3 Abstracts by UC Trainees Selected for ASCO National Meeting Book

Three abstracts by University of Cincinnati researchers were published in the American Society of Clinical Oncologist National Meeting’s book. The annual meeting was held May 29 to June 2, 2015, in Chicago. 

The abstracts were selected out of more than 5,900 which were reviewed by ASCO’s Scientific Program Committee and leadership. 

Nagla Karim, MD, PhD, associate professor in the Division of Hematology Oncology at the UC College of Medicine and a member of both the Cincinnati Cancer Center and UC Cancer Institute, was the mentor for all three trainees who were the first authors on these studies.

"This shows the research excellence present within the College of Medicine and our trainees who are exploring ways to better treat patients using existing clinical data,” she says. 

Survival in End-Stage Lung Cancer Patients Who Take Anticoagulants

First and Second Authors: Shuchi Gulati, MD, and Mahendar Yellu, MD, clinical fellows in the Division of Hematology Oncology beginning in July and September. 

Low molecular heparin, a class of anticoagulants, is an approved treatment to prevent for formation of blood clots in patients with cancer. However, its role in improving survival in this patient population is unclear. 

Researchers involved in this study looked at retrospective data on patients with advanced lung cancer—Stages III and IV—to see who may have been on the medication and how it improved their outcomes. The data used was logged between the years 2004 and 2014 and excluded patients with early stage lung cancer and who had incomplete information.

Researchers also looked at demographics (age, gender, and ethnicity), results from tissue samples and all of medications being taken by the patient. Patients both taking and not taking this anticoagulant were identified. 

The Kaplan-Meier method, a statistical analysis used to estimate survival based on lifetime data, and the Cox model, a statistical technique for exploring the relationship between the survival of a patient and several explained variables, were used. A subgroup analysis was performed for patients on this anticoagulant with history of clotting to calculate the maximum likelihood of a clot occurring.

From 197 patients with advanced lung cancer, 28 were found to be on the drug. Their average age at the time of diagnosis was about 62 years old, and average survival with the medication was 460 days and 539 without the medication. The subgroup had a lower survival rate of about 322 days when compared to patients without clots. None of the patients on the anticoagulant had a major bleeding event listed as a cause of death. 

The results did not show a clear improvement with use of the low molecular heparin in advanced stage lung cancer patients and even saw a trend towards higher death rates in patients treated with the anticoagulant; however, patients who had blood clots or a stroke had lower survival when compared to patients who used the anticoagulant without blood clots or a stroke. Future studies using a larger patient population should evaluate these findings.

Antidepressant Use in Patients With Advanced Lung Cancer 

First and Second Authors: Nabeela Iffat Siddiqi, MD, Internal Medicine Resident at the University of Cincinnati, Mahendar Yellue, MD, clinical fellow in the Division of Hematology Oncology starting in September.

Research, done by looking at a large number of gene expression datasets in already existing data, has identified Tricyclic antidepressants (compounds used as antidepressants) as possibly being beneficial for lung cancer patient outcomes.

These compounds were found to cause cell death in chemotherapy resistant tumor cells in humans.

This study also used respective patient data to identify those with advanced lung cancer—Stages III and IV—between 2004 and 2014. Patients with early stage lung cancer and with incomplete data were excluded.  

Researchers also looked at demographics (age and gender), results from tissue samples, antidepressant use and date of death. Patients both taking and not taking antidepressants were identified, and thosepatients not using antidepressants were used as the control group. Other antidepressants including duloxetine, trazodone, and mirtazapine were grouped together. 

The Kaplan-Meier method, a statistical analysis used to estimate survival based on lifetime data, and the Cox model, a statistical technique for exploring the relationship between the survival of a patient and several explained variables, were used. 

Of the 197 patients reviewed, 45 were on antidepressants. The average survival rate for patients on Tricyclic antidepressants was 307 days when compared to 560 days in the control group. The group of patients taking selective serotonin re-uptake inhibitors, a class of compounds also used as antidepressants, had an average survival of 436 days compared to 539 days; however, the Cox model showed that patients in this group had a potential trend to live longer. Patients taking other antidepressants aside from these had an average survival rate of 805 days compared to 531 days.

This study shows that Tricyclic antidepressants had a negative impact on overall survival rates for patients which opposes what was found in preclinical trials. Other classes of antidepressants had no statistical impact on survival; however, the data on selective serotonin re-uptake inhibitors showed a trend toward improved survival. Researchers say further studies in a larger population are needed to explore these results. 

The Spectrum of Outcomes for Patients With Metastatic Uveal Melanoma

First Author: Ayham Deeb, MD, clinical instructor in the Division of Hematology Oncology.

Uveal melanoma, which is cancer of the uvea in the eye—the uvea means the iris, the ciliary muscle which controls the shape of the lens and the choroid which contains all of the eye’s blood vessels—is the rarest form of all melanomas and has a distinct way of forming molecularly in the body. Once it metastasizes, or spreads, the outcomes become very poor; however, overall survival is not the same among all patients with metastatic uveal melanoma and more information is needed on the spectrum of outcomes.

In this study, researchers examined the different variables that could influence survival in this specific melanoma and retrospectively reviewed patients’ disease characteristics at the time of diagnosis and at the time metastasis was detected, including the time between these two events.

Information about 42 patients—22 male and 20 female—with an average age of 62 was included in this study. In these patients:

• Around 60 percent had a tumor that started in the choroid and involved the ciliary area of the uvea in around 40 percent of this group.
• All patients had metastatic disease—in around 55 percent the cancer spread only liver, in about 26 percent the cancer spread both in and outside of the liver and in about 10 percent the cancer spread outside of the liver.
• The average interval between the initial date of eye treatment and the initial date of metastasis detection was almost three years (about 35 months), while the average interval from initial treatment to the date of death or the last follow-up was about four years (51 months). 
• The average overall survival of this group was about 10 months and was longer in females than in males.
• The patients with interval to metastasis detection of less than two years had less survival in comparison to patients with an interval of more than two years. 
• Having only metastasis that spread outside of the liver was associated with better survival in comparison to only liver or both liver and outside of the liver metastases. 
• The influence of age at the date of metastasis detection was not significant. 
• Having an exclusively choroidal tumor versus a tumor that involved the ciliary area did not predict survival.

This analysis showed that, overall, uveal melanoma is associated with very poor outcomes and the short interval for development of metastasis and liver metastasis significantly worsened survival for these patients, while those patients who experienced spread of the cancer outside of the liver region and female patients had better survival rates. 

Additional factors may come into play in the analysis of survival time following detection of metastasis. Researchers say further studies on this are needed.