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Objectives: To evaluate patients with clinical (c)T4 prostate cancer (PCa), which represent both a heterogenous and understudied population, who often present with locally advanced disease and obstructive symptoms causing significant morbidity and mortality. We analysed whether receiving definitive local therapy influenced symptomatic and oncological outcomes. Methods: Retrospective analysis of 154 patients with cT4 PCa treated at a single institution in 1996–2020. Systemic therapy with or without local treatment (surgery, radiotherapy [RT], or both). Uni‐ and multivariate analyses of associations between clinicopathological features (including obstructive symptoms) and receipt of local therapy on overall survival (OS) and disease control were done with Cox regression. Results: The median follow‐up time was 5.9 years. Most patients had adenocarcinoma (88%), Gleason score 9–10 (77%), and median baseline prostate‐specific antigen (PSA) of 20 ng/mL; most (54%) had metastatic cT4N0–1M1 disease; 24% regionally advanced cT4N1M0, and 22% localised cT4N0M0. Local therapies were RT (n = 44), surgery (n = 28), or both (n = nine). Local therapy was associated with improved OS (hazard ratio [HR] 0.3, P < 0.001), longer freedom from local recurrence (HR 0.39, P = 0.002), less local progression (HR 0.41, P = 0.02), fewer obstructive symptoms with progression (HR 0.31, P = 0.01), and less death from local disease (HR 0.25, P = 0.002). On multivariate, local therapy was associated with improved survival (HR 0.58, P = 0.02), and metastatic disease (HR 2.93, P < 0.001) or high‐risk pathology (HR 2.05, P = 0.03) was associated with worse survival. Conclusion: Definitive local therapy for cT4 PCa was associated with improved symptomatic outcomes and survival even among men with metastatic disease. Pending prospective evaluation, these findings support definitive treatment with local therapy for cT4 disease in select cases. [ABSTRACT FROM AUTHOR]

Introduction: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT. Methods: We reviewed ICC patients that found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by propensity score and a National Cancer Database (NCDB) cohort by frequency technique. The median biologically effective dose was 97.5 Gy (interquartile range 80.5–97.9 Gy) for L-RT. Patients treated with other local therapies or supportive care alone were excluded. We analyzed survival with Cox proportional hazard modeling. Results: We identified 61 patients who received L-RT and 220 who received chemotherapy alone. At median follow-up of 11 months after diagnosis, median OS was 9 months (95% confidence interval [CI] 8–11) and 21 months (CI: 17–26) for patients receiving chemotherapy alone and L-RT, respectively. TRLF was the cause of death more often in the patients who received chemotherapy alone compared to those who received L-RT (82% vs. 47%; p = 0.001). On multivariable propensity score-matched analysis, associations with lower risk of death included duration of upfront chemotherapy (hazard ratio [HR] 0.82; p = 0.005) and receipt of L-RT (HR: 0.40; p = 0.002). The median OS from diagnosis for NCDB chemotherapy alone cohort was shorter than that of the institutional L-RT cohort (9 vs. 22 months; p < 0.001). Conclusion: For M1 ICC, L-RT associated with a lower rate of death due to TRLF and longer OS versus those treated with chemotherapy alone. Prospective studies of L-RT in this setting are warranted. [ABSTRACT FROM AUTHOR]

Background: Single‐institution studies have shown the oncologic benefit of ablative liver radiotherapy (A‐RT) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, adoption of A‐RT across the United States and its associated outcomes are unknown. Methods: We queried the National Cancer Data Base for nonsurgically managed patients with ICC diagnosed between 2004 and 2018. Patients were labeled A‐RT for receipt of biologically effective doses (BED10) ≥ 80.5 Gy and conventional RT (Conv‐RT) for lower doses. Associations with A‐RT use and overall survival were identified using logistic and Cox regressions, respectively. Results: Of 27,571 patients, the most common treatments were chemotherapy without liver RT (45%), no chemotherapy or liver RT (42%), and liver RT ± chemotherapy (13%). Use of liver RT remained constant over time. Of 1112 patients receiving liver RT with known doses, RT was 73% Conv‐RT (median BED10, 53 Gy; median, 20 fractions) and 27% A‐RT (median BED10, 100 Gy; median, 5 fractions). Use of A‐RT increased from 5% in 2004 to 48% in 2018 (Ptrend <.001). With a median follow‐up of 52.3 months, median survival estimates for Conv‐RT and A‐RT were 12.8 and 23.7 months (P <.001), respectively. On multivariable analysis, stage III and IV disease correlated with a higher risk of death, whereas chemotherapy and A‐RT correlated with a lower risk. Conclusions: Although A‐RT has been increasingly used, use of liver RT as a whole in the United States remained constant despite growing evidence supporting its use, suggesting continued unmet need. A‐RT is associated with longer survival versus Conv‐RT. Lay Summary: Bile duct cancer is a rare, deadly disease that often presents at advanced stages.Single‐institution retrospective studies have demonstrated that use of high‐dose radiotherapy may be associated with longer survival, but larger studies have not been conducted.We used a large, national cancer registry of patients diagnosed between 2004 and 2018 to show that liver radiotherapy use remains low in the United States, despite growing evidence that patients who receive it live longer. Furthermore, we showed that patients who received high‐dose radiotherapy lived longer than those who received lower doses.Greater awareness of the benefits of liver radiotherapy is needed to improve patient outcomes. In this analysis of 27,571 patients in the United States with unresected intrahepatic cholangiocarcinoma diagnosed between 2004 and 2018, use of liver radiotherapy remained constant despite growing evidence supporting that its use is associated with longer survival. Among patients who received liver radiotherapy, higher doses have been increasingly used; patients who received higher doses had longer survival than those receiving lower doses (median 23.7 vs 12.8 months, respectively). [ABSTRACT FROM AUTHOR]

Background: As the prevalence of therapeutic approaches involving transplanted cells increases, so does the need to noninvasively track the cells to determine their homing patterns. Of particular interest is the fate of transplanted embryonic stem cell-derived hematopoietic progenitor cells (HPCs) used to restore the bone marrow pool following sublethal myeloablative irradiation. The early homing patterns of cell engraftment are not well understood at this time. Until now, longitudinal studies were hindered by the necessity to sacrifice several mice at various time points of study, with samples of the population of lymphoid compartments subsequently analyzed by flow cytometry or fluorescence microscopy. Thus, long-term study and serial analysis of the transplanted cells within the same animal was cumbersome, making difficult an accurate documentation of engraftment, functionality, and cell reconstitution patterns. Methods: Here, we devised a noninvasive, nontoxic modality for tracking early HPC homing patterns in the same mice longitudinally over a period of 9 days using mesoporous silica nanoparticles (MSNs) and magnetic resonance imaging. Results: This approach of potential translational importance helps to demonstrate efficient uptake of MSNs by the HPCs as well as retention of MSN labeling in vivo as the cells were traced through various organs, such as the spleen, bone marrow, and kidney. Altogether, early detection of the whereabouts and engraftment of transplanted stem cells may be important to the overall outcome. To accomplish this, there is a need for the development of new noninvasive tools. Conclusions: Our data suggest that multifunctional MSNs can label viably blood-borne HPCs and may help document the distribution and homing in the host followed by successful reconstitution. [ABSTRACT FROM AUTHOR]