Perspektiven in Diagnostik und Therapie des oligometastasierten Lungenkarzinoms

Zusammenfassung

Das Stadium der Oligometastasierung ist definiert als eine klinisch und radiologisch an Anzahl und Tumorvolumen limitierte und im Verlauf stabile Metastasierung. Ist das Metastasierungsausmaß auf 1 oder 2 Organsysteme und die Anzahl der Metastasen auf maximal 5 Metastasen begrenzt, so können unterschiedliche lokal ablative Verfahren, wie die chirurgische Resektion und stereotaktische Strahlentherapie, ihre Berechtigung haben. Die biologischen Grundlagen der Oligometastasierung als eines intermediären Tumorstadiums sind heute noch weitestgehend unverstanden. Da aussagekräftige prädiktive Biomarker fehlen, beruht die Patientenauswahl weiterhin auf etablierten klinischen Prognosefaktoren. Hierzu zählen der thorakale Lymphknotenstatus des primären Lungenkarzinoms und das zeitliche Auftreten der Metastasierung als synchron oder metachron. Vor jeder Operation oder lokal ablativen Strahlentherapie mit kurativem Ansatz muss stets eine weitergehende Polymetastasierung mittels FDG-PET/CT und MRT des Schädels ausgeschlossen werden. Neben publizierten retrospektiven Fallserien finden sich aktuell 3 prospektiv randomisierte Studien, die einen signifikanten Behandlungsvorteil hinsichtlich des progressionsfreien Überlebens der Patienten mit lokal ablativer Therapie gegenüber der Vergleichskohorte belegen. Ein günstiger Effekt auf das Langzeitüberleben nach lokal ablativer Therapie ist ebenso wahrscheinlich. Zur zukünftigen Festlegung des Stellenwertes lokal ablativer Verfahren innerhalb moderner onkologischer Therapiekonzepte unter Einschluss der Immuntherapie und molekular stratifizierter Behandlungen sind weitere Phase III-Studien in Entwicklung.

Abstract

Oligometastatic disease is defined as an intermediary disease state with a limited number and volume of metastatic lesions. In the presence of five or fewer lesions, confined to two or fewer organ systems, local ablative therapy including stereotactic radiotherapy and surgical resection, may be justified. The biological bases of this intermediary disease state are not entirely understood. In the absence of reliable biomarkers, patient selection for local ablative therapy still relies on such clinical prognostic factors as thoracic lymph node status and whether the metastases in question are synchronous or metachronous. Any local ablative intervention – whether surgical resection or stereotacic radiotherapy – must be preceded by FDG-PET/CT and cMRT to exclude frank metastatic disease. In addition to various retrospective case studies, three prospective randomized studies suggest significantly greater progression free survival following local ablative therapy. A positive effect on overall survival seems just as likely. In the age of immune therapies and treatment stratification based on molecular markers the future of local ablative treatments in the context of modern oncology is not entirely well defined; further phase III studies are being developed.

Schlüsselwörter

lokal ablative Therapie - Oligometastasierung - Lungenkarzinom - Thoraxonkologie

Keywords

local ablative therapy - oligometastases - lung cancer - thoracic oncology

Publication History

Article published online:
08 April 2021

• Literatur

• 1 Edwards AT. MALIGNANT DISEASE OF THE LUNG. Br Med J 1931; 1: 129-146.2 DOI: 10.1136/bmj.1.3655.129.
• 2 Ramalingam S, Belani C. Systemic chemotherapy for advanced non-small cell lung cancer: recent advances and future directions. Oncologist 2008; 13 (Suppl. 01) 5-13 DOI: 10.1634/theoncologist.13-S1-5.
• 3 Quint LE, Tummala S, Brisson LJ. et al. Distribution of distant metastases from newly diagnosed non-small cell lung cancer. Ann Thorac Surg 1996; 62: 246-250 DOI: 10.1016/0003-4975(96)00220-2.
• 4 Albain KS, Crowley JJ, LeBlanc M. et al. Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol 1991; 9: 1618-1626 DOI: 10.1200/JCO.1991.9.9.1618.
• 5 Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol 1995; 13: 8-10 DOI: 10.1200/jco.1995.13.1.8.
• 6 Yano T, Okamoto T, Haro A. et al. Local treatment of oligometastatic recurrence in patients with resected non-small cell lung cancer. Lung Cancer 2013; 82: 431-435 DOI: 10.1016/j.lungcan.2013.08.006.
• 7 Torok JA, Gu L, Tandberg DJ. et al. Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer. Clin Lung Cancer 2017; 18: e57-70 DOI: 10.1016/j.cllc.2016.06.011.
• 8 Niibe Y, Hayakawa K. Oligometastases and Oligo-recurrence: The New Era of Cancer Therapy. Jpn J Clin Oncol 2010; 40: 107-111
• 9 Dingemans AMC, Hendriks LEL, Berghmans T. et al. Definition of Synchronous Oligometastatic Non–Small Cell Lung Cancer—A Consensus Report. J Thorac Oncol 2019; 14: 2109-119 DOI: 10.1016/j.jtho.2019.07.025.
• 10 Tönnies S, Tönnies M, Kollmeier J. et al. Impact of preoperative 18F-FDG PET/CT on survival of resected mono-metastatic non-small cell lung cancer. Lung Cancer 2016; 93: 28-34
• 11 Chee KG, Nguyen DV, Brown M. et al. Positron emission tomography and improved survival in patients with lung cancer: The Will Rogers phenomenon revisited. Arch Intern Med 2008; 168: 1541-1549 DOI: 10.1001/archinte.168.14.1541.
• 12 Ashworth AB, Senan S, Palma DA. et al. An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer. Clin Lung Cancer 2014; 15: 346-355 DOI: 10.1016/j.cllc.2014.04.003.
• 13 Schanne DH, Heitmann J, Guckenberger M. et al. Evolution of treatment strategies for oligometastatic NSCLC patients – A systematic review of the literature. Cancer Treat Rev 2019; 80: 101892 DOI: 10.1016/j.ctrv.2019.101892.
• 14 Giaj-Levra N, Giaj Levra M, Berghmans T. et al. Oligometastatic non-small cell lung cancer (NSCLC): Does number of metastasis matter?. Lung Cancer 2020; 139: 216-218 DOI: 10.1016/j.lungcan.2019.11.005.
• 15 Magilligan DJ, Duvernoy C, Malik G. et al. Surgical Approach to Lung Cancer with Solitary Cerebral Metastasis: Twenty-Five Years’ Experience. Ann Thorac Surg 1986; 42: 360-364 DOI: 10.1016/S0003-4975(10)60536-X.
• 16 Patchell RA, Tibbs PA, Walsh JW. et al. A Randomized Trial of Surgery in the Treatment of Single Metastases to the Brain. N Engl J Med 1990; 322: 494-500 DOI: 10.1056/NEJM199002223220802.
• 17 Muacevic A, Wowra B, Siefert A. et al. Microsurgery plus whole brain irradiation versus Gamma Knife surgery alone for treatment of single metastases to the brain: a randomized controlled multicentre phase III trial. J Neurooncol 2008; 87: 299-307 DOI: 10.1007/s11060-007-9510-4.
• 18 Andrews DW, Scott CB, Sperduto PW. et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial. Lancet 2004; 363: 1665-1672 DOI: 10.1016/S0140-6736(04)16250-8.
• 19 Tsao M, Xu W, Sahgal A. A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases. Cancer 2012; 118: 2486-2493 DOI: 10.1002/cncr.26515.
• 20 Kocher M, Soffietti R, Abacioglu U. et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: Results of the EORTC 22952-26001 study. J Clin Oncol 2011; 29: 134-141 DOI: 10.1200/JCO.2010.30.1655.
• 21 Brown PD, Jaeckle K, Ballman KV. et al. Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases a randomized clinical trial. JAMA - J Am Med Assoc 2016; 316: 401-409 DOI: 10.1001/jama.2016.9839.
• 22 Qin H, Wang C, Jiang Y. et al. Patients with single brain metastasis from non-small cell lung cancer equally benefit from stereotactic radiosurgery and surgery: a systematic review. Med Sci Monit 2015; 21: 144-152 DOI: 10.12659/MSM.892405.
• 23 Mahajan A, Ahmed S, McAleer MF. et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 2017; 18: 1040-1048 DOI: 10.1016/S1470-2045(17)30414-X.
• 24 Prabhu RS, Press RH, Patel KR. et al. Single-Fraction Stereotactic Radiosurgery (SRS) Alone Versus Surgical Resection and SRS for Large Brain Metastases: A Multi-institutional Analysis. Int J Radiat Oncol Biol Phys 2017; DOI: 10.1016/j.ijrobp.2017.04.006.
• 25 Billing PS, Miller DL, Allen MS. et al. Surgical treatment of primary lung cancer with synchronous brain metastases. J Thorac Cardiovasc Surg 2001; 122: 548-553 DOI: 10.1067/mtc.2001.116201.
• 26 Bonnette P, Puyo P, Gabriel C. et al. Surgical management of non-small cell lung cancer with synchronous brain metastases. Chest 2001; 119: 1469-1475 DOI: 10.1378/chest.119.5.1469.
• 27 Kozower BD, Larner JM, Detterbeck FC. et al. Special treatment issues in non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American college of chest physicians evidence-based clinical practice guidelines. Chest 2013; 143 DOI: 10.1378/chest.12-2362.
• 28 Magnuson WJ, Lester-Coll NH, Wu AJ. et al. Management of brain metastases in tyrosine kinase inhibitor-Naïve epidermal growth factor receptor-mutant non-small-cell lung cancer: A retrospective multi-institutional analysis. J Clin Oncol 2017; 35: 1070-1077 DOI: 10.1200/JCO.2016.69.7144.
• 29 Abrams HL, Spiro R, Goldstein N. Metastases in Carcinoma; Analysis of 1000 Autopsied Cases. Cancer 1950; 3: 74-85
• 30 Burt M, Heelan RT, Coit D. et al. Prospective evaluation of unilateral adrenal masses in patients with operable non-small-cell lung cancer: Impact of magnetic resonance imaging. J Thorac Cardiovasc Surg 1994; 107: 584-589 DOI: 10.1016/S0022-5223(94)70106-7.
• 31 Porte HL, Roumilhac D, Graziana JP. et al. Adrenalectomy for a solitary adrenal metastasis from lung cancer. Ann Thorac Surg 1998; 65: 331-335 DOI: 10.1016/S0003-4975(97)01284-8.
• 32 Ettinghausen SE, Burt ME. Prospective evaluation of unilateral adrenal masses in patients with operable non-small-cell lung cancer. J Clin Oncol 1991; 9: 1462-1466 DOI: 10.1200/JCO.1991.9.8.1462.
• 33 Tamura T, Kurishima K, Watanabe H. et al. Characteristics of clinical N0 metastatic non-small cell lung cancer. Lung Cancer 2015; 89: 71-75 DOI: 10.1016/j.lungcan.2015.04.002.
• 34 McNicholas MMJ, Lee MJ, Mayo-Smith WW. et al. An imaging algorithm for the differential diagnosis of adrenal adenomas and metastases. Am J Roentgenol 1995; 165: 1453-1459 DOI: 10.2214/ajr.165.6.7484585.
• 35 Gupta NC, Graeber GM, Tamim WJ. et al. Clinical utility of PET-FDG imaging in differentiation of benign from malignant adrenal masses in lung cancer. Clin Lung Cancer 2001; 3: 59-64 DOI: 10.3816/CLC.2001.n.019.
• 36 Kim HK, Choi YS, Kim K. et al. Preoperative evaluation of adrenal lesions based on imaging studies and laparoscopic adrenalectomy in patients with otherwise operable lung cancer. Lung Cancer 2007; 58: 342-347 DOI: 10.1016/j.lungcan.2007.07.001.
• 37 Feliciotti F, Paganini AM, Guerrieri M. et al. Laparoscopic Anterior Adrenalectomy for the Treatment of Adrenal Metastases. Surg Laparosc Endosc Percutaneous Tech 2003; 13: 328-333 DOI: 10.1097/00129689-200310000-00009.
• 38 Tanvetyanon T, Robinson LA, Schell MJ. et al. Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: A systematic review and pooled analysis. J Clin Oncol 2008; 26: 1142-1147 DOI: 10.1200/JCO.2007.14.2091.
• 39 Scorsetti M, Alongi F, Filippi AR. et al. Long-term local control achieved after hypofractionated stereotactic body radiotherapy for adrenal gland metastases: A retrospective analysis of 34 patients. Acta Oncol (Madr) 2012; 51: 618-623 DOI: 10.3109/0284186X.2011.652738.
• 40 Celik E, Semrau R, Baues C. et al. Robot-assisted extracranial stereotactic radiotherapy of adrenal metastases in oligometastatic non-small cell lung cancer. Anticancer Res 2017; 37: 5285-5291 DOI: 10.21873/anticanres.11954.
• 41 Holy R, Piroth M, Pinkawa M. et al. Stereotactic Body Radiation Therapy (SBRT) for treatment of adrenal gland metastases from non-small cell lung cancer. Strahlentherapie Und Onkol 2011; 187: 245-251 DOI: 10.1007/s00066-011-2192-z.
• 42 Ercolani G, Ravaioli M, Luca Grazi G. et al. The role of liver resections for metastases from lung carcinoma. HPB 2006; 8: 114-115 DOI: 10.1080/13651820500471970.
• 43 Mahadevan A, Blanck O, Lanciano R. et al. Stereotactic Body Radiotherapy (SBRT) for liver metastasis - clinical outcomes from the international multi-institutional RSSearch® Patient Registry. Radiat Oncol 2018; 13 DOI: 10.1186/s13014-018-0969-2.
• 44 Opitz I, Patella M, Payrard L. et al. Prognostic factors of oligometastatic non-small-cell lung cancer following radical therapy: a multicentre analysis. Eur J Cardio-Thoracic Surg 2020; 57: 1166-1172 DOI: 10.1093/ejcts/ezz384.
• 45 Tönnies M, Pfannschmidt J, Bauer TT. et al. Metastasectomy for synchronous solitary non-small cell lung cancer metastases. Ann Thorac Surg 2014; 98: 249-256 DOI: 10.1016/j.athoracsur.2014.03.028.
• 46 Xu Q, Wang Y, Liu H. et al. Treatment outcome for patients with primary NSCLC and synchronous solitary metastasis. Clin Transl Oncol 2013; 15: 802-809 DOI: 10.1007/s12094-013-1008-2.
• 47 Takahashi Y, Adachi H, Mizukami Y. et al. Patient outcomes post-pulmonary resection for synchronous bone-metastatic non-small cell lung cancer. J Thorac Dis 2019; 11: 3836-3845 DOI: 10.21037/jtd.2019.09.17.
• 48 Salah S, Tanvetyanon T, Abbasi S. Metastatectomy for extra-cranial extra-adrenal non-small cell lung cancer solitary metastases: Systematic review and analysis of reported cases. Lung Cancer 2012; 75: 9-14
• 49 Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg 1975; 70: 606-612 DOI: 10.1016/S0022-5223(19)40289-4.
• 50 Girard N, Deshpande C, Lau C. et al. Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases. Am J Surg Pathol 2009; 33: 1752-1764 DOI: 10.1097/PAS.0b013e3181b8cf03.
• 51 Postmus PE, Brambilla E, Chansky K. et al. The IASLC lung cancer staging project: Proposals for revision of the M descriptors in the forthcoming (seventh) edition of the TNM classification of lung cancer. J Thorac Oncol 2007; 2: 686-693 DOI: 10.1097/JTO.0b013e31811f4703.
• 52 Tönnies M, Kollmeier J, Bauer TT. et al. Kurativer chirurgischer Therapieansatz bei solitär pulmonal metastasierten nicht-kleinzelligen Lungenkarzinomen (NSCLC). Pneumologie 2012; 66: 218-223 DOI: 10.1055/s-0032-1308917.
• 53 Okubo K, Bando T, Miyahara R. et al. Resection of pulmonary metastasis of non-small cell lung cancer. J Thorac Oncol 2009; 4: 203-207 DOI: 10.1097/JTO.0b013e3181949c6a.
• 54 Okada M, Tsubota N, Yoshimura M. et al. Evaluation of TMN classification for lung carcinoma with ipsilateral intrapulmonary metastasis. Ann Thorac Surg 1999; 68: 326-330 DOI: 10.1016/S0003-4975(99)00465-8.
• 55 Hörner-Rieber J, Bernhardt D, Blanck O. et al. Long-term Follow-up and Patterns of Recurrence of Patients With Oligometastatic NSCLC Treated With Pulmonary SBRT. Clin Lung Cancer 2019; 20: e667-677 DOI: 10.1016/j.cllc.2019.06.024.
• 56 Gomez DR, Blumenschein GR, Lee JJ. et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol 2016; 17: 1672-1682 DOI: 10.1016/S1470-2045(16)30532-0.
• 57 Gomez DR, Tang C, Zhang J. et al. Local consolidative therapy vs. Maintenance therapy or observation for patients with oligometastatic non–small-cell lung cancer: Long-term results of a multi-institutional, phase II, randomized study. J Clin Oncol 2019; 37: 1558-1565 DOI: 10.1200/JCO.19.00201.
• 58 Iyengar P, Wardak Z, Gerber DE. et al. Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: A phase 2 randomized clinical trial. JAMA Oncol 2018; 4: 1-8 DOI: 10.1001/jamaoncol.2017.3501.
• 59 Palma DA, Olson R, Harrow S. et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet 2019; 393: 2051-2058 DOI: 10.1016/S0140-6736(18)32487-5.
• 60 Bauml JM, Mick R, Ciunci C. et al. Pembrolizumab after Completion of Locally Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer: A Phase 2 Trial. JAMA Oncol 2019; 5: 1283-1290 DOI: 10.1001/jamaoncol.2019.1449.
• 61 Reynders K, Illidge T, Siva S. et al. The abscopal effect of local radiotherapy: Using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev 2015; 41: 503-510 DOI: 10.1016/j.ctrv.2015.03.011.
• 62 Van den Begin R, Engels B, Collen C. et al. The METABANK score: A clinical tool to predict survival after stereotactic radiotherapy for oligometastatic disease. Radiother Oncol 2019; 133: 113-119 DOI: 10.1016/j.radonc.2019.01.001.