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Clinical impact of post-progression survival in patients with locally advanced non-small cell lung cancer after chemoradiotherapy

Hisao Imai

Hisao Imai

  • Division of Respiratory Medicine, Gunma Prefectural Cancer CenterOta, Japan
  • Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversitySaitama, Japan
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Imai, Hisao
, 
Daijiro Kobayashi

Daijiro Kobayashi

Division of Radiation Oncology, Gunma Prefectural Cancer CenterGunma, Japan
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Kobayashi, Daijiro
, 
Kyoichi Kaira

Kyoichi Kaira

Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversitySaitama, Japan
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Kaira, Kyoichi
, 
Sayaka Kawashima

Sayaka Kawashima

Division of Pharmacy, Gunma Prefectural Cancer CenterGunma, Japan
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Kawashima, Sayaka
, 
Ken Masubuchi

Ken Masubuchi

Division of Respiratory Medicine, Gunma Prefectural Cancer CenterOta, Japan
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Masubuchi, Ken
, 
Masumi Murata

Masumi Murata

Division of Radiation Oncology, Gunma Prefectural Cancer CenterGunma, Japan
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Murata, Masumi
, 
Takeshi Ebara

Takeshi Ebara

  • Division of Radiation Oncology, Gunma Prefectural Cancer CenterGunma, Japan
  • Department of Radiation Oncology, Kyorin University, School of MedicineTokyo, Japan
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Ebara, Takeshi
, 
Yoshizumi Kitamoto

Yoshizumi Kitamoto

Division of Radiation Oncology, Gunma Prefectural Cancer CenterGunma, Japan
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Kitamoto, Yoshizumi
 and 
Koichi Minato

Koichi Minato

Division of Respiratory Medicine, Gunma Prefectural Cancer CenterOta, Japan
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Minato, Koichi
  
Feb 25, 2022
Clinical impact of post-progression survival in patients with locally advanced non-small cell lung cancer after chemoradiotherapy's Cover Image
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Article Category: Research Article
Published Online: Feb 25, 2022
Page range: 228 - 237
Received: Nov 02, 2021
Accepted: Jan 13, 2022
DOI: https://doi.org/10.2478/raon-2022-0006
Keywords
© 2022 Hisao Imai, Daijiro Kobayashi, Kyoichi Kaira, Sayaka Kawashima, Ken Masubuchi, Masumi Murata, Takeshi Ebara, Yoshizumi Kitamoto, Koichi Minato, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Flow chart showing patient selection. The patients were treated with concurrent chemoradiotherapy between January 2011 and December 2018.PFS = progression-free survival
Flow chart showing patient selection. The patients were treated with concurrent chemoradiotherapy between January 2011 and December 2018.PFS = progression-free survival

Figure 2

PROGRESSION-FREE survival (PFS) and post-progression survival (PPS) in the overall population.
PROGRESSION-FREE survival (PFS) and post-progression survival (PPS) in the overall population.

Figure 3

Kaplan-Meier survival plots showing the (A) progression-free survival (PFS) and (B) overall survival (OS) of all patients.Median progression-free survival: 10.8 months; median overall survival: 31.6 months; median follow-up: 31.5 months.
Kaplan-Meier survival plots showing the (A) progression-free survival (PFS) and (B) overall survival (OS) of all patients.Median progression-free survival: 10.8 months; median overall survival: 31.6 months; median follow-up: 31.5 months.

Figure 4

Correlations between (A) overall survival (OS) and progression-free survival (PFS) and (B) between overall survival and post-progression survival (PPS).*The r values represent Spearman’s rank correlation coefficient. **The R2 values represent the linear regression.
Correlations between (A) overall survival (OS) and progression-free survival (PFS) and (B) between overall survival and post-progression survival (PPS).*The r values represent Spearman’s rank correlation coefficient. **The R2 values represent the linear regression.

Figure 5

(A) Kaplan-Meier plots showing post-progression survival (PPS) according to Glasgow prognostic score (GPS) at relapse, GPS 0–1, median = 25.7 months; GPS 2, median = 6.7 months. (B) Kaplan-Meier plots showing PPS according to liver metastases at recurrence, Without liver metastases, median = 21.3 months; With liver metastases, median = 4.2 months
(A) Kaplan-Meier plots showing post-progression survival (PPS) according to Glasgow prognostic score (GPS) at relapse, GPS 0–1, median = 25.7 months; GPS 2, median = 6.7 months. (B) Kaplan-Meier plots showing PPS according to liver metastases at recurrence, Without liver metastases, median = 21.3 months; With liver metastases, median = 4.2 months

Baseline patient characteristics

Characteristic N = 45
Gender
        Male/female 33/12
Median age at chemoradiotherapy (years) 71 (41–80)
Median age at progressive disease (years) 71 (42–82)
Performance Status at progressive disease
        0/1/2/3/4 15/22/4/4/0
Smoking history
        Yes/No 36/9
Histology
        Adenocarcinoma/squamous cell carcinoma/others 23/16/6
Clinical stage at diagnosis
        IIIA/IIIB/IIIC 28/14/3
Driver mutation/translocation
        EGFR/ALK/ROS-1/BRAF/others/negative or unknown 6/2/1/0/0/36
PD-L1 TPS
        < 1% / 1–49% / 50%/unknown 6/5/8/26
Progression-free survival (months) .
        < 6 / 6 13/32
Overall response to chemoradiotherapy
        CR/PR/SD/PD/NE 0/26/15/4/0
Glasgow prognostic score (GPS)
        0–1/2 32/13
Administration of tyrosine kinase inhibitors
        Yes/No 11/34
Administration of immune checkpoint inhibitors
        Yes/No 12/33
Administration of durvalmab
        Yes/No 2/43
Recurrent pattern
        Local recurrence/distant metastasis 17/28
Intracranial metastases at recurrence
        Yes/No 7/38
Liver metastases at recurrence
        Yes/No 3/42
Bone metastases at recurrence
        Yes/No 15/30
Oligorecurrrence
        Yes/No 11/34
Radiotherapy after recurrence (any site)
        Yes/No 19/26
Number of drug therapies after chemoradiotherapy
        0/1/2/3/4 14/18/9/2/2
        Median (range) 1
Median (range) radiation dosage (Gy) 60 (58–70)
Chemotherapy regimen
        CDDP + VNR 1
        CDDP + S-1 0
        CBDCA + PTX 30
        Low dose CBDCA 14

Univariate Cox regression analysis of patient characteristics for post-progression survival

Median Post-progression survival
PPS Univariate analysis Multivariate analysis
Factors (months) HR 95% CI p value HR 95% CI p value
Gender
        Male/female 18.1/25.7 1.49 0.63–4.07 0.37
Age at recurrence (years)
        < 75 / 75 20.0/19.5 0.78 0.36–1.77 0.54
PS at recurrence
        0–1 / 2 21.3/2.8 0.42 0.18–1.09 0.07
Smoking history
        Yes/No 16.7/25.7 1.87 0.71–6.39 0.21
Histology
        Adenocarcinoma/non-adenocarcinoma 25.7/10.5 0.37 0.17–0.79 0.0099 1.06 0.36–3.04 0.90
Driver mutation/translocation
        Yes/No 27.3/15.1 0.32 0.07–0.95 0.038 0.61 0.13–2.23 0.47
Best overall response of chemoradiotherapy
        PR/non-PR 15.1/22.1 1.82 0.86–4.11 0.11
Progression-free survival
        < 6 months / 6 months 6.4 / 24.4 1.97 0.89–4.19 0.09
Glasgow prognostic score (GPS) at recurrence
        0–1/2 25.7/6.7 0.23 0.11–0.52 0.0006 0.2 0.06–0.55 0.0019
Recurrence pattern
        Local recurrence/distant metastasis 40.7/16.7 0.45 0.18–1.03 0.05
Intracranial metastases at recurrence
        Yes/No 6.7/21.3 1.75 0.64–4.09 0.25
Liver metastases at recurrence
        Yes/No 4.2/21.3 6.82 1.50–22.8 0.016 12.7 2.40–56.8 0.0048
Bone metastases at recurrence
        Yes/No 18.1/20.0 1.40 0.60–3.06 0.41
Oligorecurrence at recurrence
        Yes/No 22.1/19.2 0.77 0.30–1.75 0.55

The treatments after post-chemoradiotherapy recurrence

first-line second-line third-line ≧fourth-line Total
Platinum combination 11 3 2 0 16
Platinum combination + ICIs 0 0 0 0 0
Docetaxel 0 4 2 0 6
Docetaxel+ ramcirumab 0 0 0 0 0
Pemetrexed 0 0 2 0 2
S1 1 0 0 3 4
Others (single agents) 0 1 0 0 1
EGFR-TKIs 6 1 0 0 7
ALK-TKIs 3 1 0 0 4
ICI monotherapy 1 5 2 1 9
Ipilimumab+nivolumab 1 0 0 0 1
Investigational agents 0 0 0 0 0
Radiotherapy alone 12 1 0 0 13
Best supportive care 10 - - - 10
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