Characterizing a learning curve for robotic-assisted bronchoscopy: Analysis of skills acquisition in a high-volume academic center.

OBJECTIVE: Shape-sensing robotic-assisted bronchoscopy is an emerging technology for the sampling of pulmonary lesions. We seek to characterize the shape-sensing robotic-assisted bronchoscopy learning curve at an academic center. METHODS: Shape-sensing robotic-assisted bronchoscopy procedures performed by 9 proceduralists at a single institution were analyzed. Cumulative sum analyses were performed to examine diagnostic sampling and procedure time over each operator's first 50 cases, with the acceptable yield threshold set to 73%. RESULTS: During the study period, 442 patients underwent sampling of 551 lesions. Each operator sampled 61 lesions (interquartile range, 60-63 lesions). Lesion size was 1.90 cm (interquartile range, 1.33-2.80 cm). The median procedure time for single-target cases decreased from 62 minutes during the first 10 cases to 39 minutes after case 40 (P < .001). The overall diagnostic yield was 72% (range, 58%-83%). Six of 9 operators achieved proficiency over the study period. An aggregated cumulative sum analysis of those who achieved competency demonstrated a steep improvement between lesions 1 and 21 and crossing of the competency threshold by lesion 25. Temporal analysis of yield-related lesion characteristics demonstrated that at approximately lesion 20, more challenging lesions were increasingly targeted, as evidenced by smaller target size, higher rates of unfavorable radial endobronchial ultrasound views, and a negative bronchus sign. CONCLUSIONS: Skills acquisition in shape-sensing robotic-assisted bronchoscopy is variable. Approximately half of proceduralists become facile with the technology within 25 lesions. After the initial learning phase, operators increasingly target lesions with more challenging features. Overall, these findings can inform certification and competency standards and provide new users with expectations related to performance over time.

The Third-Time Recurrence of a Thoracic Solitary Fibrous Tumor in a Patient Presenting With Paraneoplastic Hypoinsulinemic Hypoglycemia (Doege-Potter Syndrome).

We present a case of a 76-year-old Caucasian female with a recurrent solitary fibrous tumor (SFT) of the pleura, showcasing a rare manifestation of hypoglycemia associated with Doege-Potter syndrome (DPS). Having undergone two previous surgeries for SFT, the patient presented to the emergency department with severe fatigue, recurrent episodes of loss of consciousness, and hypoglycemia, despite lacking a history of diabetes mellitus. Radiological evaluation revealed a substantial recurrent SFT in the left lung, prompting excision through a left posterolateral thoracotomy. Remarkably, the patient's altered mental status and hypoglycemia resolved postoperatively. The case meets the criteria for aggressive SFT behavior, warranting consideration for adjuvant radiation therapy to control the risk of recurrence. This report highlights the nuanced interplay between SFT recurrence, paraneoplastic syndromes like DPS, and the potential benefits of adjuvant therapeutic strategies in managing these complex clinical scenarios.

Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a revolutionary paradigm in the treatment of thoracic malignancies and chemoimmunotherapy is a current standard care in this field. Chemotherapeutic agents are known to induce not only direct cytotoxic effects on tumor cells but also immune modulating effects, such as stimulating immunogenic cell death (ICD). Currently, either pemetrexed (PEM) or taxane plus platinum are combined with ICIs for patients with non-small cell lung cancer (NSCLC); however, it is still unknown whether these agents are immunologically optimal partners for ICIs. METHODS: To determine the immunologically optimal chemotherapeutic agent, we first evaluated the ability of several chemotherapeutic agents, including platinum, PEM, taxane, and 5-fluorouracil (5-FU) to induce ICD using several thoracic tumor cell lines in vitro. ICD was evaluated by the cell surface expression of calreticulin (CRT) and adenosine-triphosphate (ATP) secretion. We further performed an antitumor vaccination assay in vivo. RESULTS: 5-FU induced cell surface expression of CRT and ATP secretion most efficiently among the several chemotherapeutic agents. This effect was enhanced when it was combined with platinum. In the antitumor vaccination assay in vivo, we found that vaccination with dying-AB1-HA (a murine malignant mesothelioma cell line) cells treated with 5-FU, but neither PEM nor PTX, reduced the tumor growth of living-AB1-HA cells inoculated 1 week after vaccination by recruiting CD3+ CD8+ T cells into the tumor microenvironment. CONCLUSION: Our findings indicate that fluoropyrimidine can be an immunologically optimal partner of ICIs through the induction of ICD for thoracic malignancies.

Pneumonectomy for Primary Lung Tumors and Pulmonary Metastases: A Comprehensive Study of Postoperative Morbidity, Early Mortality, and Preoperative Clinical Prognostic Factors.

BACKGROUND: Pneumonectomy is a major surgical resection that still remains a high-risk operation. The current study aims to investigate perioperative risk factors for postoperative morbidity and early mortality after pneumonectomy for thoracic malignancies. METHODS: We retrospectively analyzed all patients who underwent pneumonectomy for thoracic malignancies at our institution between 2014 and 2022. Complications were assessed up to 30 days after the operation. Mortality for any reason was recorded after 30 days and 90 days. RESULTS: A total of 145 out of 169 patients undergoing pneumonectomy were included in this study. The postoperative 30-day complication rate was 41.4%. The 30-day-mortality was 8.3%, and 90-day-mortality 17.2%. The presence of cardiovascular comorbidities was a risk factor for major cardiopulmonary complications (54.2% vs. 13.2%, p < 0.01). Postoperative bronchus stump insufficiency (OR: 11.883, 95% CI: 1.288-109.591, p = 0.029) and American Society of Anesthesiologists (ASA) score 4 (OR: 3.023, 95% CI: 1.028-8.892, p = 0.044) were independent factors for early mortality. CONCLUSION: Pneumonectomy for thoracic malignancies remains a high-risk major lung resection with significant postoperative morbidity and mortality. Attention should be paid to the preoperative selection of patients.

Cardiovascular Outcomes Associated With Exposure To Radiation Therapy In Thoracic Malignancies: An Insight Study Using the National Inpatient Database.

Background Thoracic irradiation is a widely used therapeutic and palliative treatment option for thoracic neoplasms. However, short- and long-term cardiovascular adverse effects of radiation exposure remain a major concern. The short-term adverse effects are observed within months of exposure such as pericardial diseases; meanwhile, the long-term complications are usually insidious and manifest over decades, such as congestive heart failure, coronary artery disease, cardiomyopathy, conduction disorders, constrictive pericarditis, and valvular heart disease. Hence, long-term cardiovascular adverse effects are challenging to predict, and the association with radiation exposure remains difficult to establish. Methodology This retrospective, observational study was conducted using data from the National Inpatient Sample (NIS) database from 2016 to 2019. Adult patients with primary thoracic malignancies who underwent radiation therapy (RT) were defined using principal and secondary International Classification of Diseases, Tenth Revision codes. Other malignancies that can be treated with RT and all secondary malignancies were excluded from the primary comparison group. Cardiac outcomes were defined as the prevalence of congestive heart failure, coronary artery disease, cardiomyopathy, conduction disorders, pericardial diseases, and valvular heart diseases in the primary group. The multivariate logistic and the linear regression analyses were used to adjust for confounders. Results When compared to the general population, adults with thoracic malignancies exposed to RT had higher odds of developing chronic pericarditis (adjusted odds ratio (aOR) = 2, 95% confidence interval (CI) = 1.9-2.2, p < 0.001), acute pericarditis (aOR = 2.3, 95% CI = 1.9-2.9, p < 0.001), constrictive pericarditis (aOR = 2.8, 95% CI = 2.1-3.7, p < 0.001), conduction disorders (aOR = 1.3, 95% CI = 1.2-1.35, p < 0.001), coronary artery disease (aOR = 1.24, 95% CI = 1.2-1.27, p < 0.001), heart failure (aOR = 1.44, 95% CI = 1.4-1.5, p < 0.001), and valvular heart disease (aOR = 1.37, 95% CI = 1.3-1.4, p < 0.001). There was no difference in the odds of developing cardiac arrest (aOR = 1, 95% CI = 0.9-1.10, p = 0.6) or acute myocardial infarction (aOR = 1.1, 95% CI = 1-1.15, p < 0.001). When compared to adults with thoracic malignancies not exposed to RT, adults with thoracic malignancies who were exposed to RT had higher odds of developing acute myocardial infarction (aOR = 1.14, 95% CI = 1.1-1.18, p < 0.001), chronic pericarditis (aOR = 1.3, 95% CI = 1.2-1.3, p < 0.001), acute pericarditis (aOR = 1.6, 95% CI = 1.2-2.1, p < 0.001), constrictive pericarditis (aOR = 2.2, 95% CI = 1.5-3.2, p < 0.001), conduction disorders (aOR = 1.1, 95% CI = 1.08-1.13, p < 0.001), coronary artery disease (aOR = 1.14, 95% CI = 1.12-1.16, p < 0.001), heart failure (aOR = 1.2, 95% CI = 1.17-1.23, p < 0.001), and valvular heart disease (aOR = 1.3, 95% CI = 1.2-1.35, p < 0.001). The odds were similar between the two groups for developing cardiac arrest (aOR = 0.86, 95% CI = 0.8-0.98, p = 0.05). Conclusions Adults with thoracic malignancies who were treated with RT have higher odds of developing chronic pericarditis, acute pericarditis, constrictive pericarditis, conduction disorders, coronary artery disease, heart failure, and valvular heart disease while similar odds of developing cardiac arrest or acute myocardial infarction compared to the general adult population.

Longitudinal use of three different navigational bronchoscopy systems to sample lung nodules in a single patient.

Bronchoscopic techniques to sample suspicious lung nodules have progressed from traditional bronchoscopy to guided navigational bronchoscopy systems. Here we present the case of a patient who underwent navigational bronchoscopies using three different systems over a period of 41 months that diagnosed two primary and one metastatic thoracic malignancy. As guided bronchoscopy systems for the diagnosis of lung nodules continue to advance, it is important to recognize that the full utilization of accessible tools and technologies combined with shared decision making may often lead to a successful procedure and accurate diagnosis.

The Role of Surgery in Stage I Small Cell Lung Cancer: A National VA Database Analysis.

BACKGROUND: Historically, limited stage Small Cell Lung Cancer (SCLC) has been treated with concurrent chemoradiation (CRT). While current NCCN guidelines recommend consideration of lobectomy in node-negative cT1-T2 SCLC, data regarding the role of surgery in very limited SCLC is lacking. METHODS: Data from the National VA Cancer Cube were compiled. A total of 1,028 patients with pathologically confirmed stage I SCLC were studied. Only 661 patients that either received surgery or CRT were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Two survival curves were compared by a Wald test. Subset analysis was performed based on the location of the tumor in the upper vs. lower lobe as delineated by ICD-10 codes C34.1 and C34.3. RESULTS: Four-hundred and forty-six patients received concurrent CRT; while 223 underwent treatment that contained surgery (93 surgery only, 87 surgery/chemo, 39 surgery/chemo/radiation and 4 surgery/radiation). The median OS for the surgery-inclusive treatment was 3.87 years (95% CI 3.21-4.48) while median OS for the CRT cohort was 2.45 years (95% CI 2.17-2.74). HR of death for surgery-inclusive treatment when compared to CRT is 0.67 (95% CI 0.55-0.81; P < .001). Subset analysis based on the location of the tumor in both the upper or lower lobes showed improved survival with surgery as compared to CRT regardless of the location. HR for the upper lobe was 0.63 (95% CI 0.50-0.80; P < .001) and lower lobe 0.61 (95% CI 0.42-0.87; P = .006). Multivariable regression analysis accounting for age and ECOG-PS shows a HR 0.60 (95% CI 0.43-0.83; P = .002) favoring surgery. CONCLUSIONS: Surgery was used in less than a third of patients with stage I SCLC who received treatment. Surgery-inclusive multimodality treatment was associated with a longer overall survival as compared to chemoradiation, independent of age, performance status or tumor location. Our study suggests a more expansive role for surgery in stage I SCLC.

Personalised Assessment and Rapid Intervention in Frail Patients With Lung Cancer: The Impact of an Outpatient Occupational Therapy Service.

INTRODUCTION: Lung cancer and its treatments cause or accelerate frailty, detrimentally affecting function and quality of life. Occupational therapists (OTs) provide global assessments and interventions, but services are often available for inpatients. The impact of holistic assessment and early intervention in the outpatient setting is unknown. MATERIALS AND METHODS: A tertiary cancer center in North East England piloted a Lung Cancer Outpatient OT Service for patients with thoracic malignancy and a Clinical Frailty Scale Score (CFS) ≥ 5. Service effectiveness was evaluated through calculation of admission avoidance, hospital length-of-stay reduction, completion/impact of advance care planning and patient/family feedback. Demographics, frailty level, required interventions, and onward referrals were recorded. RESULTS: A total of 153 patients (median age of 71 (range 46-90) received OT assessment and intervention. 48% were in the lowest socioeconomic quintile. Median CFS score was 5 (mildly frail (range: 4-7)) at initial assessment. Total of 918 interventions were delivered (median: 5, IQR: 3-7, Range 0-22). 48% of patients engaged in future planning (national average: 10%-15% P < .0001) and 78.5% achieved preferred place of death (national average 30%). An estimated 37 hospital admissions were avoided. In admitted patients, average inpatient stay when known to the service was 6.5 days less than other frail lung cancer patients in our unit (95% CI 4-9.1 days P < .0001). Higher CFS was associated with poor survival (P < .05). CONCLUSION: Outpatient OT services can avoid and shorten hospital admissions through advance care planning, management of functional disruption, onward referral to other allied health professionals and palliative care. A comprehensive multidisciplinary outpatient service may benefit patients further and should be the focus of future research.

Feasibility of an embedded palliative care clinic model for patients with an advanced thoracic malignancy.

PURPOSE: Early palliative care (PC) with standard oncology care has demonstrated improved patient outcomes, but multiple care delivery models are utilized. This study prospectively evaluated the feasibility of an embedded PC clinic model and collected patient-reported outcomes (PROs) and caregiver needs. METHODS: In this observational study of embedded outpatient PC for patients with advanced thoracic malignancies treated at The Ohio State University Thoracic Oncology clinic, patients received same-day coordinated oncology and palliative care visits at one clinic location. PC encounters included comprehensive symptom assessment and management, advanced care planning, and goals of care discussion. Multiple study assessments were utilized. We describe the feasibility of evaluating PROs and caregiver needs in an embedded PC model. RESULTS: Forty patients and 28 caregivers were enrolled. PROs were collected at baseline and follow-up visits. Over a 12-month follow-up, 36 patients discontinued study participation due to hospice enrollment, death, study withdrawal, or COVID restrictions. At baseline, 32 patients (80%) rated distress as moderate-severe with clinically significant depression (44%) and anxiety (36%). Survey completion rates significantly decreased over time: 3 months (24 eligible, 66% completed), 6 months (17 eligible; 41% completed), 9 months (9 eligible; 44% completed), and 12 months (4 eligible; 50% completed). CONCLUSION: We found that an embedded PC clinic was feasible, although there were challenges encountered in longitudinal collection of PROs due to high study attrition. Ongoing assessment and expansion of this embedded PC model will continue to identify strengths and challenges to improve patient and caregiver outcomes.

Comparison of the sensitivity of different criteria to select lung cancer patients for screening in a cohort of German patients.

INTRODUCTION: Trials of CT-based screening for lung cancer have shown a mortality advantage for screening in North America and Europe. Before introducing a nationwide lung cancer screening program in Germany, it is important to assess the criteria used in international trials in the German population. METHODS: We used data from 3623 lung cancer patients from the data warehouse of the German Center for Lung Research (DZL). We compared the sensitivity of the following lung cancer screening criteria overall and stratified by age and histology: the National Lung Screening Trial (NLST), the Danish Lung Cancer Screening Trial (DLCST), the 2013 and 2021 US Preventive Services Task Force (USPSTF), and an adapted version of the Prostate, Lung, Colorectal, and Ovarian no race model (adapted PLCOm2012) with 6-year risk thresholds of 1.0%/6 year and 1.7%/6 year. RESULTS: Overall, the adapted PLCOm2012 model (1%/6 years), selected the highest proportion of lung cancer patients for screening (72.4%), followed by the 2021 USPSTF (70.0%), the adapted PLCOm2012 (1.7%/6 year) (57.4%), the 2013 USPTF (57.0%), DLCST criteria (48.7%), and the NLST (48.5%). The adapted PLCOm2012 risk model (1.0%/6 year) had the highest sensitivity for all histological types except for small-cell and large-cell carcinomas (non-significant), whereas the 2021 USPTF selected a higher proportion of patients. The sensitivity levels were higher in males than in females. CONCLUSION: Using a risk-based selection score resulted in higher sensitivities compared to criteria using dichotomized age and smoking history. However, gender disparities were apparent in all studied eligibility criteria. In light of increasing lung cancer incidences in women, all selection criteria should be reviewed for ways to close this gender gap, especially when implementing a large-scale lung cancer screening program.

Feasibility of shape-sensing robotic-assisted bronchoscopy for biomarker identification in patients with thoracic malignancies.

OBJECTIVE: Molecular diagnostic assays require samples with high nucleic acid content to generate reliable data. Similarly, programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) requires samples with adequate tumor content. We investigated whether shape-sensing robotic-assisted bronchoscopy (ssRAB) provides adequate samples for molecular and predictive testing. METHODS: We retrospectively identified diagnostic samples from a prospectively collected database. Pathologic reports were reviewed to assess adequacy of samples for molecular testing and feasibility of PD-L1 IHC. Tumor cellularity was quantified by an independent pathologist using paraffin-embedded sections. Univariable and multivariable linear regression models were constructed to assess associations between lesion- and procedure-related variables and tumor cellularity. RESULTS: In total, 128 samples were analyzed: 104 primary lung cancers and 24 metastatic lesions. On initial pathologic assessment, ssRAB samples were deemed to be adequate for molecular testing in 84% of cases; on independent review of cellular blocks, median tumor cellularity was 60% (interquartile range, 25%-80%). Hybrid capture-based next-generation sequencing was successful for 25 of 26 samples (96%), polymerase chain reaction-based molecular testing (Idylla; Biocartis) was successful for 49 of 52 samples (94%), and PD-L1 IHC was successful for 61 of 67 samples (91%). Carcinoid and small cell carcinoma histologic subtype and adequacy on rapid on-site evaluation were associated with higher tumor cellularity. CONCLUSIONS: The ssRAB platform provided adequate tissue for next-generation sequencing, polymerase chain reaction-based molecular testing, and PD-L1 IHC in >80% of cases. Tumor histology and adequacy on intraoperative cytologic assessment might be associated with sample quality and suitability for downstream assays.

Clinical application of comprehensive genomic profiling panel to thoracic malignancies: A single-center retrospective study.

BACKGROUND: The usefulness of comprehensive genomic profiling (CGP) panels for thoracic malignancies after completion of the standard treatment is unclear. METHODS: The results of CGP panels for malignant thoracic diseases performed at our hospital between December 2019 and June 2022 were collected. We examined whether CGP panel results led to new treatment, correlated with the effectiveness of immune checkpoint inhibitors (ICIs), or revealed secondary findings related to hereditary tumors. RESULTS: A total of 60 patients were enrolled, of which 52 (86.6%) had lung cancer. In six (10%) patients, the panel results led to treatment with insurance-listed molecular-targeted agents; four patients had EGFR mutations not detected by the real-time polymerase chain reaction assay and two had MET ex.14 skipping mutations. In small-cell lung cancer, the tumor mutation burden was high in 4/6 (66.7%) patients and pembrolizumab was available. Another MET ex.14 skipping mutation was detected in two cases with EGFR-tyrosine kinase inhibitor resistance. ICI efficacy was ≤1 year in patients with STK-11, KEAP1, and NEF2L2 mutations. A BRCA2 mutation with a high probability of germline mutation was detected in one patient. A thymic carcinoma with no detectable oncogenic mutation responded to second-line treatment with Tegafur-Gimeracil-Oteracil Potassium (TS-1) for ≥9 years. CONCLUSIONS: CGP panels are useful in thoracic malignancies, especially lung cancer, because they can detect overlooked driver mutations and genetic alterations. We believe that the significance of conducting a CGP panel prior to treatment may also exist, as it may lead to the prediction of ICI treatment efficacy.

A fatal case associated with Catabacter hongkongensis bacteremia in lung cancer patient: A case report.

Catabacter hongkongensis is a bacterium first isolated in 2007 and has since been detected in the blood of about fifteen patients with disease such as gastrointestinal malignancy, intestinal obstruction, or acute intestinal infection. We describe herein the case of a patient newly diagnosed with metastatic lung cancer, who died from a fatal infection possibly related to Catabacter hongkongensis bacteremia. By reviewing all cases reported in the literature, our case report supports that this infection is associated with a very high mortality in cancer patients.

Disparate Time-to-Treatment and Varied Incidence of Actionable Non-Small Cell Lung Cancer Molecular Alterations in British Columbia: A Historical Cohort Study.

Background: non-small cell lung cancer (NSCLC) outcomes remain suboptimal for early-stage disease despite emerging advances in systemic therapy for the peri-operative period. Next-generation sequencing (NGS) identifies driver mutations for which targeted therapies have been developed that improve survival. The BC lung cancer screening program, which was initiated in May 2022, is expected to identify people with early and late stages of NSCLC. It is crucial to first understand the molecular epidemiology and patterns of time to initiate treatment across its five health authorities (HA) to optimize the delivery of care for NSCLC in BC. In this way, we may harness the benefits of targeted therapy for more people with NSCLC as novel advances in therapy continue to emerge. Objective: to compare (a) the frequency of actionable NSCLC molecular alterations among HAs and (b) the time to treatment initiation. Methods: a retrospective observational study was conducted with prospectively collected data from the BC CGL Database. Adults with late stage NSCLC who underwent targeted NGS were included for the time period from May 2020 to June 2021. Demographics, actionable molecular alterations, PDL-1 expression, and time to treatment across HAs were examined. Using appropriate statistical tests for comparison among HAs, p>0.05 was deemed significant. Results: 582 patients underwent NGS/IHC and analysis during the study period. The mean age was 71 (10.1), and 326 (56%) patients were female. A significantly higher proportion of all EGFRm+ were identified within Vancouver Coastal Health (VCHA) and Fraser Health Authority (FHA) compared to the other health authorities (p < 0.001). This also holds true for common sensitizing EGFRm+ alone (p < 0.001) and for sensitizing EGFRm+ when adjusted for females and smoker status (OR 0.75; 95% CI 0.62, 0.92; p = 0.005). Patients residing within the Northern, Interior, and Island HAs were less likely to receive treatment at the same rate as those in VCHA and FHA HAs. Conclusion: actionable NSCLC driver mutations are present in all regional HAs, with disparity noted in time to initiate treatment between HAs. This provides evidence for the importance of molecular testing for patients in all BC HAs to guide personalized and timely NSCLC treatment.

Impact of telemedicine adoption on accessibility and time to treatment in patients with thoracic malignancies during the COVID-19 pandemic.

BACKGROUND: To ensure safe delivery of oncologic care during the COVID-19 pandemic, telemedicine has been rapidly adopted. However, little data exist on the impact of telemedicine on quality and accessibility of oncologic care. This study assessed whether conducting an office visit for thoracic oncology patients via telemedicine affected time to treatment initiation and accessibility. METHODS: This was a retrospective cohort study of patients with thoracic malignancies seen by a multidisciplinary team during the first surge of COVID-19 cases in Philadelphia (March 1 to June 30, 2020). Patients with an index visit for a new phase of care, defined as a new diagnosis, local recurrence, or newly discovered metastatic disease, were included. RESULTS: 240 distinct patients with thoracic malignancies were seen: 132 patients (55.0%) were seen initially in-person vs 108 (45.0%) via telemedicine. The majority of visits were for a diagnosis of a new thoracic cancer (87.5%). Among newly diagnosed patients referred to the thoracic oncology team, the median time from referral to initial visit was significantly shorter amongst the patients seen via telemedicine vs. in-person (median 5.0 vs. 6.5 days, p < 0.001). Patients received surgery (32.5%), radiation (24.2%), or systemic therapy (30.4%). Time from initial visit to treatment initiation by modality did not differ by telemedicine vs in-person: surgery (22 vs 16 days, p = 0.47), radiation (27.5 vs 27.5 days, p = 0.86, systemic therapy (15 vs 13 days, p = 0.45). CONCLUSIONS: Rapid adoption of telemedicine allowed timely delivery of oncologic care during the initial surge of the COVID19 pandemic by a thoracic oncology multi-disciplinary clinic.

Randomized phase II trial of a first-in-human cancer cell lysate vaccine in patients with thoracic malignancies.

BACKGROUND: Although most malignancies express cancer-testis antigens (CTA), immune responses to these proteins are limited in thoracic oncology patients. This trial was undertaken to examine if a cancer cell lysate vaccine could induce immunity to CTA, and to ascertain if metronomic cyclophosphamide and celecoxib enhances vaccine-induced immune responses. METHODS: Eleven patients with primary thoracic malignancies and 10 patients with extrathoracic neoplasms metastatic to the chest rendered NED by conventional therapies were randomized to receive H1299 lung cancer cell lysates (10 mg protein/vaccine) with Iscomatrix™ adjuvant via deep intradermal injection q 4 weeks ×6 with or without daily oral metronomic cyclophosphamide/celecoxib. The primary endpoint was serologic response to purified CTA assessed 1 month after the 6th vaccination. Secondary endpoints included assessment of the effects of cyclophosphamide and celecoxib on frequency and magnitude of vaccine-induced immune responses to CTA. Exploratory endpoints included evaluation of the effects of the vaccine regimens on peripheral immune subsets. Standard of care imaging studies were obtained at baseline and 1 month after the 3rd and 6th vaccinations. RESULTS: All patients exhibited local and systemic inflammatory responses lasting 72-96 hours following vaccinations. There were no dose limiting treatment related toxicities. Fourteen patients (67%) completed all six vaccinations. Eight of 14 patients (57%) exhibited serologic responses to NY-ESO-1. One patient developed antibodies to GAGE7; several patients exhibited reactivity to XAGE and MAGE-C2. Vaccine therapy decreased the percent of Tregs (P=0.0068), PD-1 expression on Tregs (P=0.0027), PD-L1 expression on CD14+ monocytes (P=0.0089), PD-L1 expression on classical monocytes (P=0.016), and PD-L1 expression on intermediate monocytes (P=0.0031). Cyclophosphamide/celecoxib did not appear to increase immune responses or enhance vaccine-induced alterations in peripheral immune subsets. CONCLUSIONS: H1299 lysate vaccines with Iscomatrix™ induce immune responses to CTA and modulate peripheral immune subsets in a manner that may enhance antitumor immunity in patients with thoracic malignancies.

CT Guided Needle Biopsy of Peripheral Lesions-Lesion Characteristics That May Increase the Diagnostic Yield and Reduce the Complication Rate.

Computed tomography-guided needle biopsy (CT-GNB) has a high diagnostic yield for lung cancer but higher complication rates compared to those of other biopsy modalities. We sought to clarify in which thoracic lesions we could achieve a quick pathological diagnosis using CT-GNB, considering the risks and benefits. We retrospectively enrolled 110 patients who underwent CT-GNB and 547 patients who underwent transbronchial biopsy (TBB) for parenchymal lung lesions in clinical practice. The diagnostic rates of CT-GNB and TBB were 87.3% and 75.3%. After failed diagnosis with other biopsy modalities, 92.3% of patients were finally diagnosed using CT-GNB and 65.8% using TBB. In cases with a negative bronchial sign, there was a statistically higher diagnostic rate with CT-GNB than with TBB (p < 0.001: 89.4% vs. 0%). Complication rates were higher with CT-GNB (50.9%) than with TBB (16.3%). However, there were lower rates of complications in cases with inhomogeneous tumors, subpleural lesions, and when more than 15 mm of the punctured needle length was within the target. We conclude that CT-GNB is an effective biopsy modality with a high diagnostic rate that is especially recommended when the bronchus sign is negative. It can be safely performed if risk factors for complications are taken into account.

A Retrospective Study on Using a Novel Single Needle Cone Puncture Approach for the Iodine-125 Seed Brachytherapy in Treating Patients With Thoracic Malignancy.

BACKGROUND: Patients with progressive thoracic malignancy characterized by large irregular tumors with necrosis and life-threatening symptoms lack effective treatments. We set out to develop a single needle cone puncture method for the Iodine-125 seed (SNCP-125I) brachytherapy, and aim to report the initial results. METHODS: 294 patients with advanced thoracic malignancy were treated with local SNCP-125I brachytherapy between March 2009 and July 2020, followed by thorough evaluation of clinical outcome, overall survival (OS), progression-free survival (PFS) and procedure-related complications after treatment. RESULTS: The overall response rate (ORR) among the treated patients was 81.0% (238/294). Life-threatening symptoms due to tumor oppression, hemoptysis and large irregular tumor with necrosis were successfully alleviated after the SNCP-125I treatment with a remission rate at 91% to 94%. The median OS and PFS were 13.6 months and 5.8 months, respectively. Procedure-related side effects including pneumothorax (32/294), blood-stained sputum (8/294), subcutaneous emphysema (10/294), puncture site bleeding (16/294) and chest pain (6/294) were observed. Patients who were able to follow with chemotherapy or immunotherapy experienced extended OS and PFS, as compared with patients who opted to receive hospice care (16.5 months Vs. 11.2 months). Further pathological and immunological analysis showed that SNCP-125I induced tumor lymphocytes infiltration and long-term tumor necrosis. CONCLUSION: SNCP-125I brachytherapy effectively eliminates life-threatening symptoms due to local tumor oppression, hemoptysis and large irregular and necrotic tumors in patients with unresectable chest malignancy and significantly induces local tumor regression. SNCP-125I brachytherapy combines with chemotherapy significantly prolong OS and PFS compare with SNCP-125I brachytherapy alone.