On the critical importance of CTCs Several pape
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Posted On: 09/09/2020 9:04:41 AM
On the critical importance of CTCs
Several papers have highlighted the importance of CTC in the diagnostic, characterization and follow up of Cancer patients. CTC have shown to strongly correlate with survival for patients. Some links below:
Role of Circulating Tumor Cell (CTC) Monitoring in Evaluating Prognosis of Triple-Negative Breast Cancer Patients in China
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493060/
Results 286 TNBC patients: Compared with preoperative levels, the average CTC content in peripheral blood of breast cancer patients was significantly increased at 3 days after surgery, and then decreased to the preoperative baseline level by 7 days after surgery. The 3-year overall survival rate and progression-free survival rate in patients with CTC >5/7.5 mL peripheral blood were significantly lower than in patients with CTC <5/7.5 mL peripheral blood detected preoperatively and at 3 and 7 days postoperatively.
Circulating Tumor Cells Predict Survival in Early Average-to-High Risk Breast Cancer Patients
https://academic.oup.com/jnci/article/106/5/dju066/2607122
Results of 2026 patients: The prognosis was worst in patients with at least five CTCs per 30mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06)
Circulating Tumor Cell Assessment in Presumed Early Stage Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy: A Prospective Pilot Study
https://pubmed.ncbi.nlm.nih.gov/30244877/
Results 48 non-small cell lung cancer Patients: CTC monitoring after SBRT for presumed early stage NSCLC may give lead-time notice of disease recurrence or progression. Conversely, negative CTC counts after treatment may provide reassurance of disease control. CTC analysis is thus potentially useful in enhancing clinical diagnosis and follow-up in this population.
The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper
https://www.sciencedirect.com/science/article...via%3Dihub
Results for 2436 MBC: For all patients, Stage IV indolent patients had longer median overall survival than those with Stage IV aggressive (36.3 months vs. 16.0 months, P < 0.0001) and similarly for de novo MBC patients (41.4 months Stage IV indolent vs. 18.7 months Stage IV aggressive, p < 0.0001). Moreover, patients with Stage IV indolent disease had significantly longer overall survival across all disease subtypes compared to the aggressive cohort: hormone receptor-positive (44 months vs. 17.3 months, P < 0.0001), HER2-positive (36.7 months vs. 20.4 months, P < 0.0001), and triple negative (23.8 months vs. 9.0 months, P < 0.0001). Similar results were obtained regardless of prior treatment or disease location.
We confirm the identification of two subgroups of MBC, Stage IV indolent and Stage IV aggressive, independent of clinical and molecular variables. Thus, CTC count should be considered an important tool for staging of advanced disease and for disease stratification in prospective clinical trials.
And so on.
The conclusion is clear: CTCs are an excellent biomarker of overall survival rate (ORS). A CTC threshold of 5 cells per 7.5 ml defines to a great extent ORS in several types of cancers.
Most of oncology drugs objective is to extent ORS for patients. This defines the success (or lack of) of a therapy.
Now, we have a drug that has showed that has the ability to reduce CTCs to zero or close to zero. If I remember correctly, we have at least 5 patients with reported counts of zero:
Patient #1 injected 9/27/2019
Patient #2 injected 11/25/2019 (mother in law)
Patient #3 injected 1/3/2020
Patient #4 Injected 1/7/2020
Patient #5 Injected 1/28/2020
Some of these patients have been in treatment for almost a year now. Heck, if the counts are still low for even ONE of them we have a wonder drug.
The big price is Oncology. Maybe I should say the HUMONGOUS price is Oncology. If we are still doing well with these patients and those in the basket trial … the question is if it is low or high three digits for the SP (not exaggerating here).
Now, the question is: how are our Oncology trial patients doing ??? It would be nice to have an update of the mTNBC and basket trials understanding that COVID slowed down everything. If some of them still have low counts we have already demonstrated LL works for this indication.
Several papers have highlighted the importance of CTC in the diagnostic, characterization and follow up of Cancer patients. CTC have shown to strongly correlate with survival for patients. Some links below:
Role of Circulating Tumor Cell (CTC) Monitoring in Evaluating Prognosis of Triple-Negative Breast Cancer Patients in China
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493060/
Results 286 TNBC patients: Compared with preoperative levels, the average CTC content in peripheral blood of breast cancer patients was significantly increased at 3 days after surgery, and then decreased to the preoperative baseline level by 7 days after surgery. The 3-year overall survival rate and progression-free survival rate in patients with CTC >5/7.5 mL peripheral blood were significantly lower than in patients with CTC <5/7.5 mL peripheral blood detected preoperatively and at 3 and 7 days postoperatively.
Circulating Tumor Cells Predict Survival in Early Average-to-High Risk Breast Cancer Patients
https://academic.oup.com/jnci/article/106/5/dju066/2607122
Results of 2026 patients: The prognosis was worst in patients with at least five CTCs per 30mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06)
Circulating Tumor Cell Assessment in Presumed Early Stage Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy: A Prospective Pilot Study
https://pubmed.ncbi.nlm.nih.gov/30244877/
Results 48 non-small cell lung cancer Patients: CTC monitoring after SBRT for presumed early stage NSCLC may give lead-time notice of disease recurrence or progression. Conversely, negative CTC counts after treatment may provide reassurance of disease control. CTC analysis is thus potentially useful in enhancing clinical diagnosis and follow-up in this population.
The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper
https://www.sciencedirect.com/science/article...via%3Dihub
Results for 2436 MBC: For all patients, Stage IV indolent patients had longer median overall survival than those with Stage IV aggressive (36.3 months vs. 16.0 months, P < 0.0001) and similarly for de novo MBC patients (41.4 months Stage IV indolent vs. 18.7 months Stage IV aggressive, p < 0.0001). Moreover, patients with Stage IV indolent disease had significantly longer overall survival across all disease subtypes compared to the aggressive cohort: hormone receptor-positive (44 months vs. 17.3 months, P < 0.0001), HER2-positive (36.7 months vs. 20.4 months, P < 0.0001), and triple negative (23.8 months vs. 9.0 months, P < 0.0001). Similar results were obtained regardless of prior treatment or disease location.
We confirm the identification of two subgroups of MBC, Stage IV indolent and Stage IV aggressive, independent of clinical and molecular variables. Thus, CTC count should be considered an important tool for staging of advanced disease and for disease stratification in prospective clinical trials.
And so on.
The conclusion is clear: CTCs are an excellent biomarker of overall survival rate (ORS). A CTC threshold of 5 cells per 7.5 ml defines to a great extent ORS in several types of cancers.
Most of oncology drugs objective is to extent ORS for patients. This defines the success (or lack of) of a therapy.
Now, we have a drug that has showed that has the ability to reduce CTCs to zero or close to zero. If I remember correctly, we have at least 5 patients with reported counts of zero:
Patient #1 injected 9/27/2019
Patient #2 injected 11/25/2019 (mother in law)
Patient #3 injected 1/3/2020
Patient #4 Injected 1/7/2020
Patient #5 Injected 1/28/2020
Some of these patients have been in treatment for almost a year now. Heck, if the counts are still low for even ONE of them we have a wonder drug.
The big price is Oncology. Maybe I should say the HUMONGOUS price is Oncology. If we are still doing well with these patients and those in the basket trial … the question is if it is low or high three digits for the SP (not exaggerating here).
Now, the question is: how are our Oncology trial patients doing ??? It would be nice to have an update of the mTNBC and basket trials understanding that COVID slowed down everything. If some of them still have low counts we have already demonstrated LL works for this indication.
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