This video highlights some of the latest developments guiding precision medicine for lung cancer in clinical practice.
Ramaswamy Govindan, MD
We summarize here key findings from the comprehensive analysis of squamous cell lung cancer by The Cancer Genome Atlas group and discuss the clinical implications of these findings.
Dr. Ramaswamy Govindan, Washington U at St. Louis, discusses patient screening, new research in targeted therapies, as well as the continued role of traditional chemotherapy in lung cancer.
Influenza infection is a potential cause of additional morbidity and mortality in patients who are immunocompromised because of cancer or its treatment. Of particular note, influenza infection may delay or interrupt chemotherapy and necessitate hospitalization. Successful immunization depends on an intact immune system that can produce antibodies in response to antigen exposure. Patients with cancer often have a suppressed immune system, resulting from their disease and/or immunosuppressive therapies, and as a consequence they may have a suboptimal serologic response to influenza vaccination. Since vaccination is the only proven method for preventing influenza infection, the Advisory Committee on Immunization Practices recommends seasonal influenza vaccination for adults without contraindications who have disease- or medication-related immunosuppression. Patients with cancer should be given the trivalent inactivated vaccine. Preliminary data suggest that administering the vaccine between cycles of chemotherapy may yield the best results.
Bronchioloalveolar carcinoma (BAC) is a unique subtype of lung adenocarcinoma that has received increasing attention in recent years. Levy and colleagues have provided a comprehensive review of the clinical and pathologic characteristics of this disease, as well as the clinical evidence available to guide treatment of patients with BAC.
Lung cancer in “never-smokers” constitutes only a small proportion of patients with lung cancer. Nevertheless, the topic has recently attracted a good deal of attention. Initially this was due to the fact that never-smokers with lung cancer had better outcomes with epidermal growth factor receptor–tyrosine kinase (EGFR-TK) inhibitors, compared to tobacco smokers with lung cancer. More recently the identification of molecular changes unique to lung cancer in never-smokers has generated further interest in this disease. These findings have the potential to enhance our knowledge of lung cancer biology and lead to the development of new, more effective treatments for lung cancer. In this review, we summarize the existing body of knowledge on lung cancer in never-smokers.
In this edition of Clinical Quandaries, Ramalingam et al present a 67-year-old man who seeks care for a new, asymptomatic left upper lobe lung mass, which was found incidentally on a routine chest x-ray as part of a preoperative work-up for an elective surgery. Further staging studies included a computed tomography (CT) scan of the chest and a positron-emission tomography (PET) scan followed by a magnetic resonance imaging (MRI) scan of the liver. Pathology from a fine-needle aspiration biopsy of the left lingular lesion was consistent with poorly differentiated adenocarcinoma and immunohistochemical stains consistent with a lung primary. The left lingular lesion and the prevascular lymph node were felt to be the only sites of involvement, making this stage IIIA (T1, N2, M0) lung cancer.
Despite the high prevalence of brain metastases in patients with metastatic lung cancer, these patients have been excluded from enrollment in clinical trials of new therapeutic drugs. The reasons for exclusion have centered on concerns that the blood-brain barrier may impede drug delivery into brain metastases, that brain metastases confer a dismal survival for metastatic lung cancer patients, and that brain metastases carry risk for cerebrovascular hemorrhage. A focused, updated review of these issues, however, clearly shows that these particular concerns are unwarranted. An extensive review of clinical trials on the efficacy of chemotheraputic agents against lung cancer brain metastases is also provided. This collective information describes an area in need of therapeutic development and supports an initiative to evaluate novel targeted therapies for lung cancer brain metastases.
The 1-year survival for patients with metastatic non–small-cell lung
cancer is only around 35%. We are evaluating the combination of
irinotecan (Camptosar) and carboplatin (Paraplatin) in patients with
stage IIIB and IV non–small-cell lung cancer. The first five patients
received irinotecan, 250 mg/m2 over 90 minutes followed by carboplatin
at an area under the concentration-time curve of 5 over 1 hour. The
dose of irinotecan was subsequently reduced to 200 mg/m2 in view of
febrile neutropenia in one of five patients. Chemotherapy cycles are
repeated every 21 days. Patients are reevaluated every two cycles. Of a
planned 42 patients, 37 have been enrolled so far. Of the 37 enrolled
patients, 25 received at least two cycles, 20 received at least four cycles,
and 12 received all six planned cycles. Grade 4 neutropenia (absolute
Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2)
enzyme. In preclinical studies, COX-2 inhibition results in decreased
cell proliferation and potentiation of chemotherapy and radiation. We
report preliminary results of a phase II study conducted by the Hoosier
Oncology Group in patients with potentially resectable esophageal cancer.
All patients received cisplatin at 75 mg/m2 given on days 1 and 29
and fluorouracil (5-FU) at 1,000 mg/m2 on days 1 to 4 and 29 to 32
with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) was
administered at 200 mg orally twice daily beginning on day 1 until
surgery and then at 400 mg orally twice daily until disease progression
or unexpected toxicities, or for a maximum of 5 years. Esophagectomy
was performed 4 to 6 weeks after completion of chemoradiation. The
primary study end point was pathologic complete response (pCR). Secondary
end points included response rate, toxicity, overall survival, and
correlation between COX-2 expression and pCR. Thirty-one patients
were enrolled from March 2001 to July 2002. Respective grade 3/4 toxicities
were experienced by 58%/19% of patients, and consisted of granulocytopenia
(16%), nausea/vomiting (16%), esophagitis (10%), dehydration
(10%), stomatitis (6%), and diarrhea (3%). Seven patients (24%)
required initiation of enteral feedings. There have been seven deaths
so far, resulting from postoperative complications (2), pulmonary embolism
(1), pneumonia (1), and progressive disease (3). Of the 22 patients
(71%) who underwent surgery, 5 had pCR (22%). We conclude
that the addition of celecoxib to chemoradiation is well tolerated. The
pCR rate of 22% in this study is similar to that reported with the use of
preoperative chemoradiation in other trials. Further follow-up is necessary
to assess the impact of maintenance therapy with celecoxib on