Improved outcomes for borderline resectable adenocarcinoma of the pancreas after neoadjuvant chemotherapy in a community cancer center.

BACKGROUND: Borderline resectable adenocarcinoma of the pancreas involves the major vascular structures adjacent to the pancreas and has traditionally led to poor resection rates and survival. Newer chemotherapy regimens have demonstrated improved response and resection rates. We performed a retrospective review of borderline resectable pancreatic cancers who presented to a community cancer program to determine the effect of neoadjuvant chemotherapy to improve resection rates and overall survival. METHODS: Records of all patients diagnosed with adenocarcinoma of the pancreas from January 1, 2015 to December 31, 2019 were reviewed to determine stage at presentation, resectablility status, treatment methods, surgical resection and survival. Borderline resectable status was determined by preoperative imaging in agreement with published criteria from the National Comprehensive Cancer Network (NCCN) Guidelines 2.2021. Data was collected and analyzed by standard t-test. This study was approved by the institution's IRB. RESULTS: During this time period 322 patients were diagnosed with ductal adenocarcinoma of the pancreas of which 151 (47%) were unresectable, 31 (10%) were locally advanced, 70 (22%) were borderline resectable, and 69 (21%) were resectable at the time of presentation. 36 (51%) of the borderline resectable patients underwent neoadjuvant chemotherapy at our institution with either FOLFIRINOX or gemcitibine/nab-Paclitaxel regimens and served as the basis for this analysis. After neoadjuvant chemotherapy 24 (68%) of the borderline-resectable patients were deemed suitable for surgical exploration. At exploration, 15 (64%) were resected with 9 (60%) achieving margin-free resection on final pathology. The overall survival of those that underwent resection was increased by 19.6 months compared to those that did not undergo surgery (35.4 versus 15.8 mos, p < 0.01). Overall morbidity after resection was 46% (33% class 1 or 2, 13% class 3) with 0% mortality at 90 days. CONCLUSIONS: Use of neoadjuvant chemotherapy for borderline resectable adenocarcinoma of the pancreas results in improved resection rates and overall survival in resected patients. This management strategy for ductal adenocarcinoma of the pancreas is safe and feasible in a community-based cancer program.

Targeted polymeric nanoparticles for drug delivery to hypoxic, triple-negative breast tumors.

High recurrence and metastasis to vital organs are the major characteristics of triple-negative breast cancer (TNBC). Low vascular oxygen tension promotes resistance to chemo- and radiation therapy. Neuropilin-1 (NRP-1) receptor is highly expressed on TNBC cells. The tumor-penetrating iRGD peptide interacts with the NRP-1 receptor, triggers endocytosis and transcytosis, and facilitates penetration. Herein, we synthesized a hypoxia-responsive diblock PLA-diazobenzene-PEG copolymer and prepared self-assembled hypoxia-responsive polymersomes (Ps) in an aqueous buffer. The iRGD peptide was incorporated into the polymersome structure to make hypoxia-responsive iRGD-conjugated polymersomes (iPs). Doxorubicin (DOX) was encapsulated in the polymersomes to prepare both targeted and non-targeted hypoxia-responsive polymersomes (DOX-iPs and DOX-Ps, respectively). The polymeric nanoparticles released less than 30% of their encapsulated DOX within 12 hours under normoxic conditions (21% oxygen), whereas under hypoxia (2% Oxygen), doxorubicin release remarkably increased to over 95%. The targeted polymersomes significantly decreased TNBC cells' viability in monolayer and spheroid cultures under hypoxia compared to normoxia. Animal studies displayed that targeted polymersomes significantly diminished tumor growth in xenograft nude mice. Overall, the targeted polymersomes exhibited potent anti-tumor activity in monolayer, spheroid, and animal models of TNBC. With further developments, the targeted nanocarriers discussed here might have the translational potential as drug carriers for the treatment of TNBC.