This study introduces the prostate cancer linear energy transfer sensitivity index (PCLSI) as a novel method to predict relative biological effectiveness (RBE) in prostate cancer using linear energy transfer (LET) in proton therapy based on screening for DNA repair mutations.

Five prostate cancer cell lines with DNA repair mutations known to cause sensitivity to LET and DNA repair inhibitors were examined using published data. Relative Du145 LET sensitivity data were leveraged to deduce the LET equivalent of olaparib doses. The PCLSI model was built using three of the prostate cancer cell lines (LNCaP, 22Rv1 and Du145) with DNA mutation frequency from patient cohorts. The PCLSI model was compared against two established RBE models, McNamara and McMahon, for LET-optimized prostate cancer treatment plans.

The PCLSI model relies on the presence of eight DNA repair mutations: AR, ATM, BRCA1, BRCA2, CDH1, ETV1, PTEN and TP53, which are most likely to predict increased LET sensitivity and RBE in proton therapy. In the LET-optimized plan, the PCLSI model indicates that prostate cancer cells with these DNA repair mutations are more sensitive to increased LET than the McNamara and McMahon RBE models, with expected RBE increases ranging from 11%–33% at 2keV/µm.

The PCLSI model predicts increasing RBE as a function of LET in the presence of certain genetic mutations. The integration of LET-optimized proton therapy and genetic mutation profiling could be a significant step toward the use of individualized medicine to improve outcomes using RBE escalation without the potential toxicity of physical dose escalation.

Patients receiving hematopoietic stem cell transplants (HSCT) are at increased risk for Clostridioides difficile infection (CDI). The purpose of this study was to assess the effectiveness of oral vancomycin prophylaxis (OVP) for CDI in HSCT patients.

Single-center, retrospective cohort.

Tertiary care academic medical center in New Jersey.

Patients ≥18 years old during admission for the HSCT were included. Patients who were admitted <72 hours or who had an active CDI prior to HSCT day 0 were excluded.

Medical records of patients admitted between January 2015 and August 2022 to undergo an allogeneic or autologous HSCT were reviewed. The primary end point was the incidence of in-hospital CDI. Secondary end points included the incidence of vancomycin-resistant enterococci (VRE) bloodstream infections, VRE isolated from any clinical culture, gram-negative bloodstream infections, hospital survival, and hospital length of stay. Exploratory end points, including 1-year survival, relapse, and incidence of graft-versus-host disease, were also collected.

A total of 156 HSCT patients were included. There was 1 case of CDI (1 of 81, 1.23%) in the OVP group compared to 8 CDI cases (8 of 75, 10.67%) in the no OVP group (P = .0147). There were no significant (P > .05) between-group differences in incidence of gram-negative bloodstream infections, hospital survival, and length of stay. There were zero clinical cultures positive for VRE.

In-hospital incidence of CDI in HSCT patients was significantly decreased with OVP. Randomized controlled trials are needed in this high-risk population to assess the efficacy and risks of OVP for CDI.