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Testing for C-Kit Gene

Guest kjbran@msn.com

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Guest kjbran@msn.com

Hi--First time post. Mom diagnosed with Extensive SCLC 8/02. (Symptoms started--rib pain 6/23/02) Sent for chest x-ray on 6/23--negative. Old family physician dx her with pleurisy and treated her with antibx. Pain persisted--Saw her regular primary care physician who ordered CT scan. CT 7/02 showed small lung tumor and multiple liver lesions. Saw pulmonologist 8/02 who told her probable small cell and arranged for liver biopsy. too risky to take lung biopsy. Diagnosed with SCLC with rib, liver, and brain mets. (MRI revealed brain mets). She started chemotherapy Cisplatin and Etopside 8/28/03 and completed whole brain radiation 9/02. Completed 7 total rounds of cisplatin and etoposide with a couple hospitalizations for blood/platelet transfusions. (She had a rigor reaction to platelets--so subsequent transfusions were done in the hospital). Last chemo was 1/03. Her CT scan on 10/02 (after 3 rounds) revealed lung tumor gone, and liver lesions shrinking, bone stable. CT 1/6/03 revealed lung tumor gone, liver lesions not measurable, and bone scan stable. She had repeat CT on 3/31/03 which revealed one lymph node in mediastinum suspicious, 3 measurable liver lesions 3x4 cm, bone scan stable. She had a PET Scan 4/7/03 which confirmed recurrent SCLC. She is asymptomatic--62 years old watches my 22-month old son Tuesday through Friday, still cooks, cleans, etc...Amazing woman!!! She has no shortness of breath, liver function is normal, and rib pain is controlled with minimal medication. THANK GOD!!! The plan is for mom to start Topotecan on 4/14/03--she is participating in a study chaired by her oncologist office. It is given once a week (instead of 5 times a week every 21 days). She will have CT,bone scan after every 4th treatment to measure progress. As long as there is no growth she will continue treatment. We pray it works. I had asked her oncologist about Gleevec--she told me she was at a meeting in New York over the weekend and they talked about it, but it is hypothetical at this point. I called the Mayo clinic and s/w representative. They are opening trial in approximately one month for patient's with recurrent SCLC. I have two questions:

1. How do they test for c-Kit--do they need tissue from malignant tumor??

2. Has anyone used Topotecan for recurrence of SCLC and did it work???

Thanks and thoughts and prayers to all of you!!! Believe in Miracles and know GOD has a plan for all of us!!!

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I just wanted to say welcome. I am sorry that your Mom has LC, My Mom was DX in 10/02 with SCLC. The fact that she feels good is a blessing! I will pray for her. I have heard that Topectan is the common drug used for reoccurence. I wish the best with your Moms treatments. Hope to hear more from you. The people here are so helpful and supportive. :D


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Not sure if they need tissue for the test. It seems like it would be more accurate if they get more tumor cells. However, I found this article which says they are trying to find micrometastasis using RT-PCR in blood and marrow. I have read that this technique (RT-PCR) is used to detect c-kit.

If any researcher ever finds a way to find micrometastasis with a blood test, it may obsolete CT scans.

Comparative evaluation of micrometastasis (MM) in primary breast cancer as detected by immunocytochemistry (ICC), flow cytometry (FC), and reverse transcription-polymerase chain reaction (RT-PCR).

Year: 2002 Printable Version

Abstract No: 1719 Category: Molecular Diagnostics and Staging

Author(s): John W Park, Janet H Scott, Teresa H Seo, Shou Shye, Tom Frey, Thomas Moss, Blaise Bossy, Kenneth D Bauer, E. S Hwang, Michael Campbell, Laura J Esserman, Univ of California San Francisco, Comprehensive Cancer Center, San Francisco, CA; BD Biosciences, San Jose, CA; IMPATH/BIS, Los Angeles, CA; ChromaVision Medical Systems Inc, San Juan Capistrano, CA.

Abstract: Purpose: We applied multiple independent approaches to detect circulating tumor cells (micrometastases, MM), including existing and new techniques, in a prospective series of breast cancer patients to evaluate methods with each other, to compare blood vs. marrow results, and to correlate MM with other markers of risk. Methods: Paired marrow and blood collected at time of breast surgery were analyzed in parallel by multiple assays: an established ICC assay (ICC); immunomagnetic capture+automated ICC (autoICC); immunomagnetic capture+flow cytometry (IC/FC); and RT-PCR assays for mammaglobin (Mgb), PSA, HER2. Results: 216 primary (Stages I-III) breast cancer patients were enrolled. MM were detected in marrow with widely varying sensitivities: ICC 21%; autoICC 61%; IC-FC 47%; RT-PCR(Mgb) 16%; RT-PCR(PSA) 13%; RT-PCR(HER2) 4%. Direct comparisons showed significant correlations between ICC vs. IC-FC (p<0.001) and vs. autoICC (N=91, p=0.03) but not with any RT-PCR assay. Presence of MM also correlated with certain standard clinicopathologic parameters. MM were detected much less frequently in blood than marrow overall (autoICC, 1 vs. 61%; IC-FC, 5 vs. 47%), and with generally lower counts. For IC-FC, mean #MM/ml was 1.34?0.24 in blood vs. 9.46?0.75 in marrow. Finally, intracellular cytokine profiles of CD4+ and CD8+ T-cells in peripheral blood showed reduced expression in patients vs. normal controls, consistent with depressed types 1&2 T-cell responses. Unexpectedly, T-cell abnormalities correlated significantly with the level of marrow MM (p from <0.001 to 0.05 for CD4/IFN-γ, CD4/IL-2, CD8/IFN-γ,and CD8/IL-2) but not with standard clinicopathologic parameters. Conclusion: This is the first comprehensive study of leading and emerging methods for MM detection in marrow and blood, and demonstrates wide differences in detection rates among assays, higher detection in marrow vs. blood, and significant correlations between some assays. Detection of marrow MM also correlated with multiple immunologic abnormalities.

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Hello John, I went to a thoracic onocology lecture last October given by the University of Minnesota. Dr. Michael Maddaus lectured on the "Current Status of the Molecular Substaging of NSCLC."

The search for a more accurate means of staging is entering a new and exciting phase ushered in by advances in molecular approaches that have increased the capacity to detect metastatic disease through the use of oncogenes and other oncogenic factors. These molecular tools, which include immunohistochenical (IHC) and nucleic acid-based approaches, have strongly impacted our sensitivity of detection of micrometastatic. Small numbers of micrometastatic cells not previouly appreciated by routime pathological analysis can now routimely be identified in the lymph nodes, blood and bone marrow of surgically resected patients.

When I asked him if these tests could some day be used as a screening tool , the cost etc he said perhaps , they are relatively inexpensive . The research right now is aimed at making more accurate staging because many are told they have neg. lymph nodes etc then 6 months down the road find out there was metastasis that could not be seen by the pathologist at the time they had surgery. With more accuracy they would know who needs chemo etc.

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