High-Risk Non-Small Cell Lung Cancer Treated With Active Scanning Proton Beam Radiation Therapy and Immunotherapy.

Purpose: Non-small cell lung cancer (NSCLC) is a deadly malignancy that is frequently diagnosed in patients with significant medical comorbidities. When delivering local and regional therapy, an exceedingly narrow therapeutic window is encountered, which often precludes patients from receiving aggressive curative therapy. Radiation therapy advances including particle therapy have been employed in an effort to expand this therapeutic window. Here we report outcomes with the use of proton therapy with curative intent and immunotherapy to treat patients diagnosed with high-risk NSCLC. Methods and Materials: Patients were determined to be high risk if they had severe underlying cardiopulmonary dysfunction, history of prior thoracic radiation therapy, and/or large volume or unfavorable location of disease (eg, bilateral hilar involvement, supraclavicular involvement). As such, patients were determined to be ineligible for conventional x-ray-based radiation therapy and were treated with pencil beam scanning proton beam therapy (PBS-PBT). Patients who demonstrated excess respiratory motion (ie, greater than 1 cm in any dimension noted on the 4-dimensional computed tomography simulation scan) were deemed to be ineligible for PBT. Toxicity was reported using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Overall survival and progression-free survival were calculated using the Kaplan-Meier method. Results: A total of 29 patients with high-risk NSCLC diagnoses were treated with PBS-PBT. The majority (55%) of patients were defined as high risk due to severe cardiopulmonary dysfunction. Most commonly, patients were treated definitively to a total dose of 6000 cGy (relative biological effectiveness) in 30 fractions with concurrent chemotherapy. Overall, there were a total of 6 acute grade 3 toxicities observed in our cohort. Acute high-grade toxicities included esophagitis (n = 4, 14%), dyspnea (n = 1, 3.5%), and cough (n = 1, 3.5%). No patients developed grade 4 or higher toxicity. The majority of patients went on to receive immunotherapy, and high-grade pneumonitis was rare. Two-year progression-free and overall survival was estimated to be 51% and 67%, respectively. COVID-19 was confirmed or suspected to be responsible for 2 patient deaths during the follow-up period. Conclusions: Radical PBS-PBT treatment delivered in a cohort of patients with high-risk lung cancer with immunotherapy is feasible with careful multidisciplinary evaluation and rigorous follow-up.

Pembrolizumab-Associated Cutaneous and Pulmonary Sarcoidosis in Non-Small Cell Lung Cancer Treatment.

Immune checkpoint inhibitor (ICI) therapy has reshaped the treatment landscape in many cancers including non-small cell lung cancer (NSCLC). ICI-therapy can lead to a diverse array of immune-related adverse effects (irAEs), and prompt recognition and management are key to successful treatment. With wide-spread use of ICI therapy in clinical practice, rare irAEs are being increasingly recognized. This report documents a patient with advanced NSCLC who developed pembrolizumab-associated sarcoidosis with multiorgan involvement. Multidisciplinary management led to timely diagnosis and treatment, leading to improvement in symptoms. This case raises awareness of sarcoidosis as a rare side effect of pembrolizumab.

Comparison of the GenCut Core Biopsy System to Transbronchial Biopsy Forceps for Flexible Bronchoscopic Lung Biopsy.

BACKGROUND: Pulmonary nodules are increasingly detected on screening and routine chest imaging, leading to an increase in diagnostic procedures. Bronchoscopy with transbronchial biopsy (TBBx) is the most common diagnostic modality, with diagnostic yield between 43% and 86%, largely dependent on the use of navigational modalities. In 2015 a new biopsy tool by Medtronic, the GenCut core biopsy system [GenCut transbronchial needle aspiration (TBNA)], was developed with the intention of improving yield in lung nodule biopsies. Our goal was to determine the efficacy of this new device when used in addition to TBBx. PATIENTS AND METHODS: This is a prospective observational study of 324 consecutive bronchoscopic lung biopsies in which both TBBx and GenCut TBNA were performed on the same lesion. We recorded patient and nodule characteristics, along with the bronchoscopic modalities used. The primary outcome was the diagnostic yield with the addition of the GenCut TBNA, and the key secondary outcome was the complication rate. RESULTS: Of the 324 nodule biopsies analyzed, 164 (50.6%) were diagnostic via TBBx or GenCut TBNA.In all, 97 (59%) were positive in both TBBx and GenCut TBNA, 43 (26.2%) were positive only in TBBx, and 24 (14.6%) were positive only in GenCut TBNA. Overall, the addition of the GenCut TBNA increased the diagnostic yield by 7.4% (P<0.01). There were 7 complications: 5 pneumothoraxes and 2 episodes of bleeding. CONCLUSION: The diagnostic yield is improved by using the GenCut core biopsy system in addition to traditional TBBx forceps when performing bronchoscopy for pulmonary nodules, without an increase in complications. These biopsy methods should be used in tandem for the greatest yield.

Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways prior to treatment. Five fraction SBRT approaches have been advocated to mitigate treatment induced toxicity. In this report, we examine the mature clinical outcomes of a diverse cohort of ES-NSCLC patients with both peripheral and central tumors treated with a conservative 5 fraction SBRT approach and evaluate the role of lobar gross endobronchial disease (LGED) in predicting overall survival and treatment-related death. METHODS: Medically inoperable biopsy-proven, lymph node-negative ES-NSCLC patients were treated with SBRT. Bronchoscopy was completed prior to treatment in all centrally located cases. The Kaplan-Meier method was used to estimate overall survival (OS), local control (LC), regional control (RC), distant metastasis free survival (DMFS) and disease-free survival (DFS). Overall survival was stratified based on clinical stage, histology, tumor location and LGED. Toxicities were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. RESULTS: From December 2010 to December 2015, 50 consecutive patients were treated uniformly with a 50 Gy in 5 fraction SBRT approach (tumor BED10 ≥ 100 Gy) and followed for a minimum of 5 years or until death. At a median follow up of 42 months for all patients, 3-year OS was 50%. Three-year OS did not statistically differ between stage I and stage II disease (51% vs. 47%; p=0.86), adenocarcinoma and squamous cell carcinoma (50% vs. 45%; p=0.68), or peripheral and central tumors (56% vs. 45%; p=0.46). Five central tumors were found to have LGED, and 3-year OS for this cohort was quite poor at 20%. Cox regression analysis identified LGED as a predictor of OS while controlling for age, stage and location (OR:4.536, p-value=0.038). Despite the relatively low dose delivered, treatment likely contributed to the death of 4 patients with central tumors. Lobar gross endobronchial disease was an independent predictor for grade 5 pulmonary toxicity (n=4, p=0.007). Specifically, 3 of the 5 patients with LGED developed fatal radiation-induced bronchial stricture. Three-year LC, RC, DMFS and DFS results for the group were similar to contemporary studies at 90%, 90%, 82% and 65%. CONCLUSIONS: Central location of ES-NSCLC is a well-established predictor for severe SBRT-related toxicity. Here we identify LGED as a significant predictor of poor overall survival and grade 5 pulmonary toxicity. The relatively high rates of severe treatment-related toxicity seen in patients with central ES-NSCLC may be due in part to LGED. Underlying LGED may cause irreparable damage to the lobar airway, unmitigated by SBRT treatment thus increasing the risk of severe treatment-related toxicity. These findings should be verified in larger data sets. Future prospective central ES-NSCLC clinical trials should require staging bronchoscopy to identify LGED and further assess its clinical significance.

A 67-Year-Old Woman With Abdominal Pain and Dyspnea.

CASE PRESENTATION: A 67-year-old woman presented to her primary physician with a year of periumbilical abdominal discomfort with diarrhea, bloating, and unintentional weight loss. While undergoing workup for the abdominal pain, she presented to the ED with dyspnea that worsened over a few weeks. She had no associated chest pain, lower extremity edema, fevers, or chills, but endorsed orthopnea. The patient's medical history included hypothyroidism and diabetes mellitus. Her family history was significant for coronary disease in her father and hypertension in her mother. She had no recent travel; she is a nonsmoker and rare alcohol drinker. She worked in administration.

Abscopal effect in pulmonary carcinoid tumor following ablative stereotactic body radiation therapy: a case report.

BACKGROUND: The abscopal effect was described as early as the 1950s, when untreated tumors demonstrated a response after radiation therapy was delivered to an untreated, distant site. The mechanisms underlying this global response to otherwise localized therapy remain unknown, though there is increasing evidence that increased antigen expression following ablative radiotherapy may play a role. CASE PRESENTATION: We report a case of a 69-year-old African American woman with a history of metastatic typical pulmonary carcinoid with multiple lung nodules who had a significant decrease in size of an untreated left upper lobe nodule after stereotactic body radiation therapy to an oligoprogressive left lower lobe lesion. CONCLUSIONS: To our knowledge, this report describes the first case of an abscopal effect in a typical pulmonary carcinoid. Further research is needed regarding the mechanisms responsible for this finding and the role of combining radiation therapy and cancer immunotherapy in patients with pulmonary carcinoid tumors.

Family Presence at First Cardiopulmonary Resuscitation and Subsequent Limitations on Care in the Medical Intensive Care Unit.

BACKGROUND: The association of family-witnessed cardiopulmonary resuscitation (CPR) and subsequent advance directives in the medical intensive care unit is unknown. OBJECTIVE: To compare clinical outcomes, including subsequent limitations on care, of family-witnessed vs family-unwitnessed CPR in the inpatient setting. METHODS: Analysis of demographics and outcomes pertaining to family presence in a retrospective cohort of consecutive patients receiving first CPR in the medical intensive care unit of a tertiary academic medical center. RESULTS: In 5 years, 323 patients underwent attempted CPR, of which 49 attempts (15.2%) were witnessed by family. In patients with return of spontaneous circulation, 40.9% of those whose first CPR was witnessed by family later had a do not attempt resuscitation order, which did not differ from patients whose first CPR was unwitnessed by family (31.8%). Family-witnessed CPR in the unit was associated with significantly lower rates of return of spontaneous circulation (44.9%) than was family-unwitnessed CPR (62.0%; P = .02). Of all patients with a first CPR, 42 (13.0%) survived to hospital discharge. Only 1 patient with return of spontaneous circulation after first family-witnessed CPR survived to hospital discharge. In-hospital mortality for all patients requiring subsequent CPR was 97.1%. CONCLUSIONS: For unclear reasons, family-witnessed CPR in the medical intensive care unit is associated with a similar rate of subsequent CPR efforts and lower rates of return of spontaneous circulation and survival to hospital discharge.

Patient evaluation for rapid pleurodesis of malignant pleural effusions.

BACKGROUND: Malignant pleural effusions (MPEs) represent advanced stage disease with potentially significant patient discomfort due to dyspnea. Palliative management options include repetitive thoracenteses, placement of a tunneled pleural catheter (TPC), chemical pleurodesis, or some combination of these procedures. The rapid pleurodesis procedure combines thoracoscopic talc pleurodesis and insertion of a TPC at the same time with the goals of reducing both the length of hospitalization and the duration of catheter use. The rapid pleurodesis procedure has previously been described to achieve both of these goals in a pilot study of 30 patients with fully expandable lungs. Both symptoms of dyspnea and quality of life improved with few complications. Additional data on procedural effectiveness is needed to optimize patient selection for this procedure. METHODS: We performed a retrospective analysis of patients who had undergone rapid pleurodesis protocol at two academic institutions over a 40-month period. Data was collected and analyzed on time to removal of the TPC, chemotherapy, malignancy type, complications, age, and catheter occlusion. RESULTS: A total of 29 patients underwent the rapid pleurodesis protocol with a median hospital length of stay of 2 days. Total length of hospitalization was not significantly different between patients with and without primary lung cancer. Median duration of the indwelling TPC was 10 days. Patients with primary lung cancer and those actively or recently undergoing chemotherapy maintained the catheter longer than their counterparts. CONCLUSIONS: The rapid pleurodesis protocol should be considered a viable treatment option for select patients with symptomatic recurrent MPEs undergoing chemical pleurodesis.

Diagnosis and management of pulmonary nodules.

There are an increased number of pulmonary nodules discovered on CT scan images in part due to those performed for lung cancer screening. Risk stratification and patient involvement is critical in determining management ranging from interval imaging to invasive biopsy or surgery. A definitive diagnosis requires tissue biopsy. The choice of a particular biopsy technique depends on the risks/benefits of the procedure, the diagnostic yield and local expertise. This review will focus on the evaluation and management of pulmonary nodules based on the Fleischner Society and American College of Chest Physician guidelines. There have been recent changes to both societies' recommendations for incidental detection of solid and subsolid nodules, risk stratification, imaging, minimally invasive diagnostic techniques and definitive surgical options.