Prognosis and conditional survival among women with newly diagnosed ovarian cancer.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Treatment patterns and clinical outcomes among patients with relapsed/refractory classical Hodgkin's lymphoma.

Aim: Limited real-world data exist on treatment patterns and clinical outcomes for patients with relapsed/refractory (R/R) classical Hodgkin's lymphoma (cHL). Methods: This study used the ConcertAI Oncology Dataset to assess treatment patterns, real-world progression-free survival (rwPFS), and real-world overall survival (rwOS) in adults with R/R cHL diagnosed from 2000 to 2019. Results: Among 226 (79%) treated patients, there was substantial treatment heterogeneity. Median rwPFS was 21.0 months in the second line (2L) of therapy. Median rwOS was 146.7 months in 2L and decreased to 40.6 months in the fifth line. Conclusion: Patients were exposed to a myriad of treatments in the R/R setting. These data support a relation between rwPFS and rwOS and highlight the need for effective therapeutic options.

Real-World Characteristics, Treatment Patterns, Health Care Resource Use, and Costs of Patients with Diffuse Large B-Cell Lymphoma in the U.S.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma in the U.S., but current real-world data are limited. This study was conducted to describe real-world characteristics, treatment patterns, health care resource utilization (HRU), and health care costs of patients with treated DLBCL in the U.S. MATERIALS AND METHODS: A retrospective study was conducted using the Optum Clinformatics Data Mart database (January 2013 to March 2018). Patients with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis for DLBCL after October 2015 and no prior International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis for unspecified DLBCL or primary mediastinal large B-cell lymphoma were classified as incident; those with such codes were classified as prevalent. An adapted algorithm identified lines of therapy (e.g., first line [1L]). All-cause HRU and costs were calculated per-patient-per-year (PPPY) among patients with a ≥1L. RESULTS: Among 1,877 incident and 651 prevalent patients with ≥1L, median age was 72 years and 46% were female. Among incident patients, 22.6% had at least two lines (2L), whereas 38.4% of prevalent patients had ≥2L. The most frequent 1L therapy was rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Incident patients had 1.3 inpatient and 42.0 outpatient (OP) visits PPPY, whereas prevalent patients had 0.8 and 31.3 visits PPPY, respectively. Total costs were $137,156 and $81,669 PPPY for incident and prevalent patients, respectively. OP costs were the main driver of total costs at $88,202 PPPY, which were higher within the first year. CONCLUSION: This study showed that a large portion of patients require additional therapy after 1L treatment to manage DLBCL and highlighted the substantial economic burden of patients with DLBCL, particularly within the first year following diagnosis. IMPLICATIONS FOR PRACTICE: Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) carry a substantial clinical and economic burden. A large portion of these patients require additional therapy beyond first-line treatment. There is significant unmet need among patients with DLBCL who require additional therapy beyond first-line treatment. Patients who do not respond to first-line therapy and are not eligible for transplants have very high health care resource utilization and costs, especially in the first 12 months following initiation of treatment.

Association of clinico-genomic characteristics with tumor mutational burden in small cell lung cancer patients.

Aim: We evaluated the relationship between clinical and genomic characteristics and tumor mutational burden (TMB) in small cell lung cancer. Materials & methods: In a retrospective analysis of small cell lung cancer patients aged ≥18, we assessed treatment patterns and survival in relation to TMB; the association of clinical and genomic characteristics with TMB was determined by multivariate regression. High TMB (TMB-H) was defined as ≥10 mutations/megabase. Results: Among 186 patients, treatment patterns and overall survival were similar for TMB-H and non-TMB-H patients. TMB was determined for 179 patients, 41.9% of whom were TMB-H. Short variants of LRP1B, FAT3, MLL3, MED12 and NOTCH3 were significantly associated with TMB-H (p ≤ 0.01). Conclusion: Neither treatment patterns nor survival differed by TMB status.

Management of Pilonidal Disease and Hidradenitis Suppurativa.

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.

Real-World Data Quality Framework for Oncology Time to Treatment Discontinuation Use Case: Implementation and Evaluation Study.

BACKGROUND: 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). OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of Updated Clinical Practice Guidelines on Outpatient Treatment for Clostridioides difficile Infection and Associated Clinical Outcomes.

Background: The 2017 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) Clostridium (Clostridioides) difficile infection (CDI) guideline update recommended treatment with fidaxomicin or vancomycin for CDI. We aimed to examine outpatient CDI treatment utilization before and after the guideline update and compare clinical outcomes associated with fidaxomicin versus vancomycin use. Methods: A pre-post study design was employed using Medicare data. CDI treatment utilization and clinical outcomes (4- and 8-week sustained response, CDI recurrence) were compared between patients indexed from April-September 2017 (preguideline period) and those indexed from April-September 2018 (postguideline period). Clinical outcomes associated with fidaxomicin versus vancomycin were compared using propensity score-matched analyses. Results: From the pre- to postguideline period, metronidazole use decreased (initial CDI: 81.2% to 53.5%; recurrent CDI: 49.7% to 27.6%) while vancomycin (initial CDI: 17.9% to 44.9%; recurrent CDI: 48.1% to 66.4%) and fidaxomicin (initial CDI: 0.87% to 1.63%; recurrent CDI: 2.2% to 6.0%) use increased significantly (P < .001 for all). However, clinical outcomes did not improve. In propensity score-matched analyses, fidaxomicin versus vancomycin users had 4-week sustained response rates that were higher by 13.5% (95% confidence interval [CI], 4.0%-22.9%; P = .0058) and 30.0% (95% CI, 16.8%-44.3%; P = .0002) in initial and recurrent CDI cohorts, respectively. Recurrence rates were numerically lower for fidaxomicin in both cohorts. Conclusions: Vancomycin use increased and metronidazole use decreased after the 2017 guideline update. Fidaxomicin use increased but remained low. Improved outcomes associated with fidaxomicin relative to vancomycin suggest benefits from its greater use in Medicare patients.

Characteristics, treatment patterns, healthcare resource use, and costs among pediatric patients diagnosed with neurofibromatosis type 1 and plexiform neurofibromas: a retrospective database analysis of a medicaid population.

OBJECTIVES: The objectives of this study were to describe the characteristics and initial treatment patterns, healthcare resource use (HCRU), and costs of patients newly diagnosed with neurofibromatosis type 1 (NF1)-related plexiform neurofibromas (PN). METHODS: This was a retrospective study of individuals enrolled in the IBM MarketScan Multi-State Medicaid database from 1 October 2014 to 31 December 2017. Patients aged ≤18 years at the index date (first diagnosis of NF1 or PN, whichever occurred later) with at least 1 ICD-10-CM diagnosis code for both NF1 and PN were included. All-cause HCRU and the associated direct costs during the follow-up period were calculated per patient per year (PPPY) in 2018 USD. RESULTS: A total of 383 patients were included with a mean follow-up of 448 days. Most patients were diagnosed by a specialist (63.5%). During the follow-up period, pain medications were used by 58.5% of patients, 25.1% were treated with chemotherapy, 7.1% received surgery for PN, 1.6% received MEK inhibitors, and 0.8% received radiation. Mean PPPY inpatient, outpatient, ER, pharmacy, and other visits were 1.4, 17.3, 1.6, 13.6, and 25.8, respectively. Mean ± SD (median) total PPPY healthcare costs were $17,275 ± $61,903 ($2889), with total medical costs of $14,628 ± $56,203 ($2334) and pharmacy costs of $2646 ± $13,303 ($26). CONCLUSIONS: This study showed that many pediatric patients newly diagnosed with NF1 and PN were initially treated with supportive care only, highlighting a substantial unmet medical need. This study also highlights the considerable economic burden among patients with NF1 and PN.

Treatment patterns, healthcare resource utilization, and costs of patients diagnosed with primary mediastinal B-cell lymphoma in the United States.

AIMS: With the advent of ICD-10-CM codes for PMBCL on 10/01/2015, assessment of treatment patterns and healthcare burden among US patients is possible. This study sought to describe the real-world treatment patterns and economic outcomes of patients with PMBCL. METHODS: Data from the Optum Clinformatics DataMart database was used (January 2013-March 2018). Patients with a first PMBCL ICD-10-CM diagnosis (with or without an antecedent ICD-10-CM diagnosis of DLBCL/other lymphoma, which may have been assigned before PMBCL confirmation) after 10/01/2015 (index date) and no ICD-9-CM diagnosis code for unspecified PMBCL/DLBCL were identified as incident patients. Those with PMBCL ICD-10-CM and unspecified ICD-9-CM diagnosis for PMBCL/DLBCL before 10/01/2015 (index date) were identified as prevalent patients. Patients were observed from the index date up to the earliest among death, end of data availability, or end of continuous health plan enrollment. An adapted algorithm was used to identify lines of therapy (LOT). RESULTS: Among 118 incident and 30 prevalent PMBCL patients, 14% and 20% of patients received ≥2 LOTs, respectively. In incident patients, 48% received ≥1 LOT, 14% ≥2, and 4% ≥3 LOTs. Among prevalent patients, 63% received ≥1 LOT and 20% ≥2 LOTs. The most frequently recorded 1 L therapy was R-CHOP both among incident and prevalent patients. Mean total healthcare costs for incident and prevalent patients were $149,340 and $92,799 per patient per year, respectively, with higher costs ≤12 months ($187,241 and $167,553). Outpatient costs were the main driver (accounting for 60.5% and 64.6% for incident and prevalent patients, respectively). LIMITATIONS: Potential underuse of ICD-10-CM codes shortly after discontinuation of ICD-9-CM codes in 01/2015; regimens identified for each LOT using the claims-based algorithm may not reflect the regimen administered. CONCLUSION: The multiple LOTs necessary for a sizeable minority of patients and the high costs of care highlight the significant unmet needs of PMBCL patients.

Real-World Healthcare Resource Utilization in Patients with Classical Hodgkin Lymphoma Treated with Pembrolizumab and Nivolumab in the USA.

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.

Treatment, Resource Use and Costs Among Pediatric Patients with Neurofibromatosis Type 1 and Plexiform Neurofibromas.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition which predisposes individuals to tumors of the nervous system, skin, bones, and eyes. Plexiform neurofibromas (PNs) occur in 20-50% of NF1 cases, causing multiple morbidities and conferring a risk of malignancy. NF1 with PN is poorly characterized in the literature with regard to treatment patterns, healthcare resource utilization, and costs in the real world. METHODS: This was a retrospective analysis of data from a commercial claims database in the US between October 2014 and March 2018. Persons with at least 1 diagnostic code for both NF1 and PN, aged ≤18 years on the index date, and continuously enrolled for ≥12 months before the index date were included. The index date was defined as the date of the first diagnosis of NF1 or PN during the study period, whichever occurred later. Healthcare resource utilization during follow-up included outpatient, inpatient, emergency room (ER), and pharmacy encounters; corresponding costs were calculated as the mean per patient per year (PPPY) in 2018 US dollars. Treatments were classified as PN surgery, pain medication, chemotherapy, radiotherapy, and targeted therapies. All analyses were descriptive. RESULTS: A total of 301 patients were included. In the follow-up period, nearly all patients (99.7%) had outpatient visits, while 81.1% had pharmacy visits, 25.2% had ER visits, and 13.0% had inpatient visits. Mean ± SD [median] total healthcare costs PPPY were $38,292 ± $80,556 [$16,037]. During follow-up, 44.2% of patients used pain medications, 23.9% received chemotherapy, 5.0% underwent surgery for PN, 1.3% received radiotherapy, and 1.0% received targeted therapies. CONCLUSION: Commercially insured pediatric patients diagnosed with NF1 and PN were treated primarily with supportive care, highlighting a substantial unmet need in the United States.

Identifying susceptibility networks for drug-induced non-immune neutropenia.

Systems toxicology, a branch of toxicology that studies drug effects at the level of biological systems, offers exciting opportunities to discover toxicity-related sub-networks using high-throughput technologies. This paper takes a computational approach to systems toxicology and investigates the use of automated signalling path detection for discovery of potential biomarkers of drug-induced non-immune neutropenia. The algorithm utilises a gene expression change measure to mine a large protein interaction network and identify chemical-toxicity signalling paths. Cytoscape-based analysis of detected signalling paths with statistically significant path expression scores reveals 'hub' proteins and a smaller sub-network of path proteins. The importance of 'hub' and drug-toxicity signalling path proteins in haematological and apoptotic signal transduction networks is investigated in order to understand the value of automated signalling path detection approach.

A systems biology approach for detecting toxicity-related hotspots inside protein interaction networks.

Drug-induced neutropenia can be fatal when severe and therefore requires an improved understanding of its mechanism(s) of toxicity. Systems biology provides an opportunity to understand adverse events after drug administration using analysis of biomolecular networks. In this study, a human protein interaction network was analyzed to identify proteins that are most central to topological paths connecting a drug's target proteins to hematopoiesis-related proteins. For a set of non-immune neutropenia inducing drugs, 9 proteins were found to be common to putative signaling paths across all drugs evaluated. All 9 proteins showed relevance to neutrophil biology. Geneset enrichment analysis showed that proteins associated with cancer-related processes such as apoptosis provide topological linkages between drug targets and proteins involved in neutrophil production. The algorithm can be applied towards analysis of any toxicity where the drugs and the physiological processes involved in the toxic mechanism are known.

Classification of rheumatoid arthritis status with candidate gene and genome-wide single-nucleotide polymorphisms using random forests.

Using the North American Rheumatoid Arthritis Consortium (NARAC) candidate gene and genome-wide single-nucleotide polymorphism (SNP) data sets, we applied regression methods and tree-based random forests to identify genetic associations with rheumatoid arthritis (RA) and to predict RA disease status. Several genes were consistently identified as weakly associated with RA without a significant interaction or combinatorial effect with other candidate genes. Using random forests, the tested candidate gene SNPs were not sufficient to predict RA patients and normal subjects with high accuracy. However, using the top 500 SNPs, ranked by the importance score, from the genome-wide linkage panel of 5742 SNPs, we were able to accurately predict RA patients and normal subjects with sensitivity of approximately 90% and specificity of approximately 80%, which was confirmed by five-fold cross-validation. However, in a complete training-testing framework, replication of genetic predictors was less satisfactory; thus, further evaluation of existing methodology and development of new methods are warranted.