Overall survival in low-comorbidity patients with stage I non-small cell lung cancer who chose stereotactic body radiotherapy compared to surgery.

OBJECTIVE: To evaluate trends in the utilization of stereotactic body radiotherapy (SBRT) and to compare overall survival (OS) of patients with early-stage non-small cell lung cancer (NSCLC) undergoing SBRT versus those undergoing surgery. METHODS: The National Cancer Database was queried for patients without documented comorbidities who underwent surgical resection (lobectomy, segmentectomy, or wedge resection) or SBRT for clinical stage I NSCLC between 2012 and 2018. Peritreatment mortality and 5-year OS were compared among propensity score-matched cohorts. RESULTS: A total of 30,658 patients were identified, including 24,729 (80.7%) who underwent surgery and 5929 (19.3%) treated with SBRT. Between 2012 and 2018, the proportion of patients receiving SBRT increased from 15.9% to 26.0% (P < .001). The 30-day mortality and 90-day mortality were higher among patients undergoing surgical resection versus those receiving SBRT (1.7% vs 0.3%, P < .001; 2.8% vs 1.7%, P < .001). In propensity score-matched patients, OS favored SBRT for the first several months, but this was reversed before 1 year and significantly favored surgical management in the long term (5-year OS, 71.0% vs 41.8%; P < .001). The propensity score-matched analysis was repeated to include only SBRT patients who had documented refusal of a recommended surgery, which again demonstrated superior 5-year OS with surgical management (71.4% vs 55.9%; P < .001). CONCLUSIONS: SBRT is being increasingly used to treat early-stage lung cancer in low-comorbidity patients. However, for patients who may be candidates for either treatment, the long-term OS favors surgical management.

Brief Report: Increasing Prevalence of Ground-Glass Nodules and Semisolid Lung Lesions on Outpatient Chest Computed Tomography Scans.

Introduction: The increased use of cross-sectional imaging frequently identifies a growing number of lung nodules that require follow-up imaging studies and physician consultations. We report here the frequency of finding a ground-glass nodule (GGN) or semisolid lung lesion (SSL) in the past decade within a large academic health system. Methods: A radiology system database review was performed on all outpatient adult chest computed tomography (CT) scans between 2013 and 2022. Radiology reports were searched for the terms "ground-glass nodule," "subsolid," and "semisolid" to identify reports with findings potentially concerning for an adenocarcinoma spectrum lesion. Results: A total of 175,715 chest CT scans were performed between 2013 and 2022, with a steadily increasing number every year from 10,817 in 2013 to 21,916 performed in the year 2022. Identification of GGN or SSL on any outpatient CT increased from 5.9% in 2013 to 9.2% in 2022, representing a total of 2019 GGN or SSL reported on CT scans in 2022. The percentage of CT scans with a GGN or SSL finding increased during the study period in men and women and across all age groups above 50 years old. Conclusions: The total number of CT scans performed and the percentage of chest CT scans with GGN or SSL has more than doubled between 2013 and 2022; currently, 9% of all chest CT scans report a GGN or SSL. Although not all GGN or SSL radiographic findings represent true adenocarcinoma spectrum lesions, they are a growing burden to patients and health systems, and better methods to risk stratify radiographic lesions are needed.

Comparing a Novel Hand-Held Device for Chest Tube Insertion to the Traditional Open Tube Thoracostomy for Simple Pneumothorax in a Porcine Model.

BACKGROUND: Tube thoracostomy is the most effective treatment for pneumothorax, and on the battlefield, is lifesaving. In combat, far-forward adoption of open thoracostomy has not been successful. Therefore, the ability to safely and reliably perform chest tube insertion in the far-forward combat theatre would be of significant value. The Reactor is a hand-held device for tube thoracostomy that has been validated for tension pneumothorax compared to needle decompression. Here we investigate whether the Reactor has potential for simple pneumothorax compared to open thoracostomy. Treatment of pneumothorax before tension physiology ensues is critical. METHODS: Simple pneumothoraces were created in 5 in-vivo swine models and confirmed with x-ray. Interventions were randomized to open technique (OT, n = 25) and Reactor (RT, n = 25). Post-procedure radiography was used to confirm tube placement and pneumothorax resolution. Video Assisted Thoracoscopic Surgery (VATS) was used to evaluate for iatrogenic injuries. 50 chest tubes were placed, with 25 per group. RESULTS: There were no statistical differences between the groups for insertion time, pneumothorax resolution, or estimated blood loss (p = .91 and .83). Injury rates between groups varied, with 28% (n = 7) in the Reactor group and 8% (n = 2) the control group (p = .06). The most common injury was violation of visceral pleura (10%, n = 5, both groups) and violation of the mediastinum (8%, n = 4, both groups). CONCLUSION: The Reactor device was equal compared to open thoracostomy for insertion time, pneumothorax resolution, and injury rates. The device required smaller incisions compared to tube thoracostomy and may be useful adjunct in simple pneumothorax management.

A guide for managing patients with stage I NSCLC: deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 1: a guide to decision-making.

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options (lobectomy, segmentectomy, wedge, Stereotactic Body Radiotherapy, thermal ablation), weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: Based on a systematic review from 2000-2021, evidence regarding relevant outcomes was assembled, with attention to aspects of applicability, uncertainty and effect modifiers. A framework was developed to present this information a format that enhances decision-making at the point of care for individual patients. Results: While patients often cross over several boundaries, the evidence fits into categories of healthy patients, compromised patients, and favorable tumors. In healthy patients with typical (i.e., solid spiculated) lung cancers, the impact on long-term outcomes is the major driver of treatment selection. This is only slightly ameliorated in older patients. In compromised patients increasing frailty accentuates short-term differences and diminishes long-term differences especially when considering non-surgical vs. surgical approaches; nuances of patient selection (technical treatment feasibility, anticipated risk of acute toxicity, delayed toxicity, and long-term outcomes) as well as patient values are increasingly influential. Favorable (less-aggressive) tumors generally have good long-term outcomes regardless of the treatment approach. Discussion: A framework is provided that organizes the evidence and identifies the major drivers of decision-making for an individual patient. This facilitates blending available evidence and clinical judgment in a flexible, nuanced manner that enhances individualized clinical care.

A guide for managing patients with stage I NSCLC: deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 2: systematic review of evidence regarding resection extent in generally healthy patients.

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options (lobectomy, segmentectomy, wedge, stereotactic body radiotherapy, thermal ablation), weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: A PubMed systematic review from 2000-2021 of outcomes after lobectomy, segmentectomy and wedge resection in generally healthy patients is the focus of this paper. Evidence was abstracted from randomized trials and non-randomized comparisons with at least some adjustment for confounders. The analysis involved careful assessment, including characteristics of patients, settings, residual confounding etc. to expose degrees of uncertainty and applicability to individual patients. Evidence is summarized that provides an at-a-glance overall impression as well as the ability to delve into layers of details of the patients, settings and treatments involved. Results: In healthy patients there is no short-term benefit to sublobar resection vs. lobectomy in randomized and non-randomized comparisons. A detriment in long-term outcomes is demonstrated by adjusted non-randomized comparisons, more marked for wedge than segmentectomy. Quality-of-life data is confounded by the use of video-assisted approaches; evidence suggests the approach has more impact than the resection extent. Differences in pulmonary function tests by resection extent are not clinically meaningful in healthy patients, especially for multi-segmentectomy vs. lobectomy. The margin distance is associated with the risk of recurrence. Conclusions: A systematic, comprehensive summary of evidence regarding resection extent in healthy patients with attention to aspects of applicability, uncertainty and effect modifiers provides a foundation on which to build a framework for individualized clinical decision-making.

A guide for managing patients with stage I NSCLC: deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 3: systematic review of evidence regarding surgery in compromised patients or specific tumors.

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options [lobectomy, segmentectomy, wedge, stereotactic body radiotherapy (SBRT), thermal ablation], weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: A PubMed systematic review from 2000-2021 of outcomes after lobectomy, segmentectomy and wedge resection in older patients, patients with limited pulmonary reserve and favorable tumors is the focus of this paper. Evidence was abstracted from randomized trials and non-randomized comparisons (NRCs) with adjustment for confounders. The analysis involved careful assessment, including characteristics of patients, settings, residual confounding etc. to expose degrees of uncertainty and applicability to individual patients. Evidence is summarized that provides an at-a-glance overall impression as well as the ability to delve into layers of details of the patients, settings and treatments involved. Results: In older patients, perioperative mortality is minimally altered by resection extent and only slightly affected by increasing age; sublobar resection may slightly decrease morbidity. Long-term outcomes are worse after lesser resection; the difference is slightly attenuated with increasing age. Reported short-term outcomes are quite acceptable in (selected) patients with severely limited pulmonary reserve, not clearly altered by resection extent but substantially improved by a minimally invasive approach. Quality-of-life (QOL) and impact on pulmonary function hasn't been well studied, but there appears to be little difference by resection extent in older or compromised patients. Patient selection is paramount but not well defined. Ground-glass and screen-detected tumors exhibit favorable long-term outcomes regardless of resection extent; however solid tumors <1 cm are not a reliably favorable group. Conclusions: A systematic, comprehensive summary of evidence regarding resection extent in compromised patients and favorable tumors with attention to aspects of applicability, uncertainty and effect modifiers provides a foundation for a framework for individualized decision-making.

A guide for managing patients with stage I NSCLC: deciding between lobectomy, segmentectomy, wedge, SBRT and ablation-part 4: systematic review of evidence involving SBRT and ablation.

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options [lobectomy, segmentectomy, wedge, stereotactic body radiotherapy (SBRT), thermal ablation], weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making. Methods: A PubMed systematic review from 2000-2021 of outcomes after SBRT or thermal ablation vs. resection is the focus of this paper. Evidence was abstracted from randomized trials and non-randomized comparisons with at least some adjustment for confounders. The analysis involved careful assessment, including characteristics of patients, settings, residual confounding etc. to expose degrees of uncertainty and applicability to individual patients. Evidence is summarized that provides an at-a-glance overall impression as well as the ability to delve into layers of details of the patients, settings and treatments involved. Results: Short-term outcomes are meaningfully better after SBRT than resection. SBRT doesn't affect quality-of-life (QOL), on average pulmonary function is not altered, but a minority of patients may experience gradual late toxicity. Adjusted non-randomized comparisons demonstrate a clinically relevant detriment in long-term outcomes after SBRT vs. surgery. The short-term benefits of SBRT over surgery are accentuated with increasing age and compromised patients, but the long-term detriment remains. Ablation is associated with a higher rate of complications than SBRT, but there is little intermediate-term impact on quality-of-life or pulmonary function tests. Adjusted comparisons show a meaningful detriment in long-term outcomes after ablation vs. surgery; there is less difference between ablation and SBRT. Conclusions: A systematic, comprehensive summary of evidence regarding Stereotactic Body Radiotherapy or thermal ablation vs. resection with attention to aspects of applicability, uncertainty and effect modifiers provides a foundation for a framework for individualized decision-making.

Surgical Management of Pneumothorax and Pleural Space Disease.

Pleural space diseases constitute a wide range of benign and malignant conditions, including pneumothorax, pleural effusion and empyema, chylothorax, pleural-based tumors, and mesothelioma. The focus of this article is the surgical management of the 2 most common pleural disorders seen in modern thoracic surgery practice: spontaneous pneumothorax and empyema.

Revisiting Indications for Brain Imaging During the Clinical Staging Evaluation of Lung Cancer.

Introduction: Available guidelines are inconsistent as to whether patients with newly diagnosed clinical stage II NSCLC should receive routine brain imaging. Methods: The National Cancer Database was queried for the prevalence of isolated brain metastases among patients with newly diagnosed NSCLC in 2016 and 2017. Patients with metastases in locations other than the brain were excluded. The prevalences were then stratified by clinical T and N classifications and further stratified into a summary stage, which was calculated based on T and N classifications. The summary stage represents the clinical stage that would have been available at the time of decision for brain imaging. Results: A total of 6,949 of 149,958 patients (4.6%) with clinical stages I, II, III, or brain-limited stage IV NSCLC had dissemination limited to the brain. As T and N stages increased, prevalence of brain metastases generally increased. Among patients with node-negative (N0) NSCLC, the prevalence of brain-only metastases increased from 1.2% in patients with T1a to 3.8% among patients with T4 (p < 0.001). Among patients with T1a, the prevalence of brain-only metastases increased from 1.2% for patients with N0 to 7.9% for patients with N3 (p < 0.001). The prevalence of brain-limited metastases generally increased with increasing summary stage. The prevalence of brain-only metastases among patients with stage IA was 1.7% whereas that among patients with stage IIIA was 6.7% (p < 0.001). Of note, the prevalence of brain-limited metastases was approximately 6% for both summary stages II and III. Conclusions: Considering the similarity in prevalence of isolated brain metastases and the potential hazards associated with brain imaging in early stage NSCLC, practitioners may consider a more liberal use of brain imaging when interpreting conflicting guidelines.

Navigating by Stars: Using CMS Star Ratings to Choose Hospitals for Complex Cancer Surgery.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) developed risk-adjusted "Star Ratings," which serve as a guide for patients to compare hospital quality (1 star = lowest, 5 stars = highest). Although star ratings are not based on surgical care, for many procedures, surgical outcomes are concordant with star ratings. In an effort to address variability in hospital mortality after complex cancer surgery, the use of CMS Star Ratings to identify the safest hospitals was evaluated. METHODS: Patients older than 65 years of age who underwent complex cancer surgery (lobectomy, colectomy, gastrectomy, esophagectomy, pancreaticoduodenectomy) were evaluated in CMS Medicare Provider Analysis and Review files (2013-2016). The impact of reassignment was modeled by applying adjusted mortality rates of patients treated at 5-star hospitals to those at 1-star hospitals (Peters-Belson method). RESULTS: There were 105 823 patients who underwent surgery at 3146 hospitals. The 90-day mortality decreased with increasing star rating (1 star = 10.4%, 95% confidence interval [CI] = 9.8% to 11.1%; and 5 stars = 6.4%, 95% CI = 6.0% to 6.8%). Reassignment of patients from 1-star to 5-star hospitals (7.8% of patients) was predicted to save 84 Medicare beneficiaries each year. This impact varied by procedure (colectomy = 47 lives per year; gastrectomy = 5 lives per year). Overall, 2189 patients would have to change hospitals each year to improve outcomes (26 patients moved to save 1 life). CONCLUSIONS: Mortality after complex cancer surgery is associated with CMS Star Rating. However, the use of CMS Star Ratings by patients to identify the safest hospitals for cancer surgery would be relatively inefficient and of only modest impact.

Approach to the Subsolid Nodule.

Most focal persistent ground glass nodules (GGNs) do not progress over 10 years. Research suggests that GGNs that do not progress, those that do, and solid lung cancers are fundamentally different diseases, although histologically they seem similar. Surveillance of GGNs to identify those that gradually progress is safe and does not risk losing a window. GGNs with 5 mm solid component or less than 10 mm consolidation (mediastinal and lung windows, respectively, on thin slice CT) are highly curable with resection. The optimal type of resection is unclear; sublobar resection is reasonable but an adequate margin is critically important.

Postischemic conditioning does not reduce muscle injury after tourniquet-induced ischemia-reperfusion injury in rats.

BACKGROUND: The widespread application of tourniquets has reduced battlefield mortality related to extremity exsanguinations. Tourniquet-induced ischemia-reperfusion injury (I/R) can contribute to muscle loss. Postischemic conditioning (PostC) confers protection against I/R in cardiac muscle and skeletal muscle flaps. The objective of this study was to determine the effect of PostC on extremity muscle viability in an established rat hindlimb tourniquet model. METHODS: Rats were randomly assigned to PostC-1, PostC-2, or no conditioning ischemic groups (n = 10 per group). Postischemic conditioning, performed immediately after tourniquet release, consisted of four 15-second cycles (PostC-1) or eight 15-second cycles (PostC-2) of alternating occlusion and perfusion of hindlimbs. Twenty-four hours later, muscles were excised. The primary end points were muscle edema and viability; secondary end points were histologic and markers of oxidative stress. RESULTS: Ischemia-reperfusion injury decreased viability in all tourniquet limbs, but viability was not improved in either PostC group. Likewise, I/R resulted in substantial muscle edema that was not reduced by PostC. The predominant histologic feature was necrosis, but no significant differences were found among groups. Markers of oxidative stress were increased similarly among groups after I/R, although myeloperoxidase activity was significantly increased only in the no conditioning ischemic group. A protective effect from PostC was not observed in our model suggesting that PostC was not effective in reducing I/R skeletal muscle injury or any benefits of PostC were not sustained for 24 hours when tissues were assessed. CONCLUSION: These negative findings are pertinent as the military investigates different strategies to extend the safe time for tourniquet application.

Transfusion for shock in US military war casualties with and without tourniquet use.

STUDY OBJECTIVE: We assess whether emergency tourniquet use for transfused war casualties admitted to military hospitals is associated with survival. METHODS: A retrospective review of trauma registry data was made of US casualties in Afghanistan and Iraq. Patients with major limb trauma, transfusion, and tourniquet use were compared with similar patients who did not receive tourniquet use. A propensity-matching analysis was performed by stratifying for injury type and severity by tourniquet-use status. Additionally, direct comparison without propensity matching was made between tourniquet use and no-tourniquet use groups. RESULTS: There were 720 casualties in the tourniquet use and 693 in the no-tourniquet use groups. Of the 1,413 casualties, 66% (928) also had nonextremity injury. Casualties with tourniquet use had worse signs of hemorrhagic shock (admission base deficit, admission hemoglobin, admission pulse, and transfusion units required) than those without. Survival rates were similar between the 2 groups (1% difference; 95% confidence interval -2.5% to 4.2%), but casualties who received tourniquets had worse shock and received more blood products. In propensity-matched casualties, survival rates were not different (2% difference; 95% confidence interval -6.7% to 2.7%) between the 2 groups. CONCLUSION: Tourniquet use was associated with worse shock and more transfusion requirements among hospital-admitted casualties, yet those who received tourniquets had survival rates similar to those of comparable, transfused casualties who did not receive tourniquets.

Poloxamer-188 reduces muscular edema after tourniquet-induced ischemia-reperfusion injury in rats.

BACKGROUND: Skeletal muscle injury can result in significant edema, which can in turn lead to the development of acute extremity compartment syndrome (CS). Poloxamer-188 (P-188), a multiblock copolymer surfactant, has been shown to decrease edema by sealing damaged membranes in a number of tissues after a variety of injury modalities. The objective is to determine whether the administration of P-188 significantly reduces skeletal muscle edema associated with ischemia/reperfusion injury (I-R). METHODS: Male Sprague-Dawley rats underwent 180 minutes of tourniquet-induced ischemia. Five minutes before tourniquet release, rats received either a bolus of (1) P-188 (150 mg/kg; P-188 group) or (2) vehicle (Vehicle group) via a jugular catheter (n=10 per group). After 240 minutes reperfusion, both groups received a second bolus of either P-188 (P-188) or vehicle (Vehicle) via a tail vein catheter. Sixteen hours later, rats were killed; muscle weights were determined, infarct size (2,3,5-triphenyltetrazolium chloride method), and blinded histologic analysis (hematoxylin and eosin) were performed on the gastrocnemius and tibialis anterior muscles, as well as indices of antioxidant status. RESULTS: P-188 resulted in significantly less edema (wet weight) and reduced an index of lipid peroxidation compared with Vehicle (p<0.05). Wet:dry weight ratios were less in the P-188 group (indicating less edema). Muscle viability as indicated by 2,3,5-triphenyltetrazolium chloride staining or routine histology did not reveal statistically significant differences between groups. CONCLUSION: P-188 significantly reduced ischemia-reperfusion-related muscle edema and lipid peroxidation but did not impact muscle viability. Excess edema can lead to acute extremity CS, which is associated with significant morbidity and mortality. P-188 may provide a potential adjunctive treatment for the reduction of CS.

Clinical application of an acellular biologic scaffold for surgical repair of a large, traumatic quadriceps femoris muscle defect.

Many battlefield injuries involve penetrating soft tissue trauma often accompanied by skeletal muscle defects, known as volumetric muscle loss. This article presents the first known case of a surgical technique involving an innovative tissue engineering approach for the repair of a large volumetric muscle loss. A 19-year-old Marine presented with large volumentric muscle loss of the right thigh as a result of an explosion. The patient reported muscle weakness with right knee extension, secondary to volumentric muscle loss, primarily involving the vastus medialis muscle. This persisted 3 years postinjury, despite extensive physical therapy. With all existing management options exhausted, restoration of a portion of the lost vastus medialis muscle was attempted by surgical implantation of a multi-layered scaffold composed of extracellular matrix derived from porcine intestinal submucossa. The patient had no complications, was discharged home on postoperative day 5, and resumed physical therapy after 4 weeks. Four months postoperatively, the patient demonstrated marked gains in isokinetic performance. Computer tomography indicated new tissue at the implant site. This approach offers a treatment option to a heretofore untreatable injury and will allow us to improve future surgical treatments for volumetric muscle loss.