Surgical Management of Oligopersistent and Oligoprogressive ALK+ Lung Cancer

Following resistance to targeted treatment, oligoprogression can occur whereby a previously controlled site or sites of metastases progress after the majority of other sites of disease stabilize on systemic therapy. Interestingly, this patient developed MET amplification as the mechanisms of TKI resistance after being on alectinib therapy for more than two years.

Limited data exist on the optimal management of oligometastatic ALK-positive non-small cell lung cancer. This video presents an oncologically unique and complex case where both oligopersistent and oligoprogressive disease are managed surgically with excellent outcomes and prolonged survival. While radiation has traditionally been central to many treatment paradigms, this case demonstrates surgery can also play an important role.

The Patient

The patient is a fifty-two-year-old woman who initially presented with hemoptysis. Imaging demonstrated a PET-avid 6 cm left upper lobe mass with concern for malignancy along with uptake of contralateral mediastinal lymph nodes and a lesion in the right tenth rib. A biopsy confirmed non-small cell lung cancer with adenocarcinoma and squamous cell carcinoma components. An ALK mutation was also identified, and the patient was initiated on alectinib for IIIC/IV disease. Imaging through five months demonstrated disease response to targeted treatment with reduction in size of the primary lesion. However, disease progression of the left upper lobe primary lesion was noted at eight months.

Following multidisciplinary discussion, the decision was made to pursue surgical resection. The patient underwent thoracoscopic left upper lobectomy and pathology revealed a 3.6 cm squamous cell carcinoma with negative lymph nodes and no viable adenocarcinoma identified. The patient was continued on adjuvant alectinib therapy. Chest CT scans were negative for recurrence up to fourteen months postoperatively.

Eighteen months postoperatively, the patient was noted to have a PET-avid partially necrotic appearing right lower paratracheal node suspicious for metastasis. Review of prior imaging demonstrated presence of adenopathy in this region, which had initially responded to alectinib, but was now deemed oligoprogressive. Following multidisciplinary discussion, local therapy was deemed appropriate. Radiation would normally be considered the standard of care in this setting but given the central location of the lesion and proximity to the airway, surgical resection was again recommended.

The Surgery

Surgical access was debated, and a robotic-assisted approach was selected in consideration of the location of the lesion and exposure required to best visualize the node. Utilizing a standard five-port technique, the upper lobe was retracted inferiorly, exposing the paratracheal space where minimal adhesions were noted. As the pleura was incised, the node was encountered and noted to be adherent to the superior vena cava. The azygous vein was then resected to enhance exposure. A combination of blunt dissection and cautery were used to carefully identify the plane between the node and the SVC, allowing surgeons to circumferentially dissect out the lesion down to the level of the aorta. The lesion was safely removed in its entirety, and the patient was discharged on day one following an uneventful postoperative course.

Surgical pathology showed metastatic adenocarcinoma and molecular testing confirmed ALK fusion along with MET amplification. Following discussion with medical oncology, the patient continued on alectenib to be followed by surveillance. Imaging at two months demonstrated no evidence of disease.

References

1. 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. Clinical Lung Cancer. 2014;15(5):346-355. doi:10.1016/j.cllc.2014.04.003
2. Cooper AJ, Sequist LV, Lin JJ. Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management. Nat Rev Clin Oncol. 2022;19(8):499-514. doi:10.1038/s41571-022-00639-9
3. Dagogo-Jack I, Yoda S, Lennerz JK, et al. MET Alterations Are a Recurring and Actionable Resistance Mechanism in ALK-Positive Lung Cancer. Clinical Cancer Research. 2020;26(11):2535-2545. doi:10.1158/1078-0432.CCR-19-3906
4. Eichhorn F, Winter H. How to handle oligometastatic disease in nonsmall cell lung cancer. European Respiratory Review. 2021;30(159). doi:10.1183/16000617.0234-2020
5. Euhus CJ, Ripley TR, Medina CG. The Role of Surgery for Oligometastatic Non-Small Cell Lung Cancer. Cancers (Basel). 2022;14(10):2524. doi:10.3390/cancers14102524
6. Fujita S, Masago K, Katakami N, Yatabe Y. Transformation to SCLC after Treatment with the ALK Inhibitor Alectinib. Journal of Thoracic Oncology. 2016;11(6):e67-e72. doi:10.1016/j.jtho.2015.12.105
7. Fukui T, Tachihara M, Nagano T, Kobayashi K. Review of Therapeutic Strategies for Anaplastic Lymphoma Kinase-Rearranged Non-Small Cell Lung Cancer. Cancers (Basel). 2022;14(5):1184. doi:10.3390/cancers14051184
8. 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(18):1558-1565. doi:10.1200/JCO.19.00201
9. Gong J, Gregg JP, Ma W, et al. Squamous Cell Transformation of Primary Lung Adenocarcinoma in a Patient With EML4-ALK Fusion Variant 5 Refractory to ALK Inhibitors. Journal of the National Comprehensive Cancer Network. 2019;17(4):297-301. doi:10.6004/jnccn.2019.7291
10. Hubbeling H, Choudhury N, Flynn J, et al. Outcomes With Local Therapy and Tyrosine Kinase Inhibition in Patients With ALK/ROS1/RET-Rearranged Lung Cancers. JCO Precision Oncology. Published online October 6, 2022. doi:10.1200/PO.22.00024
11. Itchins M, Pavlakis N. The quantum leap in therapeutics for advanced ALK+ non-small cell lung cancer and pursuit to cure with precision medicine. Front Oncol. 2022;12:959637. doi:10.3389/fonc.2022.959637
12. Izumi H, Yamasaki A, Ueda Y, et al. Squamous Cell Carcinoma Transformation from EGFR-mutated Lung Adenocarcinoma: A Case Report and Literature Review. Clinical Lung Cancer. 2018;19(1):e63-e66. doi:10.1016/j.cllc.2017.10.005
13. Jasper K, Stiles B, McDonald F, Palma DA. Practical Management of Oligometastatic Non–Small-Cell Lung Cancer. JCO. 2022;40(6):635-641. doi:10.1200/JCO.21.01719
14. Kaiho T, Nakajima T, Iwasawa S, Yonemori Y, Yoshino I. ALK Rearrangement Adenocarcinoma with Histological Transformation to Squamous Cell Carcinoma Resistant to Alectinib and Ceritinib. Onco Targets Ther. 2020;13:1557-1560. doi:10.2147/OTT.S236706
15. Lang P, Gomez DR, Palma DA. Local Ablative Therapies in Oligometastatic NSCLC: New Data and New Directions. Semin Respir Crit Care Med. 2020;41(03):369-376. doi:10.1055/s-0039-3400290
16. Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Annals of Oncology. 2020;31(8):1056-1064. doi:10.1016/j.annonc.2020.04.478
17. Opitz I, Patella M, Payrard L, et al. Prognostic factors of oligometastatic non-small-cell lung cancer following radical therapy: a multicentre analysis. European Journal of Cardio-Thoracic Surgery. 2020;57(6):1166-1172. doi:10.1093/ejcts/ezz384
18. Palma DA, Nguyen TK, Louie AV, et al. Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non–Small Cell Lung Cancer. JAMA Oncol. 2019;5(5):681-688. doi:10.1001/jamaoncol.2018.6993
19. Pan Y, Deng C, Qiu Z, Cao C, Wu F. The Resistance Mechanisms and Treatment Strategies for ALK-Rearranged Non-Small Cell Lung Cancer. Front Oncol. 2021;11:713530. doi:10.3389/fonc.2021.713530
20. Park YH, Park S, Han J, Sun JM. Histologic transformation of ALK-rearranged adenocarcinoma to squamous cell carcinoma after treatment with ALK inhibitor. Lung Cancer. 2019;127:66-68. doi:10.1016/j.lungcan.2018.11.027
21. Peeters STH, Van Limbergen EJ, Hendriks LEL, De Ruysscher D. Radiation for Oligometastatic Lung Cancer in the Era of Immunotherapy: What Do We (Need to) Know? Cancers (Basel). 2021;13(9):2132. doi:10.3390/cancers13092132
22. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer. N Engl J Med. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795
23. Pfannschmidt J, Dienemann H. Surgical treatment of oligometastatic non-small cell lung cancer. Lung Cancer. 2010;69(3):251-258. doi:10.1016/j.lungcan.2010.05.003
24. Rashdan S, Iyengar P, Minna JD, Gerber DE. Narrative review: molecular and genetic profiling of oligometastatic non-small cell lung cancer. Transl Lung Cancer Res. 2021;10(7):3351-3368. doi:10.21037/tlcr-21-448
25. Remon J, Hendriks LEL, Mountzios G, et al. MET alterations in NSCLC-Current Perspectives and Future Challenges. J Thorac Oncol. Published online October 29, 2022:S1556-0864(22)01865-2. doi:10.1016/j.jtho.2022.10.015
26. Román-Jobacho A, Hernández-Miguel M, García-Anaya MJ, Gómez-Millán J, Medina-Carmona JA, Otero-Romero A. Oligometastatic non-small cell lung cancer: Current management. J Clin Transl Res. 2021;7(3):311-319.
27. Santos PMG, Li X, Gomez DR. Local Consolidative Therapy for Oligometastatic Non-Small Cell Lung Cancer. Cancers (Basel). 2022;14(16):3977. doi:10.3390/cancers14163977
28. Shahi J, Poon I, Ung YC, et al. Stereotactic Body Radiation Therapy for Mediastinal and Hilar Lymph Node Metastases. International Journal of Radiation Oncology*Biology*Physics. 2021;109(3):764-774. doi:10.1016/j.ijrobp.2020.10.004
29. Tan VS, Palma DA. Top Ten Lessons Learned from Trials in Oligometastatic Cancers. Cancer Res Treat. Published online December 16, 2022. doi:10.4143/crt.2022.1460
30. Werner RS, Opitz I. Patient Selection for Local Aggressive Treatment in Oligometastatic Non-Small Cell Lung Cancer. Cancers (Basel). 2021;13(24):6374. doi:10.3390/cancers13246374

Disclaimer

The information and views presented on CTSNet.org represent the views of the authors and contributors of the material and not of CTSNet. Please review our full disclaimer page here.