Effectiveness of Stereotactic Ablative Radiotherapy for Systemic Therapy Respondents with Inoperable Pulmonary Oligometastases and Oligoprogression

Chin-Beng Ho; Jo-Ting Tsai; Chun-You Chen; Her-Shyong Shiah; Hsuan-Yu Chen; Lai-Lei Ting; Chia-Chun Kuo; I-Chun Lai; Hsin-Yi Lai; Chi-Li Chung; Kai-Ling Lee; Huey-En Tzeng; Kuen-Haur Lee; Hsin-Lun Lee; Shang-Wen Chen; Jeng-Fong Chiou

doi:10.3390/diagnostics13091597

Effectiveness of Stereotactic Ablative Radiotherapy for Systemic Therapy Respondents with Inoperable Pulmonary Oligometastases and Oligoprogression

Diagnostics (Basel). 2023 Apr 29;13(9):1597. doi: 10.3390/diagnostics13091597.

Authors

Chin-Beng Ho^{1

2

3}, Jo-Ting Tsai^{4

5}, Chun-You Chen^{6

7}, Her-Shyong Shiah^{8

9}, Hsuan-Yu Chen^{1

10

11}, Lai-Lei Ting³, Chia-Chun Kuo^{1

3

6}, I-Chun Lai^{11

12}, Hsin-Yi Lai¹³, Chi-Li Chung^{14

15

16}, Kai-Ling Lee¹⁴, Huey-En Tzeng^{9

17}, Kuen-Haur Lee^{1

9}, Hsin-Lun Lee^{3

5

6}, Shang-Wen Chen^{5

18

19}, Jeng-Fong Chiou^{1

3

5}

Affiliations

¹ Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei Medical University, Taipei 110301, Taiwan.
² Department of Radiation Oncology, Camillian Saint Mary's Hospital Luodong, Yilan 265502, Taiwan.
³ Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110301, Taiwan.
⁴ Department of Radiation Oncology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235041, Taiwan.
⁵ Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan.
⁶ Taipei Cancer Center, Taipei Medical University, Taipei 110301, Taiwan.
⁷ Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei 116079, Taiwan.
⁸ Division of Hematology and Oncology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231016, Taiwan.
⁹ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110301, Taiwan.
¹⁰ Institute of Statistical Science, Academia Sinica, Taipei 115201, Taiwan.
¹¹ Department of Heavy Particles and Radiation Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan.
¹² School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
¹³ Department of Medical Imaging, Taipei Medical University Hospital, Taipei Medical University, Taipei 110301, Taiwan.
¹⁴ Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei 110301, Taiwan.
¹⁵ School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan.
¹⁶ Division of Thoracic Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan.
¹⁷ Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung 407219, Taiwan.
¹⁸ Department of Radiation Oncology, China Medical University Hospital, Taichung 404327, Taiwan.
¹⁹ Graduate Institute of Biomedical Sciences, School of Medicine, College of Medicine, China Medical University, Taichung 404333, Taiwan.

Abstract

Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status (p = 0.003), disease-free interval < 24 months (p = 0.041), and biologically effective dose (BED₁₀) < 100 Gy (p = 0.006) were independently associated with inferior OS. BED₁₀ ≥ 100 Gy (p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status (p = 0.017) and EPD (p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED₁₀ ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.

Keywords: extrapulmonary disease; metastasectomy; oligometastases; oligoprogression; pulmonary metastases; stereotactic ablative radiotherapy (SABR).

Grants and funding

The work was supported by the Research Grants for Newly Hired Faculty of Taipei Medical University (TMU109-AE1-B27).