Figure 1
Flow chart showing patient selection. The patients were treated with concurrent chemoradiotherapy between January 2011 and December 2018.
PFS = progression-free survival
Table 1
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 |
[i] ALK = anaplastic lymphoma kinase; BRAF = v-raf murine sarcoma viral oncogene homolog B1; CBDCA = carboplatin; CDDP = cisplatin; CR = complete response; EGFR = epidermal growth factor receptor; NE = not evaluated; PD = progressive disease; PD-L1 = programmed cell death 1 ligand 1; PS = performance status; PR = partial response; PTX = paclitaxel; ROS -1 = c-ros oncogene 1; S-1 = an oral fluoropyrimidine derivative; SD = stable disease; TPS = tumor proportion score; VNR = vinorelbine
Figure 2
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.
Table 2
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 |
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.
Table 3
Univariate Cox regression analysis of patient characteristics for 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 | |||
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