Phase 1 Study of Hypofractionated Proton Beam Radiation Therapy in Adjuvant Pancreatic Cancer (PROTON-PANC).

PURPOSE: Despite improvement in systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) frequently experience local recurrence. We sought to determine the safety of hypofractionated proton beam radiation therapy (PBT) during adjuvant chemotherapy. METHODS AND MATERIALS: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022. Patients had PDAC of the pancreatic head and underwent R0 or R1 resection and adjuvant modified FOLFIRINOX (mFFX) chemotherapy. The primary endpoint was to determine the dosing schedule of adjuvant PBT (5 Gy × 5 fractions) using limited treatment volumes given between cycles 6 and 7 of mFFX. Patients received PBT on days 15 to 19 in a 28-day cycle before starting cycle 7 (dose level 1, DL1) or on days 8 to 12 in a 21-day cycle before starting cycle 7 (DL2). RESULTS: The median patient age was 66 years (range, 52-78), and the follow-up time from mFFX initiation was 12.5 months (range, 6.2-37.4 months). No patients received preoperative therapy. Four had R1 resections and 5 had node-positive disease. Three patients were enrolled on DL1 and 6 patients on DL2. One dose-limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed 12 cycles of mFFX (range, 7-12; median, 11). No patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence-free. The median time to recurrence was 12 months (95% CI, 4 to not reached [NR]), and median overall survival was NR (95% CI, 6 to NR; 2-year survival rate, 57%). CONCLUSIONS: PBT integrated within adjuvant mFFX was well tolerated, and no local recurrence was observed. These findings warrant further exploration in a phase 2 trial.

Intensity modulated radiation therapy with stereotactic body radiation therapy boost for unfavorable prostate cancer: five-year outcomes.

Purpose: Intensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost. Materials and methods: Between 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) according to an institutional protocol. For the first year, the patient's PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan-Meier method. Results: The median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%). Conclusion: The incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years.

Gastric intestinal metaplasia development in African American predominant United States population.

BACKGROUND: Gastric cancer significantly contributes to cancer mortality globally. Gastric intestinal metaplasia (GIM) is a stage in the Correa cascade and a premalignant lesion of gastric cancer. The natural history of GIM formation and progression over time is not fully understood. Currently, there are no clear guidelines on GIM surveillance or management in the United States. AIM: To investigate factors associated with GIM development over time in African American-predominant study population. METHODS: This is a retrospective longitudinal study in a single tertiary hospital in Washington DC. We retrieved upper esophagogastroduodenoscopies (EGDs) with gastric biopsies from the pathology department database from January 2015 to December 2020. Patients included in the study had undergone two or more EGDs with gastric biopsy. Patients with no GIM at baseline were followed up until they developed GIM or until the last available EGD. Exclusion criteria consisted of patients age < 18, pregnancy, previous diagnosis of gastric cancer, and missing data including pathology results or endoscopy reports. The study population was divided into two groups based on GIM status. Univariate and multivariate Cox regression was used to estimate the hazard induced by patient demographics, EGD findings, and Helicobacter pylori (H. pylori) status on the GIM status. RESULTS: Of 2375 patients who had at least 1 EGD with gastric biopsy, 579 patients were included in the study. 138 patients developed GIM during the study follow-up period of 1087 d on average, compared to 857 d in patients without GIM (P = 0.247). The average age of GIM group was 64 years compared to 56 years in the non-GIM group (P < 0.001). In the GIM group, adding one year to the age increases the risk for GIM formation by 4% (P < 0.001). Over time, African Americans, Hispanic, and other ethnicities/races had an increased risk of GIM compared to Caucasians with a hazard ratio (HR) of 2.12 (1.16, 3.87), 2.79 (1.09, 7.13), and 3.19 (1.5, 6.76) respectively. No gender difference was observed between the study populations. Gastritis was associated with an increased risk for GIM development with an HR of 1.62 (1.07, 2.44). On the other hand, H. pylori infection did not increase the risk for GIM. CONCLUSION: An increase in age and non-Caucasian race/ethnicity are associated with an increased risk of GIM formation. The effect of H. pylori on GIM is limited in low prevalence areas.