차세대염기서열분석(NGS) 기반 유전자 패널검사-고형암(난소암)

초록

평가배경 차세대염기서열분석 기반 유전자 패널검사-고형암[Next generation sequencing technology base genetic panel test-solid tumor]은 비유전성 고형암 환자의 검체에서 핵산을 추출한 후 수십~수백 개의 유전자를 하나의 패널로 구성하여 증폭하고 이를 대규모 염기서열분석을 통해 다양한 체세포성 암 관련 유전자 돌연변이를 동시에 검출하는 검사로서, 치료약제 선택 및 치료반응성 예측 등의 목적으로 이용된다. 차세대염기서열분석(next generation sequencing, NGS) 기반 유전자 패널검사는 2017년 3월부터 조건부 선별급여 본인부담률 50%로 등재, 2019년 5월 암질환 급여기준 확대로 본인부담률 50%/90% 변경, 2023년 12월 본인부담률 50%/80%/90%로 변경되어 사용 중이다. 동 검사는 신의료기술평가 없이 급여화된 검사로, 수요조사를 통해 발굴된 안건이다. 다양한 대체 의료기술이 존재하는 현시점에서 기존기술 대비 동 검사의 안전성 및 효과성 등에 대한 근거를 확인하고자, 2024년 제3차 의료기술재평가위원회(2024. 3. 8.)에서 재평가 계획서 및 소위원회 구성안에 대한 심의를 받고 재평가를 수행하였다. 평가목적 본 평가의 목적은 난소암 환자에서 NGS 기반 유전자 패널검사가 유전자 돌연변이를 추가 검출하고, 약제 선별 등 치료방향을 결정하는 목적으로 사용 시 임상적 유용성에 대한 근거를 제공하기 위함이다. 평가방법 난소암 환자에서 NGS 기반 유전자 패널검사의 임상적 안전성 및 효과성 등을 평가하기 위해 문헌고찰을 수행하였다. 모든 평가방법은 평가목적을 고려하여 “NGS 기반 유전자 패널검사-고형암(폐암, 대장암, 유방암, 난소암) 공동 소위원회(이하 ‘소위원회’라 한다)”의 논의를 거쳐 확정하였다. 소위원회는 혈액종양내과 3인, 병리과 1인, 진단검사의학과 1인, 호흡기내과 1인, 외과(유방) 1인, 소화기내과 1인, 산부인과 1인, 근거기반의학 1인, 총 10인으로 구성하였다. 본 평가의 대상자는 난소암 환자이며, 참고표준 및 비교검사는 단일 유전자검사(중합효소연쇄반응, 염기서열분석, 동소교잡반응, 형광동소교잡반응, 면역조직화학검사 등)로 설정하였다. 결과변수는 안전성 및 효과성을 확인하였으며, 안전성은 검사 관련 부작용 및 이상반응, 검사실패율, 조직재생검률 지표로 설정하였고, 효과성은 추가검출률(incremental detection rate, IDR), 유전자별 약제 선별, 치료반응(객관적 반응률, 질병조절률)으로 설정하였다. 연구문헌은 핵심질문을 토대로 국외 3개(Ovid-MEDLINE, Ovid-EMBASE, EBM Reviews- Cochrane Central Register of Controlled Trials), 국내 3개(KoreaMed, 한국의학논문데이터베이스(KMbase), 한국교육학술정보원(RISS) 데이터베이스에서 검색하였다(최종검색일: 2024. 5. 3.). 최종 선택연구는 사전에 정한 자료추출 서식을 활용해 자료를 추출하였다. 모든 과정은 2명의 평가자가 독립적으로 수행하였고, 의견이 불일치한 경우 평가자 간 합의를 통해 일치된 결과를 도출하였으며, 자료정리는 질적 검토를 적용하여 기술하였다. 또한 새로운 바이오마커가 지속적으로 등장함에 따라 항암치료 패러다임이 빠르게 변화하고 있어 관련 학회의 최신 가이드라인과 국내 현황에 대해 검토하였다. 가이드라인은 국내 임상진료지침 정보센터(Korean Medical Guideline Information Center), 국제 진료지침 네트워크(Guideline International Network), 영국 국립보건임상연구소(National Institute for Health and Care Excellence), 미국 종합암네트워크(National Comprehensive Cancer Network, NCCN)에서 ‘ovarian cancer’, ‘next generation sequencing’, ‘NGS’, ‘multigene profiling’ 등 주요어를 조합하여 검색하였고, 검색된 가이드라인을 활용하여 국내외 의료기술평가기관 및 전문학회, 국제기구에서 발간한 가이드라인을 수기 검색하였다(2024. 10. 14.). 또한, 국내 현황은 국내 식품의약품안전처 의약품안전나라, 보건복지부, 건강보험심사평가원 누리집을 참고하여 정리하였고, 이후 소위원회에서 가이드라인 및 국내 현황 조사결과의 적절성을 확인하였다. 본 평가는 소위원회의 검토 결과를 바탕으로 의료기술재평가위원회에서 최종심의 후 결론을 결정하였다. 평가결과 난소암 환자에서 NGS 기반 유전자 패널검사의 문헌고찰 결과, 최종 선택연구는 6편(비교연구 3편, 증례연구 3편, 대상자 수 1,149명)이었다. 연구대상자는 대부분 진행성, 재발성 상피성 난소암이었으며, 분자학적 아형의 분포는 문헌별로 상이하였다. 또한 모든 문헌에서 초기 병기(stage I/II) 난소암을 일부 포함하고 있었다. 중재검사의 검체는 모두 종양조직이었다. 종양패널 종류는 문헌별로 상이하였고, 패널에 포함된 유전자 수는 최소 2개, 최대 382개의 다중 유전자를 포함하고 있었다. 비교검사는 혈액을 이용한 Sanger 염기서열분석이 확인되었다. 다만 1편의 문헌에서 BRCA 유전자 생식세포(germline BRCA, gBRCA) 검사를 위해 2007년~2015년까지는 Sanger 염기서열분석, 2015년 이후로는 다중유전자 패널검사를 수행하였다. 또한 평가에 포함된 가이드라인은 4편이었으며, 국내 현황 조사결과 난소암에서 BRCA 유전자 및 상동재조합결핍(homologous recombination deficiency, HRD) 관련 표적치료제와 기존검사의 급여현황을 확인하였다. 임상적 유용성 결과 NGS 기반 유전자 패널검사의 안전성은 검사 관련 부작용 및 이상반응, 검사실패(미검출)율, 조직재생검률에 대해 평가하였다. 동 검사 관련 부작용 및 이상반응, 조직재생검률을 보고한 문헌은 없었다. 검사실패(미검출)율은 비교연구 1편에서 보고하였고, BRCA 돌연변이 검출에서 Sanger 염기서열분석(gBRCA) 대비 중재검사(tumor BRCA, tBRCA)의 실패율은 6.4%(3/47례)였으며, 그 원인은 결과해석의 오류(1례)와 종양검체의 품질저하(2례)로 보고하였다. 효과성은 표적유전자 돌연변이의 IDR, 유전자별 약제선별 및 치료반응에 대해 평가하였다. 난소암에서 단일 유전자검사 대비 중재검사의 BRCA1/2 유전자 돌연변이의 IDR은 비교연구 3편에서 보고하였다. 상피성 난소암 대상 2편에서 gBRCA 대비 somatic BRCA (sBRCA)의 IDR은 각 25.9%, 4.29%로 확인되었고, 고등급 장액성 난소암(high-grade serous carcinoma, HGSC) 대상 1편에서는 gBRCA 대비 tBRCA IDR은 4.08%로 확인되었다. 표적유전자 변이 확인에 따른 약제 선별(률) 및 치료반응을 보고한 문헌은 4편이었다. BRCA1/2 변이 확인에 따른 PARP 억제제 선별(매칭)률은 4편 중 1편에서 gBRCA 또는 sBRCA1/2+ 대상 7%(8/115), Sanger 염기서열분석(gBRCA) 검사를 받은 환자를 대상으로 3.3%(8/239)로 확인되었다. 3편 중 1편에서 tBRCA1/2+에 따른 표적치료 매칭률은 폴리 중합효소(poly ADP-ribose polymerase, PARP) 억제제의 경우 치료 가능한(actionable molecular alterations) 변이를 하나 이상 가진 대상이 19.2%(14/73), 전체 대상은 16%(14/86)이었으며, 허가된 적응증내 치료는 치료 가능한 변이를 하나 이상 가진 대상에서 56.2%(41/73)로 확인되었다. 2편 중 1편에서 치료 가능한 변이가 하나 이상 발견된 환자 대상 표적치료 매칭률은 20.8%(11/53), tBRCA1+에 따른 PARP 억제제 매칭률은 5.7%(3/53), 그 외 PIK3CA, PTEN 등 변이 확인에 따른 mTOR 억제제 또는 임상시험 매칭률은 15.1(8/53)%이었다. 치료반응은 부분반응(partial response) 0%, 안정병변(stable disease, SD) 18.2%, 질병진행(progressive disease, PD) 36.4%, 단기치료로 평가 불가능 45.5%로 보고하였다. 나머지 1편에서 표적치료 매칭률은 표적 치료가 가능한 대상 10.5%(6/57), 전체 대상 7.14%(6/84)로 확인되었다. BRCA1/2+인 5명은 PARP 억제제(Olaparib)로 치료를 받았으며, PIK3CA+ 1명은 임상시험에 등록되어 AKT 억제제로 치료받았다. 치료반응은 유지요법으로 PARP 억제제 치료 환자는 5명 중 4명이었으며, 이 중 3명은 5개월 이상 재발이 없었고, 1명은 7개월 차 PD로 확인되었다. 나머지 1명은 4차 단일요법으로 PARP 억제제 치료를 받았고, 결과분석 시점까지 SD였으며 7개월간 치료를 지속하였다. AKT 억제제로 치료받은 1명은 결과분석 시점까지 SD였으며 2개월간 치료를 지속하였다. 가이드라인 및 국내 현황 조사결과 NCCN (2024) 가이드라인 검토 결과, 난소암에서 초기치료 시 gBRCA 변이가 없는 경우에도 체세포 검사를 통해 sBRCA1/2, 이형접합성상실(loss of heterozygosity, LOH), HRD 상태를 포함한 분자 변이를 확인할 필요가 있으며, 재발 단계에서 표적치료의 가능성을 확인하기 위해 분자 검사를 권고하였다. 또한 유럽종양학회(European Society for Medical Oncology) (2024)에 따르면, HGSC에서 HRD 추정 유병률이 약 50%인 점을 고려할 때 HRD 상태 확인은 난소암에서 1차 유지요법으로 PARP 억제제를 사용하는데 있어 임상적 유용성이 있다고 언급하였다. HRD와 관련하여 현재 임상에서 사용되는 HRD 검사는 기능적 HRD를 예측하는데 정확도가 높지 않으나, gBRCA1/2 변이가 없는 환자에서 PARP 억제제의 유지요법을 선별하기 위해 HRD 상태를 확인하여 Bevacizumab을 포함한 1차치료 이후 완전 또는 부분 반응이 확인된 HRD+ 종양에서는 Bevacizumab + Olaparib 유지요법을 권고하였다. 국내 현황 조사결과, 최근 진행성 난소암/난관암/일차복막암 대상 유지요법으로 Niraparib의 단독요법 투여대상이 기존 ‘BRCA 변이’ 환자에서 ‘HRD 양성(BRCA 변이 또는 유전체 불안정성)’으로 확대 시행되었다. 결론 및 제언 의료기술재평가 소위원회는 현재의 문헌적 근거와 국내 임상상황 등을 종합적으로 고려하여 다음과 같이 제언하였다. NGS 기반 유전자 패널검사의 안전성은 검사 관련 부작용 및 이상반응, 조직재생검률이 선택연구에서 보고된 바 없고, 실패(미검출)율 6.4%(3/47례)는 종양검체의 품질저하 및 결과해석에서 발생한 오류로 이는 임상적으로 수용 가능하다는 의견이었다. 또한 동 검사는 체외진단 검사로서 종양 및 혈액 채취 과정 이외 인체에 직접적인 위해를 가하지 않고, 검체채취는 기존의 생검과 유사한 정도의 안전성이 있을 것으로 판단하였다. 실제 임상에서도 품질관리(quality control)가 되지 않은 검체는 동 검사에 부적합한 것으로 간주하고 검사에서 제외하고 있으므로 종양내 이질성(종양순도) 및 선행치료 여부를 충분히 고려하고 검체를 채취할 시 안전한 기술로 판단하였다. 효과성은 치료 가능한 표적유전자(BRCA) 돌연변이 검출에 있어 동 검사의 추가검출률은 4.1~25.9%로 기존 단일 유전자검사 대비 유사하거나 높은 수준으로 추가적 이득이 확인되며, 유전자별 표적치료제 선별에 있어 치료 가능한 표적 변이 대상자 또는 전체 대상자의 20% 내외로 표적치료를 매칭하여 일부 개선된 치료반응을 보고하고 있는 점에서 동 검사는 임상적 유용성이 있다는 의견이었다. 그러나 선택연구가 동일집단내 비교결과를 제시하거나 증례연구로 근거의 수준이 높지 않은 점을 고려했을 때, 소위원회는 진행성 난소암 환자에서 NGS 유전자 패널검사 이후 해당 유전자 변이를 표적으로 하는 치료제의 효과성에 대한 문헌적 근거가 아직은 충분하지 않다고 판단하였다. 가이드라인 및 국내 현황 조사결과와 관련하여 현재 공신력 있는 가이드라인에서 진행성 난소암 대상 PARP 억제제 선별을 위해 BRCA1/2, HRD, LOH 상태 등을 포함한 포괄적인 종양기반 NGS 검사를 시행할 것을 권고하고 있으며, 전체 난소암 중 HRD 유병률이 약 50%인 점, 최근 진행성 난소암/난관암/일차복막암 대상 1차치료 유지요법으로 Niraparib 단독요법 투여대상이 ‘BRCA 변이’에서 ‘HRD 양성’으로 적응증이 확대 시행된 점 등을 종합적으로 고려했을 때, 진행성 난소암/난관암/일차복막암에서 동 검사는 BRCA1/2 돌연변이 및 HRD 상태를 확인하고 PARP 억제제 선별 등 치료방향을 결정하는데 임상적으로 유용하다고 판단하였다. 다만 현재 일부 상업용 NGS 유전자 패널에서 HRD 상태 확인이 가능하며, 성능은 유사의료기술(Myriad MyChoice assay)과 유사한 수준이나, HRD 점수를 계산하는 방법이 표준화되어 있지 않아 HRD 결과를 일반화하기 위해서는 국내 실정에 맞는 표준화 방안이 필요하다고 제언하였다. 2024년 제11차 의료기술재평가위원회(2024. 11. 8.)는 ‘NGS 기반 유전자 패널검사-고형암(난소암)’에 대해 공동 소위원회에서 제시한 결론 및 분과위원회 의견을 검토하여 원안대로 결정하였다.

Background The next generation sequencing (NGS) technology-based genetic panel test-solid tumor is a diagnostic test in which nucleic acids are extracted from specimens of colorectal cancer patients, dozens to hundreds of genes are amplified into a single panel, and various somatic cancer-related gene mutations are simultaneously detected through large-scale sequencing analysis. This test is used to select therapeutic agents and predict treatment responses. In March 2017, the NGS-based gene panel test was listed as having a 50% copayment rate under conditional selective reimbursement. However, following the expansion of cancer disease reimbursement criteria in May 2019, the copayment rate was modified to 50% and 90%. As of December 2023, the copayment rate is set at 50%, 80%, or 90%. The test is currently in clinical use. This test has been covered by insurance without being subjected to a new health technology assessment and was identified through a demand survey. To provide evidence of the safety and effectiveness of the technology compared to the current comparator technology, when various alternative health technologies are available, the Third Health Technology Reassessment Committee in 2024 (March 8, 2024) has deliberated on the reassessment plan and subcommittee composition, followed by a reassessment. Objectives This assessment aimed to provide evidence on the clinical utility of the NGS-based gene panel test for patients with ovarian neoplasms to detect additional genetic mutations and determine treatment directions, such as drug selection. Method A literature review was conducted to assess the clinical safety and effectiveness of the NGS-based gene panel test for patients with ovarian neoplasms. All assessment methods were determined through discussions by the Joint Subcommittee on the NGS-Based Gene Panel Test for Solid Cancers (Lung Cancer, Colorectal Cancer, Breast Neoplasms, and Ovarian Neoplasms) (hereinafter referred to as the “subcommittee”) considering the assessment objectives. The subcommittee consisted of three members from the Department of Hematology and Oncology, one member from the Department of Pathology, one member from the Department of Laboratory Medicine, one member from the Department of Pulmonary Medicine, one member from the Department of Surgery (Breast), one member from the Department of Gastroenterology, one member from the Department of Obstetrics and Gynecology, and one member who was an expert in evidence-based medicine. The subjects of this assessment were patients with ovarian neoplasms, and the reference standards and comparator tests were set as single-gene tests (polymerase chain reaction, nucleotide sequencing, in situ hybridization, fluorescent in situ hybridization, immunohistochemistry, etc.). The outcome variables were safety and effectiveness. The safety indicators included adverse events and test-related adverse events, the test failure rate, and the tissue regeneration rate. The effectiveness indicators included gene-specific drug selection and the treatment response (objective response rate and disease control rate). Based on the key questions, three foreign databases (Ovid-MEDLINE, Ovid-EMBASE, and EBM Reviews - Cochrane Central Register of Controlled Trials) and three domestic databases (KoreaMed, Korean Medical Paper Database (KMbase), and Korean Education and Research Information Service (RISS)) were used for the search (last searched on May 3, 2024). The studies finally selected were used to extract data based on a pre-determined data-extraction form. All processes were performed independently by two assessors, and any disagreements were resolved based on a consensus between the assessors. The data were summarized using qualitative review methods. With new biomarkers continuously emerging, the paradigm of cancer treatment is rapidly changing. Therefore, the latest guidelines from relevant academic societies and the current situation in Korea were reviewed. The guidelines were searched using key terms including “ovarian cancer,” “next generation sequencing,” “NGS,” and “multigene profiling” in the Korean Medical Guideline Information Center, the Guideline International Network, the United Kingdom National Institute for Health and Care Excellence, and the United States National Comprehensive Cancer Network (NCCN) (October 14, 2024). In addition, the domestic status was investigated by referring to data from the National Drug Safety Information Portal of the Ministry of Food and Drug Safety (MFDS), the Ministry of Health and Welfare website, and the Health Insurance Review & Assessment Service website. Subsequently, the subcommittee confirmed the appropriateness of the guidelines and the results of the investigation into the domestic status. This assessment was finalized by the Health Technology Reassessment Committee based on the subcommittee review results. Results A literature review of NGS-based gene panel tests for patients with ovarian neoplasms resulted in six final studies (three comparative studies and three case studies, with 1,044 subjects). Most of the study subjects had progressive, recurrent epithelial ovarian neoplasms, and the distribution of molecular subtypes varied across the literature. In addition, all studies included some cases of early-stage (stage I/II) ovarian neoplasms. All specimens for the intervention test were tumor tissues. The types of tumor panels varied depending on the literature; the panels included a minimum of two and a maximum of 382 genes. The comparator test was identified as Sanger sequencing using blood. However, only one study used Sanger sequencing for germline BRCA (gBRCA) testing from 2007 to 2015, with the multi-gene panel test being used after 2015. In addition, four guidelines were included in the assessment, and a survey of the current status in Korea confirmed the reimbursement status of targeted therapies and conventional tests for BRCA genes and homologous recombination deficiency (HRD) in ovarian neoplasms. Clinical utility results The safety of NGS-based gene panel testing was assessed in terms of adverse effects and reactions related to the test, the test failure (non-detection) rate, and the tissue regeneration rate. There were no reports of adverse effects or reactions related to the test or tissue regeneration rates in the literature. The test failure (non-detection) rate was reported in one comparative study, and the failure rate of the intervention test (tumor BRCA, tBRCA) compared to Sanger sequencing (gBRCA) in BRCA mutation detection was reported to be 0.4% (3/47 cases). The causes were reported as errors in the interpretation of the results (one case) and substandard quality of tumor specimens (two cases). The effectiveness was assessed based on the intrinsically disordered regions (IDRs) of target gene mutations, drug selection based on the gene, and the treatment response. The IDR of BRCA1/2 gene mutations for single-gene tests versus the intervention test in ovarian neoplasms was reported in three comparative studies. In two studies of epithelial ovarian neoplasms, the IDR of gBRCA versus somatic BRCA (sBRCA) was 25.9% and 4.29%, respectively, and in one study of high-grade serous carcinoma (HGSC), the IDR of gBRCA versus tBRCA was 4.08%. Four studies reported drug selection (rates) and treatment responses based on target gene mutation identification. The poly ADP-ribose polymerase (PARP) inhibitor selection (matching) rate based on the identification of a BRCA1/2 mutation was 7% (8/115) for patients with gBRCA or sBRCA1/2+ and 3.3% (8/239) for patients tested via Sanger sequencing (gBRCA) in one of the four studies. In one of the three studies, the targeted therapy matching rate based on the tBRCA1/2+ status was 19.2% (14/73) in patients with one or more actionable molecular alterations for PARP inhibitors and 16% (14/86) in the overall population. Treatment within the approved indication was found to be 56.2% (41/73) for patients with one or more actionable molecular alterations. In one of the two studies, the targeted therapy matching rate for patients with one or more actionable molecular alterations was 20.8% (11/53), the PARP inhibitor matching rate according to tBRCA1+ was 5.7% (3/53), and the mTOR inhibitor or clinical trial matching rate based on the identification of other mutations, such as PIK3CA and PTEN, was 15.1% (8/53). The treatment response was reported as a partial response (0%), stable disease (SD) (18.2%), and progressive disease (PD) (36.4%), and it was not possible to evaluate with short-term treatment in 45.5% of cases. In the remaining study, the targeted therapy matching rate was 10.5% (6/57) of the population eligible for targeted therapy and 7.14% (6/84) of the overall population. Five patients with BRCA1/2+ disease received treatment with PARP inhibitors (olaparib), and one patient with PIK3CA+ disease was enrolled in a clinical trial and received treatment with AKT inhibitors. The treatment response was maintained with PARP inhibitor therapy in four of five patients, with three patients remaining relapse-free for more than 5 months and one patient showing PD at 7 months. The remaining patient received PARP inhibitor therapy as a fourth-line monotherapy and still had SD at the time of the analysis, continuing treatment for 7 months. One patient treated with AKT inhibitors still had SD at the time of the outcome analysis and continued treatment for 2 months. Survey of guidelines and domestic status According to the 2024 NCCN guidelines, even in cases of ovarian cancer without gBRCA mutations, molecular alterations including sBRCA1/2, loss of heterozygosity (LOH), and the HRD status should be identified through somatic testing during initial treatment. Furthermore, molecular testing is recommended to evaluate the possibility of administering targeted therapy in recurrent stages. According to the European Society for Medical Oncology (2024), considering that the estimated prevalence of HRD in HGSC is approximately 50%, confirming the HRD status is clinically useful for the use of PARP inhibitors as first-line maintenance therapy for ovarian neoplasms. Currently, available HRD tests used in clinical practice have limited accuracy in predicting functional HRD, but it was recommended that the HRD status be assessed to select patients without gBRCA1/2 mutations for maintenance therapy with PARP inhibitors. In HRD+ tumors that demonstrated a complete or partial response following first-line therapy, including bevacizumab, maintenance therapy with bevacizumab + olaparib was recommended. According to the results of a domestic survey, the target population for maintenance therapy with niraparib monotherapy for progressive ovarian neoplasms, fallopian tube neoplasms, and primary peritoneal cancer has been expanded from patients with BRCA mutations to those who are HRD-positive (BRCA mutation or genomic instability). Conclusion and Recommendations The subcommittee comprehensively considered the current literature and domestic clinical situations to make the following recommendations. The safety of NGS-based gene panel testing was deemed clinically acceptable, as evidenced by the absence of test-related adverse events, adverse reactions, or tissue regeneration rates documented in the literature. However, a failure rate of 6.4% (3/47 cases) was observed, attributable to the substandard quality of tumor specimens and potential errors in the interpretation of results. In addition, as an in vitro diagnostic test, this test did not cause direct harm to the human body other than the tumor and blood collection process, and the sample collection was judged to have a similar degree of safety to a conventional biopsy. Since specimens that have not been subjected to quality control in actual clinical practice were considered unsuitable for this test and were excluded from the test, it was judged to be a safe technology when collecting specimens after fully considering the intratumor heterogeneity (tumor purity) and prior treatment. In terms of effectiveness, the additional detection rate of the test, of 4.1 to 25.9% for treatable target gene mutations (PIK3CA, BRCA), was similar to or higher than that of conventional single-gene tests, and the clinical utility of the test for gene-specific targeted therapy selection was confirmed by matching targeted therapies to patients with treatable targeted mutations, or approximately 20% of all patients, with some reports of an improved treatment response. However, given that the selected studies did not provide within-population comparisons or high-quality evidence, as in case studies, the subcommittee concluded that the evidence in the literature on the effectiveness of therapies targeting gene variants after the use of the NGS gene panel test for patients with advanced ovarian neoplasms is insufficient. Based on the results of the guideline review and domestic status survey, current authoritative guidelines recommend conducting comprehensive tumor-based NGS tests, including those pertaining to BRCA1/2, HRD, and the LOH status, for the selection of PARP inhibitors for patients with progressive ovarian neoplasms. Approximately 50% of all ovarian neoplasms exhibit HRD positivity. Recently, the indication for niraparib monotherapy as first-line maintenance therapy for progressive ovarian neoplasms, fallopian tube neoplasms, and primary peritoneal cancer has been expanded from a “BRCA mutation” to “HRD-positive.” Considering these factors comprehensively, this test has been determined to be clinically useful for confirming BRCA1/2 mutations and the HRD status, as well as for determining treatment directions, such as PARP inhibitor selection, in patients with progressive ovarian neoplasms, fallopian tube neoplasms, or primary peritoneal cancer. However, it should be noted that certain commercial NGS gene panels have been found to confirm the HRD status, exhibiting a level of performance that is comparable to that of analogous health technologies, such as the Myriad MyChoice assay. However, the method for calculating HRD scores is not standardized. Therefore, it is recommended that a standardization plan suitable for domestic conditions be established to generalize the HRD results. The 11th Health Technology Reassessment Committee (November 8, 2024) reviewed the conclusions presented by the joint subcommittee and the opinions of the panel on the “NGS-based gene panel test-solid tumor (ovarian neoplasms)” and decided to uphold the original recommendation.

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• 질환 및 건강상태 > 신생물
• 중재의 종류 > 검사
• 진료과 > 산부인과
• 진료과 > 병리과
• 진료과 > 혈액종양내과
• 진료과 > 진단검사의학과