Cervix: Poster Abstract: Low dose radiation and chemotherapy significantly reduces hypoxic cell population in locally advanced cervix cancer-results of a phase II study
This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
Tumor hypoxia is one of the major causes of high incidence of treatment failures to chemoradiation which is the standard of care in locally advanced cervical cancer. The necessity of newer treatment options that can circumvent hypoxia is highly relevant in this group. Use of low dose radiation to enhance the efficacy of cell cycle specific chemotherapy by mechanism of chemopotentiation is one of the elegant approaches reported in the literature. We have already published the feasibility, efficacy and tolerance of low dose radiation and chemotherapy in neoadjuvant setting in cervical cancer. In this report we evaluated the role of this novel treatment regimen in reducing the hypoxic tumor cell population in cervical cancer.
Total 24 patients with stage IIB-IIIB squamous cell carcinoma cervix were treated with initial 2 cycles of paclitaxel and carboplatin and concurrent low dose radiotherapy prior to standard chemoradiation. Response was assessed clinically, radiologically (by MRI) and pathologically (four quadrant representative punch biopsy from the cervix) after 3 weeks of neoadjuvant treatment prior to chemoradiation. Immunohistochemistry of HIF-1a was done in the biopsy samples to determine the proportion, intensity and scoring of hypoxic cells.
The proportion of positivity of base line HIF-1α was 42% (10 out of 24 patients). Low, moderate and high expressions were seen in 8%, 17% and 17% respectively. We observed nuclear positivity in 20%, and fine granular perinuclear cytoplasmic positivity in 80% cases. We failed to observe any association between expressions of HIF 1α in relation to the distance from blood vessels in tumor cord. The average age of patients in hypoxia positive and negative groups were 51.7 vs 48.36 yrs (p > 0.05). There was no difference of mean hemoglobin level (11.3 to 11.1, p > 0.05.) or MRI based tumor volume at baseline (57.1 vs. 52.4, p > 0.05) in HIF 1α positive and negative groups respectively. Low dose radiation and chemotherapy significantly reduced the tumor volume in bulky hypoxic tumors. The tumor volume reduction rate (TVRR) was significantly higher in hypoxic group (TVRR HIF_neg vs. TVRR HIF_pos 68.9 vs. 86.3, p = 0.02, t-test). There was significant improvement of diffusion MRI derived apparent diffusion coefficient (ADC) in hypoxic tumors with low dose radiation and chemotherapy (0.75 vs. 1.27, p = 0.12, Wilcoxon signed-rank test). Median score of percentage of hypoxic cells after neoadjuvant treatment were significantly higher in patients who developed subsequent local recurrence than the rest of the group (77% vs. 5% p = 0.009, Mann Whitney U test).
Overall all HIF 1 positivity was 42% in the present study. A predominantly perinuclear pattern of HIF 1 staining was found in cervix cancer. Low dose radiation and chemotherapy significantly reduced the hypoxic tumor bulk in cervical cancer.