Safety of Radiation Therapy in Patients With Prostate Cancer and Inflammatory Bowel Disease: A Systematic Review.

PURPOSE: Inflammatory bowel disease (IBD) has historically been considered a relative contraindication for pelvic radiation therapy (RT). To date, no systematic review has summarized the toxicity profile of RT for patients with prostate cancer and comorbid IBD. METHODS AND MATERIALS: A PRISMA-guided systematic search was conducted on PubMed/Embase for original investigations that reported gastrointestinal (GI; rectal/bowel) toxicity in patients with IBD undergoing RT for prostate cancer. The substantial heterogeneity in patient population, follow-up, and toxicity reporting practices precluded a formal meta-analysis; however, a summary of the individual study-level data and crude pooled rates was described. RESULTS: Twelve retrospective studies with 194 patients were included: 5 examined predominantly low-dose-rate brachytherapy (BT) monotherapy, 1 predominantly high-dose-rate BT monotherapy, 3 mixed external beam RT (3-dimensional conformal or intensity modulated RT [IMRT]) + low-dose-rate BT, 1 IMRT + high-dose-rate BT, and 2 stereotactic RT. Among these studies, patients with active IBD, patients receiving pelvic RT, and patients with prior abdominopelvic surgery were underrepresented. In all but 1 publication, the rate of late grade 3+ GI toxicities was <5%. The crude pooled rate of acute and late grade 2+ GI events was 15.3% (n = 27/177 evaluable patients; range, 0%-100%) and 11.3% (n = 20/177 evaluable patients; range, 0%-38.5%), respectively. Crude rates of acute and late grade 3+ GI events were 3.4% (6 cases; range, 0%-23%) and 2.3% (4 cases; range, 0%-15%). CONCLUSIONS: Prostate RT in patients with comorbid IBD appears to be associated with low rates of grade 3+ GI toxicity; however, patients must be counseled regarding the possibility for lower-grade toxicities. These data cannot be generalized to the underrepresented subpopulations mentioned above, and individualize decision-making is recommended for those high-risk cases. Several strategies should be considered to minimize the probability of toxicity in this susceptible population, including careful patient selection, minimizing elective (nodal) treatment volumes, using rectal sparing techniques, and employing contemporary RT advancements to minimize exposure to GI organs at risk (eg, IMRT, magnetic resonance imaging-based target delineation, and high-quality daily image guidance).

MALT1 Protease Plays a Dual Role in the Allergic Response by Acting in Both Mast Cells and Endothelial Cells.

The signaling protein MALT1 plays a key role in promoting NF-κB activation in Ag-stimulated lymphocytes. In this capacity, MALT1 has two functions, acting as a scaffolding protein and as a substrate-specific protease. MALT1 is also required for NF-κB-dependent induction of proinflammatory cytokines after FcεR1 stimulation in mast cells, implicating a role in allergy. Because MALT1 remains understudied in this context, we sought to investigate how MALT1 proteolytic activity contributes to the overall allergic response. We compared bone marrow-derived mast cells from MALT1 knockout (MALT1-/-) and MALT1 protease-deficient (MALTPD/PD) mice to wild-type cells. We found that MALT1-/- and MALT1PD/PD mast cells are equally impaired in cytokine production following FcεRI stimulation, indicating that MALT1 scaffolding activity is insufficient to drive the cytokine response and that MALT1 protease activity is essential. In addition to cytokine production, acute mast cell degranulation is a critical component of allergic response. Intriguingly, whereas degranulation is MALT1-independent, MALT1PD/PD mice are protected from vascular edema induced by either passive cutaneous anaphylaxis or direct challenge with histamine, a major granule component. This suggests a role for MALT1 protease activity in endothelial cells targeted by mast cell-derived vasoactive substances. Indeed, we find that in human endothelial cells, MALT1 protease is activated following histamine treatment and is required for histamine-induced permeability. We thus propose a dual role for MALT1 protease in allergic response, mediating 1) IgE-dependent mast cell cytokine production, and 2) histamine-induced endothelial permeability. This dual role indicates that therapeutic inhibitors of MALT1 protease could work synergistically to control IgE-mediated allergic disease.