In June 2012, a graduate student named Zacariah Labby submitted his doctoral dissertation to the Committee on Medical Physics at the University of Chicago’s Pritzker School of Medicine.
For the past five years, he had worked under world-renowned mesothelioma experts Dr. Samuel Armato and Dr. Hedy Lee Kindler. While studying mesothelioma response evaluation models, he noticed a big problem.
Some patients who doctors thought were getting better passed away before patients whose disease was progressing.
This led Labby to believe that current criteria may not accurately determine a mesothelioma patient’s response. Doctors may accidentally misclassify stable tumors as progressive, unnecessarily limiting the patient’s treatment options.
Labby then launched a study to optimize the classification criteria. He rearranged patients in categories until there was an improved correlation between image-based response and patient survival.
Based on his optimized criteria, just over 22 percent of the patients in Labby’s study were originally misclassified.
His findings will appear in the November issue of the Journal of Thoracic Oncology.
Problems with the Current Mesothelioma Evaluation Models
Most doctors use CT scans to evaluate a mesothelioma tumor’s response to treatment.
They also measure the thickness of the tumor, then classify patients as having either responsive, stable or progressive disease.
The standard rules say that if a tumor decreases by more than 30 percent, the patient has a partial response. If the tumor increases by 20 percent or more, it is considered progressive disease.
Unfortunately, not all mesothelioma patients fit this model.
Standard criteria were developed to apply to all solid tumors. As Labby’s team pointed out, there are no specific considerations for the unique growth pattern of mesothelioma.
Mesothelioma tumors often overlap with the muscles in the adjacent chest wall. This makes it difficult for doctors to correctly identify the boundaries of the tumor.
Additionally, pleural effusions fluid buildups that affect up to 90 percent of mesothelioma patients can look like cancerous tissue on a CT scan.
“There is room for doubt on the applicability of such criteria for classification of response in a disease so typically aspherical as mesothelioma,” Labby wrote in his dissertation.
Tailoring Response Criteria to Mesothelioma Patients
To develop mesothelioma-specific criteria, Labby studied a cohort of 78 pleural mesothelioma patients receiving chemotherapy at Sir Charles Gairdner Hospital in Western Australia.
Doctors took between two and five CT scans of each patient throughout their treatment. On average, they measured the tumor response every 45 days. Researchers also collected final survival data.
Labby adjusted the response criteria in 1 percent increments until all patients in the group had a survival rate that matched their classification. He determined that the standard criteria misclassified 17 patients.
Labby believed that some of the patients in his study could have qualified for clinical trials if classified under his criteria. Both of the patients who were considered to have progressive disease under standard criteria were reclassified as having stable disease under Labby’s optimized criteria.
Misclassified patients may miss out on potentially lifesaving treatments. Some may not qualify for standard therapies, while others may miss the cutoff for clinical trials.
“These techniques will hopefully impact the tools clinicians use to assess patient response in both phase II clinical trials and routine patient care,” explained Labby in his dissertation.