Impact of radiation fractionation on pseudoprogression in older patients with glioblastoma: a retrospective cohort study.

In this issue of the Journal of Clinical Oncology, Roa et al present results of a prospective randomized clinical trial of patients 60 years of age with glioblastoma multiforme (GBM), the most common and lethal of all primary brain tumors in adults. Patients either received a standard course of radiation therapy (RT), 60 Gy in 30 fractions over 6 weeks, or short-course RT, 40 Gy in 15 fractions over 3 weeks, without chemotherapy. The primary end point of the trial was overall survival. Of the 100 patients randomly assigned, 95 were eligible and analyzable. The median survival times and 1-year survival rates were similar between the two regimens; 5.1 months and 9% for standard RT, and 5.6 months and 15% for short-course RT, respectively. All patients had died by 2 years. On the surface, the authors’ conclusion that “the abbreviated course of RT appears to be a reasonable treatment option for older patients with GBM” seems quite reasonable. However, the data require closer scrutiny, and the conclusion needs several qualifications, before all elderly patients with GBM are treated with shortcourse RT alone. A number of prognostic factors play an important role in determining the survival of patients with GBM. In a recent re-analysis of the original Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis database, of 1,672 GBM patients, the most important prognostic factors were age, Karnofsky Performance Status (KPS), extent of surgical resection, and neurologic function. Age had the greatest impact on survival, with “older” defined as 50 years of age. Older GBM patients were divided into two groups. The more favorable group had KPS 70, gross or subtotal resection, and better neurologic function; their median survival time and 1-year survival rates were 11.2 months and 46%, respectively. The less favorable group had either KPS 70, biopsy alone, or poor neurologic function; their median survival time and 1-year survival rates were 7.5 months and 28%, respectively. Both RTOG groups of older GBM patients had better median survival times and 1-year survival rates than either the standard or short-course treatment arms of the Roa et al study. Why did these patients fare so poorly? First, they were a prognostically unfavorable group from the start, with a low median KPS of only 70 in both treatment arms. Second, biopsy alone was performed in 39% of patients, with only 9% of patients undergoing gross total resection, compared to biopsy in 17% and gross total resection in 19% of 645 patients treated on three consecutive RTOG clinical trials. In that study, the median survival time was 6.6 months with biopsy alone, compared to 11.3 months with resection. A similar observation was recently made by the Glioma Outcomes Project in a group of 565 patients with malignant glioma (primarily GBM) diagnosed between 1997 and 2001. The value of debulking GBM in the elderly has also now been shown in a small Finnish randomized clinical trial recently reported by Vourinen et al. In that study, 23 patients 65 years old with malignant glioma (83% with GBM) were randomly assigned to biopsy only or to surgical resection, followed by RT. The median survival time of 5.6 months was significantly longer with resection, compared to 2.8 months with biopsy. When compared to biopsy, resection is also associated with improved quality-of-life in older GBM patients. Third, patients in the Roa et al study were not allowed to have chemotherapy until recurrence. Although the benefit of up-front chemotherapy for malignant glioma is modest, a meta-analysis of 3,004 patients treated on 12 controlled clinical trials of postoperative RT in which patients were randomly assigned to RT, with or without chemotherapy, showed a 6% increase in the 1-year survival rate (from 40% to 46%) with chemotherapy, and a 15% relative decrease in the risk of death— differences which were significant, irrespective of histology, age, performance status, or extent of surgical resection. The value of combined RT and chemotherapy in the elderly with GBM has now been shown in a JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 22 NUMBER 9 MAY 1 2004

Results of Early Reoperation for Suspected Pseudoprogression in Patients with Glioblastoma Multiforme

Hypofractionated Versus Standard Radiation Therapy With or Without Temozolomide for Older Glioblastoma Patients

The incidence and prevalence of inflammatory bowel diseases (IBD) in older adults are rising. There is a limited comparative assessment of risk of disease- and treatment-related complications in older patients (older than 60 years) with adult-onset (age at disease onset, 18-59 years; AO-IBD) vs elderly-onset IBD (age at disease onset, older than 60 years; EO-IBD). We compared clinical outcomes in older patients with IBD with AO-IBD vs EO-IBD. We conducted a retrospective cohort study comparing risk of disease-related complications (IBD-related surgery, hospitalization, treatment escalation, clinical flare, or disease complication) and treatment-related complications (serious infection, malignancy, or death) in older patients with AO-IBD vs EO-IBD through Cox proportional hazard analysis, adjusting for age at cohort entry, disease phenotype, disease duration, prior surgery and/or hospitalization, medication use, disease activity at cohort entry, and comorbidities. We included 356 older patients with IBD (AO-IBD, 191 patients, 67 ± 5 y at cohort entry; EO-IBD, 165 patients, 72 ± 8 y at cohort entry). No significant differences were observed in the risk of disease-related complications in older patients with prevalent vs incident IBD (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.58-1.25), although risk of IBD-related surgery was lower in older patients with prevalent IBD (aHR, 0.47; 95% CI, 0.25-0.89). Older patients with prevalent IBD were significantly less likely to experience treatment-related complications (aHR, 0.58; 95% CI, 0.39-0.87). Patients with AO-IBD have lower risk of treatment-related complications as they age compared with patients with EO-IBD, without a significant difference in risk of disease-related complications.

ALL in Older Adults

Reported outcomes for parenteral nutrition (PN)-related complications in older adult patients with acute intestinal failure who are receiving PN in the acute hospital setting are limited. Our study aims to compare PN-related complications between older and younger adult patients. A retrospective descriptive study of inpatients who were administered PN from January 1, 2019, to December 31, 2019, was performed. Patients were categorized into older (≥65 years old) and younger (<65 years old) adult groups. Two hundred thirty-five patients were included. There were 103 patients in the older adult group (mean age: 73.9 [SD: 6.9] years) and 132 patients in the younger adult group (mean age: 52.4 [SD: 12.5] years). There was a significantly higher Charlson Comorbidity Index score and lower Karnofsky score in the older adult group. The older adult group received significantly lower total energy (20.8 [SD: 7.8] vs 22.8 [SD: 6.3] kcal/kg/day), dextrose (3.1 [SD: 1.4] vs 3.6 [SD: 1.4] g/kg/day), and protein (1.1 [SD: 0.4] vs 1.2 [SD: 0.3] g/kg/day) than the younger group received. The mean length of stay was significantly shorter in the older adult group (35.9 [SD: 21.3] vs 59.8 [SD: 55.3]; P < 0.05). There was no significant difference in PN-related complications and clinical outcomes (catheter-related bloodstream infections, hypoglycemia or hyperglycemia, fluid overload, or inpatient mortality) between the two groups. Despite more comorbidities in the older adult, the usage of PN in older adult patients with acute intestinal failure was associated with neither an increased rate of PN-related complications nor worse clinical outcomes when compared with that of younger patients.

To validate a volume-weighted voxel-based multiparametric clustering (VVMC) method for magnetic resonance imaging data that is designed to differentiate between pseudoprogression and early tumor progression (ETP) in patients with glioblastoma in an independent test set. This retrospective study was approved by the local institutional review board, with waiver of the need to obtain informed consent. The study patients were grouped chronologically into a training set (108 patients) and a test set (54 patients). The reference standard was pathologic findings or subsequent clinical-radiologic study results. By using the optimal cutoff determined in the training set, the diagnostic performance of VVMC was subsequently tested in the test set and was compared with that of single-parameter measurements (apparent diffusion coefficient [ADC], normalized cerebral blood volume [nCBV], and initial area under the time-signal intensity curve). Interreader agreement was highest for VVMC (intraclass correlation coefficient, 0.87-0.89). Receiver operating characteristic curve analysis revealed that VVMC performed the best as a classifier, although statistical significance was not demonstrated with respect to the nCBV in the training set. In the test set, the diagnostic accuracy of VVMC was higher than that of any single-parameter measurements, but this trend reached significance only for the ADC. When the entire population was considered, VVMC had significantly better diagnostic accuracy than did any single parameter (P = .003-.046 for reader 1; P = .002-.016 for reader 2). Results of fivefold cross validation confirmed the trends in both the training set and the test set. VVMC is a superior and more reproducible imaging biomarker than single-parameter measurements for differentiating between pseudoprogression and ETP in patients with glioblastoma. Online supplemental material is available for this article.

BACKGROUND Glioblastoma multiforme (GBM) is the most aggressive grade IV glioma in adults. While surgical resection followed by chemoradiotherapy remains the standard treatment, elderly patients (&amp;gt; 70 years) or those with poor functional status often cannot tolerate conventional radiotherapy regimens. The Karnofsky Performance Status (KPS), a widely used functional scale, has been identified as a key predictor of clinical benefit. This study evaluates the efficacy of different moderate hypofractionated radiotherapy (HFRT) regimens combined with temozolomide in newly diagnosed GBM patients, stratified by KPS. METHODS A systematic review was conducted using PubMed, Embase, Scopus, Web of Science, CENTRAL, and Google Scholar. Studies were included if they involved de novo GBM patients with a mean age &amp;gt; 70 years treated with moderate HFRT. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included partial response (PR), stable disease (SD), and progression (PD) rates. A proportion meta-analysis was performed using a random-effects model in R Studio. Risk of bias was assessed using the ROBINS-I tool. RESULTS Nine studies met the inclusion criteria, encompassing a total of 342 patients, using HFRT regimens ranging from 30-52.5 Gy in 6-15 fractions. The longest PFS (8.5 months) was observed with 45 Gy in 15 fractions, while the highest OS (15.8 months) was reported with 40 Gy in 15 fractions. Pooled estimates were 0.13 (95% CI: 0.05-0.31) for PR, 0.05 (95% CI: 0.01-0.23) for SD, and 0.05 (95% CI: 0.01-0.28) for PD, with substantial heterogeneity. Most studies had a moderate to serious risk of bias. CONCLUSION Moderate hypofractionated radiotherapy (40-45 Gy in 15 fractions) combined with temozolomide appears to offer an optimal balance between efficacy and tolerability in elderly patients (&amp;gt; 70 years) with newly diagnosed GBM and a KPS &amp;gt; 70. Dose escalation showed no survival benefit and was associated with poorer outcomes in patients with lower KPS. Stratification by KPS remains essential for personalized treatment planning. Further prospective, well-designed clinical trials are needed to standardize radiotherapy dosing, improve patient selection criteria, and enhance therapeutic strategies based on functional status.

Improving Consistency and Quality of Care for Older Adults With Cancer: The Challenges of Developing Consensus Guidelines for Radiation Therapy

Postoperative conventional daily radiotherapy probably improves survival for adults with good performance status and HGG compared to no postoperative radiotherapy. Hypofractionated radiotherapy has similar efficacy for survival compared to conventional radiotherapy, particularly for individuals aged 60 years and older with glioblastoma. There are insufficient data regarding hyperfractionation versus conventionally fractionated radiation (without chemotherapy) and for accelerated radiation versus conventionally fractionated radiation (without chemotherapy). There are HGG subsets who have poor prognosis even with treatment (e.g. glioblastoma histology, older age and poor performance status). These HGG individuals with poor prognosis have generally been excluded from randomised trials based on poor performance status. No randomised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these people with poor prognosis. Since the last version of this review, we found no new relevant studies. The search identified three new trials, but all were excluded as none had a conventionally fractionated radiotherapy arm.

BackgroundDiabetes is a global health problem, and its incidence and complications increase with the duration of the disease and over time. This increase in complications in older patients can lead to disability and a lower quality of life. This study aimed to investigate the rate of diabetes control and complications in older adults.MethodThis was a cross-section of an ongoing cohort of patients with type 2 diabetes mellitus (T2DM) aged 65 years and older. The clinical and laboratory characteristics of older adult patients with T2DM in good and intermediate health conditions were collected between 2010 and 2022.ResultsA total of 2,770 older adult patients with T2DM were enrolled, including 1,530(55.3%) female and 1,240 (44.7%) male participants. Metabolic syndrome, hypertension, and coronary artery disease were the most common comorbidities, affecting 1,889 (71.4%), 1,495 (54.4%), and 786 (29.2%) patients, respectively. Albuminuria was present in 626 (22.6%) patients, while retinopathy was detected in 408 (14.7%) patients, including 6% with proliferative retinopathy. Most patients were treated with oral antidiabetic agents (88.9%), with metformin being the most prescribed medication (85.6%). Statins were prescribed to 71.8% of the patients. The most prescribed antihypertensive medications were angiotensin receptor blockers and angiotensin-converting enzyme inhibitors, prescribed to 54% and 15% of patients, respectively. The hemoglobin A1c (HbA1c) goal (HbA1c < 7.5%) was achieved in 1,350 (56.4%) patients, and the low-density lipoprotein cholesterol (LDL-C) goal (LDL < 100) was achieved in 1,165 (45.6%) patients. Blood pressure control (BP < 140/90) was achieved in 1,755 (65.4%) patients. All three goals were achieved in 278 (10.3%) patients. There were no significant differences in clinical laboratory results and the patients’ characteristics based on gender.ConclusionThe rate of progression of complications in older adult patients is higher than the effectiveness of the treatment, indicating the need for increased social support for this age group.

Older patients are considered to have increased risk for complications after major surgery, but age alone is not a reliable predictor of postoperative complications. However, no universal screening test adequately predicts postoperative complications in older patients. This prospective study recorded pertinent baseline geriatric assessment variables to identify risk factors for postoperative complications in hepatocellular carcinoma (HCC) for patients aged ≥70 years who undergo hepatectomy. We retrospectively analyzed 71 consecutive patients ≥70 years of age. Patients had geriatric assessments of baseline and later cognition, nutritional and functional status, and burden of comorbidities, completed preoperatively and at 1, 3, and 6 months postoperatively. Postoperative morbidities were recorded. Postoperative morbidities developed in 18 patients (25 %). Univariate analysis identified serum albumin, operating time and blood loss, cirrhosis, geriatric 8 (G8), and Mini Nutritional Assessment as possible risk factors for postoperative complications, but only G8 < 14 survived multivariate analysis as an independent predictor of complications. Our findings indicate that the G8 score, based on patients' nutritional assessments, is a useful screening method for older HCC patients who qualify for elective liver resection. Preoperative G8 scores can help forecast postoperative complications in older HCC patients. Future studies with larger numbers of patients, limited to HCC and liver resections, are needed to verify our results.

The purpose of this systematic review was to synthesize studies published since the last systematic review in 2015 that compare outcomes of primary total knee arthroplasty (TKA) in older patients (≥ 80 years) and in younger patients (< 80 years), in terms of complication rates and mortality.An electronic literature search was conducted using PubMed, Embase®, and Cochrane Register. Studies were included if they compared outcomes of primary TKA for osteoarthritis in patients aged 80 years and over to patients aged under 80 years, in terms of complication rates, mortality, or patient-reported outcomes (PROs).Thirteen studies were eligible. Surgical complications in older patients ranged from 0.6–21.1%, while in younger patients they ranged from 0.3–14.6%. Wound complications in older patients ranged from 0.5–20%, while in younger patients they ranged from 0.8–22.0%. Medical complications (cardiac, respiratory, thromboembolic) in older patients ranged from 0.4–17.3%, while in younger patients they ranged from 0.2–11.5%.Mortality within 90 days in older patients ranged between 0–2%, while in younger patients it ranged between 0.0–0.03%.Compared to younger patients, older patients have higher rates of surgical and medical complications, as well as higher mortality following TKA. The literature also reports greater length of stay for older patients, but inconsistent findings regarding PROs. The present findings provide surgeons and older patients with clearer updated evidence, to make informed decisions regarding TKA, considering the risks and benefits within this age group. Patients aged over 80 years should therefore not be excluded from consideration for primary TKA based on age alone.Cite this article: EFORT Open Rev 2021;6:1052-1062. DOI: 10.1302/2058-5241.6.200150

Isolated systolic hypertension occurs in around 8% of Chinese people aged 60 years or older. In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications in older patients with isolated systolic hypertension. All patients were initially started on masked placebo. After stratification for centre, sex and previous cardiovascular complications, alternate patients (n=1253) were assigned nitrendipine at 10-40 mg daily, with the addition of captopril at 12.5-50.0 mg daily or hydrochlorothiazide at 12.5-50.0 mg daily, or both, if a sufficient blood pressure fall was not obtained. In the remaining 1141 control patients, matching placebos were administered similarly. At entry, sitting blood pressure averaged 170.5 mmHg systolic and 86.0 mmHg diastolic, age averaged 66.5 years and total serum cholesterol was 5.1 mmol/l. After 2 years of follow-up, sitting systolic and diastolic blood pressures had fallen by 10.9 mmHg and 1.9 mmHg in the placebo group and by 20.0 mmHg and 5.0 mmHg in the active treatment group. The intergroup differences were 9.1 mmHg systolic (95% confidence interval 7.6-10.7 mmHg ) and 3.2 mmHg diastolic (95% confidence interval 2.4-4.0). Active treatment reduced total strokes by 38% (from 20.8 to 13.0 endpoints per 1000 patient-years, P=0.01), all-cause mortality by 39% (from 28.4 to 17.4 endpoints per 1000 patient-years, P=0.003), cardiovascular mortality by 39% (from 15.2 to 9.4 endpoints per 1000 patient-years, P=0.03), stroke mortality by 58% (from 6.9 to 2.9 endpoints per 1000 patient-years, P=0.02), and ail fatal and nonfatal cardiovascular endpoints by 37% (from 33.3 to 21.4 endpoints per 1000 patient-years, P=0.004). Antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension. Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths, 39 strokes or 59 major cardiovascular endpoints.

BackgroundEarly warning system (EWS) scores are implemented on surgical wards to identify patients at high risk of postoperative clinical deterioration, but its predictive value in older patients is unclear. This study assessed the prognostic value of EWS scores to predict severe postoperative complications in older patients compared to younger patients.MethodsThis study utilized data from the TRACE study. EWS scores were routinely measured on postoperative days one (POD1) and three (POD3). The cohort was divided by age: < 70 years and ≥ 70 years. Performance measures of EWS scores on POD1 and POD3 were assessed to predict severe postoperative complications. Missed event rates (proportion of events not detected by the EWS threshold) and nonevent rates (proportion of EWS values above the threshold without an adverse event) were calculated.ResultsAmong 4866 patients, 39.3% were ≥ 70 years old. Severe complications occurred in 6.1% of older compared to 5.8% of younger patients (P = 0.658). EWS scores on POD1 and POD3 did not differ between age groups. For severe complications, EWS showed moderate discrimination in both older (POD1: C-statistic 0.65 (95%CI 0.59–0.70); POD3: 0.63 (95%CI 0.57–0.69)) and younger patients (POD1: 0.68 (95%CI 0.65–0.72); POD3: 0.65 (95%CI 0.61–0.70)). Overall, calibration was good. For EWS score ≥ 3, the missed event rate was at least 69% and nonevent rate 75%.ConclusionsPredicted performance of the EWS score was moderate among older and younger patients. A limitation of the EWS score is the high rate of missed events and nonevents.