Surgical intervention as part of an aggressive multimodality treatment plan results in improved outcomes for patients with advanced hepatic metastases of neuroendocrine origin. Future directions may include earlier surgical intervention with adjuvant therapies reserved for aggressive recurrent disease.
Immunotherapy is now a cornerstone for cancer treatment, and much attention has been placed on the identification of prognostic and predictive biomarkers. The success of biomarker development is dependent on accurate and timely collection of biospecimens and high-quality processing, storage and shipping. Tumors are also increasingly used as source material for the generation of therapeutic T cells. There have been few guidelines or consensus statements on how to optimally collect and manage biospecimens and source material being used for immunotherapy and related research. The Society for Immunotherapy of Cancer Surgery Committee has brought together surgical experts from multiple subspecialty disciplines to identify best practices and to provide consensus on how best to access and manage specific tissues for immuno-oncology treatments and clinical investigation. In addition, the committee recommends early integration of surgeons and other interventional physicians with expertise in biospecimen collection, especially in clinical trials, to optimize the quality of tissue and the validity of correlative clinical studies in cancer immunotherapy.
SSTR subtype expression needs to be correlated to somatostatin analog therapy. Immunohistochemical profiling of various SSTR subtypes as a part of routine surgical pathologic analysis of enteropancreatic ETs may become a useful predictor of responsiveness of ETs to various SSTR analogs.
Background: The human cellular apoptosis susceptibility protein (hCAS) is a Ran- binding protein playing a role as mitotic spindle checkpoint regulator and as nuclear export factor. hCAS expression is frequently altered in metastatic cancers. To date the role of hCAS in pancreatic cancer is unknown. Therefore this study aimed to investigate the role of hCAS in human pancreatic cancer in vitro and in vivo. Methods: The hCAS protein expression was determined using Western immunoblotting in human pancreatic cancer cell lines (AsPc-1, BxPc-3, Capan-2, MiaPaCa-2, Panc-1, and SW1990) and immortalized normal human pancreatic ductal epithelial cell (HPNE) and HPNE-Kras. siRNA induced hCAS knockdown pancreatic cancer cells were compared to scrambled siRNA cells with regard to proliferative (MTT assay), cell death, cell cycle (Trypan blue and Flow cytometry), malignant transformation (colony formation assay) and protein expression (Western and confocal microscopy). hCAS KD MiaPaCa-2 cells were xenografted in SCID nude mice. Tumor growth, expression of hCAS, proliferation index (Ki-67), and caspase-3 were immunostained in tumor tissues and compared with scr siRNA MiaPaCa-2 cells. Expression of hCAS was determined in human pancreatic tumor tissues using immunohistochemical stain. Results: hCAS protein expression was low in HPNE cells compared to HPNE-Kras. Lowest expression of hCAS noted in BxPc-3 cells compared to other pancreatic cancer cells. When compared to Scr-MiaPaCa-2, KD-MiaPaCa-2 cells demonstrated lower proliferation, G2/M phase cell cycle arrest, increased apoptosis, as well as inhibition of malignant transformation. Pancreatic ductal carcinomas (PCA) were hCAS strongly positive. Normal pancreatic ducts (ND) were hCAS weakly positive. hCAS KD-MiaPaCa-2 tumor growth was retarded in mice compared to Scr-MiaPaCa-2 tumors. hCAS KD-MiaPaCa-2 tumors showed hCAS depletion, lower proliferative index, increased caspase-3 immunostaining and PARP1 cleavage. Conclusion: This is the first report of hCAS expression in human pancreatic cancer. Our data suggest that hCAS is a regulator of cell proliferation, cell cycle regulation and apoptosis. hCAS may represent a potential chemopreventive and therapeutic target for human pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1667. doi:10.1158/1538-7445.AM2011-1667
Purpose: Targeting dual/multiple angiogenesis receptor has been shown to augment tumor response. Lenvatinib, a multikinase inhibitor aimed towards FGFR/ PDGFR/ KIT/RET has shown potent antitumor activity in preclinical models. This study aims to understand the effectiveness and safety of lenvatinib and capecitabine combined with radiation in patients with locally advanced rectal cancer (LARC). Methods: Patients with MRI or endoscopic ultrasound confirmed stage II or stage III rectal cancer were enrolled in 3 cohorts. All cohorts received standard dose 850 mg/m2 PO BID of capecitabine and external beam radiation (180 cGY) on day 1-5 weekly for 5 ½ to 6 weeks. Oral lenvatinib was administered in dose escalation manner in 3 cohorts of 3 patients per dose level (DL), with an expansion cohort at the MTD [cohort 1:14 mg daily; cohort 2: 20 mg daily; cohort 3:24 mg daily]. At the MTD dose, 10 additional patients were added to further evaluate safety and efficacy. Results: Twenty patients were enrolled and received at least 1 dose of study drug. One patient was deemed not eligible due to having stage IV disease at the time of diagnosis and is only reviewed for toxicity. 3/19 patients had stage II and 16/19 had stage III cancer at time of enrollment. 73.6% (14/19) patients enrolled were male and 26.4% (5/19) were female. The median age was 55 years (42,73). There was no noted dose limited toxicity at maximum tolerated dose (24 mg) of lenvatinib. There were no grade 4 adverse events. The most common grade 3 toxicities were hypertension observed in 15% (3/20) and lymphopenia in 15% (3/20) patients. Other grade 3 toxicities included rectal pain, hyponatremia, lymphopenia, leukocytosis and transaminitis, each noted in 5% (1/20) patients respectively. 19 patients underwent surgery in 6-10 weeks following completion of dual-targeted therapy and radiation. Median time to surgery was 62 days. There were no peri-operative adverse events. 14/19 patients underwent low anterior resection and 5 have had abdominoperineal resection. 7/19 (36.8%) showed complete pathological response (cPR), and downstaging were seen in 73.7% of the patients (14/19). The mean neoadjuvant rectal cancer score (NAR) was 10.4 and median NAR was 8.43. Conclusion: The combination of lenvatinib and capecitabine plus radiation shows encouraging safety and efficacy results. Larger randomized study is warranted to verify our findings. Citation Format: Ankita Tandon, Jessica M. Frakes, Rutika Mehta, Sarah Hoffe, Iman Imanirad, Maria E. Martinez Jimenez, Julian Sanchez, Mokenge Malafa, Seth Felder, Sophie Dessureault, Richard D. Kim. Final result of lenvatinib and capecitabine in combination with external beam radiation in treatment of locally advanced rectal cancer: Phase I clinical trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4293.
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