Arnold M. Herskovic

Brain metastases in patients with renal cell carcinoma: prognosis and treatment.

Thirty-four patients with renal cell carcinoma and brain metastases were reviewed to define important prognostic factors and treatment results. The following covariates were analyzed to determine their influence on survival: disease-free interval, serum calcium, number of central nervous system (CNS) metastases, weight loss, performance score, age, radiation therapy, surgery, and surgery plus radiation. The mean survival for all patients was 7.0 months (range, seven days to 32 months). The patients with a good performance score of 0-2 survived significantly longer (mean survival, 10.2 months) than those with a poor performance score of 3-4 (mean survival, 2.8 months; p = 0.0019). Surgery was associated with significantly improved survival (mean survival, 13.8 months versus mean survival, 4.2 months; p = 0.014). However, all the surgical patients were from the good performance score group, suggesting patient selection. Radiation was associated with an improved mean survival of 8.6 months versus 3.2 months. Performance score is a significant prognostic factor. Furthermore, the data support treatment with radiation therapy for patients with multiple CNS metastases and surgery followed by postoperative radiation therapy for patients with single CNS metastases.

Cognitive Sparing during the Administration of Whole Brain Radiotherapy and Prophylactic Cranial Irradiation: Current Concepts and Approaches

Whole brain radiotherapy (WBRT) for the palliation of metastases, or as prophylaxis to prevent intracranial metastases, can be associated with subacute and late decline in memory and other cognitive functions. Moreover, these changes are often increased in both frequency and severity when cranial irradiation is combined with the use of systemic or intrathecal chemotherapy. Approaches to preventing or reducing this toxicity include the use of stereotactic radiosurgery (SRS) instead of WBRT; dose reduction for PCI; exclusion of the limbic circuit, hippocampal formation, and/or neural stem cell regions of the brain during radiotherapy; avoidance of intrathecal and/or systemic chemotherapy during radiotherapy; the use of high-dose, systemic chemotherapy in lieu of WBRT. This review discusses these concepts in detail as well as providing both neuroanatomic and radiobiologic background relevant to these issues.

Intracranial Metastatic Disease Spares the Limbic Circuit: A Review of 697 Metastatic Lesions in 107 Patients

PURPOSE We report the incidence of metastatic involvement of the limbic circuit in a retrospective review of patients treated at our institution. This review was performed to assess the feasibility of selectively sparing the limbic system during whole-brain radiotherapy and prophylactic cranial irradiation. METHODS AND MATERIALS We identified 697 intracranial metastases in 107 patients after reviewing contrast-enhanced CT and/or MR image sets for each patient. Lesions were localized to the limbic circuit or to the rest of the brain/brain stem. Patients were categorized by tumor histology (e.g., non-small-cell lung cancer, small-cell lung cancer, breast cancer, and other) and by total number of intracranial metastases (1-3, oligometastatic; 4 or more, nonoligometastatic). RESULTS Thirty-six limbic metastases (5.2% of all metastases) were identified in 22 patients who had a median of 16.5 metastases/patient (limbic metastases accounted for 9.9% of their lesions). Sixteen metastases (2.29%) involved the hippocampus, and 20 (2.86%) involved the rest of the limbic circuit; 86.2% of limbic metastases occurred in nonoligometastatic patients, and 13.8% occurred in oligometastatic patients. The incidence of limbic metastases by histologic subtype was similar. The incidence of limbic metastases in oligometastatic patients was 4.9% (5/103): 0.97%, hippocampus; 3.9%, remainder of the limbic circuit. One of 53 oligometastatic patients (1.9%) had hippocampal metastases, while 4/53 (7.5%) had other limbic metastases. CONCLUSIONS Metastatic involvement of the limbic circuit is uncommon and limited primarily to patients with nonoligometastatic disease, supporting our hypothesis that it is reasonable to selectively exclude or reduce the dose to the limbic circuit when treating patients with prophylactic cranial irradiation or whole-brain radiotherapy for oligometastatic disease not involving these structures.

Sparing of the Neural Stem Cell Compartment During Whole-Brain Radiation Therapy: A Dosimetric Study Using Helical Tomotherapy

PURPOSE To assess the feasibility of dosimetrically sparing the hippocampus and neural stem cell (NSC) compartment during whole-brain radiotherapy (WBRT) and prophylactic cranial irradiation (PCI). METHODS AND MATERIALS We contoured the brain/brainstem on fused magnetic resonance /computed tomography images as the planning target volume (PTV) in 10 patients, excluding the hippocampus and NSC compartment as organs at risk. PCI and WBRT helical tomotherapy plans were prepared for each patient, with 1.0-cm field width, a pitch of 0.285, and a modulation factor of 2.5. We attempted to maximally spare the hippocampus and NSC compartment while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with a V(100) of ≥95%. Plan quality was assessed by calculating mean dose, equivalent uniform dose (EUD), and biologically equivalent dose (BED) for organs at risk and the percent volume of the PTV receiving the prescribed dose of V(100). RESULTS In the PCI plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.5 Gy/13.1 Gy/15.7 Gy(2) (BED assuming alpha/beta ratio of 2Gy) and 11.5 Gy/13.1 Gy/12.3 Gy(10) (BED assuming alpha/beta ratio of 10Gy), respectively. In the WBRT plans, mean doses/EUD/BED for the hippocampus and NSC compartment were 11.8 Gy/14.8 Gy/16.8 Gy(2) and 11.8 Gy/14.8 Gy/12.8 Gy(10), respectively. The mean V(95) for the rest of the brain (PTV) was 96.9% for both the PCI and WBRT plans. Mean PCI and WBRT treatment times were 15.93 min (range, 14.28 min-17.50 min) and 20.18 min (range, 18.43 min-22.32 min), respectively. CONCLUSIONS It is dosimetrically feasible to spare the hippocampus and NSC compartment using helical tomotherapy during the administration of whole-brain irradiation.

Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: A dosimetric study using helical tomotherapy.

Introduction:  The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI).

ORIGINAL ARTICLE: Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: A dosimetric study using helical tomotherapy

Introduction:  The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI).

High-Grade Glioma Relationship to the Neural Stem Cell Compartment: A Retrospective Review of 104 Cases

PURPOSE To assess the incidence of involvement of the neural stem cell (NSC) compartment by high-grade astrocytomas in a series of adult patients. METHODS AND MATERIALS One hundred four initial diagnostic cranial magnetic resonance imaging series were reviewed. For each series, the gross tumor volume (GTV; enhancing tumor on T(1)), edema (hyperintensity on T(2) FLAIR), and the NSC compartment (hippocampal formation and lateral ventricle plus a 5-mm expansion) were identified. Involvement of NSC by GTV and edema was assessed. For tumors not involving NSC, we measured distances from NSC to GTV and edema. Maximum diameters of GTV were measured for each case. Subset analysis was performed for GTV of ≤ 2 cm and ≤ 3 cm in maximum diameter to assess the incidence of involvement of NSC by this group of smaller tumors. For 10 representative tumors, minimum distances from GTV center to NSC were calculated. RESULTS A total of 103/104 (99.0%) tumors, regardless of GTV maximum diameter, demonstrated involvement of NSC. A total of 101/104 (97.1%) tumors had NSC involvement by GTV, and 2/104 (1.9%) patients showed edema only. For GTV not involving NSC, the mean distance from NSC to GTV was 0.8 cm (range, 0.5--1.4 cm). The mean shortest distance from the center of GTV to NSC was 1.5 cm (range, 0.9--2.6 cm). Involvement of NSC by GTV was 90.9% (10/11 tumors) for GTV of ≤ 2 cm and 95.7% (22/23 tumors) for GTV of ≤ 3 cm. CONCLUSIONS Our results support the hypothesis that the NSC compartment represents the putative site of origin for these tumors. NSC involvement does not appear to represent a volumetric phenomenon.

ORIGINAL ARTICLE: Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: A dosimetric study using helical tomotherapy: Limbic sparing WBRT and PCI

Introduction:  The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI).