The selection of tandem angle and imaging during intracavitary brachytherapy of carcinoma cervix - An experience from a regional cancer center.

Introduction: Carcinoma cervix (CACX) is a common gynecological malignancy and locally advanced CACX is treated with radical chemoradiation, followed by brachytherapy boost. The appropriate selection of tandem angle is needed for optimal dose distribution and to avoid perforations. The aim of our study was to assess the appropriate tandem angle selection based on uterine angle measured on external beam radiotherapy (EBRT) planning imaging and to assess the need for repeat imaging and image-guided placement of tandem during intracavitary brachytherapy based on risk factors. Methods: This is a single-institute, two-arm retrospective, observational study to improve quality of brachytherapy in CACX patients (n = 206), with uterine perforation/suboptimal tandem placement (UPSTP) in arm A and optimally inserted in arm B. The uterine angle was measured from EBRT planning CT-scan and correlated with brachytherapy planning CT-scan and other risk factors in relation to UPSTP. Results: The uterine angle was 30o (±30o) and 17o (±21o) on EBRT and brachytherapy planning CT-scan, respectively, and significantly was different (P < 0.00001). There were 40 (19%) perforations and 52 (25%) suboptimal tandem placements (uterine subserosal/muscle insertion). The most common site of perforation was posterior then anterior and central. There was higher chance of UPSTP with hydrometra, huge uterus with tumor (HMHU) or retroverted uterus (RU), P = 0.006 and 0.14, respectively. The persistence of HMHU or RU during brachytherapy leads to higher UPSTP, P = 0.000023 and 0.18, respectively. Conclusion: Uterine angle measurement on EBRT planning CT-scan varies significantly when measured on brachytherapy planning CT-scan and cannot be used for selection of tandem. Reimaging before brachytherapy should be considered in advanced CACX with HMHU or RU at presentation and image-guided placement of tandem should be used if HMHU or RU persists during brachytherapy.

Significance of Combined Analysis of High-Risk Human Papillomaviruses Polymerized Chain Reaction Analysis and Immunohistochemical Expression of p16INK4A in Cervical Cancer in a Cohort of South-Indian Population.

Introduction Cervical cancer is the fourth most frequent cancer in women worldwide, and it continues to be a big issue in developing countries. The current case-control study sought to determine the presence of high-risk human papillomaviruses (hr-HPV) in the development of cervical cancer, as well as their relationship with the cell cycle inhibitor gene p16INK4A in cervical cancer. Methods The association between p16INK4A protein and the presence of hr-HPV DNA in cervical lesions was explored in this study, which included 150 cervical cancer patients and 100 normal cervix samples. The immunohistochemistry approach was used to identify the expression of the p16INK4A protein, while the semi-quantitative polymerized chain reaction (PCR) method was used to identify the genomic identity of hr-HPV. Results About 90.67% (n=136) of the 150 case samples were found to be hr-HPV positive. Within the 136 HPV-positive samples, 45 (33.08%) show moderate expression of the p16INK4A protein, whereas 91 (66.91%) show overexpression, which is statistically significant (0.05). Among the 136 HPV-positive samples, 22.08% (N=30) were classified as having cervical intraepithelial neoplasia (CIN), with 56.66% (n=17) having CIN3, 36.66% (n=11) having CIN2, and 6.67% (n=2) having CIN1. Conclusion Based on the semi-quantitative immune staining scoring method of p16INK4A protein, genomic expression of HPV demonstrates that the expression of p16INK4A protein increases with the infectious load of the hr-HPV genome in the host cell. The result directly shows that immunostaining of the p16INK4A protein, in conjunction with the assessment of high-risk HPV in the host genome, will aid in the identification of cervical cancer in the cervix.

Genotypic and haplotype analysis of Interleukin-6 and -18 gene polymorphisms in association with clinicopathological factors in breast cancer.

Cytokines are multifunctional glycoproteins that play a vital role in the tumor microenvironment and progression of breast cancer. Genetic polymorphisms may influence the immune responses restrained by pro- and anti-inflammatory cytokine expression in tumors. Hence, the present study evaluated the contribution of Interleukin (IL) 6 (rs1800797, rs1800796, and rs1800795) and IL18 (rs1946518, rs187238, and rs549908) genotypes and their haplotypes to the risk, progression of breast cancer in South Indian population. The polymorphisms of IL6 -597G > A, -572C > G & -174G > C, and IL18 -607C > A, -137G > C, 105A > T were genotyped through PCR-RFLP and As-PCR assays in the blood DNA of 600 subjects. We have performed haplotype, LD, univariate, multivariate logistic regression, and Kaplan-Meier analyses for the obtained data. The frequency of AA genotype & A-allele of IL6 -597G > A, and CC genotype & C-allele of IL6 -174G > C polymorphism was higher in breast cancer patients and was found to be significantly associated with late (advanced) stage, metastasis, etc. Further, IL18 -607C > A, -137G > C, and 105A > T polymorphisms were found to be associated with lobular carcinoma subtype, PgR -ve, and HER2 +ve breast cancer patients. In survival analysis, we have observed that the C-allele of IL6 -174G > C polymorphism to be significantly associated with 5 years of overall survival in breast cancer subjects. All SNPs of the IL6 and IL18 genes showed perfect LD; the G-C-C, A-G-G, and A-C-C haplotype combinations of IL6 gene conferred 2.09, 2.25, and 4.72 folds risk for breast cancer respectively. Hence, our results suggest the importance of genotypic and haplotype analysis of IL6 and IL18 gene variants in the progression and risk prediction of breast cancer.

Evaluation of Rare Types of Breast Cancer among Indian Patients - a Retrospective Study from a Regional Cancer Center.

INTRODUCTION: Breast cancer (BC) is the most common cancer among Indian women and invasive duct cell carcinoma (IDCC) the most common histology (80-90%) followed by noninvasive duct cell carcinoma (non-IDCC) subtypes (about 10%). Most of the non-IDCC are rare (<1-2%), and literature on this topic is sparse. Age is an important prognostic factor and varies with ethnicity. The aim of our study is to evaluate the incidence and age at presentation of different types of BC. MATERIAL AND METHODS: This is a single institute retrospective observational study evaluating BC over the last 7 years at our institute. We evaluated the demographic and pathological features. RESULTS: There were a total of 2725 patients, of these 89.7% had IDCC and 10.2% had non-IDCC. There were 13 subtypes of non-IDCC, the most common being sarcoma/phyllodes (2.4%) and lobular (2.3%). The other subtypes were very rare (<1.5% each). The non-IDCC male BC was very rare (0.07%). The median age at presentation was similar for IDCC and non-IDCC types (50 years). The p value for age at presentation was significant for mucinous (0.0001), phyllodes (<0.0001), and sarcoma breast (0.009) when compared with IDCC. CONCLUSION: The incidence of IDCC, non-IDCC, and rare subtypes of non-IDCC are comparable to literature except lobular (lower) and phyllodes/sarcoma (higher). Indian patients presented a decade earlier for both IDCC and non-IDCC types. Tubular and papillary presented at an age comparable to IDCC, in contrast to the West. Given these differences, the prognosis of non-IDCC needs to be evaluated in future studies on Indian BC patients.

Synergistic effect of collagenase-1 (MMP1), stromelysin-1 (MMP3) and gelatinase-B (MMP9) gene polymorphisms in breast cancer.

BACKGROUND: Extracellular matrix degradation by matrix metalloproteinases (MMPs) is an important mechanism involved in tumor invasion and metastasis. Genetic variations of MMPs have shown association with multiple cancers. The present study is focused to elucidate the association of MMP-1, 3 and 9 genetic variants with respect to epidemiological and clinicopathological variables by haplotype, LD, MDR, survival in silico analyses among South Indian women. MATERIAL AND METHODS: MMP3-1171 5A/6A and MMP9-1562 C/T SNPs were genotyped by Allele specific polymerase chain reaction and MMP1-1607 1G/2G polymorphism by restriction fragment length polymorphism assays respectively, in 300 BC patients and age-matched 300 healthy controls. Statistical analysis was performed using the SNPStats and SPSS software. Linkage disequilibrium and gene-gene interactions were performed using Haploview and MDR software respectively. Further, transcription factor binding sites in the promoter regions of SNPs under study were carried out using AliBaba2.1 software. RESULTS: We have observed an increased frequency of 2G-allele of MMP1, 6A-allele of MMP3 and T-allele of MMP9 (p<0.05) respectively in BC subjects. The 2G-6A haplotype (minor alleles of MMP-1 and MMP-3 respectively) has shown an increased susceptibility to BC. Further, MMP polymorphisms were associated with the clinical characteristics of BC patients such as steroid hormone receptor status, lymph node involvement and metastasis. SNP combinations were in perfect LD in controls. MDR analysis revealed a positive interaction between the SNPs. 5-years survival rate and cox-regression analysis showed a significant association with clinicopathological variables. CONCLUSION: Our results suggest that MMP1-1607 1G/2G, MMP3-1171 5A/6A and MMP9-1562 C/T gene polymorphisms have synergistic effect on breast cancer. The interactions of MMPs clinical risk factors such as lymph node involvement has shown a strong correlation and might influence the 5-years survival rate, suggesting their potential role in the breast carcinogenesis.

Recommendations to Support Nurses and Improve the Delivery of Oncology and Palliative Care in India.

CONTEXT: Nurses in India often practice in resource-constrained settings and care for cancer patients with high symptom burden yet receive little oncology or palliative care training. AIM: The aim of this study is to explore challenges encountered by nurses in India and offer recommendations to improve the delivery of oncology and palliative care. METHODS: Qualitative ethnography. SETTING: The study was conducted at a government cancer hospital in urban South India. SAMPLE: Thirty-seven oncology/palliative care nurses and 22 others (physicians, social workers, pharmacists, patients/family members) who interact closely with nurses were included in the study. DATA COLLECTION: Data were collected over 9 months (September 2011- June 2012). Key data sources included over 400 hours of participant observation and 54 audio-recorded semi-structured interviews. ANALYSIS: Systematic qualitative analysis of field notes and interview transcripts identified key themes and patterns. RESULTS: Key concerns of nurses included safety related to chemotherapy administration, workload and clerical responsibilities, patients who died on the wards, monitoring family attendants, and lack of supplies. Many participants verbalized distress that they received no formal oncology training. CONCLUSIONS: Recommendations to support nurses in India include: prioritize safety, optimize role of the nurse and explore innovative models of care delivery, empower staff nurses, strengthen nurse leadership, offer relevant educational programs, enhance teamwork, improve cancer pain management, and engage in research and quality improvement projects. Strong institutional commitment and leadership are required to implement interventions to support nurses. Successful interventions must account for existing cultural and professional norms and first address safety needs of nurses. Positive aspects from existing models of care delivery can be adapted and integrated into general nursing practice.