Adjuvant therapy for lung neuroendocrine neoplasms

Table 2 Summary of the available studies examining the use of adjuvant therapy in the treatment of stage I, II, and III typical carcinoid and atypical carcinoid

Study information; Stage and Subgroup	Ref.
	Westin et al[23], 2017	Wegner et al[21], 2019	Gosain et al[22], 2019	Nussbaum et al[24], 2015	Anderson et al[25], 2017	Herde et al[26], 2018	Chong et al[27], 2014	Buonerba et al[29], 2010
AT	Chemotherapy	Chemotherapy, radiation or chemoradiation	Chemotherapy	Chemotherapy	Chemotherapy	Chemoradiation or radiation alone	Chemoradiation	Chemotherapy; SSA
Study	Retrospective; NCDB	Retrospective; NCDB	Retrospective; NCDB	Retrospective; NCDB	Retrospective; NCDB	Retrospective; Single Institution	Retrospective; Single Institution	Case Report
Subgroup	TC/AC	TC/AC	TC/AC	TC	AC	TC/AC	TC/AC	AC
Stage	IIB,III	I,II,III	I,II,III	IIB,III	I,II,III	I,II,III	IIB,IIIA	I
Other	node +	NA	NA	node +	Comparing node + and node -	NA	NA	NA
I; TC	NA	Surgery without AT3	Surgery without AT	NA	NA	AT in patients with adverse pathologic features9	NA	NA
I; AC	NA	Surgery without AT3	Surgery without AT@ (5-yr OS of 84% in obs vs 52% AT; P < 0.01)	NA	Surgery without AT in node - (OS at 12 and 60 mo in AT 86.7% and 73.3%, vs obs 87.9% and 72.3% P = 0.54).	AT in patients with adverse pathologic features9	NA	Chemotherapy followed by SSA; 10-yr PFS
II; TC	Surgery without AT (inferior OS with AT)1	Surgery without AT3	Surgery without AT	Surgery without AT5,6 (5-yr OS 81.9% obs, vs 69.7% AT; P = 0.042)	NA	AT in patients with adverse pathologic features9	chemotherapy may be beneficial in a subset of patients8	NA
II; AC	Surgery without AT (no OS benefit)2	Surgery without AT3	Surgery without AT (5-yr survival of 81% in obs vs 55% AT; P = 0.34).	NA	Surgery without AT in node +7	AT in patients with adverse pathologic features9	chemotherapy may be beneficial in a subset of patients8	NA
III; TC	Surgery without AT (inferior OS with AT)1	Surgery without AT4	Surgery without AT	Surgery without AT5,6 (5-yr OS 81.9% obs, vs 69.7% AT; P = 0.042)	NA	AT in patients with adverse pathologic features9	chemotherapy may be beneficial in a subset of patients8	NA
III; AC	Surgery without AT (no OS benefit)2	Surgery without AT4	Surgery without AT but trend towards benefit (46% in obs vs 54% AT; P = 0.24)	NA	Surgery without AT in node +7	AT in patients with adverse pathologic features9	chemotherapy may be beneficial in a subset of patients8	NA

¹Stage IIB, III grouped together and was associated with inferior OS (HR: 3.8; 95%CI: 1.9-7.0; P = 0.004).

²Stage IIB, III grouped together with no befit in OS (HR: 1.1; 95%CI: 0.68-1.78; P = 0.6).

³TC and AC stage I and II tumors grouped together to show a median survival of 114 months versus 117 months with observation (P = 0.30).

⁴TC and AC stage III tumors favored observation with a median survival of 79 mo vs 63 mo (P = 0.89).

⁵Adjuvant treatment showed a harmful effect.

⁶When baseline patient features were matched a statistical difference in OS no longer existed but there was a towards detriment (69.7% vs 80.9%; P = 0.096).

⁷Node + stage II and III grouped together; OS at 12 and 60 mo in AT 98.9% and 47.9%, vs obs 98.4% and 67.1%; P = 0.46.

⁸Stage IIB and IIIA grouped together; at 2-yr follow up, there was a 28% recurrence rate for those with local regional disease.

⁹Stage I, II, III AC and TC grouped together; overall AT showed a 20% recurrence rate.

AT: Adjuvant therapy; AC: Atypical carcinoid; Obs: Observation; OS: Overall survival; NA: Not applicable; NCDB: National cancer database; PFS: Progression free survival; SSA: Somatostatin analogue; TC: Typical carcinoid.