James Cury

Protons safely allow coverage of high-risk nodes for patients with regionally advanced non-small-cell lung cancer.

Our objective was to determine if protons allow for the expansion of treatment volumes to cover high-risk nodes in patients with regionally advanced non-small-cell lung cancer. In this study, 5 consecutive patients underwent external-beam radiotherapy treatment planning. Four treatment plans were generated for each patient: 1) photons (x-rays) to treat positron emission tomography (PET)-positive gross disease only to 74 Gy (XG); 2) photons (x-rays) to treat high-risk nodes to 44 Gy and PET-positive gross disease to 74 Gy (XNG); 3) protons to treat PET-positive gross disease only to 74 cobalt gray equivalent (PG); and 4) protons to treat high-risk nodes to 44 CGE and PET-positive gross disease to 74 CGE (PNG). We defined high-risk nodes as mediastinal, hilar, and supraclavicular lymph nodal stations anatomically adjacent to the foci of PET-positive gross disease. Four-dimensional computed tomography was utilized for all patients to account for tumor motion. Standard normal-tissue constraints were utilized. Our results showed that proton plans for all patients were isoeffective with the corresponding photon (x-ray) plans in that they achieved the desired target doses while respecting normal-tissue constraints. In spite of the larger volumes covered, median volume of normal lung receiving 10 CGE or greater (V10Gy/CGE), median V20Gy/CGE, and mean lung dose were lower in the proton plans (PNG) targeting gross disease and nodes when compared with the photon (x-ray) plans (XG) treating gross disease alone. In conclusion, proton plans demonstrated the potential to safely include high-risk nodes without increasing the volume of normal lung irradiated when compared to photon (x-ray) plans, which only targeted gross disease.

Pulmonary Hypertension Secondary to COPD

The development of pulmonary hypertension in COPD adversely affects survival and exercise capacity and is associated with an increased risk of severe acute exacerbations. Unfortunately not all patients with COPD who meet criteria for long term oxygen therapy benefit from it. Even in those who benefit from long term oxygen therapy, such therapy may reverse the elevated pulmonary artery pressure but cannot normalize it. Moreover, the recent discovery of the key roles of endothelial dysfunction and inflammation in the pathogenesis of PH provides the rationale for considering specific pulmonary vasodilators that also possess antiproliferative properties and statins.

Approach to acute exacerbation of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia with a median survival of 3 years after diagnosis. Acute exacerbation of IPF (AE-IPF) is now identified as a life-threatening complication. It presents as worsening dyspnea with new ground glass opacities superimposed upon a radiographic usual interstitial pneumonia (UIP) pattern. It is a diagnosis of exclusion. The prognosis of AE-IPF is poor and treatment strategies lack standardization. In order to rule out any reversible etiology for an acute decompensation of a previously stable IPF patient diagnostic modalities include computerized tomographic angiogram (CTA) coupled with high-resolution computerized tomography (HRCT) imaging of the chest, bronchoalveolar lavage (BAL) and echocardiogram with bubble study. Avoiding risk factors, identifying underlying causes and supportive care are the mainstays of treatment. Anti-inflammatory and immunosuppressant medications have not shown to improve survival in AE-IPF. Most of the patients are managed in a critical care setting with mechanical ventilation. Lung transplantation is a promising option but most institutions are not equipped and not every patient is a candidate.

A Phase 2 Trial of Concurrent Chemotherapy and Proton Therapy for Stage III Non-Small Cell Lung Cancer: Results and Reflections Following Early Closure of a Single-Institution Study

PURPOSE Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). METHODS AND MATERIALS From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. RESULTS Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. CONCLUSIONS Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.

Characteristics and Outcomes of Cocaine-Related Spontaneous Intracerebral Hemorrhages

To date there is only one single-center study that has exclusively reported characteristics, location, and outcomes of spontaneous intracerebral hemorrhages (ICH) among cocaine users. We aimed to describe the radiological location and characteristics along with clinical outcomes of spontaneous ICH in a similar population. We conducted a retrospective chart review of consecutive patients admitted to a tertiary care hospital, with a spontaneous ICH, who had a urine drug screen performed within 48 hours of admission. Exposure to cocaine was defined by a positive urine drug screen within 48 hours of hospital admission. Demographics, radiographic features of ICH, and short-term clinical outcomes of patients with a positive urine drug screen were analyzed and compared with the cocaine negative group. Among the 102 patients analyzed, 20 (19.6%) had documented exposure to cocaine. There was a predominance of males in both groups with significantly more Blacks in the cocaine positive group (P = 0.0246). A statistically significant number of patients with cocaine use had ICH in a subcortical location (P = 0.0224) when compared to cocaine negative patients. There was no difference in GCS, ICH volume, intraventricular extension, ICU days, hospital days, hospital cost, mortality, and ICH score. ICH in cocaine use is more frequently seen in the subcortical location.

Severe Hyponatremia Due to Valproic Acid Toxicity

Hyponatremia is a very commonly encountered clinical entity with potentially dangerous effects and for which many precipitating factors have been identified. We present a case of valproic acid (VPA) overdose causing profound hyponatremia, with one of the lowest serum sodium levels ever documented in literature. A 54-year-old woman with hypothyroidism, hypertension and bipolar disorder presented with somnolence after intentionally ingesting 7,500 mg VPA. She was drowsy but easily arousable with no hemodynamic compromise and an unremarkable physical exam. There was no clinical suspicion for organic neurological or pulmonary disease, adrenal insufficiency or volume depletion. She was found to have a serum sodium of 99 mEq/L, low plasma osmolality (211 mOsm/kg H2O), and high urine osmolality (115 mOsm/kg H2O). Her urine sodium was 18 mEq/L. She was euthyroid (TSH: 3.06 mIU/L) and compliant with thyroxine replacement. She was admitted to the intensive care unit for close monitoring and VPA was withheld. Over 36 hours her VPA level fell from 59.3 mg/L to 22.8 mg/L, serum sodium steadily rose to 125 mEq/L and there was concomitant improvement in her mental status. At 72 hours, she was transferred for an inpatient psychiatric evaluation and her sodium level was 135 mEq/L. She luckily did not experience any seizures or decline in neurological function. The clinical presentation in this patient is consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) leading to a dramatic fall in sodium to a level of 99 mEq/L. Chronic VPA use has been associated with SIADH and chronic hyponatremia. Review of records in this patient from 1 year prior revealed that her last measured sodium level was 127 mEq/L. It is therefore most likely that our case is one of acute on chronic hyponatremia provoked by VPA overdose in the setting of chronic VPA use. Whilst our patient’s course was relatively benign, this case illustrates a rare consequence of VPA toxicity, which if unnoticed in another patient may be tragic.

Diagnostic yield of EBUS-TBNA for the evaluation of centrally located peribronchial pulmonary lesions.

Background:The purpose of this study was to evaluate the diagnostic yield of endobronchial ultrasound with real-time–guided transbronchial needle aspiration (EBUS-TBNA), endobronchial forceps biopsy (EBBx), and 2D fluoroscopic-guided transbronchial forceps biopsy (TBLBx) for centrally located peribronchial lung lesions. Methods:A retrospective chart review of consecutive patients who underwent EBUS-TBNA of centrally located peribronchial lesions, that is, medial margin of the mass within inner third of hemithorax by computerized tomography scan. Patients who underwent EBUS-TBNA for lymph node sampling were excluded. Results:Thirty-two cases met the inclusion criteria. The mean age was 69±12 years. Sixteen (50%) were male patients. Of the 32 EBUS-TBNA cases, 13 underwent concomitant TBLBx (group 1), 8 had concomitant EBBx (group 2), and 11 had EBUS-TBNA alone (group 3). In group 1, the diagnostic yield of EBUS-TBNA was 95% (n=12/13), whereas the yield of TBLBx was 61% (n=8/13). In group 2, the diagnostic yield of EBUS-TBNA was 100% (n=8/8), whereas EBBx was positive in 75% (n=6/8). In group 3, the diagnostic yield of EBUS-TBNA was 91% (n=10/11). Overall diagnostic yield of EBUS-TBNA of centrally located peribronchial lung lesions was 94% (n=30/32). Conclusion:Where available, EBUS-TBNA of centrally located peribronchial lung lesions should be given a strong consideration given its high diagnostic yield.

Selective nodal irradiation of regionally advanced non‐small‐cell lung cancer with proton therapy and IMRT: A dosimetric comparison

Objectives:  Evaluate the dosimetric impact of selective/elective nodal treatment with dose‐escalated radiotherapy for regionally advanced non‐small‐cell lung cancer (NSCLC) using proton therapy (PT) or intensity‐modulated radiotherapy (IMRT).

A 62-Year-Old Woman With Dyspnea, Leukocytosis, and Diffuse Ground-Glass Opacities

62-year-old female presented to the ambulatory clinic with progressive shortness of breath over the course of approximately 1 year. She denied cough, fever, chills, chest pain, hemoptysis, or orthopnea. Approximately 1 year before presentation, she was admitted to the hospital for abdominal pain, distention, and early satiety. At that time she was diagnosed with chronic idiopathic myelofi brosis after bone marrow biopsy. She responded well on hydroxyurea and eventually discharged home. She also denied any occupational or environmental exposures prior to presentation.

Safety and accuracy of semirigid pleuroscopy performed by pulmonary fellows at a major university hospital: our initial experience.

Background:Pleuroscopy is considered a safe procedure with a high diagnostic accuracy but this record is based on studies published by pulmonologists experienced in performing the procedure. Methods:Review of 40 consecutive patients who underwent semirigid pleuroscopy by a pulmonary fellow under the supervision of a pulmonologist. Results:Pleuroscopy was performed for diagnosis of pleural effusion (n=33), or treatment of pleural effusion (n=4) or pneumothorax (n=3). The mean age±SD of the patients was 58.23±12.98 years and 23 patients were male. Pleuroscopy was performed with a flex-rigid pleuroscope under local anesthesia and conscious sedation. An ultrasound was used to choose the entry site. The dose of midazolam and fentanyl used was 6.45±2.87 mg and 173.39±77.17 mcg, respectively. The duration of the procedure was 69.3±25.3 minutes. The amount of pleural fluid removed was 1.5±0.94 L. The overall diagnostic accuracy of pleuroscopy was 87.8%, and the sensitivity, specificity, negative and positive predictive value for malignancy was 93.9%, 100%, 92.3% and 100%, respectively. There were a few complications: desaturation (n=2), hypotension (n=5), extensive subcutaneous emphysema (n=3), and persistent air leak (n=1). There was no case of significant bleeding or death from the procedure. Six of the 7 cardiopulmonary complications occurred during the first 4 procedures performed by the fellows. Conclusions:The diagnostic accuracy of pleuroscopy remains high in the hands of pulmonary fellows. However, the procedure can be associated with a slightly higher rate of complications when performed by fellows in training, especially in the early part of their learning curve. Most of the few complications observed were not caused by the procedure per se and resulted from over-zealous use of medications for conscious sedation.