Jonathan Weller

Advanced breast cancer is associated with the development of brain metastases in 20%–40% of patients. Differential post‐radiotherapy recurrence patterns depending on hormone receptor (HR) and human epidermal growth receptor 2 (HER2) status have been reported. We investigated recurrence patterns after microsurgical resection stratified for HR and HER2 expression. The institutional database was screened for patients who had undergone tumor resection for breast cancer brain metastases between 2013 and 2023. Patient and imaging data were analyzed. Response Assessment in Neuro‐Oncology (RANO) guidelines were applied. Sixty‐seven patients were identified. Nineteen patients (28%) were diagnosed with HR+/HER2−, 31 patients (46%) with HER2+, and 17 patients (25%) with triple‐negative (TN) brain metastases. Local, i.e., in or adjacent to the resection cavity, or distant brain‐specific progression‐free survival (PFS) was shortest in patients with TN status, followed by patients with HER2+ and HR+/HER2− brain metastases (median: 170 vs. 419 vs. 1152 days; p < .01). Patients with HER2+ brain metastases showed earlier local progression than patients with HR+/HER2− status (HR 0.25; 95% CI 0.08–0.75; p = .01). The receptor status of the brain metastases diverged from the primary tumor in 13 patients (21%). In five patients (8%), a newly gained HR or HER2 expression was detected. Post‐surgery recurrence patterns of breast cancer brain metastases are associated with the tumor biology. TN brain metastases show earliest local and distant recurrence, confirming the pressing need for better local and systemic treatments. As HER2+ brain metastases tend to recur locally, refinement of local strategies might be warranted.

Conditional survival provides insights into the evolution of prognosis over time and reveals changing associations of prognostic factors during disease progression. Data on the temporal evolution of prognostic factors in glioblastoma remain scarce. We analyzed 315 patients with IDH‐wildtype glioblastoma from a prospectively collected registry (01/2008–06/2017). Our primary outcome was 12‐month conditional survival (CS), defined as the probability of surviving the next 12 months given survival for “ s ” months. This analysis was conducted at five landmarks ( s = 0, 6, 12, 18, 24) for baseline prognostic factors, including tumor volume compartments. 12‐month conditional survival estimates at s = 0, 6, 12, 18, and 24 months from diagnosis were 0.51 (95% CI 0.45–0.56), 0.46 (95% CI 0.39–0.52), 0.41 (95% CI 0.33–0.49), 0.43 (95% CI 0.33–0.52), and 0.56 (95% CI 0.42–0.67), respectively. At diagnosis ( s = 0), 12‐month survival estimates varied significantly with age >60 at diagnosis, preoperative tumor rim volume >20 cm ³ , absence of O ⁶ ‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation, postoperative KPS ≥70, residual postoperative tumor >1 cm ³ , or biopsy only. Residual tumor volume mainly influences survival in the initial months following surgery, while MGMT promoter methylation and age remain significant predictors beyond this period. These findings may refine stratification strategies in recurrent glioblastoma trials.

Background: Survival times of patients with IDH-mutant gliomas are variable and can extend to decades. Many studies provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored characteristics of short- and long-term survivors within a cohort of patients with extended follow-up. Methods: This single-center, case-control study included 86 patients diagnosed between 1998 and 2023 who either died within 6 years after diagnosis or survived at least 15 years. Patient characteristics and prognostic factors were stratified by short- (< 6 years) versus long-term (≥ 15 years) survival. Results: Forty-seven patients (55%) diagnosed with astrocytoma and 39 patients (45%) with oligodendroglioma were included retrospectively. Median follow-up of the survivors was 16.6 years (range 15-28.9). Thirty-four deaths (40%) had been reported at database closure. Long-term survival was associated with CNS WHO grade 2 (p < 0.01), smaller tumor volumes (p = 0.01), lack of contrast enhancement (p < 0.01), wait-and-scan strategies (p < 0.01) and female sex (p = 0.04). In multivariate analyses for oligodendroglioma, larger T2 tumor volumes were associated with shorter survival (HR 1.02; 95% CI 1.01–1.05; p = 0.04). In patients with astrocytoma, lack of contrast enhancement (HR 0.38; 95% CI 0.15–0.94; p = 0.04) and wait-and-scan strategies (HR 5.75; 95% CI 1.66–26.61; p = 0.01) were associated with longer survival. Conclusion: Large T2 tumor volume and contrast enhancement may be important risk factors for shorter survival, while age might be of lesser importance. Wait-and-scan strategies may yield excellent long-term survival in some patients with astrocytoma.

BACKGROUND AND OBJECTIVES: Isocitrate dehydrogenase (IDH)–mutant astrocytomas central nervous system World Health Organization grade 2 and 3 show heterogeneous appearance on MRI. In the premolecular era, the discrepancy between T1 hypointense and T2 hyperintense tumor volume in absolute values has been proposed as a marker for diffuse tumor growth. We set out to investigate if a ratio of T1 to T2 tumor volume (T1/T2 ratio) is associated with resectability and overall survival (OS) in patients with IDH-mutant astrocytomas. METHODS: Patient data from 2 centers (Sahlgrenska University Hospital, Center A; LMU University Hospital, Center B) were collected retrospectively. Inclusion criteria were as follows: pre and postoperative MRI scans available for volumetric analysis (I), diagnosis of an IDH-mutant astrocytoma between 2003 and 2021 (II), and tumor resection at initial diagnosis (III). Tumor volumes were manually segmented. The T1/T2 ratio was calculated and correlated with extent of resection, residual T2 tumor volume, and OS. RESULTS: The study comprised 134 patients with 65 patients included from Center A and 69 patients from Center B. The median OS was 134 months and did not differ between the cohorts (P = .29). Overall, the median T1/T2 ratio was 0.79 (range 0.15-1.0). Tumors displaying a T1/T2 ratio of 0.33 or lower showed significantly larger residual tumor volumes postoperatively (median 17.9 cm³ vs 4.6 cm³, P = .03). The median extent of resection in these patients was 65% vs 90% (P = .03). The ratio itself did not correlate with OS. In multivariable analyses, larger postoperative tumor volumes were associated with shorter survival times (hazard ratio 1.02, 95% CI 1.01-1.03, P < .01). CONCLUSION: The T1/T2 ratio might be a good indicator for diffuse tumor growth on MRI and is associated with resectability in patients with IDH-mutant astrocytoma. This ratio might aid to identify patients in which an oncologically relevant tumor volume reduction cannot be safely achieved.

Purpose: To assess accuracy, the frequency of hemorrhagic complications and computed tomography (CT) radiation dose parameters in pediatric patients undergoing landmark-guided external ventricular drain (EVD) placement in an emergency setting. Methods: Retrospective analysis comprised 36 EVD placements with subsequent CT control scans in 29 patients (aged 0 to 17 years) in our university hospital from 2008 to 2022. The position of the EVD as well as the presence and extension of bleeding were classified according to previously established grading schemes. Dose length product (DLP), volume-weighted CT dose index (CTDI_vol) and scan length were extracted from the radiation dose reports and compared to the diagnostic reference values (DRLs) issued by the German Federal Office for Radiation Protection. Results: After the initial EVD placement, optimal positioning of the catheter tip into the ipsilateral frontal horn or third ventricle (Grade I), or a functional positioning in the contralateral lateral ventricle or the non-eloquent cortex (Grade II), was achieved in 28 and 8 cases, respectively. In 32 of 36 procedures, no evidence of hemorrhage was present in the control CT scan. Grade 1 (vol (median [25%; 75% quartile]) was 39.92 [30.80; 45.55] mGy, DLP yielded 475.50 [375.00; 624.75] mGy*cm and the scan length result was 136 [120; 166] mm. Exceedances of the DRL values were observed in 14.5% for CTDI_vol, 12.7% for DLP and 65.6% for the scan length. None of these values was in the range requiring a report to the national authorities. Conclusion: Landmark-based emergency EVD placement in pediatric patients yielded an optimal position in most cases already after the initial insertion. Complications in terms of secondary hemorrhages are rare. CT dose levels associated with the intervention are below the reportable threshold of the national DRLs in Germany.

Purpose: The role of temozolomide chemotherapy alone in isocitrate dehydrogenase (IDH)-mutant astrocytomas has not been conclusively determined. Radiotherapy might be superior to temozolomide. Recent studies have linked temozolomide with induction of hypermutation and poor clinical course in some IDH-mutant gliomas. Methods: In this retrospective study, 183 patients with astrocytoma, IDH-mutant, CNS WHO grade 2 or 3 and diagnosed between 2001 and 2019 were included. Patients initially monitored by wait-and-scan strategies or treated with radiotherapy or temozolomide alone were studied. Patient data were correlated with outcome. Matched pair and subgroup analyses were conducted. Results: Radiotherapy was associated with longer progression-free survival than temozolomide (6.2 vs 3.4 years, p = 0.02) and wait-and-scan strategies (6.2 vs 4 years, p = 0.03). Patients treated with radiotherapy lived longer than patients treated with temozolomide (14.4 vs 10.7 years, p = 0.02). Survival was longer in the wait-and-scan cohort than in the temozolomide cohort (not reached vs 10.7 years, p < 0.01). Patients from the wait-and-scan cohort receiving temozolomide at first progression had significantly shorter survival times than patients treated with any other therapy at first progression (p < 0.01). Post-surgical T2 tumor volume, contrast enhancement on MRI and WHO grade were associated with overall survival in univariate analyses (p < 0.01). Conclusion: The results suggest superiority of radiotherapy over temozolomide and wait-and-scan strategies regarding progression-free survival and superiority of radiotherapy over temozolomide regarding overall survival. Our results are consistent with the notion that early temozolomide might compromise outcome in some patients.

PURPOSE The role of temozolomide chemotherapy alone in isocitrate dehydrogenase (IDH)-mutant astrocytomas has not been conclusively determined. Radiotherapy might be superior to temozolomide. Recent studies have linked temozolomide with induction of hypermutation and poor clinical course in some IDH-mutant gliomas. METHODS In this retrospective study, 183 patients with astrocytoma, IDH-mutant, CNS WHO grade 2 or 3 and diagnosed between 2001 and 2019 were included. Patients initially monitored by wait-and-scan strategies or treated with radiotherapy or temozolomide alone were studied. Patient data were correlated with outcome. Matched pair and subgroup analyses were conducted. RESULTS Radiotherapy was associated with longer progression-free survival than temozolomide (6.2 vs 3.4 years, p = 0.02) and wait-and-scan strategies (6.2 vs 4 years, p = 0.03). Patients treated with radiotherapy lived longer than patients treated with temozolomide (14.4 vs 10.7 years, p = 0.02). Survival was longer in the wait-and-scan cohort than in the temozolomide cohort (not reached vs 10.7 years, p < 0.01). Patients from the wait-and-scan cohort receiving temozolomide at first progression had significantly shorter survival times than patients treated with any other therapy at first progression (p < 0.01). Post-surgical T2 tumor volume, contrast enhancement on MRI and WHO grade were associated with overall survival in univariate analyses (p < 0.01). CONCLUSION The results suggest superiority of radiotherapy over temozolomide and wait-and-scan strategies regarding progression-free survival and superiority of radiotherapy over temozolomide regarding overall survival. Our results are consistent with the notion that early temozolomide might compromise outcome in some patients.

Introduction: The role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy. Methods: Patients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy. Presurgical MRI T2 tumor volumes were obtained by manual segmentation. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of histological progression to grade 3 were analyzed. Results: PFS was longest after PCV (9.1 years), compared to 5.1 years after W&S, 4.4 years after RES and 3.6 years after TMZ. The rate of histological progression from grade 2 to 3 within 10 years was 9% for the PCV, 29% for the W&S, 67% for the RES and 75% for the TMZ group (p = 0.01). In the W&S group, patients treated with PCV at first relapse had a longer PFS from intervention than those treated with TMZ (7.2 vs 4.0 years, p = 0.04). Multivariate analysis identified smaller tumor volume prior to any intervention (p = 0.02) to be prognostic for PFS. Conclusions: PCV chemotherapy alone is an effective treatment for WHO grade 2 oligodendroglioma, with long PFS and low rate of histological progression.

Interstitial photodynamic therapy (iPDT) using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) as a cytotoxic photosensitizer could be a feasible treatment option for malignant gliomas. In a monocentric cohort of consecutive patients treated between 2006 and 2018, a risk profile analysis of salvage iPDT for local malignant glioma recurrences and associated outcome measures are presented here. It was considered indicated in patients with circumscribed biopsy-proven malignant glioma recurrences after standard therapy, if not deemed eligible for safe complete resection. A 3D treatment-planning software was used to determine the number and suitable positions of the cylindrical diffusing fibers placed stereotactically to ensure optimal interstitial irradiation of the target volume. Outcome measurements included the risk profile of the procedure, estimated time-to-treatment-failure (TTF), post-recurrence survival (PRS) and prognostic factors. Forty-seven patients were treated, of which 44 (median age, 49.4 years, range, 33.4–87.0 years, 27 males) could be retrospectively evaluated. Recurrent gliomas included 37 glioblastomas (WHO grade IV) and 7 anaplastic astrocytomas (WHO grade III). Thirty (68.2%) tumors were O-6-methylguanine-DNA methyltransferase (MGMT)-methylated, 29 (65.9%)—isocitrate dehydrogenase (IDH)-wildtype. Twenty-six (59.1%) patients were treated for their first, 9 (20.5%)—for their second, 9 (20.5%)—for the third or further recurrence. The median iPDT target volume was 3.34 cm³ (range, 0.50–22.8 cm³). Severe neurologic deterioration lasted for more than six weeks in one patient only. The median TTF was 7.1 (95% confidence interval (CI), 4.4–9.8) months and the median PRS was 13.0 (95% CI, 9.2–16.8) months. The 2- and 5-year PRS rates were 25.0% and 4.5%, respectively. The treatment response was heterogeneous and not significantly associated with patient characteristics, treatment-related factors or molecular markers. The promising outcome and acceptable risk profile deserve further prospective evaluation particularly to identify mechanisms and prognostic factors of favorable treatment response.