Practical Radiation Oncology (2011) 1, 279–281
www.practicalradonc.org
Teaching Case
Treatment of hemoptysis associated with aspergilloma using external beam radiotherapy: A case report and literature review Jason M. Samuelian DO a,⁎, Albert A. Attia MD b , Courtney A. Jensen MD b , Arta M. Monjazeb MD, PhD b , A. William Blackstock MD b a
Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas Department of Radiation Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina
b
Introduction Pulmonary aspergillosis mycetoma commonly forms from saprophytic colonization of preexisting pulmonary cavities of Aspergillus fumigatus, the most common saprophytic species of Aspergillus in human disease, producing a fungus ball or a mycetoma.1,2 The most common symptom associated with aspergillosis mycetoma is hemoptysis, seen in up to 70% of patients.1 Bleeding usually occurs from bronchial blood vessels and may be due to local invasion of blood vessels lining the cavity, endotoxins released from the fungus, or mechanical irritation of the exposed vasculature inside the cavity by the rolling fungus ball,3 and may become life threatening. There is no consensus on the treatment of aspergilloma, which is considered only when patients become symptomatic. Inhaled, intracavitary, and endobronchial instillations of antifungal agents have been attempted, as have intravenously administered amphotericin B and oral itraconazole, without consistent success.4 Therefore, when medical management has failed, the standard of care for massive hemoptysis has been surgical intervention. Invasive therapeutic options include pulmonary or bronchial artery embolization, ligation, or lung resection (pneumonectomy or lobectomy). Surgical intervention requires adequate pulmonary reserve and risks significant Conflicts of interest: None. ⁎ Corresponding author. Department of Radiation Oncology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail address: [email protected] (J.M. Samuelian).
mortality as well as multiple morbidities such as hemorrhage, residual pleural space, bronchopleural fistula, and empyema. Analysis of recent surgical series revealed mortality rates ranging from 0% to 4% and major morbidity rates ranging from 23% to 33%.5 The use of radiotherapy in hemoptysis associated with aspergilloma has been previously described in Europe and South Africa,6-8 but is yet to be detailed in the North American literature. These cases also had limited followup, ranging from 6-8 months. We report a case in which severe refractory hemoptysis from an aspergilloma has been treated with radiotherapy.
Case report A 64-year-old current smoker initially presented with a decade-long history of progressive dyspnea on exertion with cough but no hemoptysis. She was treated for presumed community-acquired pneumonia without success. In 2003, she was hospitalized for acute bronchitis and was diagnosed with chronic obstructive pulmonary disease (COPD). She was started on small-volume nebulizer therapy with inhaled glucocorticoids and a long acting Bagonist with slight improvement in her symptoms. This symptomatic improvement remained until May 2004, when she noted a gradual onset of fatigue, malaise, dyspnea, and small-volume hemoptysis. She was hospitalized and treated with antibiotic therapy for presumed pneumonia. The pneumonia did not resolve after several
1879-8500/$ – see front matter © 2011 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.prro.2011.04.004
280
J.M. Samuelian et al
weeks of treatment, which prompted further evaluation with a computed tomography (CT) scan. This revealed underlying centrilobular emphysema with apical bullous disease as well as a right upper lobe posterior segment cavitary lesion consistent with an abscess. The dyspnea on exertion persisted and the patient underwent transthoracic fine-needle aspiration of the cavitary lesion on August 29, 2004, which revealed granulomatous inflammation and negative cytology. This procedure was complicated by a pneumothorax that did not resolve spontaneously and required a chest tube. The patient then developed extensive subcutaneous emphysema, which persisted for several days, and a CT scan showed that the lung was not fully inflated. On August 30, 2004, the patient underwent video-assisted thoracoscopic surgery with talc pleurodesis and did reasonably well postoperatively. Her symptoms showed modest improvement after video-assisted thoracoscopic surgery, despite continued dyspnea, productive cough, and hemoptysis, which the patient described as qblood clots mixed with yellow phlegm.q She was then referred for pulmonary rehabilitation in January 2005. Throughout this time, she continued outpatient medical therapy for COPD and was able to reduce her smoking to 1-2 cigarettes per day. Her right upper lobe cavitary lesion was followed with serial chest X-rays that showed a slight decrease in size when compared to several months prior. She then had several admissions throughout the year for presumed COPD exacerbations, which were treated with antibiotics and corticosteroids. CT scan of the chest in September 2005 revealed a cavitary lesion in the right upper lobe with the appearance of a fungus ball (Fig 1). Sputum cultures also yielded hyphae, fibrin, and mucus consistent with
Figure 1
Practical Radiation Oncology: October-December 2011
Aspergillus fumigatus, and she was subsequently diagnosed with aspergillosis mycetoma and treated with oral itraconazole. Over the next 2 years, her dyspnea, cough, and hemoptysis remained stable. In 2007, her hemoptysis began increasing in frequency and quantity until she was expectorating roughly one-fourth to one-half cup blood every morning. She was treated with embolization of the right bronchial artery in April, which did not improve her hemoptysis. During this admission, her hemoglobin was 8.2 g/dl, requiring transfusion of packed red blood cells. She then had several subsequent hospital admissions for hemoptysis and infection, including a 3-week admission for severe pseudomonas pneumonia. The hemoptysis persisted and in September 2007 she underwent embolizations of the right lateral thoracic artery and right fifth intercostal artery. Despite these therapies, she continued to have intractable hemoptysis requiring further admissions, and in December 2007 she underwent a third embolization procedure without improvement. She was then referred to our department for possible radiotherapy to the mycetoma, and was deemed a candidate for radiotherapy secondary to persistent hemoptysis and failure of standard therapeutic options. The patient received 2800 cGy in 8 fractions delivered weekly as 350 cGy per fraction to the mycetoma. The clinical treatment volume was defined as the mycetoma plus 1 centimeter. The planning target volume was defined as the clinical treatment volume plus 0.5 centimeter. The field setup was anterior posterior/posterior-anterior. Overall, she tolerated her treatment well with no significant side effects. The hemoptysis improved gradually after several fractions, with near-resolution at 7 weeks; after having received 8 fractions, the hemoptysis had completely resolved. The patient's hemoglobin levels subsequently stabilized to normal levels, and her clinical status improved. Post-radiation CT scan of the chest revealed a decrease in the size of the cavitary lesion. The patient was followed at 6-month intervals post therapy. At 21 months post-radiation therapy, the frequency and volume of her hemoptysis decreased, to 1 teaspoon once or twice monthly, as compared to approximately one-half cup daily. At 24 months followup, she states that she has had very few episodes of small-volume hemoptysis over the last 6 months. Her functional status has improved greatly; the patient is able to work full-time and walks 1 mile per day. She has not required further transfusion for anemia. The cavitary lesion has decreased in size, and is still present but is stable on recent imaging. To date, no additional lesions have developed in the ipsilateral or contralateral lungs, and no additional biopsies have been performed since treatment. To date, no additional pulmonary function testing has been indicated; the patient continues to follow up at regular intervals for surveillance.
Practical Radiation Oncology: October-December 2011
Discussion Radiotherapy is used relatively infrequently in the treatment of benign diseases due to fear of late complications or secondary malignancies. Some references even cite that radiation may itself result in pulmonary cavitation and subsequent fungal colonization.9 Nevertheless, radiation has been utilized in the treatment of life threatening bleeding from benign disease when all other acceptable modalities have failed. Few publications have described the use of radiation in the management of hemoptysis from aspergilloma. Following an extensive literature search, we discovered 2 publications describing the use of radiotherapy in the treatment of hemoptysis arising from a mycetoma. A third publication was in Spanish and we were unable to translate it.7 The first description of this treatment was in the form of a case report from the UK published by Shneerson et al in 1980.6 Their patient was treated with 2000 rads given in 5 fractions over 7 days on Co60, employing a single anterior field. Eight weeks later, the patient had a re-bleed and required a further 1000 rads given in 5 fractions over 7 days using opposed parallel fields. At 8 months follow-up, the patient had no further hemoptysis or change in his lung function. The aspergilloma did not change in size. A series of 5 patients treated with radiotherapy in South Africa for life threatening hemoptysis secondary to a mycetoma was published in 2002.8 Each received external beam radiotherapy of 3.5 Gy once a week continuing for 1 fraction after the hemoptysis stopped. Three patients required 7 Gy, 1 required 10.5 Gy, and the fifth patient required 14 Gy before the hemoptysis had resolved. Irradiation was successful in achieving hemostasis in all 5 patients, with no reported post-treatment toxicities at 6 months follow-up. Radiotherapy is an effective modality for the treatment of life-threatening hemoptysis secondary to a mycetoma. The recommended initial treatment is surgical intervention as it has the potential to remove the source of hemoptysis. Nevertheless, there is morbidity and mortality associated with invasive procedures. Based on our institution's experience and the reviewed literature above,
Radiotherapy for hemoptysis from aspergilloma
281
it appears that radiotherapy is a safe alternative for refractory hemoptysis, with little associated toxicity when performed correctly. There is no consensus as to the exact dose necessary for resolution of hemoptysis from pulmonary mycetoma. From previous reports, it appears that patients require few fractions of radiation for resolution of their symptoms. Our patient received 3.5 Gy per fraction on a weekly basis with the intent to treat for 1 fraction beyond resolution of the hemoptysis. In summary, we suggest that radiotherapy be considered in patients with aspergillomas presenting with severe hemoptysis who are unfit for surgery; however, with the low number of cases reported, more experience is needed to verify the efficacy and safety of this modality.
References 1. Faulkner SL, Vernon R, Brown PP, Fisher RD, Bender HW Jr. Hemoptysis and pulmonary aspergilloma: operative versus nonoperative treatment. Ann Thorac Surg. 1978;25:389-392. 2. Hinson KF, Moon AJ, Plummer NS. Broncho-pulmonary aspergillosis; a review and a report of eight new cases. Thorax. 1952;7:317-333. 3. Solit RW, McKeown JJ Jr, Smullens S, Fraimow W. The surgical implications of intracavitary mycetomas (fungus balls). J Thorac Cardiovasc Surg. 1971;62:411-422. 4. Hammerman KJ, Sarosi GA, Tosh FE. Amphotericin B in the treatment of saprophytic forms of pulmonary aspergillosis. Am Rev Respir Dis. 1974;109:57-62. 5. Lee JG, Lee CY, Park IK, et al. Pulmonary aspergilloma: analysis of prognosis in relation to symptoms and treatment. J Thorac Cardiovasc Surg. 2009;138:820-825. 6. Shneerson JM, Emerson PA, Phillips RH. Radiotherapy for massive haemoptysis from an aspergilloma. Thorax. 1980;35:953-954. 7. Fernández Vázquez E, Zamarrón Sanz C, Alvarez Dobaño JM, Penela Penela P, González Patiño E. Hemoptysis caused by aspergilloma treated with radiotherapy. [Article in Spanish] An Med Interna. 1994;11:516-517. 8. Falkson C, Sur R, Pacella J. External beam radiotherapy: a treatment option for massive haemoptysis caused by mycetoma. Clin Oncol (R Coll Radiol). 2002;14:233-235. 9. Makker H, McConnochie K, Gibbs AR. Postirradiation pulmonary fibrosis complicated by aspergilloma and bronchocentric granulomatosis. Thorax. 1989;44:676-677.
www.practicalradonc.org
Teaching Case
Treatment of hemoptysis associated with aspergilloma using external beam radiotherapy: A case report and literature review Jason M. Samuelian DO a,⁎, Albert A. Attia MD b , Courtney A. Jensen MD b , Arta M. Monjazeb MD, PhD b , A. William Blackstock MD b a
Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas Department of Radiation Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina
b
Introduction Pulmonary aspergillosis mycetoma commonly forms from saprophytic colonization of preexisting pulmonary cavities of Aspergillus fumigatus, the most common saprophytic species of Aspergillus in human disease, producing a fungus ball or a mycetoma.1,2 The most common symptom associated with aspergillosis mycetoma is hemoptysis, seen in up to 70% of patients.1 Bleeding usually occurs from bronchial blood vessels and may be due to local invasion of blood vessels lining the cavity, endotoxins released from the fungus, or mechanical irritation of the exposed vasculature inside the cavity by the rolling fungus ball,3 and may become life threatening. There is no consensus on the treatment of aspergilloma, which is considered only when patients become symptomatic. Inhaled, intracavitary, and endobronchial instillations of antifungal agents have been attempted, as have intravenously administered amphotericin B and oral itraconazole, without consistent success.4 Therefore, when medical management has failed, the standard of care for massive hemoptysis has been surgical intervention. Invasive therapeutic options include pulmonary or bronchial artery embolization, ligation, or lung resection (pneumonectomy or lobectomy). Surgical intervention requires adequate pulmonary reserve and risks significant Conflicts of interest: None. ⁎ Corresponding author. Department of Radiation Oncology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail address: [email protected] (J.M. Samuelian).
mortality as well as multiple morbidities such as hemorrhage, residual pleural space, bronchopleural fistula, and empyema. Analysis of recent surgical series revealed mortality rates ranging from 0% to 4% and major morbidity rates ranging from 23% to 33%.5 The use of radiotherapy in hemoptysis associated with aspergilloma has been previously described in Europe and South Africa,6-8 but is yet to be detailed in the North American literature. These cases also had limited followup, ranging from 6-8 months. We report a case in which severe refractory hemoptysis from an aspergilloma has been treated with radiotherapy.
Case report A 64-year-old current smoker initially presented with a decade-long history of progressive dyspnea on exertion with cough but no hemoptysis. She was treated for presumed community-acquired pneumonia without success. In 2003, she was hospitalized for acute bronchitis and was diagnosed with chronic obstructive pulmonary disease (COPD). She was started on small-volume nebulizer therapy with inhaled glucocorticoids and a long acting Bagonist with slight improvement in her symptoms. This symptomatic improvement remained until May 2004, when she noted a gradual onset of fatigue, malaise, dyspnea, and small-volume hemoptysis. She was hospitalized and treated with antibiotic therapy for presumed pneumonia. The pneumonia did not resolve after several
1879-8500/$ – see front matter © 2011 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.prro.2011.04.004
280
J.M. Samuelian et al
weeks of treatment, which prompted further evaluation with a computed tomography (CT) scan. This revealed underlying centrilobular emphysema with apical bullous disease as well as a right upper lobe posterior segment cavitary lesion consistent with an abscess. The dyspnea on exertion persisted and the patient underwent transthoracic fine-needle aspiration of the cavitary lesion on August 29, 2004, which revealed granulomatous inflammation and negative cytology. This procedure was complicated by a pneumothorax that did not resolve spontaneously and required a chest tube. The patient then developed extensive subcutaneous emphysema, which persisted for several days, and a CT scan showed that the lung was not fully inflated. On August 30, 2004, the patient underwent video-assisted thoracoscopic surgery with talc pleurodesis and did reasonably well postoperatively. Her symptoms showed modest improvement after video-assisted thoracoscopic surgery, despite continued dyspnea, productive cough, and hemoptysis, which the patient described as qblood clots mixed with yellow phlegm.q She was then referred for pulmonary rehabilitation in January 2005. Throughout this time, she continued outpatient medical therapy for COPD and was able to reduce her smoking to 1-2 cigarettes per day. Her right upper lobe cavitary lesion was followed with serial chest X-rays that showed a slight decrease in size when compared to several months prior. She then had several admissions throughout the year for presumed COPD exacerbations, which were treated with antibiotics and corticosteroids. CT scan of the chest in September 2005 revealed a cavitary lesion in the right upper lobe with the appearance of a fungus ball (Fig 1). Sputum cultures also yielded hyphae, fibrin, and mucus consistent with
Figure 1
Practical Radiation Oncology: October-December 2011
Aspergillus fumigatus, and she was subsequently diagnosed with aspergillosis mycetoma and treated with oral itraconazole. Over the next 2 years, her dyspnea, cough, and hemoptysis remained stable. In 2007, her hemoptysis began increasing in frequency and quantity until she was expectorating roughly one-fourth to one-half cup blood every morning. She was treated with embolization of the right bronchial artery in April, which did not improve her hemoptysis. During this admission, her hemoglobin was 8.2 g/dl, requiring transfusion of packed red blood cells. She then had several subsequent hospital admissions for hemoptysis and infection, including a 3-week admission for severe pseudomonas pneumonia. The hemoptysis persisted and in September 2007 she underwent embolizations of the right lateral thoracic artery and right fifth intercostal artery. Despite these therapies, she continued to have intractable hemoptysis requiring further admissions, and in December 2007 she underwent a third embolization procedure without improvement. She was then referred to our department for possible radiotherapy to the mycetoma, and was deemed a candidate for radiotherapy secondary to persistent hemoptysis and failure of standard therapeutic options. The patient received 2800 cGy in 8 fractions delivered weekly as 350 cGy per fraction to the mycetoma. The clinical treatment volume was defined as the mycetoma plus 1 centimeter. The planning target volume was defined as the clinical treatment volume plus 0.5 centimeter. The field setup was anterior posterior/posterior-anterior. Overall, she tolerated her treatment well with no significant side effects. The hemoptysis improved gradually after several fractions, with near-resolution at 7 weeks; after having received 8 fractions, the hemoptysis had completely resolved. The patient's hemoglobin levels subsequently stabilized to normal levels, and her clinical status improved. Post-radiation CT scan of the chest revealed a decrease in the size of the cavitary lesion. The patient was followed at 6-month intervals post therapy. At 21 months post-radiation therapy, the frequency and volume of her hemoptysis decreased, to 1 teaspoon once or twice monthly, as compared to approximately one-half cup daily. At 24 months followup, she states that she has had very few episodes of small-volume hemoptysis over the last 6 months. Her functional status has improved greatly; the patient is able to work full-time and walks 1 mile per day. She has not required further transfusion for anemia. The cavitary lesion has decreased in size, and is still present but is stable on recent imaging. To date, no additional lesions have developed in the ipsilateral or contralateral lungs, and no additional biopsies have been performed since treatment. To date, no additional pulmonary function testing has been indicated; the patient continues to follow up at regular intervals for surveillance.
Practical Radiation Oncology: October-December 2011
Discussion Radiotherapy is used relatively infrequently in the treatment of benign diseases due to fear of late complications or secondary malignancies. Some references even cite that radiation may itself result in pulmonary cavitation and subsequent fungal colonization.9 Nevertheless, radiation has been utilized in the treatment of life threatening bleeding from benign disease when all other acceptable modalities have failed. Few publications have described the use of radiation in the management of hemoptysis from aspergilloma. Following an extensive literature search, we discovered 2 publications describing the use of radiotherapy in the treatment of hemoptysis arising from a mycetoma. A third publication was in Spanish and we were unable to translate it.7 The first description of this treatment was in the form of a case report from the UK published by Shneerson et al in 1980.6 Their patient was treated with 2000 rads given in 5 fractions over 7 days on Co60, employing a single anterior field. Eight weeks later, the patient had a re-bleed and required a further 1000 rads given in 5 fractions over 7 days using opposed parallel fields. At 8 months follow-up, the patient had no further hemoptysis or change in his lung function. The aspergilloma did not change in size. A series of 5 patients treated with radiotherapy in South Africa for life threatening hemoptysis secondary to a mycetoma was published in 2002.8 Each received external beam radiotherapy of 3.5 Gy once a week continuing for 1 fraction after the hemoptysis stopped. Three patients required 7 Gy, 1 required 10.5 Gy, and the fifth patient required 14 Gy before the hemoptysis had resolved. Irradiation was successful in achieving hemostasis in all 5 patients, with no reported post-treatment toxicities at 6 months follow-up. Radiotherapy is an effective modality for the treatment of life-threatening hemoptysis secondary to a mycetoma. The recommended initial treatment is surgical intervention as it has the potential to remove the source of hemoptysis. Nevertheless, there is morbidity and mortality associated with invasive procedures. Based on our institution's experience and the reviewed literature above,
Radiotherapy for hemoptysis from aspergilloma
281
it appears that radiotherapy is a safe alternative for refractory hemoptysis, with little associated toxicity when performed correctly. There is no consensus as to the exact dose necessary for resolution of hemoptysis from pulmonary mycetoma. From previous reports, it appears that patients require few fractions of radiation for resolution of their symptoms. Our patient received 3.5 Gy per fraction on a weekly basis with the intent to treat for 1 fraction beyond resolution of the hemoptysis. In summary, we suggest that radiotherapy be considered in patients with aspergillomas presenting with severe hemoptysis who are unfit for surgery; however, with the low number of cases reported, more experience is needed to verify the efficacy and safety of this modality.
References 1. Faulkner SL, Vernon R, Brown PP, Fisher RD, Bender HW Jr. Hemoptysis and pulmonary aspergilloma: operative versus nonoperative treatment. Ann Thorac Surg. 1978;25:389-392. 2. Hinson KF, Moon AJ, Plummer NS. Broncho-pulmonary aspergillosis; a review and a report of eight new cases. Thorax. 1952;7:317-333. 3. Solit RW, McKeown JJ Jr, Smullens S, Fraimow W. The surgical implications of intracavitary mycetomas (fungus balls). J Thorac Cardiovasc Surg. 1971;62:411-422. 4. Hammerman KJ, Sarosi GA, Tosh FE. Amphotericin B in the treatment of saprophytic forms of pulmonary aspergillosis. Am Rev Respir Dis. 1974;109:57-62. 5. Lee JG, Lee CY, Park IK, et al. Pulmonary aspergilloma: analysis of prognosis in relation to symptoms and treatment. J Thorac Cardiovasc Surg. 2009;138:820-825. 6. Shneerson JM, Emerson PA, Phillips RH. Radiotherapy for massive haemoptysis from an aspergilloma. Thorax. 1980;35:953-954. 7. Fernández Vázquez E, Zamarrón Sanz C, Alvarez Dobaño JM, Penela Penela P, González Patiño E. Hemoptysis caused by aspergilloma treated with radiotherapy. [Article in Spanish] An Med Interna. 1994;11:516-517. 8. Falkson C, Sur R, Pacella J. External beam radiotherapy: a treatment option for massive haemoptysis caused by mycetoma. Clin Oncol (R Coll Radiol). 2002;14:233-235. 9. Makker H, McConnochie K, Gibbs AR. Postirradiation pulmonary fibrosis complicated by aspergilloma and bronchocentric granulomatosis. Thorax. 1989;44:676-677.
