Despite significant efforts to translate nanotechnology for cancer application, lack of identification of biodistribution/accumulation of these nanovehicles in vivo remains a substantial barrier for ...successful implementation of theranostic nanoparticles in the clinic. The purpose of the study was to develop a tumor-targeted theranostic nanovehicle for pancreatic cancer detectable by multispectral optoacoustic tomography (MSOT). To improve the tumor specificity of our mesoporous silica nanoparticle (MSN), we utilized a dual targeting strategy: 1) an elevated tumor receptor, urokinase plasminogen activator receptor (UPAR), and 2) the acidic tumor microenvironment. The tumor specificity of the MSN particle was improved with the addition of both chitosan, targeting acidic pH, and urokinase plasminogen activator (UPA), targeting UPAR. Drug release assays confirmed pH responsive release of gemcitabine in vitro. The UPAR specific binding of MSN-UPA nanoparticles was confirmed by reduction in fluorescence signal following MSN-UPA nanoparticle treatment in UPAR positive cells blocked with a UPAR-blocking antibody. Based upon Indocyanine Green encapsulation within the nanoparticles, UPA ligand targeted MSNs demonstrated increased intensity compared to untargeted MSNs at both pH7.4 (7×) and 6.5 (20×); however the signal was much more pronounced at a pH of 6.5 using tissue phantoms (p<0.05). In vivo, MSN-UPA particles demonstrated orthotopic pancreatic tumor specific accumulation compared to liver or kidney as identified using multispectral optoacoustic tomography (p<0.05) and confirmed by ex vivo analysis. By tracking in vivo nanoparticle biodistribution with MSOT, it was shown that pH responsive, ligand targeted MSNs preferentially bind to pancreatic tumors for payload delivery.
Urokinase plasminogen activator (UPA) targeted mesoporous silica nanoparticles that selectively target UPA receptor (UPAR) positive pancreatic cancer cells facilitate tumor detection using multispectral optoacoustic tomography. Display omitted
The role of radiation therapy in the management of unresectable pancreatic cancer is controversial. One concern about concurrent chemoradiation relates to the timing of chemotherapy. In contrast to ...conventional radiation therapy, stereotactic body radiation therapy (SBRT) delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here, we report our results of patients treated with SBRT and chemotherapy for inoperable pancreatic cancer.
Thirty-eight patients treated with SBRT and chemotherapy for locally advanced, borderline resectable, and medically inoperable pancreatic cancer at our institution from January 2008 to December 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction over 5 days. Toxicities were scored using the Common Terminology Criteria for Adverse Events version 3. Survival was calculated using the Kaplan-Meier method.
The median age was 70 years (range, 45 to 90 y). Eastern Cooperative Oncology Group performance status ranged from 0 to 3. Thirty-four patients received concurrent chemotherapy. Four patients received sequential chemotherapy. Median overall survival was 14.3 months and median progression-free survival was 9.2 months from diagnosis. From radiation, overall survival and progression-free survival were 12.3 and 6.8 months, respectively. The overall local control rate was 79%. Acute toxicity was minimal. Severe late SBRT-related toxicities included 1 grade 3 gastric outlet obstruction, 1 grade 4 biliary stricture, and 1 grade 5 gastric hemorrhage.
SBRT combined with chemotherapy for unresectable pancreatic cancer is convenient, feasible, and generally well tolerated. Outcomes of SBRT combined with chemotherapy compare favorably to results obtained with chemotherapy and conventional radiation therapy.
Concurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body ...radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC.
Patients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires.
Between September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment.
SBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity.
Hematuria following prostate radiotherapy is a known toxicity that may adversely affect a patient's quality of life. Given the higher dose of radiation per fraction using stereotactic body radiation ...therapy (SBRT) there is concern that post-SBRT hematuria would be more common than with alternative radiation therapy approaches. Herein, we describe the incidence and severity of hematuria following stereotactic body radiation therapy (SBRT) for prostate cancer at our institution.
Two hundred and eight consecutive patients with prostate cancer treated with SBRT monotherapy with at least three years of follow-up were included in this retrospective analysis. Treatment was delivered using the CyberKnife® (Accuray) to doses of 35-36.25 Gy in 5 fractions. Toxicities were scored using the CTCAE v.4. Hematuria was counted at the highest grade it occurred in the acute and late setting for each patient. Cystoscopy findings were retrospectively reviewed. Univariate and multivariate analyses were performed. Hematuria-associated bother was assessed via the Expanded Prostate Index Composite (EPIC)-26.
The median age was 69 years with a median prostate volume of 39 cc. With a median follow-up of 48 months, 38 patients (18.3%) experienced at least one episode of hematuria. Median time to hematuria was 13.5 months. In the late period, there were three grade 3 events and five grade 2 events. There were no grade 4 or 5 events. The 3-year actuarial incidence of late hematuria ≥ grade 2 was 2.4%. On univariate analysis, prostate volume (p = 0.022) and history of prior procedure(s) for benign prostatic hypertrophy (BPH) (p = 0.002) were significantly associated with hematuria. On multivariate analysis, history of prior procedure(s) for BPH (p < 0.0001) and α1A antagonist use (p = 0.008) were significantly associated with the development of hematuria.
SBRT for prostate cancer was well tolerated with hematuria rates comparable to other radiation modalities. Patients factors associated with BPH, such as larger prostate volume, alpha antagonist usage, and prior history of procedures for BPH are at increased risk for the development of hematuria.
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