The incidence of brain metastases in breast cancer according to molecular subtype and stage: a 10-year single institution analysis.

BACKGROUND: Breast cancer (BC) is the second most common etiology of brain metastases (BrM). We aimed to examine the incidence of BrM among all BC patients presenting to a large tertiary cancer centre over one decade. METHODS: We included all BC patients presenting consecutively between 2009 and 2019 and cross referenced that cohort to a radiotherapy database, identifying patients treated for BrM at any time following their initial presentation. Cumulative incidences (CI) of BrM diagnoses were calculated using death as a competing risk and compared using the Fine-Gray method. Overall survival was estimated using the Kaplan Meier method. RESULTS: We identified 12,995 unique patients. The CI of BrM in patients who initially presented with Stage 0-4 disease was 2.1%, 3.7%, 9.4%, 10.6%, and 28.7%, respectively at 10 years. For 8,951 patients with available molecular subtype data, 6,470 (72%), 961 (11%), 1,023 (11%), and 497 (6%) had hormone-receptor (HR)-positive/ERBB2-, HR-negative/ERBB2-, HR-positive/ERBB2 + , and HR-negative/ERBB2 + disease, respectively; the CI of BrM in each was 7.6%, 25.3%, 24.1%, and 26.6%, at 10 years following BC diagnosis, respectively. Median overall survival (OS) following BC diagnosis and BrM diagnosis was 28 years 95% CI [25, 32] and 10 months 95% CI [9, 12], respectively. CONCLUSIONS: From a large, registry-based study, we observed that patients with ERBB2 + and triple negative BC have the highest incidence of BrM. Our data supports prospective surveillance brain MRI studies. Given advancements in BrM treatment, clinicians should have a low threshold for brain imaging in BC patients with high risk subtypes.

Palliative Care as a Component of High-Value and Cost-Saving Care During Hospitalization for Metastatic Cancer.

PURPOSE: Randomized controlled trials have demonstrated that palliative care (PC) can improve quality of life and survival for outpatients with advanced cancer, but there are limited population-based data on the value of inpatient PC. We assessed PC as a component of high-value care among a nationally representative sample of inpatients with metastatic cancer and identified hospitalization characteristics significantly associated with high costs. METHODS: Hospitalizations of patients 18 years and older with a primary diagnosis of metastatic cancer from the National Inpatient Sample from 2010 to 2019 were analyzed. We used multivariable mixed-effects logistic regression to assess medical services, patient demographics, and hospital characteristics associated with higher charges billed to insurance and hospital costs. Generalized linear mixed-effects models were used to determine cost savings associated with provision of PC. RESULTS: Among 397,691 hospitalizations from 2010 to 2019, the median charge per admission increased by 24.9%, from $44,904 in US dollars (USD) to $56,098 USD, whereas the median hospital cost remained stable at $14,300 USD. Receipt of inpatient PC was associated with significantly lower charges (odds ratio [OR], 0.62 [95% CI, 0.61 to 0.64]; P < .001) and costs (OR, 0.59 [95% CI, 0.58 to 0.61]; P < .001). Factors associated with high charges were receipt of invasive medical ventilation (P < .001) or systemic therapy (P < .001), Hispanic patients (P < .001), young age (18-49 years, P < .001), and for-profit hospitals (P < .001). PC provision was associated with a $1,310 USD (-13.6%, P < .001) reduction in costs per hospitalization compared with no PC, independent of the receipt of invasive care and age. CONCLUSION: Inpatient PC is associated with reduced hospital costs for patients with metastatic cancer, irrespective of age and receipt of aggressive interventions. Integration of inpatient PC may de-escalate costs incurred through low-value inpatient interventions.

Prospective evaluation of patient-reported anxiety and experiences with adaptive radiation therapy on an MR-linac.

Purpose: An integrated magnetic resonance scanner and linear accelerator (MR-linac) was implemented with daily online adaptive radiation therapy (ART). This study evaluated patient-reported experiences with their overall hospital care as well as treatment in the MR-linac environment. Methods: Patients pre-screened for MR eligibility and claustrophobia were referred to simulation on a 1.5 T MR-linac. Patient-reported experience measures were captured using two validated surveys. The 15-item MR-anxiety questionnaire (MR-AQ) was administered immediately after the first treatment to rate MR-related anxiety and relaxation. The 40-item satisfaction with cancer care questionnaire rating doctors, radiation therapists, the services and care organization and their outpatient experience was administered immediately after the last treatment using five-point Likert responses. Results were analyzed using descriptive statistics. Results: 205 patients were included in this analysis. Multiple sites were treated across the pelvis and abdomen with a median treatment time per fraction of 46 and 66 min respectively. Patients rated MR-related anxiety as "not at all" (87%), "somewhat" (11%), "moderately" (1%) and "very much so" (1%). Positive satisfaction responses ranged from 78 to 100% (median 93%) across all items. All radiation therapist-specific items were rated positively as 96-100%. The five lowest rated items (range 78-85%) were related to general provision of information, coordination, and communication. Overall hospital care was rated positively at 99%. Conclusion: In this large, single-institution prospective cohort, all patients had low MR-related anxiety and completed treatment as planned despite lengthy ART treatments with the MR-linac. Patients overall were highly satisfied with their cancer care involving ART using an MR-linac.

Meta-Analysis of STereotactic body radiothERapy in non-spine BONE metastaseS (MASTER-BONES).

PURPOSE: The efficacy and safety of stereotactic body radiation (SBRT) for patients with non-spine bone metastases (NSBM) remains in question. A systematic review and meta-analysis was performed to evaluate SBRT treatment outcomes in NSBM. METHODS AND MATERIALS: Eligible studies were retrieved from Medline, Embase, Scielo, the Cochrane Library, and annual meeting proceedings until July 6, 2023. We adhered to the PRISMA and MOOSE guideline recommendations. Quantitative synthesis was performed using a random effects model. RESULTS: Seven retrospective studies, with a total of 807 patients (1048 lesions) treated with stereotactic body radiation were included, with median follow-up ranging from 7.6-26.5 months. The most common stereotactic body radiation sites were pelvis (39.2%), ribs (25.8%), femur (16.7%), and humerus/shoulder region (8.7%). At 1-year, the LF and FR were 7% (95%CI 5.5-8.5%; I2=0, n= 75/1048), and 5.3% (95%CI 3-7.5%;I2=0, n= 65/1010). The 2-year cumulative LF incidence was 12.1% (95% CI: 10-15.5%). The OS and PFS at 1-year were 82% (95%CI 75-88%;I2=82%, n= 746/867), and 33.5%(95%CI 26-41%;I2=0%, n= 51/152), with a median of 20.2 months (95%CI: 10.9-49.1 months) and 8.3 months (95% CI: 6.3-10.3%) for OS and PFS, respectively. Meta-regression analysis revealed a significant relationship between planning target volume and fracture rate (p<0.05). Ribs 2.5% followed by the femur 1.9% (95%CI:0-6.1%) were the most common fracture sites. The occurrence of pain flare, fatigue and dermatitis were 7 %, 5.4 %, and 0.65 %, respectively. CONCLUSIONS: Stereotactic body radiation proves both safety and efficacy for non-spine bone metastases and serious complications (grade 3) are infrequent. Careful consideration of target volume is crucial due to its link with a higher fracture risk.

Advances and Challenges in Trials of Local Therapy for Patients With Oligometastatic or Oligoprogressive Disease.

The paradigm of oligometastatic disease (OMD), characterized by a limited number of metastases potentially amenable to local therapies, presents unique opportunities and challenges in clinical trial design and implementation. Although local ablative therapies, such as stereotactic body radiation therapy, have shown promise in improving outcomes for patients with OMD, there is a lack of large-scale randomized phase III trials supporting their widespread use. This paper outlines the key challenges in trial design and implementation in the oligometastatic setting, including appropriate patient selection, the definition of the oligometastatic state, trial design considerations, endpoint selection, and logistical considerations related to enrollment and follow-up. We suggest potential strategies to address these challenges, emphasizing the importance of a comprehensive, patient-centric approach, and the integration of multidisciplinary teams in trial design and implementation. The aim is to encourage the design of well-structured clinical trials, ultimately refining best practices and enhancing patient outcomes in the management of OMD.

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location pose unique safety considerations. We performed a systematic review and meta-analysis to summarize the current safety and efficacy data and provide practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: We performed a systematic review using PubMed and EMBASE databases of patients with ultra-central lung tumors treated with SBRT. Studies reporting local control (LC) and/or toxicity were included. Studies with <5 treated lesions, non-English language, re-irradiation, nodal tumors, or mixed outcomes in which ultra-central tumors could not be discerned were excluded. Random-effects meta-analysis was performed for studies reporting relevant endpoints. Meta-regression was conducted to determine the effect of various covariates on the primary outcomes. RESULTS: 602 unique studies were identified of which 27 (one prospective observational, the remainder retrospective) were included, representing 1183 treated targets. All studies defined ultra-central as the planning target volume (PTV) overlapping the proximal bronchial tree (PBT). The most common dose fractionations were 50 Gy/5, 60 Gy/8, and 60 Gy/12 fractions. The pooled 1- and 2-year LC estimates were 92 % and 89 %, respectively. Meta-regression identified biological effective dose (BED10) as a significant predictor of 1-year LC. A total of 109 grade 3-4 toxicity events, with a pooled incidence of 6 %, were reported, most commonly pneumonitis. There were 73 treatment related deaths, with a pooled incidence of 4 %, with the most common being hemoptysis. Anticoagulation, interstitial lung disease, endobronchial tumor, and concomitant targeted therapies were observed risk factors for fatal toxicity events. CONCLUSION: SBRT for ultra-central lung tumors results in acceptable rates of local control, albeit with risks of severe toxicity. Caution should be taken for appropriate patient selection, consideration of concomitant therapies, and radiotherapy plan design.

A Phase II Study of Optimized Individualized Adaptive Radiotherapy for Hepatocellular Carcinoma.

PURPOSE: We hypothesized that optimizing the utility of stereotactic body radiotherapy (SBRT) based on the individual patient's probability for tumor control and risk of liver injury would decrease toxicity without sacrificing local control in patients with impaired liver function or tumors not amenable to thermal ablation. PATIENTS AND METHODS: Patients with Child-Pugh (CP) A to B7 liver function with aggregate tumor size >3.5 cm, or CP ≥ B8 with any size tumor were prospectively enrolled on an Institutional Review Board-approved phase II clinical trial to undergo SBRT with baseline and midtreatment dose optimization using a quantitative, individualized utility-based analysis. Primary endpoints were change in CP score of ≥2 points within 6 months and local control. Protocol-treated patients were compared with patients receiving conventional SBRT at another cancer center using overlap weighting. RESULTS: A total of 56 patients with 80 treated tumors were analyzed with a median follow-up of 11.2 months. Two-year cumulative incidence of local progression was 6.4% [95% confidence interval (CI, 2.4-13.4)]. Twenty-one percent of patients experienced treatment-related toxicity within 6 months, which is similar to the rate for SBRT in patients with CP A liver function. An analysis using overlap weighting revealed similar local control [HR, 0.69; 95% CI (0.25-1.91); P = 0.48] and decreased toxicity [OR, 0.26; 95% CI (0.07-0.99); P = 0.048] compared with conventional SBRT. CONCLUSIONS: Treatment of individuals with impaired liver function or tumors not amenable to thermal ablation with a treatment paradigm designed to optimize utility may decrease treatment-related toxicity while maintaining tumor control.

Dyspnea in patients with stage IV non-small cell lung cancer: a population-based analysis of disease burden and patterns of care.

Background: Patients with metastatic non-small cell lung cancer (NSCLC) experience significant morbidity with dyspnea being a common symptom with a prevalence of 70%. The objective of this study was to determine factors associated with a moderate-to-severe dyspnea score based on the Edmonton Symptom Assessment System (ESAS), as well as resultant patterns of intervention and factors correlated to intervention receipt. Methods: Using health services administrative data, we conducted a population-based study of all patients diagnosed with metastatic NSCLC treated from January 2007 to September 2018 in the province of Ontario. The primary outcomes of interest are the prevalence of moderate-to-severe dyspnea scores, and the receipt of dyspnea-directed intervention. Differences in baseline characteristic between moderate-to-severe dyspnea and low dyspnea score cohorts were assessed by comparative statistics. Predictors of intervention receipt for patients with moderate-to-severe dyspnea scores were estimated using multivariable modified Poisson regression. Results: The initial study cohort included 13,159 patients diagnosed with metastatic NSCLC and of these, 9,434 (71.7%) reported a moderate-to-severe dyspnea score. Compared to patients who did not report moderate-to-severe dyspnea scores, those who reported a moderate-to-severe dyspnea score were more likely to complete a greater number of ESAS surveys, be male, have a higher Elixhauser comorbidity index (ECI) score, and receive subsequent systemic therapy after diagnosis. Most patients with a moderate-to-severe dyspnea score received intervention (96%), of which the most common were palliative care management (87%), thoracic radiotherapy (56%) and thoracentesis (37%). Multivariable regression identified older patients to be less likely to undergo pleurodesis. Thoracentesis was less common for patients living in rural and non-major urban areas, lower income areas, and earlier year of diagnosis. Receipt of thoracic radiotherapy was less common for older patients, females, those with ECI ≥4, patients living in major urban areas, and those with later year of diagnosis. Finally, palliative care referrals were less frequent for patients with ECI ≥4, age 60-69, residence outside of major urban areas, earlier year of diagnosis, and lower income areas. Conclusions: Dyspnea is a prevalent symptom amongst patients with metastatic NSCLC. Subpopulations of patients with moderate-to-severe dyspnea scores were in which inequities may exist in access to care that require further attention and evaluation.

Hypofractionated stereotactic radiosurgery (HSRS) as a salvage treatment for brain metastases failing prior stereotactic radiosurgery (SRS).

INTRODUCTION: Various treatment options exist to salvage stereotactic radiosurgery (SRS) failures for brain metastases, including repeat SRS and hypofractionated SRS (HSRS). Our objective was to report outcomes specific to salvage HSRS for brain metastases that failed prior HSRS/SRS. METHODS: Patients treated with HSRS to salvage local failures (LF) following initial HSRS/SRS, between July 2010 and April 2020, were retrospectively reviewed. The primary outcomes were the rates of LF, radiation necrosis (RN), and symptomatic radiation necrosis (SRN). Univariable (UVA) and multivariable (MVA) analyses using competing risk regression were performed to identify predictive factors for each endpoint. RESULTS: 120 Metastases in 91 patients were identified. The median clinical follow up was 13.4 months (range 1.1-111.1), and the median interval between SRS courses was 13.1 months (range 3.0-56.5). 115 metastases were salvaged with 20-35 Gy in 5 fractions and the remaining five with a total dose ranging from 20 to 24 Gy in 3-fractions. 67 targets (56%) were postoperative cavities. The median re-treatment target volume and biological effective dose (BED10) was 9.5 cc and 37.5 Gy, respectively. The 6- and 12- month LF rates were 18.9% and 27.7%, for RN 13% and 15.6%, and for SRN were 6.1% and 7.0%, respectively. MVA identified larger re-irradiation volume (hazard ratio [HR] 1.02, p = 0.04) and shorter interval between radiosurgery courses (HR 0.93, p < 0.001) as predictors of LF. Treatment of an intact target was associated with a higher risk of RN (HR 2.29, p = 0.04). CONCLUSION: Salvage HSRS results in high local control rates and toxicity rates that compare favorably to those single fraction SRS re-irradiation experiences reported in the literature.

Pain and Interventions in Stage IV Non-Small Cell Lung Cancer: A Province-Wide Analysis.

Pain is a common symptom in stage IV non-small cell lung cancer (NSCLC). The objective of the study was to examine the use of interventions and factors associated with interventions for pain. A population-based cohort study in Ontario, Canada was conducted with patients diagnosed with stage IV NSCLC from January 2007 to September 2018. An Edmonton Symptom Assessment System (ESAS) score of ≥4 defined moderate-to-severe pain following diagnosis. The study cohort included 13,159 patients, of which 68.5% reported at least one moderate-to-severe pain score. Most patients were assessed by a palliative care team (85.4%), and the majority received radiation therapy (73.2%). The use of nerve block was rare (0.8%). For patients ≥65 years of age who had drug coverage, 59.6% received an opiate prescription. Patients with moderate-to-severe pain were more likely to receive palliative assessment or radiation therapy compared to patients with none or mild pain. Patients aged ≥70 years and with a greater comorbidity burden were associated with less likelihood to receive radiation therapy. Patients from rural/non-major urban residence and with a greater comorbidity burden were also less likely to receive palliative care assessment. Factors associated with interventions for pain are described to inform future symptom management in this population.

Post-COVID-19 Syndrome Comprehensive Assessment: From Clinical Diagnosis to Imaging and Biochemical-Guided Diagnosis and Management.

The COVID-19 outbreak was first reported in 2019, causing massive morbidity and mortality. The majority of the COVID-19 patients survived and developed Post-COVID-19 Syndrome (PC19S) of varying severity. Currently, the diagnosis of PC19S is achieved through history and symptomatology that cannot be explained by an alternative diagnosis. However, the heavy reliance on subjective reporting is prone to reporting errors. Besides, there is no unified diagnostic assessment tool to classify the clinical severity of patients. This leads to significant difficulties when managing patients in terms of public resource utilization, clinical progression monitorization and rehabilitation plan formulation. This narrative review aims to review current evidence of diagnosis based on triple assessment: clinical symptomatology, biochemical analysis and imaging evidence. Further assessment tools can be developed based on triple assessment to monitor patient's clinical progression, prognosis and intervals of monitoring. It also highlights the high-risk features of patients for closer and earlier monitoring. Rehabilitation programs and related clinical trials are evaluated; however, most of them focus on cardiorespiratory fitness and psychiatric presentations such as anxiety and depression. Further research is required to establish an objective and comprehensive assessment tool to facilitate clinical management and rehabilitation plans.

Ensuring Superior Reporting of Radiation Therapy Noninferiority Trials: A Systematic Review.

Purpose: Although the frequency of noninferiority trials is increasing, the consistency of the reporting of these trials can vary. The aim of this systematic review was to assess the reporting quality of radiation therapy noninferiority trials. Methods and Materials: The PubMed, Embase, and Cochrane databases were queried for randomized controlled radiation therapy trials with noninferiority hypotheses published in English between January 2000 and July 2022, and this was performed by an information scientist. Descriptive statistics were used to summarize data. Results: Of 423 records screened, 59 (14%) were included after full-text review. All were published after 2003 and open label. The most common primary cancer type was breast (n = 15, 25%). Altered radiation fractionation (n = 26, 45%) and radiation de-escalation (n = 11, 19%) were the most common types of interventions. The most common primary endpoints were locoregional control (n = 17, 29%) and progression-free survival (n = 14, 24%). Fifty-three (90%) reported the noninferiority margin, and only 9 (17%) provided statistical justification for the margin. The median absolute noninferiority margin was 9% (interquartile range, 5%-10%), and the median relative margin was 1.51 (interquartile range, 1.33-2.04). Sample size calculations and confidence intervals were reported in 54 studies (92%). Both intention-to-treat and per-protocol analyses were reported in 27 studies (46%). In 31 trials (53%), noninferiority of the primary endpoint was reached. Conclusions: There was variability in the reporting of key components of noninferiority trials. We encourage consideration of additional statistical reasoning such as guidelines or previous trials in the selection of the noninferiority margin, reporting both absolute and relative margins, and the avoidance of statistically vague or misleading language in the reporting of future noninferiority trials.

Conventionally fully fractionated Gamma Knife Icon re-irradiation of primary recurrent intracranial tumors: the first report indicating feasibility and safety.

OBJECTIVE: With the incorporation of real-time image guidance on the Gamma Knife system allowing for mask-based immobilization (Gamma Knife Icon [GKI]), conventionally fully fractionated (1.8-3.0 Gy/day) GKI radiation can now be delivered to take advantage of an inherently minimal margin for delivery uncertainty, sharp dose falloff, and inhomogeneous dose distribution. This case series details the authors' preliminary experience in re-irradiating 7 complex primary intracranial tumors, which were considered to have been previously maximally radiated and situated adjacent to critical organs at risk. METHODS: The authors retrospectively reviewed all patients who received fractionated re-irradiation using GKI at the Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada, between 2016 and 2021. Patients with brain metastases, and those who received radiotherapy courses in 5 or fewer fractions, were excluded. All radiotherapy doses were converted to the equivalent total dose in 2-Gy fractions (EQD2), with the assumption of an α/ß ratio of 2 for late normal tissue toxicity and 10 for the tumor. RESULTS: A total of 7 patients were included in this case series. Three patients had recurrent meningiomas, as well as 1 patient each with ependymoma, intracranial sarcoma, pituitary macroadenoma, and papillary pineal tumor. Six patients had undergone prior linear accelerator-based conventional fractionated radiotherapy and 1 patient had undergone prior proton therapy. Patients were re-irradiated with a median (range) total dose of 50.4 (30-63.4) Gy delivered in a median (range) of 28 (10-38) fractions with GKI. The median (range) target volume was 6.58 (0.2-46.3) cm3. The median (range) cumulative mean EQD2 administered to the tumor was 121.1 (107.9-181.3) Gy, and the median (range) maximum point EQD2 administered to the brainstem, optic nerves, and optic chiasm were 91.6 (74.0-111.5) Gy, 58.9 (6.3-102.9) Gy, and 59.9 (36.7-127.3) Gy, respectively. At a median (range) follow-up of 15 (6-42) months, 6 of 7 patients were alive with 4 having locally controlled disease. Only 3 patients experienced treatment-related toxicities, which were self-limited. CONCLUSIONS: Fractionated radiotherapy using GKI may be a safe and effective method for the re-irradiation of complex progressive primary intracranial tumors, where the aim is to minimize the potential for serious late effects.

Gamma knife icon based hypofractionated stereotactic radiosurgery (GKI-HSRS) for brain metastases: impact of dose and volume.

OBJECTIVE: Gamma Knife Icon-based hypofractionated stereotactic radiosurgery (GKI-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the GKI stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control and adverse radiation effect (ARE) outcomes following 5 fraction GKI-HSRS for intact brain metastases. METHODS: Patients with intact brain metastases treated with 5-fraction GKI-HSRS were retrospectively reviewed. Survival, local control, and adverse radiation effect rates were determined. Univariable and multivariable regression (MVA) were performed on potential predictive factors. RESULTS: Two hundred and ninety-nine metastases in 146 patients were identified. The median clinical follow-up was 10.7 months (range 0.5-47.6). The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5) in 5 daily fractions and 52% (range, 45-93), respectively. The median overall survival (OS) was 12.7 months, and the 1-year local failure rate was 15.2%. MVA identified a total dose of 27.5 Gy vs. ≤ 25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥ 4.5 cc (HR 7.29, p < 0.001) as a significant predictor of symptomatic ARE. CONCLUSION: Moderate total doses in 5 daily fractions of GKI-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE.

COVID-19's impact on interest in gastrointestinal topics.

There has been a disparity in familiarity regarding the public interest in gastroenterology terminologies during the COVID-19 pandemic. This study aimed to understand the outcomes of the public's view on gastrointestinal topics and their potential social effects. This study is a comparative analysis of American Google Trends gastrointestinal terminology during the COVID-19 pandemic compared to a similar time frame (March 2018-February 2020) to determine how trends in the patient-seeking behavior of gastrointestinal terminology changed throughout the pandemic. The analysis discovered a substantial decrease in search volumes of gastrointestinal topics, more significantly in the first pandemic months. Later in the pandemic, search volumes trended toward pre-pandemic years in terms of public interest. In the case of gastrointestinal procedures, endoscopy and colonoscopies, they surpassed pre-pandemic interest levels statistically (p-values of 0.01 and 0.002). The public's decreased interest in gastrointestinal topics at the beginning of the COVID-19 pandemic may have adverse effects on the healthcare maintenance of patients who could have had a positive outcome in their gastrointestinal health with proper monitoring. Although gastrointestinal internet searches increased toward pre-pandemic levels as the seasons progressed, further research is needed to determine the social impact of decreased public interest.

Sequelae of COVID-19 among previously hospitalized patients up to 1 year after discharge: a systematic review and meta-analysis.

OBJECTIVE: Although complications and clinical symptoms of COVID-19 have been elucidated, the prevalence of long-term sequelae of COVID-19 is less clear in previously hospitalized COVID-19 patients. This review and meta-analysis present the occurrence of different symptoms up to 1 year of follow-up for previously hospitalized patients. METHODS: We performed a systematic review from PubMed and Web of Science using keywords such as "COVID-19", "SARS-CoV-2", "sequelae", "long-term effect" and included studies with at least 3-month of follow-up. Meta-analyses using random-effects models were performed to estimate the pooled prevalence for different sequelae. Subgroup analyses were conducted by different follow-up time, regions, age and ICU admission. RESULTS: 72 articles were included in the meta-analyses after screening 11,620 articles, identifying a total of 167 sequelae related to COVID-19 from 88,769 patients. Commonly reported sequelae included fatigue (27.5%, 95% CI 22.4-33.3%, range 1.5-84.9%), somnipathy (20.1%, 95% CI 14.7-26.9%, range 1.2-64.8%), anxiety (18.0%, 95% CI 13.8-23.1%, range 0.6-47.8%), dyspnea (15.5%, 95% CI 11.3-20.9%, range 0.8-58.4%), PTSD (14.6%, 95% CI 11.3-18.7%, range 1.2-32.0%), hypomnesia (13.4%, 95% CI 8.4-20.7%, range 0.6-53.8%), arthralgia (12.9%, 95% CI 8.4-19.2%, range 0.0-47.8%), depression (12.7%, 95% CI 9.3-17.2%, range 0.6-37.5%), alopecia (11.2%, 95% CI 6.9-17.6%, range 0.0-47.0%) over 3-13.2 months of follow-up. The prevalence of most symptoms reduced after > 9 months of follow-up, but fatigue and somnipathy persisted in 26.2% and 15.1%, respectively, of the patients over a year. COVID-19 patients from Asia reported a lower prevalence than those from other regions. CONCLUSIONS: This review identified a wide spectrum of COVID-19 sequelae in previously hospitalized COVID-19 patients, with some symptoms persisting up to 1 year. Management and rehabilitation strategies targeting these symptoms may improve quality of life of recovered patients.

Stereotactic body radiotherapy versus surgery for early-stage non-small cell lung cancer: an updated meta-analysis involving 29,511 patients included in comparative studies.

OBJECTIVE: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC) by means of a meta-analysis of comparative studies. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines, searches were performed on PubMed, MEDLINE, Embase, and Cochrane Library for eligible studies. The meta-analysis compared the hazard ratios (HR) for overall survival (OS), cancer-specific survival (CSS), and local control (LC). Subgroup and meta-regression analyses evaluated the association of extent of surgical resection, study publication year, tumor staging, propensity score matching, proportion of chemotherapy use, and proportion of pathological lymph node involvement with CSS and OS. RESULTS: Thirty studies involving 29,511 patients were included (surgery group: 17,146 patients and SBRT group: 12,365 patients). There was a significant difference in favor of surgery vs. SBRT in the 3-year OS (HR = 1.35; 95% CI: 1.22-1.44; I2 = 66%) and 3-year CSS (HR = 1.23; 95% CI: 1.09-1.37; I2 = 17%), but not in the 3-year LC (HR = 0.97; 95% CI: 0.93-1.08; I2 = 19%). In the subgroup analysis for OS, no significant difference between surgery and SBRT groups was observed in the T1N0M0 subgroup (HR = 1.26; 95% CI: 0.95-1.68; I2 = 0%). In subgroup analysis for CSS, no significant difference was detected between the sublobar resection subgroup and the SBRT group (HR = 1.21; 95% CI: 0.96-1.53; I2 = 16%). CONCLUSIONS: Surgery generally resulted in better 3-year OS and CSS than did SBRT; however, publication bias and heterogeneity may have influenced these findings. In contrast, SBRT produced LC results similar to those of surgery regardless of the extent of surgical resection. These findings may have important clinical implications for patients with comorbidities, advanced age, poor pulmonary reserve, and other factors that may contraindicate surgery.