Table 4.
Treatment and prognosis of brain metastasis from cancer of unknown primary (BM-CUP) in retrospective studies.
| Studies | N of BM- CUP | Treatment of BM | Survival | Local Control | Causes of Death | Determinants of Survival |
|---|---|---|---|---|---|---|
| Gough et al., 2020 [66] | 55 | Surgery | Median survival = 6 m; survival at 1 y = 29.1%; at 5 y = 0. | Median time to recurrence = 6 m | NS | Decreased survival associated with other metastases, older age and ECOG score. No significant difference between CUP Vs known primary tumour. |
| Matsunaga et al., 2019 [27] | 152 | GKRS | Median survival = 6 m; survival at 6 m = 79.3%, at 12 m = 14.9% | Response at 6m: complete = 4.4%, partial = 74.2%, stable = 13.3%, progressive disease = 8.1% | Systemic progression = 67% brain progression = 33%; | Decreased survival associated with higher age, lower KPS score, extracranial MTS, multiple BM |
| Dziggel et al., 2018 [31] | 8 | SRS | Survival at 6 m = 63%; at 12 m = 63%. Median survival time was not reached during the follow up. | Local control 100% at 12 m; freedom from new cerebral lesions at 6 m = 86%, 10 m = 64% | NS | Improved survival associated with male gender, single BM |
| Rades et al., 2018 [38] | 140 | WBRT | Survival at 6 m = 33%; at 12 m = 18%. | Local control: 6 m = 36% 12 m = 24%. | NS | Improved survival associated with ECOG-score, extra-cerebral lesions |
| Han et al., 2016 [25] | 10 | GKRS | Median survival = 35.3 m | Median times to new lesion detection = 4.6 months | Systemic progression = 79%, brain progression = 16%; unrelated cause = 5% | NS. No significant difference between CUP Vs known primary tumour |
| Niranjan et al., 2010 [8] | 29 | SRS | Median survival = 12 m | Local control after 18.6 m = 88.5%. Progression free survival at 6 m = 96.4%, at 12 m = 81.9% | Systemic progression = 90%, brain progression = 10% | Decreased survival associated with location in the brainstem |
| Yamamoto et al., 2009 [36] | 32 | GKRS | Median surviva l = 6.5–7 m | NS | NS | Improved survival associated with n of lesions, tumour volumes, non-symptomatic, well-controlled primary, no extracranial MTS, KPS > 80%, >2 procedures |
| Rades et al., 2007 [32] | 101 | WBRT=Long course (10 × 3 Gy) Vs short-course WBRT (5 × 4 Gy) | Median survival in RPA-I = 7.1 m, in RPA-II = 4.2 m, in RPA-III = 2.3 m | Local control at 6 m: short WBRT = 80%, long WBRT = 50% | NS | Improved survival associated with KPS > 70, no extracranial metastases, RPA-class = 1 |
| D’Ambrosio and Agazzi, 2007 [22]; Agazzi et al., 2004 [19] | 35 | WBRT + Surgery/SRS | Median survival (after diagnosis) = 3.2 m | NS | Systemic progression in most (NS) | No significant difference between CUP Vs known primary. In CUP, no difference if identification of the primary |
| Bartelt and Lutterbach, 2003 [14] | 47 | WBRT | Survival at 3m = 68%, at 6 m = 39%, at 12 m = 26%, at 24 m = 5% | NS | NS | Improved survival associated with KPS > 70 and resection. No significant difference between CUP Vs known primary tumour. |
| Petrovich et al., 2002 [40] | 14 | GKRS | Median survival = 6 m | NS | Systemic progression = 70%, brain progression = 23%, unknown = 7%. | Improved survival associated with KPS > 70, less active systemic disease, total intracranial tumour volume (<3 cm) |
| Yuile and Tran, 2002 [41] | 25 | WBRT | Median survival = 4 m | NS | NS | Improved survival associated with Radiation dose >40 Gy, degree of surgery, primary site (lung) |
| Rudà et al., 2001 [61] | 33 | WBRT + surgery | Median survival = 10 m; Survival at 6 m = 76%, at 12 m = 42%, at 24 m = 15% | NS | NS | Improved survival associated with single BM |
| Hall et al., 2000 [42] | 34 | WBRT | Survival (after diagnosis): at 2 y = 12.3%, at 3 y = 6.6%, at 5 y = 0% | NS | Systemic progression in most (NS) | Improved survival associated with younger age, single of BM, surgical resection, WBRT, CT |
| Maesawa et al., 2000 [17] | 15 | SRS | Median survival = 15 m survival at 2 y = 53.3%, at 3 y = 20% | Crude local tumour control rate = 92.6%. Tumour control rate at 4 y = 91.3% | Systemic progression = 53%, Brain progression = 20%, unknown = 27% | Improved survival associated with BM location (other than brainstem), extracranial disease. Detection of the primary site did not affect survival |
| Lagerwaard et al., 1999 [16] | 102 | Surgery and/or RT | Median survival (after diagnosis) = 5.5 m; Survival at 6 m = 48%, at 1 y = 22%, at 2 y = 10% |
NS | Brain progression = 57%. | Improved survival associated with surgery+RT, ECOG, response to steroid treatment, systemic activity, serum LDH, unknown primary, age, number of BM |
| Nguyen et al., 1998 [18] | 27 | WBRT + surgery | Median survival = 13.4 m Survival at 12 m = 56%, at 18 m = 38%, at 5 y = 15%, at 8 y = 12% | 5 y = 72% | Systemic progression in most (NS) | Improved survival associated with gross total resection and RT |
| Nussbaum et al., 1996 [43] | 33 | WBRT + surgery/CT | Median survival (after diagnosis) = 7 m | NS | NS | Improved survival associated with surgery, RT, CT and younger age. |
| Salvati et al., 1995 [10] | 100 | Surgery | Survival at 6 m = 43%, at 1 y = 19% | Intracranial progression/relapse = 60% | Perioperative mortality = 6%; brain progression = 38%; systemic progression = 66% | Improved survival associated with unknown primary, RT, number of MTS in different organs <2 |
| Debevec, 1990 [44] | 75 | WBRT | Median survival = 9.5 m; survival at 1 y = 41%. | NS | Brain progression = 60% | NS |
| Merchut, 1989 [7] | 56 | WBRT/surgery | Survival at 6 m = 55%, at 1 y = 13% | NS | NS | NS |
| Eapen et al., 1988 [23] | 43 | Surgery and/or WBRT | Survival at 6 m = 52%, 12 m = 20% | NS | Brain progression = 68.3%, systemic progression = 31.7% | Improved survival associated with single BM |
| Chevalier et al., 1985 [21] | 67 | Surgery and/or WBRT | Survival (after diagnosis) at 6 m = 44%, at 12 m = 16%, at 24 m = 5% | NS | NS | NS. No significant difference between CUP Vs found primary tumour |
| Yardeni et al., 1984 [45] | 26 | Surgery | Median survival = 3.5 m, survival at 1 y = 19.2%, 2 y = 11.5% | NS | NS | NS. No correlation between survival and age or extracranial metastasis. |
| Zimm et al., 1981 [28] | 16 | Surgery + WBRT/CT 1 | Median survival (after diagnosis) = 7.2 m | NS | Brain progression = 75% | Improved survival associated with younger age, single BM, ambulatory performance status <1, presenting symptoms (headache, personality change, visual disturbances) |
| Ebels and van der Meulen, 1978 [46] | 19 | Surgery | Median survival = 6.8 m | NS | NS | NS |
Median survival is intended as after treatment where not specified. GKRS = gamma knife radiosurgery; SRS = stereotactic radiosurgery; WBRT = whole brain radiotherapy; MRI = magnetic resonance imaging; NS = not specified; n = number; m = months; y = years; MTS = metastases; KPS = Karnofsky Performance Status; RPA=recursive partitioning analysis score; ECOG = eastern cooperative oncology group performance score; CT = chemotherapy; LDH = lactate dehydrogenase; 1 = intracarotid artery infusions of BCNU, 70–90 mg/m2.