Nivolumab induced hyperprogressive disease in advanced esophageal squamous cell carcinoma

Figures & data

Table 1. Results of NGS examination

	Tissue sample		Blood sample
Gene	Abundance	Alteration type	Abundance	Alteration type
EGFR	CN: 4.55	Amplification
TP53	44.60%	Exon 6, p.Y220C, missense	7.20%	Exon 6, p.Y220C, missense
NOTCH1	57.73%	Exon 6, p.C359Y, missense	4.72%	Exon 6, p.C359Y, missense
HLA-A	55.20%	Exon 5, p.S337P, missense	7.54%	Exon 5, p.S337P, missense
EP300	30.14%	Exon 28, p.W1509R, missense	10.34%	Exon 28, p.W1509R, missense
ARID1A			0.83%	Exon 7, non-sense
ASXL1			1.74%	Exon 12, p.P1035S, missense
PIK3CA			1.94%	Exon 10, p.E545K, missense
HSD3B1			1.60%	Exon 4, p.Y181C, missense
PTCH1			1.93%	Exon 18, p.E970K, missense
FAT3			2.50%	Exon 9, p.T1874A, missense
LRP1B			2.24%	Exon 18, p.D2621H, missense
FGF10			1.34%	Exon 10, p.V77F, missense
PPM1D			0.57%	Exon 6, non-sense
SMAD4			1.29%	Exon 11, non-sense
TERT			1.22%	Exon 9, p.R858Q, missense

Figure 1. Clinical and histological data of the patient from our center. (a) The timeline of treatments for a patient with advanced esophageal squamous carcinoma. (b) The PD-L1 expression in tissue sample by IHC using 22C3 (X200)

Figure 2. CT scan and tumor markers of the patient experienced HPD after nivolumab treatment. (a) The CT scan before and after nivolumab treatment. In this case, HPD was defined as a disease condition after anti-PD1/PD-L1 treatment which has a short TTF (less than 1 month) and a more than 50% increase than baseline in the size of the lesion. (b) The alterations in tumor markers during nivolumab treatment

Table 2. The HPD incidences among patients received ICIs

Study ID	Cancer type	ICIs	Number of patients	HPD incidences
Kanjanapan, 2019^Citation1	Solid tumors	Any	182	7%
Champiat, 2017^Citation6	Solid tumors	Any	131	9%
Sasaki, 2019^Citation8	GC	Nivolumab	62	21%
Ferrara, 2018^Citation10	NSCLC	Any	406	13.8%
Saâda-Bouzid, 2017^Citation25	HNSCC	Any	34	29%
Kim, 2019^Citation27	NSCLC	Any	263	21%

Abbreviations

GC: gastric cancer

NSCLC: non-small cell lung cancer

HNSCC: head and neck squamous cell carcinoma

Figure 3. Potential mechanisms associated with HPD induced by immunotherapy. In addition to PI3K/AKT pathway, several genetic alterations and clinical factors have been stated to be involved in HPD, which including mouse double minute 2 (MDM2) or MDM4 amplification, alteration of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). The potential cell signaling pathways contributed to HPD were displayed

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