Effectiveness of Digital Breast Tomosynthesis Compared with Digital Mammography

In this article, the research team looked to determine whether improved initial outcomes of using DBT could be sustained over time.  The study was completed over 4 years and included 44,468 screenings attributable to 23,958 women.  The research team looked to compared recall rates, cancer cases per recalled patients, and biopsy and interval cancer rates.  Each women was followed over the course of 4 years and received either 1, 2, or 3 DBT screenings.  The number of screenings were then used as an intervention to determine the patient’s health.

The results of the study showed that the use of DBT remained significantly reduced compared with using digital mammography alone.  Overall, the study found that digital breast tonosynthesis outcomes are not only sustainable but provide significant recall reduction and a decline in interval cancers.

McDonald ES, Oustimov A, Weinstein SP, et al.  Effectiveness of digital breast tomosynthesis compared with digital mammography.  JAMA Oncol. doi:10.1001/jamaoncol.2015.553.  

(Article was published online first.)

Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition

For years now, COX-2 inhibitors have been used to treat pain and inflammation. Recently, much research has suggested that they may potentially be able to reduce tumour processes. COX-2 can be upregulated by tumor promotors, revealing that it may be involved in pathological processes of various types of cancer. Currently, there are hundreds of clinical trials being conduced testing the anti-tumor properties of COX-2 inhibitors such as celecoxib.

The investigators in this study created new COX-2 inhibitors derived from an analysis of currently known COX-2 inhibitors. One of the dihydropyrazole sulphonamide derivatives developed, 4d, demonstrated high COX-2 selectivity and anticancer properties. Further, it was shown that 4d could stop the cell cycle at the G2/M phase. It also induced apoptosis in A549 (tumor cell-line) cells. Overall, it seems that compound 4d could potentially be utilized for cancer treatment.

Qiu H, Wang P, Zhen L, et al. Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition. Pharmacol Res. 2016;104:86-96.

 

Improving Pediatric Outcomes in Oncology through Genomics

Within the past decade, target therapies have been prescribed using genomic data to more precisely diagnose cancer and predict future outcomes. The pediatric field is lacking by not targeting mutated oncogenic drivers and rare ALK translocated malignancies. Pediatric cancer does not have as many mutations, and many studies on focused on the disease state. New evidence shows that post therapy relapse samples accumulate more mutations and may lead to chemotherapy resistance.

A study with 102 children and young adults (up to age 22) involved exam sequencing of paired blood mononuclear cell and tumor DNAs along with tumor RNA sequencing. 69% had solid tumors. The study was designed to identify germ-line mutations that could cause an effect, tumor-specific alterations that would alter the histopathologic diagnosis, change risk status or both, and medically targetable somatic mutations.

Potentially actionable findings were found in 46% of cases and action was taken in 23 of those 42 patients (54%). A change of therapy was initiated for 14 patients (15%), a gremlin mutation was found to be clinically relevant in 9 patients, and 9 of the 14 patients had clinical benefit from the intervention.

This data is very relevant and suggests a promising field of research. With genomic sequencing, therapies were personalized in order to better target the cancer. As pharmacists, we should consider this and acknowledge that patients may require different treatment even with the same disease state. The research and sequencing in adults can and should be applied to children to better care for their cancer.

JAMA. 2015;314(9):881-883. 

A classic drug could become our cheapest and safest new cancer drug.

When you think of drugs used to treat cancer, you often think of drugs that are expensive that attack not only the cancer cells but also your own cells. They often cause severe side effects and aren’t always effective. There is a class of very common and relatively inexpensive drugs, however, that are showing promise in their ability to treat tumor cells.

 

Bisphosphonates are a very common class of drug that are often prescribed to treat osteoporosis. They work by inhibiting osteoclasts that break down bone into minerals to be used by the body. Another property of bisphosphonates that is being investigated is their effect on tumor cells. They have shown evidence to work against tumor cells in five different ways. They can trigger tumor cells to undergo apoptosis, inhibit tumor cell adhesion, and prevent tumor angiogenesis or blood vessel development. In addition to these direct effects on tumor cells, bisphosphonates can help the body better defend against the tumor cells by inhibiting macrophages produced by the tumor as well as activating a certain class of cytotoxic T-cells. Lastly, bisphosphonates exhibit a synergistic relationship with a number of anti-tumor drugs, providing an opportunity for them to be added to cancer patients’ existing medication regimens.

 

These properties of bisphosphonates are exciting and worth devoting more time and money into researching them. A cheap, and safe drug that can be used to treat cancer could be a potential breakthrough in the complex and expensive field of oncology. With more research, we could very well see bisphosphonates as a part of every cancer patient’s medication regimen.

 

Acker, H. H., Anguille, S., Willemen, Y., Smits, E. L., & Tendeloo, V. F. (2016). Bisphosphonates for cancer treatment: Mechanisms of action and lessons from clinical trials. Pharmacology & Therapeutics, 158, 24-40.

 

 

A Look into Neoadjuvant Trial Design and It’s Potential for Anticancer Drug Development

There is a very low success rate among anticancer agents in the drug development process, particularly between stage 2 and 3 clinical trials.  There is a noticeably lower success rate for oncology drugs to progress from one clinical trial to the next (57%) as compared to non-oncology medications.  Researchers at the Sloan Kettering Cancer Center in New York attempted to look for possible explanations for the phenomenon.  What they hypothesize is that the ability of clinical trials to predict the efficacy of novel drugs is inaccurate due to the outdated methods of determining end point response in solid tumors.  They assert that the current methods used, most notably the Response Evaluation Criteria in Solid Tumors (RECIST), were developed decades ago using arbitrary methods of grading tumor response that were never intended to be used for clinical significant outcomes.

The researchers suggest that improvements in the drug development process should start by using efficacy grading techniques that were intended for clinical outcomes, and are reflective of current capabilities in medical imaging.  The recommendation that they make involve using pathological complete response (pCR), which takes into account the effects that drugs have on metastatic cancer cells rather than just the impact on solid tumor tissue cells. This method is currently used for neoadjuvant trials, and could be used to predict improvements in overall survival for novel drug compounds.  In a review of numerous clinical studies the authors found usage of pCR methods in neoadjuvant methods to determine efficacy correlated to improved survival outcomes in breast cancer, muscle-invasive bladder cancer, and Non-small cell lung cancer.

The FDA has already approved pCR as a relevant indicator of neoadjuvant efficacy and as a surrogate indicator of increased survival in some breast cancer patients.  However, it is possible that this modern means of assessing cancer response could lead to an increase in the approval of new cancer drugs based on better ability to measure cancer response in patients.  The question that remains is: does this new method of efficacy evaluation seem like it will increase options for oncologists to improve survival rates, or is it possible that it will lower standards of approval to the detriment of cancer patients?

 Article Link

Funt, S. A., & Chapman, P. B. (2016). The Role of Neoadjuvant Trials in Drug Development for Solid Tumors. Clinl Cancer Res. 2016; Published OnlineFirst February 3, 2016; doi: 10.1158/1078-0432.CCR-15-196.

iCat in Pediatric Extracranial Solid Tumors

We hear about cancer related news almost every day, but pediatric cancer is unique because its targeted therapies are less available. Harris and colleagues just this past month studied the effects of individualized cancer therapy (iCat) recommendations and the feasibility of determining alterations in genomic sequences that can be targeted for treatment of pediatric extracranial (out side of the skull) solid tumors. The study was done from September 5, 2012 to November 19th, 2013 in 4 academic medical centers. There was also a one-year follow-up from the time of the visit. In order to be included in the study the patient criteria was 30 years of age or younger and with high risk, recurrent, or refractory extracranial solid tumors. Once selected, the tumors were profiled for their genetic sequencing. If an actionable alteration in the sequence was in fact present and iCat recommendation was made as long as an appropriate drug was available. Of the 100 participants it was found that 43 had results of potential clinical significance. They came to the conclusion that a clinical genomics study in pediatric oncology is feasible. It was also concluded that a large portion of pediatric solid tumors have actionable alterations in their genome.

Each case of cancer is different, especially in children. With new knowledge of certain places that we can begin treatment, such as an iCat, we are coming closer to an increase in survival rates. In my opinion there is still an immense amount of research that needs to be done, especially with pediatric cancer and stopping it from relapsing later in the child’s life. The use of genomics in this study really interested me because it is exactly what we talked about in class, targeted drug therapy. With the use of this I think we as the science community need to continue on looking at cancer and discovering drugs and therapies to overcome it. I believe that any tool that can help a health care professional make an informed decision on treatments is well worth it.

 

JAMA Oncol. http://oncology.jamanetwork.com/article.aspx?articleid=2484355 (published online January 28, 2016)

Oncology Pathways- Preventing a Good Idea From Going Bad

The focus of this article, primarily was to review the possibility and feasibility of having pre-approved pathways when treating certain cancers. Meaning that when a patient is diagnosed with cancer they apply for pre-approved treatment plans for that specific cancer. Medicare have developed piolet programs to see the feasibility of such programs. Overall, these pre-approved pathways would cut down on drug costs for the insurance company. It would decrease the need for the often time consuming process of pre-authorization. Many cancer patients face the issue of having to wait for an insurance company to approve a drug or treatment plan. The process often involves a lot of paper work as the patient needs to prove to the insurer that they need this drug or treatment plan and there are no alternative, cheaper methods. This process often can elongate a treatment for a patient and often influences the overall recovery of a patient. These pathways would also allow for a degree of variation from the pathways at a predefined value such as 20%. Thus, allowing for a degree variation to better serve a specific patient. These plans would also incentivize drug companies to lower the cost of drugs. For example, if two drugs are both shown to be effective in treating a specific cancer but one costs less than the other. Within these set oncological pathways often clinicians would utilize the cheaper drug. Leading drug companies to be competitive when pricing.  Not only does the article talk about the pros of oncology pathways, but it discusses the cons as well.

One of the major cons is who decides what is approved in oncology pathways. Should it be the insurers we create these pathways, or should these pathways be designed by a group of physicians. Another issue presented was should physicians be allowed to utilize pathways that are accepted across all insurers, or should each individual insurer have their own unique approved pathways. The article went in to great detail about how physicians should control these oncology pathways. Yet, I think these pathways would greatly benefit by having input from a wide range of health professionals, including but not limited to pharmacists. More research needs to be done in terms of cost effectiveness of these oncology pathways. But, I think these pathways show promise in how healthcare is moving towards a more patient center focus.

Citation:

Polite BN, Page RD, Nabhan C. Oncology Pathways—Preventing a Good Idea From Going Bad. JAMA Oncol. Published online February 04, 2016. doi:10.1001/jamaoncol.2015.5778.

http://oncology.jamanetwork.com.pitt.idm.oclc.org/article.aspx?articleid=2485187#ArticleInformation