Response of Scalp and Skull Metastasis to Anti-PD-1 Antibody Combined with Regorafenib Treatment in a Sorafenib-Resistant Hepatocellular Carcinoma Patient and a Literature Review

Figures & data

Figure 1 Contrast imaging of primary liver lesions on MRI subsequent to sorafenib-regorafenib therapy combined with sintilimab. (A) The largest liver lesion in Segment 6 at admission. (B) A posterior portal vein tumor thrombus indicated by the arrow at admission. (C) Tumor in Segment 6 is rendered inactive by treatment. (D) Disappearance of PVTT.

Figure 2 Evolution of HCC lung metastasis. (A and B) No signs of metastasis at admission, (C and D) Multiple lung lesions after therapy with sorafenib for 1 year, (E and F) Volume of lung lesions decrease after treatment with regorafenib combined with sintilimab for 3 months. (G and H) Complete remission of lung metastasis.

Figure 3 Evolution of the primary liver lesion on computed tomography. (A) Liver lesion in Segment 6 at admission, (B and C) Changes in the segment 6 lesion post-microwave irradiation, (D and E) The tumor continually progresses. (F) Main portal vein tumor thrombus emerges. Red arrow indicates main portal vein tumor thrombus.

Figure 4 Evolution of the scalp and skull metastasis on computed tomography and whole-body bone scan by single-photon emission computed tomography (SPECT) using 99mTc. (A and B) the scalp and skull metastases occur on the frontal site, (C and D) the scalp and skull lesions shrink significantly, (E) SPETCT shows no active signal at admission, (F) SPECT indicates frontal skull marked by arrow, left sacroiliac joint, and left iliac increased radioactivity, (G and H) radioactivity of the skull disappears.

Figure 5 AFP levels over time. The first red arrow indicates the treatment of laparoscopic microwave and sorafenib after finding AFP level is 46,502 ng/mL, and second red arrow indicates the use of regorafenib and sintilimab after AFP level elevates to more than 65000ng/mL.

Table 1 Clinical Characteristics of the Reported HCC Scalp and Skull Metastasis

No.	Reference	Year	Age	Sex	Risk Factor	Manifestation	Primary Lesion	Vascular Invasion	Skull Spread	Involvement	Other Spread	Management	Follow-Up	Prognosis
1	Sanders et al^Citation40	2020	77	F	HBV	Scalp mass	Multiple, infiltrative	None	Frontal region	Scalp, skull	None	BSC	2 months	Expired
2	Sadik et al^Citation41	2019	54	M	HCV	Scalp mass	Single	IVC, RAT	Superior sagittal sinus	Scalp, skull	Lung, rib	Craniotomy	26 days	Expired
3	Han et a^Citation25	2017	66	M	S.J.	Scalp mass, headache, dizziness	None	None	Left occipital region	Scalp, skull, dura	None	Selective embolization, craniotomy	9 months	Alive
4	Ferraz et al^Citation42	2016	55	M	None	Scalp mass with local pain	Single, infiltrative	None	Right frontal region	Scalp, skull	Clavicle, sternum, hip, lumbar spine	Craniotomy, radiotherapy	6 months	Expired
5	Kim et al^Citation43	2015	41	M	ND	Sudden headache, vomiting, drowsiness	Multiple	ND	Right occipital region	Skull, epi-dura	Ribs, pelvis	BSC	4 months	Expired
6	Subasinghe et al^Citation44	2015	56	M	None	Scalp mass	Single	None	Occipital region	Scalp, skull	Left scapula	Excision of the scalp mass, RFA for liver mass	ND	ND
7	Susheela et al^Citation45	2015	40	M	HBV	Scalp mass	Multiple	ND	Frontal region	Scalp, skull	Lung, dorsal vertebrae	Radiotherapy, sorafenib	12 months	Expired
8	Chye et al^Citation46	2015	69	F	HCV	Headache, nausea, vomiting, dizziness	Single	None	Left temporal region	Scalp, skull, epi-dura, dura	None	Radiotherapy for brain, TACE for liver mass	ND	ND
9	Guo et al^Citation47	2014	49	M	HBV	Scalp mass	Single	None	Right parietal-occipital region	Scalp, skull	None	Craniotomy, TACE for liver mass	18 months	Expired
10	Azarpira et al^Citation48	2014	38	M	HBV	Scalp mass	None	None	Right temporal region	Scalp, skull, dura	None	Radiotherapy, chemotherapy	3 months	Alive
11	Turan et al^Citation49	2013	70	M	HBV	Scalp mass	Single	None	Frontal region	Scalp, skull	Lung, adrenal glands, ribs, lumbar vertebrae, and pelvis	Craniotomy, sorafenib	11 months	Expired
12	Brunetti et al^Citation50	2012	79	M	ND	Scalp mass	Multiple	ND	Parietal-occipital region	Scalp, skull	Mandible	Biopsy	ND	ND
13	Ermis et al^Citation51	2012	72	M	HCV	Scalp mass	Multiple	PVTT	Right frontal-parietal region	Scalp, skull	Thoracic vertebrae, ribs, sternum, right sacroiliac joint	Biopsy	ND	ND
14	Goto et al^Citation52	2010	56	M	HBV	Scalp mass	Multiple	None	Left occipital-temporal region	Scalp, skull	Thoracic vertebrae	Radiotherapy for brain, TACE for liver mass	ND	Expired
15	Woo et al^Citation53	2010	46	M	ND	Severe headache, unconsciousness	ND	ND	Right temporal region	Skull, epi-dura, dura	ND	Craniotomy	5 days	Expired
16	Fukushima et al^Citation26	2010	58	M	ND	Scalp mass	None	None	Left temporal region	Scalp, skull	None	Craniotomy	ND	ND
17	Kanai et al^Citation54	2009	56	M	HCV	Severe headache, unconsciousness	Single, huge	None	Left occipital region	Scalp, skull, epi-dura	ND	Craniotomy	21 days	Expired
18	Shim et al^Citation55	2008	71	M	HCV, alcohol	Scalp mass	Two	None	Occipital region	Scalp, skull	None	Craniotomy,	9 months	Alive
												TACE for liver mass
19	Hsu et al^Citation56	2008	53	M	HBV	Scalp mass, visual field defect	Multiple	None	Left parietal-occipital region	Scalp, skull, epi-dura	None	TACE, craniotomy, radiotherapy	10 months	Alive
20	Hsieh et al^Citation57	2006	46	M	HBV	Scalp mass	None	None	Left frontal region	Scalp, skull	Spine, left femur	Craniotomy, radiotherapy, chemotherapy	15 months	Alive
21	Simone et al^Citation30	2005	61	M	HCV	Scalp mass	Multiple	None	Left parietal region	Scalp, skull	Sternum, lung	Craniotomy, chemotherapy	ND	ND
22	Nam et al^Citation58	2005	65	M	HCV, alcohol	Scalp mass	Multiple	None	Frontal region	Scalp, skull, dura	Sternum, ribs	Biopsy, radiotherapy	26 months	Alive
23	Jegou et al^Citation59	2004	55	M	ND	Scalp mass	Single	None	Left frontal region	Scalp, skull	Adrenal gland	Biopsy	ND	ND
24	Chan et al^Citation60	2004	75	F	None	Scalp mass	Single	None	Right frontal region	Scalp, skull	None	Craniotomy	ND	ND
25	Torres et al^Citation61	2002	66	F	HCV	Scalp mass	Two	None	Occipital region	Scalp, skull	None	Biopsy	42 days	Expired
26	Hayashi et al^Citation62	2000	70	M	ND	Left-sided hemiparesis	ND	ND	Right parietal region	Scalp, skull, epi-dura	ND	Craniotomy	2 months	Expired
27	Nakagawa et al^Citation63	1992	52	M	ND	ND	ND	ND	ND	Scalp, skull, epi-dura	ND	Craniotomy	ND	Expired

Abbreviations: F, female; M, male; ND, not described; BSC, best supportive care; IVC, inferior vena cava; RFA, radiofrequency ablation; PVTT, portal vein tumor thrombus; S.J., Schistosoma japonicum; RAT, right atrium thrombus.

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