Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study.

Background: In the appropriate clinical setting, the diagnosis of idiopathic pulmonary fibrosis (IPF) requires a pattern of usual interstitial pneumonia to be present on high-resolution chest CT (HRCT) or surgical lung biopsy. A molecular usual interstitial pneumonia signature can be identified by a machine learning algorithm in less-invasive transbronchial lung biopsy samples. We report prospective findings for the clinical validity and utility of this molecular test.

Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules.

Importance: Use of next-generation sequencing of RNA and machine learning algorithms can classify the risk of malignancy in cytologically indeterminate thyroid nodules to limit unnecessary diagnostic surgery.

Objective: To measure the performance of a genomic sequencing classifier for cytologically indeterminate thyroid nodules.

Design, Setting, And Participants: A blinded validation study was conducted on a set of cytologically indeterminate thyroid nodules collected by fine-needle aspiration biopsy between June 2009 and December 2010 from 49 academic and community centers in the United States.

Identification of usual interstitial pneumonia pattern using RNA-Seq and machine learning: challenges and solutions.

Background: We developed a classifier using RNA sequencing data that identifies the usual interstitial pneumonia (UIP) pattern for the diagnosis of idiopathic pulmonary fibrosis. We addressed significant challenges, including limited sample size, biological and technical sample heterogeneity, and reagent and assay batch effects.

Results: We identified inter- and intra-patient heterogeneity, particularly within the non-UIP group.

Analytical performance of Envisia: a genomic classifier for usual interstitial pneumonia.

Background: Clinical guidelines specify that diagnosis of interstitial pulmonary fibrosis (IPF) requires identification of usual interstitial pneumonia (UIP) pattern. While UIP can be identified by high resolution CT of the chest, the results are often inconclusive, making surgical lung biopsy necessary to reach a definitive diagnosis (Raghu et al., Am J Respir Crit Care Med 183(6):788-824, 2011).

Usual Interstitial Pneumonia Can Be Detected in Transbronchial Biopsies Using Machine Learning.

Rationale: Usual interstitial pneumonia (UIP) is the histopathologic hallmark of idiopathic pulmonary fibrosis. Although UIP can be detected by high-resolution computed tomography of the chest, the results are frequently inconclusive, and pathology from transbronchial biopsy (TBB) has poor sensitivity. Surgical lung biopsy may be necessary for a definitive diagnosis.

Dendritic Versus Tumor Cell Presentation of Autologous Tumor Antigens for Active Specific Immunotherapy in Metastatic Melanoma: Impact on Long-Term Survival by Extent of Disease at the Time of Treatment.

In patients with metastatic melanoma, sequential single-arm and randomized phase II trials with a therapeutic vaccine consisting of autologous dendritic cells (DCs) loaded with antigens from self-renewing, proliferating, irradiated autologous tumor cells (DC-TC) showed superior survival compared with similar patients immunized with irradiated tumor cells (TC). We wished to determine whether this difference was evident in cohorts who at the time of treatment had (1) no evidence of disease (NED) or (2) had detectable disease. Eligibility criteria and treatment schedules were the same for all three trials.

MammaPrint molecular diagnostics on formalin-fixed, paraffin-embedded tissue.

MammaPrint, a prognostic 70-gene profile for early-stage breast cancer, has been available for fresh tissue. Improvements in RNA processing have enabled microarray diagnostics for formalin-fixed, paraffin-embedded (FFPE) tissue. Here, we describe method optimization, validation, and performance of MammaPrint using analyte from FFPE tissue.

Should high-dose interleukin-2 still be the preferred treatment for patients with metastatic melanoma?

For more than 20 years interleukin-2 (IL2) was the preferred treatment for medically fit metastatic melanoma patients, but recently two new agents, ipilimumab and vemurafenib, were approved for stage IV disease. Single-institution data were used to determine the long-term survival rate for IL2-treated melanoma patients, and whether use of inpatient IL2 had declined recently. Between May 1987 and April 2010, 150 patients were hospitalized for high-dose, intravenous (i.

Drug-Addicted Oncology Practice: The Drug Test.

Purpose: The buy-and-bill model of pharmaceuticals has been an economic reality for medical oncology practices for more than 30 years. Infusion services, once just a supportive service, grew exponentially in most practices between 1991 and 2000, to the point at which revenue from these services created a high, which made all things possible, including care of underinsured or uninsured patients. This altered state was further enhanced in the early part of this past decade when the introduction of high-cost chemotherapeutics and biologic agents created the euphoria of big business and a true dollar distortion for even the smallest oncology practice.

Should high-dose interleukin-2 still be the preferred treatment for patients with metastatic renal cell cancer?

Interleukin-2 (IL-2) was the preferred treatment for medically fit patients with advanced kidney cancer, but recently, several targeted therapies have been approved for metastatic renal cell carcinoma. We wished to determine the long-term survival rate for patients with kidney cancer treated with IL-2 and whether the use of intense inpatient IL-2 has declined since the introduction of targeted therapies. Patients who received IL-2 were identified from clinical trial enrollment, pharmacy logs, and financial billing records.

A retrospective study of induction chemotherapy with docetaxel, cisplatinum, and 5-fluorouracil followed by concurrent radiotherapy with cetuximab in locally advanced head and neck cancer.

Background: The objective was to study the results of induction chemotherapy followed by external beam radiation therapy with concurrent cetuximab in the treatment of locally advanced head and neck cancer.

Methods: Seventeen patients with stage III or IV squamous cell carcinomas of the head and neck who received docetaxel, cisplatinum, and 5-fluorouracil followed by radiation therapy with concurrent cetuximab were retrospectively analyzed. All radiation was delivered with image-guided intensity-modulated radiation treatments.

Phase II trial of dendritic cells loaded with antigens from self-renewing, proliferating autologous tumor cells as patient-specific antitumor vaccines in patients with metastatic melanoma: final report.

Unlabelled: Between January 2001 and September 2007, we treated 54 metastatic melanoma patients with patient-specific tumor cell vaccines consisting of dendritic cells (DCS), derived from their peripheral blood cells that were cultured in interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor (GM-CSF), which had phagocytosed irradiated autologous tumor cells from a continuously proliferating, self-renewing, autologus tumor cell (TC) culture. The loaded DCs were injected subcutaneously in 500 microg of GM-CSF weekly x three, and then monthly for 5 months, for a total of up to 8 injections. The 34 men and 20 women had a median age of 50.

Patient-specific vaccines derived from autologous tumor cell lines as active specific immunotherapy: results of exploratory phase I/II trials in patients with metastatic melanoma.

Seventy-four (74) patients with metastatic melanoma were treated with patient-specific vaccines derived from autologous tumor cell lines. Cryopreserved irradiated tumor cells were injected weekly for 3 weeks, then monthly for 5 months. At a median follow up >6 years, the median event-free survival (EFS) was 4.

High-dose chemotherapy and autologous stem cell rescue for metastatic breast cancer: superior survival for tandem compared with single transplants.

During 1990-1999, we treated 60 patients with breast cancer who had distant metastases with high-dose chemotherapy and autologous stem cell rescue (HDC) after they had responded to induction chemotherapy. HDC regimens were MiTepa (60 mg/m2 mitoxantrone by continuous intravenous infusion over 3 days plus 300 mg/m2 thiotepa intravenously over 2 hours daily x 3 days) and ICE (12 g/m2 ifosfamide, 1800 mg/m2 carboplatin, 2 g/m2 etoposide; all 3 by continuous intravenous over 4 days). At a median follow up >8 years, the median failure-free survival (FFS) was 13.

Tumor-infiltrating lymphocytes and interleukin-2: dose and schedules of administration in the treatment of metastatic cancer.

Purpose: The potential for therapeutic use of tumor-infiltrating lymphocytes (TIL), as adoptive cellular therapy has been touted for many years with some encouraging reports in patients with metastatic melanoma.

Materials And Methods: We previously described methodologies for TIL production and phenotypic characterization of TIL generated in our laboratory between 1991 and 1995 in semipermeable bags and between 1996 and 2000 in bioreactors. Patients treated in the earlier era were to have received a hybrid bolus and a 12-hour continuous infusion of interleukin (IL)-2 (total, 48 MIU), while in the latter era 4 days of interferon- alpha preceded the TIL and IL-2; which was given by a hybrid schedule that included bolus and 72- hour continuous IL-2 (total, 96 MIU).

Phase I/II trial of melanoma patient-specific vaccine of proliferating autologous tumor cells, dendritic cells, and GM-CSF: planned interim analysis.

Aim: The aim of this study was to investigate the feasibility, safety, and clinical efficacy of patient-specific dendritic cell vaccines in patients with metastatic melanoma. A planned interim analysis was conducted on the first 20 patients.

Methods: Tumor cell lines were established from metastatic tumor, expanded to 200 million cells, and then incubated with interferon-gamma for patients who were candidates for therapy.

Phase I/II trial of autologous tumor cell line-derived vaccines for recurrent or metastatic sarcomas.

Aim: We previously reported the laboratory methodology for producing patient-specific irradiated autologous tumor-cell products derived from short-term cultured tumor cells. We attempted to determine the feasibility, safety, and clinical effects of autologous tumor vaccine-derived sarcomas.

Patients And Methods: Efforts were made to establish tumor cell lines in tissue culture with expansion to 100 million cells for patients who were candidates for therapy.

Autologous tumor cell line-derived vaccine for patient-specific treatment of advanced renal cell carcinoma.

Aim: We previously reported the laboratory methodology for producing patient-specific irradiated autologous tumor-cell products derived from short-term cultured tumor cells from resected renal cell carcinoma, and described preliminary clinical results. In this study, we report the final clinical results and efforts to define vaccine potency on the basis of clinical outcome for these 25 patients with advanced renal cell carcinoma.

Materials And Methods: Approximately 10(8) cells from successful short-term cell lines were irradiated, frozen in aliquots of 10(7) cells, then thawed and administered subcutaneously (s.

Does continuous-infusion interleukin-2 increase survival in metastatic melanoma?

Pharmacy logbooks and clinical trial records were used to identify all 60 patients with metastatic melanoma who were treated as inpatients with intermediate-dose, continuous-infusion interleukin-2 (IL-2) in Hoag Hospital during 1987 to 1998. The hospital tumor registry was used to identify contemporary controls who had not received inpatient IL-2, matched for having distant metastatic melanoma, and by year and stage at original diagnosis, gender, and age. The mean time from original diagnosis to the documentation of distant metastatic disease was similar in both groups, 24 to 26 months.

Irradiated cells from autologous tumor cell lines as patient-specific vaccine therapy in 125 patients with metastatic cancer: induction of delayed-type hypersensitivity to autologous tumor is associated with improved survival.

Objective: We established short-term cultures of pure tumor cells for use as autologous tumor cell vaccines in an effort to study the effects of patients-specific immunotherapy.

Patients And Methods: Surgically resected fresh tumor was obtained from patients with metastatic cancer. Successful tumor cell lines (5 x 10(7)) were expanded to 10(8) cells, irradiated, and cryopreserved for clinical use.