A priori error estimates for state constrained semilinear parabolic optimal control problems

We consider the finite element discretization of semilinear parabolic optimization problems subject to pointwise in time constraints on mean values of the state variable. In contrast to many results in numerical analysis of optimization problems subject to semilinear parabolic equations, we assume weak second order sufficient conditions. Relying on the resulting quadratic growth condition of the continuous problem, we derive rates of convergence as temporal and spatial mesh sizes tend to zero

Multigoal-oriented optimal control problems with nonlinear PDE constraints

In this work, we consider an optimal control problem subject to a nonlinear PDE constraint and apply it to the regularized $p$-Laplace equation. To this end, a reduced unconstrained optimization problem in terms of the control variable is formulated. Based on the reduced approach, we then derive an a posteriori error representation and mesh adaptivity for multiple quantities of interest. All quantities are combined to one, and then the dual-weighted residual (DWR) method is applied to this combined functional. Furthermore, the estimator allows for balancing the discretization error and the nonlinear iteration error. These developments allow us to formulate an adaptive solution strategy, which is finally substantiated via several numerical examples

Neoadjuvant phase II trial of chemo-radiotherapy (CRT) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDA).

Background: (PDA) is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10e30% of patients are long-term survivors. Micro-metastatic disease has been hypothesized as contributing to recurrence. Emerging data suggest a role for neoadjuvant therapy with (CRT) to target occult micro-metastatic disease. Aim: The aim of the study is to report our institutional experience with a novel neoadjuvant CRT regimen in (R) and (BR) PDA. Methods: Design e Prospective Phase II trial. Eligibility e Patients with (R) and (BR) PDA as defined by the NCCN criteria for resectability. Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with Gemcitabine and Intensity modulated Radiotherapy (IMRT). Gemcitabine was dosed at standard dosing at 1000 mg/m2 on Days 1, 8, 22 and 29 of IMRT. All subjects then received 50.4 Gy to the Gross Tumor Volume. Serial Imaging was performed to determine tumor response and resectability. Results: From April 2014 to June 2017, 24 patients were enrolled. Median age is 63.5 years (range 44 to 80). 23 patients had (BR) disease and 1 patient had (R) disease. 58% of patient had Stage 2 PDA, 29% had Stage I PDA and 12.5% had Stage III PDA. All patients received induction chemotherapy with FOLFOX. 13 patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R 1 resection (15.4%). For patients who underwent resection, the median PFS was 31 m, 1 year PFS rate was 69.2% (95% CI: 0.48e0.99) and 2-year PFS rate was 51.9 % (95% CI: 0.3e0.89). Median OS was 34.8 m (95% CI: 1.045 to infinity), 1 year OS rate was 91.7 % (95% CI: 0.77e1.0) and 2 year OS rate was 75% (95% CI: 0.54e1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range 18e2154), which decreased to 146.9 (range 18e462) after CRT prior to resection. Conclusions: Neo adjuvant therapy for (BR) and (R) PDA with CRT facilitated R0 resection in 84% patients who underwent surgery in a prospective phase II trial. These results warrant further investigation of neoadjuvant CRT in a larger cohort of patients. Disclosures: Authors have no financial interest or relationship to disclose

Neoadjuvant Phase II Trial of Chemoradiotherapy in Patients With Resectable and Borderline Resectable Pancreatic Cancer

BACKGROUND: Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease. AIM: To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer. MATERIALS AND METHODS: Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT). RESULTS: From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection. CONCLUSION: Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery

Randomized trial of a question prompt list to increase patient active participation during interactions with black patients and their oncologists

OBJECTIVE: Communication during racially-discordant interactions is often of poor quality and may contribute to racial treatment disparities. We evaluated an intervention designed to increase patient active participation and other communication-related outcomes during interactions between Black patients and non-Black oncologists. METHODS: Participants were 18 non-Black medical oncologists and 114 Black patients at two cancer hospitals in Detroit, Michigan, USA. Before a clinic visit to discuss treatment, patients were randomly assigned to usual care or to one of two question prompt list (QPL) formats: booklet (QPL-Only), or booklet and communication coach (QPL-plus-Coach). Patient-oncologist interactions were video recorded. Patients reported perceptions of the intervention, oncologist communication, role in treatment decisions, and trust in the oncologist. Observers assessed interaction length, patient active participation, and oncologist communication. RESULTS: The intervention was viewed positively and did not increase interaction length. The QPL-only format increased patient active participation; the QPL-plus-Coach format decreased patient perceptions of oncologist communication. No other significant effects were found. CONCLUSION: This QPL booklet is acceptable and increases patient active participation in racially-discordant oncology interactions. Future research should investigate whether adding physician-focused interventions might improve other outcomes. PRACTICE IMPLICATIONS: This QPL booklet is acceptable and can improve patient active participation in racially-discordant oncology interactions

Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates

PURPOSE: Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. PATIENTS AND METHODS: Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non-small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti-PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. RESULTS: Anti-PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti-PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of \u3e 70% of PD-1 molecules on circulating T cells ≥ 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment. CONCLUSION: Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted