Chaudhuri在美國放射腫瘤學(xué)會(huì)（ASTRO）第59屆年會(huì)上介紹了研究結(jié)果一項(xiàng)新的研究。該研究，血檢對于檢出癌癥可能預(yù)測局部非小細(xì)胞肺癌（NSCLC）患者的治療結(jié)果，并為醫(yī)生個(gè)體化治療復(fù)發(fā)性疾病提供更多的時(shí)間。研究中循環(huán)腫瘤DNA（ctDNA）在治療后不久即具有可檢測到水平的患者均在兩年內(nèi)復(fù)發(fā)，而所有在治療后不久沒有可檢測到的ctDNA的患者中只有1例復(fù)發(fā)，其余仍然無病長期生存。相反，傳統(tǒng)的影像，不能預(yù)測復(fù)發(fā)或生存。肺癌的侵襲特性使長期管理尤其具有挑戰(zhàn)性。由于NSCLC趨向于進(jìn)展，即使在治療后，因此，定期監(jiān)測復(fù)發(fā)是必要的。然而，通常用于監(jiān)測的計(jì)算機(jī)斷層（CT）掃描常常無法檢出顯微鏡下的腫瘤沉積，也無法分辨是疾病復(fù)發(fā)變化還是治療引起的正常組織變化?！把獧z可以檢測出治療后殘留的微量腫瘤，或許可以改善復(fù)發(fā)監(jiān)測，并可能為醫(yī)生提供數(shù)月的額外時(shí)間來調(diào)整治療從而改善患者的結(jié)局和生活質(zhì)量，”研究的第一作者、斯坦福大學(xué)放射腫瘤科總住院醫(yī)師Aadel Chaudhuri醫(yī)學(xué)博士說?！拔覀兊难芯拷Y(jié)果表明，與CT掃描不同，cDNA分析可以發(fā)現(xiàn)治療完成后不久局部肺癌患者是否通過放療或手術(shù)可能已治愈，或者是否其體內(nèi)仍然有癌細(xì)胞存在。盡管我們預(yù)期分子殘留病變的ctDNA檢測或可以預(yù)測臨床結(jié)局差，但是我們?nèi)泽@訝該檢測是多么強(qiáng)烈的預(yù)測復(fù)發(fā)和生存。”研究背景在治療前即刻以及在治療完成后不久，ctDNA的存在作為Ⅰ-Ⅲ期NSCLC患者的一個(gè)標(biāo)記物估量分子殘留病變（MRD）。對于半數(shù)接受化放療（n＝13/27）的患者，還在治療中期（平均3周，范圍1.4–3.7周）測定ctDNA水平。通過深度測序（CAPP-Seq）癌癥個(gè)體化表達(dá)譜用來評估是否存在ctDNA。使用實(shí)體瘤療效評價(jià)標(biāo)準(zhǔn)（RECIST）評估利用CT成像監(jiān)測掃描?；颊吣挲g中位數(shù)是67歲（范圍，47–91歲），大多數(shù)（67%）是男性。所有41例患者均接受根治性治療，包括放化療（66%）、單純放療（27%）和單純手術(shù)（7%）。該研究的中位隨訪時(shí)間為35個(gè)月（范圍，7-56個(gè)月）。結(jié)果研究人員在41例患者中的38例（93%）治療前檢出了ctDNA。這38例患者中的34例在治療結(jié)束的4個(gè)月內(nèi)采血（預(yù)設(shè)的MRD界標(biāo)）并適于后續(xù)分析。治療前具有ctDNA MRD的34例患者中，超過一半（56%，n=19）在治療后有可檢出的殘留病變。所有這些患者隨后發(fā)生肺癌復(fù)發(fā)，與之相比，沒有可檢出ctDNA MRD的15例患者中只有1例復(fù)發(fā)。與沒有可檢測到ctDNA MRD的患者相比，在治療后具有可檢測的ctDNA MRD患者有更差的無進(jìn)展期和生存期（無進(jìn)展風(fēng)險(xiǎn)比（HR）= 44，P<0.0001；疾病特異性生存率HR=27.7，P<0.0001）。在同一時(shí)間的CT成像不能預(yù)測生存。治療前的ctDNA水平也與生存結(jié)局無關(guān)。在13例治療中期評估的患者中8例ctDNA占總游離DNA的0.1%或以上。對于這些患者，治療中期的ctDNA水平預(yù)測最終疾病進(jìn)展（HR=2.7，P=0.006）。治療中期ctDNA<0.1%的患者治療后兩年無進(jìn)展生存率為60%，與之相比，ctDNA水平≥0.1%的患者則沒有1例患者（HR=4.4，P=0.037）。鏈接：在未來我們可以對患者提供個(gè)性化的處理，靶向手術(shù)后復(fù)發(fā)的腫瘤部位。使用ctDNA，即使病人沒有疾病的臨床癥狀，我們也可以識別，也能監(jiān)測治療的工作進(jìn)行得如何。這代表了手術(shù)后肺癌復(fù)發(fā)的新希望，因?yàn)樵诎霐?shù)以上的患者中，肺癌復(fù)發(fā)率高達(dá)一半。”北京301醫(yī)院在一項(xiàng)項(xiàng)前瞻性的研究，ctDNA具有較好的一致性和更高的陽性預(yù)測值，提示血漿ctDNA可能是監(jiān)測腫瘤更好的分子標(biāo)記物。國內(nèi)首篇對肺癌患者術(shù)前術(shù)后ctDNA檢測的報(bào)道，揭示了基于二代測序平臺的ctDNA檢測技術(shù)在早期非小細(xì)胞肺癌患者評價(jià)中的巨大應(yīng)用潛力。Circulating tumor DNA detection in lung cancer patients before and after surgery.Sci Rep 2016 Sep 19;6:33519PMID:27641744http://www.ascopost.com/News/58079ASTRO 2017: Biomarker Blood Test Predicts Survival Following Localized Lung Cancer TreatmentBy The ASCO PostPosted: 9/26/2017 1:51:04 PMLast Updated: 9/27/2017 1:18:14 PMFindings were presented by Chaudhuri et alat the59th Annual Meeting of the American Society for Radiation Oncology (ASTRO).Key PointsAmong the 34 patients with ctDNA MRD pretreatment, more than half (56%, n = 19) had detectable residual disease after treatment. All of these patients subsequently developed recurrent lung cancer, compared with only 1 of the 15 patients without detectable ctDNA MRD.Patients with detectable ctDNA MRD after treatment had worse freedom from progression and survival than patients without detectable ctDNA MRD.In 8 of the 13 patients assessed mid-treatment, ctDNA accounted for 0.1% or more of all cell-free DNA. For these patients, mid-treatment ctDNA levels predicted eventual disease. 60% of the patients with less than 0.1% ctDNA mid-treatment were progression-free at 2 years following treatment, compared to none of the patients with 0.1% or higher levels of ctDNA.A new study demonstrates that a blood test to detect cancer may predict treatment outcomes for patients with localized non–small cell lung cancer (NSCLC) and afford physicians additional lead time to personalize treatment for recurrent disease. Patients in the study with detectable levels of circulating tumor DNA (ctDNA) shortly after treatment all had recurrences within 2 years, while all but one of the patients without detectable ctDNA shortly after treatment remained disease-free and survived long-term. Conventional imaging, conversely, was not prognostic for recurrence or survival.The aggressive nature of lung cancer can make long-term management especially challenging. Because NSCLC tends to progress, even following treatment, regular monitoring for recurrence is necessary. The computed tomography (CT) scans typically used for monitoring, however, are often unable to detect microscopic tumor deposits or to distinguish normal tissue changes caused by treatment from changes caused by recurrent disease.“Blood tests that can detect minute traces of cancer that remain after treatment could improve recurrence monitoring and potentially offer physicians months of additional lead time to tailor treatments and improve our patients’ outcomes and quality of life,” saidAadel Chaudhuri, MD, PhD, lead author of the study and Chief Resident in Radiation Oncology atStanford University.“Our findings suggest that ctDNA analysis, unlike CT scans, can identify shortly after treatment completion if a patient with localized lung cancer has likely been cured by radiation or surgery or if he or she still has cancer cells present in their body. While we expected that ctDNA detection of molecular residual disease would predict poor clinical outcomes, we were surprised by how strongly predictive the test was for recurrence and survival.”Study BackgroundPresence of ctDNA was measured as a marker of molecular residual disease (MRD) in patients with stage I–III NSCLC immediately before treatment and shortly after treatment was completed. ctDNA levels also were measured mid-treatment (average = 3 weeks, range = 1.4–3.7 weeks) for half of the patients receiving chemoradiation (n = 13 of 27 patients). Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq) was used to assess whether ctDNA was present. Surveillance scans using CT imaging were evaluated using the Response Evaluation Criteria In Solid Tumors(RECIST).The median patient age was 67 years (range, 47–91 years), and most patients (67%) were male. All 41 patients were treated with curative intent, including with chemoradiation therapy (66%), radiation therapy alone (27%), and surgery alone (7%). Median follow-up for the study was 35 months (range, 7–56 months).FindingsResearchers detected ctDNA pretreatment in 38 of the 41 patients (93%). Thirty-four of these 38 patients had blood drawn within 4 months of treatment completion (the prespecified MRD landmark) and were eligible for subsequent analysis.Among the 34 patients with ctDNA MRD pretreatment, more than half (56%, n = 19) had detectable residual disease after treatment. All of these patients subsequently developed recurrent lung cancer, compared with only one of the 15 patients without detectable ctDNA MRD.Patients with detectable ctDNA MRD after treatment had worse freedom from progression and survival than patients without detectable ctDNA MRD (freedom from progression hazard ratio (HR) = 44.0,P< .0001; disease-specific survival HR = 27.7,P< .0001). CT imaging at the same time was not prognostic for survival. ctDNA levels before treatment also were not associated with survival outcomes.In 8 of the 13 patients assessed mid-treatment, ctDNA accounted for 0.1% or more of all cell-free DNA. For these patients, mid-treatment ctDNA levels predicted eventual disease progression (HR = 2.7,P= .006). Sixty percent of the patients with less than 0.1% ctDNA mid-treatment were progression-free at 2 years following treatment, compared to none of the patients with 0.1% or higher levels of ctDNA (HR = 4.4,P= .037).Commentary“In the future, clinicians may be able to use ctDNA analysis to identify patients who could benefit from additional treatment after first-line therapy,” saidMaximilian Diehn, MD, PhD, senior author of the study and Assistant Professor of Radiation Oncology at Stanford.“In a related study also presented at this year’s ASTRO Annual Meeting, we found that ctDNA analysis detected disease recurrence an average 5.5 months earlier than standard-of-care CT imaging for localized lung cancer and helped with interpretation of equivocal follow-up imaging. This suggests that ctDNA analysis could open a window to treat patients with residual cancer early, while disease burden is minimal.”The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO) and does not necessarily reflect the ideas and opinions of ASCO.

腋網(wǎng)綜合征（Axillary Web Syndrome, AWS）是乳腺癌術(shù)后的常見并發(fā)癥。其嚴(yán)重與否取決于傷口的發(fā)展或腋窩處結(jié)締組織的情況。腋網(wǎng)綜合征會(huì)很疼痛，并且影響患側(cè)上臂的活動(dòng)，以下是關(guān)于AWS的詳細(xì)梳理。AWS形成原因AWS最常見的形成原因就是乳腺癌腋窩清掃術(shù)。當(dāng)乳腺癌手術(shù)治療時(shí)，一般會(huì)行改良根治術(shù)或保乳術(shù)。乳腺癌患者也會(huì)接受前哨淋巴結(jié)活檢或腋窩淋巴結(jié)清掃術(shù)，這是由于腋窩淋巴結(jié)為乳腺癌最常見的轉(zhuǎn)移部位之一。前哨淋巴結(jié)活檢和腋窩淋巴結(jié)清掃術(shù)的主要區(qū)別就是切除多少淋巴結(jié)。前哨淋巴結(jié)活檢只涉及到幾個(gè)腋下淋巴結(jié)，具體視情況而定。但是腋窩淋巴結(jié)清掃術(shù)涉及到較多的淋巴結(jié)。AWS可以在術(shù)后的幾天或者幾周后出現(xiàn)。有些患者在術(shù)后幾月才會(huì)出現(xiàn)相關(guān)癥狀?，F(xiàn)在關(guān)于AWS的發(fā)生機(jī)制尚不確定。一個(gè)合理的理論是手術(shù)會(huì)使腋窩的血管和結(jié)締組織受損，導(dǎo)致炎癥發(fā)生，最終導(dǎo)致周圍軟組織的硬化。AWS的發(fā)生率沒有很多統(tǒng)計(jì)學(xué)的數(shù)據(jù)支持，不能確定。AWS診斷時(shí)一般可見硬化的網(wǎng)狀或帶狀的手術(shù)瘢痕，但也有未見傷疤但是有自覺癥狀的患者。癥狀A(yù)WS也叫做“繩”病，因?yàn)樵诨颊咂は驴梢娎K狀或條索狀的組織。AWS的癥狀由嚴(yán)重狀況的不同而不同，大體來說包括以下幾種：瘢痕組織淋巴結(jié)切除的區(qū)域可見瘢痕組織形成。盡管每個(gè)人的厚度不同，但是很容易觀察或者摸到。在一些病例中，手術(shù)瘢痕可從腋窩延上臂內(nèi)側(cè)一直延展到肘部、腕部或者手指處。有些患者可能是一個(gè)長瘢痕，有些則是很多小的條索狀瘢痕。疼痛AWS患者可能會(huì)非常疼痛。皮膚也會(huì)感覺有牽拉和緊的感覺。如果疼痛感和緊繃感存在，患者的自然反應(yīng)可能就是減少手臂活動(dòng)。例如，他們會(huì)盡量避免將手臂舉過頭頂。通過限制上臂活動(dòng)減少疼痛，可以讓她們的情況更糟，由于限制患側(cè)上臂活動(dòng)可以讓她們的組織更緊更硬。體力活動(dòng)減少像剛才提到的，他們通過減少上臂活動(dòng)減輕疼痛。當(dāng)患者手臂不能舉過頭頂時(shí)，會(huì)限制她們做很多事情，甚至像穿衣服都很難受，導(dǎo)致體力活動(dòng)減少。AWS的治療盡管AWS不是一個(gè)可以威脅生命的并發(fā)癥，但是嚴(yán)重地影響患者生活質(zhì)量。如果情況輕微，不影響患者的活動(dòng)范圍，可能不需要系統(tǒng)治療。當(dāng)推薦患者治療時(shí)，應(yīng)該以放松瘢痕組織、改善活動(dòng)范圍和減輕不適感為目的。視瘢痕組織范圍的情況，可能治療僅僅可以減輕一部分條索瘢痕導(dǎo)致的緊繃感。例如，如果瘢痕組織從腋窩一直延伸至腕部，那么肘部的區(qū)域可能仍然會(huì)感覺緊繃。治療方法如下：正確的的牽拉鍛煉在醫(yī)學(xué)指南的規(guī)定和醫(yī)生、物理治療師的指導(dǎo)下進(jìn)行拉伸鍛煉。具體的拉伸策略根據(jù)瘢痕組織的不同而有所差別。下面是指南中的推薦動(dòng)作之一：◆向側(cè)方抬起手臂，保持肘部挺直；◆從側(cè)方盡力慢慢舉起手，直到感覺有拉伸感；◆堅(jiān)持持續(xù)拉伸30秒；◆持續(xù)重復(fù)該動(dòng)作，每次力爭將手舉地更高。堅(jiān)持拉伸30秒十分關(guān)鍵，如果持續(xù)時(shí)間較短，那么將起不到鍛煉軟組織，改善活動(dòng)范圍的作用。按摩多種按摩手段可以對AWS起到緩解作用，例如幫助神經(jīng)滑動(dòng)、軟組織松解等等。不同的按摩方法可以幫助結(jié)締組織控制、促進(jìn)疤痕組織分解、改善上臂活動(dòng)受限狀況。按摩需要由專業(yè)的按摩治療師實(shí)施現(xiàn)在，對于瘢痕組織分解后到底會(huì)發(fā)生什么的具體機(jī)制尚不明確。一個(gè)理論說，瘢痕組織會(huì)被身體重吸收。術(shù)后患者應(yīng)該向?qū)I(yè)人士尋求按摩治療，以免組織的進(jìn)一步受損。激光治療物理治療師可以應(yīng)用低級別激光治療AWS，通過發(fā)射聚焦的激光直接打碎硬化的瘢痕組織。激光治療可能不對所有人都有效。例如，它會(huì)收到瘢痕組織厚度的局限。一些患者可能需要多療程的激光治療。激光治療也有一些副作用，需要臨床醫(yī)生對利弊做出權(quán)衡。AWS的家庭護(hù)理需要尋求專業(yè)人士的幫助指導(dǎo)家庭護(hù)理。例如，他們可能告訴患者在家里如何進(jìn)行拉伸鍛煉的方法。其他的家庭護(hù)理措施包括：非甾體類止痛藥：盡管非甾體類止痛藥不能幫助患者解決根本問題，但是可以明顯緩解疼痛，對患者的拉伸鍛煉也有輔助作用。溫?zé)嵬夥螅簯?yīng)用溫?zé)嵬夥蟮姆椒梢宰尵植扛邮孢m。但是也要遵醫(yī)囑適度進(jìn)行溫?zé)嵬夥?，因?yàn)橥夥筮^多可以刺激淋巴液的產(chǎn)生，可能讓癥狀加重。

NCCN指南(2015.V1)：以下內(nèi)容摘錄編譯自2015.V1版的NCCN小細(xì)胞肺癌指南，主要為小細(xì)胞肺癌（SCLC）的化療方案選擇以及目前所做的臨床試驗(yàn)進(jìn)展。對于所有SCLC患者，化療是治療的基本組成。手術(shù)切除的病人推薦輔助化療。對于局限期SCLC和PS較好（0-2）的病人，推薦化療同步胸部放療（1級）。對于廣泛期病人，推薦單獨(dú)化療，不過也有對某些病人為了緩解癥狀使用放療。對于廣泛期和腦轉(zhuǎn)移病人，可在全腦放療之前或之后給予化療，取決于病人是否有神經(jīng)病學(xué)癥狀。單藥或者多藥聯(lián)合方案在SCLC患者中都有應(yīng)用。依托泊苷和順鉑（EP）方案是最常用的初始聯(lián)合化療方案，該方案取代了烷化劑/蒽環(huán)類為基礎(chǔ)的方案，基于其在局限期疾病中療效和不良反應(yīng)的優(yōu)勢。EP同步胸部放療推薦用于治療局限期SCLC病人（1級）。在聯(lián)合胸部放療時(shí)，EP使食管炎、肺部毒性和血液學(xué)毒性的風(fēng)險(xiǎn)增加。對于同步化放療的病人不推薦使用骨髓生長因子。在臨床實(shí)踐中，卡鉑通常取代順鉑以降低嘔吐、神經(jīng)病變和腎病的風(fēng)險(xiǎn)，但是會(huì)造成骨髓抑制的風(fēng)險(xiǎn)增加。臨床試驗(yàn)表明順鉑和卡鉑方案的療效相當(dāng)。有很多聯(lián)合方案在廣泛期SCLC中進(jìn)行評估，但支持其優(yōu)于EP方案的證據(jù)都很少一致。伊立替康和鉑類藥物的聯(lián)合對EP方案提出了最大的挑戰(zhàn)。一項(xiàng)日本進(jìn)行的III期研究表明伊立替康+順鉑帶來的中位生存期為12.8個(gè)月，而EP方案為9.4個(gè)月（p=0.002）。但是，之后美國進(jìn)行的兩個(gè)大型III期研究也是比較了伊立替康+順鉑對比EP方案，并未發(fā)現(xiàn)緩解率和OS的差異。一項(xiàng)III期試驗(yàn)（n=220）發(fā)現(xiàn)伊立替康+卡鉑相比于卡鉑+口服依托泊苷對于OS有輕微的改善（8.5 vs 7.1個(gè)月，p=0.04）。基于這些發(fā)現(xiàn)，NCCN指南添加了卡鉑+伊立替康方案用于廣泛期疾病的治療。很多策略被評估用以改善廣泛期SCLC患者的結(jié)局，包括添加第三種藥物到標(biāo)準(zhǔn)兩藥方案中。在兩項(xiàng)試驗(yàn)中，添加異環(huán)磷酰胺（或者環(huán)磷酰胺+一種蒽環(huán)類）到EP方案中顯示一定程度的生存優(yōu)勢。但是，這些發(fā)現(xiàn)都不是很一致，而且添加一種烷化劑，伴或不伴蒽環(huán)類，都會(huì)顯著增加血液學(xué)毒性。同樣，添加紫杉醇到順鉑或卡鉑+依托泊苷中，在II期試驗(yàn)中顯示出一定希望，但在III期試驗(yàn)中未發(fā)現(xiàn)能改善生存，還會(huì)增加毒性。在4-6個(gè)周期后維持治療或者鞏固化療可以輕微延長緩解期，但是不改善生存，毒性風(fēng)險(xiǎn)還增加?？寡苌芍委熞苍赟CLC患者中進(jìn)行了評估。對于局限期SCLC患者，一項(xiàng)II期研究探索了伊立替康、卡鉑和貝伐珠單抗同步放療，之后貝伐珠單抗維持治療的療效，該研究提前終止了，因?yàn)闅夤苁彻墀浀陌l(fā)生率很高。在廣泛期SCLC患者中，兩項(xiàng)II期試驗(yàn)考察了鉑類為基礎(chǔ)的化療聯(lián)合貝伐珠單抗的療效，發(fā)現(xiàn)緩解率和生存數(shù)據(jù)的希望。一項(xiàng)III期研究正在進(jìn)行，確定貝伐珠單抗的加入是否能提高廣泛期SCLC患者的療效。目前，NCCN指南還不推薦貝伐珠單抗的使用?？偠灾?，目前試圖通過添加更多藥物、使用劑量加強(qiáng)化療方案、維持治療、換到非交叉耐藥化療方案等來改善長期生存的方法，相比于標(biāo)準(zhǔn)療法都沒有產(chǎn)生明顯的優(yōu)勢。詳解各種化療方案初始化療或者輔助化療：局限期（最多4-6個(gè)周期）：順鉑（60mg/m2d1）和依托泊苷（120mg/m2d1,2,3）順鉑（80mg/m2d1）和依托泊苷（100mg/m2d1,2,3）卡鉑（AUC 5-6 d1）和依托泊苷（100mg/m2d1,2,3）化療+放療期間，推薦順鉑/依托泊苷（1級）同步化療+放療時(shí)不推薦使用骨髓生長因子（對于GM-CSF是1級）廣泛期（最多4-6個(gè)周期）：順鉑（75mg/m2d1）和依托泊苷（100mg/m2d1,2,3）順鉑（80mg/m2d1）和依托泊苷（80mg/m2d1,2,3）順鉑（25mg/m2d1,2,3）和依托泊苷（100mg/m2d1,2,3）卡鉑（AUC 5-6 d1）和依托泊苷（100mg/m2d1,2,3）順鉑（60mg/m2d1）和伊立替康（60mg/m2d1,8,15）順鉑（30mg/m2）和伊立替康（65mg/m2d1,8）卡鉑（AUC 5 d1）和伊立替康（50mg/m2d1,8,15）后續(xù)化療：優(yōu)選臨床試驗(yàn)復(fù)發(fā)<2-3個(gè)月，ps0-2：< strong="">紫杉醇多西他賽拓?fù)涮婵?PO或者IV伊立替康替莫唑胺 75mg/m2/d x 21天吉西他濱異環(huán)磷酰胺復(fù)發(fā)>2-3個(gè)月到6個(gè)月：拓?fù)涮婵?PO或者IV（1級）紫杉醇多西他賽伊立替康吉西他濱長春瑞濱口服依托泊苷替莫唑胺 75mg/m2/d x 21天環(huán)磷酰胺/阿霉素/長春新堿（CAV）復(fù)發(fā)>6個(gè)月：原始方案注：如無特殊注明，推薦等級為2A。