Clinical Diagnostics - Lung

Globally, lung cancer remains the leading cause of cancer-related death with an estimated 157,300 cancer deaths for 2010 In the United States.

Cancer Facts and Figures 2010.

Globocan 2008

Early diagnosis of lung cancer for patients at high risk of recurrence is a clear unmet medical need. The American Cancer Society projects in 2008 a total of 215,020 people were diagnosed and 161,840 people died from lung cancer.

The diagnosis of lung cancer presents many challenges. When sick and symptomatic patients are being screened for cancer, diagnostic findings are often inconclusive and fail to detect the presence of malignancy in patients with suspected cancer.

Lung cancer may be seen on chest radiographs and computed tomography (CT scans). The diagnosis is confirmed with a biopsy. This is usually performed by bronchoscopy or CT-guided biopsy. At the time of first bronchoscopy in approximately 30% of the suspected cancer cases, cytology and histology do not provide conclusive results leading to unnecessary time consuming and costly procedures.

Treatment and prognosis depend upon the histological type of cancer, the stage (degree of spread), and the patient's performance status. Current lung cancer treatments include surgery, chemotherapy and/or radiation.

Adjuvant chemotherapy after surgery is not recommended for lung cancer patients that are stage I (15%) as this therapy is costly and toxic. However approximately 30-40% of patients with resected stage I lung cancer suffer disease recurrence which is usually fatal. Here is a need for diagnostic tests to assess the risk of recurrence and to identify which early stage patients should receive adjuvant chemotherapy.

Increased DNA methylation indicates high risk of cancer and therefore supports the needs of further investigation. MDxHealth has established extensive programs in the development of lung cancer diagnostics including biomarkers for lung cancer and related conditions. Using its patented MSP methlyation technology and in collaboration with Johns Hopkins Medical Center, the company identified prospective biomarkers associated with the characterization and evaluation of lung cancer in an exploratory clinical trial in 2007. Results from this initial clinical trial led to a publication in the New England Journal of Medicine.

MDxHealth is developing two products in the lung cancer field to improve the accuracy of standard diagnostic procedures for early detection of lung cancer and to address the risk of recurrence in stage I patients.

Products

ConfirmMDx for Lung Cancer is a molecular diagnostic test designed for the diagnostic evaluation of routinely collected bronchoscopy and/or sputum samples. The test provides physicians with a tool to aide in the accurate assessment of the presence or absence of cancer cells.

InformMDx for Lung Cancer is a molecular prognostic test which will provide physicians with a new tool to aide with risk assessment of Stage I lung cancer patients and with confirmation of whether the patient is either at low risk or high risk of recurrence. This test, when used in conjunction with other clinical risk factors, will help physicians in their determination of which patients may benefit from more aggressive treatment, including chemotherapy. A preliminary study of this test as published in the NEJM and showed that it could accurately predict the 30-40% of stage I lung cancers that would recur after surgery.

Literature

Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, Glöckner S, Piantadosi S, Gabrielson E, Pridham G, Pelosky K, Belinsky SA, Yang SC, Baylin SB, Herman JG., DNA methylation markers and early recurrence in stage I lung cancer., N Engl J Med. 2008 Mar 13;358(11):1118-28. Belinsky SA, Grimes MJ, Casas E, Stidley CA, Franklin WA, Bocklage TJ, Johnson DH, Schiller JH., Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum., Br J Cancer. 2007 Apr 23;96(8):1278-83.

Belinsky SA, Liechty KC, Gentry FD, Wolf HJ, Rogers J, Vu K, Haney J, Kennedy TC, Hirsch FR, Miller Y, Franklin WA, Herman JG, Baylin SB, Bunn PA, Byers T., Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort., Cancer Res. 2006;66(6):3338-44.

Belinsky SA, Klinge DM, Dekker JD, Smith MW, Bocklage TJ, Gilliland FD, Crowell RE, Karp DD, Stidley CA, Picchi MA., Gene promoter methylation in plasma and sputum increases with lung cancer risk., Clin Cancer Res. 2005;11(18):6505-11.

Divine KK, Pulling LC, Marron-Terada PG, Liechty KC, Kang T, Schwartz AG, Bocklage TJ, Coons TA, Gilliland FD, Belinsky SA., Multiplicity of abnormal promoter methylation in lung adenocarcinomas from smokers and never smokers., Int J Cancer. 2005;114(3):400-5

Machida EO, Brock MV, Hooker CM, Nakayama J, Ishida A, Amano J, Picchi MA, Belinsky SA, Herman JG, Taniguchi S, Baylin SB., Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer., Cancer Res. 2006;66(12):6210-8.

MDxHealth’s products are not currently cleared or approved by the FDA.