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

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

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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

Catégorie d'article: Research Article

Publié en ligne: 15 sept. 2024

Pages: 432 - 443

Reçu: 09 déc. 2023

Accepté: 26 août 2024

DOI: https://doi.org/10.2478/raon-2024-0054

Mots clés
chemoradiotherapy, chemotherapy, older patients, efficacy, limited disease, radiotherapy, safety, small cell lung cancer

© 2024 Ayako Shiono et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

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

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

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

Catégorie d'article: Research Article

Publié en ligne: 15 sept. 2024

Pages: 432 - 443

Reçu: 09 déc. 2023

Accepté: 26 août 2024

DOI: https://doi.org/10.2478/raon-2024-0054

Mots cléschemoradiotherapy, chemotherapy, older patients, efficacy, limited disease, radiotherapy, safety, small cell lung cancer

© 2024 Ayako Shiono et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

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

Mots clés
chemoradiotherapy, chemotherapy, older patients, efficacy, limited disease, radiotherapy, safety, small cell lung cancer