Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center.

OBJECT: Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. METHODS: Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990-2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. RESULTS: Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2-77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24-34 months) and 9 months (95% CI 6-11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3-1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6-11 months). CONCLUSIONS: The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

Refining patient selection for neoadjuvant chemotherapy before radical cystectomy.

PURPOSE: We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy. MATERIALS AND METHODS: We identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease specific, progression-free and overall) and rate of pathological up staging. An independent cohort of patients from another institution was used to confirm our findings. RESULTS: We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased 5-year overall survival (47.0% vs 64.8%) and decreased disease specific (64.3% vs 83.5%) and progression-free (62.0% vs 84.1%) survival probabilities compared to low risk patients (p <0.001). Survival outcomes were confirmed in the validation subset. On final pathology 49.2% of low risk patients had disease up staged. CONCLUSIONS: The 5-year disease specific survival of low risk patients was greater than 80%, supporting the distinction of high risk and low risk muscle invasive bladder cancer. The presence of high risk features identifies patients with a poor prognosis who are most likely to benefit from neoadjuvant chemotherapy, while many of those with low risk disease can undergo surgery up front with good expectations and avoid chemotherapy associated toxicity.

Hiding in plain view: genetic profiling reveals decades old cross contamination of bladder cancer cell line KU7 with HeLa.

PURPOSE: KU7 is a popular urothelial carcinoma cell line that was isolated from the bladder of a patient at Keio University in 1980. It has subsequently been widely used in laboratories around the world. We describe how routine cell line authentication revealed that KU7 was cross contaminated almost 30 years ago with HeLa, a cervical carcinoma cell line. MATERIALS AND METHODS: Presumed KU7 clones dating from 1984 to 1999 were provided by M.D. Anderson Cancer Center, Vancouver Prostate Centre, Kyoto University, Tokyo Medical University and Keio University. HeLa was obtained from ATCC. Genomic DNA was isolated and short tandem repeat analysis was performed at the M.D. Anderson Cancer Center Characterized Cell Line Core Facility, Johns Hopkins University Fragment Analysis Facility and RIKEN BioResource Center, Ibaraki, Japan. Comparative genomic hybridization was performed on a platform (Agilent Technologies, Santa Clara, California) at Vancouver Prostate Centre. RESULTS: The short tandem repeat profile of all KU7 clones was an exact match with that of HeLa. Comparative genomic hybridization of all samples revealed an abundance of shared chromosomal aberrations. Slight differences in some genomic areas were explained by genomic drift in different KU7 clones separated by many years. CONCLUSIONS: Our analysis identified that cross contamination of KU7 with HeLa occurred before 1984 at the source institution. All KU7 clones in the urological literature should be considered HeLa and experimental results should be viewed in this light. Our results emphasize the need to authenticate cell lines in oncological research.

Ethics of research training for NIH T32 surgical investigators.

As part of the revised curriculum of the NIH T32 Training Grant mechanism, 6 hr of formal instruction in ethics of research are now required. We therefore implemented a four-session seminar (6 hr total time) structured around assigned readings, didactic presentations, and group discussions. The objective of this research project was to assess whether this new program provided our trainees with a framework for ethical conduct in research. Twelve trainees completed the ethics course; 8 trainees who had not yet taken the ethics course served as a control group. All trainees answered a 72-item questionnaire of our own design that examined a variety of issues in research ethics. We compared the responses of seminar participant and nonparticipant groups using the Fisher exact test and Student t test for nominal and ordinal data, respectively. Both groups of trainees perceived that too much emphasis was placed on quantity rather than quality of publications. Both groups felt that this pressure emanated from department chairmen rather than laboratory mentors (P < 0.0001). In contrast to these shared perceptions, the two groups demonstrated many differences in their comprehension of research ethics. For example, compared to the controls, trainees who participated in the ethics course believed that they could define potential NIH standards for data storage and research mentorship (P < 0.05), understood gratuitous manuscript authorship (P < 0.05), were comfortable in dealing with outlier or discordant data (P < 0.10), and, most pertinently, were fully prepared to seek third-party input into an ethical dilemma involving their own work (P < 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Bradley v. University of Texas M.D. Anderson Cancer Center.

KIE: The U.S. Court of Appeals, Fifth Circuit, affirmed a lower court's holding that an HIV positive surgical technician, Brian Bradley, was no longer "qualified" to continue in that position within the meaning of the Rehabilitation Act of 1973. Bradley had also contended that the hospital's reassignment was retaliation against him for disclosing his HIV status to a newspaper and therefore constituted a violation of his First Amendment right of free speech. The court found that the newspaper interview was not a motivating factor in the hospital's actions. The hospital validly determined that the work of a surgical technician creates some risk of viral transmission. Although the risk of Bradley's transmitting the disease to a patient was low, the risk was not inconsequential given the possibly fatal repercussions of an accident resulting in such transmission.^ieng

Philosophy of care, decision making, and ethical considerations.

The very nature of critical care opens the door to controversy, for it is in the intensive care unit that staggering amounts of money and human resources are expended. The outcome is frequently suboptimal, and the feeling often persists that our patients, who should be the beneficiaries of our efforts, are paying a tremendous price in the form of isolation from loved ones, life-support systems that do not allow them to communicate with their families or caretakers, and the physical pain of multisystem failure. As Carlon has recently asked, are we allocating our limited resources inappropriately because we are unable to select patients who will not survive despite our intensive care units? This concern may be justified. However, the work we do in the intensive care unit has another, more positive intangible result. Many of the breakthroughs in medicine have been achieved by dedicated pioneers who tried to accomplish something that had not been accomplished before. At first their efforts were often challenged as being useless or overly extravagant or were even opposed as a violation of God's will or the laws of nature. Developing new forms of treatment, some of which can only be tested in an intensive care unit, is a challenge for all of us. We must, of course, balance what we are trying to accomplish with what we spend, since too much as well as too little emphasis on new techniques is suboptimal. If we persevere, some of what we find impossible to achieve today will become possible tomorrow, will become the norm of the future, and will, we hope, give way to still better innovations as medicine continues to evolve.