Background Differences in long-term outcomes of single-fraction stereotactic radiosurgery (SRS) between Gamma Knife (GK) and Linear Accelerator (LINAC) systems for vestibular schwannoma (VS) management remain unclear. To investigate differences in safety and efficacy between modalities, we conducted a meta-analysis of studies over the past decade. Methods MEDLINE, EMBASE, and Cochrane databases were queried for studies with the following inclusion criteria: English-language, published between January 2010—April 2020, cohort size ≥ 30, and mean/median follow-up ≥ 5 years. Odds ratios (OR) compared rates of tumor control, hearing preservation, and cranial nerve toxicities before and after SRS. Results Thirty-nine studies were included (29 GK, 10 LINAC) with 6,516 total patients. Tumor control rates were 93% (95% CI 91-94%) and 94% (95% CI 91-97%) for GK and LINAC, respectively. Both GK (OR 0.06, 95% CI 0.02-0.13) and LINAC (OR 0.47, 95% CI 0.29-0.76) reduced odds of serviceable hearing. Neither GK (OR 0.71, 95% CI 0.41-1.22) nor LINAC (OR 1.13, 95% CI 0.64-2.00) impacted facial nerve function. GK decreased odds of trigeminal nerve impairment (OR 0.55, 95% CI 0.32-0.94) while LINAC did not impact trigeminal nerve function (OR 1.45, 95% CI 0.81-2.61). Lastly, LINAC offered decreased odds of tinnitus (OR 0.15, 95% CI 0.03-0.87) not observed with GK (OR 0.70, 95% CI 0.48-1.01). Conclusions VS tumor control and hearing preservation rates are comparable between GK and LINAC SRS. GK may better preserve trigeminal nerve function, while LINAC decreases tinnitus rates. Future studies are warranted to investigate the efficacy of GK and LINAC SRS more directly.
Objective We sought to assess the diagnostic yield of advanced noninvasive imaging in the evaluation of patients with pulsatile tinnitus. Background Pulsatile tinnitus can be caused by high-risk cerebrovascular pathologies such as arteriovenous fistulae. The role of advanced noninvasive imaging, including magnetic resonance angiography and magnetic resonance venography, in the diagnostic evaluation of pulsatile tinnitus is not well defined. Design and methods We performed a retrospective cohort study of patients presenting for outpatient diagnostic evaluation of pulsatile tinnitus from January 2018 to March 2020 at Weill Cornell Medicine. Patients with non-pulsatile tinnitus and established etiologic diagnoses were excluded. Systematic chart abstraction was summarized using standard descriptive statistics. Univariate logistic regression was used to identify factors associated with nondiagnostic noninvasive imaging. Results A total of 187 patients (139 (74.3%) women) took part in this study, with a mean age of 48.6 years (standard deviation ( SD) = 15.5 years) and a mean body mass index (BMI) of 26.9 kg/m2 ( SD = 6.1 kg/m2). Of the 187 patients, 121 (64.7%) underwent exclusively noninvasive imaging, and 66 (35.3%) patients also had digital subtraction angiography (DSA). In patients who had exclusively noninvasive imaging, 62 (51.2%) patients received a diagnosis. In patients who underwent noninvasive and DSA imaging, 14 (21.2%) patients received a diagnosis based on DSA. Patients who were older at symptom onset (odds ratio (OR) = 1.05; 95% confidence interval (CI) 1.01–1.09) and those with a lower BMI (OR = 0.88, 95% CI 0.77–0.98) were more likely to have nondiagnostic noninvasive imaging. Conclusion Noninvasive cerebrovascular imaging often uncovers the etiology of pulsatile tinnitus. DSA remains useful for additional evaluation for patients with specific associated features.
BACKGROUND: There is increased use of neoadjuvant fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in the management of localized pancreatic ductal adenocarcinoma (PDAC), yet there are few validated biomarkers of treatment response. STUDY DESIGN: Consecutive patients (n = 196) with resectable, borderline resectable or locally advanced PDAC (2012–2019) receiving FOLFIRINOX as initial treatment and with targeted sequencing of a pretreatment biopsy were identified in a prospective institutional database. Genomic alterations were determined in the 4 driver mutations (KRAS, TP53, CDKN2A, SMAD4), and associations between genomic alterations and clinical outcomes were assessed. RESULTS: Alterations in KRAS (n = 172, 87.8%) and TP53 (n = 131, 66.8%) were common; alterations in CDKN2A (n = 49, 25.0%) and SMAD4 (n = 36, 18.4%) were less frequently observed. A total of 105 patients (53.6%) were able to undergo resection, of whom 8 (7.6%) had a complete/near-complete pathologic response. There were no somatic alterations associated with major pathologic response. Alterations in SMAD4 were associated with a lower rate of surgical resection (27.8% vs 59.4%, p < 0.001); this was additionally observed in a multivariable regression model accounting for resectability status (OR 0.35, 95% confidence interval [CI] 0.15–0.85). Thirty-three patients (16.8%) developed metastatic disease while on neoadjuvant therapy. SMAD4 alterations were associated with a significant risk of metastatic progression on therapy when controlling for resectability status (OR 3.31, 95% CI 1.44–7.60). CONCLUSIONS: SMAD4 alterations are associated with more frequent development of metastasis during neoadjuvant FOLFIRINOX and lower probability of reaching surgical resection. Evaluation of alternative chemotherapy regimens in patients with SMAD4 alterations will be important to distinguish whether this represents a prognostic or predictive biomarker.
Purpose: There is increasing use of neoadjuvant chemotherapy in the management of localized pancreatic ductal adenocarcinoma (PDAC), yet there are few validated biomarkers to guide therapy selection. We aimed to determine whether somatic genomic biomarkers predict response to induction FOLFIRINOX or gemcitabine/nab-paclitaxel. Experimental Design: This single-institution cohort study included consecutive patients (N = 322) with localized PDAC (2011–2020) who received at least one cycle of FOLFIRINOX (N = 271) or gemcitabine/nab-paclitaxel (N = 51) as initial treatment. We assessed somatic alterations in four driver genes (KRAS, TP53, CDKN2A, and SMAD4) by targeted next-generation sequencing, and determined associations between these alterations and (1) rate of metastatic progression during induction chemotherapy, (2) surgical resection, and (3) complete/major pathologic response. Results: The alteration rates in driver genes KRAS, TP53, CDKN2A, and SMAD4 were 87.0%, 65.5%, 26.7%, and 19.9%, respectively. For patients receiving first-line FOLFIRINOX, SMAD4 alterations were uniquely associated with metastatic progression (30.0% vs. 14.5%; P = 0.009) and decreased rate of surgical resection (37.1% vs. 66.7%; P < 0.001). For patients receiving induction gemcitabine/nab-paclitaxel, alterations in SMAD4 were not associated with metastatic progression (14.3% vs. 16.2%; P = 0.866) nor decreased rate of surgical resection (33.3% vs. 41.9%; P = 0.605). Major pathologic response was rare (6.3%) and not associated with type of chemotherapy regimen. Conclusions: SMAD4 alterations were associated with more frequent development of metastasis and lower probability of reaching surgical resection during neoadjuvant FOLFIRINOX but not gemcitabine/nab-paclitaxel. Confirmation in a larger, diverse patient cohort will be important before prospective evaluation of SMAD4 as a genomic biomarker to guide treatment selection.
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