Locally Advanced Pancreatic Ductal Adenocarcinoma: Challenges and Progress

Figures & data

Table 1 Risk Factors

Environmental Risk Factor
Cigarette Smoking and Other Tobacco Products^Citation8,Citation18^–^Citation20
Obesity	Hormonal and inflammatory effects^Citation24,Citation25
	Diet^Citation26^–^Citation28
	Reduced physical activity^Citation29
Type 2 diabetes^Citation31^–^Citation35,Citation37
Alcohol Consumption^Citation43

Table 2 Common Histotypes of Pancreatic Cancers

Simplified Histological Classification
Ductal adenocarcinoma
Mucinous cystic neoplasm
Serous cystadenoma
Intraductal papillary mucinous neoplasm
Acinar cell carcinoma
Acinar cell cystadenocarcinoma
Intraductal papillary mucinous neoplasm with an associated invasive carcinoma
Intraductal tubule-papillary neoplasm with associated invasive carcinoma
Pancreatoblastoma
Serous cystadenocarcinoma
Mixed acinar/ductal/neuroendocrine carcinoma
Solid-pseudopapillary neoplasm
Neuroendocrine neoplasms

Table 3 Summary of Molecular Subtypes

Molecular Subtypes	Features	Clinical Outcome	Therapeutic Response
Classical	High expression of epithelial and adhesion-related genes	Best prognosis	Gemcitabine-resistant; Erlotinib-sensitive
Quasi-Mesenchymal	High expression of mesenchyme-related genes	Worst prognosis	Gemcitabine-sensitive; Erlotinib-resistant
Exocrine-like	High expression of tumour cell-derived and genes-linked to digestive enzyme	Intermediate prognosis	Not reported

Note: Data from Collisson et al. ⁶⁷

Table 4 Particle Therapy Studies

Authors	Type of Study	Particle	Number of Patients	Dose/Fractionation/Chemotherapy	Overall Survival	Toxicity > G3 (Number of Patients)
Terashima et al, 2012^Citation125	Mono-centric Prospective; Phase I–II,	Proton	50	P1: 50 GyE/25 fractions (5), P2: 70.2 GyE/26 fractions (5), P3: 67.5 GyE/25 fractions (40), All with concurrent gemcitabine	1-year:76.8% P3 patients: 1-year:78.8%	P1 G3 Anorexia (1) G3 Epigastralgia (1) P2 G3 Anorexia (1) G3 gastric ulcer (1), P3: G3 Anorexia (4) G3 GI ulcer (3); G5: death from GI bleeding (1)
Shinoto et al, 2016^Citation129	Mono-centric Prospective, Phase I	Carbon ions	71	43.2–55.2 GyE/12 fractions, Gemcitabine	1-year: 73%, 2-year: 35% Median:19.6 months	G3 Anorexia (6), G3 gastrointestinal (1)
Shinoto et al, 2018^Citation128	Mono-centric retrospective study	Carbon ions	46	55.2 GyE/12fractions, Gemcitabine	2-year: 53% Median:25.1 months	G3 anorexia (1); G3 gastrointestinal (2)
Kawashiro et al, 2018^Citation119	Multi-centric retrospective study	Carbon ions	72	52.8 GyE or 55.2 GyE 12 fractions Concurrent Gemcitabine (in 78% pts)	1 -year: 73% 2 -year: 46% Median: 21.5 months	G3 anorexia (2); G3 duodenal-ulcer (1)

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