Effect of histology on stereotactic body radiotherapy for non-small cell lung cancer oligometastatic pulmonary lesions

BACKGROUND: Stereotactic body radiotherapy (SBRT) is commonly used to provide targeted treatment to metastatic lung disease. Investigation is needed to understand the influence of histology on treatment outcomes. We report how tumor histology affects local control (LC) in a cohort of patients with non-small cell lung cancer (NSCLC) receiving SBRT for oligometastatic and recurrent pulmonary lesions. METHODS: Patients who received SBRT to recurrent or oligometastatic NSCLC pulmonary lesions from 2015-2019 at our institution were included in this retrospective cohort study. Minimum follow-up was 2 months. Kaplan-Meier (KM) analysis was performed to assess local progression-free survival (LPFS). Local failure cumulative incidence curves using death as a competing risk factor were also generated. RESULTS: A total of 147 treated lesions from 83 patients were included: 95 lesions from 51 patients with lung adenocarcinoma and 52 lesions from 32 patients with lung squamous cell carcinoma (SqCC). Median follow-up was 23 [interquartile range (IQR): 9.5-44.5] months for adenocarcinoma, and 11.5 (6-32.25) months for SqCC. Two-year LC was 89% for adenocarcinoma and 77% for SqCC (P=0.04). Median overall survival (OS) was 24.5 (10-46.25) months for adenocarcinoma and 14.5 (7.75-23.25) months for SqCC. Adenocarcinoma had improved LPFS over SqCC (P=0.014). SqCC was associated with increased local failure risk that approached statistical significance (P=0.061) with death as a competing risk. Overall toxicity incidence was 8.2% with no G3+ toxicities. CONCLUSIONS: For SBRT-treated oligometastatic or recurrent NSCLC pulmonary lesions, adenocarcinoma histology is associated with improved 2-year LC and LPFS compared to SqCC and reduced incidence of local recurrence (LR) with death as a competing risk

A single-institutional experience with low dose stereotactic body radiation therapy for liver metastases

AimThis study reports a single-institutional experience treating liver metastases with stereotactic body radiation therapy (SBRT).Materials and methods107 patients with 169 lesions were assessed to determine factors predictive for local control, radiographic response, and overall survival (OS). Machine learning techniques, univariate analysis, and the Kaplan-Meier method were utilized.ResultsPatients were treated with a relatively low median dose of 30 Gy in 3 fractions. Fractions were generally delivered once weekly. Median biologically effective dose (BED) was 60 Gy, and the median gross tumor volume (GTV) was 12.16 cc. Median follow-up was 7.36 months. 1-year local control was 75% via the Kaplan-Meier method. On follow-up imaging, 43%, 40%, and 17% of lesions were decreased, stable, and increased in size, respectively. 1-year OS was 46% and varied by primary tumor, with median OS of 34.3, 25.1, 12.5, and 4.6 months for ovarian, breast, colorectal, and lung primary tumors, respectively. Breast and ovarian primary patients had better OS (p

Development and validation of a unifying pre-treatment decision tool for intracranial and extracranial metastasis-directed radiotherapy

BackgroundThough metastasis-directed therapy (MDT) has the potential to improve overall survival (OS), appropriate patient selection remains challenging. We aimed to develop a model predictive of OS to refine patient selection for clinical trials and MDT.Patients and methodsWe assembled a multi-institutional cohort of patients treated with MDT (stereotactic body radiation therapy, radiosurgery, and whole brain radiation therapy). Candidate variables for recursive partitioning analysis were selected per prior studies: ECOG performance status, time from primary diagnosis, number of additional non-target organ systems involved (NOS), and intracranial metastases.ResultsA database of 1,362 patients was assembled with 424 intracranial, 352 lung, and 607 spinal treatments (n=1,383). Treatments were split into training (TC) (70%, n=968) and internal validation (IVC) (30%, n=415) cohorts. The TC had median ECOG of 0 (interquartile range [IQR]: 0-1), NOS of 1 (IQR: 0-1), and OS of 18 months (IQR: 7-35). The resulting model components and weights were: ECOG = 0, 1, and > 1 (0, 1, and 2); 0, 1, and > 1 NOS (0, 1, and 2); and intracranial target (2), with lower scores indicating more favorable OS. The model demonstrated high concordance in the TC (0.72) and IVC (0.72). The score also demonstrated high concordance for each target site (spine, brain, and lung).ConclusionThis pre-treatment decision tool represents a unifying model for both intracranial and extracranial disease and identifies patients with the longest survival after MDT who may benefit most from aggressive local therapy. Carefully selected patients may benefit from MDT even in the presence of intracranial disease, and this model may help guide patient selection for MDT

The zeta potential of normal and osteoporotic bone

Four questions motivated this work: (1) Is the zeta potential different comparing normal and osteoporotic bone? (2) Does the etiology producing osteoporosis affect zeta potential response? (3) Do zeta potential changes have physiologic significance? (4) Can a structural model be developed for the bone surface - bone fluid interface explaining changes in the zeta potential? Stress generated potentials are electrokinetic in origin and proportional to the zeta potential. However, little attention has been directed toward understanding the fiducial zeta potential state at the physiologic bone surface - bone fluid interface using stress generated potential and particle microelectrophoresis protocols. To obtain physiologic values of the zeta potential in bone, the measurement must be performed using Neuman\u27s fluid, which mimics bone extracellular fluid. Additionally, the zeta potential of bone is spatially heterogenous. The following models of osteoporosis were studied: aging, disuse, estrogen deficiency, calcium deficiency, etidronate treatment, and clinical osteopenia. Statistically significant zeta potential changes occurred when statistically significant changes were produced in bone mineral density. The cause of the observed osteoporosis affects the amplitude and sign of the zeta potential response. The positive hypothesis states that endogenous electrical fields have a physiologic role in the mechanism of bone remodeling. This field exhibits an amplitude dose-response relationship, and the zeta potential determines the amplitude of this field. An observation of no zeta potential change for all clinical factors causing osteoporosis would have argued against the hypothesis. However, statistically significant zeta potential changes were observed and are consistent with the hypothesis. Results from the osteoporotic models and from controlled variations in calcium, phosphate, and fluoride concentration in physiologic bone extracellular fluid were used to propose a structural model of the electrical double layer in bone. In this model, the zeta potential depends on the bone substrate proper (composed of collagen, mineral, and boundary regions), stationary layer (wherein ions, ionic complexes, and proteins are adsorbed), and bone extracellular fluid. The zeta potential of calcium-deficient hydroxyapatite was negative in Neuman\u27s fluid, and was consistent with this model. Eta potential differences between normal and osteoporotic bone indicate a subtle structural difference between normal and osteoporotic bone

Temporomandibular Joint Internal Derangement Score (TIDS): novel magnetic resonance imaging assessment score and its relation to invasive treatment in patients with clinical temporomandibular joint pathology

Purpose: A new magnetic resonance imaging (MRI) based scoring system for temporomandibular joint (TMJ) internal derangement was developed to predict disease severity and the likelihood of invasive treatment. Patients and methods: Reports and images from bilateral TMJ MRI studies of 100 consecutive patients with TMJ pain were retrospectively reviewed. A Temporomandibular Joint Internal Derangement Score (TIDS) score was composed of 6 MRI characteristics: joint effusion, disc displacement, disc nonrecapture, disc degenerative changes, abnormal condyle translation, and condyle arthritis. The primary endpoint was whether disease severity merited invasive treatment (arthrocentesis, arthroscopy, arthroplasty, or discectomy). Primary analyses were conducted as univariate regression, with the level of significance set at \u3c .05. Multivariate regression was also used to assess the impacts of each variable upon the need for invasive treatment. Results: Invasive treatment was performed in 29 patients and planned in an additional 9 patients. Patients with clinical bilateral pathology were no more likely to undergo invasive treatment than those with unilateral clinical pathology. Statistically significant correlations were found between bilateral invasive treatment and the presence of bilateral joint effusions (p = 0.0037) and disc displacement (p = 0.014), as well as with increasing values of right TIDS (p = 0.0015) and bilateral TIDS (p = 0.0090). Bilateral TIDS of greater than 6 was correlated with both bilateral invasive treatment (p = 0.0033) and with invasive treatment of any kind (p = 0.041). In each instance of TIDS \u3e 6, the patient demonstrated multiple signs of bilateral TMJ pathology. On multivariate regression, only disc recapture failed to trend towards statistical significance in both the six and twelve component regressions, which trended towards significance only in the twelve component analysis. Conclusion: A TIDS score was developed to serve as an adjunct to the clinical assessment of TMJ pathology. Bilateral TIDS score greater than 6 was statistically significantly correlated with the severity of TMJ pathology

Symptomatic cholelithiasis in an ectopic retrocolic retroduodenal subhepatic duplicated gallbladder

Gallbladder duplication is a rare anatomic variant of biliary anatomy, which can present diagnostic and treatment challenges. In this case, a 49-year-old male presented with classic symptoms of biliary colic to his primary care physician, and while computed tomography (CT) noted the presence of gallstones, neither CT nor ultrasound was able to locate a gallbladder within the gallbladder fossa. Initial surgery found and cauterized a rudimentary gallbladder, but symptoms persisted, requiring a second surgery and secondary analysis of CT, ultrasound, and magnetic resonance imaging with magnetic resonance cholangiopancreatography. Imaging helped clarify the diagnosis of gallbladder duplication (ductular type), where the first gallbladder\u27s cystic duct inserted high on the common hepatic duct, and the second retroplaced gallbladder\u27s cystic duct inserted into the midportion of the common bile duct. Thorough understanding of the numerous gallbladder duplication variants, careful interpretation of modern imaging, and close collaboration between surgeon and radiologist are essential for optimal management of patients with gallbladder duplications

Particle Therapy for Breast Cancer

Particle therapy has received increasing attention in the treatment of breast cancer due to its unique physical properties that may enhance patient quality of life and reduce the late effects of therapy. In this review, we will examine the rationale for the use of proton and carbon therapy in the treatment of breast cancer and highlight their potential for sparing normal tissue injury. We will discuss the early dosimetric and clinical studies that have been pursued to date in this domain before focusing on the remaining open questions limiting the widespread adoption of particle therapy

Preliminary toxicity results using partial breast 3D-CRT with once daily hypo-fractionation and deep inspiratory breath hold

Abstract Background To evaluate the clinical outcomes of patients treated with 3D conformal Hypo-fractionated, deep Inspiratory breath-hold (DIBH), Partial breast radiotherapy, termed “HIP.” HIP was implemented to merge the schedule of once-daily breast hypofractionation with partial breast treatment. Methods We identified 38 breast cancers in 37 patients from 2013 to 2014 treated at our institution with HIP following lumpectomy for early stage breast cancer. Patients received a hypo-fractionated course (≤ 20 fractions) of once daily radiation to the partial breast (lumpectomy cavity + margin) utilizing DIBH regardless of laterality. Clinical and treatment-related characteristics were obtained, including target volume and organ at risk (OAR) dosimetric characteristics. Patients were followed clinically and with at least yearly mammograms for up to 36 months (range 5–36 months). Acute and late toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Results Patients received a median dose of 42.56 Gy in 16 Fractions (Fx) (range 40.05–53.2 Gy; and 15–20 Fx). OAR doses were low, with a mean heart dose of 0.37 Gy, an ipsilateral lung V20 mean of 4%, and a contralateral lung V5 of 1%. Acute toxicity (≤ grade 2) was present in 79% (n = 30) of the cases, with dermatitis being the most common finding (63%). Late grade 1–2 toxicity was present in 42% (n = 16) of the cases, with hyperpigmentation being the most common finding (n = 9). There were no severe acute or late toxicities (≥ grade 3). At a median follow up of 21 months, there were no local, regional, or distant failures. Conclusions We report limited toxicity in this low risk cohort of patients with early stage breast cancer treated with HIP, a unique and logical combination of 3-D conformal external beam radiotherapy, moderate hypo-fractionation, and DIBH

Association of Heterozygous Hemochromatosis C282Y Gene Mutation with Hand Osteoarthritis.

OBJECTIVE: To determine if there is an association between radiographic osteoarthritis (OA) of the hand and the presence of hemochromatosis HFE gene mutations. METHODS: One hundred seventy-six patients with radiographic OA of the hand were randomly selected from an academic rheumatology practice. We measured serum transferrin saturation (TS) and ferritin levels, and genotyped for the presence of the 2 common HFE mutations, C282Y and H63D. The prevalences of HFE mutations in these patients were compared to those in a hemochromatosis screening study from the same primary care patient base. RESULTS: There was a significantly increased prevalence of the C282Y mutation in the OA population compared to the unselected controls (12.5 vs 7.8%; p = 0.029). The prevalence of C282Y in OA was higher among older patients: 15.75% in the group older than 65 years versus 4.08% in the younger group. The mean TS level was higher among OA patients who were heterozygous for C282Y compared to those who lacked both HFE mutations (35.75 vs 25.93%; p \u3c 0.0001). This difference was also found in the general population. CONCLUSION: This is the first report to show an increased risk of OA among individuals who are heterozygous for the C282Y HFE mutation. The increase in this mutation in patients older than 65 suggests that this is associated with a late onset subset of OA. If this association is substantiated by larger randomized controlled studies, it could have major therapeutic implications in the development of specific therapy directed at individuals heterozygous for C282Y HFE mutation