A retrospective evaluation of therapeutic efficacy and safety of chemoradiotherapy in older patients (aged ≥ 75 years) with limited-disease small cell lung cancer: insights from two institutions and review of the literature

Shiono, Ayako; Imai, Hisao; Endo, Satoshi; Katayama, Kazuki; Sato, Hideaki; Hashimoto, Kosuke; Miura, Yu; Okazaki, Shohei; Abe, Takanori; Mouri, Atsuto; Kaira, Kyoichi; Masubuchi, Ken; Kobayashi, Kunihiko; Minato, Koichi; Kato, Shingo; Kagamu, Hiroshi

doi:10.2478/raon-2024-0054

Figures & Tables

Kaplan-Meier analysis of the progression-free survival of the 32 patients. The median progression-free survival was 11.9 months.

Kaplan-Meier analysis of the overall survival of 32 patients. The median overall survival was 21.1 months.

Progression-free survival (PFS) of the concurrent and sequential chemoradiotherapy groups. The median PFS was 13.0 months in the concurrent group and 9.0 months in the sequential group (p = 0.67).

The overall survival (OS) of the concurrent and sequential chemoradiotherapy groups. The median OS was 19.2 months in the concurrent group and 23.5 months in the sequential group (p = 0.46).

Baseline patient characteristics

Characteristic	Total (N = 32)	Concurrent CRT group (n = 19)	Sequential CRT group (n = 13)	p^a
Sex
Male / female	27 / 5	16 / 3	11 / 2	> 0.99
Age (years)
Median	78	77	79	0.05^b
Range	75–92	75–81	76–92
ECOG-PS, n
0 / 1 / 2 / 3 / 4	12 / 19 / 1 / 0 / 0	6 / 12 / 1 / 0 / 0	6 / 7 / 0 / 0 / 0
Smoking status, n
Yes / no	32 / 0	19 / 0	13 / 0	> 0.99
Histology, n
Small cell carcinoma / combined small cell carcinoma	29 / 3	18 / 1	11 / 2	0.55
Disease stage, n
I / II / III / postoperative recurrence	5 / 4 / 23 / 0	4 / 2 / 13 / 0	1 / 2 / 10 / 0
History of postoperative adjuvant chemotherapy, n
Yes / no	0 / 32	0 / 19	0 / 13	> 0.99
Number of cycles chemotherapy administered, n
Median	4	4	4	0.19b
Range	1–5	1–4	2–5
Chemotherapy regimen, n
CBDCA+etoposide / CDDP+etoposide	28 / 4	16 / 3	12 /1	0.63
With or without G-CSF prophylaxis, n
Yes / no	27 / 5	17 / 2	10 / 3	0.37
Radiation irradiation method, n
Conventional / accelerated hyperfractionated radiotherapy	26 / 6	14 / 5	12 / 1	0.36
Completion of chemotherapy, n
Yes / no	21 / 11	11 / 8	10 / 3	0.45
Completion of radiotherapy, n
Yes / no	31 / 1	18 / 1	13 / 0	> 0.99
Prophylactic cranial irradiation, n
Yes / no	2 / 30	2 / 17	0 / 13	0.50
Reason for discontinuation of chemotherapy administration^b, n
Progressive disease	1^c	0
Adverse events	7	6	1
Others	3	2	1
Alive at data cutoff, n
Alive / death	8 / 24	4 / 15	4 / 9	0.68

Findings of previous studies on chemoradiotherapy in older patients with limited-disease small cell lung cancer

Report [ref]	Year	Region	Age (years)	Study type	Sample size	PS	Stage	Treatment	Response rate (%) (All, con CRT vs. seq CRT)	PFS (months) (All, con CRT vs. seq CRT)	OS (months) (All, con CRT vs. seq CRT)	Interruption of treatment	Grade 3 or higher^a
Jeremic et al.¹⁷	1998	Yugoslavia	≥ 70	Prospective, Phase 2	72	KPS≥60	Limited disease	concurrent CRT (CBDCA+ETP)	75	NR	15	NR	Leukopenia 8.3%, Thrombocytopenia 11%, Infection 4.2%, Pneumonitis 18%
Shimizu et al.¹⁸	2007	Japan	≥ 75	Retrospective	7	0–1	II–III	concurrent CRT (CBDCA+ETP or CDDP+ETP)	100	NR	24.7	Imcompleted intent cycles of chemotherapy 3/7 (42.8%)	Leukopenia 100%, Neutropenia 100%, Thrombocytopenia 57.1%, FN 42.8%, Pneumonitis 28.5%
Okamoto et al.¹⁹	2010	Japan	≥ 70	Retrospective	12	0–1	II–III	concurrent CRT (CDDP+ETP)	100	14.2	24.1	Imcompleted intent cycles of chemotherapy 5/12 (41.7%)	Leukopenia 100%, Neutropenia 100%, Thrombocytopenia 33%, FN 67%, Pneumonitis 8%
Shukuya et al.²⁰	2013	Japan	≥ 75	Retrospective	20	0–1	II–III	concurrent CRT (CBDCA+ETP or CDDP+ETP); n=5, sequential CRT (CBDCA+ETP or CDDP+ETP); n=15	NR, 100 vs. 80	NR, 208 days vs. 216 days	601 days (seq CRT with CBDCA+ETP)	Con vs. seq CRT; Imcompleted intent cycles of chemotherapy 2/5 (40%) vs., 2/15 (13.3%)	Con vs. seq CRT; Leukopenia 100% vs. 53%, Neutropenia 100% vs. 93%, Thrombocytopenia 20% vs. 27%, FN 60% vs. 13%, Infection 0% vs. 7%, Pneumonitis 0% vs. 27%
Okamoto et al.²¹	2014	Japan	≥ 70	Prospective, Phase 1	12	0–1	Limited disease	concurrent CRT (split CDDP+ETP)	91.6	11.5	17	Imcompleted intent cycles of chemotherapy 5/12 (41.6%)	Leukopenia 100%, Neutropenia 100%, Thrombocytopenia 33%, FN 33%, Pneumonitis 16% (level 2 cohort)
Corso et al.²²	2015	U.S.A	≥ 70	Retrospective	4362^b	NR	I–III	concurrent CRT; n=3472, sequential CRT; n=1136	NR	NR	15.6, 17.0 vs. 15.4	NR	NR
Kubo et al.²³	2016	Japan	≥ 76	Prospective, Phase 2	22	0–2	I–III	sequential CRT (CDDP+TOP)	68	9.1	22.2	Imcompleted intent treatment course of CRT 41%	Neutropenia 96%, Thrombocytopenia 50%, FN 32%, Pneumonitis 18%
Misumi et al.²⁴	2017	Japan	≥ 70	Prospective, Phase 1/2	35^c	0–2	I–III	sequential CRT (CBDCA+CPT11)	88.6	11.2	27.1	Imcompleted intent cycles of chemotherapy 7/35 (20.0%)	Neutrophils 51%, Platelets 11.4%, FN 5.7%, Pneumonitis 5.7%
Stinchcombe et al.²⁵	2019	USA	≥ 70	Pooled analysis	254	NR	Limited disease	concurrent CRT (CBDCA+ETP or CDDP+ETP)	NR	10.6	17.8	Imcompleted intent treatment course of CRT	Neutropenia 56%, Pneumonitis 2%
Christodoulou et al.²⁶	2019	Europe	≥ 70	Prospective, Phase 3 (subgroup)	67	0–2	I–III	concurrent CRT (CDDP+ETP)	NR	18	29	135/250 (54%) Imcompleted intent cycles of chemotherapy 25/67 (37.3%)	Neutropenia 84%, Thrombocytopenia 28%, Infection 13%, Pneumonitis 3%
Killingberg et al.²⁷	2023	Norway	≥ 70	Prospective, Phase 2 (subgroup)	53	0–2	I–III	concurrent CRT (CBDCA+ETP or CDDP+ETP)	70	12.2	24	Imcompleted TRT as planned 8%, Imcompleted four cycles of chemotherapy 15%	Neutropenia 80%, Thrombocytopenia 30%, Infection 4%, Pneumonitis 4%
Current study		Japan	≥ 75	Retrospective	32	0–2	I–III	concurrent CRT (CBDCA+ETP or CDDP+ETP); n=19, sequential CRT (CBDCA+ETP or CDDP+ETP); n=13	96.9, 94.7 vs. 100	11.8, 13.0 vs. 9.0	21.1, 19.2 vs. 23.5	Con vs. seq CRT; Imcompleted intent cycles of chemotherapy 6/19 (31.6%) vs. 1/13 (7.7%)	Con vs. seq CRT; White blood cell decreased 84.2% vs. 30.8%, Neutrophil count decreased 78.9% vs. 61.5%, Platelet count decreased 26.3% vs. 15.4%, FN 10.5% vs. 7.7%, Infection 15.8% vs. 7.7%, Pneumonitis 5.3% vs. 7.7%

Adverse events

Adverse event	All patients (N = 32)				Concurrent CRT (n = 19)				Sequential CRT (n = 13)				p^a

	Any Grade	%	Grade≥3	%	Any Grade	%	Grade≥3	%	Any Grade	%	Grade≥3	%
Led to discontinuation	7	21.9	6	18.8	6	31.6	6	31.6	1	7.7	0	0.0	0.06
Led to death	-		2	6.3	-	-	1	5.3	-	-	1	7.7	> 0.99
Treatment related^b
White blood cell decreased	28	87.5	20	62.5	18	94.7	16	84.2	10	76.9	4	30.8	0.004
Neutrophil count decreased	26	81.3	23	71.9	18	94.7	15	78.9	8	61.5	8	61.5	0.43
Anemia	28	87.5	6	18.8	16	84.2	5	26.3	12	92.3	1	7.7	0.36
Platelet count decreased	27	84.4	7	21.9	16	84.2	5	26.3	11	84.6	2	15.4	0.67
Febrile neutropenia	3	9.4	3	9.4	2	10.5	2	10.5	1	7.7	1	7.7	> 0.99
Diarrhea	3	9.4	1	3.1	2	10.5	1	5.3	1	7.7	0	0.0	> 0.99
Constipation	14	43.8	1	3.1	9	47.4	0	0.0	5	38.5	1	7.7	0.41
Dermatitis radiation	8	25.0	1	3.1	2	10.5	1	5.3	6	46.2	0	0.0	> 0.99
Pneumonitis	29	90.6	2	6.3	18	94.7	1	5.3	11	84.6	1	7.7	> 0.99
Infection	7	21.9	4	12.5	4	21.1	3	15.8	3	23.1	1	7.7	0.63
Pneumothorax	2	6.3	2	6.3	2	10.5	2	10.5	0	0.0	0	0.0	0.50
Hypotension	1	3.1	1	3.1	1	5.3	1	5.3	0	0.0	0	0.0	> 0.99
Generalized muscle weakness	1	3.1	1	3.1	1	5.3	1	5.3	0	0.0	0	0.0	> 0.99
Acute coronary syndrome	1	3.1	1	3.1	1	5.3	1	5.3	0	0.0	0	0.0	> 0.99

Overview of subsequent chemoradiotherapy treatments

	Second-line	Third-line	≥ Fourth-line
Carboplatin+etoposide	7	0	0
Carboplatin+etoposide+atezolizumab/durvalmab	2	0	0
Carboplatin+irinotecan	0	1	0
Carboplatin+paclitaxel	0	1	0
Amurubicin	4	2	0
Nogitecan	0	0	0
Irinotecan	0	0	0
Others	0	2	0
Best supportive care	14	-	-
No recurrence	5

Treatment response

Response	Total (N = 32)	Concurrent CRT (n = 19)	Sequential CRT (n = 13)	p^a
Complete response	3	3	0
Partial response	28	15	13
Stable disease	0	0	0
Progressive disease	0	0	0
Not evaluated	1	1	0
Response rate (%) (95% CI)	96.9 (82.9–100)	94.7 (73.5–100)	100 (−)	> 0.99
Disease control rate (%) (95% CI)	96.9 (82.9–100)	94.7 (73.5–100)	100 (−)	> 0.99

A retrospective evaluation of therapeutic efficacy and safety of chemoradiotherapy in older patients (aged ≥ 75 years) with limited-disease small cell lung cancer: insights from two institutions and review of the literature

Figures & Tables

FIGURE 1A.

FIGURE 1B.

FIGURE 2A.

FIGURE 2B.

Baseline patient characteristics

Findings of previous studies on chemoradiotherapy in older patients with limited-disease small cell lung cancer

Adverse events

Overview of subsequent chemoradiotherapy treatments

Treatment response

Paradigm

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