Clinical significance of pulmonary nodules detected by CT and Not CXR in patients treated for favorable histology Wilms tumor on national Wilms tumor studies‐4 and ‐5: A report from the Children's Oncology Group

Abstract

Background Metastatic lung disease in Wilms tumor (WT) patients was traditionally identified by chest radiograph (CXR). It is unclear whether patients with small lesions, detectable only by computed tomography (“CT-only” lesions), require the more intensive therapy, including doxorubicin and lung irradiation, given to patients with metastases detectable by CXR. Procedures This study involved 417 patients with favorable histology WT and isolated lung metastases (detected by CXR or CT) who were registered on National Wilms Tumor Study (NWTS)-4 or -5. Outcomes by method of detection (CXR vs. CT only), use of lung radiation, and 2- or 3-drug chemotherapy (dactinomycin and vincristine +/− doxorubicin) were determined and compared using the log-rank test. Results There were 231 patients with lung lesions detected by CXR and 186 by CT only. Of the patients with CT-only nodules, 37 received only 2 drugs and 101 did not receive lung radiation. Five-year event-free survival (EFS) was greater for patients receiving 3 drugs (including doxorubicin) with or without lung radiation than for those receiving 2 drugs (80% vs. 56%; p=0.004). There was no difference seen in 5-year overall survival (OS) between the 3-drug and 2-drug subsets (87% vs 86%; p=0.91). There were no significant differences in EFS (82% vs. 72%; p=0.13) or OS (91% vs. 83%; p = 0.46) for patients with CT-only nodules whether they received lung radiation or not. Conclusions Our results suggest that patients with CT-only lung lesions may have improved EFS but not OS from the addition of doxorubicin but do not appear to benefit from pulmonary radiation.

Omission of doxorubicin from the treatment of stage II–III, intermediate-risk Wilms' tumour (SIOP WT 2001): an open-label, non-inferiority, randomised controlled trial

“…29 Nonetheless, doxorubicin is still thought to contribute to eff ectiveness in some settings, including high-risk blastemal-type Wilms' tumour 30 and metastatic disease, even when the metastatic volume is low and detectable only by CT. 31 Anthracyclines cause dose-related cardiotoxicity, and cause an additive eff ect in left-sided stage III tumours in which fl ank irradiation might encompass part of the heart muscle. 10,11 International follow-up guidelines suggest that survivors who receive at least 250 mg/m² of doxorubicin-the dose given in our three-drug regimen-need continual cardiac surveillance.…”

Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol

“…Overall, ~17% of patients with Wilms tumours present with stage IV disease at diagnosis, which is defined as haematogenous metastases to the lungs, liver, or other sites, or extra-abdominal lymph node metastases. Pulmonary metastases are by far the most frequently observed [21][22][23] . The increasing use of chest CT as routine imaging for staging has resulted in the detection of small pulmonary nodules not visible on chest radiography (CT-only nodules).…”

Management of pediatric renal tumor: Past and future trials of the Japan Wilms Tumor Study Group

“…10 Recently the quality of image analysis has markedly improved: now, even very small lung metastases can be detected on chest computed tomography (CT). In the new study protocol for patients with lung metastasis, the evaluation of lung metastasis will be done using CT. We are preparing a protocol that states that when lung metastasis disappears after 6 or 12 weeks of chemotherapy the patient will not receive radiation to the lungs.…”