A prospective randomized trial comparing accelerated concurrent chemoradiotherapy with conventional concurrent chemoradiotherapy in locally advanced carcinoma cervix (IIA-IVA).

INTRODUCTION: Cervical cancer ranks fourth in women worldwide. The management requires a multidisciplinary approach. Concomitant chemoradiotherapy with cisplatin, followed by brachytherapy, is the standard approach. Accelerated radiotherapy (ART) can be used to decrease the treatment duration which can further lead to better outcomes. MATERIALS AND METHODS: Stages II, III, and IVA of carcinoma cervix were studied for 1 year. Ninety patients were randomized in control and study arms, 45 patients in each arm. The total dose of radiation was 50 Gy/25#/5 weeks from Monday to Friday in the control arm and 50 Gy/25#/4 weeks from Monday to Saturday in the study arm, with injection cisplatin 40 mg/m 2 intravenous infusion weekly in both the arms. RESULTS: The response was similar in both the arms at the first follow-up as well as at median follow-up. However, acute toxicities in the ART arm were more, but they were managed conservatively. CONCLUSION: ART can be used in patients of cervical cancers to decrease the total treatment time. The results were similar in both the groups but need to be studied over more number of patients.

Circulating miR-320a Acts as a Tumor Suppressor and Prognostic Factor in Non-small Cell Lung Cancer.

Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold; p < 0.0001) in NSCLC patients (n = 80) compared to matched control plasma samples from healthy subjects (n = 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels (p < 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissues via immunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated that AKT3 was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients.

Circulating microRNA-590-5p functions as a liquid biopsy marker in non-small cell lung cancer.

Despite the availability of various diagnostic procedures, a tissue biopsy is still indispensable for the routine diagnosis of lung cancer. However, inaccurate diagnoses can occur, leading to inefficient cancer management. In this context, use of circulating microRNAs (miRNAs) may serve as diagnostic tools as liquid biopsies, and as biomarkers to better understand the molecular mechanisms involved in the progression of cancer. We identified miR-590-5p as a potential prognostic marker in the progression of non-small cell lung cancer (NSCLC). We were able to detect this miRNA in blood plasma samples of NSCLC patients through quantitative real-time PCR. Our data showed an ~7.5-fold downregulation of miR-590-5p in NSCLC patients compared to healthy controls, which correlated with several clinicopathological features. Further, overexpression of miR-590-5p led to decreased cell viability, proliferation, colony formation, migration, and invasion potential of lung cancer cells, whereas its knockdown showed the opposite effect. In addition, the levels of several proteins involved in the epithelial-to-mesenchymal transition negatively correlated with miR-590-5p levels in lung adenocarcinoma cells and tumors of NSCLC patients. Further, dual-luciferase reporter assays identified STAT3 as a direct target of miR-590-5p, which negatively regulated STAT3 activation and its downstream signaling molecules (eg, Cyclin D1, c-Myc, Vimentin, and ß-catenin) involved in tumorigenesis. Taken together, our study suggests that miR-590-5p functions as a tumor suppressor in NSCLC through regulating the STAT3 pathway, and may serve as a useful biomarker for the diagnosis/prognosis of NSCLC, and as a potential therapeutic target for the treatment of NSCLC.

Four percent formalin application for the management of radiation proctitis in carcinoma cervix patients: An effective, safe, and economical practice.

CONTEXT: Radiotherapy is a very effective treatment modality for pelvic malignancies such as carcinoma of the cervix. However, it is quite common for chronic radiation proctitis (CRP) to manifest after radical radiotherapy. CRP is a source of significant morbidity, and there is a lack of effective treatment modalities. There also exists a general lack of guidelines on management of CRP. AIMS: To assess the benefit from 4% formalin application for the treatment of Grade >2 CRP among patients previously treated with radical radiotherapy for cervical carcinoma. SETTINGS AND DESIGN: This retrospective descriptive study involved 29 eligible patients who were treated from November 2010 - November 2015 for CRP with 4% formalin application. MATERIALS AND METHODS: Of the 1864 patients of carcinoma cervix treated during the said patients, 29 patients fulfilled the eligibility criteria. Eligible patients were invited telephonically for follow-up and were assessed for response and complications of the procedure. RESULTS: The treatment of hemorrhagic radiation proctitis with local formalin instillation is effective, well tolerated and safe procedure. The procedure is inexpensive, technically simple and can be done on an outpatient basis. 62% patients had complete freedom from rectal bleed, while 34.5% patients had partial benefit. Only one patient required diversion colostomy for persistent bleeding.

The Nonsynonymous Polymorphisms Val276Met and Gly393Ser of E2F1 Gene are Strongly Associated with Lung, and Head and Neck Cancers.

AIM: The early gene factor-2 (E2F), a family of transcription factors, is involved in cell cycle regulation. Deregulated expression of most of the members of the E2F family is associated with various human cancers. In this study, we investigated the association between the E2F1 genetic variants rs3213173 (C/T) (Val276Met) and rs3213176 (G/A) (Gly393Ser) with the risk of lung cancer (LC) and head and neck cancer (HNC) in 190 patients and 230 control samples. MATERIALS AND METHODS: We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mutagenic primer-based PCR-RFLP methods to genotype all target polymorphisms. RESULTS: The rs3213173 (C/T) polymorphism was associated with LC risk in the homozygous model (odds ratio [OR] = 2.954, 95% confidence interval [CI] 1.366-6.386; p = 0.004) as well as in heterozygous model (OR = 2.314; 95% CI = 1.369-3.912; p = 0.001). A significant association was also observed for the rs3213176 (G/A) polymorphism with LC risk in homozygous model, GG versus AA (OR = 2.750; 95% CI = 1.236-6.118; p = 0.01); in heterozygous model, GG versus GA (OR = 2.111; 95% CI = 1.256-3.549; p = 0.004); and in combined mutant GG versus GA+AA (OR = 2.214; 95% CI = 1.343-3.650; p = 0.001). The rs3213176 (G/A) marker was also associated with HNC risk. CONCLUSIONS: Our findings reveal that the rs3213173 (C/T) and rs3213176 (G/A) polymorphisms of the E2F1 gene are genetic risk factors for susceptibility to LC and HNC in the North Indian Population.

Metabolic Bone Superscan in Carcinoma Breast with Occult Graves' Disease: Looking Beyond Skeletal Metastases.

Extrathyroidal manifestations of autoimmune thyroid disorders include thyroid-associated ophthalmopathy, thyroid dermopathy, and thyroid acropachy. Thyroid acropachy is an extreme manifestation of autoimmune thyroid disorder characterized by clubbing and swelling of fingers and toes, with or without periosteal reaction of the distal bones. We present a 50-year-old woman, posttreatment for carcinoma breast (6 years back) and referred for bone scan for generalized body ache. Bone scan findings resulting in detailed clinical evaluation prompted toward the suspicion of a thyroidal disease with ultimate diagnosis of Graves' disease.

E2F1 genetic variants and risk of cervical cancer in Indian women.

INTRODUCTION: Altered expression of many E2F family members have been reported in various human cancers. In this study, we investigated the role of non-synonymous single nucleotide polymorphisms (rs3213172 C/T, rs3213173 C/T, and rs3213176 G/A) of the gene E2F1 with cervical cancer. METHODS: A total of 181 samples including 90 cervical cancer patients and 91 healthy controls were genotyped. The genotype frequencies of these polymorphisms in collected samples were determined by either PCR-RFLP or PCR-ARFLP methods. SHEsis software was used to analyze the haplotypes. RESULTS: Statistically significant differences in the alleles and the genotypes frequencies were observed in rs3213172 (C/T) and rs3213173 (C/T) polymorphisms. The rs3213172 (C/T) polymorphism was a risk factor for cervical cancer in dominant model (odds ratio (OR) 1.96; 95% confidence interval (CI) 1.07, 3.60; P = 0.02) and heterozygous model (OR 1.90; 95% CI 1.01, 3.57; P = 0.04). The rs3213173 (C/T) polymorphism increased the risk of cervical cancer in the homozygous model (OR 2.71; 95% CI 1.11, 6.58; P = 0.02). The rs3213176 (G/A) polymorphism was not associated with cervical cancer risk in any of the genotypic models. In the haplotypes analysis, three haplotypes (CTG, TCG, and TTA) were associated with the cervical cancer risk. CONCLUSIONS: These findings revealed that rs3213172 (C/T) and rs3213173 (C/T) polymorphisms and haplotypes (CTG, TCG, and TTA) of the E2F1 gene might play role in the susceptibility of cervical cancer. This is the first report showing an association of these polymorphisms with the cervical cancer risk.

Incidental Detection of Synchronous Lung Melanoma on 18F-FDG PET/CT in a Patient With Parotid Gland Myoepithelial Carcinoma.

The detection of synchronous or metachronous malignancies is on the rise with the advent of whole-body F-FDG PET/CT. It has shown its utility in detecting second primary carcinoma in patients undergoing imaging for evaluation of primary carcinoma, influencing the management and overall survival. Primary malignant melanoma of the lung is an extremely rare entity, accounting for 0.01% of all lung tumors. It is an even rare occurrence as a synchronous malignancy. We present the case of a 33-year-old woman with primary parotid myoepithelial carcinoma and incidental detection of second primary malignant melanoma of lung during F-FDG PET/CT imaging.

Breast cancer risk factor evaluation in a Western Himalayan state: A case-control study and comparison with the Western World.

CONTEXT: Breast cancer incidence is increasing rapidly in India. The lifestyle, built, genetic makeup, reproductive and breastfeeding patterns are quite different in Indian females when compared to the Western population. Generalizing the Western data to the population residing in the Himalayan region would breed inaccuracies. AIM: The aim of our study was to identify risk factors in our own population in a Western Himalayan state of Himachal Pradesh, India. SUBJECTS AND METHODS: A case-control study with 377 cases of invasive breast cancer and 346 hospital-based controls was conducted for 1 year. The data were collected by interviewing the individuals during their visit to hospital using a questionnaire. The data were analyzed using standard statistical techniques using SPSS version 17 software. RESULTS: Factors found to have strong association with invasive breast cancer on multivariate analysis are late age at first childbirth >30 years, which is the strongest risk factor associated, late age of menopause > 50 years, high socioeconomic class, and age of female above 50 years. CONCLUSION: In our females, age >50 years, late age of menopause (>50 years), late age at first childbirth (>30 years), and high socioeconomic status were found to be major risk factors associated with breast cancer. Several factors implicated in the Western data were not found to be significant in our study. We need to identify such aspects in reproductive and breastfeeding patterns of women and spread awareness regarding the same.

Comparison of Effects of Hemoglobin Levels Upon Tumor Response among Cervical Carcinoma Patients Undergoing Accelerated Hyperfractionated Radiotherapy versus Cisplatin Chemoradiotherapy.

PURPOSE: Blood hemoglobin levels are known to influence response to radiotherapy. This retrospective analysis compared the effect of hemoglobin levels upon response to radiation among patients treated with radiation alone (by accelerated hyperfractionated radiotherapy) versus those treated with concurrent cisplatin chemoradiotherapy. MATERIALS AND METHODS: Among patients treated for locally advanced carcinoma of the cervix (LACC) during 2009-10, a total of 60 fulfilled the eligibility criteria. In this time frame, external beam radiotherapy was delivered with either concurrent chemoradiotherapy (CRT, n=31) (45 Gy over 25 fractions, with weekly cisplatin at 40 mg/m2), or with accelerated hyperfractionated radiotherapy (AHRT, n=29) (20 Gy over 10 daily fractions over the first two weeks, followed by 30 Gy over 20 fractions over the next two weeks, with two fractions of 1.5 Gy per day, without the use of chemotherapy). Mean weekly hemoglobin (MWH) levels of all patients were calculated as the arithmetic means of weekly recorded blood hemoglobin levels. As per MWH, patients in both of the AHRT or the CRT groups were classified into two subgroups- those with MWH between 10-10.9 g/dL, or with MWH>11 g/dL. Complete response (CR) to external beam RT phase (prior to brachytherapy) was declared after clinical examinations and computed tomography. The CR rate was noted for both MWH sub-groups within each of the AHRT and CRT groups. RESULTS: Within the AHRT group, patients with MWH>11 g/dL had a much better CR rate in comparison to those with MWH:10-10.9 g/dL (80% vs. 21.1%) which was statistically significant (p 0.0045). Within the CRT group, there was no significant difference in the outcomes within the MWH>11 g/dL and MWH:10-10.9 g/dL sub-groups ( CR rates of 80% vs. 61.9%, p=0.4285). CONCLUSIONS: The importance of maintaining a minimum hemoglobin level of 11 g/dL during RT is much greater for patients treated with RT alone, than for patients treated with concurrent chemoradiotherapy. Enhanced haemoglobin levels during RT may to an extent negate the ill-effects that may otherwise arise due to non-use of concurrent chemotherapy.

Uncertainty concerning the 4-field box technique for Stage-IB2 carcinoma of the uterine cervix.

Radiation Therapy (RT) plays a pivotal role in the curative approach for carcinoma of the cervix. Inspite of the emergence of various new conformal techniques in RT, conventional techniques still hold vital importance. Majority of the patients worldwide are treated with 2D-RT techniques. 2D-RT techniques have been proven to be non-inferior and simpler in comparison to 3D-RT in the context of carcinoma of the cervix. However, inadequate target volume coverage with improper portal design can preclude the chances of cure. We demonstrate the need for abolishing guesswork in terms of target volume determination through the example of a patient's sagittal magnetic resonance image showing a case of the retroverted uterus which would have been likely to be missed from the treatment portals if they were designed using definitions based on bony landmarks.

Extranodal lymphoma masquerading as carcinoma of the breast in an HIV-positive male patient.

This report describes a male patient infected with the HIV, with antiretroviral therapy (ART)-induced gynaecomastia. He presented with a right-sided breast mass which clinically resembled a carcinoma. A core biopsy suggested non-Hodgkin's lymphoma of diffuse large B cell histology. Also presented are his 18-fluoro-deoxy-glucose-positron emission tomography (FDG PET)-CT scan findings which showed a highly avid mass (standardised uptake value (SUV) 34.5) in his right breast. In spite of a very good clinical response after the first cycle of chemotherapy, his disease relapsed at multiple sites and progressed early. This case illustrates the aggressive course of HIV-associated extranodal lymphomas, and also highlights the issues concerning the use of ART and chemotherapy.

Bee-sting, a non-resolving wound and a progressive mass over the right eye preceding the ultimate diagnosis of frontal bone Ewing's sarcoma.

A healthy young lady suffered a bee-sting over her right eyelid which was followed by pain, redness and swelling at, above and beyond the right eyelid. Although the initial swelling subsided, the patient noticed a small 'lump', superior to the eyelid which persisted after the rest of the swelling disappeared. This lump subsequently progressed over a span of 3 months and then caused ulceration of the overlying skin. Further testing revealed the lump to be an Ewing's sarcoma arising from the frontal bone. The patient was treated with standard chemotherapy (16 cycles of vincristine, doxorubicin, cyclophosphamide alternating with cycles of ifosfamide and etoposide) and radiotherapy and has remained disease-free 18-months after completion of treatment. This report reminds the reader about a not-so-uncommon mode of presentation of malignancies, that is, they being discovered after attention drawn by a rather common injury or trauma.

Dermatomyositis and chest radiography leading to the diagnosis of lung cancer and subsequent confusions in staging due to the presence of tuberculosis.

This clinical scenario describes dermatomyositis as a presenting feature of carcinoma of the lung. However, the coincident existence of tuberculosis in the opposite lung gave rise to a false impression of contralateral lung metastasis and hence confusions with regard to staging ensued, which were clarified after further investigation confirmed a unilateral lung adenocarcinoma and contralateral tuberculosis. The patient was initiated on oral antiepidermal growth factor receptor therapy with erlotinib, as well as on multi-drug therapy for tuberculosis. This report intends to illustrate that paraneoplastic syndromes such as dermatomyositis can be the presenting feature of lung cancer, and also that the co-incident presence of carcinoma and tuberculosis can cause confusions with regard to staging and management.

Undue delay in the diagnosis of lung cancer due to the clinician's preoccupation with pre-existing tuberculosis.

The authors report the case of a seminomadic older patient who had already received a course of antitubercular treatment and within a few weeks of completion suffered resurgence of symptoms. His treating physician assumed it to be relapse of tuberculosis and hence re-started the patient on antitubercular treatment. Though the mass lesion on CT scan procured by the primary care physician suggested the possibility of a neoplasm, areas of necrosis within the mass led to a 'cavitary appearance', which unfortunately happens to be a feature of tuberculosis. Once the patient presented to the authors, they performed cytological investigations which established that the patient had lung cancer co-existing with tuberculosis, which indeed was the reason for his progressive symptoms in spite of antitubercular treatment.

Diffuse hepatic and splenic Tc-99m MDP tracer uptake in case of multiple myeloma.

Tc-99m methylene diphosphonate (MDP) bone scintigraphy has long been used for the evaluation of benign as well as malignant skeletal conditions. However, non-osseous tracer uptake on a bone scan is an unusual finding. There is a need to understand the pathophysiological basis of the non-osseous uptake, which may have a clinical relevance or deteriorating effect on the quality of the bone scan. We describe a case of multiple myeloma, where extraosseous uptake in the form of diffuse hepatic and splenic uptake, with almost normal skeletal tracer distribution, has been seen on the bone scan.