Diagnostic Yield of Endobronchial Ultrasound-Guided Mediastinal Lymph Node Transbronchial Forceps Biopsies (EBUS-TBFB).

OBJECTIVE: The diagnostic accuracy and yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is not well established in lymphoma and other mediastinal-related diseases. The objective of this study was to examine the yield of a combined technique of EBUS-TBNA and endobronchial ultrasound-guided transbronchial forceps biopsies (EBUS-TBFB) compared with each modality alone in lymphoma and other mediastinal-related diseases. METHODS: This was a retrospective review of cases of mediastinal lymphadenopathy of unknown etiology accessed using TBNA and TBFB. The McNemar test was used to compare the diagnostic yield of TBNA, TBFB, and the combined technique. RESULTS: The combined approach yielded a definitive diagnosis in 31/35 cases (88.6%). In 9/10 cases (90%), Hodgkin's and non-Hodgkin's lymphomas were diagnosed and subtyped without further need for invasive testing. All of the granulomatous inflammation cases were confirmed using the combined technique. Two cases led to adequate whole-genome sequencing of lung cancer, and one patient was diagnosed as having dedifferentiated liposarcoma despite a nondiagnostic preprocedural mediastinoscopy. There was only one procedure-related complication, a pneumomediastinum that required no further intervention. There were no significant adverse events. CONCLUSIONS: The combination of EBUS-TBFB and EBUS-TBNA is safe and provides a high yield in the diagnosis of mediastinal adenopathy of unknown etiology, especially lymphoma. Furthermore, the larger samples obtained from TBFB increased its sensitivity to detect granulomatous disease and provided specimens for clinical trials of malignancy when needle aspirates were insufficient.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Use for Subclassification and Genotyping of Lung Non-Small-Cell Carcinoma.

OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the primary method for the diagnosis and staging of lung cancer. The purpose of this study was to assess the yield of EBUS-TBNA in the subtyping and genotyping of lung adenocarcinoma. METHODS: Sixty-nine patients at Indiana University Hospital and Sidney and Lois Eskenazi Hospital with possible or confirmed lung adenocarcinoma underwent EBUS-TBNA using a 21-gauge Olympus needle without suction. Samples were sent for molecular testing after rapid onsite specimen evaluation. A total of 6 to 10 passes were placed in a cell block. RESULTS: Sixty-nine samples from patients with non-small-cell lung cancer were sent for molecular testing for epidermal growth factor receptor. Results were obtained in all of the patients. Mutations were found in three patients (4.3%). Fifty-eight samples were sent for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (100% yield), 10 of which had mutations (17.2%). Fifty-one samples were sent for proto-oncogene tyrosine-protein kinase ROS testing (1 [7.8%] mutant). Tissue samples were inadequate in three patients (94.1% yield). Sixty-three samples were sent for anaplastic lymphoma receptor tyrosine kinase testing (3 [4.8%] mutant, 6 [9.5%] inadequate, 90.5% yield). CONCLUSIONS: EBUS-TBNA with a 21-gauge needle is appropriate for the analysis of multiple mutations and the genotyping of lung adenocarcinoma.

Monitoring for and Characterizing Crizotinib Progression: A Chart Review of ALK-Positive Non-Small Cell Lung Cancer Patients.

INTRODUCTION: Crizotinib is recommended as first-line therapy for ALK-positive non-small cell lung cancer (NSCLC), but within a year of treatment initiation many patients develop resistance. With the recent approval of second-generation ALK inhibitors, this study assessed how physicians monitor for and diagnose progression and how they alter treatment following progression on crizotinib. METHODS: A panel of oncologists from the United States were surveyed regarding their monitoring practices and criteria for diagnosing progression on crizotinib. The physicians also retrospectively provided data (March-June 2016) from the medical charts of their adult patients with locally advanced or metastatic ALK-positive NSCLC who progressed on crizotinib after the approval (April 2014) of the first second-generation ALK inhibitor, ceritinib. RESULTS: A total of 28 physicians responded to the survey. Data was abstracted on 74 patients. In the physician survey, most physicians (71%) reported monitoring for radiographic progression every 3-4 months. When new lesions were detected, physician response varied. Following a symptomatic isolated lesion, most physicians (75%) would add local therapy and resume crizotinib. Following multiple symptomatic lesions, 96% and 64% of physicians would switch to a new therapy depending on whether the lesions were extracranial or isolated to the brain, respectively. For the patient cohort, physician-defined progression on crizotinib was diagnosed after a median of 10 months, and within 30 days of diagnosis, 86% of patients discontinued crizotinib. Among all patients who discontinued crizotinib, 77% switched to ceritinib, 14% to chemotherapy, and 1% to alectinib. The remaining 7% did not receive additional systemic antineoplastic therapy. CONCLUSION: The findings from this physician survey and retrospective chart review study suggest that physician response to the development of new lesions in crizotinib-treated ALK-positive NSCLC patients varies with location and extent of the lesions. Once patients were considered to have progressed, most of them were immediately switched to ceritinib. FUNDING: Novartis Pharmaceuticals Corporation.

Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer Patients Receiving Ceritinib: A Chart Review Study.

INTRODUCTION: This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. METHODS: US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib. RESULTS: Medical charts of 58 ALK-positive NSCLC patients treated with ceritinib were reviewed (median age 63 years; 41% male; 21% with prior chemotherapy experience). At ceritinib initiation, 44 patients had multiple distant metastases, most commonly in the liver (60%), bone (53%), and brain (38%). Initial ceritinib dose varied: 71% received 750 mg, 19% 600 mg, and 10% 450 mg. Although median follow-up after ceritinib initiation was short (3.8 months), most patients achieved either a complete or partial response (69%) on ceritinib, regardless of metastatic sites present at initiation or initial dose. Median PFS on ceritinib was 12.9 months. 17% of patients had a gastrointestinal AE reported during follow-up. The majority of events occurred in patients instructed to fast; no patients instructed to take a lower dose of ceritinib with food reported gastrointestinal AEs. CONCLUSION: These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs. Future studies with larger sample size and longer follow-up are warranted, including an ongoing randomized trial to assess the gastrointestinal tolerability of ceritinib 450 and 600 mg with low-fat meals. FUNDING: Novartis Pharmaceutical Corporation.

Characteristics, treatment patterns, and survival among ALK+ non-small cell lung cancer (NSCLC) patients treated with crizotinib: A chart review study.

OBJECTIVES: Second-generation ALK inhibitors are recently available for ALK+ non-small cell lung cancer (NSCLC) patients previously treated with crizotinib. This study described characteristics, treatment sequencing, and outcomes among locally advanced/metastatic crizotinib-experienced ALK+ NSCLC patients. MATERIALS AND METHODS: From July 2014 to June 2015, a retrospective patient chart review was conducted among physicians from the US, EU, Korea, and Latin America. Participating clinicians identified their ALK+ NSCLC patients who received crizotinib and reported on their clinical characteristics, treatments, and survival using a pre-defined case report form. Kaplan-Meier analyses were used to describe overall survival (OS) and clinician-defined progression-free survival (PFS). RESULTS: Participating clinicians reviewed charts of 158 ALK+ NSCLC patients treated with crizotinib during the study period. Crizotinib was most commonly received in the second-line setting (41% of patients), though this varied across geographical regions. Roughly half (53%) of the patients who discontinued crizotinib received further antineoplastic therapy; second-generation ALK inhibitors (44%) and chemotherapy (42%) regimens were used most frequently. Following crizotinib discontinuation, median OS was 8.2 months. Among patients who did not initiate a second-generation ALK inhibitor following crizotinib, median OS was 4.9 months; among those who did, median OS was not reached. Among patients who received chemotherapy immediately following crizotinib discontinuation, time to clinician-defined PFS from post-crizotinib chemotherapy initiation was 3.6 months. CONCLUSION: Following crizotinib discontinuation, many patients received no further antineoplastic therapy, and OS was poor among patients who did not receive a second-generation ALK inhibitor. Recently available second-generation ALK inhibitors may provide important treatment options for ALK+ NSCLC patients.

Financial impact of palliative care consultation in a public hospital.

BACKGROUND: Palliative care programs assist with prognostication, symptom control, and communication with patient and family. Hospitals often require financial justification for new programs Objective: Study the financial impact of the palliative care consultation (PCc) service in a public hospital. SETTING/SUBJECTS: From January to December 2005, 258 deaths occurred on the medicine service. Of those deceased patients, 116 were studied. DESIGN: Inclusion criteria were 50 or more years of age, length of stay (LOS) 3 days or more, admission to an internal medicine service, and death during that hospitalization. MEASUREMENTS: Charges, diagnosis-related groups (DRGs), DRG weights, and demographic variables were examined. RESULTS: Of the 116 deceased patients studied, 61 patients received a PCc, while 55 did not. Most patients had Medicare or Medicaid (82.8%). Both groups were similar in terms of demographic characteristics. Average LOS was 14.4 days for patients with a PCc versus 12.2 days for those without (p = 0.57). Median charges for the group without a PCc were $42,731, versus a median of $35,824 for those with a PCc. There was no significant variation of DRG weights within the same DRG. DRG weight was significantly positively correlated with charges. Both PCc and DRG weight were significant predictors of charges, with 36% of charges variability explained by PCc and DRG weight. CONCLUSIONS: PCc significantly reduced charges in adult patients who died during their last hospitalization, even though the average LOS was higher for those who received a PCc versus those who did not.

Topiramate in the treatment of neuropathic pain in patients with cancer.

INTRODUCTION: Neuropathic pain has been reported to affect 40%-50% of patients with cancer. PATIENTS AND METHODS: Consecutive patients selected from the outpatient/adult patient palliative care clinic of the Roudebush Veterans Affairs Medical Center and the Indiana University Palliative Clinic were reviewed. A verbal pain linear analogue assessment scale was used to assess neuropathic pain. Pain medication history was also reviewed in addition to percent pain relief. The following variables were extracted from the medical record: pain characteristics, location, cause, date of initiation of therapy, maximal tolerated dose, pain scores on the visit of optimal tolerated dose, other concurrent medications, number of months of pain before initiation of topiramate therapy, and total duration of topiramate therapy. Decrease in worst, best, and average pain was recorded, as were the development of any adverse effects. RESULTS: Of the 13 patients on second- and third-line therapy, 53.8% had >/= 30% decrease in worst pain; 69.2% had >/= 30% decrease in average pain, and 53.8% had >/= 30% decrease in best pain. Eight of 13 patients (61.5%) experienced adverse effects. Five patients discontinued (38.5%) topiramate because of adverse events. CONCLUSION: Because our retrospective study showed topiramate to be a beneficial second- and third-line therapy in patients with cancer who did not experience adequate pain control on previous regimens, further prospective studies are needed to establish this medication in the armamentarium of neuropathic cancer pain management.