Lung Cancer

Stage IB non–small-cell lung carcinoma (NSCLC) represents a subset of early-stage, resectable NSCLC, usually treated with curative intent, but with historically modest 5-year survival rates ranging from 40% to 67% with surgical resection alone.[1,2] Disappointingly, modern adjuvant chemotherapy trials including stage IB patients have shown little evidence of chemotherapeutic benefit.

The appropriate treatment of patients with stage IIIA (N2) non–small-cell lung cancer (NSCLC) is unclear. With this case report and review, we address the history, assessment, and management of a 67-year-old patient with this diagnosis, and then discuss the challenges in managing N2 disease, as well as the roles of systemic therapy, surgery, and postoperative radiation therapy.

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.

Nereus Pharmaceuticals, Inc. has begun enrolling patients in an open-label phase 1b study evaluating its vascular disrupting agent NPI-2358 in combination with docetaxel (Taxotere) in patients with non-small-cell lung cancer who previously failed at least one chemotherapy regimen.

n a phase III trial of the investigational chemoprotective agent dimesna (Tavocept, also known as BNP7787) in patients with advanced non-small-cell lung cancer, the drug did not significantly prevent or reduce the severity of chemotherapy-induced neuropathy, its primary endpoint, BioNumerik Pharmaceuticals, Inc and ASKA Pharmaceutical Co. (Tokyo, Japan) announced in a press release.

Accuray Incorporated has announced that approximately 90% of the more than 125 CyberKnife centers worldwide are now treating lung cancer with the CyberKnife Robotic Radiosurgery System. CyberKnife centers in 12 countries have treated more than 5,000 lung cancer patients to date with the CyberKnife System, the company said in a news release.

The always-controversial International Early Lung Cancer Action Program has been struck a serious blow with news that the trial was funded in part by a cigarette manufacturer, according to an article in the New York Times (March 26, 2008).

In a phase II, multicenter trial, sunitinib (Sutent) showed activity as a single agent in heavily pretreated non-small-cell lung cancer patients. The overall objective response rate was 11.1%, and median overall survival was 23.4 weeks (Socinski et al: J Clin Oncol 26:650-656, 2008).

A new method for converting between different definitions of lung volume may help standardize radiation dose reporting for patients receiving radiation therapy for lung cancer, finds a study using four-dimensional CT imaging. 4D-CT is a series of CT scans that measure how much a tumor moves when a patient breathes and allows radiation oncologists to personalize radiation treatment for this motion.

Drs. Kelsey, Marks, and Wilson open their excellent review article by asking “Where do we stand?” with respect to postoperative radiation therapy (PORT) for non–small-cell lung cancer (NSCLC).[1] Frankly, PORT has not exactly been standing tall for the past decade-leaning, crouching, or perhaps squatting might be a better verb.

Kelsey et al have written an excellent review on postoperative radiotherapy (PORT) for non–small-cell lung cancer (NSCLC). As pointed out in this thorough yet concise review, there are inconsistencies in the recommendation of PORT for NSCLC.

Lung cancer is the leading cause of cancer mortality in the United States. Local recurrence after surgery for operable disease has long been recognized as a hindrance to long-term survival. Postoperative radiation therapy was logically explored as a means to improve local control and survival. Multiple randomized trials were conducted, many showing improved local control, but none demonstrated a statistically significant survival benefit.

"Researchers defend NLST protocol against its critics" (ONI, January 2008, page 14) quoted three individuals in the United States who strongly support the NLST [National Lung Screening Trial] and no one on the other side of the issue.

A new MRI technique—inhaled hyperpolarized helium-3 diffusion MRI—shows lung damage in nonsmokers exposed to second-hand smoke

In a surprising discovery, reported at RSNA 2007, researchers from Germany have found that whole-body staging of patients with recently diagnosed malignant melanoma using either MRI or PET/CT could miss a substantial number of metastatic lesions

Two minimally invasive staging methods used together may be an accurate substitute for mediastinoscopy for some lung cancer patients with suspected metastatic mediastinal lymph nodes

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.

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 first interim results from the first study of dasatinib (Sprycel) as induction therapy of Ph+ acute lymphoblastic leukemia (ALL) show complete and early hematologic responses with good overall compliance

Positron emission tomography (PET) can be used to better characterize patterns of local failure after definitive radiation therapy for non-small-cell lung cancer, which may help to improve that therapy

The efficacy of cetuximab (Erbitux) plus chemoradiation in patients with locally advanced non-small-cell lung cancer does not appear to vary with the tumor's epidermal growth factor receptor expression, according to preliminary results of a phase II trial

First phase III trial of Zactima in NSCLC completes enrollment

A 68-year-old man with a history of small-cell lung cancer with bony metastases was admitted with diarrhea. The patient had completed chemotherapy one week earlier with cisplatin and etoposide, along with radiation therapy, and irinotecan (Camptosar). The patient was found to be neutropenic.

Radiation therapy (RT) is an important treatment modality for multiple thoracic malignancies. Incidental irradiation of the lungs, which are particularly susceptible to injury, is unavoidable and often dose-limiting. The most radiosensitive subunit of the lung is the alveolar/capillary complex, and RT-induced lung injury is often described as diffuse alveolar damage. Reactive oxygen species generated by RT are directly toxic to parenchymal cells and initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating a self-sustaining cycle of inflammation and chronic oxidative stress. Replacement of normal lung parenchyma by fibrosis is the culminating event. Depending on the dose and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea. Fibrosis of the lung, which can also cause dyspnea, is the late complication. Imaging studies and pulmonary function tests can be used to quantify the extent of lung injury. While strict dose-volume constraints to minimize the risk of injury are difficult to impose, substantial data support some general guidelines. New modalities such as intensity-modulated radiation therapy and stereotactic body radiation therapy provide new treatment options but also pose new challenges in safely delivering thoracic RT.

Radiation therapy (RT) is an important treatment modality for multiple thoracic malignancies. Incidental irradiation of the lungs, which are particularly susceptible to injury, is unavoidable and often dose-limiting. The most radiosensitive subunit of the lung is the alveolar/capillary complex, and RT-induced lung injury is often described as diffuse alveolar damage. Reactive oxygen species generated by RT are directly toxic to parenchymal cells and initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating a self-sustaining cycle of inflammation and chronic oxidative stress. Replacement of normal lung parenchyma by fibrosis is the culminating event. Depending on the dose and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea. Fibrosis of the lung, which can also cause dyspnea, is the late complication. Imaging studies and pulmonary function tests can be used to quantify the extent of lung injury. While strict dose-volume constraints to minimize the risk of injury are difficult to impose, substantial data support some general guidelines. New modalities such as intensity-modulated radiation therapy and stereotactic body radiation therapy provide new treatment options but also pose new challenges in safely delivering thoracic RT.

A major issue facing radiologists who use computer-aided detection systems for early detection of lung cancer is deciding when a CAD finding truly represents malignancy.

ASA404 lung cancer trial expanded

Patients with locally advanced non-small-cell lung cancer and a good performance status have better overall survival and a lower risk of local-regional progression if they receive concomitant chemoradiation instead of sequential chemoradiation, according to a meta-analysis from the NSCLC Collaborative Group presented at this year's ASTRO meeting

The lack of an effective, detailed workup algorithm for positive results in multicenter lung cancer screening trials leads to a lower cancer yield from invasive procedures and later diagnoses for participants

New drugs on the horizon could reduce the adverse effects of radiation to the lung, allowing higher doses for lung cancer patients, according to studies presented at the 49th ASTRO annual meeting.