Real-world prevalence of homologous recombination repair gene (BRCA1/2 and ATM) mutations (HRRm) in patients (pts) with advanced prostate cancer (aPC) as detected by comprehensive genomic profiling (CGP) of circulating cell-free DNA (cfDNA).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 256-256
Author(s):  
Nicolas Sayegh ◽  
Umang Swami ◽  
Pedro C. Barata ◽  
Michael B. Lilly ◽  
Roberto Nussenzveig ◽  
...  
Keyword(s):  
Real World ◽  
Tumor Tissue ◽  
Parp Inhibitors ◽  
World Population ◽  
Chi Square ◽  
Repair Gene ◽  
Variants Of Unknown Significance ◽  
Pathogenic Variants ◽  
Comprehensive Genomic Profiling ◽  
Chi Square Test

256 Background: PARP inhibitors, olaparib and rucaparib recently improved survival outcomes (in the Profound and Triton-2 trials) in pts with aPC harboring HRRm. Notably, ~35% of pts screened for the PROfound trial did not meet eligibility solely due to the lack of adequate quality/quantity of tumor tissue required for CGP (De Bono, NEJM, 2020). cfDNA analysis non-invasively assesses tumor-derived genomic alterations. We evaluated the prevalence of HRRm in a real-world aPC population, who had commercially available cfDNA assay results available. Methods: cfDNA based CGP (using a clinically-validated 73- to 74-gene panel i.e. Guardant360 or G360) from consecutive aPC pts between 11/2016–8/2020 were used for detection of HRRm. Frameshift and nonsense mutations were included as pathogenic. Variants of unknown significance were excluded. In this unmatched study, the prevalence of each HRRm was compared with those reported in literature using the chi square test. Results: cfDNA CGP from 7701 aPC pts were available for interrogation of BRCA1/BRCA2 mutations, & from 4671 aPC pts for ATM mutations. Prevalence of BRCA1 and 2 as detected by cfDNA was similar to historical CGP of primary tissue. Prevalence of BRCA1 was higher than historical CGP of metastatic tissue. Prevalence of ATM in cfDNA was higher than historic tumor tissue CGP but similar to prior reports from cfDNA testing (Table). Conclusions: In this large real-world population of pts with aPC undergoing routine cfDNA CGP by a CLIA certified lab, prevalence of HRRm was similar (or higher for BRCA1 and ATM) to what has been previously reported from the tumor tissue. These data provide the rationale for utilizing cfDNA CGP as a routine test for detection of HRRm in men with aPC to identify men who are candidates for PARPi. [Table: see text]

Analysis of real-world (RW) data for metastatic breast cancer (mBC) patients (pts) with somatic BRCA1/2 (sBRCA) or other homologous recombination (HR)-pathway gene mutations (muts) treated with PARP inhibitors (PARPi).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10512-10512
Author(s):  
Felipe Batalini ◽  
Russell Madison ◽  
Dean C. Pavlick ◽  
Ethan Sokol ◽  
Tamara Snow ◽  
...  
Keyword(s):  
Cox Regression ◽  
Gene Mutations ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Free Survival ◽  
Pathogenic Variants ◽  
Kaplan Meier ◽  
Pathway Gene ◽  
Comprehensive Genomic Profiling

10512 Background: PARPi are approved for treatment of pts w/ HER2-negative mBC and germline BRCA1/2 (g BRCA) pathogenic or likely pathogenic variants (muts); however, clinical benefit has also been demonstrated in mBC pts w/ sBRCA or other HR-pathway gene muts. Using a RW Clinico-Genomic Database (CGDB), we assessed outcomes for pts w/ gBRCA muts compared to pts w/ either s BRCA or other HR-pathway muts treated w/ PARPi. Methods: 6,329 mBC pts from ̃280 US cancer clinics were included in the Flatiron Health (FH) -Foundation Medicine (FM) CGDB, which includes comprehensive genomic profiling (CGP) linked to de-identified, electronic health record (EHR)-derived clinical data. Eligible pts had mBC, received care in the FH network from 1/1/2011-9/1/2020, and had tissue CGP by FM. Pts classified as gBRCA: positive germline result in EHR and BRCA mut predicted germline per FM’s somatic, germline, zygosity algorithm (SGZ) (Sun et al PMID 29415044). Non-g BRCA: negative germline results in EHR and a somatic BRCA (s BRCA) mut per SGZ or BRCA wild-type w/ another HR mut per CGP result. Pts w/o a documented gBRCA result in EHR, unknown FM BRCA SGZ result, or conflicting results were excluded. RW overall survival (rwOS) and RW progression-free survival (rwPFS) from start of PARPi for pts w/ gBRCA and non- gBRCA mBC were compared using Kaplan-Meier analysis and Cox regression adjusted for mBC line number, prior platinum, age at PARPi initiation, race, and receptor status. Results: Among pts who received PARPi in the mBC setting, 44 had gBRCA and 18 had non -gBRCA: 9 s BRCA (5 BRCA1, 4 BRCA2), 4 PALB2, 2 ATM, and 1 each of ATM+CDK12, BARD1+FANCF+RAD54L, and CHEK2. Of HR muts 76% were confirmed biallelic: 33/44 gBRCA (11 unknown), 8/9 sBRCA, 3/4 PALB2, and 3/5 other (1 unknown). Neither median rwPFS nor rwOS from start of PARPi were significantly different between the non-g BRCA and g BRCA cohorts (rwPFS: 7.0 [4.6-11.3] vs 5.5 [4.3-7.2] months (mos), aHR: 1.19 [0.57 – 2.43]; rwOS: 15.0 [7.95-16.3] vs 11.5 [9.46-NA] mos, aHR: 0.85 [0.36-1.98]). For 9 pts w/ sBRCA mut, median rwPFS was 7.1 mos (range 1.4-12.4) and all pts had progressed by data cut off. Conclusions: Despite small pt numbers and limitations from RW data, our results suggest that pts w/ biallelic non-g BRCA mBC may derive similar benefit from PARPi when tumor CGP detects a s BRCA mut or germline or somatic mut in other HR-pathway genes. These findings are consistent w/ the results from TBCRC-048 (Tung et al PMID 33119476) and support further randomized trials exploring the efficacy of PARPi in this population.[Table: see text]

Sequence decision making for cabazitaxel (Cbz) versus abiraterone (Abt) or enzalutamide (Enz) post-docetaxel (Dtx) in a publicly funded health care system.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 57-57
Author(s):  
Alexander Watson ◽  
Richard Gagnon ◽  
Eugene Batuyong ◽  
Nimira S. Alimohamed ◽  
Richard M. Lee-Ying
Keyword(s):  
Real World ◽  
Performance Status ◽  
Patient Choice ◽  
Rank Test ◽  
First Line ◽  
Chi Square ◽  
The Real ◽  
Therapeutic Decisions ◽  
Chi Square Test ◽  
Castrate Resistant

57 Background: The TROPIC trial demonstrated an overall survival (OS) benefit of Cbz after Dtx in metastatic castrate-resistant prostate cancer (mCRPC). However, the novel anti-androgens (NAA) Abi and Enz have demonstrated similar improvements post-Dtx. The recent CARD trial suggests Cbz may provide the greatest OS benefit in selected patients who were rapid progressors ( < 12 months, RP) on first NAA, however Cbz use and efficacy in the real-world is uncertain. We sought to quantify the real-world use of Cbz and evaluate outcomes post-Dtx. Methods: mCRPC patients who received Dtx at the two tertiary referral centres in the Canadian province of Alberta from October 2012 (Cbz funding approval) to December 31st 2017 were assessed. We examined Cbz eligibility per TROPIC and CARD trial criteria, tracked therapies received, and documented objective and subjective reasoning for therapeutic decisions. OS was measured using the Kaplan-Meier method and the log-rank test was used to compare outcomes. The Chi-Square test was used to compare relative therapy utilization. Results: 463 mCRPC patients received Dtx over the study period, including 83 (18%) for castrate sensitive disease. At Dtx progression, 262 patients (56%) were eligible for Cbz per TROPIC trial criteria, while only 162 (62%) of those were RP on first NAA. Post-Dtx OS was lower among TROPIC-eligible patients receiving Cbz compared to those receiving Abi or Enz (9.1 vs 14.2 months, p = 0.001). This OS difference was not demonstrated among RP patients (11.2 vs 12 months, p = 0.664). The most common reasons for TROPIC ineligibility were Dtx intolerance (13%), serious comorbidities (12%), unacceptable blood counts (11%), performance status (9%) or, for CARD ineligible patients, no progression within 12 months on first NAA (38%). The most common agent immediately post-Dtx was Abi (n = 180, 39%), followed by Enz (n = 129, 28%). Significantly fewer patients (n = 56, 12%) received Cbz immediately post-Dtx (p = 0.001), and 149 (32%) received Cbz overall. First line post-Dtx, 286 patients (62%) did not have a documented discussion about Cbz, and in 172 cases (38%) consideration of Cbz was never documented. Patient choice against Cbz chemotherapy was recorded in 15% of discussions. Conclusions: In a real-world cohort of mCRPC patients, Cbz was a significantly less common choice than Abi or Enz after progression on Dtx. In a majority of these cases, no first line discussion of Cbz was documented, and in documented discussions, patient choice was the driving factor in a minority. OS post-Dtx in patients who met TROPIC trial criteria was lower for those receiving Cbz, noting that, unlike in TROPIC, these patients also received NAAs. This OS difference was not seen in those who also progressed rapidly on first NAA. These data suggest ongoing hesitation towards Cbz use in mCRPC and support careful selection of patients who may obtain benefit.

scholarly journals The Elderly’s Demand for Community-Based Care Services and Its Determinants: A Comparison of the Elderly in the Affordable Housing Community and Commercial Housing Community of China

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Tiantian Gu ◽  
Dezhi Li ◽  
Lingzhi Li
Keyword(s):  
Affordable Housing ◽  
The Elderly ◽  
Policy Implications ◽  
World Population ◽  
Community Based ◽  
Chi Square ◽  
Care Services ◽  
Nanjing City ◽  
Chi Square Test ◽  
Commercial Housing

With the rapid aging of the world population, great pressure has been placed on the provision of community-based care in China. This paper aimed to compare the demand and its determinants for various community-based care services among the elderly in the affordable housing community (AHC) and commercial housing community (CHC) of China. Two community-based surveys were conducted separately in the AHC and CHC of Nanjing City, China. In total, 408 valid questionnaires were returned from the Daishan AHC while 8422 valid questionnaires were received from the CHCs. The chi square test indicated that the respondents in the AHC had significantly higher demands for five types of services (the meal-aid service, the cleaning-aid service, the bath-aid service, the rehabilitation therapy service, and the first-aid service) than those in the CHCs of Nanjing. Further, the Cochran–Mantel–Haenszel test showed that factors influencing the elderly’s demands for these services varied across communities. Several policy implications could be obtained to improve the efficiency of community-based care provision.

Expression of matrix metalloproteinases (MMP1, 2, 9, and 11) in metastatic lymph node tissue of breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21138-21138
Author(s):  
A. Fink-Retter ◽  
D. Gschwantler-Kaulich ◽  
G. Hudelist ◽  
I. Walter ◽  
K. Czerwenka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Tumor Tissue ◽  
Metastatic Lymph Node ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Chi Square ◽  
Breast Tumor Tissue ◽  
Metastatic Lymph ◽  
Chi Square Test

21138 Background: Invasive growth requires degradation of extracellular matrix. A number of Zn 2+ -dependent matrix metalloproteinases (MMPs) is associated with this process and leads to local invasion and metastasis in malignant breast tumors. Especially the expression of MMP-2 and MMP-9 has been associated with high potential of metastasis in breast cancer. Methods: We determined the expression patterns of epithelial (E) and stromal (S) MMP-1, MMP-2, MMP-9 and MMP-11 by immunohistochemistry in tissue arrays, containing 50 paraffin-embedded sets of tissues obtained from the malignant tumor of the breast, and 50 paraffin-embedded sets of tissues from metastatic lymph nodes (purchased from Biomax, Biomax Inc, Rockville, MD). Results: MMP2-S and MMP9-S protein expression was significantly higher in lymph node tumor tissue when compared to breast tumor tissue (10% vs. 2%; p=0.005; 78.3% vs. 94.8%, p=0.01 Chi Square test, respectively). MMP9-E showed a borderline significance in lymph node tumor tissue (92.6% vs. 73.5%; p=0.05 Chi Square test). While in breast tumor tissue significant correlations were observed between all MMPs except MMP2-S, these associations were less pronounced in lymph node tumor tissue. Conclusions: We suggest that the expression of MMP-2 and MMP-9 in breast cancer tissue is associated with a high invasive and metastatic potential. This might be confirmed by our finding that MMP2-S, MMP9-S and MMP9-E are increased expressed in metastatic lymph node tissue. This is in line with other studies which showed that MMP-2 and MMP-9 expression in primary breast cancer tissue samples was associated with breast cancer progression and invasion. No significant financial relationships to disclose.

Characteristics of colorectal cancer (CRC) patients with BRCA1 and BRCA2 mutations.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 606-606 ◽  
Author(s):  
Madiha Naseem ◽  
Joanne Xiu ◽  
Mohamed E. Salem ◽  
Richard M. Goldberg ◽  
Ari M. Vanderwalde ◽  
...  
Keyword(s):  
Predictive Biomarkers ◽  
Parp Inhibitors ◽  
Brca1 And Brca2 ◽  
Chi Square ◽  
Statistical Correlations ◽  
Pathogenic Variants ◽  
Tumor Mutational Burden ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations ◽  
Next Generation Sequencing Ngs

606 Background: Between 3-5% of CRC patients have BRCA1/2 pathogenic mutations. This study aims to identify associations between BRCA1 and BRCA2 mutations and clinical characteristics in CRC. Methods: A total of 6396 CRC tumor samples were tested with Next-Generation Sequencing (NGS) on a 592-gene panel, pathogenic or presumed pathogenic variants were counted as mutations (mt). Microsatellite instability (MSI) and tumor mutational burden (TMB) were tested by NGS. Statistical correlations were investigated using ANOVA, Chi-square and t-test. Results: Among tumors sampled, 53% derived from male patients and median age was 60 years. BRCA1 mt were detected in 1.1% (n = 72) of tumors, while BRCA2 in 2.8% (n = 179). BRCA1 mt were more frequent in women (W;65%) than men (M;35%) (p = 0.0019) while no relationship with sex was seen for BRCA2 mt (42% F vs. 58% M). No significant associations with age were noticed. Majority of pathogenic mt in BRCA1 (52%; n = 34) and BRCA2 (62%; n = 103) occurred in MSI-High (MSI-H) cases. MSI-H pts had more frameshift mt in both BRCA1/2 than MSS pts. MSS cases had lower rates of BRCA1 and 2 pathogenic mt (44% and 37%, respectively). Right-sided tumors were significantly associated with BRCA1 (p = 0.0056) and BRCA2 (p < 0.0001) mt in MSI-H cases only. BRCA1/2 mt were associated with higher TMB in all CRCs, including MSI-H and MSS cases (p < 0.001). POLE mt (n = 31) were associated with higher BRCA1/2 mt rates (9.6%, 55% respectively). Among MSS cases with POLE wild-type status, BRCA1 (p = 0.0269) and BRCA2 (p = 0.0151) mt were associated with high TMB and combining both BRCA1/2 mutations led to an even higher TMB (3.6%; p = 0.001). Conclusions: This is the first study to show that BRCA1/2 mutations are more frequent in MSI-H, and independently associated with higher TMB, pathogenic POLE mutations, and right-sided tumors in MSI-H CRCs. Given their relationship with TMB, the presence of BRCA1/2 mutations may be potential predictive biomarkers for checkpoint or PARP inhibitors in CRC, a finding that should be prospectively evaluated.

HUBUNGAN DUKUNGAN SUAMI DENGAN KEIKUTSERTAAN IBU DALAM MENGIKUTI PROGRAM KB IUD

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Ina Kuswanti ◽  
Galuh Kartika Sari
Keyword(s):  
Family Planning ◽  
Family Planning Program ◽  
World Population ◽  
Planning Program ◽  
Chi Square ◽  
Cross Sectional ◽  
Chi Square Test ◽  
Husband Support ◽  
Relationship Of

ABSTRACT  The increase in the world population in 2025 is expected to break the8.1 billion mark. Based on BKKBN data in 2015, the participation of mothers in participating in family planning program is dominated by KBN Non MKJP, which is 74.55%, while 25.45% using KB MKJP. Government policies and efforts to curb the increase in population include increasing the use of long-term contraceptives. However, the achievement rate of IUD family planning acceptors to date is still relatively low, due to the low support of husbands, thus affecting the participation of mothers following IUD KB program. Factors that cause low husband support is the lack of awareness of husbands to cooperate in creating an effective family planning program. The purpose of this study is to know the relationship of husband support with mother participation in IUD family planning program at Gedong Tengen Public Health Center Yogyakarta.  The type of research was an analytical survey with Cross Sectional approach. The subjects of the research were the acceptor mother of 37 acceptor who got by accidental technique. The data analysis used was chi square test. The results of this study are Husband's support for IUD program is mostly in less than 20 people (54.1%). The participation of mothers in IUD family planning program mostly did not use KB IUD as many as 23 people (62.2%). There is a relationship of husband support with mother participation in follow KB program of IUD proved by chi square test known X value equal to 5,889 bigger than Xtabel equal to 3,841 and significant value equal to 0,015 (P <5%). The conclusion of this study are There is a husband support relationship with mother participation in participating IUD family planning program at Puskesmas Gedong Tengen Yogyakarta

scholarly journals Pengetahuan Dan Dukungan Suami Dalam Penggunaan KB Suntik

2020 ◽  
Vol 7 (2) ◽  
pp. 149-153
Author(s):  
Nurmaliza Ema ◽  
Wiwi Sartika ◽  
Siti Qomariah
Keyword(s):  
Family Planning ◽  
Sampling Technique ◽  
Bivariate Analysis ◽  
P Value ◽  
World Population ◽  
Chi Square ◽  
Cross Sectional ◽  
Chi Square Test ◽  
Cross Sectional Design ◽  
Husband Support

The use of contraceptives is one way to control the population explosion. It is estimated that in 2013 the world population growth acceleration will experience a higher increase. In 2025 the world's population will increase to 8.1 billion, and will continue to grow in 2050 to become 9.6 billion. This study aimed to see the relationship between knowledge and support from husbands in the use of injection family planning at the Afiyah Pratama Clinic. This research method with analytic survey using cross sectional design. It will be held on December 1 to 31 2019 at the Afiyah Pratama Clinic. With the population, namely family planning acceptors who visited dikilinik with a total of 57 respondents. The sampling technique was using Accidental Sampling. The research instrument used was a questionnaire. Data processing procedures include Editing, Coding, Processing, Cleaning. The analysis used was univariate, bivariate and multivariate. Bivariate analysis using the chi-square test with a confidence level of 95%. From the research results, it was found that the knowledge obtained p-value = .002, while husband's support was p-value = .000. So it can be concluded that the husband's knowledge and support greatly influence the use of contraceptives.   Keywords: Knowledge, Husband Support, KB injection ABSTRAK   Penggunaan alat kontrasepsi merupakan salah satu cara untuk mengendalikan ledakan penduduk. Diperkirakan pada tahun 2013  percepatan pertumbuhan penduduk di dunia mengalami peningkatan lebih tinggi. Pada tahun 2025 penduduk dunia akan naik menjadi 8,1 miliar , dan akan terus berkembang pada tahun 2050 menjadi 9,6 miliar. Penelitian ini bertujuan untuk melihat hubungan pengetahuan dan dukungan suami dalam penggunaaan KB Suntik di Klinik Pratama Afiyah. Metode penelitian ini dengan survey analitik menggunakan  design cross sectional. Pelaksanaannya pada tanggal 01 sampai 31 Desember 2019 di Klinik Pratama Afiyah. Dengan populasi yaitu ibu aseptor KB yang berkunjung dikilinik dengan jumlah 57 responden. Tehnik pengambilan sampel dengan Accidental Sampling. Instrument penelitian yang digunakan adalah kuesioner. Prosedur pengolaan data dengan Editing, Coding, Processing, Cleaning.  Analisis yang digunakan secara univariat, bivariate dan multivariate. Analisa Bivariat menggunakan  uji  chi-square dengan tingkat kepercayaan 95%. Dari hasil penelitian didapatkan bahwa pengetahuan didapatkan nilai p-value=.002, sedangkan dukungan suami p-value=.000. Jadi dapat disimpulkan bahwa pengetahuan dan dukungan suami sangat mempengaruhi dalam penggunaan kontrasepsi KB. Kata Kunci: Pengetahuan, Dukungan Suami,  KB suntik..

Real-world burden of chemotherapy-induced myelosuppression: Results of a U.S. online survey of patients with cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19299-e19299
Author(s):  
Robert S. Epstein ◽  
Matti S. Aapro ◽  
Upal K. Basu Roy ◽  
Tehseen Salimi ◽  
JoAnn Krenitsky ◽  
...  
Keyword(s):  
Real World ◽  
Online Survey ◽  
Response Selection ◽  
Chi Square ◽  
Major Life ◽  
Institutional Review ◽  
Patient Reported ◽  
Life Impact ◽  
Chi Square Test ◽  
The Impact

e19299 Background: Research into the real-world impact of chemotherapy (CT)-induced myelosuppression on patients’ lives is limited. This study aimed to investigate the impact of CT-induced myelosuppression on patients with lung, breast, or colorectal cancer (CRC). Methods: Following Institutional Review Board approval to proceed with exception, a survey of participants identified from an online U.S. patient panel was conducted in Nov/Dec 2019. Participants who had been treated with CT in the past year and experienced ≥1 episode of myelosuppression (‘a decrease in bone marrow activity resulting in the reduced production of blood cells’) were eligible for participation. The survey was administered with predominantly close-ended questions, and lay definitions of key terms were provided to aid response selection. Descriptive statistics were used to summarize key findings. P values were calculated using the Chi-square test. Results: 301 participants completed the online survey (breast cancer, n = 153 [51%]; lung cancer, n = 100 [33%]; CRC, n = 48 [16%]). Most participants were aged > 40 years, 60% were female, 60% were currently employed, and 75% had been diagnosed with cancer within the last 3 years. Anemia, neutropenia, lymphopenia, and thrombocytopenia were reported by 61%, 59%, 37%, and 34% of participants, respectively. Fatigue was the most commonly noted side-effect of CT (reported by 72% of participants), with 55% of participants rating it as highly bothersome (9 or 10 on a 1–10 scale of ‘bothersomeness’). Most participants (89%) considered myelosuppression to have a moderate or major impact on life (major life impact, 40%; moderate life impact, 49%; minor life impact, 12%). Patient-reported impact of myelosuppression was significantly higher among participants aged < 50 years vs those aged ≥50 years (p = 0.01); however, no significant differences were observed when participants were stratified by sex, employment status, comorbidities (depression, diabetes, hypertension), or type of cancer. Significantly more participants with fatigue, considering themselves to have a weakened immune system, or noticing easy bruising/bleeding reported a major life impact vs those without these side effects (44% vs 27%, 52% vs 26%, and 50% vs 34%, respectively; all p < 0.01). Conclusions: These data provide further insights into the substantial real-world patient burden of symptoms arising from CT and associated with myelosuppression. Preventing or proactively managing CT-induced myelosuppression could have a major impact on patients’ quality of life.

scholarly journals Prevalence of DNA Repair Gene Mutations in Blood and Tumor Tissue and Impact on Prognosis and Treatment in HNSCC

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3118
Author(s):  
Kimberly M. Burcher ◽  
Andrew T. Faucheux ◽  
Jeffrey W. Lantz ◽  
Harper L. Wilson ◽  
Arianne Abreu ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Cell Cancer ◽  
Gene Mutations ◽  
Parp Inhibitors ◽  
Circulating Tumor Dna ◽  
Outcome Data ◽  
Precision Oncology ◽  
Repair Gene ◽  
Primary Tumors ◽  
Dna Repair Gene

PARP inhibitors are currently approved for a limited number of cancers and targetable mutations in DNA damage repair (DDR) genes. In this single-institution retrospective study, the profiles of 170 patients with head and neck squamous cell cancer (HNSCC) and available tumor tissue DNA (tDNA) and circulating tumor DNA (ctDNA) results were analyzed for mutations in a set of 18 DDR genes as well as in gene subsets defined by technical and clinical significance. Mutations were correlated with demographic and outcome data. The addition of ctDNA to the standard tDNA analysis contributed to identification of a significantly increased incidence of patients with mutations in one or more genes in each of the study subsets of DDR genes in groups of patients older than 60 years, patients with laryngeal primaries, patients with advanced stage at diagnosis and patients previously treated with chemotherapy and/or radiotherapy. Patients with DDR gene mutations were found to be significantly less likely to have primary tumors within the in oropharynx or HPV-positive disease. Patients with ctDNA mutations in all subsets of DDR genes analyzed had significantly worse overall survival in univariate and adjusted multivariate analysis. This study underscores the utility of ctDNA analysis, alone, and in combination with tDNA, for defining the prevalence and the role of DDR gene mutations in HNSCC. Furthermore, this study fosters research promoting the utilization of PARP inhibitors in HNSCC precision oncology treatments.

scholarly journals Disease burden and treatment sequence of polymyositis and dermatomyositis patients in Japan: a real-world evidence study

2021 ◽  
Author(s):  
Celine Miyazaki ◽  
Yukata Ishii ◽  
Natalia M. Stelmaszuk
Keyword(s):  
Resource Utilization ◽  
Real World ◽  
Healthcare Resource ◽  
Patient Characteristics ◽  
Healthcare Resource Utilization ◽  
Systemic Steroid ◽  
Treatment Burden ◽  
Chi Square ◽  
Systemic Steroids ◽  
Chi Square Test

Abstract Introduction/objectives Since new consensus on polymyositis (PM) and dermatomyositis (DM) were released in Japan, an updated evidence on treatment landscape and PM/DM burden was essential. This study evaluates treatment burden and overall treatment cost of PM/DM-related inpatient and outpatient visits, treatments, and procedures/patient/year. Method This retrospective, observational study analyzed insurance claims from Japan Medical Data Center (JMDC) database. Patients with at least one PM/DM diagnosis/one dispensation of treatment between 1 January 2009 and 31 December 2019 were enrolled. Patient characteristics, treatment patterns and sequence, treatment choices, healthcare resource utilization (HCRU), and related costs were assessed. Chi-square test and linear regression model were used to assess impact of patient characteristics on treatment choice. Results Patients (836/4,961) receiving a relevant treatment were analyzed. Heart disease (35%), interstitial lung disease (27%), and diabetes mellitus (26%) were frequently identified as comorbidities. Concomitant dispensation of immunosuppressants and systemic steroids was largely found in first and second line of treatment (LoT) while systemic steroids remained as single dominant treatment across all LoTs. HCRU was very low for inpatient visits (0.68 [1.43]) or rehabilitation (4.74 [14.57]). The mean (SD) number of inpatient visits decreased from first (1.23 [2.32]) to third year (0.11 [0.54]). Total mean (SD) healthcare cost per patients per year was ¥ 3,815,912 (7,412,241), with overall drug dispensation compounding to 80% of total cost. Conclusions High concomitant immunosuppressant and systemic steroid prescriptions in first LoT recommend early optimal treatment to manage PM/DM. Although inpatient costs are low, outpatient dispensation costs increase overall economic burden. Key Points• Japan faces treatment challenges in the prognosis of polymyositis (PM) and dermatomyositis (DM) and thus, we assessed the real-world treatment landscape, practice, patterns, and healthcare resource utilization as an evidence to support healthcare outcome improvement and treatment burden reduction.• Systemic steroids were the dominant preferred choice of treatment, but it increases the overall cost of the treatment due to the resultant comorbidities considering possible side-effects promotion.• Thus, an increased awareness towards the disease management among patients and medical doctors is required for better management goals based on this real-world practice evidence.

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