Local Cancer Recurrence: The Realities, Challenges, and Opportunities for New Therapies.

Locoregional recurrence negatively impacts both long-term survival and quality of life for several malignancies. For appropriate-risk patients with an isolated, resectable, local recurrence, surgery represents the only potentially curative therapy. However, oncologic outcomes remain inferior for patients with locally recurrent disease even after macroscopically complete resection. Unfortunately, these operations are often extensive, with significant perioperative morbidity and mortality. This review highlights selected malignancies (mesothelioma, sarcoma, lung cancer, breast cancer, rectal cancer, and peritoneal surface malignancies) in which surgical resection is a key treatment modality and local recurrence plays a significant role in overall oncologic outcome with regard to survival and quality of life. For each type of cancer, the current, state-of-the-art treatment strategies and their outcomes are assessed. The need for additional therapeutic options is presented given the limitations of the current standard therapies. New and emerging treatment modalities, including polymer films and nanoparticles, are highlighted as potential future solutions for both prevention and treatment of locally recurrent cancers. Finally, the authors identify additional clinical and research opportunities and propose future research strategies based on the various patterns of local recurrence among the different cancers.

A Pilot Study Using Machine Learning Algorithms and Wearable Technology for the Early Detection of Postoperative Complications After Cardiothoracic Surgery.

OBJECTIVE: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS: This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90-days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS: A total of 56 patients undergoing cardiothoracic surgery met inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (IQR: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events a median of 2 (IQR: 1-3) days prior to symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS: Machine learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-prior to symptom onset-after cardiothoracic surgery.

Multimodality Management of Thoracic Tumors: Initial Experience With a Multidisciplinary Thoracic Ablation Conference.

BACKGROUND: This study aimed to describe lesion-specific management of thoracic tumors referred for consideration of image-guided thermal ablation (IGTA) at a newly established multidisciplinary ablation conference. METHODS: This retrospective single-center cohort study included consecutive patients with non-small cell lung cancer (NSCLC) or thoracic metastases evaluated from June 2020 to January 2022 in a multidisciplinary conference. Outcomes included the management recommendation, treatments received (IGTA, surgical resection, stereotactic body radiation therapy [SBRT], multimodality management), and number of tumors treated per patient. Pearson's chi-square test was used to assess for a change in management, and Poisson regression was used to compare the number of tumors by treatment received. RESULTS: The study included 172 patients (58 % female; median age, 69 years; 56 % thoracic metastases; 27 % multifocal primary lung cancer; 59 % ECOG 0 [range, 0-3]) assessed in 206 evaluations. For the patients with NSCLC, IGTA was considered the most appropriate local therapy in 12 %, equal to SBRT in 22 %, and equal to lung resection in 3 % of evaluations. For the patients with thoracic metastases, IGTA was considered the most appropriate local therapy in 22 %, equal to SBRT in 12 %, and equal to lung resection in 3 % of evaluations. Although all patients were referred for consideration of IGTA, less than one third of patients with NSCLC or thoracic metastases underwent IGTA (p < 0.001). Multimodality management allowed for treatment of more tumors per patient than single-modality management (p < 0.01). CONCLUSIONS: Multidisciplinary evaluation of patients with thoracic tumors referred for consideration of IGTA significantly changed patient management and facilitated lesion-specific multimodality management.

Drug Delivery Opportunities in Esophageal Cancer: Current Treatments and Future Prospects.

With one of the highest mortality rates of all malignancies, the 5-year survival rate for esophageal cancer is under 20%. Depending on the stage and extent of the disease, the current standard of care treatment paradigm includes chemotherapy or chemoradiotherapy followed by surgical esophagogastrectomy, with consideration for adjuvant immunotherapy for residual disease. This regimen has high morbidity, due to anatomic changes inherent in surgery, the acuity of surgical complications, and off-target effects of systemic chemotherapy and immunotherapy. We begin with a review of current treatments, then discuss new and emerging targets for therapies and advanced drug delivery systems. Recent and ongoing preclinical and early clinical studies are evaluating traditional tumor targets (e.g., human epidermal growth factor receptor 2), as well as promising new targets such as Yes-associated protein 1 or mammalian target of rapamycin to develop new treatments for this disease. Due the function and location of the esophagus, opportunities also exist to pair these treatments with a drug delivery strategy to increase tumor targeting, bioavailability, and intratumor concentrations, with the two most common delivery platforms being stents and nanoparticles. Finally, early results with antibody drug conjugates and chimeric antigenic receptor T cells show promise as upcoming therapies. This review discusses these innovations in therapeutics and drug delivery in the context of their successes and failures, with the goal of identifying those solutions that demonstrate the most promise to shift the paradigm in treating this deadly disease.

Decreased Lung Metastasis in Triple Negative Breast Cancer Following Locally Delivered Supratherapeutic Paclitaxel-Loaded Polyglycerol Carbonate Nanoparticle Therapy.

Breast cancer is among the most prevalent malignancies, accounting for 685,000 deaths worldwide in 2020, largely due to its high metastatic potential. Depending on the stage and tumor characteristics, treatment involves surgery, chemotherapy, targeted biologics, and/or radiation therapy. However, current treatments are insufficient for treating or preventing metastatic disease. Herein, we describe supratherapeutic paclitaxel-loaded nanoparticles (81 wt % paclitaxel) to treat the primary tumor and reduce the risk of subsequent metastatic lesions in the lungs. Primary tumor volume and lung metastasis are reduced by day 30, compared to the paclitaxel clinical standard treatment. The ultrahigh levels of paclitaxel afford an immunotherapeutic effect, increasing natural killer cell activation and decreasing NETosis in the lung, which limits the formation of metastatic lesions.

Synthetic Pressure Sensitive Adhesives for Biomedical Applications.

Pressure sensitive adhesives are components of everyday products found in homes, offices, industries, and hospitals. Serving the general purpose of fissure repair and object fixation, pressure sensitive adhesives indiscriminately bind surfaces, as long as contact pressure is administered at application. With that being said, the chemical and material properties of the adhesive formulation define the strength of a pressure sensitive adhesive to a particular surface. Given our increased understanding of the viscoelastic material requirements as well as the intermolecular interactions at the binding interface required for functional adhesives, pressure sensitive adhesives are now being explored for greater use. New polymer formulations impart functionality and degradability for both internal and external applications. This review highlights the structure-property relationships between polymer architecture and pressure sensitive adhesion, specifically for medicine. We discuss the rational, molecular-level design of synthetic polymers for durable, removable, and biocompatible adhesion to wet surfaces like tissue. Finally, we examine prevalent challenges in biomedical wound closure and the new, innovative strategies being employed to address them. We conclude by summarizing the progress of current research, identifying additional clinical opportunities, and discussing future prospects.

First-in-Human Intrathoracic Implantation of Multidrug-Eluting Microdevices for In Situ Chemotherapeutic Sensitivity Testing as Proof of Concept in Nonsmall Cell Lung Cancer.

OBJECTIVE: To evaluate the safety and feasibility of implantation and retrieval of a novel implantable microdevice (IMD) in NSCLC patients undergoing operative resection. BACKGROUND: Adjuvant therapy has limited impact on postsurgical outcomes in NSCLC due to the inability to predict optimal treatment regimens. METHODS: An IMD measuring 6.5 mm by 0.7 mm, containing micro-reservoirs allowing for high-throughput localized drug delivery, was developed and loaded with 12 chemotherapeutic agents. Five patients with peripheral lung lesions larger than 1.0 cm were enrolled in this phase 1 clinical study. IMDs were inserted into tumors intraoperatively under direct vision, removed with the resected specimen, and retrieved in pathology. Surrounding tissues were sectioned, stained, and analyzed for tissue drug response to the IMD-delivered microdoses of these agents by a variety of pharmacodynamic markers. RESULTS: A total of 14 IMDs were implanted intraoperatively with 13 (93%) successfully retrieved. After technique refinement, IMDs were reliably inserted and retrieved in open, Video-Assisted Thoracoscopic Surgery, and robotic cases. No severe adverse reactions were observed. The one retained IMD has remained in place without movement or any adverse effects. Analysis of patient blood revealed no detection of chemotherapeutic agents. We observed differential sensitivities of patient tumors to the drugs on the IMD. CONCLUSIONS: A multi-drug IMD can be safely inserted and retrieved into lung tumors during a variety of surgical approaches. Future studies will encompass preoperative placement to better examine specific tumor responsiveness to therapeutic agents, allowing clinicians to tailor treatment regimens to the microenvironment of each patient.

Efficacy and Safety of Supraclavicular Thoracic Outlet Decompression.

OBJECTIVES: We aimed to report efficacy, safety, and health-related quality of life (HRQoL) outcomes of a multidisciplinary treatment approach including supraclavicular thoracic outlet decompression among patients with thoracic outlet syndrome (TOS). BACKGROUND: TOS is a challenging condition where controversy remains in diagnosis and treatment, primarily given a lack of data exploring various treatment approaches and associated patient outcomes. METHODS: Patients who underwent unilateral, supraclavicular thoracic outlet decompression, or pectoralis minor tenotomy for neurogenic, venous, or arterial TOS were identified from a prospectively maintained database. Demography, use of preoperative botulinum toxin injection, and participation in multidisciplinary evaluation were measured. The primary endpoints were composite postoperative morbidity and symptomatic improvement compared with baseline. RESULTS: Among 2869 patients evaluated (2007-2021), 1032 underwent surgery, including 864 (83.7%) supraclavicular decompressions and 168 (16.3%) isolated pectoralis minor tenotomies. Predominant TOS subtypes among surgical patients were neurogenic (75.4%) and venous TOS (23.4%). Most patients (92.9%) with nTOS underwent preoperative botulinum toxin injection; 56.3% reported symptomatic improvement. Before surgical consultation, few patients reported participation in physical therapy (10.9%). The median time from first evaluation to surgery was 136 days (interquartile range: 55, 258). Among 864 patients who underwent supraclavicular thoracic outlet decompression, complications occurred in 19.8%; the most common complication was chyle leak (8.3%). Four patients (0.4%) required revisional thoracic outlet decompression. At a median follow-up of 420 days (interquartile range: 150, 937) 93.3% reported symptomatic improvement. CONCLUSION: Based on low composite morbidity, need for very few revisional operations, and high rates of symptomatic improvement, a multidisciplinary treatment approach including primarily supraclavicular thoracic outlet decompression is safe and effective for patients with TOS.

The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II-III and metastatic breast cancers.

PURPOSE: The antigenic targets of immunity and the role of vaccination in breast cancer are unknown. We performed a phase I study of an autologous GM-CSF-secreting breast cancer vaccine in patients with metastatic and stage II-III breast cancer. METHODS: Tumor cells from patients with metastatic (n = 15) and stage II-III (n = 7) disease were transduced with a replication-defective adenoviral vector encoding GM-CSF, and then irradiated. Twelve and seven patients with metastatic and stage II-III disease, respectively, received weekly vaccination for three weeks, followed by every other week until disease progression or vaccine supply was exhausted (metastatic) or until six total vaccine doses were administered (stage II-III). RESULTS: Among those patients with metastatic disease who received vaccinations, eight had progressive disease at two months, three had stable disease for 4-13 months, and one has had no evidence of disease for 13 years. Of the patients with stage II-III disease, five died of metastatic disease between 1.16 and 8.49 years after the start of vaccinations (median 6.24 years) and two are alive as of September 2021. Toxicities included injection site reactions, fatigue, fever, upper respiratory symptoms, joint pain, nausea, and edema. Four of five evaluable patients with metastatic disease developed a skin reaction with immune cell infiltration after the fifth injection of unmodified, irradiated tumor cells. CONCLUSION: We conclude that tumor cells can be harvested from patients with metastatic or stage II-III breast cancer to prepare autologous GM-CSF-secreting vaccines that induce coordinated immune responses with limited toxicity. TRIAL REGISTRATION AND DATE OF REGISTRATION: clinicaltrials.gov, NCT00317603 (April 25, 2006) and NCT00880464 (April 13, 2009).

Added Value of Magnetic Resonance Over Computed Tomography in Distinguishing Nonneoplastic Complex Thymic Cysts From Malignant Cystic Thymic Neoplasms.

PURPOSE: The aim of the study was to evaluate cystic thymic masses by using computed tomography (CT) and magnetic resonance (MR) scoring systems to differentiate nonneoplastic thymic cysts from cystic thymic neoplasms. METHODS: This retrospective multisite study included adult patients who underwent CT and MR imaging of the chest between 2007 and 2020 with any of the following impressions on cross-sectional imaging studies: "thymic mass with cystic component," "unilocular or multilocular cystic thymic lesion," "complex thymic cyst," "thymic cyst with hemorrhage." Two blinded radiologists reviewed and recorded specific imaging features as well as overall impressions on both CT and MR using a Likert scale scoring system. Data were analyzed, and diagnostic accuracy of CT and MR was compared using areas under the receiver operating characteristic curves (AUC). RESULTS: Fifty-six patients were included, of which 45 (80%) had benign masses. Total of 21 patients (38%) had indeterminate scores on CT of which 3 (14%) were malignant, while only 6 (11%) had indeterminate scores on MR and 1 was malignant. Magnetic resonance scoring system (AUC, 0.95) performed better than CT scoring system (AUC, 0.86) in distinguishing benign versus malignant lesions (P = 0.06). Lack of enhancement within the mass was completely predictive of benign etiology (P < 0.001). Wall thickness of an enhancing cyst was predictive of malignancy, with AUC 0.93. CONCLUSIONS: Magnetic resonance yielded higher specificity allowing a larger number of lesions to be confidently assigned a benign diagnosis. This could help in averting unnecessary follow-up, biopsies, or surgery. The authors recommend follow-up imaging with MR for prevascular masses, even those appearing "solid" on CT.

Estimating the Impact of Extended Delay to Surgery for Stage I Non-small-cell Lung Cancer on Survival.

OBJECTIVE: The purpose of this study is to evaluate the impact of extended delay to surgery for stage I NSCLC. SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, patients with NSCLC may experience delays in care, and some national guidelines recommend delays in surgery by >3 months for early NSCLC. METHODS: Using data from the National Lung Screening Trial, a multi-center randomized trial, and the National Cancer Data Base, a multi-institutional oncology registry, the impact of "early" versus "delayed" surgery (surgery received 0-30 vs 90-120 days after diagnosis) for stage I lung adenocarcinoma and squamous cell carcinoma (SCC) was assessed using multivariable Cox regression analysis with penalized smoothing spline functions and propensity score-matched analyses. RESULTS: In Cox regression analysis of the National Lung Screening Trial (n = 452) and National Cancer Data Base (n = 80,086) cohorts, an increase in the hazard ratio was seen the longer surgery was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed surgery for stage IA1 adenocarcinoma and IA1-IA3 SCC (all P > 0.13). For stage IA2-IB adenocarcinoma and IB SCC, delayed surgery was associated with worse survival (all P < 0.004). CONCLUSIONS: The mortality risk associated with an extended delay to surgery differs across patient subgroups, and difficult decisions to delay care during the COVID-19 pandemic should take substage and histologic subtype into consideration.

Finding the "True" N0 Cohort: Technical Aspects of Near-infrared Sentinel Lymph Node Mapping in Non-small Cell Lung Cancer.

OBJECTIVE: To examine technical-, patient-, tumor-, and treatment-related factors associated with NIR guided SLN identification. BACKGROUND: Missed nodal disease correlates with recurrence in early stage NSCLC. NIR-guided SLN mapping may improve staging and outcomes through identification of occult nodal disease. METHODS: Retrospective analysis of 2 phase I clinical trials investigating NIR-guided SLN mapping utilizing ICG in patients with surgically resectable NSCLC. RESULTS: In total, 66 patients underwent NIR-guided SLN mapping and lymphadenectomy after peritumoral ICG injection. There was significantly increased likelihood of SLN identification with injection dose ≥1 mg compared to <1 mg (65.2% vs 35.0%, P = 0.05), lung ventilation after injection (65.2% vs 35.0%, P = 0.05), and albumin dissolvent (68.1%) compared to fresh frozen plasma (28.6%) and sterile water (20.0%) (P = 0.01). In patients receiving the optimized ICG injection, there was significantly increased likelihood of SLN identification with radiologically solid nodules compared to sub-solid nodules (77.4% vs 33.3%, P = 0.04) and anatomic resection compared to wedge resection (88.2% vs 52.2%, P = 0.04). Disease-free and overall survival are 100% in those with a histologically negative SLN identified (n = 25) compared to 73.6% (P = 0.02) and 63.6% (P = 0.01) in patients with node negative NSCLC established via routine lymphadenectomy alone (n = 22). CONCLUSIONS: SLN(s) are more reliably identified with ICG dose ≥1 mg, albumin dissolvent, post-injection lung ventilation, radiologically solid nodules, and anatomic resections. To date, N0 status when established via NIR SLN mapping seems to be associated with decreased recurrence and improved survival after surgery for NSCLC.

Expansile Nanoparticles Encapsulate Factor Quinolinone Inhibitor 1 and Accumulate in Murine Liver upon Intravenous Administration.

Expansile nanoparticles (eNPs) are a promising pH-responsive polymeric drug delivery vehicle, as demonstrated in multiple intraperitoneal cancer models. However, previous delivery routes were limited to intraperitoneal injection and to a single agent, paclitaxel. In this study, we preliminarily evaluate the biodistribution and in vivo toxicity of eNPs in mice after intravenous injection. The eNPs localize predominantly to the liver, without detectable acute toxicity in the liver or other key organs. On the basis of these results, we encapsulated FQI1, a promising lead compound for treatment of hepatocellular carcinoma, in eNPs. eNPs are taken up by cancerous and noncancerous human liver cells in vitro, although at different rates. FQI1-loaded eNPs release FQI1 in a pH-dependent manner and limit proliferation equivalently to unencapsulated FQI1 in immortalized hepatocytes in vitro. eNPs are a versatile platform delivery system for therapeutic compounds and have potential utility in the treatment of liver disease.

Overuse of Diagnostic Brain Imaging Among Patients With Stage IA Non-Small Cell Lung Cancer.

BACKGROUND: Among patients diagnosed with stage IA non-small cell lung cancer (NSCLC), the incidence of occult brain metastasis is low, and several professional societies recommend against brain imaging for staging purposes. The goal of this study was to characterize the use of brain imaging among Medicare patients diagnosed with stage IA NSCLC. METHODS: Using data from linked SEER-Medicare claims, we identified patients diagnosed with AJCC 8th edition stage IA NSCLC in 2004 through 2013. Patients were classified as having received brain imaging if they underwent head CT or brain MRI from 1 month before to 3 months after diagnosis. We identified factors associated with receipt of brain imaging using multivariable logistic regression. RESULTS: Among 13,809 patients with stage IA NSCLC, 3,417 (25%) underwent brain imaging at time of diagnosis. The rate of brain imaging increased over time, from 23.5% in 2004 to 28.7% in 2013 (P=.0006). There was significant variation in the use of brain imaging across hospital service areas, with rates ranging from 0% to 64.0%. Factors associated with a greater likelihood of brain imaging included older age (odds ratios [ORs] of 1.16 for 70-74 years, 1.13 for 75-79 years, 1.31 for 80-84 years, and 1.46 for ≥85 years compared with 65-69 years; all P<.05), female sex (OR, 1.09; P<.05), black race (OR 1.23; P<.05), larger tumor size (ORs of 1.23 for 11-20 mm and 1.28 for 21-30 mm tumors vs 1-10 mm tumors; all P<.05), and higher modified Charlson-Deyo comorbidity score (OR, 1.28 for score >1 vs score of 0; P<.05). CONCLUSIONS: Roughly 1 in 4 patients with stage IA NSCLC received brain imaging at the time of diagnosis despite national recommendations against the practice. Although several patient factors are associated with receipt of brain imaging, there is significant geographic variation across the United States. Closer adherence to clinical guidelines is likely to result in more cost-effective care.

Feasibility and acceptability of "healthy directions" a lifestyle intervention for adults with lung cancer.

OBJECTIVE: The aims of this feasibility study of an adapted lifestyle intervention for adults with lung cancer were to (1) determine rates of enrollment, attrition, and completion of 5 nurse-patient contacts; (2) examine demographic characteristics of those more likely to enroll into the program; (3) determine acceptability of the intervention; and (4) identify patient preferences for the format of supplemental educational intervention materials. METHODS: This study used a single-arm, pretest and posttest design. Feasibility was defined as ≥20% enrollment and a completion rate of 70% for 5 nurse-patient contact sessions. Acceptability was defined as 80% of patients recommending the program to others. Data was collected through electronic data bases and phone interviews. Descriptive statistics, Fisher's exact test and Wilcoxon rank sum test were used for analyses. RESULTS: Of 147 eligible patients, 42 (28.6%) enrolled and of these, 32 (76.2%) started the intervention and 27 (N = 27/32; 84.4%; 95% CI, 67.2%-94.7%) completed the intervention. Patients who were younger were more likely to enroll in the study (P = .04) whereas there were no significant differences by gender (P = .35). Twenty-three of the 24 (95.8%) participants' contacted posttest recommended the intervention for others. Nearly equal numbers of participants chose the website (n = 16, 50%) vs print (n = 14, 44%). CONCLUSION: The intervention was feasible and acceptable in patients with lung cancer. Recruitment rates were higher and completion rates were similar as compared to previous home-based lifestyle interventions for patients with other types of cancer. Strategies to enhance recruitment of older adults are important for future research.

Stretch-Induced Drug Delivery from Superhydrophobic Polymer Composites: Use of Crack Propagation Failure Modes for Controlling Release Rates.

The concept of using crack propagation in polymeric materials to control drug release and its first demonstration are reported. The composite drug delivery system consists of highly-textured superhydrophobic electrosprayed microparticle coatings, composed of biodegradable and biocompatible polymers poly(caprolactone) and poly(glycerol monostearate carbonate-co-caprolactone), and a cellulose/polyester core. The release of entrapped agents is controlled by the magnitude of applied strain, resulting in a graded response from water infiltration through the propagating patterned cracks in the coating. Strain-dependent delivery of the anticancer agents cisplatin and 7-ethyl-10-hydroxycamptothecin to esophageal cancer cells (OE33) in vitro is observed. Finally the device is integrated with an esophageal stent to demonstrate delivery of fluorescein diacetate, using applied tension, to an ex vivo esophagus.

Synthesis and Characterization of Hybrid Polymer/Lipid Expansile Nanoparticles: Imparting Surface Functionality for Targeting and Stability.

The size, drug loading, drug release kinetics, localization, biodistribution, and stability of a given polymeric nanoparticle (NP) system depend on the composition of the NP core as well as its surface properties. In this study, novel, pH-responsive, and lipid-coated NPs, which expand in size from a diameter of approximately 100 to 1000 nm in the presence of a mildly acidic pH environment, are synthesized and characterized. Specifically, a combined miniemulsion and free-radical polymerization method is used to prepare the NPs in the presence of PEGylated lipids. These PEGylated-lipid expansile NPs (PEG-L-eNPs) combine the swelling behavior of the polymeric core of expansile NPs with the improved colloidal stability and surface functionality of PEGylated liposomes. The surface functionality of PEG-L-eNPs allows for the incorporation of folic acid (FA) and folate receptor-targeting. The resulting hybrid polymer/lipid nanocarriers, FA-PEG-L-eNPs, exhibit greater in vitro uptake and potency when loaded with paclitaxel compared to nontargeted PEG-L-eNPs.

Image-guided video assisted thoracoscopic surgery (iVATS) - phase I-II clinical trial.

PURPOSE: To facilitate localization and resection of small lung nodules, we developed a prospective clinical trial (ClinicalTrials.gov number NCT01847209) for a novel surgical approach which combines placement of fiducials using intra-operative C-arm computed tomography (CT) guidance with standard thoracoscopic resection technique using image-guided video-assisted thoracoscopic surgery (iVATS). METHODS: Pretrial training was performed in a porcine model using C-arm CT and needle guidance software. Methodology and workflow for iVATS was developed, and a multi-modality team was trained. A prospective phase I-II clinical trial was initiated with the goal of recruiting eligible patients with small peripheral pulmonary nodules. Intra-operative C-arm CT scan was utilized for guidance of percutaneous marking with two T-bars (Kimberly-Clark, Roswell, GA) followed by VATS resection of the tumor. RESULTS: Twenty-five patients were enrolled; 23 underwent iVATS, one withdrew, and one lesion resolved. Size of lesions were: 0.6-1.8 cm, mean = 1.3 ± 0.38 cm.. All 23 patients underwent complete resection of their lesions. CT imaging of the resected specimens confirmed the removal of the T-bars and the nodule. Average and total procedure radiation dose was in the acceptable low range (median = 1501 µGy*m(2), range 665-16,326). There were no deaths, and all patients were discharged from the hospital (median length of stay = 4 days, range 2-12). Three patients had postoperative complications: one prolonged air-leak, one pneumonia, and one ileus. CONCLUSIONS: A successful and safe step-wise process has been established for iVATS, combining intra-operative C-arm CT scanning and thoracoscopic surgery in a hybrid operating room.