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 Magnetic Resonance-guided Online Adaptive Radiotherapy for Oligometastatic Breast Cancer: A Case Report.

We present a case of durable local control achieved in a patient treated with stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) for an abdominal lymph node in the setting of oligometastatic breast cancer. A 50-year-old woman with a history of triple positive metastatic invasive ductal carcinoma of the left breast, stage IV (T3N2M1), underwent neoadjuvant chemotherapy, mastectomy, adjuvant radiotherapy and maintenance hormonal treatment with HER2 targeted therapies. At 20 months after definitive treatment of her primary, imaging showed an isolated progressive enlargement of lymph nodes between hepatic segment V/IVB and the neck of the pancreas. Radiofrequency ablation was considered, however, this approach was decided not to be optimal due to the proximity to stomach, and pancreatic duct. The patient was treated with SMART for 40 Gray in 5 fractions. Two and a half years later, the patient remains without evidence of disease progression. She experienced Grade 2 acute and late toxicity that was successfully managed with medications. This experience shows that SMART is a feasible and effective treatment to control the abdominal oligometastatic disease for breast cancer

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

Content Validity of Anatomic Site-Specific Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item Sets for Assessment of Acute Symptomatic Toxicities in Radiation Oncology

Purpose: To improve assessment of symptomatic toxicity in cancer clinical trials and complement clinician-based toxicity reporting, the US National Cancer Institute developed a measurement system called the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The objective of this study was to examine the content validity of PRO-CTCAE in patients undergoing radiation therapy and to establish anatomic site-specific item sets for implementation in cancer research. Methods and Materials: Patients receiving radiation to the brain, head and neck, breast, thorax, abdomen, or pelvis were recruited during the final week of radiation. Participants described side effects qualitatively and completed anatomic site-specific checklists indicating the presence or absence of symptomatic toxicities drawn from the PRO-CTCAE library. Items endorsed by ≥20% of participants were selected for inclusion. Symptomatic toxicities described qualitatively were content analyzed and summarized. Symptomatic toxicities not reflected in the PRO-CTCAE item library were tabulated. Results: We conducted 389 interviews of patients receiving radiation to the brain (n = 46), head and neck (n = 69), breast (n = 134), thorax (n = 30), abdomen (n = 27), female pelvis (n = 36), or male pelvis (n = 47). Median age was 62 years; 62% were female. The 53 solicited PRO-CTCAE symptoms reflected all reported radiation-induced toxicities with the exception of phlegm/mucus production and mouth/throat pain with swallowing in patients receiving head and neck radiation, eye dryness/irritation in patients undergoing brain radiation, and obstructive urinary symptoms in men receiving pelvic radiation. The PRO-CTCAE items “skin burns” and “pain” require greater specificity to adequately reflect toxicities experienced during radiation. Conclusions: PRO-CTCAE demonstrates strong content validity as a measure of symptomatic toxicities in patients receiving radiation. These results provide empirical support for the definition of site-specific PRO-CTCAE item sets to assess the symptomatic toxicities of radiation therapy. The site-specific PRO-CTCAE item sets developed herein are currently being deployed in our department via an electronic platform to capture treatment-related toxicity

Using prognosis to guide inclusion criteria, define standardised endpoints and stratify follow-up in active surveillance for prostate cancer.

OBJECTIVES: To test whether using disease prognosis can inform a rational approach to active surveillance (AS) for early prostate cancer. PATIENTS AND METHODS: We previously developed the Cambridge Prognostics Groups (CPG) classification, a five-tiered model that uses prostate-specific antigen (PSA), Grade Group and Stage to predict cancer survival outcomes. We applied the CPG model to a UK and a Swedish prostate cancer cohort to test differences in prostate cancer mortality (PCM) in men managed conservatively or by upfront treatment in CPG2 and 3 (which subdivides the intermediate-risk classification) vs CPG1 (low-risk). We then applied the CPG model to a contemporary UK AS cohort, which was optimally characterised at baseline for disease burden, to identify predictors of true prognostic progression. Results were re-tested in an external AS cohort from Spain. RESULTS: In a UK cohort (n = 3659) the 10-year PCM was 2.3% in CPG1, 1.5%/3.5% in treated/untreated CPG2, and 1.9%/8.6% in treated/untreated CPG3. In the Swedish cohort (n = 27 942) the10-year PCM was 1.0% in CPG1, 2.2%/2.7% in treated/untreated CPG2, and 6.1%/12.5% in treated/untreated CPG3. We then tested using progression to CPG3 as a hard endpoint in a modern AS cohort (n = 133). During follow-up (median 3.5 years) only 6% (eight of 133) progressed to CPG3. Predictors of progression were a PSA density ≥0.15 ng/mL/mL and CPG2 at diagnosis. Progression occurred in 1%, 8% and 21% of men with neither factor, only one, or both, respectively. In an independent Spanish AS cohort (n = 143) the corresponding rates were 3%, 10% and 14%, respectively. CONCLUSION: Using disease prognosis allows a rational approach to inclusion criteria, discontinuation triggers and risk-stratified management in AS