Gradual and Remarkable Tumor Shrinkage Following Seven-Fraction Stereotactic Radiosurgery Alone With a Marginal Dose of 48.3 Gy for Large Lobar Possibly Intra-sulcal Brain Metastasis From Renal Cell Carcinoma

Abstract

Brain metastases (BMs) from renal cell carcinoma (RCC) have the tendency of slow and insufficient tumor shrinkage along with prolongation of massive peritumoral edema following stereotactic radiosurgery (SRS). Herein, we describe a case of large lobar RCC-BM, with possible intra-sulcal location, treated with 7-fraction (fr) SRS without subsequent anti-cancer medication, which resulted in gradual and remarkable tumor shrinkage with extrication from the mass effect. A 59-year-old woman was incidentally diagnosed with bilateral RCC associated with multiple lung metastases and subsequently presented with symptomatic single BM of 32 mm in the maximum diameter (9.54 cm³) two months later while vacillating. A biopsy of the kidney showed clear cell carcinoma. The patient was deemed medically inoperable for BM due to unfit conditions, including severe deep venous thromboses and thrombocytopenia. Considering the tumor volume, irregular tumor configuration, non-superficial location, and mass effect, 98% of the gross tumor volume (GTV D_98%) was covered by 48.3 Gy in 7 fr with 64% isodose. Dose distribution was optimized with volumetric modulated arcs with the affirmative allowance of very inhomogeneous GTV dose. Anti-cancer medication was limited to nivolumab plus ipilimumab followed by everolismus 12 days before and during SRS, respectively. Subsequently, the patient transitioned to palliative care due to a declining general condition. Although long-term administration of steroids was required, gradual and marked tumor shrinkage (1.25 cm³, 13.1% of the initial volume) and mitigation of the peritumoral edema was observed during six months after SRS. The main location of the initial BM was deemed as intra-sulcal in the intraparietal sulcus and originated in the cerebral cortex. The patient died nine months after SRS. The gradual but remarkable tumor response obtained with 7-fr SRS alone, in this case, provides a basis to further optimize fractionated SRS dosage to enhance efficacy and safety for large and/or symptomatic RCC-BMs not amenable to immediate surgical removal, in combination with anti-cancer pharmacotherapy, if feasible, including tyrosine kinase inhibitors, which may enhance efficacy against BM and mitigate adverse effects relevant to high dose SRS.

Keywords: brain metastasis; coagulopathy; fractionation; immune ckeckpoint inhibitor; large tumor; renal cell carcinoma; stereotactic radiosurgery; tyrosine kinase inhibitor; volumetric modulated arc-based radiosurgery.

Figure 1. Magnetic resonance images before 7-fraction stereotactic radiosurgery.

The images show T2-weighted image (WI) (A); contrast-enhanced (CE) T1-WI (B-D); axial views (A, B); coronal view (C); and sagittal view (D). (A-D) All images were co-registered on dedicated software and are shown in the same magnification and coordinates. A solid and irregular-shaped mass lesion (arrow in B) in the right parietal lobe is associated with massive peritumoral edema and mass effect.

Figure 2. Target definition, dose distributions and dose-volume histograms for stereotactic radiosurgery.

The images show axial views (A-C); coronal views (D-F); target definition (A, D); representative isodose distributions (B, C, E, F); representative isodose surfaces: absolute doses (upper) and the corresponding biological effective doses with an alpha/beta ratio of 10 (BED₁₀) (G); dose-volume histograms (DVHs) (H). (A, D) A gross tumor volume (GTV) and an isotropic 2-mm margin-added object (GTV + 2 mm) for evaluation. (B, E) GTV and 64% (48.3 Gy) isodose surface (IDS) relative to the maximum dose. (C, F) The concentrically laminated steep dose gradients inside and outside the GTV boundary generated with volumetric-modulated arcs.

Figure 3. Magnetic resonance images obtained at one day before and at completion of stereotactic radiosurgery.

Images show axial T2-WI (A-D); before SRS (A, C); at completion of SRS (7 fr) (B, D); the GTV contoured on the planning T2-WI (C); and the GTV contour (dashed) superimposed on the T2-WI at 7 fr. (A-D) All images were co-registered and are shown in the same magnification and coordinates. (B, D) At completion of 7 fr SRS, a slight dorsal displacement of the GTV without significant volume change is observed due to slight mitigation of the peritumoral edema (arrow in D). WI: weighted image; SRS: stereotactic radiosurgery; fr: fraction; GTV: gross tumor volume

Figure 4. Computed tomography and magnetic resonance images before and after stereotactic radiosurgery.

The images show axial images (A-C, F-H); sagittal images (D, E, I, J); computed tomography images (A, F); CE-T1-WI (B, D, G, I); T2-WI (C, E, H, J); before SRS (A-E); at 1.9 months after SRS (F); and at 6.0 months (G-J). (A-J) All images were co-registered and are shown in the same magnification (A-J) and coordinates (A-F). (F) At 1.9 months after SRS, considerable shrinkage of the BM was observed along with modest alleviation of the perilesional edema and mass effect. (G-J) At 6.0 months, marked shrinkage of the BM and mitigation of the peritumoral edema were observed along with extrication from the mass effect. CE: contrast-enhanced; WI: weighted image; SRS: stereotactic radiosurgery; BM: brain metastasis

Figure 5. T2-weighted images before and six months after stereotactic radiosurgery.

The images show axial T2-WIs (A-J); before SRS (A-E); and at 6.0 months after SRS (F-J). (A-J) All images were co-registered and are shown in the same magnification and coordinates. (A-E) An irregularly-shaped mass (arrow in B) is surrounded by a slightly high-intensity rim (dashed arrows in B), with a high-intensity structure, possibly trapped cerebrospinal fluid, intervening these structures. (F-J) At 6.0 months after SRS, the regressed low-intensity irregular mass with continuity to part of the cortexes is mainly located between the cortexes in the intraparietal sulcus (dashed arrow in F). WI: weighted image; SRS: stereotactic radiosurgery