Faculty Bibliography

BACKGROUND:There is a strong correlation between the level of circulating female sex hormones and the parturient growth of meningiomas. As a result, rapid changes in meningioma size occur during pregnancy, putting both the mother and fetus at risk. Large, symptomatic meningiomas require surgical resection, regardless of the status of pregnancy. However, the preferred timing of such complex intervention is a matter of debate. The rarity of this clinical scenario and the absence of prospective trials make it difficult to reach evidence-based conclusions. The aim of this study was to create evidence-based management guidelines for timing of surgery for pregnancy-related intracranial meningiomas. METHOD:The English literature from 1990 to 2016 was systematically reviewed according to PRISMA guidelines for all surgical cases of pregnancy-related intracranial meningiomas. Cases were divided into two groups: patients who have had surgery during pregnancy and delivered thereafter (group A) and patients who delivered first (group B). Groups were compared for demographic, clinical and radiological features, as well as for neurosurgical, obstetrical and neonatological outcomes. Statistical analysis was performed to assess differences. RESULTS:A total of 104 surgical cases were identified and reviewed, of which 86 were suitable for comparison and statistical analysis. Thirty-five patients (40%) underwent craniotomy for resection during pregnancy or at delivery (group A) and 51 patients (60%) underwent surgery after delivery (group B). Groups showed no significant differences in characteristics such as age at diagnosis, number of gestations, presenting symptoms, tumor site and tumor size. Despite a comparable distribution over the gestational trimesters, group A had significantly more patients diagnosed prior to the 27th gestational week (46 vs 17.5%, p = 0.0075). Group A was also associated with a significantly higher rate of both emergent craniotomies (40 vs 19.6%, p = 0.0048) and emergent Caesarian deliveries (47 vs 17.8%, p = 0.00481). The time from diagnosis to surgery was significantly longer in group B (11 weeks vs 1 week in group A, p = 0.0013). The rate of premature delivery was high but similar in both groups (∼70%). Risks of maternal mortality or fetal mortality were associated with group A (odds ratio = 14.7), but did not reach statistical significance. CONCLUSIONS:While surgical resection of meningioma during pregnancy may be associated with increased maternal and fetal mortalities, the overall neurosurgical, obstetrical and neonatological outcomes, as well as many clinical characteristics, are similar to patients undergoing resection postpartum. We believe that fetal survival chances have a significant impact on decision-making, as patients diagnosed at a later stage in pregnancy (≥27th week of gestation) were more likely to undergo delivery first. This complicated clinical scenario requires the close cooperation of multiple disciplines. While the mother's health and well-being should always be paramount in guiding management, we hope that the overall good outcomes observed by this systematic review will encourage colleagues to aim for term pregnancies whenever possible in order to reduce prematurity-related problems.

Schwannomas of cranial nerves in the absence of systemic neurofibromatosis are relatively rare. Among these, schwannomas of the trochlear nerve are even less common. They can be found incidentally or when they cause diplopia or other significant neurological deficits. Treatment options include observation only, neuro-ophthalmological intervention, and/or neurosurgical management via resection or sterotactic radiosurgery (SRS). In recent years, the latter has become an attractive therapeutic tool for a number of benign skull base neoplasm including a small number of reports on its successful use for trochlear Schwannomas. However, no treatment algorithm for the management of these tumors has been proposed so far. The goal of this manuscript is to illustrate a case series of this rare entity and to suggest a rational treatment algorithm for trochlear schwannomas, based on our institutional experience of recent cases, and a pertinent review of the literature. Including our series of 5 cases, a total of 85 cases reporting on the management of trochlear schwannomas have been published. Of those reported, less than half (40 %) of patients underwent surgical resection, whereas the remainder were managed conservatively or with SRS. Seventy-six percent (65/85) of the entire cohort presented with diplopia, which was the solitary symptom in over half of the cases (n = 39). All patients who presented with symptoms other than diplopia or headaches as solitary symptoms underwent surgical resection. Patients in the non-surgical group were mostly male (M/F = 3.5:1), presented at an older age and had shorter mean diameter (4.6 vs. 30.4 mm, p < 0.0001) when compared to the surgical group. Twelve patients in the entire cohort were treated with SRS, none of whom had undergone surgical resection before or after radiation treatment. Trochlear schwannoma patients without systemic neurofibromatosis are rare and infrequently reported in the literature. Of those, patients harboring symptomatic trochlear Schwannomas do not form a single homogenous group, but fall into two rather distinct subgroups regarding demographics and clinical characteristics. Among those patients in need of intervention, open microsurgical resection as well as less invasive treatment options exist, which all aim at safe relief of symptoms and prevention of progression. Both open microsurgical removal as well as SRS can achieve good long-term local control. Consequently, a tailored multidisciplinary treatment algorithm, based on the individual presentation and tumor configuration, is proposed.

Ependymomas of the posterior fossa in adults are relatively rare, represent less than 1% of adult intracranial gliomas. Most of the cases are WHO grade II. Due to their rarity, there are no randomized studies regarding the best management of these tumors. It seems that surgical resection has a major role in their management. Unlike the scenario in children, these tumors can be cured by gross total resection without adjuvant therapy in the majority of cases. Hence, knowing the different surgical approaches, with their pros and cons, is important in order to offer the patient the best treatment. In this paper, we review the current literature on surgery for ependymomas of the posterior fossa in adults, and the advantages and risks of the principal surgical approaches, namely the telo-velar and the transvermian, are discussed.

BACKGROUND:Stereotactic ablative radiotherapy (SABR) is an emerging therapy for primary renal cell carcinoma. The authors assessed safety, efficacy, and survival in a multi-institutional setting. Outcomes between single-fraction and multifraction SABR were compared. METHODS:Individual patient data sets from 9 International Radiosurgery Oncology Consortium for Kidney institutions across Germany, Australia, the United States, Canada, and Japan were pooled. Toxicities were recorded using Common Terminology Criteria for Adverse Events, version 4.0. Patient, tumor, and treatment characteristics were stratified according to the number of radiotherapy fractions (single vs multiple). Survival outcomes were examined using Kaplan-Meier estimates and Cox proportional-hazards regression. RESULTS:Of 223 patients, 118 received single-fraction SABR, and 105 received multifraction SABR. The mean patient age was 72 years, and 69.5% of patients were men. There were 83 patients with grade 1 and 2 toxicity (35.6%) and 3 with grade 3 and 4 toxicities (1.3%). The rates of local control, cancer-specific survival, and progression-free survival were 97.8%, 95.7%, and 77.4%, respectively, at 2 years; and they were 97.8%, 91.9%, and 65.4%, respectively, at 4 years. On multivariable analysis, tumors with a larger maximum dimension and the receipt of multifraction SABR were associated with poorer progression-free survival (hazard ratio, 1.16 [P < .01] and 1.13 [P = .02], respectively) and poorer cancer-specific survival (hazard ratio, 1.28 [P < .01] and 1.33 [P = .01], respectively). There were no differences in local failure between the single-fraction cohort (n = 1) and the multifraction cohort (n = 2; P = .60). The mean ( ± standard deviation) estimated glomerular filtration rate at baseline was 59.9 ± 21.9 mL per minute, and it decreased by 5.5 ± 13.3 mL per minute (P < .01). CONCLUSIONS:SABR is well tolerated and locally effective for treating patients who have primary renal cell carcinoma and has an acceptable impact on renal function. An interesting observation is that patients who receive single-fraction SABR appear to be less likely to progress distantly or to die of cancer. Cancer 2018;124:934-42. © 2017 American Cancer Society.

BACKGROUND:Stereotactic body radiotherapy (SBRT) is an emerging treatment option for liver metastases in patients unsuitable for surgery. We investigated factors associated with clinical outcomes for liver metastases treated with SBRT from a multi-center, international patient registry. METHODS:. Overall survival (OS) and local control (LC) were evaluated using Kaplan Meier analysis and log-rank test. RESULTS:(52 vs 39 months). There was no difference in LC based on histology of the primary tumor. CONCLUSIONS:In a large, multi-institutional series of patients with liver metastasis treated with SBRT, reasonable LC and OS was observed. OS and LC depended on dose and tumor volume, while OS varied by primary tumor. Future prospective trials on the role of SBRT for liver metastasis from different primaries in the setting of multidisciplinary management including systemic therapy, is warranted. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov: NCT01885299 .

PURPOSE/OBJECTIVE:Stereotactic radiation therapy (SRT) enables focused, short course, high dose per fraction radiation delivery to brain tumors that are less ideal for single fraction treatment because of size, shape, or close proximity to sensitive structures. We sought to identify optimal SRT treatment regimens for maximizing local control while minimizing morbidity. METHODS AND MATERIALS/METHODS:We performed a retrospective review of patients treated with SRT for solid brain metastases using variable dose schedules between 2001 and 2011 at 3 academic hospitals. Endpoints included (1) local control, (2) acute toxicity (Common Toxicity Criteria for Adverse Events v3.0), and (3) symptomatic radionecrosis. Kaplan-Meier and a competing risks methodology were used to estimate the actuarial rate of local failure and assess the association of clinical and treatment covariates with time to local failure. RESULTS:= .01, adjusted hazards ratio, 0.87). Five patients experienced seizures within 10 days of SRT and 5 patients developed radionecrosis. All patients with documented radionecrosis received prior radiation to the index lesion. CONCLUSIONS:Our series of SRT for brain metastases found total prescription dose to be the only factor associated with local control. Both acute and long-term toxicity events from SRT were modest.

Brain metastases are relatively uncommon in gynecological malignancies, and there is limited available data on their management. The present study reports the outcomes of patients with brain metastasis from gynecological malignancies who were treated with stereotactic radiosurgery (SRS). Patients with brain metastasis from a gynecological primary site were treated with SRS using the Cyberknifeâ„¢ frameless SRS system. Primary lesions were treated with a single fraction of 16-22 Gy. A total of 3 resection cavities were treated with 8 Gy 3 times, meaning a total of 24 Gy, and 1 recurrent lesion was re-irradiated with 5 Gy 5 times, meaning a total of 25 Gy. All patients were followed up with regular magnetic resonance imaging and clinical examinations 1 month after treatment and every 2 months thereafter. A total of 20 lesions in 8 patients were included in this study; 1 patient presented with metastatic endometrial cancer and the remaining 7 presented with metastatic ovarian cancer. The median age was 61 years (range, 48-78 years). All patients had received systemic therapy prior to developing brain metastasis. A total of 3 patients underwent surgical resection and 1 patient was administered re-irradiation for recurrence. There were 3 local failures in 2 patients. The actuarial 1-, 2- and 3-year local control rates were 91, 91 and 76%, respectively. The median overall survival time was 29 months. No SRS-associated toxicities or neurological mortalities were observed. In conclusion, brain metastasis from gynecological malignancies is uncommon, however, SRS is a safe and effective treatment modality for local control as a primary or adjuvant treatment in patients with this disease.

BACKGROUND:Survival in pancreatic cancer remains poor with curative potential dependent on operative resection. We reviewed national adherence to practice guidelines to evaluate regional variation in the treatment and survival of patients with pancreatic cancer. METHODS:Retrospective cohort review of adults with pancreatic adenocarcinoma using the National Cancer Data Base from 2006 to 2013. Overall survival was compared by the Kaplan-Meier method and Cox proportional hazards models. Sequential multivariate logistic regression models were generated for odds of: a) diagnosis in stage I/II, b) resection, and c) receipt of multimodality therapy, defined as operative resection plus chemotherapy with or without radiation. Five geographic regions of the United States were used for analyses. RESULTS:A total of 115,952 patients were identified. At least 22% of patients in all stages received no treatment, with only 38.4% and 32.3% of stage I and II patients receiving multimodality therapy. On unadjusted analysis, the Northeast had the greatest survival for all stages of disease, most pronounced for stage I where patients lived 2 to 3 more months (log-rank P < .0001). While adjusted odds of early diagnosis and resection were comparable or greater across regions relative to the Northeast, patients who underwent resection in the Northeast were significantly more likely to receive multimodality therapy. Multivariate Cox modeling for patients receiving multimodality therapy accounted for differences in 3 of 4 remaining regions. CONCLUSION:Regional variations exist in pancreatic cancer treatment and survival. While providing multimodality cancer-directed therapy can help mitigate these differences, survival with pancreatic cancer needs to be interpreted in the context of overall health, underlying risk factors, and life expectancy.

BACKGROUND:The role of conventional radiotherapy in the management of pancreatic cancer has yet to be elucidated. Over the past decade, stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option in pancreatic cancer care. This study evaluated the survival impact of SBRT on patients with unresected pancreatic cancer. METHODS:The National Cancer Data Base was queried for unresected patients who received chemotherapy for nonmetastatic pancreatic adenocarcinoma between 2004 and 2012. Four treatment groups were identified: chemotherapy alone, chemotherapy combined with external-beam radiotherapy (EBRT), chemotherapy combined with intensity-modulated radiotherapy (IMRT), and chemotherapy combined with SBRT. Propensity score models predicting the odds of receiving SBRT were created to control for potential selection bias, and patients were matched by propensity scores. The survival analysis was performed with the Kaplan-Meier method. RESULTS:A total of 14,331 patients met the inclusion criteria. Chemotherapy alone was delivered to 5464 patients (38.1%); 6418 (44.8%), 322 (2.3%), and 2127 (14.8%) received chemotherapy along with EBRT, IMRT, and SBRT, respectively. The unadjusted median survival before matching was 9.9, 10.9, 12.0, and 13.9 months for patients treated with chemotherapy, EBRT, IMRT, and SBRT, respectively. In separate matched analyses, SBRT remained superior to chemotherapy alone (log-rank P < .0001) and EBRT (log-rank P = .0180). After matching, survival did not differ between patients receiving IMRT and patients receiving SBRT (log-rank P = .0492). CONCLUSIONS:SBRT is associated with a significantly better outcome than chemotherapy alone or in conjunction with traditional EBRT. These results support the idea that SBRT is a promising treatment approach for patients with unresected pancreatic cancer. Cancer 2017;123:4158-4167. © 2017 American Cancer Society.

Adjuvant chemotherapy plays a critical role in the treatment of resected pancreatic cancer patients. However, the role of adjuvant radiation remains controversial. This study compares survival between resected pancreatic cancer patients who received adjuvant radiation and no adjuvant radiation. Medical records of patients with pancreatic ductal adenocarcinoma who underwent surgical resection from January 2003 through 2013 at medical centers in Boston and Leiden were retrospectively reviewed. Propensity score matching was used to correct for potential selection bias in the allocation of adjuvant chemoradiation versus chemotherapy alone. Three hundred fifty total patients were identified, of whom 138 (39.4%) received adjuvant radiation. On pathological staging, 245 (70.0%) had positive lymph nodes, and these patients gained a significant survival benefit from adjuvant radiation (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.56-0.99) in the complete cohort. After propensity score matching, adjuvant radiation lost its prognostic significance in the complete cohort. However, after matching, patients who survived longer than 12 months and had positive lymph nodes (n = 108) demonstrated a significant (log-rank p = 0.04) survival benefit from adjuvant radiation. This study, while non-randomized, suggests that adjuvant radiation may be associated with a survival benefit for resected pancreatic cancer patients in specific situations.