Multi-institutional Retrospective Review Research Articles

Smell Preservation following Unilateral Endoscopic Transnasal Approach to Resection of Olfactory Groove Meningioma: A Multi-institutional Experience.

Introduction Olfactory groove meningiomas (OGMs) are often associated with loss of smell following resection. Loss of smell has a measurable impact on quality of life. Smell preservation has been previously described in open approaches for early stage or unilateral OGMs. Evidence of smell preservation in endoscopic approaches is lacking. Design A multi-institutional retrospective review was performed on consecutive patients who underwent unilateral endoscopic endonasal resection of OGM. A gross total resection was achieved with preservation of the contralateral olfactory cleft and bulb. Olfactory function was assessed with a six-point olfactory symptom score and the Sniffin' Sticks 12-item smell identification test (SS-12). Contralateral olfactory bulb volume was measured on postoperative magnetic resonance imaging. Results Four patients (age 42.0 ± 7.5, 75% female) were assessed. Olfactory function was assessed at 21.8 ± 5.6 months following surgery. All patients reported some degree of smell preservation (75% described a slight/mild impairment in smell or better). Olfactory identification was preserved with an SS-12 score of 9 ± 1.4 (anosmia defined as ≤6). The olfactory bulb volume was calculated to be 47.4 ± 15.9 mm 3 (normal >40 mm 3 ). Conclusion Smell preservation is possible following unilateral endoscopic endonasal resection of carefully selected OGM.

Off label targeted therapy use in adolescents and young adults with sarcoma.

e21504 Background: Outcomes for patients with metastatic or recurrent sarcomas remains dismal with < 20% overall survival. Due to the rarity of sarcomas, the development, testing, and approval of new therapies takes years. Most early phase clinical trials are restricted to adults leaving young patients with limited options. Little is known about the prevalence and clinical characteristics of patients receiving off-label targeted therapy (OLTT). In this multi-institutional retrospective review we evaluated OLTT use in this population. Methods: Patients with recurrent sarcoma diagnosed between the years of 2008 – 2016 were identified at six institutions. Charts were reviewed for OLTT use and additional clinical characteristics. ANOVA [Analysis of Variance] and Kruskal Wallis Rank sum tests were used for normally and non-normally distributed continuous data. Categorical data was analyzed using chi-squared tests or fisher exact tests. Results: The prevalence of OLTT use was 29% for the patients included in our analysis. Of the 99 cases, the mean age for OLTT was 18 years, ranging 3 – 34 years. Nearly half had recurrent tumor in multiple sites at the time of OLTT use, and 64% did not undergo resection prior to OLTT. Lack of clinical trial availability was the most common reason for OLTT use (31% of cases). The most common OLTT drug class used were tyrosine kinase inhibitors. Progression in 81% of cases was the primary reason for stopping OLTT and toxicity limited use in 12% of cases. One case had a complete response, 5 cases had a partial response and 4 cases had stable disease per RECIST. Conclusions: OLTT use is exceedingly prevalent in patients with recurrent sarcoma. Clinical trials for children and adolescents with recurrent sarcoma will identify optimal agents to improve outcomes in this understudied population.

Rethinking breast cancer surveillance in women with BRCA-associated ovarian cancer in the post-solo trial era.

5565 Background: Patients with BRCA mutations are at increased risk of developing both breast (BC) and epithelial ovarian cancer (EOC). Optimal breast cancer surveillance guidelines for BRCA mutation carriers following EOC has not been defined due to high risk of EOC recurrence. The recent SOLO-1 trial demonstrated a survival benefit of olaparib maintenance therapy for newly diagnosed women with advanced stage EOC. Olaparib reduced the risk of disease-progression or death by 70% compared to placebo with a median progression-free survival (PFS) of 36 months. Methods: An IRB-approved, multi-institutional study retrospective chart review was performed. Patients had BRCA-associated EOC diagnosed between 1990-2015 without a history of prior BC or mastectomy. All women received combination chemotherapy for EOC. The observed breast cancer free survival was adjusted to reflect the enhanced 3-year PFS observed in olaparib-treated women from the SOLO-1 trial. Kaplan-Meier survival curves were performed. Results: 191 patients with BRCA-associated EOC were included (135 BRCA1, 55 BRCA2, 1 BRCA1 and BRCA2). Median age was 53 years. Most women had advanced stage, high-grade serous EOC (75%). The median overall survival was 7.7 years for BRCA 1, and 9.7 years for BRCA2 mutation carriers. Annual mammography and MRI were performed in 43% and 34% of women, respectively, with a median of 4 mammograms and 3 MRI per patient. 16 women (8.3%) were diagnosed with BC over a median follow up of 80 months: 7 (44%) DCIS and 9 (56%) invasive ductal carcinoma. 14 (88%) women had early stage (0-2) BC. 28 (15%) of women had risk-reducing mastectomy performed an average of 2.1 years following their EOC diagnosis. The incidence of BC increased from 5.6% to 11% at 5- and 10-years post EOC, and in the predicted model with olaparib, from 10% to 17% at 5- and 10-years, assuming olaparib does not impact breast cancer incidence. Conclusions: The risk of metachronous BC following BRCA-associated EOC increases over time. In the post SOLO trial era, BC surveillance strategies in women with EOC should be optimized to reflect improved outcome. [Table: see text]

Recurrence rates in cervical cancer patients treated with abdominal versus minimally invasive radical hysterectomy: A multi-institutional analysis of 700 cases.

5504 Background: Compare outcomes between open and minimally invasive radical hysterectomy. Methods: Retrospective multi-institutional review of patients undergoing radical hysterectomy for stage IA1, IA2 and IB1 squamous, adeno- or adeno-squamous carcinoma between 01/01/2010 - 12/31/2017. Results: From 704 cases that met the inclusion criteria, 185 (26.3%) underwent open and 519 (73.7%) underwent minimally invasive surgery (MIS). Women treated with open surgery were older, had larger tumors on preoperative assessment as well as on final pathology assessment, had higher proportion of patients with IB1 stage and adjuvant therapy. Patients undergoing open surgery had longer median follow-up compared to MIS (44 vs. 30.3 months, p < 0.001). The two groups were similar in regard to race distribution, body mass index, comorbidities and preoperative histology. There were 13/185 (7%) recurrences and 10/185 (5.4%) deaths in the open compared to 42/519 (8.1%) recurrences and 26/519 (5%) deaths in MIS (p = n.s for both). However, on multivariate analysis, after controlling for race, comorbidities, preoperative tumor size, histology, grade and smoking status, MIS had higher odds of recurrence (OR 2.24, 95% CI 1.04 - 4.87, p = 0.04). On a second model, in addition to prior mentioned factors, we included lymphovascular space invasion, receipt of adjuvant therapy and vaginal margin status. Undergoing MIS remained associated with higher odds of recurrence (OR 2.37, 95% CI 1.1 - 5.1, p = 0.031). On sub-group analysis of cases with preoperative tumor size less than equal to 2 cm, there were 5/121 (4.1%) recurrence in open and 25/415 (6%) recurrences in MIS group (p = 0.34). Multivariate analysis did not show a higher rate of recurrence in MIS arm in this subgroup. In 26 cases of MIS where no vaginal manipulator was used, no recurrences were noted. In comparison 19/270 (7%) recurrences were noted in intra-uterine manipulator (V-care/Zumi/Rumi) and 22/210 (11%) in vaginal manipulators (EEA sizer/Colpo Probe) groups (p = 0.119). Conclusions: In this large retrospective analysis, patients undergoing MIS for early stage cervical cancer had higher odds of recurrence. In patients with 2 cm or less tumor on preoperative assessment, recurrence rates were similar between the two groups. Role of manipulator in increasing recurrence should be further studied in this patient population.

Thyroid eye disease presenting with superior rectus/levator complex enlargement

ABSTRACTPurpose: To describe the demographic and clinical characteristics of patients with thyroid eye disease (TED) who present with predominate superior rectus/levator complex involvement.Methods: A multi-institutional retrospective review was performed to identify patients with TED who presented with superior isolated or predominate rectus/levator involvement. Baseline and subsequent visits were reviewed to characterize the clinical course.Results: Nineteen patients were identified. All patients had imaging demonstrating an enlarged levator/superior rectus complex. At presentation, the mean clinical activity score (CAS) was 2.1 (range: 0–5). Nineteen (100%) patients had proptosis on the affected side. Lid abnormalities, including upper/lower eyelid retraction and ptosis were higher on affected side compared to the unaffected side. Eleven (58%) patients had vertical misalignment. Mean thyroid stimulating immunoglobulin (TSI) was 3.7 (range: 1–7.1). Mean follow-up time was 18 months (range: 0–60 months). At last follow-up, the mean CAS was 1.3 (range 0–5). Ten (53%) patients had proptosis. Eleven (58%) patients had vertical misalignment. Repeat imaging in eight patients showed interval enlargement of other extraocular muscles.Conclusions: The presentation of TED with superior rectus/levator complex enlargement may be under-appreciated. Orbital imaging, as well as laboratory evaluation, may help support a diagnosis of TED. In the setting of abnormal TSI and/or thyrotropin receptor antibody, presence of upper eyelid retraction, and an otherwise unremarkable laboratory and systemic evaluation, a presumptive diagnosis of TED may be made, and the patient can be followed closely, as he/she is likely to develop involvement of other extraocular muscles, consistent with a more typical presentation of TED.

Variability in perioperative evaluation and resource utilization in pediatric patients with suspected biliary dyskinesia: A multi-institutional retrospective cohort study

IntroductionBiliary dyskinesia (BD) is a common indication for pediatric cholecystectomy. While diagnosis is primarily based on diminished gallbladder ejection fraction (GB-EF), work-up and management in pediatrics is controversial. MethodsWe conducted a multi-institutional retrospective review of children undergoing cholecystectomy for BD to compare perioperative work-up and outcomes. ResultsSix hundred seventy-eight patients across 16 institutions were included. There was no significant difference in gender, age, or BMI between institutions. Most patients were white (86.3%), non-Hispanic (79.9%), and had private insurance (55.2%). Gallbladder ejection fraction (EF) was reported in 84.5% of patients, and 44.8% had an EF <15%. 30.7% of patients were initially seen by pediatric surgeons, 31.3% by pediatric gastroenterologists, and 23.4% by the emergency department with significant variability between institutions (p < 0.001). Symptoms persisted in 35.3% of patients post-operatively with a median follow-up of 21 days (IQR 13, 34). On multivariate analysis, only non-white race and the presence of psychiatric comorbidities were associated with increased risk of post-operative symptoms. ConclusionThere is significant variability in evaluation and follow-up both before and after cholecystectomy for BD. Prospective research with standardized data collection and follow-up is needed to develop and validate optimal care pathways for pediatric patients with suspected BD. Study typeCase Series, Retrospective Review. Level of evidenceLevel IV.

Management of intussusception in patients with melanoma.

Increased cross-sectional imaging for surveillance of metastatic melanoma has led to more diagnoses of asymptomatic intussusception. We performed a multi-institutional retrospective review of patient records with a history of metastatic melanoma and a diagnosis of intussusception. Patients were divided into three groups: 1) asymptomatic patients without current evidence of melanoma (no evidence of disease [NED]); 2) asymptomatic intussusception and known active metastatic melanoma; 3) symptomatic intussusception and known active metastatic melanoma; the number of patients requiring surgery and intraoperative findings were recorded. We reviewed 73 patients diagnosed with intussusception from 2004 to 2017. Among asymptomatic patients with NED (n = 16), 14 spontaneously resolved and 2 underwent pre-emptive surgery without abnormal intraoperative findings. Of asymptomatic patients with active metastatic disease (n = 32), 25 were initially observed and 7 underwent pre-emptive surgery and 9 of the 25 initially observed patients required surgery for development of symptoms. In this group, all 16 patients undergoing surgery (50% of the group) had intraoperative findings of intussusception and/or metastatic intestinal melanoma.. All symptomatic patients with metastatic melanoma (n = 25) underwent surgery; all had intraoperative findings of intussusception and/or metastatic melanoma except 1 (Meckel's diverticulum). Asymptomatic patients with NED do not require surgery and intussusception will likely resolve spontaneously. Asymptomatic patients with known metastatic melanoma may be initially observed, but a low threshold for surgery should be maintained. Symptomatic patients with known metastases should undergo surgery.

Is fecal diversion necessary during ileal pouch creation after initial subtotal colectomy in pediatric ulcerative colitis?

Pediatric patients with medically refractory ulcerative colitis (UC) often undergo an initial subtotal colectomy end ileostomy (STC-I). The role of fecal diversion in the subsequent completion proctectomy/ileal-pouch anal anastomosis (CP-IPAA) remains controversial. A multi-institutional retrospective review was performed of pediatric UC patients who underwent an STC-I followed by CP-IPAA from 2008 to 2016. 37 patients were included [diverted (n = 20), undiverted (n = 17)]. Children who underwent undiverted CP-IPAA had a longer length of stay (days) compared to the diverted group (9, 6.5-13 vs. 6, 5-6, p = 0.002). The 30-day complication rate was significantly higher in the undiverted group (p = 0.003) although the difference in anastomotic leak, readmission rate, unplanned computer tomography use, and reoperation was not statistically significant. Three patients with undiverted CP-IPAA required additional surgery in the perioperative period for fecal diversion. The mean long-term follow-up was 25.68 ± 21.56 months. There were no significant differences in functional pouch outcomes. Patients who underwent an undiverted CP-IPAA after initial STC-I had significantly more complications in the immediate postoperative period compared to diverted patients, although this did not translate into long-term differences in functional outcomes. Questions remain regarding careful patient selection and counseling for undiverted pouches in the pediatric UC population.

Are Emergently Placed Nephrostomy Tubes Suitable for Subsequent Percutaneous Endoscopic Renal Surgery?

ObjectiveTo determine the percentage of emergently placed nephrostomy tubes (NT) that were subsequently deemed usable for definitive percutaneous nephrolithotomy or percutaneous antegrade ureteroscopy in patients presenting with nephrolithiasis. MethodsA multi-institutional retrospective database review was completed to identify patients who underwent emergent NT placement and then subsequent percutaneous nephrolithotomy or percutaneous antegrade ureteroscopy. Demographic, operative, and postoperative data were collected. Complications were classified using the Clavien-Dindo system. ResultsA total of 36 patients with 41 NTs met inclusion criteria. Indications for emergent NT placement were: obstruction with evidence of urinary tract infection/pyelonephritis (61%) and obstruction with acute kidney injury (39%). After recovery from the acute event and NT placement and during subsequent percutaneous surgical procedures, 9 NTs (22%) were sufficient without need for additional percutaneous access, 2 NTs (5%) were partially sufficient and were used in conjunction with an additional percutaneous access tract, and 30 NTs (73%) were unusable. ConclusionIn this multi-institutional review, only 22% of NTs placed for emergent indications were sufficient for subsequent percutaneous surgery without the creation of additional percutaneous tracts. Urologists should be prepared to obtain additional access during definitive percutaneous renal surgery in patients who have had a tube placed under emergent conditions.

Survival and Prognostic Factors in Patients with Gastrointestinal Cancers and Brain Metastases

Literature is sparse regarding the prognosis of patients with gastrointestinal (GI) cancers and brain metastases (BM). Our group previously published a prognostic index, the Graded Prognostic Assessment (GPA) for GI cancer patients with BM, based on 209 patients diagnosed from 1985-2005. The purpose of this analysis is to identify prognostic factors for GI cancer patients with newly diagnosed BM in a larger contemporary cohort. A multi-institutional (16) retrospective institutional review board-approved database of 685 GI cancer patients with new BM diagnosed from 1/1/2006-12/31/2016 was created using REDCap. Demographic data, clinical parameters and treatment were correlated with survival, time from primary diagnosis to BM (TPDBM) and cause of death. Kaplan-Meier median survival estimates were calculated and compared with log-rank tests. The median survival (MS) from time of first treatment for BM for the prior and current cohorts were 5 and 7 months, respectively (p<0.001). Eight prognostic factors (GI GPA, age, stage, KPS, extracranial metastases (ECM), number of BM, primary site and Hgb at the time of BM diagnosis) were found to be statistically significant for survival, in contrast to only one (KPS) in the prior cohort. MS (mo) by primary site were: stomach (2), transverse colon (2), pancreas (4), GE junction (4), Gallbladder (5), Left and right colon (7), rectum (7), esophagus (9), small bowel (9), rectosigmoid (10) and anus (14). Median TPDBM was 22 months. Shorter TPDBM was seen with esophageal, gastroesophageal junction, gastric cancers. The cause of death was known in 54% (370/685) and among those, neurologic only death occurred in 25% (92/370). Nearly one third of patients (219/685) presented with poor prognosis (GPA 0-1.0).Abstract MO_29_2736; Table 1FactorRangeNOS (mo)p-valueOverall1985-2005 / 2006-2016209 / 6855 / 7<0.001GPA0-1 / 1.5-2 / 2.5-3 / 3.5-4.0219 / 179 / 177 / 394 / 6 / 11 / 14<0.001KPS<70 / 70 / 80 / 90 / 10095 / 124 / 179 / 177 / 393 / 4 / 6 / 11 / 14<0.001# Brain Mets1 / 2-3 / >3337 / 204 / 13710 / 7 / 3<0.001Hgb< 11 / 11-12.5 / 12.6-14 / > 14113 /110 / 118 / 1163 /6 / 7 / 11<0.001Age25-52 / 53-61 / 62-68 / > 68166 / 163 / 190 / 16610 / 8 / 7 / 50.002StageI / II / III / IV / unknown27 / 79 / 221 / 294 / 647 / 11 / 9 / 6 / 70.004HER2negative / positive / unknown82 / 48 / 5555 / 11 / 70.06 Open table in a new tab OS has improved slightly in recent decades and varies by primary site. In stark contrast to our studies of patients with lung, melanoma, breast and renal cell cancers, a much higher percentage (32%) of GI patients with BM present with poor prognosis (GPA 0-1.0), highlighting the need for earlier diagnosis and better treatment. More prognostic factors have been identified. The impact of HER2/KRAS/EGFR/BRAF on OS by primary site will be presented. These data will be useful in counseling patients, refining clinical decision-making and the GI-GPA index and stratification of future clinical trials.

Non-Transecting Techniques Reduce Sexual Dysfunction After Anastomotic Bulbar Urethroplasty: Results of a Multi-Institutional Comparative Analysis

PurposeThe purpose of this multi-institutional study is to compare outcomes of transecting and non-transecting anastomotic bulbar urethroplasty. Materials and MethodsThis was a retrospective multi-institutional review of 352 patients undergoing either transecting or non-transecting anastomotic bulbar urethroplasty performed by one of four reconstructive urologists from September 2003 to March 2017. Study outcomes were urethroplasty success (defined as urethral patency >16Fr on cystoscopy), de novo sexual dysfunction assessed at 6-months (defined as ≥5-point change in SHIM or patient reported adverse change) and 90-day complications (Clavien ≥2). Comparison between transecting and non-transecting cohorts were made using the Mantel–Cox test, t-test or Chi-square when appropriate. Results352 patients with a mean stricture length of 1.7cm (0.5-5cm) underwent either a transecting (n=258) or non-transecting (n=94) anastomotic bulbar urethroplasty. Overall success was 94.9% at a mean follow-up of 64.2 months (6-170). 7.1% of patients experienced a 90-day complication and 11.6% reported sexual dysfunction. When comparing transecting and non-transecting techniques there was no difference in success (93.8% vs. 97.9%; p=0.18) (Mantel-Cox) or postoperative complications (8.1% vs. 4.3%; p=0.25). Patients undergoing transecting anastomotic urethroplasty were more likely to report an adverse change in sexual function (14.3% vs. 4.3%; p=0.008). On multivariate analysis, only transecting urethroplasty (p=0.01) was associated with sexual dysfunction while age (p=0.29), stricture length (p=0.42), etiology (p=0.99) and surgeon (p=0.88) were not. ConclusionsAnastomotic urethroplasty is a highly effective surgery with relatively minimal associated morbidity. Non-transecting anastomotic urethroplasty compares quite favorably to the transecting technique and likely reduces the risk of associated sexual dysfunction.

Evaluating diagnostic yield of computed tomography (CT) and magnetic resonance imaging (MRI) in pediatric unilateral sensorineural hearing loss

IntroductionOptions for imaging for evaluation of pediatric patients with unilateral sensorineural hearing loss (USNHL) include computed tomography (CT) and magnetic resonance imaging (MRI). Although both CT and MR imaging provide valuable information in the evaluation of pediatric patients with USNHL, debate remains regarding which imaging modality is most ideal and should be the preferred study for these children. The objective of this study is to evaluate and compare the diagnostic yield of CT versus MRI in children with USNHL. MethodsA multi-institutional retrospective chart review was conducted. Pediatric patients with hearing loss (diagnosis codes 389.00–389.22) seen between 2010 and 2012 at three tertiary care centers were identified. Only patients with USNHL and imaging studies were reviewed and results of CT and MRI for each patient were examined and compared. Cochleovestibular or central nervous system findings known to directly correlate to SNHL were noted as positive findings on imaging. McNemar's test was used to compare patients with positive CT and MRI results. ResultsA total of 219 patients between the ages of 0–18 years with USNHL who underwent CT and/or MRI were identified. Imaging abnormalities were found in 41/96 patients who underwent MRI with overall diagnostic yield of 42.7% and 69 of 188 patients who underwent CT with overall diagnostic yield of 36.7%. For patients who underwent both imaging modalities (n = 65), there was no statistically significant difference in positive findings detected by CT vs MRI (p > 0.05). ConclusionsBoth CT and MR imaging have similar overall diagnostic yield when used to evaluate children with USNHL. Parents and patients should be counseled regarding cost, test duration, radiation exposure, need for sedation, and diagnostic accuracy associated with each imaging modality and these factors should be considered to select the appropriate diagnostic study.

Adenomatous Neuroendocrine Tumors of the Middle Ear: A Multi-institutional Investigation of 32 Cases and Development of a Staging System.

To date, less than 150 cases of middle ear adenomatous neuroendocrine tumors (MEANTs) have been reported in the English literature. The objective of this study was to provide a contemporary analysis of these rare lesions and develop a consensus-driven staging system. Multi-institutional retrospective histopathologic, radiologic, and clinical review. Six tertiary referral centers. Thirty-two patients with pathologically confirmed MEANT. Surgical resection, adjuvant therapy. Clinical manifestations, outcomes, staging system. Patients commonly presented with progressive conductive or mixed hearing loss (90%), aural fullness (50%), and tonal tinnitus (46%). Pulsatile tinnitus (16%), carcinoid syndrome (4%), and facial nerve paresis (4%) were less commonly observed. MEANTs frequently mimicked temporal bone paraganglioma (31%) and cholesteatoma (15%) at presentation. According to a novel T/N/M/S staging system (S = secretory tumor) proposed herein, there were 6 (19%) T1, 19 (59%) T2, and 7 (22%) T3 MEANTs. T3 tumors were significantly more likely to undergo subtotal or near total resection compared with lower staged tumors secondary to adherence to critical neurovascular structures such as the petrous internal carotid artery and facial nerve (p = 0.027). Patients with T3 MEANTs were more likely to experience multiple recurrences, require adjuvant therapy with a somatostatin analogue, or develop permanent facial nerve paresis compared with lower staged tumors. At last follow up, no patients with T1 MEANTs had developed recurrence, whereas 37% (7/19) of patients with T2 MEANT and 57% (4/7) of patients with T3 MEANT experienced either disease recurrence after gross total resection (GTR) or regrowth of known residual tumor requiring additional surgery at a median duration of 72 months (95% CI, 24-84). Patients with MEANTs can present with nonspecific symptomatology that overlaps with more commonly encountered middle ear lesions. MEANT exhibits a proclivity for recurrence according to T-stage and long-term clinical follow up is necessary, particularly for advanced stage tumors.

First-line Chemotherapy Responsiveness and Patterns of Metastatic Spread Identify Clinical Syndromes Present Within Advanced KRAS Mutant Non–Small-cell Lung Cancer With Different Prognostic Significance

BackgroundUnsuccessful KRAS-specific treatment approaches in non–small-cell lung cancer (NSCLC) might reflect underlying disease heterogeneity. We sought to define clinical “syndromes” within advanced KRAS mutant NSCLC to improve future clinical trials and create a clinical framework for future molecular development. Patients and MethodsTo test a series of a priori hypotheses regarding KRAS-mutant NSCLC clinical syndromes, we conducted a multi-institutional retrospective medical record review. Survival probabilities were estimated using the Kaplan-Meier model. Between-group differences were assessed using the log-rank test. Multivariate Cox regression analyses and Wilcoxon rank sum testing were used to assess progression-free survival and overall survival (OS) differences. ResultsAmong 218 patients with advanced KRAS-mutant NSCLC, OS and progression-free survival with first-line chemotherapy did not differ by intrathoracic versus extrathoracic spread, smoking intensity, or the specific KRAS mutation. Metastatic disease at diagnosis resulted in significantly worse OS than recurrent, unresectable disease (median OS, 14.6 vs. 40.9 months; P = .001). Among the patients with metastatic disease at diagnosis, nonscalp, soft tissue metastases (syndrome X; 6% of cases; 95% confidence interval [CI], 2.5%-10.1%) signified a poor prognosis (median OS, 7.5 vs. 15.9 months for the controls; P = .021). The response to first-line chemotherapy (syndrome Y; 41% of cases; 95% CI, 32.3%-50.6%) signified a good prognosis (median OS, 26.7 vs. 11.9 months; P = .002). The overlap between these 2 syndromes was minimal (2 of 111). Multivariate analysis confirmed these observations. The hazard ratio for death for syndromes X and Y was 2.64 (95% CI, 1.13-6.14) and 0.45 (95% CI, 0.28-0.76), respectively. ConclusionChemotherapy-responsive disease and nonscalp, soft tissue spread might represent distinct clinical syndromes within KRAS-mutant NSCLC. The molecular biology underlying this heterogeneity warrants future studies.

Technical Considerations for Nephron-Sparing Surgery in Children: What Is Needed to Preserve Renal Units?

BackgroundChemotherapy is used preoperatively for children with bilateral Wilms tumor (BWT) or unilateral high-risk Wilms tumor (UHRWT) to promote tumor regression to facilitate renal preservation with nephron-sparing surgery (NSS). In adults, various surgical techniques have been described to preserve renal tissue. Few studies have examined the use of surgical adjuncts in NSS in children with renal tumors. MethodsWe performed a multi-institutional retrospective review of patients with BWT or UHRWT. Patient demographics, tumor size at diagnosis, following neoadjuvant chemotherapy, utilization of surgical adjuncts including intraoperative ultrasound (IOUS), margin status, complications, renal function, and follow-up were recorded. ResultsThe cohort comprised 23 patients: 18 BWT, 3 UHRWT, and 2 patients with solitary kidney. Twenty-two of the 23 patients had successful NSS. IOUS was used 19 times, and seven had positive margins after surgery. Cooling/vascular isolation was used six times. At a median follow-up of 18 mo, median estimated glomerular filtration rate Schwartz was 126 mL/min/1.73 m2 and median serum creatinine 0.39 mg/dL in the 22 patients who had successful NSS. There have been no tumor recurrences. ConclusionsIn patients with BWT and UHRWT, surgical adjuncts such as cooling/vascular isolation are uncommonly performed. IOUS may be helpful but does not guarantee negative microscopic margins. Level of evidenceLevel 4, Case series with no comparison group.

Invasive Fungal Sinusitis: Common Imaging Findings and Co-Relation with Intraoperative Features; A Retrospective Multi-Institutional Analysis and Review of Literature

Invasive Fungal Sinusitis: Common Imaging Findings and Co-Relation with Intraoperative Features; A Retrospective Multi-Institutional Analysis and Review of Literature

Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool.

Brain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985-2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors. A multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively. The 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0-1.0, 1.5-2.0, 2.5-3, and 3.5-4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively. The updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com.

BRAF Mutant Lung Cancer: Programmed Death Ligand 1 Expression, Tumor Mutational Burden, Microsatellite Instability Status, and Response to Immune Check-Point Inhibitors.

The efficacy of immune checkpoint inhibitors (ICPi) in BRAF mutant NSCLC is unknown. Multi-institutional retrospective chart review identified 39 patients with BRAF mutant NSCLC. The patients were divided into two groups: V600E (group A, n= 21) and non-V600E (group B, n= 18). Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB) and microsatellite instability status were assessed in 29 (74%), 11 (28%), and 12 (31%) patients, respectively. Objective response rate, progression-free survival (PFS) with ICPi, and overall survival were analyzed. High (≥50%), intermediate (1-49%), and no (<1%) PD-L1 expression was observed in 8 of 19 (42%), 6 of 19 (32%), 5 of 19 (26%), and 5 of 10 (50%), 1 of 10 (10%), and 4 of 10 (40%) cases in groups A and B, respectively. Two tumors in group A showed high TMB (25%); none were microsatellite instability status-high. Twenty-two patients (group A, n= 12; group B, n= 10) received ICPi. Objective response rate with ICPi was 25%and 33% in groups A and B, respectively (p= 1.0). Median PFS with ICPi was 3.7 months (95% confidence interval [CI]: 1.6-6.6), and 4.1 months (95% CI: 0.1-19.6) ingroups A and B, respectively (log-rank test= 0.81, p=0.37). Neither BRAF mutation type nor PD-L1 expression affected the response probability/PFS. Median overall survival was not reached (95% CI: 13-NR) and comprised 21.1months (95% CI: 1.8-NR) for patients who were and were not exposed to ICPi, respectively (log-rank test= 5.58, p= 0.018). BRAF mutant NSCLC is associated with high level of PD-L1 expression, low/intermediate TMB and microsatellite-stable status. ICPi have favorable activity both in BRAF V600E and BRAF non-V600E mutant NSCLC.

Effect of Targeted Therapies on Prognostic Factors, Patterns of Care, and Survival in Patients With Renal Cell Carcinoma and Brain Metastases

Toidentify prognostic factors, define evolving patterns of care, and the effect of targeted therapies in a larger contemporary cohort of renal cell carcinoma (RCC) patients with new brain metastases (BM). A multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new BM diagnosed from January 1, 2006, to December 31, 2015, was created. Clinical parameters and treatment were correlated with median survival and time from primary diagnosis to BM. Multivariable analyses were performed. The median survival for the prior/present cohorts was 9.6/12months, respectively (P<.01). Four prognostic factors (Karnofsky performance status, extracranial metastases, number of BM, and hemoglobin b) were significant for survival after the diagnosis of BM. Of the 6 drug types studied, only cytokine use after BM was associated with improved survival. The use of whole-brain radiation therapy declined from 50% to 22%, and the use of stereotactic radiosurgery alone increased from 46% to 58%. Nonneurologic causes of death were twice as common as neurologic causes. Additional prognostic factors refine prognostication in this larger contemporary cohort. Patterns of care have changed, and survival of RCC patients with BM has improved over time. The reasons for this improvement in survival remain unknown but may relate to more aggressive use of local brain metastasis therapy and a wider array of systemic treatment options for those patients with progressive extracranial tumor.

Impact of oophorectomy and hormone suppression in low grade endometrial stromal sarcoma: A multicenter review

ObjectivesLow grade endometrial stromal sarcoma (LG-ESS) is a rare cancer with an indolent course. We aimed to assess the effectiveness of adjuvant hormonal suppression (HT) with or without oophorectomy (BSO) in prolonging progression free survival (PFS) and overall survival (OS) in patients with LG-ESS. MethodsWe performed a multi-institutional retrospective review of patients treated for low grade LG-ESS from 1985 to 2014. Demographics, treatment and recurrence data were abstracted from medical records. Pathologic diagnosis was confirmed by a gynecologic pathologist. Long-term patient-reported outcomes were obtained via mailed survey. ResultsOne-hundred-twelve patients underwent surgery for LG-ESS; 59 had postoperative data with a median follow-up of 55months (1–325months). The mean age at diagnosis was 48.5years (22–82years). Forty-nine (61%) had stage I disease. The most common presenting symptoms were abnormal uterine bleeding (38%) and pelvic mass (17%). Seventy-one (63%) patients had BSO at the time of diagnosis. Of the 59 patients with postoperative follow-up information, 49 (73%) underwent BSO, 26 (44%) received HT, 20 (33%) were expectantly managed, and 6 (10%) received chemotherapy, radiation or both. Median PFS for the entire group was 53months and OS was 63months. PFS for those who underwent BSO compared with those who retained their ovaries was 38 vs 11months, p=0.071. PFS for HT vs no HT was 28 vs 23months, p=0.77. ConclusionsConsistent with prior series, our results support BSO to prolong PFS in LG-ESS but are limited by sample size. Larger studies with more complete follow-up are needed to determine the effect of adjuvant hormonal suppression.