Pancreatic endocrine neoplasms (Pan-NENs) are a subset of endocrine tumors with an estimated incidence of 0.9 new cases per 100,000 people and an usually indolent pattern of growth and progression (Dasari et al. 2017). The resulting long overall survival (OS), even in the presence of recurrent disease, makes it difficult to design multi-arm randomized trials due to the long observation period needed. Some authors advocate (Kulke et al. 2011) the use of progression-free survival (PFS) in both phase II and III studies for non-surgical therapy of advanced Pan-NEN, which could result in reducing the observational period and sample size. Recently, this option has been validated by a systematic review in which the authors (Imaoka et al. 2017) demonstrated that PFS is a valid surrogate measure of overall survival in unresectable patients. However, the question remains open in radically resected Pan-NENs, in which OS is longer compared to the unresectable ones (Falconi et al. 2016). Also, the use of DFS instead of OS, even if frequently reported, has never validated. These uncertainties result in difficult planning of observational or two-groups parallel studies comparing adjuvant or neoadjuvant therapy in resectable Pan-NENs (Jensen et al. 2019). Thus, the primary aim of this study is to validate the use of disease-specific survival (DFS) as a surrogate measure of OS for surgical clinical trials related to Pan-NENs. The secondary aim is to demonstrate the gain in sample size using DFS instead of OS in a hypothetical, prospective, randomized study exploring the role of adjuvant therapy with two parallel groups.
All studies that met eligibility criteria were read in full-text form by two independent investigators (C I and V A) to search the inclusion and exclusion criteria. Briefly, for the final inclusion, the studies had to meet the following criteria: (1) reporting OS and DFS survival, (2) reporting information about grading according to 2017 WHO classification (Lloyd et al. 2017) at final pathological diagnosis, and (3) reporting data about lymph node metastasis and or distant metastasis at time of surgery. Finally, if two studies were reported by the same institution (and/or authors) or presented risk of overlapping populations, either the most recent study or the one with higher quality was included. The following criteria were used to exclude studies: (1) series with un-extractable OS and/or DFS, (2) studies with mixed cohorts (e.g. operated and not operated patients), and (3) series including patients undergoing non-radical resection. When the inclusion criteria were met in the absence of exclusion ones, the study was included for the analysis. Two independent reviewers (C I and V A) carried out data extraction using a dedicated form. Any disagreement between the reviewers was solved by a discussion with the senior authors (M F and R C). A PRISMA diagram was reported to show the transparency of the conclusions reached by the authors.
t1 survival guide pdf free 19
Download File: https://caesesxsynghe.blogspot.com/?pr=2vJn04
The eight pair-wise scenarios of sample size calculation for planning a randomized two-arm study are reported in Table 3. The median survival time was nearly 12 years (144 months) for OS and nearly 10 years (122 months) for DFS, as obtained from the systematic review. All actual power and alpha values reached the required value of >0.90 and
The ACTT1 results showed improved LOS by 4 days in patients receiving RDV. The average duration of symptoms before enrollment was 9d median with a wide range. The key observation from data is that benefit was derived in patients who were started before mechanical ventilation, suggesting that the use of the drug earlier in the disease course has efficacy--consistent with its mechanism of action as an antiviral. Some argue that SOLIDARITY and DisCoVeRy trials show no mortality benefit, although the latter trial did have a similar benefit for patients on oxygen as ACTT-1. Overall, many US and NIH guidelines favor continued use for patients with severe COVID-19 requiring oxygen but not admitted to the ICU due to improvement in LOS noted by both prospective and several retrospective studies, matched control studies. PINETREE data suggested that early administration (
Bhimraj A, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 [last updated 8/30/22, accessed 12/12/2022]Comment: Regularly updated, and generally in concert with the NIH GL. One major area where our guide differs is in convalescent plasma use which we believe has a role for early illness in hospitalized patients (
(3) WHO Guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents. -guidelines-for-the-pharmacological-and-radiotherapeutic-management-of-cancer-pain-in-adults-and-adolescents
The documentation set for this product strives to use bias-free language. For the purposes of this documentation set, bias-free is defined as language that does not imply discrimination based on age, disability, gender, racial identity, ethnic identity, sexual orientation, socioeconomic status, and intersectionality. Exceptions may be present in the documentation due to language that is hardcoded in the user interfaces of the product software, language used based on RFP documentation, or language that is used by a referenced third-party product. Learn more about how Cisco is using Inclusive Language.
Bladder carcinoma is morphologically heterogeneous, a process due to intratumoral heterogeneity and ultimately reflected by the presence of the variants of bladder cancer (variant histology) [30]. The current WHO revision includes urothelial carcinoma with divergent (squamous, glandular, and trophoblastic) differentiation, nested, microcystic, micropapillary, lymphoepithelioma-like (LELC), plasmacytoid/signet ring cell/diffuse, sarcomatoid, giant cell, poorly differentiated, lipid-rich, and clear cell (glycogen-rich) as histologic variants [28]. The presence of any variant or combinations thereof is considered high risk in NMIBC; [12] the NCCN clinical guidelines also recommend immediate radical cystectomy for HGT1 with micropapillary, plasmacytoid, or sarcomatoid variants, and the AUA guidelines of NMIBC include the presence of any histologic variant as a high-risk category [31, 32]. The true incidence of variant histology in HGT1 urothelial carcinoma is uncertain, mainly based on limited reports of short case series, and ranges from 6.4 to 23% [33, 34]. Among HGT1 bladder cancer with variant histology, the micropapillary variant has received much attention, with T1 cases representing up to 40% of all-stage reported cases [9, 14, 22, 34,35,36,37]. T1 nested carcinoma represents 16% of all-stage reported cases [9, 20]. Squamous divergent differentiation is also frequently seen in HGT1 carcinomas, with a reported rate of 14% [9, 22]. Nonetheless, data concerning other variants recognized by the WHO are limited mainly to small case series in HGT1, and their actual incidence remains largely unknown [22]. The substantial interobserver discordance when the central review of diagnostic cases is performed, and the fact that most variants are not recognized in daily practice by several pathologists, may explain the limited knowledge available on the risk associated with them in practice [21, 34].
Variant histology was associated with variable aggressive clinicopathological features in the current study, including survival and recurrence rate after complete TURBT and maintenance guided BCG instillations. Interestingly, the identified variants did not all show the same risk of aggressive disease. Squamous, glandular, micropapillary, nested, microcystic, and inverted growth variants showed lower DFS than villous-like, basaloid, and LELC, which showed no recurrences. On the other hand, micropapillary, nested, glandular, and basaloid variants showed lower CSS rates than squamous, inverted, microcystic, villous-like, and LELC variants whose patients remained alive over 150 months of follow-up. Miyake et al., [12] in an extensive series of 1490 patients with NMIBC, recently reported an incidence of 6.4% with variant histology. These patients are more likely to result in cancer-related death than those with conventional urothelial carcinoma or with divergent differentiation, similar to our findings concerning risk stratification; in fact, our cases with divergent squamous differentiation were included as part of the low-risk category, and cases such as micropapillary and nested carcinomas remained as aggressive, life-threatening high-risk diseases. Likewise, Vourganti et al. [38], using data from the Surveillance, Epidemiology, and End Results (SEER) database, found no survival difference for micropapillary compared to conventional urothelial carcinoma after adjusting for stage and grade. Interestingly, these authors found similar behavior for cases reported as low-grade micropapillary NMIBC compared with high-grade micropapillary and high-grade urothelial carcinoma. This is an interesting point of practice, and a potential pitfall since rare cases of T1 micropapillary carcinomas may have bland cytology, and one may wonder if they should be categorized as low grade [38]. 2ff7e9595c
Comments