Salvage radiotherapy (SRT) after radical prostatectomy can potentially eradicate residual microscopic disease. Defining the optimal patient and treatment factors is essential and is particularly ...relevant within the context of adjuvant vs early vs delayed postoperative radiotherapy (RT).
A systematic review of all published SRT studies was performed to identify the pathologic, clinical, and treatment factors associated with relapse-free survival (RFS) after SRT. A total of 41 studies encompassing 5597 patients satisfied the study entry criteria. Radiobiologic interpretation of biochemical tumor control was used to provide the framework for the observed relationships.
Prostate-specific antigen (PSA) level before SRT (P<.0001) and RT dose (P=.0052) had a significant and independent association with RFS. There was an average 2.6% loss of RFS for each incremental 0.1 ng/mL PSA at the time of SRT (95% CI, ∼2.2-3.1). With a PSA level of 0.2 ng/mL or less before SRT, the RFS approached 64%. The dose for salvage RT in the range of 60-70 Gy seemed to be on the steep part of the sigmoidal dose-response curve, with a dose of 70 Gy achieving 54% RFS compared with only 34% for 60 Gy. There was a 2% improvement in RFS for each additional Gy (95% CI, ∼0.9-3.2). The observed dose-response was less robust on sensitivity analysis.
This study provides Level 2a evidence for initiating SRT at the lowest possible PSA. Dose escalation is also suggested by the data. Progressively better tumor control rates with SRT after radical prostatectomy are achieved with a lower PSA at initiation and with a higher RT dose. Early salvage RT may be an equivalent strategy to adjuvant RT.
Abstract Purpose/objectives To date neither the optimal radiotherapy dose nor the existence of a dose–response has been established for salvage RT (SRT). Materials/methods A systematic review from ...1996 to 2015 and meta-analysis was performed to identify the pathologic, clinical and treatment factors associated with relapse-free survival (RFS) after SRT (uniformly defined as a PSA > 0.2 ng/mL or rising above post-SRT nadir). A sigmoidal dose–response curve was objectively fitted and a non-parametric statistical test used to determine significance. Results 71 studies (10,034 patients) satisfied the meta-analysis criteria. SRT dose ( p = 0.0001), PSA prior to SRT ( p = 0.0009), ECE+ ( p = 0.039) and SV+ ( p = 0.046) had significant associations with RFS. Statistical analyses confirmed the independence of SRT dose–response. Omission of series with ADT did not alter results. Dose–response is well fit by a sigmoidal curve ( p = 0.0001) with a TCD50 of 65.8 Gy, with a dose of 70 Gy achieving 58.4% RFS vs. 38.5% for 60 Gy. A 2.0% 95% CI 1.1–3.2 improvement in RFS is achieved for each Gy. The SRT dose–response remarkably parallels that for definitive RT of localized disease. Conclusions This study provides level 2a evidence for dose-escalated SRT > 70 Gy. The presence of an SRT dose–response for microscopic disease supports the hypothesis that prostate cancer is inherently radio-resistant.
Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The results of a prospective trial of stereotactic body radiotherapy (SBRT) for prostate cancer with ...long-term patient-reported toxicity and tumor control rates are presented.
From 2003 through 2009, 67 patients with clinically localized low-risk prostate cancer were enrolled. Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology. No patient received hormone therapy. Patient self-reported bladder and rectal toxicities were graded on the Radiation Therapy Oncology Group scale (RTOG).
Median follow-up was 2.7 years. There were no grade 4 toxicities. Radiation Therapy Oncology Group Grade 3, 2, and 1 bladder toxicities were seen in 3% (2 patients), 5% (3 patients), and 23% (13 patients) respectively. Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity. Urinary incontinence, complete obstruction, or persistent hematuria was not observed. Rectal Grade 3, 2, and 1 toxicities were seen in 0, 2% (1 patient), and 12.5% (7 patients), respectively. Persistent rectal bleeding was not observed. Low-grade toxicities were substantially less frequent with QOD vs. QD dose regimen (p = 0.001 for gastrointestinal and p = 0.007 for genitourinary). There were two prostate-specific antigen (PSA), biopsy-proven failures with negative metastatic workup. Median PSA at follow-up was 0.5 ± 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94% (95% confidence interval, 85%-102%).
Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. PSA relapse-free survival compares favorably with other definitive treatments. The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer.
Abstract
Background
It is nearly impossible to overestimate the burden of chronic pain, which is associated with enormous personal and socioeconomic costs. Chronic pain is the leading cause of ...disability in the world, is associated with multiple psychiatric comorbidities, and has been causally linked to the opioid crisis. Access to pain treatment has been called a fundamental human right by numerous organizations. The current COVID-19 pandemic has strained medical resources, creating a dilemma for physicians charged with the responsibility to limit spread of the contagion and to treat the patients they are entrusted to care for.
Methods
To address these issues, an expert panel was convened that included pain management experts from the military, Veterans Health Administration, and academia. Endorsement from stakeholder societies was sought upon completion of the document within a one-week period.
Results
In these guidelines, we provide a framework for pain practitioners and institutions to balance the often-conflicting goals of risk mitigation for health care providers, risk mitigation for patients, conservation of resources, and access to pain management services. Specific issues discussed include general and intervention-specific risk mitigation, patient flow issues and staffing plans, telemedicine options, triaging recommendations, strategies to reduce psychological sequelae in health care providers, and resource utilization.
Conclusions
The COVID-19 public health crisis has strained health care systems, creating a conundrum for patients, pain medicine practitioners, hospital leaders, and regulatory officials. Although this document provides a framework for pain management services, systems-wide and individual decisions must take into account clinical considerations, regional health conditions, government and hospital directives, resource availability, and the welfare of health care providers.
To evaluate the early and late health-related quality of life (QOL) outcomes among prostate cancer patients following stereotactic body radiation therapy (SBRT).
Patient self-reported QOL was ...prospectively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer. Data from the Expanded Prostate Cancer Index Composite (EPIC) instrument were obtained at baseline and at regular intervals up to 6 years. SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions. A short course of androgen deprivation therapy was given to 14% of patients.
Median follow-up was 3 years and 194 patients remained evaluable at 5 years. A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years. The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities. Sexual QOL decline was predominantly observed within the first 9 months, a pattern not altered by the use of androgen deprivation therapy or patient age.
Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL. A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels. With a large number of patients evaluable up to 5 years following SBRT, it is unlikely that unexpected late adverse effects will manifest themselves.
Hypofractionated, stereotactic body radiotherapy (SBRT) is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of ...5 years after SBRT.
Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method) and RTOG toxicity outcomes were assessed.
At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%). Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation.
Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.
The aim of the present article is to outline a heuristic model that facilitates movement toward an integrated understanding of the youth sport system. We define the youth sport system as the set of ...interdependent persons and contexts that influence and are influenced by an athlete in youth sport. Our model builds directly from a systems perspective, and its tenets of holism, feedback loops, and roles. Specifically, we argue that the persons and contexts that surround an athlete in youth sport should be examined collectively, self-correct over time, and take on certain functions that are negotiated over time. The model extends past contributions toward integration by outlining how proximal and distal processes within youth sport can be studied in a more unified way. Looking forward, research designed to capture the nuanced ways persons and contexts influence and are influenced by one another in youth sport will be best positioned to impact theory and practice in meaningful ways.
Abstract Purpose The effectiveness of stereotactic body radiotherapy (SBRT) for localized prostate cancer is tested. Methods and materials A total of 1100 patients with clinically localized prostate ...cancer were enrolled in separate prospective phase 2 clinical trials of SBRT from 8 institutions during 2003–11 and pooled for analysis. SBRT using the CyberKnife delivered a median dose of 36.25 Gy in 4–5 fractions. Patients were low-risk (58%), intermediate-risk (30%) and high-risk (11%). A short-course of androgen deprivation therapy (ADT) was given to 14%. PSA relapse defined as a rise >2 ng/ml above nadir was analyzed with the Kaplan Meier method. Results With a median follow-up of 36 months there were 49 patients with PSA failure (4.5%), 9 of whom were subsequently determined to be benign PSA bounces. The 5-year biochemical relapse free survival (bRFS) rate was 93% for all patients; 95%, 83% and 78% for GS ⩽6, 7 and ⩾8, respectively ( p = 0.001), and 95%, 84% and 81% for low-, intermediate- and high-risk patients, respectively ( p < 0.001). No differences were observed with ADT ( p = 0.71) or as a function of total dose ( p = 0.17). A PSA bounce of >0.2 ng/ml was noted among 16% of patients. For 135 patients possessing a minimum of 5 years follow-up, the 5-year bRFS rate for low- and intermediate-risk patients was 99% and 93%, respectively. Conclusion PSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients. The current evidence supports consideration of SBRT among the therapeutic options for these patients.
The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate ...cancer.
Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed.
The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir </=0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed.
The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.
Postoperative complications can significantly impact perioperative care management and planning.
To assess machine learning (ML) models for predicting postoperative complications using independent ...and combined preoperative and intraoperative data and their clinically meaningful model-agnostic interpretations.
This retrospective cohort study assessed 111 888 operations performed on adults at a single academic medical center from June 1, 2012, to August 31, 2016, with a mean duration of follow-up based on the length of postoperative hospital stay less than 7 days. Data analysis was performed from February 1 to September 31, 2020.
Outcomes included 5 postoperative complications: acute kidney injury (AKI), delirium, deep vein thrombosis (DVT), pulmonary embolism (PE), and pneumonia. Patient and clinical characteristics available preoperatively, intraoperatively, and a combination of both were used as inputs for 5 candidate ML models: logistic regression, support vector machine, random forest, gradient boosting tree (GBT), and deep neural network (DNN). Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using Shapley Additive Explanations by transforming model features into clinical variables and representing them as patient-specific visualizations.
A total of 111 888 patients (mean SD age, 54.4 16.8 years; 56 915 50.9% female; 82 533 73.8% White) were included in this study. The best-performing model for each complication combined the preoperative and intraoperative data with the following AUROCs: pneumonia (GBT), 0.905 (95% CI, 0.903-0.907); AKI (GBT), 0.848 (95% CI, 0.846-0.851); DVT (GBT), 0.881 (95% CI, 0.878-0.884); PE (DNN), 0.831 (95% CI, 0.824-0.839); and delirium (GBT), 0.762 (95% CI, 0.759-0.765). Performance of models that used only preoperative data or only intraoperative data was marginally lower than that of models that used combined data. When adding variables with missing data as input, AUROCs increased from 0.588 to 0.905 for pneumonia, 0.579 to 0.848 for AKI, 0.574 to 0.881 for DVT, 0.5 to 0.831 for PE, and 0.6 to 0.762 for delirium. The Shapley Additive Explanations analysis generated model-agnostic interpretation that illustrated significant clinical contributors associated with risks of postoperative complications.
The ML models for predicting postoperative complications with model-agnostic interpretation offer opportunities for integrating risk predictions for clinical decision support. Such real-time clinical decision support can mitigate patient risks and help in anticipatory management for perioperative contingency planning.
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