BOSTON, MA – In March 2011, a surgical team at Brigham and Women’s Hospital performed the first full face transplantation in the United States and went on to complete a total of three full face transplantations this year. Now, in the first research publication to evaluate full face transplantation in the US, and largest series worldwide, the researchers describe details of patient preparation, novel design and execution of the operation as well as unique immunosuppression protocol allowing for lowest long-term maintenance drug regimen. They also share details of the early functional outcomes and demonstrate full face transplantation as a viable option in the treatment of severe facial deformities and injuries. This research is published in the New England Journal of Medicine in an issue.

“Unlike conventional reconstruction, facial transplantation seeks to transform severely deformed features to a near-normal appearance and function that conventional reconstructive plastic surgical techniques cannot match,” said lead author Dr. Bohdan Pomahac, Director of the Plastic Surgery Transplantation Program at Brigham and Women’s Hospital and lead surgeon in all three full face transplantation procedures. “It truly is a life-giving procedure for these patients.”

In an effort to advance the field of face transplantation, Pomahac and colleagues document the novel processes involved in a successful face transplant program from screening candidates to the transplant procedure itself and the follow up management of the recipients.

Researchers describe the rigorous screening and consent process that each patient must pass, which includes evaluation by a team of physicians who determine whether the patient is physically and mentally prepared for the procedure through numerous clinical and psychological evaulations. Once a candidate is approved by the face transplant team and the Institutional Review Board at Brigham and Women’s Hospital, Brigham and Women’s Hospital physicians work closely with the New England Organ Bank to identify the criteria for suitable donors and the process for obtaining consent for this unique transplantation.

Next, researchers outline the details of the surgeries with a focus on the multi-disciplinary collaborative efforts of an entire team of clinicians. Surgeons and staff coordinate their tasks while preparing the recipient and simultaneously retrieving the donor tissue within a limited time frame. The researchers describe the similarities and difference between each procedure, noting the various differences that occurred in the one full face transplantation recipient who also concurrently received a bilateral hand transplant.

- MFP Wire Services
- 12-29-2011

PHILADELPHIA, PA / BUFFALO, NY — Targeted drugs, which block or disrupt particular molecules involved in the growth of tumors, have been shown to be effective treatments against many types of cancer. A new phase 3 clinical trial conducted by the Gynecologic Oncology Group showed that a targeted therapy called bevacizumab (Avastin) effectively delayed the progression of advanced ovarian cancer. Patients with newly diagnosed advanced ovarian cancer now typically undergo surgery and chemotherapy, but the new research suggests an additional avenue of treatment. The results of the trial appear in an issue of the New England Journal of Medicine.

“This approach can be looked upon as a third major component of treatment for ovarian cancer and related malignancies,” says Robert A. Burger, MD, lead investigator on the Gynecologic Oncology Group study and director of the Women’s Cancer Center at Fox Chase Cancer Center. “We’ve had the combination of surgical management and cytotoxic chemotherapy for many years, but we haven’t really seen anything else in terms of a fundamental class of treatment. This represents a new way for us to control the disease.”

The placebo-controlled study, which was sponsored by the National Cancer Institute, enrolled 1,873 patients with previously untreated advanced disease from 336 sites, primarily in the United States, but also in Canada, South Korea, and Japan. The patients either had stage III ovarian cancer that could not be entirely removed with surgery, or stage IV disease, and were randomly assigned to one of three groups. For patients who received bevacizumab with chemotherapy followed by bevacizumab for up to an additional 10 months, the median time until their cancer progressed was 14.1 months, compared to 10.3 months for patients in the control group, who received chemotherapy with a placebo and then continued with a placebo. The net effect was a 28% reduction in the risk of disease of ovarian cancer progression over time. Patients who received bevacizumab only with chemotherapy, but not afterward, had a median progression-free survival of 11.2 months.

The National Cancer Institute estimates that nearly 22,000 women were diagnosed with ovarian cancer in 2011, and more than 15,000 died of the disease. For patients diagnosed before the cancer has spread, the five-year relative survival rate is about 93 percent (relative survival measures survival of cancer only, independent of other causes of death). But ovarian cancer is insidious—early symptoms, like bloating, abdominal pain, and trouble eating, are typical of many illnesses and easily dismissed as non-threatening. Women often do not learn they have the disease until it’s already spread. In 62 percent of new cases, the patient’s cancer has metastasized to distant sites, and the five-year survival rate is just under 27 percent.

Bevacizumab is already FDA-approved for use against some types of colon, lung, kidney and brain cancers; its accelerated approval for metastatic breast cancer was recently revoked by the FDA. The drug acts by binding with vascular endothelial growth factor, a protein produced by certain cancers that helps initiate the growth of new blood vessels that feed the tumor. The process of growing new blood vessels is called angiogenesis, and bevacizumab is an angiogenesis inhibitor.

“Bevacizumab blocks the growth factor vascular endothelial growth factor, which is important in the process of ovarian cancer progression,” says Burger, “and we’ve seen that this drug is also active in patients with recurrent disease.”

Angiogenesis happens at the interface between the host and the disease, which makes it an appealing target for treatment, says Burger, who also led the Phase II Gynecologic Oncology Group study on using bevacizumab in women with recurrent ovarian cancer. He says different ovarian cancers may appear identical under the microscope but differ biologically, which means they’ll respond differently to treatment.

In the New England Journal of Medicine paper, Burger and his co-authors point out that another ovarian cancer trial conducted primarily in Europe called ICON7 demonstrated positive results in using becavizumab in combination with chemotherapy and then continued for up to 7 months.

- MFP Wire Services
- 12-29-2011

SEOUL, KOREA – Smoking is a well-known risk factor for lung cancer, but nearly 25% of all lung cancer patients have never smoked. In a study published online in Genome Research, researchers have identified a previously unknown gene fusion event that could explain a significant proportion of lung cancer cases in never-smokers, and might serve as a target for new therapies.

Recent strides have been made to identify gene mutation events driving cases of lung adenocarcinoma in never-smokers, but the underlying genetic events leading to these lung cancers still remain unknown in a large number of cases. In this report, using a combination of genome sequencing and RNA sequencing, a team of researchers in South Korea has characterized a previously unknown gene fusion event in a case of lung adenocarcinoma striking a 33-year-old Korean male with no history of smoking or cancer within his family.

The group sequenced and compared the genome of the patient’s cancer and normal tissue (blood), but they found no mutations in known-cancer related genes, such as EGFR, KRAS, and EML4-ALK mutations, that were likely to explain this case. Delving deeper, they also sequenced RNA isolated from the cancer cells, which when analyzed, can reveal gene rearrangement events that are difficult to detect by genome sequencing and may be driving the cancer.

From the RNA sequencing analysis they built a list of candidate gene fusions, narrowing it down to a single gene fusion that could be a cancer-causing event. A genomic inversion event occurred on chromosome 10 in the cancer, fusing the KIF5B and RET genes. This fusion was particularly interesting because RET has been previously implicated in other gene fusion events known to drive thyroid cancers, and although it is normally expressed at low levels in the lung, chimeric RET in this patient is highly expressed. Furthermore, KIF5B contains a protein domain that is necessary for activation of the fusion gene.

They then confirmed that the KIF5B-RET fusion occurs in other lung cancer cases, finding two instances in twenty additional cases of lung cancer, indicating that this fusion event is not rare. The authors suggest that the KIF5B-RET fusion occurs in about 6% of all lung adenocarcinoma cases. The authors note that although further epidemiological studies are needed to accurately define the frequency of KIF5B-RET in lung cancers, they expect that the fusion gene may be a promising molecular target for treatment.

“We showed that genome sequencing technology could reveal a previously hidden cause of human cancer, which can be used as a therapeutic target for personal cancer therapy”, said Dr. Jeong-Sun Seo, director of the Genomic Medicine Institute-Seoul National University, chairman of Macrogen Inc., and senior author of the study.

- MFP Wire Services
- 12-26-2011