Table 1 Clinical and genetic information for six cases of DICER1-associated CNS sarcoma.
Case | Age at Dx/Sex | Race or country of origin | Tumor site | Tumor DICER1 alterations | Germline DICER1 alterations | Family history of DICER1-related tumors | Lung imaging at/around the time of DCS diagnosis (time since DCS dx) | Previous neoplasm(s), prior to treatment | DCS treatment | Clinical course | Vital status at the date of last contact; time since diagnosis |
|---|---|---|---|---|---|---|---|---|---|---|---|
DCS_1 | 8 y/M | Peru | Parietal lobe | c.2988-1G>T;c.5125G>A (p.D1709N) | Negative | No | CXR (2 mo), PET (5 mo), and chest CT (8 mo), all negative | None | Surgery: three attempts at complete resection Chemo: none Radiation: 60 Gy | No evidence of disease recurrence | Alive, without disease: 3 y 10 mo |
DCS_2 | 3 y/F | Peru | Temporal lobe | c.904-1G>A; c.5125G>A (p.D1709N); c.1124C>G (p.P375R) | Negative (p.P375R is a variant of uncertain significance) | No | Chest CT and PET scan (<1 mo) negative | None | Surgery: GTR Chemo: ifosfamide/doxorubicin Radiation: 56-Gy proton beam | Incidentally found frontal lobe lesion, thought to be low-grade glioma, being monitored | Alive, without disease: 2 y 6 mo |
DCS_3 | 15 y/F | White | Fronto-parietal lobe | c.5527+2T>C; c.5425G>A (p.G1809R) | Negative | No | CT chest (<1 mo): stable subcentimeter nodule | Age 2 y—“Ewing sarcoma” of thoracic spine with pulmonary nodulesa Tx: cyclophosphamide, doxorubicin, vincristine, and ifosfamide/etoposide +RT Age 5 y—large pleural massa Tx: resection and irinotecan/temozolomide | Surgery: resection Chemo: cyclophosphamide/topotecan ×3 cycles (based on initial Ewing sarcoma dx), then changed to ifosfamide/doxorubicin ×2 cycles, and then ifosfamide alone ×6 cycles | DCS recurrence 1- 1 y after initial DCS diagnosis Surgery: resection Radiation: 30 Gy DCS recurrence 2- 4 mo after the first recurrence: adjacent to post-op cavity. At this time, also developed PET-avid pulmonary lesion, with subsequent growth pattern, suggestive of another dominant lesion Surgery: subtotal resection Chemo: cobimetinib Progressive dx: treated with irinotecan/temozolomide Progressive in lungs with large LUL lesion and multiple pulmonary nodules | Died of progressive disease in the lungs: 1 y 11 mo |
DCS_4 | 9 y/F | White | Frontal lobe | c.5425G>A (p.G1809R) | Not tested | Unknown | CT chest (<1 mo) negative | Age 14 mo—atypical teratoid rhabdoid tumor Tx: resection and vincristine, cisplatin, cyclophosphamide, oral etoposide, and IT mafosfamide. Local recurrence 3 mo later. Tx: Re-resection and doxorubicin, etoposide, dactinomycin, and temozolomide with IT methotrexate, cytarabine, and hydrocortisone. RT 50.4 Gy | Surgery: GTR Chemo: vincristine, doxorubicin/dactinomycin, and cyclophosphamide alternating with ifosfamide and etoposide. Radiation: 36 Gy | Recurrence: almost 2 y after initial DCS diagnosis. Surgery: excision, with large re-recurrence in the resection cavity 2 mo later | Died of progressive disease: 2 y 3 mo |
DCS_5 | 5 y/F | White | Frontal lobea | c.4999G>T (p.E1667*)b, c.5425G>A (p.G1809R) | E1667* | Mother with thyroid nodules, DICER1 status unknown | CT chest (1 mo) negative | None | Surgery: GTR Chemo: none Radiation: 59.4 Gy | Single site of metastatic disease in the chest 5 mo after diagnosis. Resected and treated with ifosfamide/doxorubicin and pleural space radiation | Alive without disease: 21 mo |
DCS_6 | 4 y/M | Colombia | Temporal lobe | 14q32 deletion (containing DICER1); c.5125G>A (p.D1709N) | Large interstitial 14q32 deletion | No | CT chest (<1 mo) with single 1–2-cm lung cyst | Age 1—cystic nephroma. Tx: nephrectomy Age 4—malignant teratoid CBME | Surgery | Acute management of postsurgical edema and herniation | Died of disease: 8 days |
