Barretos Cancer Center of Brazil – The Asymmetric War On Cancer

Barretos logoI recently returned from a lecture tour at the Barretos Cancer Center of Brazil located 300 miles from Sao Paulo. This cancer center, founded in 1968, has become one of the world’s leading programs for the diagnosis and treatment of malignant disorders. Before this small town became famous for cancer care, however, it was a recognized site for rodeos. The city of Barretos sits in the middle of Brazil’s agricultural region with sugar cane and cattle the principal industries. The hospital itself is a charity where all care is delivered free of charge. Patients from all over the country arrive by bus and ambulance to undergo high-level diagnostic, surgical and medical treatment. Much of the funding comes from the government, but a large amount of the money comes from charitable donations in the form of cattle that are auctioned off to provide money. In addition, donations from the leading musicians of the nation, including Michel Telo, help in the fundraising efforts.

We arrived at Ribeiro Preto airport where we were met by a driver who brought us the 1-1/2 hour trip to Barretos. I was accompanied by a reconstructive plastic surgeon who was donating a month of her time to the Barretos program. The following morning, the director of the program, Dr. Andre Lopes Carvalho, brought me to the hospital for the lecture. The audience consisted of MDs and MD/PhDs, with many scientists and technical staff. It was well received and followed by a small coffee reception.

From there, the Director of Molecular Biology and the Chief of Pathology gave me a tour of the facility. There, in the center of Brazil was a sophisticated research institution with every capability. DNA sequencing performed on Illumina and Ion Torrent equipment. In a tour of the pathology department I was shown archived blocks from tens of thousands of cancer patients, all maintained in a central repository. My discussion with the Chief of Pathology, Dr. Cristovam Scapulatempo-Neto, was most instructive.

It must be remembered that Brazil is a nation of stark contrasts, on the one hand, abject poverty and on the other, extreme wealth. The dilemma for the medical system is to deliver care that meets the needs of the greatest number of patients at the lowest possible cost. Dr. Scapulatempo-Neto confronts an almost impossible dilemma. He cannot possibly afford the companion diagnostics so common in America, which match patients to the drugs of interest under FDA regulation, like the COBAS BRAF mutation test for Vemurafenib or the VYSIS ALK Break Apart FISH probe for Crizotinib. At several thousand dollars per test, these tests are beyond the reach of the Brazilian system. More to the point, many of the drugs are not covered by the national insurance.

To address the need, this physician has redoubled his efforts in immunohistochemistry. This technique uses special stains and antibodies to measure the presence or absence of proteins. Unlike DNA tests, which identify amplifications and mutations, immunohistochemistry identifies the end-product, the business end of cancer abnormalities. I was amazed by the accuracy and affordability of these increasingly sophisticated IHC tests. While a COBAS or VYSIS test might run thousands, he can conduct high quality IHC for 100 dollars. With a medical center that sees 10,000 new cancer patients per year, the cost savings are significant.

I realized that this was indeed an asymmetric war on cancer; low tech answers to high tech problems. I became increasingly enthusiastic about the prospect of utilizing our EVA-PCD platform in this population. After all, these medically indigent patients are barely able to receive even standard cytotoxic chemotherapies, only generic drugs, and very few newer classes of agents are available. The cost saving associated with doubling responses and restricting futile care could be enormous. While gene sequencing technologies become faster, better, and less expensive, the information that they provide for most common malignancies remains to be determined. A practical, comparatively inexpensive tissue culture platform capable of testing both cytotoxic drugs and targeted agents would be a remarkable step forward for the population in Brazil. It is my hope to collaborate with this group and bring our technology to the Brazilian population.

Rare Tumors – Challenges and Triumphs

When I am asked how our EVA-PCD laboratory platform might best be applied, I have several responses.

On the one hand, there is my catchphrase, “we cure the curable, treat the treatable and avoid futile care.” What I mean by this is that patients with potentially curable malignancies, e.g., small cell lung cancer, previously untreated ovarian, non-Hodgkin lymphoma, and some leukemias should receive the most effective treatment first line, in order to enhance the likelihood of a cure.

The majority of our patients fall into the second category, those whose tumors can be treated but are less likely to be cured. They include recurrent breast, newly diagnosed lung or pancreas, and colorectal cancer among others.

Finally, in those patients for whom very few options exist, it is arguable that they are best served, when found drug resistant, by avoiding the toxicity of ineffective therapy, or what is known as futile care.

The other way I describe our platform is to explain its capacity to explore treatment options where no reliable guidelines exist. These rare malignancies offer the opportunity to examine a broad array of treatment options, including signal transduction inhibitors in pursuit of heretofore-unrecognized therapeutic directions. Just such a case was submitted to our laboratory this spring

The patient, a 56-year old woman from Brazil, presented in February with a large mass in the left axilla. Biopsy confirmed for an ER, PR and HER2 negative (triple negative) epithelial neoplasm with a proliferative index of 80 percent. The only positive findings were p63 antigen and cytokeratins. Work-up revealed extensive metastatic disease but no other primary could be identified.

The patient underwent surgery followed by aggressive multi-agent chemotherapy. The disease rapidly progressed. Second line therapy proved ineffective. At this point a tissue sample was submitted to our lab. The EVA-PCD analysis revealed an unusual profile with a high degree of activity for sorafenib combinations.  Sorefenib was originally developed as BRAF inhibitor and ultimately received FDA approval for the treatment of advanced kidney and liver tumors, associated with the drugs cross reactivity as a VEGF inhibitor. The patient’s study also revealed persistent activity for the beta tublin inhibitors vinorelbine and paclitaxel. The treating physician used our profile to create a novel combination of vinorelbine, paclitaxel combined with sorafenib.

The pretreatment PET CT obtained in June, revealed complete replacement of the liver and extensive soft tissue and nodal metastasis to the lungs, mediastinum, retroperitoneum, as well as innumerable boney metastasis. After failing the previous chemotherapies the patient began this novel drug combination in mid June.

When I arrived in my office this week, I was met with an email that had as an attachment a slide set from a tumor board presentation that described this patient. The introductory slide was, “Tumores Raros.”(Portuguese for Rare Tumors)  Included in the presentation was the patient’s history, pathology, immunohistochemistry, treatment overview and serial CT/PET scans. The final slide compared June 2013 PET CT (taken before she began our combination) with an August 2013, (taken after 2 cycles of therapy). The results could not have been more different.  The patient had achieved a complete remission. Gone was the extensive hepatic disease. Gone were the boney metastasis. Gone were the dark nodal mets that had scattered across her torso and abdomen like shotgun pellets on an x-ray image. Contrary to every expectation this patient had responded to a drug combination that no one had ever heard of.  No one including her treating physician and me.

These experiences remind us that every patient is a unique story, unfolding in real time. This is a stellar example of personalized cancer care, a gleaming testament to the laboratory’s capabilities and even more so to the dedication of the treating physician who broke with all tradition to treat this patient correctly. I am honored to work with this courageous colleague and delighted by this spectacular outcome.

Beyond Our Borders

I recently returned from Brazil where I participated in a cancer symposium. During my visit I encountered many highly skilled physicians with expertise in breast, thoracic, gastrointestinal and orthopedic oncology. The degree of collegiality and enthusiasm was palpable. The most exciting aspect of my visit was the warm reception and extremely high level of interest in the clinical application of our laboratory platform. It was a refreshing reminder that the parochial thinking of the American oncology community is not the norm throughout the world.

Upon my return, I had the pleasure of meeting a charming 61-year-old woman from New Delhi, India. In review of her chart I recognized her name as a patient for whom we had conducted a study in February of 2012. Her husband, an accomplished businessman, had learned of our laboratory and worked diligently to obtain, process and transport a portion of his wife’s tumor from the surgical suite to our lab. Despite multiply recurrent disease and numerous prior treatments, this patient’s ovarian cancer cells revealed exquisite sensitivity to a drug combination in the laboratory. Her physicians at the Apollo Hospital of New Delhi delivered the treatment exactly as outlined by our lab, and here sitting across from me was the patient in complete remission six months later. The family had traveled from India to meet me and express their thanks.

Each of these experiences speaks volumes for the globalization of cancer care. Cancer patients, whether from Brazil, India or China are more alike than different. Each confronts a seemingly insurmountable adversary. Each in their own way seeks out the best information and advice. And each can be best managed with those treatments found uniquely effective for their tumor. Perhaps once we have conquered cancer in India and Brazil, the EVA-PCD® assay will be ultimately accepted in the United States of America.