Donald Fernandes

Low level laser therapy for concurrent chemoradiotherapy induced oral mucositis in head and neck cancer patients – A triple blinded randomized controlled trial

BACKGROUND AND PURPOSE Oral mucositis (OM) is most cumbersome acute side effect of concurrent chemoradiotherapy (CCRT) for head and neck cancer (HNC). OM associated pain affects oral functions and nutrition of the patient that may result in discontinuity of treatment. Several modalities have been tried to prevent and treat OM, but none proved completely successful until date. We used prophylactic low level laser therapy (LLLT) for the prevention and treatment of CCRT induced OM. MATERIALS AND METHODS In this triple blinded study, 221 HNC patients scheduled to undergo CCRT (Cisplatin (1, 22, 43 day)+RT=66 Grays (2 Gy/fraction), 33 fractions, 5 fractions/week, for 45 days) were block randomized into laser (n=111) and placebo (n=110) group. Laser group received LLLT (HeNe, λ=632.8 nm, power-density=24 mW, dosage=3.0 J/point, total dosage/session=36-40 J, spot-size=1cm(2), 5 sessions/week) while placebo received sham treatment daily prior to radiation. OM (RTOG/EORTC Scale), oral pain (VAS), dysphagia (FIS), weight loss and CCRT break were assessed. Data were analyzed using frequencies and percentage, generalized estimating equations (GEE) and odds ratio. RESULTS There was significant reduction in incidence of severe OM (F=16.64, df=8876, p<0.0001) and its associated pain (F=25.06, df=8876, p<0.0001), dysphagia (F=20.17, df=8876, p<0.0001) and opioid analgesics use (p<0.0001) in laser than placebo group patients. CONCLUSIONS LLLT decreased the incidence of CCRT induced severe OM and its associated pain, dysphagia and opioid analgesics use.

DNA Double-Strand Break Analysis by γ-H2AX Foci: A Useful Method for Determining the Overreactors to Radiation-Induced Acute Reactions Among Head-and-Neck Cancer Patients

PURPOSE Interindividual variability in normal tissue toxicity during radiation therapy is a limiting factor for successful treatment. Predicting the risk of developing acute reactions before initiation of radiation therapy may have the benefit of opting for altered radiation therapy regimens to achieve minimal adverse effects with improved tumor cure. METHODS AND MATERIALS DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of head-and-neck cancer patients undergoing chemoradiation therapy was analyzed by counting γ-H2AX foci, neutral comet assay, and a modified version of neutral filter elution assay. Acute normal tissue reactions were assessed by Radiation Therapy Oncology Group criteria. RESULTS The correlation between residual DSBs and the severity of acute reactions demonstrated that residual γ-H2AX foci in head-and-neck cancer patients increased with the severity of oral mucositis and skin reaction. CONCLUSIONS Our results suggest that γ-H2AX analysis may have predictive implications for identifying the overreactors to mucositis and skin reactions among head-and-neck cancer patients prior to initiation of radiation therapy.

Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

PURPOSE Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. METHODS AND MATERIALS DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. RESULTS The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). CONCLUSIONS Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

Polymorphisms in Radio-Responsive Genes and Its Association with Acute Toxicity among Head and Neck Cancer Patients

Cellular and molecular approaches are being explored to find a biomarker which can predict the development of radiation induced acute toxicity prior to radiation therapy. SNPs in radiation responsive genes may be considered as an approach to develop tools for finding the inherited basis of clinical radiosensitivity. The current study attempts to screen single nucleotide polymorphisms/deletions in DNA damage response, DNA repair, profibrotic cytokine as well as antioxidant response genes and its predictive potential with the normal tissue adverse reactions from 183 head and neck cancer patients undergoing platinum based chemoradiotherapy or radiotherapy alone. We analysed 22 polymorphisms in 17 genes having functional relevance to radiation response. Radiation therapy induced oral mucositis and skin erythema was considered as end point for clinical radiosensitivity. Direct correlation of heterozygous and mutant alleles with acute reactions as well as haplotype correlation revealed NBN variants to be of predictive significance in analysing oral mucositis prior to radiotherapy. In addition, genetic linkage disequilibrium existed in XRCC1 polymorphisms for >grade 2 oral mucositis and skin reaction indicating the complex inheritance pattern. The current study indicates an association for polymorphism in NBN with normal tissue radiosensitivity and further warrants the replication of such studies in a large set of samples.

Effectiveness of pranayama on cancer-related fatigue in breast cancer patients undergoing radiation therapy: A randomized controlled trial.

Context: Incidence of breast cancer is very high among women around the world. Breast cancer patients experience cancer-related fatigue at some points during the treatment for breast cancer. Since cancer-related fatigue is of multifactorial origin, there are no evidence-based treatment strategies for fatigue. This study tested the effectiveness of certain pranayama techniques in reducing cancer-related fatigue among breast cancer patients undergoing radiation therapy. Aims: The objective of this study was to determine the effectiveness of pranayama on cancer-related fatigue among breast cancer patients undergoing radiation therapy as measured by cancer fatigue scale. Settings and Design: Shirdi Sai Baba Cancer Hospital and Research Center, Kasturba Hospital Manipal. Materials and Methods: Study was a randomized controlled trial done among breast cancer patients receiving radiation therapy. Statistical Analysis Used: Demographic characteristics of the participants are presented as frequency and percentage. Comparison of means of cancer-related fatigue between the two groups is done by Mann-Whitney U-test and comparison of pre- and pos t-test means of cancer-related fatigue among the experimental group is done by Wilcoxon sign rank test. Results: There was a significant difference between the two groups with regard to the scores of cancer-related fatigue. The experimental group of patients who performed pranayama along with radiation therapy experienced less fatigue. Conclusions: Pranayama can be used as a supportive therapy for breast cancer patients undergoing radiation therapy.

A Brief Review of Common Oral Premalignant Lesions with Emphasis on Their Management and Cancer Prevention

Long-term outcomes associated with oral cancer and its management over the past several decades has caused concern and the value of mass oral cancer screenings has come under scrutiny. Though not all oral carcinomas are preceded by premalignant lesions as clinically visible morphological alterations occur secondary to the cellular or molecular changes, certain high risk lesions have been identified. Their management remains controversially polarized between surgical excision to prevent malignant change and conservative medical or surveillance techniques. Though oral cancer is one of the “major killers” of modern times, there seem to be no widely accepted criteria for decision making in clinical practice, the evidence base is scanty and uncertainty persists throughout investigation, diagnosis, and treatment. In this article, we have briefly discussed the common premalignant lesions, with an emphasis on their evidence based management and prevention.

Treatment outcomes after intraluminal brachytherapy following definitive chemoradiotherapy in patients with esophageal cancer

AIMS AND OBJECTIVES To report the results of treatment with intraluminal brachytherapy (ILRT) after concurrent chemoradiotherapy for esophageal carcinoma with respect to disease free survival (DFS), dysphagia free interval (DFI), and complications of treatment. MATERIALS AND METHODS The study retrospectively analyzed the records of 26 eligible patients with nonmetastatic carcinoma of the esophagus treated with definitive chemoradiotherapy followed by ILRT between 2008 and 2011. The DFS and DFI were estimated and factors likely to influence them were analyzed. RESULTS Nineteen (73%) patients were males. The mean age at presentation was 60 years (range: 47-90 years). All the patients had squamous cell carcinomas. Following treatment, the median DFS was 12.7 months (range: 0-27 months). Sixteen patients (61.5%) had local control of their disease, while one had residual disease at completion of treatment. Other than three patients who were not evaluated for recurrent dysphagia, six (23.1%) had proven local recurrence on follow-up. The estimated mean DFI was 13.8 months (range: 0-27 months). One patient died of tracheoesophageal fistula following treatment. On statistical analysis, only the location of tumor was prognostically significant, with lower third tumors performing worse. Other probable predictors of poor outcome included large volume (> 40 cc), tumor length (> 6 cm), and eccentric location. CONCLUSION ILRT boost following concurrent chemoradiotherapy is well tolerated and potentially improves outcomes. It might be beneficial in selected patients with esophageal carcinoma. Further studies are required to identify its role in definitive treatment.

Abstract 480: Analysis of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of 178 primary locally advanced oral squamous cell carcinoma cases: the prognostic implication

Background: Oral Squamous Cell Carcinomas comprise of a heterogeneous tumor cell population with of varied molecular characteristics; which makes prognostication of these tumors a complex and challenging issue. Thus, molecular profiling of these tumors is advantageous for an accurate prognostication and treatment planning. Study design: A retrospective study on a cohort of primary locally advanced oral squamous cell carcinomas (n = 178) of an Indian rural population Aim: • To evaluate the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of primary locally advanced oral squamous cell carcinomas. • To assess the reliability of this panel of biomarkers for prognostication and treatment planning of locally advanced oral squamous cell carcinomas • To identify a potential biomarker that can predict the tumor response to treatment. Patient Selection: All patients who were diagnosed with locally advanced oral squamous cell carcinomas cases between the year 2009 and 2013 were reviewed. These patients were treated with radiotherapy and adjuvant chemotherapy. The maximum duration of follow-up was 5 years and the minimum follow-up time is 1 ½ years. Material and Methods: Formalin fixed paraffin embedded tumor blocks of (n = 178) of histopathologically diagnosed cases locally advanced oral squamous cell carcinomas were selected. The areas where the tumor cells appeared most aggressive were identified in the Hematoxylin and Eosin stained tissue sections of these cases. The corresponding areas were identified in the tumor blocks and two cores of 2 mm diameter for each case were obtained and tissue microarray blocks were constructed. Four microns thick sections were cut from these tissue microarray blocks. These tissue microarray sections were immunohistochemically stained for EGFR, p53 and Bcl-2 and cyclin D1 and p16. The expression of these markers by the tumor cells was evaluated in a semi quantitatively. The dat Results: In this cohort, EGFR was the most expressed in 150/178 (84%) of the cases. The expression of EGFR was significantly associated with p53 (p = .012), and with cyclin D1 (p = .011). Kaplan Meier analysis showed a significant association (p = .038) between expression of p53 and a poor prognosis. A Poisson regression analysis showed that tumors that expressed p53 had a two times greater chance of recurrence (Unadjusted IRR -95% CI 2.08 (1.03, 4.5), Adjusted IRR- 2.29 (1.08, 4.8) compared with the tumors that did not express this biomarker. Conclusion: Molecular profiling of oral squamous cell carcinomas will enable us to categorize our patients into more realistic risk groups. With biologically guided tumor characterization, personalized treatment protocols can be designed for individual patients, which will improve the quality of life of these patients. Citation Format: Monica C. Solomon, Mammadipuli Vidyasagar, Donald Fernandes, Vasudeva Guddattu. Analysis of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in a cohort of 178 primary locally advanced oral squamous cell carcinoma cases: the prognostic implication. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 480.

Emotional aspects and pranayama in breast cancer patients undergoing radiation therapy: A randomized controlled trial

Objective: Emotional disturbances are commonly experienced by cancer patients. The aim of this study was to determine the effectiveness of certain Pranayama techniques on the emotional aspects such as impatience, worry, anxiety, and frustration among breast cancer patients undergoing radiation therapy in India. Methods: The study was conducted as a randomized controlled trial. Patients were recruited when they were seeking radiation therapy for breast cancer. They were allocated into two groups using block randomization technique. The experimental group performed Pranayama along with radiation therapy, whereas the control group received only routine care. Results: Emotional aspects of the two groups were compared at the end of the treatment. Mann-Whitney U-test was used for comparison as the data were not following normality. It showed a significant difference between the two groups with the group who performed Pranayama showing a lesser mean score for these negative emotions. Conclusions: Pranayama might help in controlling the negative emotions likely to be faced by breast cancer patients, and it can be used as a supportive therapy for breast cancer patients receiving radiation therapy.

Clinico–Pathological Correlation Of The Expression Of Cyclin D1 And Bcl–2 In Oral Squamous Cell Carcinomas –A Tissue Microarray Study

Oral squamous cell carcinomas (OSCC)containa heterogenous tumor cell population that are at different stages of differentiation and with different levels of proliferative potential. Hence, the behavioural pattern of individual cases is poorly predictable. Several molecules play a vital role in the step-wise process of oral carcinogenesis. A better understanding of the interaction of these molecules will help in identifying the subgroup of patients with poor outcomes. Aim and Objective:To analyse the immunohistochemical expression of the cyclin D1 and bcl-2 in oral squamous cell carcinomas. To evaluate the possible association between cyclin D1 and Bcl-2 during the progression of oral squamous cell carcinomas. Settings and Design: A systematic approach of tissue microarray technology and immunohistochemistry analysis for a cohort of oral squamous cell carcinoma patients. Materials and methods: Formalin Fixed Paraffin Embedded (FFPE) tissue blocks of histological proven cases of OSCC (n=119) were selected. Tissue microarray (TMA)paraffin blocks were constructed using a “handy tissue microarrayer”. 4 μm thick sections were cut from the TMA blocks and the sections were immunostained with cyclin D1 and Bcl2. A semiquantitative analysis of the immunohistochemical expression of these markers in the tumor cells was carried out.