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

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

CBDCA = carboplatin; CDDP = cisplatin; CRT = chemoradiotherapy; ECOG-PS = Eastern Cooperative Oncology Group - Performance Status; G-CSF = granulocyte colony-stimulating factor

a Comparison between the concurrent and sequential chemoradiotherapy groups

b Welch’s t-test

c The clinical progressive disease after two courses of chemotherapy, followed by definitive radiotherapy and partial response (PR)

TABLE 2.

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

CRT = chemoradiotherapy; 95% CI = 95% confidence interval

a Comparison between the concurrent and sequential chemoradiotherapy groups

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).

TABLE 3.

Adverse events

Adverse event	All patients (N = 32)				Concurrent CRT (n = 19)				Sequential CRT (n = 13)				p^a
Adverse event	Any Grade	%	Grade≥3	%	Any Grade	%	Grade≥3	%	Any Grade	%	Grade≥3	%	p^a
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

CRT = chemoradiotherapy. Bold text indicates statistically significant differences.

a Comparison between the concurrent cohort and sequential chemoradiotherapy groups of Grade ≥ 3.

b Treatment-related adverse events reported as Grade ≥ 3 in ≥ one patient.

TABLE 4.

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

TABLE 5.

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%

CBDCA = carboplatin; CDDP = cisplatin; con CRT = concurrent chemoradiotherapy; CPT11 = irinotecan; ETP = etoposide; FN = febrile neutropenia; KPS = Karnofsky performance status; NR = not reported; OS = overall survival; PFS = progression-free survival; PS = performance status; seq CRT = sequential chemoradiotherapy

a Some studies use different versions of the Common Terminology Criteria for Adverse Events.

b Patients receiving CRT with survival of at least 4 months after diagnosis

c Phase 2 cohort

Articles in this issue

DOI: https://doi.org/10.2478/raon-2024-0054 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099

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Language: English

Page range: 432 - 443

Submitted on: Dec 9, 2023

Accepted on: Aug 26, 2024

Published on: Sep 15, 2024

Published by: Association of Radiology and Oncology

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

safety,

small cell lung cancer

Related subjects:

Medicine,

Clinical medicine,

Radiology

© 2024 Ayako Shiono, Hisao Imai, Satoshi Endo, Kazuki Katayama, Hideaki Sato, Kosuke Hashimoto, Yu Miura, Shohei Okazaki, Takanori Abe, Atsuto Mouri, Kyoichi Kaira, Ken Masubuchi, Kunihiko Kobayashi, Koichi Minato, Shingo Kato, Hiroshi Kagamu, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 58 (2024): Issue 3 (September 2024)

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

TABLE 1.

TABLE 2.

FIGURE 1A.

FIGURE 1B.

FIGURE 2A.

FIGURE 2B.

TABLE 3.

TABLE 4.

TABLE 5.

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