Spontaneous Pneumothorax following Thoracic Irradiation

Spontaneous Pneumothorax following Thoracic Irradiation* Eric K. &winsky, M.D.; Martin D. Abeloff, M.D .; and Moody D. Wharam, M.D .

Spontaneous pneumothorax has ooly very rarely been reported to occur following thoracic irradiation. Four patients who developed this complication following radiation therapy are presented and the literature is reviewed. Spontaneous pneumothorax followiog thoracic irradiation tends to be recurrent, occasionally bilateral, and in most

reported cases, occurs in patients who develop roentgenographic evidence of radiation 6brosis &Rer treatment with mantle-shaped portals for Hodgkin's and DOn-Hodgkin's lymphomas. Re-expaosion often occurs without intervention.

~ntaneous pneumothorax most often occurs in

previously healthy adults between 20 and 40 years of age. 1 It is also a recognized complication of numerous pulmonary disorders characterized by interstitial inflammation and fibrosis including systemic sclerosis, sarcoidosis, malignant histiocytosis, Hamman-Rich disease, tuberous sclerosis, emphysema, cystic fibrosis, and familial fibrocystic pulmonary dysplasia.r" In one community study, the age adjusted incidence rate per primary and secondary pneumothorax was 4.2 and 3.8 per 100,000 person-years, respectively" The irradiation of pulmonary tissue during the therapy of malignant disease often results in pulmonary changes that pathologically, physiologically, and roentgenographically resemble those seen in other interstitial disorders and that have been reported to possibly predispose to spontaneous pneumothorax.5-8 Simultaneous bilateral spontaneous pneumothoraces, never previously described following radiotherapy, developed in a patient who received radiation therapy to the thorax for Hodgkin's disease. The patient, along with three other patients with Hodgkin's and non-Hodgkins lymphomas, who developed recurrent spontaneous pneumothoraces after thoracic irradiation administered during 1975 to 1984, are presented. During these ten years, approximately 342 patients with lymphomas received thoracic irradiation yielding an occurrence rate of 11.7 per 1,000. Radiation-induced interstitial changes may be responsible for the development of spontaneous pneumothorax. Following presentation of the cases, spontaneous pneumothorax, as both a complication of malignancy and thoracic irradiation, is discussed. *From The Johns Hopkins Oncology Center, The Johns Hopkins Medical Institutions, Baltimore. Supported in part by NIH-NCI-CA-06973 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services . Manuscript received March 4; revision accepted May 20. Reprint "!.~"": Dr. Abelojf, Johns Hopkins Oncology Cente,., 600

North Wo~e Strut, Baltimiire2l205

CASE REPORTS CASE

1

A 19-year-oldfemale subject was well until December 1982, when she noticed "bulging" of her left anterior chest wall. Physical examination was remarkable lOr bilateral cervical and left supraclavicular adenopathy, and protrusion of the chest wall at the left border of her sternum and second intercostal space . Initial chest roentgenogram (Fig 1) revealed a large anterior mediastinal mass, bilateral paratracheal, and left hiIar adenopathy. A thoracic cr scan showed extensive mediastinal disease with pericardial and chest wall involvement. Biopsy of a cervical lymph node diagnosed nodular sclerosing Hodgkins disease. Further staging included bilateral iliac crest bone marrow biopsies and aspirates, an abdominal cr scan, and a pedallymphangiogram, results of which were nonnal. The patient was considered to have clinical stage 2£ A nodular sclerosing Hodgkin's disease and was initially treated with three cycles of BCVPP (carmustine [BCNU] . cyclophosphamide, vinblastine. procarbazine. and prednisone). Because of poor hematologic tolerance, her regimen was changed to C-MOPP (cyclophosphamide, vincristine, procarbazine, and prednisone) which she received fur an additional three cycles until September 1983. Chest roentgenogram (Fig 2) in November 1983 was interpreted as nonnal at which time the patient began radiotherapy. With a 4 MeV linear

FICURE 1. Posteroanterior roentgenogram showing large mediastinal mass in December 1982. CHEST I 88 I 5 I NOYEMBER, 1985

703

FIGURE 2. Posteroanterior roentgenogram two months fullowing chemotherapy interpreted as normal . accelerator, 24 treatments were administered over 39 days to a mantle-shaped portal. The mediastinum received 3,720 rads, the medial aspect of the left lung 3,665 rads, the supraclavicular area 4,220 rads, and the axillae 4,086 rads. This was followed by the administration of 2,040 rads to the spleen and para-aortic nodes in January 1984. Follow-up chest roentgenograms until September 1984 (Fig 3) showed changes suggestive of radiation fibrosis in pulmonary parachymal areas adjacent to the left hilum and superior mediastinum. The patient was seen in routine follow-up in December 1984. She was completely asymptomatic, and her examination was unremarkable. Chest roentgenogram (Fig 4) showed radiation changes as previously described, but in addition, she had moderate bilateral pneumothoraces estimated to be approximately 20 percent. A chest x-ray film was repeated several weeks later and showed complete reexpansion on the right and almost complete resolution on the left.

FIGURE 4. Posteroanterior roentgenogram 11 months fullowing irradiation showing bilateral pneumothoraces in addition to radiation changes . CASE

A14-year-oldboy presented in May1982with right supraclavicular adenopathy, malaise, and weight loss. Chest x-ray film showed superior mediastinal adenopathy, and right supraclavicular lymph node biopsy diagnosed nodular sclerosing Hodgkin's disease. Lymphangiography, bilateral iliac crest bone marrow aspirates and biopsies , and staging laparotomy were all negative fur Hodgkin's involvement, and the patient was considered to have stage 2B disease and was treated with radiation therapy. With a 4 MeV linear accelerator, 24 treatments were administered over 35 days to a mantle-shaped portal. The mediastinum received 4,320 rads, the supraclavicular area 4,334 rads, and the axillae 3,843 rads. This was followed by the administration of3,600 rads to the spleen and paraaortic lymph nodes. Follow-up chest roentgenograms showed fibrotic changes in the paramediastinal and apical pulmonary parenchymal regions. The patient was well until October 1983 when he suddenly developed left-sided chest pain. Chest x-ray film showed left pneumothorax estimated to be approximately 20 percent. The pneumothorax completely resolved without intervention, and the patient did well until March 1984when he againexperienced sudden left-sided chest pain. Chest roentgenogram showed a new left pneumothorax estimated to be 15 percent which again resolved completely without intervention. CASE

FIGURE 3. Posteroanterior roentgenogram nine months fullowing thoracic irradiation showing radiation changes in the paramediastinal and left hilar areas .

704

2

3

A 15-year-old girl presented complaining of a sore throat in September 1975. Physical examination revealed right supraclavicular adenopathy. Initial diagnostic studies included a chest x-ray film, which showed a superior mediastinal mass and a leu1cocyte count of 19,000 with 30 percent blasts. Biopsy of the supraclavicular lymph node diagnosed lymphoblastic lympboma and a bone marrow biopsy revealed lymphomatous involvement. The patient was initially treated with an induction regimen consisting of vincristine and prednisone. Radiotherapy with a eoco source was begun in October 1975, the patient receiving 3,000 rads to the mediastinum over 24 days to a mantle-shaped portal. In November 1975, the patient was considered to be in a complete remission , and she received prophylactic cranial irradiation consisting of 2,400 rads and was subsequently treated with a maintenance

regimen consisting of vincristine, prednisone, 6-mercaptopurine, cyclophosphamide, systemic and intrathecal methotrexate until December 1978. Follow-up chest roentgenograms showed changes suggestive of radiation fibrosis in the paramediastina1 and biapic&l pulmonary parenchyma. In February 1977, routine chest roentgenogram revealed right pneumothorax estimated to be approximately 20 percent A follow-up roentgenogram showed complete re-expansion but, in December 1978, the patient presented complaining of acute left-sided chest pain. Chest roentgenogram showed a left apical pneumothorax which again completely resolved without intervention. She remains well in March 1985. CASE

4

A 14-year-oldgirl presented with right cervical and supraclavicular adenopathy in February 1975. A biOpsyof a supraclavicular lymph node diagnosed nodular sclerosing Hodgkins disease. Further staging included a chest roentgenogram, bilateral iliaccrest aspirates and biopsies, a liver-spleen scan, lymphangiography, and a staging laparotomy, results of which were normal. The patient was considered to have stage 2A nodular sclerosing Hodgkin 5 disease and was treated with radiotherapy. Utilizing a -Co source and a mantle-shaped portal, she received 3,600 rads to her mediastinum. Follow-up chest x-ray fllms revealed evidence of bilateral fibrosis, and the patient did well until October 1975 when she experienced the sudden onset of right-Sided chest pain. Chest x-rayfilm showed a pneumothorax estimated to be approximately 40 percent and chest tube was inserted which resulted in prompt re-expansion ofthe lung. The patient subsequently was admitted on two occasions, in November 1975 and February 1976 for left-sided pneumothoraces estimated to be 15 percent; they re-expanded without intervention. DISCUSSION

Spontaneous pneumothorax is a recognized complication of primary and metastatic pulmonary malignancies and is occasionally the presenting event. The most common group of neoplasms associated with spontaneous pneumothorax are the sarcomas.r'' including osteogenic sarcomas, fibrosarcomas, sarcomas of the synovial cell and synovial sheath, Ewing's sarcoma, and hemangioendotheliosarcomas. This complication is also associated with nonsarcomatous tumors including Hodgkin's disease," non-Hodgkins lymphomas, 12 teratomas," Wilms tumor," renal cell carcinoma," and primary pulmonary malignancies including adenocarcinema," small cell," and squamous cell carcinomas.":" Autopsy studies'':" show that the majority of spontaneous pneumothoraces secondary to malignancy are caused by direct rupture of necrotic neoplastic tissue into the pleural cavity. Others are thought to occur when tumor nodules act as ball valves producing partial bronchiolar obstruction and hyperinflation of alveoli; this results in the formation of interstitial air and subpleural blebs which eventually rupture. Spontaneous pneumothorax following thoracic irradiation has rarely been reported. The first case is the only known report of simultaneous bilateral spontaneous pneumothoraces in the literature. Libshitz and Banner" reviewed approximately 250 patients who

received radiation therapy with conventional mantle ports for lymphomas and over 1,000 patients treated postoperatively with thoracic irradiation for carinoma of the breast and found two patients who subsequently developed spontaneous pneumothorax after receiving mantle therapy for Hodgkins disease. Including the present cases, there are 11 reported instances, in the English medical literature, in which the development of spontaneous pneumothorax can be reasonably associated with the effects of thoracic irradiation (Table 1). Ten episodes followed mantle irradiation for Hodgkin's and non-Hodgkins lymphomas. Pneumothorax occurred in one patient following radiation therapy to the chest wall after mastectomy for breast carcinoma. Nine of the 11 episodes involved patients without concurrent malignant pulmonary involvement. In case 6, pulmonary' Hodgkins disease was documented by postmortem examination, and in case 7, the patients clinical course was consistent with pulmonary Hodgkins disease although never proven pathologically. At the time of diagnosis, the patients' age with Hodgkin's and non-Hodgkins lymphomas ranged from 13 to 30 years. The interval between completion of the radiation courses and the development of spontaneous pneumothorax ranged from three to 65 months in the lymphoma patients as a group, but ranged from four to 16 months in those patients who were known not to have malignant pulmonary involvement. In case 5, spontaneous pneumothorax occurred in a 55-year-old woman two months after postmastectomy chest wall irradiation. ' Additional cases ofspontaneous pneumothorax associated with thoracic irradiation can be found in the literature. Stolzenberg and Clements" described a patient with osteogenic sarcoma metastatic to lung who developed a pneumothorax during radiation therapy administered to both lung fields. There have also been several case reports describing patients with bronchogenic carcinoma, J5.11 all developing spontaneous pneumothorax during or only very shortly after the completion of radiation therapy-before significant histologic, physiologic, or roentgenographic radiation changes are known to occur, and therefore, pneumothorax in these cases, is most likely a result ofdirect neoplastic involvement, not radiationinduced. Histologic changes in virtually all pulmonary structures have been reported in pathologic material obtained four to 12 weeks after completion of pulmonary irradiation. It is uncommon for clinical radiation pneumonitis characterized by dyspnea, cough, and fever to occur less than six to 12 weeks after radiation therapy. Roentgenographic changes consistent with pneumonitis can be expected, as a rule, to occur eight weeks after 4,000 rads to a significant volume oflung, and one CHEST I 88 I 5 I NOIEMBER. 1985

70&

Table I-Spontaneous Pneumothora after ThortJclc IrrtMlitJtion: S..."..." c1ClinicGl DGIG on lIeporI8d C. . . Postradiotherapy Postradi~erapy Case Authors Age/Sex 1

l\vifOrd

Nodular sclerosing Hodgkins disease, Stage 3A; mediastinal mass present

None

301M

Unclassified Hodgkins disease, Stage 2A

None

Libshitz and Banner" 1974

141F

Nodular sclerosing Hodgkin's disease, Stage 2A; mediastinal mass present

None

MOPP Xi. RadioRx with -Co: -3,000 rads to pelvis upper abdomen. -3,500 rads in mantle distribution to mediastinum. RadioRx with 8OCo: -5,975 rads in mantle distribution to mediastinum. RadioRx with

Libshitz and

221M

Nodular sclerosing Hodgkin's disease, Stage 3B; mediastinal mass present

None

-3,900 rads in mantle distribution to mediastinum. RadioRx with

Right breast carcinoma. Postmastectomy

None

Twiford et al8 1978

3

4

Lung Prepneumothorax Involvement 1reatment

131M

et al8 1978

2

Malignancy and Stage at Diagnosis

Banner" 1974

5

Gross! 1977

6

Plowman 1i)/F et al 8 1980

Nodular sclerosing Hodgkin's disease, Stage3A;mediastinal mass present

Biopsy proven

Plowman 261F et al8 1980

Nodular sclerosing Hodgkins disease, Stage 2A; mediastinal involvement not stated

Highly probable

7

8

Present

report (Case 1)

55/F

19/F

Nodular sclerosing None Hodgkin's disease, Stage 2E A; mediastinal mass present

X-Ray

Pneum~ru

Side of

Appearance

Interval

Pneumothoru

Not stated

9 Months

Recurrent right fo~owed by left apical

Not stated

6 Months

Recurrent left apical

-co:

Radiation fibrosis

8 Months

Lea apical

8OCo:

Radiation fibrosis

4 Months

Left apical

Radiation pneumonitis

2 Months

Right apical

Radiation 6brosis and Hodgkins

3 Months

Right apical

Radiation fibrosis, probable Hodgkins

5 Months

Left apical

Radiation fibrosis

11 Months

Biapical

-3,250 in mantle cUsbibution to mediastinum. Followed unspecified chemotherapy. Chest wall irradiation, details not stated. MOPP-like regimen X3 RadioRx: -4,000 rads in distribution to mediastinum. Unspecified combination chemoRx including Bleomycin. RadioRx: -3,500 rads in mantle distribution to mediastinum. BCVPP x3, C-MOPP X3; RadioRx with 4 MeV: -3,700 rads in mantle disbibutionto mediastinum;

disease.

disease

-2,040 rads to

spleen and paraaortic nodes.

(Continued on ne.rt J'GI')

701

Spontanecu PneumaIhorax toIIowing Thor8cIc ImdIIIon (~ AbeIcC

~)

Table 1 (Continued)-SponttJneoua PneumotlaortJ% after TIaorGCic Irradiation: SUmmtJry ojClinicalData on ltepofWdCaaea

Case Authors Age/Sex

Malignancy and Stage at Diagnosis

Lung Prepneumothorax 1i'eatment Involvement

9

Present report (Case 2)

141F

Nodular sclerosing Hodgkin's disease, Stage 2B; mediastinal mass present

None

10

Present report (Case 3)

ISIF

Lymphoblastic lymphoma; mediastinal mass present

None

11

Present report (Case 4)

141F

Nodular sclerosing Hodgkin's disease, Stage 2A; mediastinal mass

None

week earlier for each 1,()()() rads increment above 4, ()()() rads." The majority of patients with clinical radiation pneumonitis become asymptomatic although nearly all will develop roentgenographic evidence of radiation fibrosis which is generally established by the ninth to 12th month following completion of therapy. iO In nine of the 11 cases of postradiation spontaneous pneumothorax in Table 1, roentgenographic changes consisterit with radiation effect were noted prior to pneumothorax; prepneumothorax roentgenographic descriptions are not given for the other two cases. The descriptions are consistent with radiation pneumonitis in the woman with breast carcinoma in case 5 and consistent with radiation fibrosis in the remaining eight patients who were all treated with mantle fields. It is interesting to note that four patients had recurrent unilateral pneumothoraces, and four patients had pneumothoraces involving both lungs at some time in their course. Radiation-induced pulmonary changes, apical pleural injury, parenchymal injury, and foeaI emphysema most likely increase the chance of forming and rupturing subpleural blebs, with the subsequent development of pneumothorax. Almost all reported cases

RadioRx with 4 MeV: -4,320 rads in mantle distribution to mediastinum. -3,600 rads to spleen and paraaortic nodes. Prednisone, vincristine induction followed by: RadioRx with eoco: -3,()()() rads in mantle distribution to mediastinum. ChemoRx with prednisone, vincristine, 6M~ MTX, cyclophosphamide. RadioRx with eoco: -3,600 rads in mantle distribution to mediastinum.

Postradiotherapy Postradiotherapy X-Ray Pneumothorax Side of Appearance Interval Pneumothorax Radiation 6brosis

16 Months

Recurrent left apical

Radiation 6brosis

16 Months

Right followed by left apical

Radiation 6brosis

7 Months

Right followed by recurrent left apical.

ofpneumothorax following thoracic irradiation occur in patients treated with mantle fields, fields that encompass and expose a relatively large amount of pleural surface area to radiation injury as compared to other radiotherapy fields. Because the size of pneumothorax and associated symptomatology was mild to moderate, since re-expansion was often spontaneous, and because patients without malignant pulmonary involvement might not have had frequent follow-up postradiotherapy chest x-ray examinations, postradiation subclinical pneumothorax might be relatively more common than previously appreciated. In summary, most cases of spontaneous pneumothorax following thoracic irradiation occur in patients with Hodgkin's disease who develop roentgenographic fibrosis after treatment with mantle fields. The pneumothorax is usually mild to moderate in size, and because re-expansion is typical, immediate intervention is often not necessary. REFERENCES

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707

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7

8 9

10

11

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