Predictors of Nodal and Metastatic Failure in Early Stage Non-Small Cell Lung Cancer after Stereotactic Body Radiation Therapy

Introduction/Background Many early-stage non-small cell lung cancer (ES-NSCLC) patients undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. Materials and Methods We included 363 patients with ES-NSCLC who received SBRT; median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): sex; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. Results A total of 111/406 (27.3%) lesions metastasized. GTV volume and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (p<0.001 and HR=1.02 per mL, p<0.05 and HR=0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV volume and prescription dose was built: [risk score=(0.01611 x GTV)–(0.00525 x dose (BED10))]. Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk-score identified significant differences in time to metastases between low-, medium-, and high-risk patients (p<0.001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. Conclusion GTV volume and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT

Superior vena cava syndrome in a patient with locally advanced lung cancer with good response to definitive chemoradiation: a case report

Abstract Background The incidence of superior vena cava syndrome within the United States is roughly 15,000 cases per year. Superior vena cava syndrome is a potentially life-threatening medical condition; however, superior vena cava syndrome is not fatal in the majority of cases. Superior vena cava syndrome encompasses a collection of signs and symptoms resulting from obstruction of the superior vena cava, including swelling of the upper body of the head, neck, arms, and/or breast. It is also associated with cyanosis, plethora, and distended subcutaneous vessels. Lung cancer, including both non-small cell lung cancer and small cell lung cancer, is the most common extrinsic cause of superior vena cava syndrome. Intrinsic disruption of superior vena cava flow can also precipitate superior vena cava syndrome. This case report describes an unusual presentation and potential etiology of superior vena cava syndrome. Case presentation Our patient was a 51-year-old black woman with locally advanced, stage IIIB non-small cell lung cancer who had no clinical symptoms of superior vena cava syndrome at the time of diagnosis. However, she did have radiographic evidence of superior vena cava stenosis caused by extrinsic compression from her large right hilar primary tumor. She was treated with definitive chemoradiation, receiving 60 Gy of external beam radiation therapy given concurrently with chemotherapy. Three months after completion of radiotherapy, she developed signs of superior vena cava syndrome, including breast and supraclavicular swelling. She had a chest computed tomography scan showing over 50% reduction in the size of a right hilar mass; however, she had continued radiographic stenosis of the superior vena cava. The distribution of stenosis appeared to be inferior to the caudal extent of pretreatment tumor volume. She had no other radiographic indications for superior vena cava syndrome. Conclusions Generally, superior vena cava syndrome is the result of extrinsic compression of the superior vena cava by tumor. Our patient’s case represents the development of superior vena cava syndrome after an excellent response of tumor with near-complete tumor response. We suspect chemoradiation therapy as a potential etiology for the precipitation of the superior vena cava syndrome, which is currently not well reported in the medical literature

Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy

Introduction It remains unclear if histology should be independently considered when choosing stereotactic ablative body radiotherapy dose prescriptions for NSCLC. Methods The study population included 508 patients with 561 lesions between 2000 and 2016, of which 442 patients with 482 lesions had complete dosimetric information. Eligible patients had histologically or clinically diagnosed early-stage NSCLC and were treated with 3 to 5 fractions. The primary endpoint was in-field tumor control censored by either death or progression. Involved lobe control was also assessed. Results At 6.7 years median follow-up, 3-year in-field control, involved lobe control, overall survival, and progression-free survival rates were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross tumor volume (GTV) (hazard ratio [HR] = 1.01 per mL, p = 0.0044) and histology (p = 0.0225) were independently associated with involved lobe failure. GTV (HR = 1.013, p = 0.001) and GTV dose (cutoff of 110 Gy, biologically effective dose with α/β = 10 [BED10], HR = 2.380, p = 0.0084) were independently associated with in-field failure. For squamous cell carcinomas, lower prescription doses were associated with worse in-field control (12 Gy × 4 or 10 Gy × 5 versus 18 Gy or 20 Gy × 3: HR = 3.530, p = 0.0447, confirmed by propensity score matching) and was independent of GTV (HR = 1.014 per mL, 95% confidence interval: 1.005–1.022, p = 0.0012). For adenocarcinomas, there were no differences in in-field control observed using the above dose groupings (p = 0.12 and p = 0.31, respectively). Conclusions In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met

Simultaneous measurement of the rates of appearance of palmitic and linoleic acid in critically ill infants

Lipolysis has been measured in humans by means of stable isotope techniques using labeled palmitic acid (PA) or glycerol as tracers. If other fatty acids (FA) such as linoleic acid (LLA) have the same rate of appearance (R(a)) as PA and therefore contribute equally to oxidative and nonoxidative metabolism is unknown. We infused albumin-bound [U-13C]PA and [U-13C]LLA in seven critically ill infants (weight 3.6 \ub1 1.3 kg, age 57 \ub1 64 d) receiving 20.9 \ub1 5.4 kcal \ub7 kg-1 \ub7 d-1 of i.v. glucose only, and measured simultaneously the R(a) of PA and LLA from the isotopic enrichment of plasma FFA by mass spectrometry. A needle biopsy of the s.c. adipose tissue was obtained for FA composition. PA in adipose tissue was higher than LLA (40 \ub1 6.7 versus 5.4 \ub1 3.2 mol %, p < 0.001). The R(a) values of PA and LLA were 5.73 \ub1 2.79 and 1.34 \ub1 0.92 \u3bcmol \ub7 kg-1 \ub7 min-1, respectively (p = 0.005). However, the ratio of the FA's R(a) to their respective mol% values in adipose tissue was lower for PA than for LLA (0.15 \ub1 0.06 versus 0.25 \ub1 0.06, p = 0.02). The R(a) of LLA acid was higher than could be expected from the FA composition of adipose tissue, thus indicating a preferential release of LLA during lipolysis. In critically ill infants receiving only i.v. glucose, the contribution of LLA to the oxidative and nonoxidative metabolism may be larger than what assumed from the FA composition of plasma and adipose tissue

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys