second course of stereotactic ablative radiation therapy.     

Successful treatment of bronchiolitis obliterans organizing pneumonia with low-dose methotrexate in a patient with Hodgkin's disease

Bronchiolitis obliterans organizing pneumonia (BOOP) is a rare disease, which is histopathologically defined by the presence of granulation tissue in the bronchioles, alveolar ducts and alveoli leading to plugging of the bronchiolar and alveolar lumen. BOOP is considered as a nonspecific response to many types of lung injury, including drugs, radiation, an underlying hematologic malignant neoplasm, autoimmune diseases, bacterial or virus infection, or an underlying lung disease, or occurs idiopathically. BOOP is mainly treated with corticosteroids, which induce a rapid clinical improvement. A frequent problem is relapse of disease when corticosteroid dosage is tapered off. We present the case of a 20-year-old patient with Hodgkin's disease developing BOOP after chemotherapy (COPP/ABVD) and irradiation. Initially, she responded well to corticosteroids, but relapsed when medication was discontinued. Complete remission of BOOP was achieved by long-term treatment with low-dose methotrexate (5-20 mg/week, i.v.).     

Severe Organizing Pneumonia after Two Cycles of Docetaxel as Fourth-Line Chemotherapy for Advanced Non-Small Cell Carcinoma of the Lung

Organizing pneumonia (formerly known as bronchiolitis obliterans organizing pneumonia, BOOP) is an inflammatory process of the bronchioles that can lead to the destruction of small airways and surrounding lung tissue. Although the majority of cases are idiopathic, certain chemicals and drugs can induce OP. Here, we report a 54-year-old male patient with advanced non-small cell lung cancer (NSCLC) who developed therapy-associated OP. He had undergone several other chemotherapies before being switched to docetaxel as monotherapy (75 mg/m²). Treatment was initially well tolerated, but after the second cycle the patient developed increasing shortness of breath. Computed tomography (CT) for staging after the second cycle showed bilateral predominantly interstitial infiltration highly suggestive of acute lung fibrosis. Bronchoscopy revealed signs of chronic bronchitis and watery discharge from both lungs. Bronchoalveolar lavage and transbronchial needle biopsy was performed. Based on histopathologic examination, diagnosis of OP was made. After cessation of docetaxel and initial high dose steroids, the infiltration ameliorated rapidly. This is the second case in the literature that associates docetaxel with rapid onset of bronchiolitis obliterans. Therefore, patients with lung cancer receiving docetaxel who develop respiratory symptoms should be suspected to develop OP.Key Words: Docetaxel, Taxane, Bronchiolitis obliterans organizing pneumonia, BOOP, Organizing pneumonia, OP     

Development of Bronchiolitis Obliterans Organizing Pneumonia With Platinum-Based Chemotherapy for Metastatic Rectal Cancer

Bronchiolitis obliterans organizing pneumonia (BOOP) is an adverse event known to occur after cancer chemotherapy and radiotherapy. We present a case of a 47-year-old patient who was diagnosed with BOOP after treatment for metastatic rectal cancer with oxaliplatin/capecitabine/bevacizumab. Removal of oxaliplatin from the regimen and replacement with irinotecan resulted in a resolution of his pulmonary symptoms.     

Radiation-induced sarcomas after breast cancer: experience of Institute Curie and review of literature]

Adjuvant radiotherapy to the breast plays a significant role in preventing local failure in women treated for early stage breast cancer. This fact is supported by multiple clinical trials demonstrating that adjuvant radiotherapy decreases the risk of local recurrence and increases the rate of breast preservation, and actually the rules of adjuvant breast irradiation are clearly established. Sarcomas are a rare but recognized complication of radiation therapy for breast carcinoma, and are associated with poor prognosis. The first case of a bone sarcoma after radiation therapy of breast cancer was described by Beck in 1922. In 1948, Cahan et al. defined the criteria for diagnosis of radiation-induced sarcoma. Since then, some studies have reported the incidence of radiation-induced sarcoma after radiotherapy for different cancers. This article reports and discusses the incidence, management and treatment outcome of radiation-induced sarcomas occurring after radiotherapy for breast cancer in our institute. The incidence, histology, latency of appearance, genesis, their treatment and the prognostic factors of these rare tumors are discussed and the literature is reviewed.     

Bronchiolitis obliterans with organizing pneumonia after rituximab therapy for non-Hodgkin's lymphoma

Rituximab is a chimeric, anti-CD20 monoclonal antibody initially approved for relapsed, refractory indolent B-cell non-Hodgkin's lymphoma (NHL), and is being applied in an increasing variety of clinical scenarios. Most adverse events are due to an infusion-related symptom complex, and severe pulmonary complications are rare. We describe a case of an NHL patient who received rituximab and developed symptomatic, biopsy-proven multinodular bronchiolitis obliterans with organizing pneumonia (BOOP). This is the first reported case of BOOP associated with single-agent rituximab, and along with two other patients we describe, as well as two prior reports of BOOP in NHL patients receiving rituximab-based combinations, strengthens the possibility of a causal relationship. Moreover, these findings suggest that the incidence of BOOP following rituximab therapy may be higher than has been previously appreciated. Physicians utilizing rituximab should be aware of this association given the difficulty of differentiating between presentations of BOOP and neoplastic pulmonary processes.     

Organizing pneumonia after stereotactic ablative radiotherapy of the lung

ABSTRACT: BACKGROUND: Organizing pneumonia (OP), so called bronchiolitis obliterans organizing pneumonia after postoperative irradiation for breast cancer has been often reported. There is little information about OP after other radiation modalities. This cohort study investigated the clinical features and risk factors of OP after stereotactic ablative radiotherapy of the lung (SABR). METHODS: Patients undergoing SABR between 2004 and 2010 in two institutions were investigated. Blood test and chest computed tomography were performed at intervals of 1 to 3 months after SABR. The criteria for diagnosing OP were: 1) mixture of patchy and ground-glass opacity, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lesion in the lung volume receiving < 0.5 Gy, and 4) no evidence of a specific cause. RESULTS: Among 189 patients (164 with stage I lung cancer and 25 with single lung metastasis) analyzed, nine developed OP. The incidence at 2 years was 5.2% (95% confidence interval; 2.6-9.3%). Dyspnea were observed in all patients. Four had fever. These symptoms and pulmonary infiltration rapidly improved after corticosteroid therapy. Eight patients had presented with symptomatic radiation pneumonitis (RP) around the tumor 2 to 7 months before OP. The prior RP history was strongly associated with OP (hazard ratio 61.7; p = 0.0028) in multivariate analysis. CONCLUSIONS: This is the first report on OP after SABR. The incidence appeared to be relatively high. The symptoms were sometimes severe, but corticosteroid therapy was effective. When patients after SABR present with unusual pneumonia, OP should be considered as a differential diagnosis, especially in patients with prior symptomatic RP.     

乳腺癌术后放射治疗诱发肉瘤

目的　通过典型病例研究 ,了解乳腺癌术后放射治疗诱发肉瘤的一般规律及特点。方法　回顾性分析了 2例乳腺癌患者的详细病程。结果　 2例乳腺癌患者术后均曾行放射治疗 ,1例采用深部X线照射和辅助化疗 ,另 1例采用60 Co照射 ,未行辅助化疗。分别于治疗后 11年和 13年出现放射治疗野内的第 2原发癌 ,病理类型均是肉瘤。结论　对于放射治疗后 10年左右 ,单纯在放射治疗野内出现的异常情况 ,应警惕可能发生放射治疗诱发的肉瘤。     

Radiation-induced long thoracic nerve palsy

The incidence of long thoracic nerve palsy after radical mastectomy has been documented to be approximately 10%. No cases have been reported after the more recent treatment for breast cancer, lumpectomy with axillary dissection. This more recent surgical procedure is customarily followed by aggressive radiation therapy to the remaining breast tissue. This is the first case report of a patient with radiation-induced long thoracic nerve palsy. The patient was a young woman who underwent left breast quadrantectomy and axillary dissection for breast cancer. After radiation therapy, she had isolated left long thoracic nerve palsy. The diagnosis was confirmed by electrodiagnostic studies. Almost full recovery occurred after 5 months.     

Breast Osteosarcoma 29 Years after Radiation Therapy for Epithelial Breast Cancer

Radiation therapy has a solid role in the management of breast adenocarcinoma. It significantly reduces the rates of disease recurrence. Nevertheless, radiation therapy is not without side effects and patients who have undergone breast irradiation are at increased risk for lung disease, sarcomas, acute leukemia and esophageal cancer. We present a case of radiation-induced breast osteosarcoma 29 years after radiation therapy and lumpectomy for breast adenocarcinoma. The patient had several disease recurrences after surgical resection and was found to have pulmonary metastases.Key words: Breast osteosarcoma, Radiation therapy, Epithelial breast cancer