Stereotactic Radiotherapy for Pancreatic Cancer: A Single-Institution Experience.

Introduction Despite treatment advances, the prognosis of locally advanced pancreatic cancer is poor. Treatment remains varied and includes systemic and radiotherapy (RT). Stereotactic body radiotherapy (SBRT), highly conformal high-dose RT per fraction, is an emerging treatment option. Materials and methods We performed a single-institution retrospective review of patients with pancreatic adenocarcinoma treated with SBRT from 2015-2017. The median dose was 27 Gy (range: 21-36 Gy) in three fractions. Endpoints included local progression (RECIST 1.1; Response Evaluation Criteria in Solid Tumors 1.1), distant metastasis, overall survival, and toxicity. Results Forty-one patients were treated, with a median follow-up of eight months. Patients who received SBRT had unresectable (49%), metastatic (17%), or borderline resectable (7%) disease, declined surgery (17%), medically inoperable (7%), or developed local recurrence following the Whipple procedure (2%). The six-month and one-year rates of local progression-free survival, distant metastasis-free survival, and overall survival were 62% and 55%, 44% and 32%, and 70% and 49%, respectively. Five patients (12%) experienced seven late gastrointestinal (GI) grade 3 events. Conclusion  SBRT may be considered a treatment option to achieve local control of pancreatic cancer and is associated with a modest risk of severe late GI toxicities. Systemic therapies remain important, given the proportion of patients who develop distant metastases.

Brachytherapy education and certification-A Canadian approach.

The Royal College of Physicians and Surgeons of Canada has established a diploma certification program in brachytherapy, with the goal of standardizing brachytherapy training and standards. The diploma may be obtained either by way of a training route or a Practice Eligibility Route. Training is undergone through a Royal College-accredited brachytherapy program, analogous to a residency program with clearly defined curriculum, objectives, and expectations. The trainee submits a portfolio demonstrating achievement of the various competencies required and typically takes 12 months to complete. The trainee is then equipped to function as a competent specialist in brachytherapy, capable of an enhanced practice in this area. To date, the University of Toronto has the only Royal College-accredited training program in brachytherapy, but other Universities are in the process of applying for accreditation. Those already in practice may apply for accreditation through a Practice Eligibility Route, by submitting evidence of competency in brachytherapy. Either route can lead to the awarding of a diploma in brachytherapy, recognized by the designation DRCPSC. The overall goal of this program is to enhance quality of care and improve patient safety by setting pan-Canadian standards for training and practice in this area.

Transition metal-mediated liposomal encapsulation of irinotecan (CPT-11) stabilizes the drug in the therapeutically active lactone conformation.

PURPOSE: To determine whether entrapped transition metals could mediate the active encapsulation of the anticancer drug irinotecan into preformed liposomes. Further, to establish that metal complexation could stabilize liposomal irinotecan in the therapeutically active lactone conformation. MATERIALS AND METHODS: Irinotecan was added to preformed 1,2-distearoyl-sn-glycero-phosphocholine/cholesterol (DSPC/chol) liposomes prepared in CuSO4, ZnSO4, MnSO4, or CoSO4 solutions, and drug encapsulation was determined over time. The roles of the transmembrane pH gradient and internal pH were evaluated. TLC and HPLC were used to monitor drug stability and liposome morphology was assessed by cryo-TEM. RESULTS: Irinotecan was rapidly and efficiently loaded into preformed liposomes prepared in unbuffered (approximately pH 3.5) 300 mM CuSO4 or ZnSO4. For Cu-containing liposomes, results suggested that irinotecan loading occurred when the interior pH and the exterior pH were matched; however, addition of nigericin to collapse any residual transmembrane pH gradient inhibited irinotecan loading. Greater than 90% of the encapsulated drug was in its active lactone form and cryo-TEM analysis indicated dark intravesicular electron-dense spots. CONCLUSION: Irinotecan is stably entrapped in the active lactone conformation within preformed copper-containing liposomes as a result of metal-drug complexation.