The static deflections of the cutting tool and thin-walled components are key sources contributing to the deviation of a machined surface from the design specifications during the end milling ...operation. The machined surface deviation is expressed using geometric tolerances such as flatness and cylindricity parameters specified as per the Geometric Dimensioning and Tolerancing (
GD&T
) standard (ASME Y14.5-2009 or ISO 1101). The present work investigates the effect of component configuration, engagement area, and workpiece curvature by comparing geometric errors during the end milling of zero and constant curvature thin-walled components. An integrated computational framework incorporating the mechanistic force model, finite element (FE)-based workpiece deflection model, cantilever beam formulation-based tool deflection model, and particle swarm optimization (PSO)-based geometric tolerance estimation model has been adopted from the previous work of authors. The effect of component geometry and cutter-workpiece transition are investigated on the geometric tolerance (flatness and cylindricity) by conducting computational studies and machining experiments under identical cutting conditions. The concept of “Equivalent Radial Depth of Cut (RDOC)” is introduced to derive component configurations with the identical cutter-workpiece transition area. The influence of workpiece curvature on the geometric tolerance parameters is also investigated in the paper. The outcomes are substantiated by performing computational studies and machining experiments. It is recognized that the relatively enhanced stiffness of the curved components offers an inherent machining advantage in comparison to straight components to the process planners.
An important question in determining long-term prognosis for women with ovarian cancer is whether risk of death changes the longer a woman lives. Large real-world datasets permit assessment of ...conditional survival (CS) given both prior overall survival (OS) and real-world progression-free survival (rwPFS).
Using a longitudinal dataset from US oncology centers, this study included 6778 women with ovarian cancer. We calculated CS rates as the Kaplan-Meier probability of surviving an additional 1 or 5 years, given no mortality (OS) or disease progression (rwPFS) event in the previous 0.5–5 years since first-line chemotherapy initiation, adjusted for factors associated with OS based on multivariable Cox regression.
Median study follow-up was 9 years (range, 1–44) from first-line initiation to data cutoff (17-Feb-2021). Median OS was 58.0 months (95% CI, 54.9–60.8); median rwPFS was 18.4 months (17.4–19.4). The adjusted 1-year CS rate (ie, rate of 1 year additional survival) did not vary based on time alive, whereas the adjusted 5-year CS rate increased from 48.5% (47.0%–50.1%) for women who had already survived 6 months to 66.4% (63.3%–69.6%) for those already surviving 5 years (thus surviving 10 years total). The adjusted 1-year CS rate increased from 90.4% (89.5%–91.4%) with no rwPFS event at 6 months to 97.6% (96.4%–98.8%) with no rwPFS event at 5 years; adjusted 5-year CS rate increased from 53.7% (52.0%–55.5%) to 85.0% (81.2%–88.9%), respectively.
This analysis extends the concept of CS by also conditioning on time progression-free. Patients with longer rwPFS experience longer survival than patients with shorter rwPFS.
•Women with ovarian cancer have an increasing probability of survival with increasing time survived after the diagnosis.•Conditional survival (CS) is the probability of surviving +y years, given already having survived x years post-diagnosis.•The 5-year CS rate increased from 54% for survival with no disease progression at 6 mos to 85% with no progression at 5 yrs.•The prognosis for ovarian cancer improved substantially with time for women alive without disease progression.
New and improved measurement methods are paramount to ensure in-process monitoring of advanced manufacturing processes and quality products. This editorial discusses the outline of the special issue ...consisting of 15 peer-reviewed manuscripts in the domain of "Measurement and Metrology in Advanced Manufacturing Processes." These research and review articles discuss the relevance, state-of-the-art methods, and ongoing research on the advancement of manufacturing processes with measurements and metrology perspectives by different research groups globally. The significance of measurement and metrology is recognized in various applications such as additive manufacturing, photopolymer jetting, submerged arc welding, micro-electrical discharge machining, and reverse manufacturing.
The importance of real-world evidence is widely recognized in observational oncology studies. However, the lack of interoperable data quality standards in the fragmented health information technology ...landscape represents an important challenge. Therefore, adopting validated systematic methods for evaluating data quality is important for oncology outcomes research leveraging real-world data (RWD).
This study aims to implement real-world time to treatment discontinuation (rwTTD) for a systemic anticancer therapy (SACT) as a new use case for the Use Case Specific Relevance and Quality Assessment, a framework linking data quality and relevance in fit-for-purpose RWD assessment.
To define the rwTTD use case, we mapped the operational definition of rwTTD to RWD elements commonly available from oncology electronic health record-derived data sets. We identified 20 tasks to check the completeness and plausibility of data elements concerning SACT use, line of therapy (LOT), death date, and length of follow-up. Using descriptive statistics, we illustrated how to implement the Use Case Specific Relevance and Quality Assessment on 2 oncology databases (Data sets A and B) to estimate the rwTTD of an SACT drug (target SACT) for patients with advanced head and neck cancer diagnosed on or after January 1, 2015.
A total of 1200 (24.96%) of 4808 patients in Data set A and 237 (5.92%) of 4003 patients in Data set B received the target SACT, suggesting better relevance of the former in estimating the rwTTD of the target SACT. The 2 data sets differed with regard to the terminology used for SACT drugs, LOT format, and target SACT LOT distribution over time. Data set B appeared to have less complete SACT records, longer lags in incorporating the latest data, and incomplete mortality data, suggesting a lack of fitness for estimating rwTTD.
The fit-for-purpose data quality assessment demonstrated substantial variability in the quality of the 2 real-world data sets. The data quality specifications applied for rwTTD estimation can be expanded to support a broad spectrum of oncology use cases.
Background
Patients with classical Hodgkin lymphoma (cHL) relapsed or refractory (R/R) disease who relapse after or are ineligible for autologous stem cell transplantation have a poor prognosis. ...Recently, the anti-PD1 monoclonal antibodies nivolumab and pembrolizumab were approved by the US Food and Drug Administration (FDA; May 2016 and March 2017, respectively) as treatment options for R/R cHL patients.
Objective
In the absence of comparative clinical trials between these agents, this observational study was conducted to evaluate the healthcare resource utilization (HRU) of patients with cHL initiated on pembrolizumab compared to nivolumab in the USA.
Patients and Method
Healthcare insurance claims from Symphony Health’s IDV® (Integrated Dataverse) (July 2014–June 2018) were used in this retrospective study. The study population included adult patients with cHL initiated on pembrolizumab or nivolumab (index date). Inverse probability of treatment weighting was used to adjust for differences in patient characteristics between cohorts. All-cause and cHL-related hospitalizations and outpatient visits were measured during the observation (post-index) period and reported per patient-year (PPY). Rates of HRU were compared between cohorts using rate ratios (RRs).
Results
A total of 92 and 218 patients initiated on pembrolizumab and nivolumab, respectively, were included in the study population. After weighting, the mean age was similar at 55 years in both cohorts, while the proportion of females was lower in the pembrolizumab cohort (35.3%) compared to the nivolumab cohort (44.1%). Mean Quan–Charlson Comorbidity Index score was well balanced after weighting in the pembrolizumab and nivolumab cohorts (4.2 and 4.3, respectively). During the observation period, patients in the pembrolizumab cohort had significantly lower rates of all-cause hospitalizations (RR 95% CI 0.33 0.09–0.80) and cHL-related hospitalizations (RR 95% CI 0.14 0.02–0.37) than those in the nivolumab cohort. Rates of all-cause and cHL-related outpatient visits were not statistically different between patients in the pembrolizumab and nivolumab cohorts.
Conclusions
In this real-world study, adult cHL patients initiated on pembrolizumab had significantly lower rates of all-cause and cHL-related hospitalizations compared to patients initiated on nivolumab.
Abstract
Background: Nivo, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, is approved in the United States and European Union for the treatment of pts with ...advanced SQ NSCLC refractory to prior chemotherapy, based on results of phase 2 (CheckMate 063) and phase 3 (CheckMate 017) trials. In these studies, PD-1 ligand (PD-L1) expression was neither predictive nor prognostic of survival benefit. Here we present results of exploratory analyses from these studies evaluating the potential correlation of baseline serum cytokines with overall survival (OS) in pts with SQ NSCLC.
Methods: Baseline serum cytokine concentrations in evaluable pts from CheckMate 063 and CheckMate 017 treated with nivo (n = 222) or doc (n = 118) were analyzed using a custom HumanMAP quantitative multiplexed immunoassay (Myriad RBM, Austin, TX). Multivariate analyses using a stepwise variable selection were performed in a Cox model using a 6:4 training:test validation in nivo-treated subjects. The performance of the association with OS of the identified cytokine set in nivo-treated subjects was tested using time-varying receiver-operating characteristic (ROC) analysis. SQ-cytoscore, generated to quantify the effect of the identified cytokine set on OS, was computed as follows: 1) calculation of the tertile bin distribution of each cytokine in the set in all pts and assignment of a point score (0, 1, or 2) for each tertile expression of each cytokine; 2) calculation of SQ-cytoscore for each pt as the sum of points; 3) categorization of pts as SQ-cytoscore “high” or “low” based on the median cutoff. OS was analyzed in pts with high vs low SQ-cytoscore treated with nivo and doc using the Kaplan-Meier method and 18-mo data cutoffs for CheckMate 063 (June 2015) and CheckMate 017 (August 2015).
Results: Of 26 evaluable baseline cytokines, a set of 14 was identified to be associated with OS. Median OS was longer in pts with high vs low SQ-cytoscore in both nivo- and doc-treated cohorts (nivo n = 102 vs 120: 15.6 vs 5.3 months, HR:0.48, 95%CI:0.36-0.64, P<0.0001; doc n = 70 vs 48: 9.1 vs 4.9 months (HR:0.39, 95%CI:0.27-0.56, P<0.0001). Among pts with high SQ-cytoscores (n = 172), median OS was 15.6 vs 9.1 months (HR:0.63, 95%CI:0.45-0.88, P = 0.0051) for nivo- vs doc-treated pts, respectively. Among pts with low SQ-cytoscores (n = 168), median OS was 5.3 vs 4.9 months (HR:0.51, 95%CI:0.37-0.71, P = 0.0009) for nivo- vs doc-treated pts, respectively.
Conclusion: In pts with advanced SQ NSCLC pooled from 2 clinical trials, a set of serum cytokines (details to be presented) potentially associated with OS benefit was identified. The benefit of a high SQ-cytoscore appeared more profound in pts treated with nivo vs doc. These preliminary findings require prospective validation in future studies.
Citation Format: Benedetto Farsaci, William J. Geese, Kaushal D. Desai, Chelsea Jin, Scott J. Antonia, Hervé Lena, Leora Horn, David Planchard, Karen L. Reckamp, Thomas E. Stinchcombe, Scott Gettinger, Hossein Borghaei, Matthew D. Hellmann, Christopher Harbison, Dong Xu, M. Anne Blackwood-Chirchir, Naiyer Rizvi. Impact of baseline serum cytokines on survival in patients (pts) with advanced squamous (SQ) non-small cell lung cancer (NSCLC) treated with nivolumab (nivo) or docetaxel (doc): Exploratory analyses from CheckMate 063 and CheckMate 017. abstract. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-072.
Pilonidal disease and hidradenitis suppurativa affect healthy young adults, causing discomfort and pain that leads to loss of work productivity and should be approached in a personalized manner. ...Patients with pilonidal disease should engage in hair removal to the sacrococcygeal region and surgical options considered. Hidradenitis suppurativa can be a morbid and challenging disease process. Medical management with topical agents, antibiotics, and biologics should be used initially but wide local excision should be considered in severe or refractory cases of the disease.
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Background: Patients with biliary tract cancers (BTC) are typically diagnosed at late stage, with limited treatment options. As such, BTC is associated with poor prognosis, high economic burden ...and reduced health-related quality of life (HRQoL). As the treatment paradigm is evolving, with multiple immunotherapies showing promise, this study aimed to assess the current disease and treatment landscape. Methods: Systematic literature reviews (Embase, MEDLINE, Cochrane, NHS-EED; database inception to Feb 10, 2023) were conducted for HRQoL and economic burden. Targeted literature reviews (Embase, MEDLINE) were conducted for epidemiology (Jan 01 2017–Feb 06 2023) and treatment guidelines/patterns (Jan 01 2012–Feb 06 2023). Conference abstracts were also searched (2019–2022). Eligibility criteria included global studies (English language) in adults with metastatic and/or unresectable BTC. Results: Overall, 264 studies were included (epidemiology=170, treatment guidelines=14, treatment patterns=50, HRQoL=12, economic burden=18). In the US, Europe and Asia, age-standardized incidence rates were 5.04, 8.39–8.78 and 9.1–10.1 (per 100,000 person-years) and prevalence rates were 0.01%, 0.02–0.34% and 0.02–2.61%, respectively. Treatment pattern studies were mainly from Asia, Europe (n=19 each) and North America (n=10). Gemcitabine gem-based chemotherapy was most common in 1L BTC (24–100%) and fluorouracil-based regimens were common in 2L+ BTC (12.3–74.3%). Median overall survival (mOS) for gem-based and fluorouracil-based 1L regimens were 7.7–14.8 months and 7–16.7 months, respectively. Disease progression/toxicity frequently led to treatment discontinuation/dose modifications. In the US, use of non-guideline-based regimens increased by line of therapy (LOT). Among the clinical studies (n=5) reporting HRQoL in 1L, n=4 assessed gem-based combinations. BTC impaired HRQoL domains for anxiety, tiredness (EORTC QLQ-BIL21), work productivity, activity impairment (WPAI scale) and depression (PHQ-9). BTC was associated with substantial economic burden. Mean total all-cause healthcare costs per patient per month (PPPM) increased by LOT (US; 1L: $19,589–25,517, 2L: $22,617–29,721, 3L: $23,256–33,534). US healthcare resource utilization in 1L was driven by outpatient visits (98%), emergency department visits (33–80%) and hospitalization (70–80%). Mean hospital stay ranged from 0.6–7 days PPPM. Conclusions: Epidemiology data varied between Western and Asian populations, but gem-based chemotherapy was identified as the standard of care across regions. There is high unmet need in advanced BTC, as existing options are characterized by poor survival outcomes and considerable economic burden. These findings indicate a need for novel approaches for the management of BTC.
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Background: Regorafenib and trifluridine/tipiracil (TAS-102) are standard of care (SoC) systemic anticancer treatments (SACT) for metastatic colorectal cancer (mCRC) patients perviously treated ...with fluoropyrimidine (5-FU), irinotecan, & oxaliplatin-based chemotherapy. However, evidence is limited on post-chemotherapy & later SACT for patients with mCRC that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This study assessed real-world patient characteristics and treatment patterns in community oncology practices among previously treated, not MSI-H/dMMR mCRC patients. Methods: This retrospective cohort study utilized The US Oncology Network (iKnowMed) electronic health record database, supplemented by chart review. The study cohort comprised adult, not MSI-H/dMMR mCRC patients treated with chemotherapy (5-FU/capecitabine, irinotecan, and oxaliplatin) who initiated subsequent SACT or received best supportive care (BSC) between 1/1/2016 & 12/31/2021. Index date for SACT users was the regimen start date. For patients on BSC and no subsequent SACT/BSC, index date was last chemotherapy administration date. Patients were followed from index date through 8/31/2022, date of death or last contact date, whichever occurred first. Descriptive statistics were used to report patient and treatment characteristics. Results: The study consisted of 292 mCRC patients, with a median age of 57 (range: 49, 68) years. The predominant histology was adenocarcinoma (n = 237, 81.2%) with 1.7% other histology and rest missing, 198 (67.8%) patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and 206 (70.5%) had primary tumors located in the colon. Liver (n = 207, 70.9%) and lung (n = 78, 26.7%) were the most common metastasis sites. Diabetes (n = 33, 11.3%) and peripheral vascular disease (n = 18, 6.2%) were the most common comorbidities. Eighty-seven (29.8%) patients received at least one chemotherapy in the adjuvant/neo-adjuvant setting, while majority (70.2%) patients received chemotherapies in the metastatic setting. Overall, 203 (69.5%) received SACT post-chemotherapy, 84 (28.8%) received BSC and 5 (1.7%) did not receive SACT/BSC. Among the SACT post-chemotherapy users, 30 (14.8%) received regorafenib, 25 (12.3%) received TAS-102 and 148 (72.9%) received other SACT. Other SACT included irinotecan-based (n = 76, 37.4%), oxaliplatin-based (n = 30, 14.8%), irinotecan and oxaliplatin-based (n = 6, 3.0%) chemotherapy, and anti-EGFR (n = 15, 7.4%) or anti-VEGF (n = 8, 3.0%) targeted therapies. Conclusions: Overall, only 27.1% of previously treated mCRC patients with tumors that were not MSI-H or dMMR received SoC. The real-world variability in choice of treatments and the high percentage of patients rechallenged with chemotherapy in subsequent lines, highlights an unmet need in this population.
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Background: TFST may be a patient-relevant indicator of efficacy beyond progression in OC, however, the association between TFST and OS is unknown. We analyzed the SEER Medicare ...database to determine whether OS varied by TFST in previously untreated patients with OC. Methods: From the SEER-Medicare linked database, we identified newly diagnosed OC patients (≥66 years) who initiated first-line chemotherapy between 2009 and 2015. Patients were followed through the end of 2016. TFST was defined as the time from initiation of first-line chemotherapy until the start of subsequent therapy or death. Cox models summarized the overall association between TFST and OS through hazard ratios (HRs), and by TFST strata for patients who had a TFST event. In case hazards were non-proportional, we examined the fit of independent parametric survival curves. Results: In the cohort of 1407 patients, 1005 patients had a TFST event. Median age was 74 years and 34.9% were alive at the time of this analysis. For population with a TFST, the median TFST was 13.1 months and median OS was 30.88 months (HR = 0.29, 95% CI: 0.26, 0.32). Among patients < 75 years, the median TFST was 13.65 months and the median OS was 37.07 months (HR = 0.24, 95% CI: 0.21, 0.28). In the full cohort of 1407 patients, the best-fitting distributions accelerated failure time models under which the (unrestricted) mean TFST and OS were 44.9 and 73.8 months respectively. This indicated that on average TFST was an acceleration of OS by a factor of 39%. Conclusions: In this elderly population of previously untreated OC, longer TFST was associated with longer OS. Limitations of this analysis include censoring of OS and immortal time bias. Table: see text
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