Adults With Exclusively Pulmonary Metastases From Ewing Sarcoma May Benefit From Whole-Lung Irradiation


Key Points

  • Although whole-lung irradiation has been used in pediatric patients with metastatic Ewing sarcoma since the 1970s, its use in comparable adult patients has not been well examined.
  • Nearly half of adult patients with metastatic Ewing sarcoma were free of pulmonary relapse 3 years after treatment with whole-lung irradiation.
  • Three-year survival outcomes were better in nonsmokers and those with exclusively pulmonary metastases than in smokers and those with extrapulmonary metastases.

Nearly half of adult patients with lung-only metastases from Ewing sarcoma who received whole-lung irradiation were free of pulmonary relapse at 3 years, according to the results of a retrospective study in the International Journal of Radiation Oncology • Biology • Physics. With few acute or late complications reported with this treatment approach and a potential therapeutic effect, Casey et al suggested that whole-lung radiotherapy be considered for this adult population, as it is for pediatric patients with Ewing sarcoma that has spread to the lungs.

Low-dose (15 Gy) whole-lung irradiation has been used in pediatric patients with metastatic Ewing sarcoma since the 1970s. However, the efficacy and toxicity of this approach in their adult counterparts have not been well examined. Thus, investigators at Memorial Sloan Kettering Cancer Center, New York, attempted to evaluate the feasibility of whole-lung irradiation in adult patients with Ewing sarcoma and pulmonary metastases.

Study Details

Casey and colleagues reported on their nearly 25-year experience with whole-lung irradiation in adults with pulmonary metastases from Ewing sarcoma. The study population consisted of 26 patients with Ewing sarcoma who were treated with 12 to 15 Gy of whole-lung irradiation for lung metastases.

At the time of whole-lung irradiation, the median age of study patients was 23 years (range, 18–40 years). Metastases were confined to the lungs in 65% of patients, and extrapulmonary metastases (most commonly of the bone) were present in 35% of patients. Bilateral pulmonary lesions were seen at diagnosis in most of the patients (23 of 26). More than half of the study patients (14 adults) had no history of smoking.

Whole-lung irradiation was recommended after chemotherapy, which consisted of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. The median time from the start of chemotherapy to the start of whole-lung irradiation was 27 weeks (range, 18–69 weeks). Targeting parallel opposed anteroposterior whole-lung fields was the treatment approach for 19 patients, and intensity-modulated radiotherapy was given to the other 7 patients. Of the 20 patients who received 15 Gy of radiation, 18 were treated with 1.5-Gy fractions daily. Local treatments of the primary site included surgery alone (eight patients), surgery and radiotherapy (six patients), and definitive radiotherapy (12 patients).

Better Outcomes and Less Acute Toxicity in Nonsmokers

The 3-year cumulative incidence of pulmonary relapse was 55%. In addition, at 3 years, pulmonary relapse occurred less often in patients with lung-only metastases than in those with extrapulmonary metastases (45% vs 76%, P = .01).

The 3-year event-free survival rate was 38%, and the overall survival rate was 45%. Again, patients with exclusively pulmonary metastases had significantly better outcomes than did those with extrapulmonary metastases, with an event-free survival of 49% vs 14% (P = .003) and an overall survival of 61% vs 13% (P = .009).

As expected, smoking status was a significant prognostic factor for event-free survival. The 3-year event-free survival rate was 61% in nonsmokers compared with 11% in smokers (P = .04).

Acute toxicities (eg, cough, dyspnea, dysphagia, nausea, and fatigue) were reported in half of the patients treated with whole-lung irradiation. All of the acute reactions were grade 1 except for one grade 2 esophagitis, one grade 2 fatigue, and one grade 2 nausea. More smokers experienced acute side effects from treatment than did nonsmokers (73% vs 36%; P = .11). No patients experienced pneumonitis or cardiac toxicity, and no late radiologic sequelae or second cancers were reported.

Closing Thoughts

The 3-year survival outcomes in these adult patients are similar to patients with Ewing sarcoma treated with whole-lung irradiation from other retrospective reports, according to the investigators. Although whole-lung irradiation may have a potential therapeutic effect in adults with Ewing sarcoma and lung-only metastases, it does not appear to be beneficial in the subgroup of patients with extrapulmonary Ewing sarcoma. For this group with a poorer prognosis, the investigators noted that a more aggressive approach, including systemic therapy and radiotherapy targeted to multiple sites of distant disease, may be appropriate.

“Any consideration of treatment with whole-lung irradiation in adults must also take into account smoking status as a potential contributing factor to lung toxicity, and all patients should be counseled to quit smoking,” concluded the investigators.

Suzanne L. Wolden, MD, of the Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, is the corresponding author of the article in the International Journal of Radiation Oncology • Biology • Physics.

The authors disclosed no potential conflicts of interest.

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