Oncology Frontier:Prof Postmus， Congratulations for winning the first Heine H. Hansen (HHH) Award. As the first HHH Award recipient， what means it to receive the award?

　　《肿瘤瞭望》：Postmus教授，恭喜您获得首届Heine H. Hansen（HHH）奖，作为首位获奖者，请您谈一谈HHH奖项的意义和重要性？

　　Dr. Postmus: This is very special not only for me， but also for all the people I worked with over 35 years in the area of lung cancer， thoracic oncology， in different disciplines—from pathology， screening， surgery， pulmonology， medical oncology， radiotherapy， nuclear medicine— every aspect that is necessary for the treatment of lung cancer. I have worked with all these people for since I started in 1978. To receive this award with the name of Heine H. Hansen， who was a kind of role model for me. He was a fantastic man. He was a real pioneer in the area of lung cancer， for he was one of the first who started research on lung cancer， and he extended his research over decades， resulting in a lot of very interesting and prominent research papers. As he inspired many people， he had a lot of people working with him， who later on became very important investigators in other parts of the world. For instance， Fred Hirsch moved to the US， but he was originally one of the students of Heine Hansen， and had worked very closely with him in his early years in pathology.

　　Postmus博士：HHH奖是一个特别的奖项，这个奖不仅仅属于我一人，而是属于35年来和我一起致力于肺癌、胸腔肿瘤研究的所有人，涵盖各个必要的学科：病理、检查、手术、呼吸病学、肿瘤内科、放射治疗、核医学等。自从1978年以来我们就一起工作。.HHH奖以Heine H. Hansen命名，他是一个了不起的人，是肺癌研究领域的真正先驱，且他的研究持续了几十年，发表了许多优秀的研究论文；他激励了许多人，很多和他一起工作的人成为各地区非常重要的研究者。例如Fred Hirsch（2015年世界肺癌大会主席）移居美国，但他原本是Heine H. Hansen博士的学生之一，他们早年一起从事于病理研究。

　　Oncology Frontier:On 17 April， 110PD “Single organ metastatic disease， a new prognostic factor for overall survival (OS) in stage IV non-small cell lung cancer (NSCLC)”is（was）discussed， could you once again give us a brief idea of your study?

　　《肿瘤瞭望》：4月17日的日程中，您的研究摘要110PD“单一器官转移：Ⅳ期非小细胞肺癌（NSCLC）总生存期（OS）的新的预后因素”将被讨论，请您简单介绍您的研究？

　　Dr. Postmus: This study is a database study， from the national cancer registry in the Netherlands， in which all kinds of things are scored. It also illustrates that there are limitations to what you can do， because you cannot tell anything more than what is incorporated in the scoring system. This study scored for a prognostic factor in two databases: one with the UICC 6 as the staging system， and the other where the UICC 7 was in practice.

　　Postmus博士：研究数据来自荷兰癌症登记处2006年1月1日至2012年12月31日组织学确诊为IV期NSCLC的患者，研究中的两个数据库分别采用第6版UICC 分期系统和第7版的UICC分期系统。

　　The huge database we used to see the impact of a single organ metastasis or a multiple organ metastasis. We could not figure out if someone had two， or three， or four metastasis in the same organ because that is not mentioned in the database. We could demonstrate that the prognostic part of it is that if you have a single organ with metastasis， the prognosis is much better in a patient with stage 4 diseases， than if you have two organs or even more organs with metastasis. We could not find out whether there is any influence of mutation， for instance in EGFR， because that is not registered in the database. None of these patients were from the period that EGFR mutation was standard practice， that is only standard since a few years. These are limitations， because we couldn’t figure out whether one single brain metastasis had a different prognosis than five brain mets. Also， in that period， stereotacticradio therapy was not there. So it’s difficult to translate this into today’s practice， but the important message is that these patients had a better prognosis. The clinical consequence could be that if you attack the site where the single organ metastasis is located， it might result in a much better prognosis as well. So this study needs to be followed with a study wherein you randomize between follow up after standard treatment for stage 4， versus the normal treatment， and in addition to that something special， such as a lung lobectomy， or taking out brain mets， or giving SABR to single organ metastasis.

　　L. Hendriks、J.L. Derks是主要研究者。研究评估了IV期NSCLC中，单个器官转移与多个器官转移（M+）、受累器官和局部病灶状态对OS的预后影响。本研究入选了11，094例患者：60%为男性，平均年龄为65岁，73%患有腺癌（AdC）。该研究未确认是否患者同一器官有多个转移灶，因为数据库中未提及。研究显示，有1个（n=5676）、2个（n=3280）和≥3个（n=2138）器官M+患者的中位OS分别为6.7个月、4.3个月和2.8个月（P <0.001）。研究证明，单个器官转移的IV期NSCLC患者，特别是同时有低TN分期的患者的预后良好。研究者未能找出基因突变（如EGFR突变）的影响，因其未在数据库中登记。研究未确认单个脑转移病灶是否比多个脑转移病灶预后更好。该研究传递的临床意义是“针对单个转移器官的病灶治疗会改善预后”。因此该研究之后还应再有一个研究：比较IV期NSCLC标准治疗后随访vs.标准治疗+局部治疗（如肺叶切除术、取出大脑转移瘤，或单器官转移的立体定向消融放射治疗[SABR]治疗）。

　　The question whether the addition of local treatment to general treatment in stage IV might improve the prognosis is currently a topic of possible research. For instance， the small cell study presented this morning by B. Slotman from VU University， in which extensive disease stage small cell patients， radiotherapy to the chest improved the outcome for the group who received radiotherapy， despite the fact that they had metastasis in many other places as well.  The same was demonstrated in a PCI study as well， where the patients had extended disease received brain radiation， which improved survival for these patients. So， apparently attacking the area with the metastasis in addition to general treatment is something that is worthwhile to study， and maybe even apply in daily practice.

　　IV期NSCLC一般治疗后加用局部治疗能否改善预后是目前的研究课题。在小细胞肺癌方面， ELCC 2015在18日上午的“Refining radiation therapy for SCLC”环节，荷兰阿姆斯特丹VU大学医学中心的Ben Slotman博士的报告“Thoracic radiation therapy for extensive disease（广泛期疾病的胸部放射治疗）”显示，广泛期小细胞肺癌患者采取胸部放疗改善治疗结果，尽管患者有多处其他部位转移。PCI研究也显示广泛期SCLC脑部放疗改善生存。所以，IV期NSCLC一般治疗之外加用“针对转移病灶”的局部治疗值得研究、甚至值得应用于临床实践。

摘要原文

Single organ metastatic disease， a new prognostic factor for overall survival (OS) in stage IV non-small cell lung cancer (NSCLC)

L. Hendriks1， J.L. Derks1， P.E. Postmus2， R.A. Damhuis3， R.M. Houben4， E.G. Troost4， M.M. Hochstenbag1， E.F. Smit5 and A.-M.C. Dingemans1

Aim: To assess the prognostic impact on OS of single vs multiple organ metastases (M+)， the organ affected， and the local disease status in stage IV NSCLC.

Methods: Data on histologically confirmed stage IV NSCLC patients (pts) diagnosed between 1-1-2006 and 31-12-2012 were retrieved from the Netherlands Cancer Registry. Multivariable survival analyses (including age， gender， histology， M-status (TNM7 M1a vs M1b and TNM6 M1)， local disease status (low: T0-2 and N0-1 vs high: T3-4 and/or N2-3)， number of organs with M + ， actual organ affected) were performed for all pts， and subsequently for 2 subgroups: 18FDG-PET-staged pts and pts receiving active anticancer treatment.

Results: 11，094 pts were selected: 60% male， mean age 65 years， 73% adenocarcinoma (AdC). Median OS for 1 (N = 5676)， 2 (N = 3280) and ≥3 (N = 2138) organs with M+ was 6.7， 4.3 and 2.8 months， respectively (p < 0.001). HR for 2 vs 1 organ(s) was 1.3 (p <0.001)， and for ≥ 3 vs 1 organ(s) 1.9 (p < 0.001). In 18FDG-PET-staged pts (N = 1517)， median OS was 8.6， 5.7 and 3.8 months， respectively (p < 0.001). HR for 2 vs 1 organ(s) was 1.4 (p < 0.001) and for ≥3 vs 1 organ(s) 2.2 (p < 0.001). In single organ M + ， OS for high vs low TN status was overall 6.5 vs 8.5 months (HR 1.4， p < 0.001) and was 8.2 vs 11.6 months (HR 1.6， p < 0.001) in those staged with 18FDG-PET. When analyzing the subgroup of pts receiving active anticancer treatment， single organ M+ and low TN-status remained significant prognostic factors: median OS for 1， 2 and ≥ 3 organ M+ was 10.4， 7.3 and 5.7 months， respectively (HR 2 vs 1 organ: 1.4， HR ≥3 organs vs 1: 1.9， p < 0.001). Median OS for high vs low TN-status was 9.9 months vs 13.7 months (HR 1.5， p < 0.001). In single organ M + ， only intrathoracic M+ (current M1a) and extrathoracic lymph node (ET-LN) M+ were associated with superior OS. HR for pulmonary M+ was 0.6， for pleural M+ 0.8 and for ET-LN M+ 0.8. Results were comparable when repeating analyses for TNM6 and TNM7 separately.

Conclusions: Single organ M+ stage IV NSCLC pts have a favorable prognosis， especially in combination with low TN status. The current M1a group has a better OS compared to other organs with M+. However， in the distant M+ group (current M1b) there is， apart from ET-LN M + ， no organ consistently associated with a superior OS.