Donald J Fernandes

Evaluation of micronuclei frequency in the cultured peripheral blood lymphocytes of cancer patients before and after radiation treatment

The frequency of micronucleated binucleate lymphocyte (MNBNC) was determined in the peripheral blood lymphocytes of patients suffering from various types of cancer before the onset of radiation treatment, middle (mid-) of the treatment and after completion of the treatment (post-treatment). The frequency of micronuclei increased significantly in the pretreatment sample of cancer patients when compared with the normal untreated healthy volunteers. During the middle of the radiotherapy an approximate two or > two-fold increase was observed in the micronuclei frequency in most of the patients when compared with the concurrent pretreatment samples. Immediately after the completion of treatment, the frequency of micronuclei further increased, and this increase was significantly higher than that of pretreatment and mid-treatment samples. Out of 27 patients analyzed, only nine patients did not have any history of smoking, tobacco chewing or alcohol consumption, while the remaining 18 patients had a history of either smoking, tobacco chewing or alcohol consumption or combination of two or all habits at the time of blood collection.

Low Level Helium Neon Laser therapy for chemoradiotherapy induced oral mucositis in oral cancer patients – A randomized controlled trial

BACKGROUND Patients receiving chemoradiotherapy (CRT) for oral cancer (OC) often develop oral mucositis (OM). OM associated pain severely affects oral functions and nutrition of the patient, resulting in narcotic analgesic use and CRT interruption. Laser therapy has shown some promising results in preventing and treating OM caused by cancer therapies. So in this trial we used prophylactic Low Level Helium Neon (He-Ne) Laser for the prevention and treatment of CRT induced OM in OC patients. MATERIALS AND METHODS This double blinded trial block randomized 121 primary OC patients scheduled to undergo CRT [RT dosage=66 Gray/33 fractions for 5 days/week and chemotherapy (3 weekly Cisplatin)] into laser (n=60) and placebo (n=61) group. Laser group received He-Ne Laser (λ=632.8 nm, P=24 mW, ED=3.5 J/cm(2)) while placebo received sham treatment just before radiation for 6.5 weeks. OM (RTOG/EORTC Scale), its associated pain, and total parenteral nutrition (TPN), were assessed on every week by a blinded assessor. Also opioid analgesic use, weight loss and any CRT break were recorded. Data was analyzed using descriptive statistics, t-test and Man Whitney U test. Level of significance was set at p<0.05. RESULTS Incidence of severe OM (29% vs. 89%, p<0.001) and its associated pain (18% vs. 71%, p<0.001), opioid analgesic use (7% vs. 21%, p<0.001)and TPN (30% vs. 39% p=0.039) was significantly less in laser than placebo group patients. Also duration of severe OM and pain experienced was less in laser than placebo group. CRT break required only for placebo group (9%) patients. CONCLUSION Low Level He-Ne Laser decreased the incidence of CRT induced severe OM and its associated pain, opioid analgesics use and TPN.

Symptomatic vertebral hemangiomas- results of treatment with radiotherapy

Objectives : Vertebral hemangiomas are benign vascular lesions occurring in spine. Though vertebral hemangiomas are frequently seen, they are rarely symptomatic. Pain is the commonest symptom. There is no agreement on single treatment modality for symptomatic lesions. Surgery, intralesional injection of absolute alcohol, methyl methacrylate injection are few methods used to treat them. Radiotherapy has been shown effective in many studies in terms of pain relief and at times in cord compression too. Results of radiotherapy in symptomatic vertebral hemangiomas treated in our centre are analyzed. Materials and methods: Six patients with symptomatic vertebral hemangiomas were treated with external radiotherapy to a dose of 36-40 Gy. Four patients had only pain as their symptom. Two patients had additional neurological deficits with paraperesis at presentation. Result in terms of pain relief was assessed at the end of RT and during follow up. Median follow up was four and half months. Results : Out of six patients, pain relief was seen in four patients who had only pain as their symptom. There was neither pain relief nor improvement in neurological deficits in remaining two patients. Conclusion : Radiotherapy is an effective and simple modality of treatment for symptomatic vertebral hemangiomas where pain is the main symptom without neurological deficits. It is non invasive and safe.

Second Primary Malignant Neoplasms: A Clinicopathological Analysis from a Cancer Centre in India

CONTEXT Patients diagnosed with a cancer have a life time risk of developing another de novo malignancy depending on various inherited, environmental and iatrogenic risk factors. Of late the detection of new primary has increased mainly due to refinement in both diagnostic and treatment modalities. Cancer victims are surviving longer and thus are more likely to develop a new metachronous malignancy. AIMS To report our observed trend of increase in prevalence of both synchronous and metachronous second malignant neoplasms among cancer victims and to review the relevant literature. SETTINGS AND DESIGN A hospital based retrospective collection of prospective data of patients diagnosed with second denovo malignancy. MATERIALS AND METHOD The study was conducted over a 5 year period from July 2008 to June 2012. All patients diagnosed with a histologically proven second malignancy as per Warren Gates criteria were included. Various details regarding sex, age at presentation, synchronous or metachronous, treatment and outcome were recorded. CONCLUSIONS The occurrence of multiple primary malignancies is not rare. Awareness of the possibility alerts the clinician in evaluation of patients with a known malignancy presenting with unusual sites of metastasis. Individualizing the treatment according to the stages of the primaries will result in durable cancer control particularly in synchronous double malignancy.

Nasal NK/T cell lymphoma presenting as a lethal midline granuloma.

Nasal NK/T cell lymphomas are aggressive, locally destructive, midfacial, necrotizing lesions. The nonspecific clinical symptoms constitute a major stumbling block in the early diagnosis and management of these lymphomas. We report here a case of probable nasal NK/T cell lymphoma in an apparently healthy male that progressed rapidly in a short span of time and was managed subsequently with chemotherapy and external beam irradiation with which the lesion regressed.

Low level laser therapy against radiation induced oral mucositis in elderly head and neck cancer patients-a randomized placebo controlled trial.

OBJECTIVES Radiotherapy (RT) is treatment of choice for Elderly Head and Neck Cancer (HNC) patients. Oral mucositis (OM) during RT affects patients routine oral activities and overall health. Low Level Laser Therapy (LLLT) provided some promising results against cancer therapy induced OM in children and adults. No study specifically evaluated effects of LLLT against RT induced OM in elderly HNC patients until date, hence we did this study. MATERIAL AND METHODS This double blinded study randomized 46 elderly HNC patients scheduled for RT [Dosage=66 Gray (2 Gy/fraction), 5 fractions/week, total 33 fractions for 6.5 weeks], into laser (22) and placebo (24) groups. Laser group patients received LLLT [Helium-Neon, λ=632.8 nm, power density=0.024 W/cm(2), dosage=3.0 J/point at six anatomical sites bilaterally i.e. 12 locations, total dose/session=36 J, beam aperture diameter=0.6 mm, beam spot size=1 cm(2), irradiated area diameter=1 cm(2), irradiation time/point=125 s, 5 sessions/week, non-contact method-distance between probe and irradiated tissues <1 cm, whereas placebo group did not receive laser. OM grades (RTOG/EORTC Scale), oral pain, weight loss, need for morphine analgesics and tube feeding, and RT break were recorded by a blinded assessor. Descriptive statistics and repeated measures ANOVA were used for analysis keeping p<0.05. RESULTS Significant reduction in the incidence and duration of severe OM (p=0.016) and severe pain (p=0.023) and weight loss (p=0.004) was observed in laser than placebo group. No difference was found for enteral feeding use (p=0.667) between two groups. CONCLUSIONS LLLT decreased the severity of OM and oral pain in elderly HNC patients. Also, lesser weight loss, morphine analgesic use and radiation break happened in laser group.

A screening model for oral cancer using risk scores: development and validation

OBJECTIVE A study was conducted to develop and validate a screening model using risk scores to identify individuals at high risk for developing oral cancer in an Indian population. METHODS Life-course data collected from a multicentre case-control study in India were used. Interview was conducted to collect information on predictors limited to the time before the onset of symptoms or cancer diagnosis. Predictors included statistically significant risk factors in the multivariable model. A risk score for each predictor was derived from respective odds ratios (OR). Discrimination of the final model, risk scores and various risk score cut-offs was examined using the c statistic. The optimal cut-off was determined as the one with good area under curve (AUC) and high sensitivity. Predictive ability of the regression model and cut-off risk score was determined by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Models were validated from a bootstrap sample. RESULTS Smoking, chewing quid and/or tobacco, alcohol, a family history of upper aero-digestive tract cancer, diet and oral hygiene behaviour were the predictors. Risk scores ranged from 0 to 28. Area under the receiver operating characteristic (ROC) curve for risk scores was good (0.866). The sensitivity (0.928) and negative predictive value (0.927) were high, while specificity (0.603) and positive predictive value (0.607) were low for a risk score cut-off of 6. CONCLUSION A risk score model to screen for individuals with high risk of oral cancer with satisfactory predictive ability was developed in the Indian population. Validation of the model in other populations is necessary before it can be recommended to identify subgroups of the population to be directed towards more extensive clinical evaluation.

Non-Hodgkin's lymphoma: is India ready to incorporate recent advances in day to day practice?

BACKGROUND Non Hodgkins Lymphoma (NHL) cure rates are increasing and morbidities are decreasing, with more active pharmacological agents and technological advancements. In spite of this, India is still battling with the prejudices of an economically and educationally impoverished patient base. METHODS AND RESULTS We analyzed NHL cases from 2000 to 2006 using data from case sheets. Of 303 cases, only 100 patients had complete workup and received some form of treatment. For 203 patients, reasons for non-compliance were: financial constraint (119), distance from center (38), inability of physician to provide guarantees of cure (13), poor prognosis/fear of recurrence (28)), preferences for alternate medicine (5). Most common investigations that could not be afforded for staging were whole body CT scans and bone marrow aspiration and biopsy. Thirteen patients were in stage III and 53 in Stage IV. The most common regimen was CHOP (Cyclophosphamide, Adriamycin, Vincristine, Prednisolone). Forty-five patients did not complete six courses of CHOP and 35 patients had significant delay. Reasons for delay were intermittent availability of cash (35), intolerable toxicities (30), absence of supportive care (21), given-up attitudes (17). Eighty-three patients suffered Grade III/IV debilitating toxicities. Overall survival at five years was 50%. CONCLUSIONS NHL in India is no different from the developed world. However, there are disparities in survivorship and outcomes, due to un-affordability and attitudes of the patients. Therefore, we suggest the development of Community Health Insurance Schemes (CHIs), with the hospital as the nodal center to address the above mentioned issues.

A Study on Dosimetric Outcomes and Acute Toxicity of Post Mastectomy Adjuvant Hypofractionated Radiotherapy for Breast Cancer.

INTRODUCTION Hypofractionated External Beam Radiotherapy (HFRT) is a relatively new adjuvant Radiotherapy (RT) schedule for breast cancers following breast conservation surgery and less commonly, following mastectomy. Here we report our experience on normal tissue exposure and acute toxicity of HFRT after mastectomy. AIM To assess the dosimetric outcomes and acute toxicity profile of adjuvant HFRT following mastectomy for breast cancer. MATERIALS AND MATERIALS This prospective observational study considered consecutive patients planned for adjuvant HFRT (42.5 Gy in 16 sessions delivered over 3 weeks) to the chest wall with/without regional nodes between October 2014 and June 2015. The dosimetric parameters including dose homogeneity to the target volume and exposure to heart and lung were analyzed. Acute haematological and dermatological toxicity was recorded until upto three months after completion of RT. RESULTS Among the 56 patients treated with HFRT, the mean age was 49 years (range: 28-69 years). Pathologically positive nodes and ≥pT3 primary was observed in 44 (78.6%) and 12 (21.4%) patients, respectively. Majority (87.5%) received prior adjunct chemotherapy. RT to the supraclavicular fossa was delivered for 39 (69.6%) patients. The mean V90 and V95 to the Planning Target Volume (PTV) were 95% (± 3.3%) and 93% (± 4%), respectively. The maximum dose received was on average 47.7 Gy (112%; range: 46.2-48.5 Gy). The mean lung dose was 10.2 Gy (± 3.5 Gy) and V20 was 20.9% (± 6%). The mean V25 to heart was 6.6% (± 4.8%) for left sided and 0% for right sided tumours (p=0.001). Acute skin toxicity peaked at completion of RT and was tolerable (grade 0, I, II and III reactions were 75%, 16% and 1.8%, respectively). No patient had ≥ grade III haematological toxicity, and treatment was not interrupted for any patient. CONCLUSION Adjuvant HFRT could be planned while meeting the dose constraints to normal tissues in all patients and was well tolerated, with mild to moderate acute adverse effects that did not warrant any therapeutic intervention or treatment interruption.

Detection of human papilloma virus in patients with squamous cell carcinoma of the esophagus planned for definitive chemo-radiotherapy, and a study of their clinical characteristics

CONTEXT To identify the incidence of human papilloma virus (HPV) infection in squamous esophageal cancer. AIMS To identify high-risk (HR) HPV positivity rates in patients with squamous carcinoma esophagus and to compare their characteristics with HPV negative counterparts. SETTINGS AND DESIGN A prospective study, in which tumor biopsies of 18 consecutive patients with squamous carcinoma of the esophagus treated with definitive chemo-radiotherapy (CT-RT) were evaluated for the presence of HPV. SUBJECTS AND METHODS Tumor biopsies of 18 consecutive patients with squamous carcinoma esophagus treated with definitive CT-RT were assessed for presence of HR HPV DNA by hybrid DNA capture technique (Digene-HC2). The clinical characteristics and treatment outcomes of the two groups were then compared. STATISTICAL ANALYSIS USED Pearsons Chi-squared test, Kaplan-Mier survival curve/log rank test. RESULTS Nine patients (50%) tested positive for HR HPV. The clinical features including age, gender, grade, location, and tumor extent were similar between the two groups. All the three patients with residual disease at the end of treatment tested positive for HPV (P = 0.058). At a mean follow-up of 52 weeks, the estimated median recurrence free survival was 37 weeks (95% confidence interval (CI): 13.6-60.4) among HPV positive patients compared to 53 weeks (95% CI: 29.6-76.4 weeks) for the HPV negative (P = 0.93). CONCLUSIONS There appears to be a high incidence of HPV among patients with squamous oesophageal cancer in coastal Karnataka. Further studies are required to evaluate its causative role and prognostic implications.