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Objective: To evaluate the efficacy and safety of early pulmonary rehabilitation (PR) (ie, <3 days of hospitalization) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)., Methods: Embase, Web of Science, PubMed and Cochrane Library were searched from their inception to 1 April 2021. Randomized controlled trials were included if they observed the efficacy of early PR in AECOPD patients. Study selection, data extraction, risk of bias and quality of evidence were assessed by two researchers independently. Assessment of the risk of bias and eidence quality were evaluated by the Cochrane Collaboration's tool and Grading of Recommendations, Assessment, Development and Evaluation system, respectively., Results: Fourteen trials (829 participants) were identified. Significant improvement was found in the 6-minute walk distance (6MWD; mean difference (MD): 69.64; 95% CI: 40.26 to 99.01; Z = 4.65, P < 0.0001, low quality). In the subgroup analysis, the exercise-training group showed marked improvement (MD: 96.14; 95% CI: 20.24 to 172.04; Z = 2.48, P = 0.001). The Saint George's Respiratory Questionnaire (SGRQ) total score was low (MD: -12.77; 95% CI: -16.03 to -9.50; Z = 7.67, P < 0.0001, moderate quality). Significant effects were not found for the duration of hospital stay, quadriceps muscle strength or five times sit to stand test. Only one serious adverse event was reported in experimental group, which was not associated with early PR., Conclusion: PR initiated <3 days of hospitalization may increase exercise capacity and improve quality of life, but the results should be interpreted prudently and dialectically, and the role of early PR in AECOPD needs further exploration., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Zhang et al.)

Background: Patients with large prostate volumes have been shown to have higher rates of genitourinary and gastrointestinal toxicities after conventional radiation therapy for prostate cancer. The efficacy and toxicity of stereotactic body radiation therapy (SBRT), which delivers fewer high-dose fractions of radiation treatment, is unknown for large prostate volume prostate cancer patients. We report our early experience using SBRT for localized prostate cancer in patients with large prostate volumes., Methods: 57 patients with prostate volumes ≥50 cm(3) prior to treatment with SBRT for localized prostate carcinoma and with a minimum follow up of two years were included in this retrospective review of prospectively collected data. Treatment was delivered using Cyberknife (Accuray) with doses of 35-36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were scored using the CTCAE v.4. Quality of life was assessed using the American Urological Association (AUA) Symptom Score and the Expanded Prostate Cancer Index Composite (EPIC)-26., Results: 57 patients (23 low-, 25 intermediate- and 9 high-risk according to the D'Amico classification) at a median age of 69 years (range, 54-83 years) received SBRT with a median follow-up of 2.9 years. The median prostate size was 62.9 cm(3) (range 50-138.7 cm(3)). 33.3% of patients received ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.5 ng/ml and decreased to a median PSA of 0.4 ng/ml by 2 years (p <0.0001). A mean baseline AUA symptom score of 7.5 significantly increased to 13 at 1 month (p = 0.001) and returned to baseline by 3 months (p = 0.21). 23% of patients experienced a late transient urinary symptom flare in the first two years following treatment. Mean baseline EPIC bowel scores of 95.8 decreased to 78.1 at 1 month (p <0.0001), but subsequently improved to 93.5 three months (p = 0.08). The 2-year actuarial incidence rates of GU and GI toxicity ≥ grade 2 were 49.1% and 1.8%, respectively. Two patients (3.5%) experienced grade 3 urinary toxicity, and no patient experienced grade 3 gastrointestinal toxicity., Conclusions: SBRT for clinically localized prostate cancer was well tolerated in men with large prostate volumes.

Purpose: Urinary incontinence (UI) following prostate radiotherapy is a rare toxicity that adversely affects a patient's quality of life. This study sought to evaluate the incidence of UI following stereotactic body radiation therapy (SBRT) for prostate cancer., Methods: Between February, 2008 and October, 2010, 204 men with clinically localized prostate cancer were treated definitively with SBRT at Georgetown University Hospital. Patients were treated to 35-36.25 Gray (Gy) in 5 fractions delivered with the CyberKnife (Accuray). UI was assessed via the Expanded Prostate Index Composite (EPIC)-26., Results: Baseline UI was common with 4.4%, 1.0% and 3.4% of patients reporting leaking > 1 time per day, frequent dribbling and pad usage, respectively. Three year post treatment, 5.7%, 6.4% and 10.8% of patients reported UI based on leaking > 1 time per day, frequent dribbling and pad usage, respectively. Average EPIC UI summary scores showed an acute transient decline at one month post-SBRT then a second a gradual decline over the next three years. The proportion of men feeling that their UI was a moderate to big problem increased from 1% at baseline to 6.4% at three years post-SBRT., Conclusions: Prostate SBRT was well tolerated with UI rates comparable to conventionally fractionated radiotherapy and brachytherapy. More than 90% of men who were pad-free prior to treatment remained pad-free three years following treatment. Less than 10% of men felt post-treatment UI was a moderate to big problem at any time point following treatment. Longer term follow-up is needed to confirm late effects.

Background: Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer., Methods: Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35-36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up., Results: All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed., Conclusions: In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy., Trial Registration: The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009-510).

SBRT is an increasingly popular treatment for localized prostate cancer, though considerable variation in technical approach is common and optimal dose constraints are uncertain. In this study, we sought to identify dosimetric and patient-related predictors of acute rectal toxicity. Patients included in this study were treated with prostate SBRT on a prospective institutional protocol. Physician-graded toxicity and patient-reported outcomes were captured at one week, one month, and three months following SBRT. DVH data were extracted and converted into relative volume differential DVHs for NTCP modeling. Patient- and disease-related covariates along with NTCP model predictions were independently tested for significant association with physician-graded toxicity or a decline in bowel-related QoL. A multivariate model was constructed using forward selection, and significant parameter cutoff values were obtained with Fischer's exact test to group patients by risk of developing physician-graded toxicity or detriments in patient-reported QoL. One hundred and three patients treated for localized prostate cancer with SBRT were included in our analysis. 52% of patients experienced a clinically significant decline in bowel-related QOL within 1 week of completion of treatment, while only 27.5% of patients developed grade 2+ physician-graded rectal toxicity. Sequential feature selection multivariate logistic regression identified rectal V22.5 Gy (p = 0.001) and D19% (p = 0.001) as independent predictors of clinically significant toxicity, while rectal V20Gy (p = 0.004) and D25.3% (p = 0.007) were independently correlated with physician-graded toxicity. Global multivariate step-wise logistic regression identified only D19% (p = 0.001) and V20Gy (p = 0.004) as independent predictors of acute bowel bother or physician-graded rectal toxicity respectively. Moderate doses to large rectal volumes, D19% and V20Gy, were associated with an increased incidence of a clinically significant decrease in patient-reported bowel QOL and physician-scored grade 2+ rectal toxicity, respectively. These dosimetric parameters may help practitioners mitigate acute toxicity in patients treated with prostate SBRT. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of pulmonary rehabilitation for exercise tolerance and quality of life improvement in idiopathic pulmonary fibrosis. Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Database, and Chongqing VIP for randomized controlled trials that compared pulmonary rehabilitation with usual care for idiopathic pulmonary fibrosis. The risk of bias and certainty of evidence were assessed using Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations, Assessment, Development and Evaluation criteria. Results: Eleven trials in total with 549 participants. Compared with usual care, pulmonary rehabilitation significantly increased 6-minute walking distance (mean difference: 35.2m, 95% confidence intervals: 25.4m–44.9m; ten trials; 447 participants; moderate), decreased the St George's Respiratory Questionnaire total scores (mean difference: −9.11, 95% confidence intervals: −10.78 to −7.43; six trials; 303 participants; moderate), and reduced the modified Medical Research Council scores were lower (mean difference: −0.76, 95% confidence intervals: −1.25 to −0.27; three trials; 196 participants; low). Improvements were noted in forced vital capacity percent-predicted (mean difference: 4.88, 95% confidence intervals: 2.67 to 7.10; four trials; 214 participants; moderate) and diffusing capacity for carbon monoxide (mean difference: 4.71, 95% confidence intervals: 0.96 to 8.46; six trials; 358 participants; low). Conclusions: Pulmonary rehabilitation may significantly improve exercise tolerance and quality of life in idiopathic pulmonary fibrosis patients, but the quality of evidence was low to moderate. Large sample, multicenter, randomized controlled trials are needed to verify the efficacy and safety of pulmonary rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Patients with a high pretreatment IPSS may have higher rates of late urinary morbidity after radiation therapy for prostate cancer (1). Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation, which may be radiobiologically favorable to the conventional low-dose external beam fractions. The urinary toxicity associated with SBRT, however, remains unclear in patients with a high IPSS (1). We report our experience using SBRT for localized prostate cancer in patients with pretreatment IPSS ≥ 15. Methods: Localized prostate cancer patients with a pre-treatment IPSS ≥ 15 treated with SBRT at Georgetown University Hospital from 2009 to 2016 were included in this retrospective review of prospectively collected data. These patients were treated to 35–36.25 Gy in five fractions delivered via CyberKnife (Accuray Inc., Sunnyvale, CA). Urinary toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4). Urinary quality of life was assessed using validated questionnaires (IPSS and EPIC-26). Results: 53 patients at a median age of 71 years (range 57–89 years) received SBRT with a minimum follow up of 3 years. The median prostate size was 37 cm3 (range 12–100 cm3) and 30.2% patients received ADT. The 3-years incidence rate of Grade 3 urinary toxicity was 7.5% with median time to toxicity of 2.9 years. There were no Grade 4 or 5 toxicities. A mean baseline IPSS score of 19.8 significantly decreased to 12.9 at 3 months post-SBRT (p = 0.002) and remained stable at 36 months (13.7). A mean baseline EPIC-26 obstructive/irritative score of 64.1 significantly improved to 80.2 at 3 months (p = 0.002). This improvement was maintained to 36 months. There was no significant change from the mean baseline EPIC-26 urinary incontinence score at any point during follow up. Conclusions: SBRT for clinically localized prostate cancer was well-tolerated in men with baseline IPSS ≥ 15 (1). Grade 3 toxicities occurred but resolved with time. Our data suggest that poor baseline urinary function does not worsen following SBRT and may even improve. High baseline IPSS score should not be considered a contraindication to SBRT. [ABSTRACT FROM AUTHOR]

Background: Clinical data suggest that stereotactic body radiation therapy (SBRT) provides similar clinical outcomes as other radiation modalities for prostate cancer. However, data reporting on the safety of SBRT after TURP is limited. Herein, we report our experience using SBRT to deliver hypofractionated radiotherapy in patients with a history of TURP including physician-reported toxicities and patient-reported quality of life. Methods: Forty-seven patients treated with SBRT from 2007 to 2016 at Georgetown University Hospital for localized prostate carcinoma with a history of prior TURP were included in this retrospective analysis. Treatment was delivered using the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) with doses of 35 Gy or 36.25 Gy in 5 fractions without prostatic urethral sparing. Toxicities were recorded and scored using the CTCAE v.4. Cystoscopy findings were retrospectively reviewed. Urinary quality of life data was assessed using the International Prostate Symptom Scoring (IPSS) and Expanded Prostate Cancer Index Composite 26 (EPIC-26). A Wilcoxon signed-rank sum test was used to determine if there was a statistically significant increase or decrease in IPSS or EPIC scores between timepoints. Minimally important differences were calculated by obtaining half the standard deviation at time of start of treatment. Results: Forty-seven patients at a median age of 72 years (range 63–84) received SBRT. The mean follow-up was 4.7 years (range 2–10 years). Late Grade 2 and grade 3 urinary toxicity occurred in 23 (48.9%) and 3 (6.4%) men, respectively. There were no Grade 4 or 5 toxicities. Approximately 51% of patients experienced hematuria following treatment. Mean time to hematuria was 10.5 months. Twenty-five cystoscopies were performed during follow-up and the most common finding was hyperemia, varices of the bladder neck/TURP defect, and/or necrotic tissue in the TURP defect. Baseline urinary QOL composite scores were low, but they did not clinically significantly decline in the first 2 years following treatment. Conclusions: In patients with prior TURP, prostate SBRT was well-tolerated. GU toxicity rates were comparable to similar patients treated with conventionally fractionated radiation therapy. Urinary quality of life was poor at baseline, but did not worsen clinically over time. Stricter dosimetric criteria could potentially improve the rate of high-grade late toxicity, but may increase the risk of peri-urethral recurrence. [ABSTRACT FROM AUTHOR]

Purpose: Retaining quality of life in patients treated with SBRT for prostate cancer remains paramount. As such, balancing the benefits of treatment against the effects of therapy on elderly patients is essential. The EORTC QLQ-ELD14 (ELD-14) is a validated questionnaire with a domain dedicated to burden of illness and treatment in the elderly. The Expanded Prostate Cancer Index Composite (EPIC)-26 is a validated questionnaire which measures urinary, bowel, sexual, and hormonal symptoms. This study reports trends in self-reported burden in patients with prostate cancer treated with SBRT and reveals convergence of self-reported burden with treatment related side effects obtained from the EPIC-26 questionnaire. Methods: All patients ≥70 years old, with localized prostate cancer treated with SBRT ± ADT at Medstar Georgetown University Hospital from 2013 to 2018 and had completed the ELD-14 were eligible for inclusion in this cross-sectional cohort study. Percentage of responses to questions related to disease and treatment burden were counted for each category ("not at all" and "a little" vs. "quite a bit" and "very much"). Additional demographic features were derived from available medical records. A total of 111 patients (median age of 74) responded to the ELD-14 questionnaire at onset of treatment and at the 2-year mark. Responses to EPIC questionnaires at matched follow-ups were scored and correlated with the self-reported burden domain of the ELD-14 using the Spearman correlation coefficient. Results: Number of patients reporting "quite a bit" or "very much" burden from prostate cancer was 6.3% prior to treatment. This was highest at 1-month (10.8%) and decreased to 9.0% at 24 months post-SBRT (X 2 = 3.836, p = 0.6986). By comparison, 3.6 and 5.4% reported "quite a bit" or "very much" burden from treatment at start of treatment and 24 months, respectively (X 2 = 1.046, p = 0.9838). Patient reported treatment burden was found to converge well with individual domains of EPIC-26. Patients undergoing ADT experienced more burden than their non-ADT counterparts. Conclusions: This cross-sectional study suggests a minority of patients reported high burden from their clinically localized prostate cancer or from their SBRT treatment. Self-reported burden converged well with lower EPIC scores in multiple domains. [ABSTRACT FROM AUTHOR]

Background Proctitis after radiation therapy for prostate cancer remains an ongoing clinical challenge and critical quality of life issue. SBRT could minimize rectal toxicity by reducing the volume of rectum receiving high radiation doses and offers the potential radiobiologic benefits of hypofractionation. This study sought to evaluate the incidence and severity of proctitis following SBRT for prostate cancer. Methods Between February 2008 and July 2011, 269 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. All patients were treated to 35-36.25Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Rectal bleeding was recorded and scored using the CTCAE v.4. Telangiectasias were graded using the Vienna Rectoscopy Score (VRS). Proctitis was assessed via the Bowel domain of the Expanded Prostate Index Composite (EPIC)-26 at baseline and at 1, 3, 6, 9, 12, 18 and 24 months post-SBRT. Results The median age was 69 years with a median prostate volume of 39 cc. The median follow-up was 3.9 years with a minimum follow-up of two years. The 2-year actuarial incidence of late rectal bleeding ≥ grade 2 was 1.5%. Endoscopy revealed VRS Grade 2 rectal telangiectasias in 11% of patients. All proctitis symptoms increased at one month post-SBRT but returned to near-baseline with longer follow-up. The most bothersome symptoms were bowel urgency and frequency. At one month post-SBRT, 11.2% and 8.5% of patients reported a moderate to big problem with bowel urgency and frequency, respectively. The EPIC bowel summary scores declined transiently at 1 month and experienced a second, more protracted decline between 6 months and 18 months before returning to near-baseline at two years post-SBRT. Prior to treatment, 4.1% of men felt their bowel function was a moderate to big problem which increased to 11.5% one month post-SBRT but returned to near-baseline at two years post-SBRT. Conclusions In this single institution cohort, the rate and severity of proctitis observed following SBRT is low. QOL decreased on follow-up; however, our results compare favorably to those reported for patients treated with alternative radiation modalities. Future prospective randomized studies are needed to confirm these observations. [ABSTRACT FROM AUTHOR]

Despite advances in treatment for metastatic prostate cancer, patients eventually progress to castrate-resistant disease and ultimately succumb to their cancer. Androgen deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer and has been shown to improve median time to progression and median survival time. Research suggests that castrate-resistant clones may be present early in the disease process prior to the initiation of ADT.These clones are not susceptible to ADT and may even flourish when androgen-responsive clones are depleted. Stereotactic body radiation therapy (SBRT) is a safe and efficacious method of treating clinically localized prostate cancer and metastases. In patients with a limited number of metastatic sites, SBRT may have a role in eliminating castrate-resistant clones and possibly delaying progression to castrate-resistant disease. [ABSTRACT FROM AUTHOR]

Background: Treating prostate cancer with SBRT could potentially minimize radiation proctitis by reducing high-dose rectal irradiation. In addition, it offers the potential radiobiologic benefits of hypofractionation. This study reports the endoscopic changes and the associated clinical rectal toxicity in these patients. Methods: We reviewed the records of patients treated from 2008-2011 for localized prostate cancer who had rectal endoscopy following SBRT. SBRT was delivered either as primary treatment in 5 fractions of 7-7.25 Gy, or as an initial boost in 3 fractions of 6.5 Gy followed by conventionally fractionated radiotherapy to 45-50.4 Gy. Endoscopic changes were graded using the Vienna Rectoscopy Score (VRS). Rectal toxicity was graded via CTCAEv.4. Rectal quality of life (QOL) was assessed via the bowel domain of the EPIC-26 questionnaire. Results: Fifty-one patients with a median 23 months follow-up were analyzed. Thirty-five patients completed SBRT monotherapy and 16 patients received SBRT as a boost to conventionally fractionated IMRT. The median interval from SBRT to rectal endoscopy was 13 months. Endoscopy revealed VRS Grade 1-2 telangiectasias for 10 patients and VRS Grade 1-2 mucosal edema for 12 patients. No rectal ulcerations, strictures or necrosis were observed. Grade 1-2 late rectal bleeding occurred in 10 patients. There were no CTCAEv.4 Grade ⩾3 toxicities. Mean EPIC bowel scores decreased from a baseline value of 96.9 to 82.3 at 1-month, but subsequently increased to 91.0 at 24 months. Conclusions: In this cohort that is skewed towards patients with rectal complaints, the rate and severity of endoscopic changes following SBRT is low. Rectal toxicity and QOL were comparable to patients treated with other radiation modalities. Prospective trials examining the endoscopic outcomes following SBRT for prostate cancer are needed for confirmation of the findings of this study. Trial registration: The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009-510). [ABSTRACT FROM AUTHOR]