磁共振成像和十二基因表達(dá)譜評(píng)分

可以指導(dǎo)乳腺導(dǎo)管原位癌治療決策

　　先進(jìn)的診斷技術(shù)，例如磁共振成像和基因表達(dá)譜,，可能有助于指導(dǎo)乳腺導(dǎo)管原位癌患者的精準(zhǔn)治療,。

　　2019年1月17日，《美國(guó)醫(yī)學(xué)會(huì)雜志》腫瘤學(xué)分冊(cè)在線發(fā)表哈佛大學(xué)麻省總醫(yī)院,、羅德島布朗大學(xué),、芝加哥西北大學(xué)、密歇根大學(xué),、賓夕法尼亞愛(ài)因斯坦醫(yī)療網(wǎng)絡(luò),、印第安納大學(xué)、國(guó)家癌癥研究所,、新奧爾良奧克斯納醫(yī)療中心,、西雅圖華盛頓大學(xué)、新澤西亨特頓醫(yī)療中心,、賓夕法尼亞朗肯瑙醫(yī)療中心,、密蘇里斯普林菲爾德慈善醫(yī)院、維克弗里斯特大學(xué),、紐約愛(ài)因斯坦醫(yī)學(xué)院,、紐約紀(jì)念醫(yī)院斯隆凱特林癌癥中心的研究報(bào)告,，分析了磁共振成像后改變?yōu)槿榉壳谐g(shù)的患者比例及其改變?cè)?，以及患者?duì)乳腺導(dǎo)管原位癌12基因評(píng)分指導(dǎo)放療的依從性。

　　該東部腫瘤學(xué)協(xié)作組（ECOG）和美國(guó)放射學(xué)會(huì)成像網(wǎng)絡(luò)（ACRIN）前瞻隊(duì)列非隨機(jī)對(duì)照研究（E4112,，NCT02352883）于2015年3月25日～2016年4月27日從75個(gè)機(jī)構(gòu)入組粗針活檢確診乳腺導(dǎo)管原位癌符合廣泛局部切除指征的女性368例,，手術(shù)前接受乳腺磁共振成像，隨后選擇手術(shù)方案時(shí)考慮磁共振成像結(jié)果,。乳腺導(dǎo)管原位癌12基因評(píng)分用于指導(dǎo)最終進(jìn)行廣泛局部切除手術(shù)并且無(wú)腫瘤切緣≥2厘米患者的放療推薦意見(jiàn),。主要研究終點(diǎn)為推算改變?yōu)槿榉壳谐g(shù)的比例及其改變?cè)颉?/span>

　　結(jié)果，339例可評(píng)估女性（平均年齡59.1±10.1歲,，其中歐洲后裔262例,，占77.3%）磁共振成像前符合廣泛局部切除指征，其中65例（19.2%,，95%置信區(qū)間：15.3%～23.7%）改變?yōu)槿榉壳谐g(shù)：

• 根據(jù)成像結(jié)果25例（38.5%）

• 根據(jù)患者偏好25例（38.5%）

• 根據(jù)切緣陽(yáng)性10例（15.4%）

• 根據(jù)基因檢測(cè)3例（4.6%）

• 根據(jù)放療禁忌2例（3.1%）

　　285例磁共振成像后廣泛局部切除作為首次手術(shù)方案,，其中274例（96.1%）實(shí)現(xiàn)成功保乳,。

　　171例女性符合乳腺導(dǎo)管原位癌12基因評(píng)分指導(dǎo)放療指征（切緣陰性、無(wú)浸潤(rùn)病變,、有評(píng)分）

• 評(píng)分<39分82例（48.0%,，95%置信區(qū)間：40.6%～55.4%）其中放棄放療75例（91.5%）

• 評(píng)分≥39分89例（52.0%，95%置信區(qū)間：44.6%～59.4%）其中接受放療84例（94.4%）

• 依從推薦意見(jiàn)159例（93.0%）

　　因此,，該研究結(jié)果表明,，根據(jù)常規(guī)成像檢查，對(duì)于符合廣泛局部切除指征的乳腺導(dǎo)管原位癌女性,，多種因素與改變?yōu)槿榉壳谐g(shù)相關(guān),。乳腺磁共振成像和12基因檢測(cè)可以分別對(duì)初次手術(shù)方案和術(shù)后是否放療進(jìn)行個(gè)體化決策，有助于醫(yī)患更精準(zhǔn)地做出治療決定,。該研究可為隨機(jī)臨床研究方案設(shè)計(jì)提供所需有用初步信息,，以確定磁共振成像和乳腺導(dǎo)管原位癌12基因評(píng)分對(duì)手術(shù)、放療,、醫(yī)療資源利用,、臨床結(jié)局的影響，實(shí)現(xiàn)更加精準(zhǔn)治療的最終目標(biāo),。

相關(guān)閱讀

• 12基因模型對(duì)乳腺導(dǎo)管原位癌預(yù)后預(yù)測(cè)的研究進(jìn)展

JAMA Oncol. 2019 Jan 17. [Epub ahead of print]

Association of Magnetic Resonance Imaging and a 12-Gene Expression Assay With Breast Ductal Carcinoma In Situ Treatment.

Constance D. Lehman; Constantine Gatsonis; Justin Romanoff; Seema A. Khan; Ruth Carlos; Lawrence J. Solin; Sunil Badve; Worta McCaskill-Stevens; Ralph L. Corsetti; Habib Rahbar; Derrick W. Spell; Kenneth B. Blankstein; Linda K. Han; Jennifer L. Sabol; John R. Bumberry; Ilana Gareen; Bradley S. Snyder; Lynne I. Wagner; Kathy D. Miller; Joseph A. Sparano; Christopher Comstock.

Massachusetts General Hospital, Harvard Medical School, Boston; Brown University School of Public Health, Providence, Rhode Island; Northwestern University, Chicago, Illinois; University of Michigan, Ann Arbor; Albert Einstein Healthcare Network, Philadelphia, Pennsylvania; Indiana University, Indianapolis; National Cancer Institute, Bethesda, Maryland; Ochsner Medical Center, New Orleans, Louisiana; University of Washington, Seattle; Gulf South National Cancer Institute Community Oncology Research Program, New Orleans, Louisiana; Hunterdon Medical Center, Flemington, New Jersey; Lankenau Medical Center, Wynnewood, Pennsylvania; Mercy Hospital, Springfield, Missouri; Wake Forest University Health Sciences, Winston Salem, North Carolina; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York; Memorial Sloan Kettering Cancer Center, New York, New York.

This nonrandomized clinical trial of women with ductal carcinoma in situ examines reasons for conversion to mastectomy after magnetic resonance imaging and adherence to radiotherapy use guided by the 12-gene ductal carcinoma in situ score.

QUESTION: What is the association of breast magnetic resonance imaging and a 12-gene expression assay with the treatment of women with ductal carcinoma in situ of the breast who are candidates for breast conservation surgery and radiotherapy?

FINDINGS: In this nonrandomized clinical trial of a prespecified primary outcome among 339 women with pure ductal carcinoma in situ, after magnetic resonance imaging, 19% of patients eligible for wide local excision converted to mastectomy; 38% of conversions were based on magnetic resonance imaging findings and 62% on other reasons. Wide local excision was the final surgical procedure in 96% of women who received it as the first procedure after magnetic resonance imaging, and adherence to radiotherapy use guided by a 12-gene assay exceeded 90%.

MEANING: Breast magnetic resonance imaging and a 12-gene assay may be used to tailor primary surgical treatment and radiotherapy, respectively, and inform patient and physician decision-making to support more targeted therapy.

IMPORTANCE: Advanced diagnostics, such as magnetic resonance imaging (MRI) and gene expression profiles, are potentially useful to guide targeted treatment in patients with ductal carcinoma in situ (DCIS).

OBJECTIVES: To examine the proportion of patients who converted to mastectomy after MRI and the reasons for those conversions and to measure patient adherence to radiotherapy guided by the 12-gene DCIS score.

DESIGN, SETTING, AND PARTICIPANTS: Analysis of a prospective, cohort, nonrandomized clinical trial that enrolled women with DCIS on core biopsy who were candidates for wide local excision (WLE) from 75 institutions from March 25, 2015, to April 27, 2016, through the Eastern Cooperative Oncology Group - American College of Radiology Imaging Network trial E4112.

INTERVENTIONS: Participants underwent breast MRI before surgery, and subsequent management incorporated MRI findings for choice of surgery. The DCIS score was used to guide radiotherapy recommendations among women with DCIS who had WLE as the final procedure and had tumor-free excision margins of 2 mm or greater.

MAIN OUTCOMES AND MEASURES: The primary end point was to estimate the conversion rate to mastectomy and the reason for conversion.

RESULTS: Of 339 evaluable women (mean [SD] age, 59.1 [10.1] years; 262 [77.3%] of European descent) eligible for WLE before MRI, 65 (19.2%; 95% CI, 15.3%-23.7%) converted to mastectomy. Of these 65 patients, conversion was based on MRI findings in 25 (38.5%), patient preference in 25 (38.5%), positive margins after attempted WLE in 10 (15.4%), positive genetic test results in 3 (4.6%), and contraindication to radiotherapy in 2 (3.1%). Among the 285 who had WLE performed after MRI as the first surgical procedure, 274 (96.1%) achieved successful breast conservation. Of 171 women eligible for radiotherapy guided by DCIS score (clear margins, absence of invasive disease, and score obtained), the score was low (<39) in 82 (48.0%; 95% CI, 40.6%-55.4%) and intermediate-high (≥39) in 89 (52.0%; 95% CI, 44.6%-59.4%). Of these 171 patients, 159 (93.0%) were adherent with recommendations.

CONCLUSIONS AND RELEVANCE: Among women with DCIS who were WLE candidates based on conventional imaging, multiple factors were associated with conversion to mastectomy. This study may provide useful preliminary information required for designing a planned randomized clinical trial to determine the effect of MRI and DCIS score on surgical management, radiotherapy, overall resource use, and clinical outcomes, with the ultimate goal of achieving greater therapeutic precision.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02352883

DOI: 10.1001/jamaoncol.2018.6269