National And Institutional Outcomes In Prostate Cancer Radiotherapy

Purposes: This thesis represents the composition of three different research topics within prostate cancer radiation therapy. Part I examines the delivery of curative therapy (CTx) in older men with localized prostate cancer across strata of potential clinical benefit and examines treatment trends over time. Part II is an institutional retrospective review of patients treated to 75.6 Gy to the prostate using intensity modulated radiation therapy (IMRT) without the explicit contouring of the seminal vesicles. Part III is a literature review of adjuvant (ART) and salvage (SRT) radiation therapy to examine the optimal timing of radiation therapy after radical prostatectomy. Methods: In Part I, we used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database to identify 64,192 men ages 67-85 with localized prostate cancer diagnosed from 1996 through 2005. We assessed CTx use, defined as either prostatectomy or radiation, across strata of potential likelihood of clinical benefit. In Part II, patients treated from January 2000 through January 2007 at our institution for clinically localized prostate cancer using IMRT were identified and consecutive patients were selected if they had more than 3 years of follow up and received at least 75.6 Gy. Clinical information was gathered, toxicity was recorded, and biochemical disease-free survival was calculated. In Part III, pub-med was searched using keywords prostate cancer and: radiation therapy; adjuvant radiation therapy; salvage radiation therapy; post-operative radiation therapy Results: Part I.. Among patients with the lowest likelihood of clinical benefit (low risk cancer and LE \u3c5 years), those diagnosed in 2004-2005 were more than twice as likely to receive CTx as those diagnosed in 1996-1997 (35.3% vs. 16.0%, respectively). Part II. Two hundred twenty three (223) eligible patients received primary IMRT for prostate cancer and the median follow up was 4.4 years. 5-year BDFS for poor, intermediate, and favorable prognostic group patients was 59.0% [95% Confidence Interval (95% CI) 41.8-72.7%], 83.4% [95% CI 72.4-90.4%], and 92.1% [95% CI 77.4-97.4%], respectively. Acute and late genitourinary and gastrointestinal Grade-3 toxicities were rare and there were no Grade-4 toxicities.Part III Although there are multiple randomized trials suggesting that early intervention with ART can improve biochemical disease-free, metastasis-free and overall survival in patients at high risk of recurrence, a similar level of evidence does not exist for the use of SRT. Conclusions: Part I. Curative therapy for prostate cancer may be increasingly utilized among patients with the lowest likelihood of clinical benefit. Part II. Dose escalation using IMRT to treat the prostate without explicit contouring of the seminal vesicles is safe and effective. Part III. We anticipate the results from randomized clinical trials to answer further questions regarding the comparison of ART to SRT following biochemical relapse

Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) for Locally Advanced Pancreatic Cancer: A Promising Approach.

Locally advanced pancreatic cancer (LAPC) is characterized by poor prognosis and low response durability with standard-of-care chemotherapy or chemoradiotherapy treatment. Stereotactic body radiation therapy (SBRT), which has a shorter treatment course than conventionally fractionated radiotherapy and allows for better integration with systemic therapy, may confer a survival benefit but is limited by gastrointestinal toxicity. Stereotactic MRI-guided adaptive radiation therapy (SMART) has recently gained attention for its potential to increase treatment precision and thus minimize this toxicity through continuous real-time soft-tissue imaging during radiotherapy. The case presented here illustrates the promising outcome of a 69-year-old male patient with LAPC treated with SMART with daily adaptive planning and respiratory-gated technique

Online Adaptive Radiation Therapy: Implementation of a New Process of Care.

Onboard magnetic resonance imaging (MRI) guided radiotherapy is now clinically available in nine centers in the world. This technology has facilitated the clinical implementation of online adaptive radiotherapy (OART), or the ability to alter the daily treatment plan based on tumor and anatomical changes in real-time while the patient is on the treatment table. However, due to the time sensitive nature of OART, implementation in a large and busy clinic has many potential obstacles as well as patient-related safety considerations. In this work, we have described the implementation of this new process of care in the Department of Radiation Oncology at the University of California, Los Angeles (UCLA). We describe the rationale, the initial challenges such as treatment time considerations, technical issues during the process of re-contouring, re-optimization, quality assurance, as well as our current solutions to overcome these challenges. In addition, we describe the implementation of a coverage system with a physician of the day as well as online planners (physicists or dosimetrists) to oversee each OART treatment with patient-specific 'hand-off' directives from the patient's treating physician. The purpose of this effort is to streamline the process without compromising treatment quality and patient safety. As more MRI-guided radiotherapy programs come online, we hope that our experience can facilitate successful adoption of OART in a way that maximally benefits the patient

Salvage External Beam Radiotherapy for Prostate Cancer After Radical Prostatectomy

ABSTRAC

An analysis of the regional heterogeneity in tissue elasticity in lung cancer patients with COPD

PurposeRecent advancements in obtaining image-based biomarkers from CT images have enabled lung function characterization, which could aid in lung interventional planning. However, the regional heterogeneity in these biomarkers has not been well documented, yet it is critical to several procedures for lung cancer and COPD. The purpose of this paper is to analyze the interlobar and intralobar heterogeneity of tissue elasticity and study their relationship with COPD severity.MethodsWe retrospectively analyzed a set of 23 lung cancer patients for this study, 14 of whom had COPD. For each patient, we employed a 5DCT scanning protocol to obtain end-exhalation and end-inhalation images and semi-automatically segmented the lobes. We calculated tissue elasticity using a biomechanical property estimation model. To obtain a measure of lobar elasticity, we calculated the mean of the voxel-wise elasticity values within each lobe. To analyze interlobar heterogeneity, we defined an index that represented the properties of the least elastic lobe as compared to the rest of the lobes, termed the Elasticity Heterogeneity Index (EHI). An index of 0 indicated total homogeneity, and higher indices indicated higher heterogeneity. Additionally, we measured intralobar heterogeneity by calculating the coefficient of variation of elasticity within each lobe.ResultsThe mean EHI was 0.223 ± 0.183. The mean coefficient of variation of the elasticity distributions was 51.1% ± 16.6%. For mild COPD patients, the interlobar heterogeneity was low compared to the other categories. For moderate-to-severe COPD patients, the interlobar and intralobar heterogeneities were highest, showing significant differences from the other groups.ConclusionWe observed a high level of lung tissue heterogeneity to occur between and within the lobes in all COPD severity cases, especially in moderate-to-severe cases. Heterogeneity results demonstrate the value of a regional, function-guided approach like elasticity for procedures such as surgical decision making and treatment planning

Surgical outcomes after neoadjuvant ablative dose radiation among patients with borderline resectable and locally advanced pancreas cancer from the multi-institutional phase 2 Stereotactic MR-Guided Adaptive Radiation Therapy (SMART) trial

Background: Acute grade 3+ toxicity was rare in the multi-institutional phase 2 stereotactic MR-guided on-table adaptive radiation therapy (SMART) trial (NCT03621644) for locally advanced and borderline resectable pancreatic cancer (LAPC/BRPC). Surgery may be considered after ablative SMART although the feasibility and safety of this is not well understood. Postoperative outcomes of the subset of patients in the SMART trial are examined here. Methods: Trial eligibility included BRPC or LAPC without metastases after a minimum of 3 months of induction chemotherapy. All patients received SMART prescribed to 50 Gy in 5 fractions using an integrated 0.35T MR-radiation therapy device equipped with cutting edge soft tissue tracking, automatic beam gating, and on-table adaptive replanning. Surgery was permitted after SMART, often after multi-disciplinary review. Perioperative details and postoperative outcomes, including morbidity, mortality, and overall survival (OS), were analyzed. Results: 136 patients across 13 sites were enrolled between 2019-2022. 44 patients (32.4%) had surgery after SMART (33 BRPC, 11 LAPC). Surgical procedures included pancreaticoduodenectomy (81.8%), distal pancreatectomy with splenectomy (9.1%), total pancreatectomy (6.8%), and distal pancreatectomy with celiac axis resection (2.3%). 52.3% required vascular resection/reconstruction, a majority of which were venous resections (65.2%), with a smaller proportion needing both venous/ arterial (21.7%), or arterial (13%). Surgery was performed after a mean 51.4 ± 52.8 days from SMART. Postoperative hospitalization was 10.5 ± 8.9 days. Nine patients (20.5%) had Clavien-Dindo complications of grade III or higher; 3 deaths resulted from post-pancreatectomy hemorrhage in patients who had portal vein resection. One-year OS in patients who had surgery versus no surgery after SMART was 66% vs. 43%, respectively. Conclusions: These are the first prospectively evaluated surgical outcomes after 5-fraction ablative SMART for BRPC/LAPC. The rate of surgery for BRPC compares favorably to radiated patients on the Alliance A021501 trial. Despite the use of ablative radiation dose and frequent need for vascular resection, the incidence of serious surgical complications was similar to what is reported after non-ablative radiation therapy. However, several deaths occurred after surgery and we therefore we urge caution when considering surgery after ablative radiation therapy. Further analysis of other variables such as the time between SMART and surgery, approaches to vascular resections, and discrete events such as delayed gastric emptying, operative duration, and post-operative pancreatic fistula are needed to better understand the surgical morbidity seen in these patients