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BACKGROUND: The majority of local relapses after breast conservation therapy occur in the proximity of the primary lesion. Studies have shown that boost radiotherapy (RT) following conventional whole-breast radiotherapy (WBRT) of 50 Gy in five weeks improves outcomes. Boost RT also increases the risk of moderate skin reactions and fibrosis. The ideal boost RT dose and timing (sequential versus simultaneous) after hypofractionated radiotherapy schedules remain unclear. This retrospective propensity score-matched analysis assessed the outcome of sequential hypofractionated boost compared to conventional fractionated boost. METHODS: The study was approved by the Institutional Review Board of the Regional Cancer Centre, Thiruvananthapuram, India. Patients with stage I-III breast cancer who have received adjuvant radiotherapy with a sequential boost of either hypofractionated RT (8 Gy in three fractions) or conventional fractionated RT (10 Gy in five fractions) after conservative breast surgery were identified from the radiotherapy planning records and included in this study. A 1:1 case matching was performed using a propensity score incorporating four known prognostic factors, namely, clinical and pathological composite stage, tumor grade, tumor biology (based on estrogen and/or progesterone and HER2 neu expression), and boost technique, which may have an impact on acute toxicity to make the two boost groups more homogenous. RESULTS: After propensity score matching (PSM), there were a total of 166 patients, with 83 patients each in both conventional and hypofractionated boost RT groups. The median follow-up period was 30.7 months. At two years, locoregional recurrence-free survival (LRFS) was 98.8% in both groups. Disease-free survival (DFS) at two years for the hypofractionated group and conventional group was 91.5% and 96.3% (hazard ratio (HR): 2.5, 95% confidence interval (CI): 0.664-9.4, p = 0.161), respectively, with no statistically significant difference. Patients with grade 3 tumors who received hypofractionated boost had a statistically significant increased risk of recurrence (DFS: 88.9% versus 100%, HR: 60.559, 95% CI: 0.138-26613.2, p = 0.011). The overall survival (OS) at two years was 100% in both groups. There was no difference in acute skin toxicity between the two groups. CONCLUSION: The present interim analysis shows similar locoregional recurrence-free survival, overall survival, and disease-free survival and acute skin toxicity for hypofractionated boost RT of 8 Gy in three fractions compared to the conventional boost of 10 Gy in five fractions. Hypofractionated boost is a feasible alternative option following hypofractionated whole-breast radiotherapy for women with breast conservation treatment. However, longer follow-up is required before forming definite conclusions.
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Background: To identify and characterize malignant and premalignant cells in sputum and matched tissue samples with reference to expression of minichromosome maintenance proteins (MCM2, MCM5) and cell division cycle protein 6 (CDC 6) and to assess their potential as biomarkers of premalignant and malignant lesions of the lung and associations with clinicopathological features. Methods: Expression of MCM2, MCM5 and 6 proteins in sputum samples and corresponding tissues was assessed by immunocytochemistry, and correlated with histological findings. Results: For characterization of malignant, metaplastic or dysplastic cells, CDC6 protein had the highest sensitivity of 87.7%. All the three markers together had a sensitivity of 94.4%. Furthermore these proteins could be employed to assess the proliferative potential of precancerous or atypical cells, as overexpression increasing with the stage of disease and degree of metastasis. Conclusion: The assessed markers can be utilized in routine cytopathology laboratories to supplement conventional morphological evaluation so that the sensitivity of sputum cytology can be enhanced. Potential applications in predicting the clinical behavior of lung lesions and predicting prognosis and survival deserve further attention.
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Background: Cancer is emerging as a major cause of morbidity and mortality in low and middle-income countries. Cancer registry figures help for planning and delivery of health services. This paper provided the first results of cancer incidence and mortality [Crude (CR) and age-standardized (ASR)] rates (world-standard population) of Trivandrum district, South India and compared with other registries under the network of National Cancer Registry Programme (NCRP), Government of India. Materials and Methods: Trivandrum district cancer registry encompasses a population of 3.3 million, compiles data from nearly 75 sources (hospitals and diagnostic laboratories) and included under the NCRP in 2012. During 2012-2014, registry recorded 15,649 incident cases and 5667 deaths. Proportion of microscopic diagnosis was 85% and 'Death certificate only' was 8%. Results: Total cancer incidence (CRs) rates were 161 and 154 (ASR: 142.2 and 126) and mortality rates were 66 and 49 (ASR: 54 and 37) per 105 males and females respectively. Common cancers in males were lung (ASR:19), oral cavity (ASR:15), colo-rectum (ASR:11.2), prostate (ASR:10.2) and lymphoma (ASR:7) and in females, breast (ASR:36), thyroid (ASR:13.4), cervix-uteri (ASR:7.3), ovary (ASR:7) and colo-rectum (ASR:7). Nationally, the highest CRs for breast, prostate, colo-rectum, corpus-uteri and urinary bladder cancers and low incidence of cervix-uteri cancer were observed in Trivandrum. Conclusion: Cancer incidence (CR) in Trivandrum was the highest in both genders in India (except Aizwal). This is mainly due to the highest lifeexpectancy in Kerala. Also, an epidemiologic transition in cancer pattern is taking place and is changing to more similar to "western" jurisdictions.
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Background: Cancer survival depends on loss to follow-up (LFU) and non-proportional hazards (non-PH). If LFU is high, survival will be over-estimated. If hazard is non-PH, rank tests will provide biased inference and Cox-model will provide biased hazard-ratio. We assessed the bias due to LFU and non-PH factor in cancer survival and provided alternate methods for unbiased inference and hazard-ratio. Materials and Methods: Kaplan-Meier survival were plotted using a realistic breast cancer (BC) data-set, with >40%, 5-year LFU and compared it using another BC data-set with <15%, 5-year LFU to assess the bias in survival due to high LFU. Age at diagnosis of the latter data set was used to illustrate the bias due to a non-PH factor. Log-rank test was employed to assess the bias in p-value and Cox-model was used to assess the bias in hazard-ratio for the non-PH factor. Schoenfeld statistic was used to test the non-PH of age. For the non-PH factor, we employed Renyi statistic for inference and time dependent Cox-model for hazard-ratio. Results: Five-year BC survival was 69% (SE: 1.1%) vs. 90% (SE: 0.7%) for data with low vs. high LFU respectively. Age (<45, 46-54 & >54 years) was a non-PH factor (p-value: 0.036). However, survival by age was significant (log-rank p-value: 0.026), but not significant using Renyi statistic (p=0.067). Hazard ratio (HR) for age using Cox-model was 1.012 (95%CI: 1.004 -1.019) and the same using time-dependent Cox-model was in the other direction (HR: 0.997; 95% CI: 0.997- 0.998). Conclusion: Over-estimated survival was observed for cancer with high LFU. Log-rank statistic and Cox-model provided biased results for non-PH factor. For data with non-PH factors, Renyi statistic and time dependent Cox-model can be used as alternate methods to obtain unbiased inference and estimates.
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BACKGROUND: Lung cancer claims highest rate of cancer related mortality worldwide, mainly due to late diagnosis and distant metastasis. Sputum cytology is the simplest, non-invasive and cost effective technique but it has low sensitivity due to lack of robust processing methods to retrieve all the diagnostic materials clogged in mucus, inflammatory exudates and blood. METHODS: This study have compared conventional pick and smear method of sputum processing with samples prepared by homogenization methods using N-acetyl-l-cysteine, Dithiothreitol (DTT), CytoRich red solution and cell blocks (CBs) with respect to screening time, quality of staining, cellularity, smear background, nuclear and cytoplasmic morphology preservation, and diagnostic efficacy. The significance of CB prepared from homogenised samples for immunocytochemistry, protein extraction, Genomic DNA and RNA extraction were also evaluated on a cohort 3,185 samples. The significance of the morphological features in each of the techniques was statistically analysed using SPSS 11 software. RESULTS: The smear background clarity, staining quality and diagnostic efficacy of samples processed in red solution was found to be superior to the conventional method (P < 0.0001), where as samples homogenized in DTT showed a better cellularity (P < 0.0001). CBs prepared from samples homogenized in red solution were found to be very significant (P < 0.0001) in increasing the diagnostic efficacy compared to other two methods. Immunocytochemistry and DNA extraction were found possible in CBs as well as from the cell suspension. A combined analysis of smears and CBs found to improve the sensitivity of sputum cytology. CONCLUSION: The study suggests homogenization of sputum in CytoRich ® red solution and cellblock preparations routinely for all samples to improve the sensitivity of sputum cytology. IHC and DNA extraction can be performed in sputum samples suggesting the role of sputum samples for ancillary techniques.
