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Cancer Stem cells, CD44 and outcomes following chemoradiation in locally advanced cervical cancer: Results from a prospective study.

In International Journal of Radiation Oncology, Biology, Physics.
By: Chopra S.
Contributor(s): Deodhar K | Pai V | Pant S | Rathod N | Goda JS | Sudhakar N | Pandey P | Waghmare S | Engineer R | Mahantshetty U | Ghosh J | Gupta S | Shrivastava S.
Material type: materialTypeLabelArticlePublisher: 2019Description: .Subject(s): Clinico‐cytopathologic spectrum | Chordomas | Immunohistochemistry | Brachyury immunostaining In: International Journal of Radiation Oncology, Biology, PhysicsSummary: Abstract PURPOSE: While cancer stem cells (CSCs) have been reported across solid tumors, there is dearth of data regarding CSC and its impact on outcomes of cervical cancer. METHODS: From October, 2013-December 2015, patients with squamous cancer of cervix (Stage IB2-IVA) were included. Pretreatment and post-treatment biopsy was obtained and immunohistochemistry (IHC) was performed for SOX-2, OCT-4, Nanog, CD44 and Podoplanin. All patients received concurrent radiation and brachytherapy to an equivalent dose of 80-84 Gy to point A with concurrent weekly cisplatin. Correlation of cancer stem cell (CSC) expression was performed with known prognostic factors. Impact of stem cell expression on disease outcomes was tested within multivariate analysis. RESULTS: One hundred fifty patients were included. The median dose to point A was 83Gy (46-89 Gy) and median of 4 (0-6) cycles of chemotherapy were administered. At baseline moderate to strong IHC expression of SOX-2, OCT-4, Nanog, CD44 and Podoplanin was observed in 12.8%, 4.8%, 24.4%, 15.5 % and 1.3% patients respectively. At median follow up of 30 months (3-51 months), loco-regional and distant relapse was observed in 12.2% and 23.1%. Of these 4.7% had both local and distant relapse. The 3-year disease free survival was 87%. On multivariate analysis moderate to high CSC expression and CD44 low status (HR=8.8 (95% CI 1.0-77.2), p<0.04) independently predicted for loco-regional relapse free survival. FIGO stage (HR=2.6 (95% CI1.3-5.4, p=0.004)) and presence of residual tumour after external radiation (HR= 3.5 (95% CI 1.8-6.5, p=0.0001) predicted for detriment in DFS. CONCLUSIONS: Presence of stem cell proteins and loss of CD44 independently predicts for reduced loco-regional control in locally advanced cervix cancer. Further investigation into interaction of stem cell and CD44 biology is warranted.
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Address for correspondence: rekhi.bharat@gmail.com

Abstract
PURPOSE:
While cancer stem cells (CSCs) have been reported across solid tumors, there is dearth of data regarding CSC and its impact on outcomes of cervical cancer.

METHODS:
From October, 2013-December 2015, patients with squamous cancer of cervix (Stage IB2-IVA) were included. Pretreatment and post-treatment biopsy was obtained and immunohistochemistry (IHC) was performed for SOX-2, OCT-4, Nanog, CD44 and Podoplanin. All patients received concurrent radiation and brachytherapy to an equivalent dose of 80-84 Gy to point A with concurrent weekly cisplatin. Correlation of cancer stem cell (CSC) expression was performed with known prognostic factors. Impact of stem cell expression on disease outcomes was tested within multivariate analysis.

RESULTS:
One hundred fifty patients were included. The median dose to point A was 83Gy (46-89 Gy) and median of 4 (0-6) cycles of chemotherapy were administered. At baseline moderate to strong IHC expression of SOX-2, OCT-4, Nanog, CD44 and Podoplanin was observed in 12.8%, 4.8%, 24.4%, 15.5 % and 1.3% patients respectively. At median follow up of 30 months (3-51 months), loco-regional and distant relapse was observed in 12.2% and 23.1%. Of these 4.7% had both local and distant relapse. The 3-year disease free survival was 87%. On multivariate analysis moderate to high CSC expression and CD44 low status (HR=8.8 (95% CI 1.0-77.2), p<0.04) independently predicted for loco-regional relapse free survival. FIGO stage (HR=2.6 (95% CI1.3-5.4, p=0.004)) and presence of residual tumour after external radiation (HR= 3.5 (95% CI 1.8-6.5, p=0.0001) predicted for detriment in DFS.

CONCLUSIONS:
Presence of stem cell proteins and loss of CD44 independently predicts for reduced loco-regional control in locally advanced cervix cancer. Further investigation into interaction of stem cell and CD44 biology is warranted.

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