Objective: 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. Study Design: Multi-institutional retrospective histopathologic, radiologic, and clinical review. Setting: Six tertiary referral centers. Patients: Thirty-two patients with pathologically confirmed MEANT. Intervention: Surgical resection, adjuvant therapy. Main Outcome Measures: Clinical manifestations, outcomes, staging system. Results: 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). Conclusions: 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.
Very poor long‐term survival in past and more recent studies for relapsed AML patients: The ECOG‐ACRIN experience
AbstractThis study examines the long‐term OS of relapsed AML patients who were enrolled to 9 successive ECOG‐ACRIN trials for newly diagnosed AML, during 1984‐2008. The objectives were to examine whether there is a trend of improvement in the survival of relapsed AML patients in the more recent studies and to search for prognostic factors that are associated with long‐term OS after relapse. A total of 3012 patients were enrolled, 1779 (59.1%) achieved CR1 and of these, 58.9% relapsed. The median follow‐up was 9.7 years. The median OS from relapse was 0.5 years and the 5‐year OS was 10 (±1)%. These results were similar even for the most recent studies. A multivariate model showed that age, cytogenetics at diagnosis, duration of CR1 and undergoing allogeneic transplantation were significantly associated with OS from relapse. Even among patients who relapsed with better prognostic factors; age < 40 and CR1 > 12 months, there was no significant OS difference between the studies. In conclusion, this large cohort appears to confirm that the survival of AML patients postrelapse continues to be dismal and has not improved during the past quarter of a century.
Canadian Association of Radiologists White Paper on Artificial Intelligence in Radiology
Artificial intelligence (AI) is rapidly moving from an experimental phase to an implementation phase in many fields, including medicine. The combination of improved availability of large datasets, increasing computing power, and advances in learning algorithms has created major performance breakthroughs in the development of AI applications. In the last 5 years, AI techniques known as deep learning have delivered rapidly improving performance in image recognition, caption generation, and speech recognition. Radiology, in particular, is a prime candidate for early adoption of these techniques. It is anticipated that the implementation of AI in radiology over the next decade will significantly improve the quality, value, and depth of radiology's contribution to patient care and population health, and will revolutionize radiologists' workflows. The Canadian Association of Radiologists (CAR) is the national voice of radiology committed to promoting the highest standards in patient-centered imaging, lifelong learning, and research. The CAR has created an AI working group with the mandate to discuss and deliberate on practice, policy, and patient care issues related to the introduction and implementation of AI in imaging. This white paper provides recommendations for the CAR derived from deliberations between members of the AI working group. This white paper on AI in radiology will inform CAR members and policymakers on key terminology, educational needs of members, research and development, partnerships, potential clinical applications, implementation, structure and governance, role of radiologists, and potential impact of AI on radiology in Canada.
Survey of the American Neurotology Society on Cochlear Implantation: Part 2, Surgical and Device-Related Practice Patterns
Objective: To examine surgical and device-related cochlear implant practice patterns across centers in the United States. Methods: Cross-sectional survey of the American Neurotology Society (ANS). Results: A total of 81 surveys were returned from ANS members who report regular involvement in cochlear implant care. Overall there was a broad distribution in age and clinical experience, with most respondents reporting Accreditation Council for Graduate Medical Education (ACGME) accreditation in neurotology and employment at an academic center. The annual volume of cochlear implant surgeries varied considerably across centers. Eighty percent of respondents report to offer all three Food and Drug Administration (FDA) approved device brands at their center. In cases where hearing preservation is not a goal, 56% of respondents prefer a perimodiolar electrode design, while 44% prefer a lateral wall electrode. With regard to insertion technique for scala tympani access, 64% prefer inserting through the round window (RW) membrane, 26% prefer an extended round window (ERW) approach, while only 10% prefer a cochleostomy. In cases where hearing preservation is a goal of surgery, 86% of respondents prefer a lateral wall electrode design, while only 14% prefer a perimodiolar electrode design. With regard to insertion technique, 86% prefer RW insertion, while only 9% prefer an ERW approach, and only 5% prefer a cochleostomy. Respondents who prefer RW electrode insertion more commonly use a lateral wall electrode, whereas those who prefer an ERW or cochleostomy approach more commonly use a periomodiolar electrode (p < 0.001). There was a statistically significant greater number of surgeons that prefer lateral wall electrodes (p < 0.001) and RW insertion (p < 0.001) for hearing preservation cases compared with non-hearing preservation cases. For implantation of a hypothetical patient with significant residual hearing, within the range of hybrid device candidacy, the great majority of surgeons prefer a conventional length electrode and only 29% prefer to implant a hybrid device. In cases where hearing preservation is a goal, the overwhelming majority of respondents (96%, n = 74) reported using at least one form of steroid application. Ninety-two percent (n = 71) used intraoperative intravenous steroids, 55% (n = 42) prescribed postoperative oral steroids, 44% (n = 34) bathed the middle ear with steroids during surgery, and 30% (n = 23) prescribed preoperative oral steroids. Together, 65% of respondents use a variation of the tight subperiosteal pocket technique for internal device fixation, 19% prefer a bony well and trough with tie-downs, 10% prefer a bony well and trough without tie-downs, and 5% prefer a screw fixation system. Of the 50 who prefer utilizing a subperiosteal pocket, 31 (62%) incorporate a bony trough and 19 (38%) perform a subperiosteal pocket alone without a bony trough. Conclusion: The results of this survey reflect the evolution in surgical and device-related preferences for cochlear implantation in the United States. An increasing number of surgeons prefer the RW approach for electrode insertion. When hearing preservation is not a goal, there is a near even preference for lateral wall and perimodiolar electrode designs; however, the great majority of surgeons prefer a lateral wall design when attempting to preserve residual acoustic hearing. Even in cases where substantial residual hearing exists, many surgeons prefer conventional length electrodes to hybrid designs. These changes reflect the prioritization of atraumatic surgery and parallel the development of thinner and more atraumatic electrodes.
Tumor Progression Following Petroclival Meningioma Subtotal Resection: A Volumetric Study
Abstract BACKGROUND One study has investigated postoperative growth rates following subtotal resection of petroclival meningiomas utilizing linear measurements, which are insensitive to the multidimensional complex growth of meningiomas, to estimate tumor volume. OBJECTIVE To describe petroclival meningioma growth patterns following less-than-complete resection utilizing volumetric analysis and to identify variables associated with tumor progression. METHODS Patients with surgically resected WHO grade I petroclival meningiomas were retrospectively reviewed (1999-2015). Image analysis software was utilized to perform volumetric analyses of tumor size and growth on serial MRI studies. The impact of preoperative and postoperative variables on tumor growth after subtotal resection was analyzed. An increase in tumor volume of at least 20% was defined as “tumor growth.” RESULTS Twenty-three patients had immediate preoperative and serial postoperative MRI studies available for review. The mean preoperative tumor volume was 20.9 cm 3 (range 0.4-54.6). The mean extent of resection was 75.5% (range 31.5%-100.0%). At a mean follow-up of 24.8 mo, 12 tumors (66.7%) exhibited radiological tumor growth, while 6 tumors did not change in size. The median annual volumetric growth rate was 2.82 cm 3 /yr (range –0.34 to 10.1). Extent of resection and immediate postoperative tumor volume were significantly correlated with the annual volumetric growth rate following resection. At last follow-up, 3 (13%) patients required further intervention. CONCLUSION The majority of petroclival meningiomas exhibit growth following subtotal resection. Extent of resection is strongly associated with risk for disease progression following surgery.
BRCA1 controls the cell division axis and governs ploidy and phenotype in human mammary cells
PURPOSE: The toxicity profile of fluorouracil (5-FU)–based chemotherapy given on 5 consecutive days at doses of 370 to 450 mg/m2 has been well documented. A meta-analysis of six North Central Cancer Treatment Group (NCCTG) cancer control trials involving 786 patients indicated that women treated with this type of regimen experienced more severe stomatitis and leukopenia than men. After these findings, an additional meta-analysis of the toxicity profiles on five NCCTG colorectal cancer treatment trials was undertaken. METHODS: Data for 1,093 women and 1,355 men from 12 different treatment arms were included. The primary end points were the incidence of stomatitis, leukopenia, alopecia, diarrhea, nausea, and vomiting, recorded with standard National Cancer Institute common toxicity criteria. Fisher’s exact test was used to compare incidence and severity across sexes, supplemented by Forrest meta-analysis plots and logistic regression. RESULTS: The incidence of four out of six toxicities studied was significantly greater for women than men; the exceptions were severe nausea and vomiting. Overall, almost half of the women compared with a third of the men experienced severe toxicity (P < .0001). Logistic regression confirmed the univariate findings while adjusting for the effects of study, dose, body mass index, and age. The differences were consistent across treatment cycles. Response rates and survival distributions were the same for both sexes. CONCLUSION: This study confirms an earlier finding that women receiving 5-FU–based chemotherapy in a 5-day bolus schedule experience toxicity more frequently and with more severity than men. These data raise the question of whether the recommended initial dose of 5-FU–based chemotherapy for women should be lower than that for men.
A Simple Stratification Factor Prognostic for Survival in Advanced Cancer: The Good/Bad/Uncertain Index
PURPOSE: This article summarizes the third step of a research program to identify variables that supplement the predictive power of the the Eastern Cooperative Oncology Group (ECOG) performance status (PS) for survival. The objective was to produce a simple, practical, stratification factor for phase III oncology clinical trials involving patients with advanced malignant disease. PATIENTS AND METHODS: A questionnaire was administered to 729 patients with metastatic colorectal or lung cancers. Patients provided a Karnofsky index and appetite rating while physicians provided a survival estimate and the ECOG-PS. Scores for each item were categorized as having a positive, neutral, or negative indication for survival. A patient was classified as having a relatively good prognosis if three or more of the four items showed a positive indication, a bad prognosis if three or more items were negative, and an uncertain prognosis otherwise (Good/Bad/Uncertain [GBU] index). RESULTS: The GBU index improved on the prognostic power of a Cox model quartile index and PS alone and increased the accuracy of survival classification estimates by 5% to 10% more than ECOG-PS alone. For patients with PS of 0 or 1, significant survival patterns exist between GBU groups (P= .002 and .0001, respectively). CONCLUSION: The GBU index may be recommended as a supplementary stratification factor for certain future phase III trials in metastatic lung or colorectal cancer where patient heterogeneity is a particular concern. The GBU represents a relatively modest increase to the cost and patient burden of a clinical trial given the additional control that is achieved over the potentially confounding concomitant to the treatment variable.
Impact of Surgical and Pathologic Variables in Rectal Cancer: A United States Community and Cooperative Group Report
PURPOSE: Substantial and successful effort has been focused on decreasing the risk of local failure after rectal cancer surgery through the use of adjuvant therapies. Our study examined data from studies conducted by United States cooperative groups to investigate the impact of surgical and pathologic variables in rectal cancer outcomes. PATIENTS AND METHODS: Surgical and pathologic reports from 673 patients with stage II/III rectal cancer enrolled onto three adjuvant clinical trials were reviewed for tumor and surgical variables. Additional information on individual institutions and operating surgeon was collected. Variables were tested for association with 5-year local recurrence and survival after adjustment for adjuvant treatments and other important prognostic factors. RESULTS: Five-year local recurrence and survival rates were 16% and 59%, respectively. Surgeons treating more than 10 study cases had lower local recurrence rates than those treating ≤ 10 (11% v 17%, P = .02). Free radial margins also correlated with local recurrence (P = .01). Type of surgery, distal margins, and tumor radial spread were not significant. Tumor adherence to adjacent structures predicted local recurrence (35% v 14%, P < .001) and survival (30% v 63%, P < .001), regardless of en bloc resection. Although T and N classification predicted survival (P < .001), only N classification correlated with local recurrence. The number and percentage of positive nodes correlated with survival, but only the percentage independently predicted local recurrence. Several pathologic and surgical variables were reported suboptimally. CONCLUSION: Moderate variability in outcomes among surgeons was detected in this high-risk population. Efforts to improve surgical results will require changes in reporting practices to allow for more accurate assessment of the quality of surgery.