Micro NMR (Sci Trans Med)

Miniaturization of technology continues to bring new innovations in science and technology. The very latest innovation which you probably have not seen yet is a miniature NMR. On a larger scale this is the old familiar MRI machine. The micro-NMR is coupled to a Smart Phone and used to analyze cell surface proteins. A study published this week in Science Translational Medicine showed that this micro-NMR (μNMR) device run by a smart phone could be used to analyze a series of proteins/markers (pCAM (epithelial cell adhesion molecule), MUC-1 (mucin 1, cell surface associated), HER2, EGFR (epidermal growth factor receptor), B7-H3, CK18, Ki-67, p53, and vimentin]) showed a 10% to 20% improved diagnostic accuracy over traditional cell staining and other traditional techniques.

The current study analyzed needle aspiration biopsies. The study was limited to intra-abdominal cancers. The researchers found that 4 markers: MUC-1, HER2, EGFR, and EpCAM provided high diagnostic accuracy. These 4 markers used in conjunction gave the  correct diagnoses in 48 of the 50 initial patients examined and in 20 of 20 in the next round. For biology, science and technology geeks this was a fascinating article. I’ll link below to the Editor’s summary.

As we wonder what our Smart Phones can do besides play music surf the web, and track our running mileage, we see that forward thinkers are finding new ways to use the smart phone along with creative and new ways to use current technology. And yes, genomics and proteomics have a future.

Reference:
Sci Transl Med 23 February 2011: Vol. 3, Issue 71, p. 71ra16 DOI: 10.1126/scitranslmed.3002048. Micro-NMR for Rapid Molecular Analysis of Human Tumor Samples. Haun J. et. al.

Evidence Based Medicine vs. Sensationalism
The New York Times, today, in a fairly sensational manner, discusses Non-Hodgkins Lymphoma and medications in vogue in reference to two medicines, including Zevalin, which at this time is used in cases of failure of other therapies. The accusastion being made is that physicians are not using Zevalin, a radioactive drug, that can only be administered in a hospital using a complex protocol, because of incentives to use more established and well studied protocols including Rituxan in conjunction with “CHOP”.

They highlight the essentially anecdotal evidence of 3 patients who have done well after failing other protocols. That is both the manner in which Bexxar and Zevalin are to be used and the manner in which they have been studied so far. While studies that will indicate if survival time is increased should be complete soon, there is no study that by the principles of Evidence Based Medicine (EBM) do this yet. EBM requires evidence of a high order in well conducted studies that effectively, objectively and statistically demonstrate the utility of a treatment.

This is a higher standard than media generated sensationalism or pharmaceutical company based marketing offer. The studies must stand on their own merit. So far the medications are being used as studied and demonstrated. They are used after failure of other treatment. They are complicated and difficult to administer. They should be used though where needed. Hopefully, the studies that will reportedly be completed soon will demonstrate their superiority, effectiveness, and utility for Non-Hodgkins Lymphoma. Knowledge is increasing fast in this area, but of course not fast enough.

A sensational article like this one, discussing treatment, witholding of treatment, and implying decicsion making is arbitrary and even selfish without even the mention of what EBM is, is not responsible.

You can do your own literature search at PUBMED for more information.

U.S. Clinical Trials – searchable database. You may find active studies using Zevalin or other products here.

Selected Literature Search ResultsExpert Rev Anticancer Ther. 2002 Oct;2(5):485-93
The current indications are: low-grade or follicular lymphoma refractory to rituximab, and relapsed or refractory, low-grade, follicular or transformed lymphoma. Additional studies have been initiated to further define the role of this new therapy in the treatment of patients with B-cell non-hodgkin’s lymphoma.

Semin Oncol. 2003 Dec;30(6 Suppl 17):17-22.
Gregory, SA. Selecting patients for treatment with 90Y ibritumomab tiuxetan (Zevalin).

Yttrium 90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was the first radioimmunotherapeutic agent approved by the US Food and Drug Administration. It is indicated for treating patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma, including patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. Proper patient selection is essential for optimizing the efficacy and safety of treatment with (90)Y ibritumomab tiuxetan. It may be advisable to use (90)Y ibritumomab tiuxetan relatively early in a patient’s course of treatment because overall and complete response rates, and the estimated median duration of response, are higher among patients who have had fewer median prior antineoplastic regimens than among those who have had a greater median number of such regimens. Furthermore, the myeloablative effect of multiple courses of chemotherapy can preclude the later use of (90)Y ibritumomab tiuxetan. In contrast, other therapies, including chemotherapy and rituximab, can be used safely and successfully after (90)Y ibritumomab tiuxetan without concerns about increased hematologic toxicity from the previous radioimmunotherapy. The main adverse event associated with (90)Y ibritumomab tiuxetan therapy is hematologic toxicity and, as a result, only patients with adequate bone marrow reserves and less than 25% lymphoma marrow involvement should currently be considered for clinical therapy.

Cancer Biother Radiopharm. 2005 Apr;20(2):185-8.

Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) induces long-term durable responses in patients with relapsed or refractory B-Cell non-Hodgkin’s lymphoma.
Wiseman GA, Witzig TE.
Mayo Clinic, Rochester, MN, USA. gwiseman@mayo.edu

AIM: Yttrium-90 ((90)Y) ibritumomab tiuxetan (Zevalin) radioimmunotherapy is an effective treatment for relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL), with overall response rates ranging from 74% to 82%. This retrospective analysis was conducted to determine the number of patients achieving long-term durable responses with (90)Y ibritumomab tiuxetan treatment. MATERIALS AND METHODS: The medical records of patients (n = 211) with relapsed, refractory, or transformed indolent CD20+ B-cell NHL who were treated with 90Y ibritumomab tiuxetan were reviewed. Time to progression (TTP) of > or =12 months was noted in 78 patients (37%), who were identified as long-term responders and were further characterized. RESULTS: Median age of the long-term responders was 58 years (range, 24-80 years) with 44% over 60 years, and 55% were male. Notably, 59% of patients had received > or =2 prior regimens, 33% had received > or =3 prior regimens, and 37% had failed to respond to immediate prior therapy. Median response duration was 28.1 months (range, 10.5-80.3+ months). Median TTP was 29.3 months (range, 12.1-81.5+ months). In patients with ongoing response, median TTP was 53.9 months (range, 49-82+ months). CONCLUSIONS: (90)Y ibritumomab tiuxetan produces durable long-term responses in patients with relapsed/refractory B-cell NHL. Failure to respond to prior therapy does not preclude achieving a long-term response with 90Y ibritumomab tiuxetan.