High ALDH-1 Expression Predicts Non-Complete Response of Radiotherapy in Stage III Squamous Cell Cervical Carcinoma Patients.

BACKGROUND: ALDH1 is a cervical cancer stem cell marker that has radioresistance profile. Recurrence and metastasis following radiotherapy are still being problems of most patients. This study aimed to determine the correlation between ALDH1 and radiotherapy response in stage III squamous cell cervical carcinoma (SCCC) of the cervix. METHODS: A total 58 of 360 patients of stage III SCCC who received external beem radiation and brachytherapy (2016-2021) at Cipto Mangunkusumo Hospital met the eligibility criteria of this study. Pre- and post-irradiation MRI examinations and ALDH expression with immunohistochemistry (Santa Cruz®) were performed on formalin-fixed paraffin-embedded of pre-treatment cervical tissue biopsy taken from RSCM pathological anatomy laboratory. Patients were divided into two groups, complete responders vs non-complete responders. ALDH-1 scores were compared between two groups to assess ALDH-1 expression. The statistical analyses were carried out by SPSS 24. RESULTS: The optimal ALDH-1 score cut-off point on the radiation response was 166.05 pg/mL which was obtained from the analysis of the ROC curve. The AUC value was 0.682 with sensitivity and specificity, 63,6% and 64%, respectively. ALDH score ≥166.05 increased the risk by 3.127 times for not achieving complete response (adj OR 3.127, 95% CI 1.034 - 9.456, p = 0.043). Pre-radiation tumor size (p = 0.593), degree of differentiation (p = 0.161), renal abnormalities (p = 0.114), and keratinization (p = 0.477) were not associated with radiation response. CONCLUSIONS: High ALDH expression was associated with non-complete radiation response in stage III squamous cell cervical carcinoma. 
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Survival of nasopharyngeal cancer in national referral hospital of Indonesia: A study on radiotherapy patients.

INTRODUCTION: Nasopharyngeal cancer in Indonesia has a poor survival rate and there is only few studies regarding nasopharyngeal cancer in Indonesia. Therefore, this study was made to present Indonesian nasopharyngeal cancer data with special focus on survival of nasopharyngeal cancer profile that receives radiation therapy. METHODS: This was a retrospective study conducted in the Department of Radiation Oncology, Dr. Cipto Mangunkusumo Hospital (RSCM). Moreover, survival analysis was done using Kaplan Meier, log rank and cox regression test. RESULTS: A total of 398 patients were included with the median follow-up time of 16 (0-65) months. The 3-year survival in patients with stage I-III was >50% while the survival of 5 years was >50% only in early stage patients. The median survival for men was 46 months and for women 42 months. For OTT ≤ 49 days survival of 3 years and 5 years is 67.1%. Stage III-IVB, size N2-N3, and overall treatment time >49 days were the prognostic factors for nasopharyngeal cancer patients. After multivariate analysis, only stage III-IVB was statistically significant as a prognostic factor independent of survival. CONCLUSION: Most of nasopharyngeal cancer patient came in advanced stage. The median time needed for patients to get radiation therapy and median OTT were good. Only stage III-IVB was statistically significant as a prognostic factor independent of survival.

Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer.

OBJECTIVES: Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy. METHODS: We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy. RESULTS: Strong expression of SOX2 (p = 0.011, p = 0.001) and OCT4 (p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively). CONCLUSIONS: Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer.

The effect of carbogen breathing and nicotinamide added to standard (chemo)radiation treatment of advanced cervical cancer in Indonesia.

OBJECTIVE: Chemoradiation is the standard therapy for advanced stages of cervical cancer. In developing countries, where 80% of cervical cancers occur, this is not always available. Carbogen breathing and oral nicotinamide (CON) therapy, aimed at overcoming tumor hypoxia, has shown to improve treatment efficacy in some epithelial tumors. This study investigates the effect of CON during (chemo)radiation of advanced stages of cervical cancer on overall survival, local and regional control, and toxicity. METHODS: From December 2006 to February 2010, 139 patients with stage IB2 to IVA cervical cancer were nonrandomly assigned to receive radiotherapy (RT) or chemoradiation (CRT) with or without CON. Differences in overall survival, local and regional control after 1 year, and toxicity were assessed in 113 evaluable patients. Thirty-two patients received RT, 16 received CRT, 45 received CON-RT, and 20 received CON-CRT. RESULTS: The CON-RT and RT groups contained significantly more patients with a poor performance status and IIIB and IVA tumors. Despite these differences in baseline characteristics, overall survival and local and regional control at 1 year were not significantly different (P = 0.10 and P = 0.19, respectively). Toxicity scores also did not differ (P = 0.60 and P = 0.73 for acute and late toxicity). CONCLUSIONS: Addition of CON to standard (chemo)radiation gives comparable survival and control rates. The effect of CON might be underestimated due to differences in baseline characteristics. Because chemotherapy cannot always be (completely) administered in low-resource settings, CON could be a worthy substitute. The CON treatment is feasible and safe.