Solitary Fibrous Tumors of Chest: Another Look with the Oncologic Perspective

Solitary fibrous tumors are mesenchymal lesions that arise at a variety of sites, most commonly the pleura. Most patients are asymptomatic at diagnosis, with lesions being detected incidentally. Nevertheless, some patients present due to symptoms from local tumor compression (eg. of the airways and pulmonary parenchyma). Furthermore, radiological methods are not always conclusive in making a diagnosis, and thus, pathological analysis is often required. In the past three decades, immunohistochemical techniques have provided a gold standard in solitary fibrous tumor diagnosis. The signature marker of solitary fibrous tumor is the presence of the NAB2-STAT6 fusion that can be reliably detected with a STAT6 antibody. While solitary fibrous tumors are most often benign, they can be malignant in 10-20% of the cases. Unfortunately, histological parameters are not always predictive of benign vs malignant solitary fibrous tumors. As solitary fibrous tumors are generally regarded as relatively chemoresistant tumors; treatment is often limited to localized treatment modalities. The optimal treatment of solitary fibrous tumors appears to be complete surgical resection for both primary and local recurrent disease. However, in cases of suboptimal resection, large disease burden, or advanced recurrence, a multidisciplinary approach may be preferable. Specifically, radiotherapy for inoperable local disease can provide palliation/shrinkage. Given their sometimes -unpredictable and often- protracted clinical course, long-term follow-up post-resection is recommended

Annual Review of Advances in Non-small Cell Lung Cancer Research: A Report for the Year 2010

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A thoracic surgery clinic dedicated to indeterminate pulmonary nodules: Too many scans and too little pathology?

ObjectiveWidespread application of computed tomographic scans has increased detection of asymptomatic pulmonary nodules. A dedicated clinic was established to encourage referral and manage large numbers of patients with such nodules.MethodsPatients were evaluated periodically by a nurse practitioner with surgeon oversight, and follow-up imaging was centralized. Patients were rescanned at intervals on the basis of radiologist recommendation.ResultsA total of 414 patients, 189 male and 225 female with a median age of 60.2 years (20.7–84.1 years), were evaluated since April 2000. Median follow-up was 1.51 years (0–6.65 years). Thirty-seven percent (153/414) were older than 60 years with at least 10 pack-years of tobacco use, whereas 30% (123/414) had never smoked. A total of 286 patients completed at least 2 years of follow-up computed tomographic evaluation. After 2 years, 24.2% (69/286) were deemed in stable condition and were discharged from further follow-up, whereas 22.4% (64/286) of patients were followed up longer than 2 years owing to the development of new nodules. Forty-five percent (127/286) of patients did not complete their recommended follow-up at our clinic. Overall, 3% (13/414) of our patients have been shown to have a malignant tumor. Only 5 patients underwent curative resection of a primary lung cancer.ConclusionIn a population of patients with indeterminate nodules in routine clinical practice, few patients required intervention and few cancers were detected. Although the benefits of a “nodule” clinic may include patient reassurance and convenience to referring physicians, a significant number of patients did not complete their follow-up in our clinic

Non–Small Cell Lung Cancer: Prognostic Importance of Positive FDG PET Findings in the Mediastinum for Patients with N0–N1 Disease at Pathologic Analysis

In non-small cell lung cancer, preoperative evaluation of the mediastinum with PET may complement the surgical and histologic findings

Differential Pathogenesis of Lung Adenocarcinoma Subtypes Involving Sequence Mutations, Copy Number, Chromosomal Instability, and Methylation

Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors.The LAD molecular subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with gene mutations and DNA copy number alterations using statistical methods and published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and interrogated to confirm subtype-alteration associations. Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation were significantly different among tumors of the molecular subtypes. Secondary analyses compared subtypes by integrated alterations and patient outcomes. Tumors having integrated alterations in the same gene associated with the subtypes, e.g. mutation, deletion and underexpression of STK11 with Magnoid, and mutation, amplification, and overexpression of EGFR with Bronchioid. The subtypes also associated with tumors having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall survival, cisplatin plus vinorelbine therapy response and predicted gefitinib sensitivity were significantly different among the subtypes.The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response. These results advance the understanding of lung adenocarcinoma etiology and nominate patient subgroups for future evaluation of treatment response

THE WASHINGTON MANUAL SURVIVAL GUIDE

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Exploring the Evolving Scope of Neoadjuvant Immunotherapy in NSCLC

While lung cancer remains the leading cause of cancer death worldwide, lung cancer mortality has notably decreased in the past decade. Immunotherapy with immune checkpoint inhibitors have played a noteworthy role in contributing to this improved survival, particularly for patients with non-small cell lung cancer (NSCLC). However, until now the benefits have primarily been seen in patients with advanced or metastatic disease. Several recent early phase and ongoing phase III trials have been assessing whether the treatment benefit of immunotherapy in NSCLC can extend to the neoadjuvant setting for resectable diseases. In this comprehensive narrative review, we evaluate the most recent efficacy and safety data from these studies. We also outline questions that will need to be further examined to legitimate neoadjuvant immunotherapy’s role in NSCLC treatment, including the best surrogate marker of response, the incorporation of liquid biopsy for disease monitoring, the ability to be combined with other treatment modalities, the need for further adjuvant therapy, and potential future treatment combinations