With a median follow-up of 13 years, a randomized comparison of radiotherapy with or without antiandrogen therapy in patients with a rising PSA level after prostatectomy showed that 2 years of ...antiandrogen therapy resulted in a significantly higher overall survival rate.
Patients with localized prostatic cancer are often treated with radical prostatectomy. More than 30% of such patients will subsequently have recurrence. This recurrence manifests first as a rising serum level of prostate-specific antigen (PSA),
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termed biochemical recurrence. Large, retrospective studies suggest that salvage radiation therapy after biochemical recurrence may be associated with long-term freedom from cancer recurrence.
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However, 50% of the patients who are treated with salvage radiation therapy will have further disease progression, particularly when there are aggressive disease features.
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The combination of radiation therapy and either androgen-deprivation therapy or antiandrogen therapy prolongs survival among some . . .
Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized ...trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS).
Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score GS ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05.
A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61).
NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa.
IMPORTANCE: Use of prone positioning in patients with acute respiratory distress syndrome (ARDS) from COVID-19 may be greater than in patients treated for ARDS before the pandemic. However, the ...magnitude of this increase, sources of practice variation, and the extent to which use adheres to guidelines is unknown. OBJECTIVES: To compare prone positioning practices in patients with COVID-19 ARDS versus ARDS treated before the pandemic. DESIGN, SETTING, AND PARTICIPANTS: We conducted a multicenter retrospective cohort study of mechanically ventilated patients with early moderate-to-severe ARDS from COVID-19 (2020–2021) or ARDS from non-COVID-19 pneumonia (2018–2019) across 19 ICUs at five hospitals in Maryland. MAIN OUTCOMES AND MEASURES: The primary outcome was initiation of prolonged prone positioning (≥ 16 hr) within 48 hours of meeting oxygenation criteria. Comparisons were made between cohorts and within subgroups including academic versus community hospitals, and medical versus nonmedical ICUs. Other outcomes of interest included time to proning initiation, duration of prone sessions and temporal trends in proning frequency. RESULTS: Proning was initiated within 48 hours in 227 of 389 patients (58.4%) with COVID-19 and 11 of 123 patients (8.9%) with historic ARDS (49.4% absolute increase 95% CI for % increase, 41.7–57.1%). Comparing COVID-19 to historic ARDS, increases in proning were similar in academic and community settings but were larger in medical versus nonmedical ICUs. Proning was initiated earlier in COVID-19 versus historic ARDS (median hours (hr) from oxygenation criteria, 12.9 vs 30.6; p = 0.002) and proning sessions were longer (median hr, 43.0 vs 28.0; p = 0.01). Proning frequency increased rapidly at the beginning of the pandemic and was sustained. CONCLUSIONS AND RELEVANCE: We observed greater overall use of prone positioning, along with shorter time to initiation and longer proning sessions in ARDS from COVID-19 versus historic ARDS. This rapid practice change can serve as a model for implementing evidence-based practices in critical care.
Long-term androgen suppression plus radiotherapy (AS+RT) is standard treatment of high-risk prostate cancer. A randomized trial, Radiation Therapy Oncology Group trial 9902, was undertaken to ...determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide (TEE) plus AS+RT would improve disease outcomes with acceptable toxicity.
High-risk (prostate-specific antigen 20-100 ng/mL and Gleason score >or=7; or Stage T2 or greater, Gleason score 8, prostate-specific antigen level <100 ng/mL) nonmetastatic prostate cancer patients were randomized to AS+RT (Arm 1) vs. AS+RT plus four cycles of TEE (Arm 2). TEE was delivered 4 weeks after RT. AS continued for 2 years for both treatment arms. RT began after 8 weeks of AS began.
The Radiation Therapy Oncology Group 9902 trial opened January 11, 2000. Excess thromboembolic toxicity was noted, leading to study closure October 4, 2004. A total of 397 patients were accrued, and the data for 381 were analyzable. An acute and long-term toxicity analysis was performed. The worst overall toxicities during treatment were increased for Arm 2. Of the 192 patients, 136 (71%) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 (37%) of 189 patients on Arm 1. Statistically significant increases in hematologic toxicity (p < 0.0001) and gastrointestinal toxicity (p = 0.017) but not genitourinary toxicity (p = 0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2.
TEE was associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer.
The Radiation Therapy Oncology Group (RTOG) initiated the single-arm, phase II study 9806 to determine the safety and efficacy of daily thalidomide with radiation therapy in patients with newly ...diagnosed glioblastoma. Patients were treated with thalidomide (200 mg daily) from day one of radiation therapy, increasing by 100–200 to 1,200 mg every 1–2 weeks until tumor progression or unacceptable toxicity. The median survival time (MST) of all 89 evaluable patients was 10 months. When compared with the historical database stratified by recursive partitioning analysis (RPA) class, this end point was not different hazard ratio (HR) = 1.18; 95 % CI: 0.95–1.46;
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= 0.93. The MST of RPA class III and IV patients was 13.9 versus 12.5 months in controls (HR = 0.99; 95 % CI: 0.73–1.36;
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= 0.48), and 4.3 versus 8.6 months in RPA class V controls (HR = 1.63, 95 % CI: 1.17–2.27;
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= 0.99). In all, 34 % of patients discontinued thalidomide because of adverse events or refusal. The most common grade 3–4 toxicities were venous thrombosis, fatigue, skin reactions, encephalopathy, and neuropathy. In conclusion, thalidomide given simultaneously with radiation therapy was safe, but did not improve survival in patients with newly diagnosed glioblastoma.
Acute respiratory distress syndrome (ARDS) is a common, but under-recognised, critical illness syndrome associated with high mortality. An important factor in its under-recognition is the variability ...in chest radiograph interpretation for ARDS. We sought to train a deep convolutional neural network (CNN) to detect ARDS findings on chest radiographs.
CNNs were pretrained on 595 506 radiographs from two centres to identify common chest findings (eg, opacity and effusion), and then trained on 8072 radiographs annotated for ARDS by multiple physicians using various transfer learning approaches. The best performing CNN was tested on chest radiographs in an internal and external cohort, including a subset reviewed by six physicians, including a chest radiologist and physicians trained in intensive care medicine. Chest radiograph data were acquired from four US hospitals.
In an internal test set of 1560 chest radiographs from 455 patients with acute hypoxaemic respiratory failure, a CNN could detect ARDS with an area under the receiver operator characteristics curve (AUROC) of 0·92 (95% CI 0·89–0·94). In the subgroup of 413 images reviewed by at least six physicians, its AUROC was 0·93 (95% CI 0·88–0·96), sensitivity 83·0% (95% CI 74·0–91·1), and specificity 88·3% (95% CI 83·1–92·8). Among images with zero of six ARDS annotations (n=155), the median CNN probability was 11%, with six (4%) assigned a probability above 50%. Among images with six of six ARDS annotations (n=27), the median CNN probability was 91%, with two (7%) assigned a probability below 50%. In an external cohort of 958 chest radiographs from 431 patients with sepsis, the AUROC was 0·88 (95% CI 0·85–0·91). When radiographs annotated as equivocal were excluded, the AUROC was 0·93 (0·92–0·95).
A CNN can be trained to achieve expert physician-level performance in ARDS detection on chest radiographs. Further research is needed to evaluate the use of these algorithms to support real-time identification of ARDS patients to ensure fidelity with evidence-based care or to support ongoing ARDS research.
National Institutes of Health, Department of Defense, and Department of Veterans Affairs.
Orthotopic liver transplantation began in Brisbane in January 1985. During the first two years of the programme an assessment committee evaluated 55 patients (38 adults, 17 children). Patients were ...either accepted for transplantation, rejected as unsuitable or deferred for elective reassessment. All of the 10 adults who were rejected for transplantation because they had "too advanced" disease died within four months of assessment. Six children who were accepted for transplantation died before a suitable donor liver could be found. In the first two years, 21 orthotopic liver transplantations were performed on 18 patients (adults, 13 patients; children, five patients). Fifteen of 21 grafts were procured from within Queensland. Twelve (67%) patients are alive at three to 23 months and all have been discharged from hospital. Deaths in adults were due to sepsis (three patients), aspiration pneumonitis (one patient), rejection and hepatic artery thrombosis (one patient) and the recurrence of a hepatocellular carcinoma five months after discharge from hospital (one patient). Two patients underwent a second transplantation procedure because of chronic rejection at four months and at 11 months, respectively, after the initial operation. One patient received a second transplant for primary graft failure at four days after the operation. A scoring system which considered the presence of pre-operative patient factors, such as coma, ascites, malnutrition and previous abdominal surgery, partly predicted the operative blood loss and patient survival. In conclusion, orthotopic liver transplantation is being performed in Australia with survival rates that are comparable with those of established overseas units.
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