Table 1:

Summary of Literature review using local drug delivery. Both pre-clinical as well as clinical investigational studies during three phases of treatment, diagnosis, resection, and metastatic disease, were reviewed. The summary of the study design and outcomes are outlined in the table.

	Author	Year Published	Animal/ Human study	Mode of Delivery	Tumor Type	Tumor Size/ Timing at Delivery	Drug
At Tumor Diagnosis
Pre-Clinical
	Yatvin	1978	in-vitro	Liposomes	N/a	N/a	Neomycin
	Lewis	2006	in-vitro	DC Bead	N/a	N/a	Doxorubicin
	Seo	2008	Mouse	Liposomes injected via tail vein	N/a	N/a	Cu-specific chelator, 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N’,N”,N”‘-tetraacetic acid (BAT)
	Paoli	2010	Mouse	Liposomes injected via tail vein	Met-1 tumor	0.5 cm	hydrophilic model drug
	Xu	2015	Mouse	Intratumoral injection	Breast	N/a	IL-21
	Conde	2015	Mouse	Bare-Gold nanoparticles implanted peri tumorally	Triple Negative Breast Cancer	100 mm3	5-fluorouracil (5-FU)-intercalated nanobeacons
	Ranjan	2012	Rabbit	Low temperature sensitive liposomes via	Vx2 tumor	1cm	Doxorubicin
	Zhang	2015	Pigs	Image guided percutaneous injection into target	N/a, Common Bile duct	N/a	Motexafin gadolinium (MGd) and trypan blue dye as well as 5-fluorouracil (5-Fu)
Clinical Investigation
	Sampath	1998	Human	Implantable biodegradable polymer within tumor	Glioma	N/a	Carmustine (BCNU)-impregnated
	Firusian	1999	Human	Direct Intratumoral injection	Solid Tumors (hepatoma, GI malignancy, breast, and thyroid)	N/a	P-32 chromic phosphate
	Hohenforst-Schmidt	2013	Human	Intratumoral-regional and intravenous administration	Non-small cell lung cancer	Stage 3a or 4	Cisplatin analogues
At Time of Resection
Pre-Clinical
	Ewend	1998	Mouse	Controlled release polymers in surgical resection bed	Breast	5 days post inoculation	Carmustine (BCNU), carboplatin, and camptothecin
	Zaharoff	2010	Mouse	Intratumoral biodegradable polysaccharide chitosan	Colon and Pancreatic	7 days post inoculation	IL-12
	Seib	2012	Mouse	Controlled release silk film at tumor	Breast	12 days post inoculation	Doxorubicin
	Chiu	2014	Mouse	Controlled release silk film at tumor resection bed	Neuroblastoma	300 mm3	Doxorubicin
	Seib	2015	Mouse	Controlled release silk film at tumor	Neuroblastoma	70 mm3	Doxorubicin and Crizotinib
	Wang	2008	Rat	Intratumoral injection of liposome	squamous cell carcinoma	2–3 cm3	Beta-emission rhenium-186
Clinical Investigation
	Westphal	2003	Human	Implantable biodegradable wafer in tumor resection bed	Malignant Glioma	N/a	1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)
	Sampson	2006	Human	Convection-enhanced delivery via stereotactic catheter	Recurrent Glioblastoma Multiforme	N/a	Antitenascin mAb 81C6
	Roberts	2014	Human	Intratumoral injection	Retroperitoneal leiomyosarcoma	N/a	Clostridium novyi
Metastatic Disease
Pre-Clinical
	Ewend	1998	Mouse	Controlled release polymers in surgical resection bed	Breast	5 days post inoculation	carmustine (BCNU), carboplatin, and camptothecin
	Zhao	2013	Mouse	Drug-loaded conventional liposomes injected into portal vein	Colon metastasized to the liver	7 days post inoculation	Doxorubicin
	Sato	2015	Mouse	Intralymphatic delivery with nano/ microbubbles in combination with ultrasound	Mammary and hepatoma	Day 3,4 post inoculation	cis-diamminedichloroplatinum
	Funayama	2013	Rat	Tumor-selective photodynamic therapy (PDT) with nanocarrier	Spinal cord metastasis	N/a	Indocyanine green
	Upadhyay	2014	Rat	Intracranial implanted microcapsules	Breast	0,6,13 days post inoculation	Temozolomide and Doxorubicin
Clinical Investigation
	Ewend	2007	Human	Polymer wafer in tumor resection bed	Metastatic brain lesions: lung, melanoma, breast, renal	N/a	Carmustine
	Brem	2013	Human	Polymer wafer in tumor resection bed	Single or multiple brain metastasis	N/a	Carmustine