Sarcopenia in pancreatic cancer: Effect on patient outcomes

Table 1 Studies analyzing the effect of sarcopenia on surgical outcomes of pancreatic cancer

Ref.	Country	No. of patients	Imaging modality	Level	Time	Definition and cutoff	Sarcopenia prevalence before surgery	Types of surgery	Perioperative complications	Survival	Additional meaningful findings or comments
Peng et al[24], 2012	United States	557	CT	L3	Before surgery	TPAI (mm2/m2), lowest quartile: < 564.2 (M), < 414.5 (F)	25%	PD, DP	(-)	(+) OS	Sarcopenia was an independent predictor of survival in multivariable analysis
Amini et al[7], 2015	United States	763	CT	L3	Before surgery	TPAI (mm2/m2), < 564.2 (M), 414.5 (F); TPVI (cm³/m2), < 17.2 (M), < 12.0 (F)	25% by TPAI, 20% by TPVI	PD, DP. TP	(+) Overall Cx. by TPVI	(+) OS by TPVI	TPVI was a better measure for defining sarcopenia rather than TPAI
Pecorelli et al[9], 2016	Italy	202	CT	L3	Before surgery	LSMI, < 52.4 cm2/m2 (M), < 38.5 cm2/m2 (F)1	65%	PD	(-)	NE	The combination of visceral obesity and sarcopenia was a predictor of perioperative Cx
Ninomiya et al[28], 2017	Japan	265	CT	L3	Before surgery	LSMI, < 43.75 cm2/m2 (M), < 38.5 cm2/m2 (F)	64%	PD, DP. TP	(-)	(-)	Sarcopenia was an independent prognostic factor only in patients with BMI ≥ 22 kg/m2
Okumura et al[29], 2017	Japan	301	CT	L3	Before surgery	LSMI, clinically relevant cutoff: < 47.1 cm2/m2 (M), < 36.6 cm2/m2 (F)	40%	PD, DP. TP	(-)	(+) OS and RFS	Low muscle attenuation, as well as low muscle mass, was associated with worse OS and RFS
Choi et al[18], 2018	South Korea	180	CT	L3	Before and after 60 d of surgery	LSMI, the lowest tertile; < 45.3 cm2/m2 (M), < 39.3 cm2/m2 (F)	33%	PD, DP	(-)	(+) OS	Accelerated muscle loss after surgery negatively impacts OS
Sugimoto et al[19], 2018	United States	323	CT	L3	Before surgery	LSMI, < 55.4 cm2/m2 (M), < 38.9 cm2/m2 (F)	62%	PD, DP. TP	NE	(-)	Smaller sex-standardized LSMI as a continuous variable is associated with a shorter OS
Gruber et al[10], 2019	Austria	133	CT	L3	Before surgery	LSMI, < 52.4 cm2/m2 (M), < 38.5 cm2/m2 (F)1	59%	PD, DP	(-)	(+) OS	Obese patients (BMI ≥ 25) with sarcopenia have higher incidence of major post-operative Cx
Ryu et al[30], 2020	South Korea	548	CT	L3	Before surgery	LSMI, < 50.18 cm2/m2 (M), < 38.63 cm2/m2 (F)	46%	PD	(-)	(+) OS	Sarcopenic obesity is a predictive factor for post-operative pancreatic fistula after PD
Rom et al[25], 2022	Israel	111	CT	L3	Before surgery	LSMI, the lowest quartile: < 44; 35 cm2/m2 (M), < 34.82 cm2/m2 (F)	25%	PD, DP	(+) Overall Cx.	(+) OS, DSS, and RFS	High intramuscular adipose tissue content correlates with poor OS and DSS

¹This cutoff value for sarcopenia was defined by Prado et al[8] (2008). BMI: Body mass index; CT: Computed tomography; Cx.: Complications; DP: Distal pancreatectomy; DSS: Disease-specific survival; F: Female; L3: Level of the lumbar 3 vertebral body; LSMI: Lumbar skeletal muscle index; M: Male; NE: Not evaluated; OS: Overall survival; PD: Pancreaticoduodenectomy; RFS: Recurrence-free survival; TPAI: Total psoas area index; TPVI: Total psoas volume index; TP: Total pancreatectomy.

Table 2 Studies analyzing the effect of sarcopenia on neoadjuvant therapy outcomes of pancreatic cancer

Ref.	Country	No. of patients	Inclusion	Imaging modality	Level	Time	Definition and cutoff	Sarcopenia prevalence before NAT	Resectability	Survival	Additional meaningful findings or comments
Cooper et al[35], 2015	United States	89	RPC	CT	L3	Before and after NAT	LSMI, < 55.4 cm2/m2 (M), < 38.9 cm2/m2 (F)	55%	(-)	(-)	SKM loss during NAT was correlated with DFS
Cloyd et al[36], 2018	United States	127	RPC, BRPC, LAPC	CT	L3	Before and after NAT, 3 mo and 12 mo after surgery (PD)	LSMI, < 55.4 cm2/m2 (M), < 38.9 cm2/m2 (F)	63%	NE	(-)	SKM gain between the postoperative period and 1-yr follow-up was correlated with improved OS
Sandini et al[13], 2018	United States and Italy	193	BRPC, LAPC	CT	L3	Before and after NAT	LSMI, < 43 cm2/m2 (M) where BMI < 25 kg/m2, < 53 cm2/m2 (M) where BMI > 25 kg/m2, < 41 cm2/m2 (F)1	44%	(-)	NE	SKM gain during NAT is correlated with better resectability
Griffin et al[14], 2019	Ireland	78	BRPC	CT	L3	Before and after NAT	LSMI, < 43 cm2/m2 (M) where BMI < 25 kg/m2, < 53 cm2/m2 (M) where BMI > 25 kg/m2, < 41 cm2/m2 (F)1	50%	(-)	(-)	Low muscle attenuation before NAT and SKM loss during NAT was correlated with decreased OS
Takeda et al[15], 2021	Japan	62	RPC	CT	L3	Before NAT	LSMI, < 43 cm2/m2 (M) where BMI < 25 kg/m2, < 53 cm2/m2 (M) where BMI > 25 kg/m2, < 41 cm2/m2 (F)1	40%	(-)	NE	Sarcopenia before NAT did not correlate with antitumor response and toxicity of therapy
Jin et al[37], 2022	China	119	RPC	CT	L3	Before and after NAT	LSMI, < 41 cm2/m2 (M), < 38.5 cm2/m2 (F)	48%	NE	(+) OS, DFS	SKM and fat wasting during NAT was correlated with decreased OS and DFS

¹This cutoff value for sarcopenia was defined by Martin et al[12] reported in 2013. BMI: Body mass index; BRPC: Borderline resectable pancreatic cancer; CT: Computed tomography; DFS: Disease-free survival; F: Female; L3: Level of the lumbar 3 vertebral body; LAPC: Locally advanced pancreatic cancer; LSMI: Lumbar skeletal muscle index; M: Male; NAT: Neoadjuvant therapy; NE: Not evaluated; OS: Overall survival; PD: Pancreaticoduodenectomy; RPC: Resectable pancreatic cancer; SKM: Skeletal muscle.

Table 3 Studies analyzing the effect of sarcopenia on palliative chemotherapy outcomes of pancreatic cancer

Ref.	Country	No. of patients	Inclusion (%)	Imaging modality	Level	Time	Definition and cutoff	Sarcopenia prevalence before CTX	CTX regimen	CTX toxicity	PFS	OS	Additional meaningful findings or comments
Kays et al[11], 2018	United States	53	LAPC (49), MPC (51)	CT	L3	Before and during CTX (median 5.6 times)	LSMI, < 52.4 cm2/m2 (M), < 38.5 cm2/m2 (F)1	49%	1st line FOLFIRINOX	NE	NE	(-)	No muscle wasting during CTX improved OS
Basile et al[16], 2019	Italy	94	LAPC (50), MPC (50)	CT	L3	Before and after 12 wk of CTX	LSMI, < 43 cm2/m2 (M) where BMI < 25 kg/m2, < 53 cm2/m2 (M) where BMI > 25 kg/m2, < 41 cm2/m2 (F)2	73%	Various	NE	(-)	(-)	Loss of skeletal muscle mass (≥ 10%) was associated with worse OS and PFS
Kurita et al[38], 2019	Japan	82	LAPC (35), MPC (65)	CT	L3	Before CTX	LSMI, clinically relevant cut-off: < 45.3 cm2/m2 (M), < 37.1 cm2/m2 (F)	51%	1st line FOLFIRINOX	(-)	(+)	(+)	Sarcopenic obesity was associated with hematologic toxicity
Lee et al[39], 2019	South Korea	57	LAPC (5), MPC (95)	CT	L3	Before and after 8 wk of CTX	LSMI, median level: unknown	50%	2nd line FOLFIRINOX	NE	(+)	(+)	Baseline LSMI was an independent predictor of survival in multivariable analysis
Kim et al[17], 2021	South Korea	251	MPC (100)	CT	L3	Before and after 8 wk of CTX	LSMI, < 43 cm2/m2 (M) where BMI < 25 kg/m2, < 53 cm2/m2 (M) where BMI > 25 kg/m2, < 41 cm2/m2 (F)2	41%	1st line gemcitabine-based CTX	(+) Overall grade ≥ 3 toxicity	(-)	(-)	Sarcopenia was a prognostic factor for OS but not for PFS in multivariable analysis
Uemura et al[21], 2021	Japan	69	LAPC (29), MPC (71)	CT	L3	Before and after 8 wk of CTX	LSMI, < 42 cm2/m2 (M), < 38 cm2/m2 (F)3	48%	1st line FOLFIRINOX	(-)	(-)	(-)	Loss of skeletal muscle mass (≥ 7.9%) is associated with worse OS
Williet et al[40], 2021	France	79	MPC (100)	CT	L3	Before CTX	TPAI, clinically relevant cutoff: 5.73 cm2/m2 (M), 4.37 cm2/m2 (F)	38%	Various	(-)	(+)	(+)	Measuring TPAI was less time-consuming than measuring LSMI
Asama et al[22], 2022	Japan	124	LAPC (29), MPC (60), RePC (15)	CT	L3	Before CTX	LSMI, < 42 cm2/m2 (M), < 38 cm2/m2 (F)3	49%	1st line Gem-Nab	(-)	(-)	(-)	In elderly patients (> 70 yr), sarcopenia was associated with worse OS
Emori et al[23], 2022	Japan	176	LAPC (14), MPC (86)	CT	L3	Before CTX	LSMI, < 42 cm2/m2 (M), < 38 cm2/m2 (F)3	53%	1st line Gem-Nab	(+) Overall grade ≥ 3 toxicity	(+)	(+)	Propensity score matching analysis was performed

¹This cutoff value for sarcopenia was defined by Prado et al[8] (2008).

²This cutoff value for sarcopenia was defined by Martin et al[12] (2013).

³This cutoff value for sarcopenia was defined by the Asian Working Group for Sarcopenia (Chen et al[20]) reported in 2014.

BMI: Body mass index; CT: Computed tomography; CTX: Chemotherapy; F: Female; FOLFIRINOX: Folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin; Gem-Nab: Gemcitabine plus nab-paclitaxel; L3: Level of the lumbar 3 vertebral body; LAPC: Locally advanced pancreatic cancer; LSMI: Lumbar skeletal muscle index; M: Male; MPC: Metastatic pancreatic cancer; NE: Not evaluated; OS: Overall survival; PFS: Progression-free survival; RePC: Recurrent pancreatic cancer; TPAI: Total psoas area index.