Clinical Significance of Circulating Serum Levels of sCD95 and TNF-α in Cytoprotection of Cervical Cancer.

Background: This study correlates the serum levels of sCD95 & TNF-α with a simple cell-based assay to evaluate the capacity of the serum sample to induce apoptosis in Jurkat cells. Interlinking of these parameters can be explored to design a minimum invasive diagnostic strategy for cervical cancer (CC). Methods: Sera samples were assessed to induce apoptosis in Jurkat cells through FACS. Serum levels of sCD95 and TNF-α were measured by ELISA. JNK phosphorylation was evaluated in sera incubated Jurkat cells. Data was scrutinized through statistical analysis. Results: Significantly higher serum levels of sCD95 and lower TNF-α levels were observed in CC patients; their sera samples inhibited induction of apoptosis in Jurkat cells through reduced JNK phosphorylation. Statistical analysis linked these three parameters for the early screening of CC. Conclusion: Distinct sera levels of sCD95 & TNF-α in CC patients showed an anti-apoptotic effect, which can be considered for early detection of CC.

Aspirin & clopidogrel non-responsiveness & its association with genetic polymorphisms in patients with myocardial infarction.

Background & objectives: Cytochrome P450, P2Y 12, cyclooxygenase-1 (COX1) and glycoprotein V1 (GPVI) gene polymorphisms are known to affect patient responsiveness towards aspirin and clopidogrel dual antiplatelet therapy (DAPT). The present study was undertaken to identify aspirin and clopidogrel non-responsiveness and its association with genetic polymorphism in patients with myocardial infarction (MI). Methods: A total of 207 MI patients who were on DAPT, were included. The DAPT non-responsiveness was determined by light transmittance aggregometry using arachidonic acid and adenosine diphosphate and high platelet reactivity by collagen. Platelet activation biomarkers, thromboxane B2 (TxB2)andsoluble CD40 ligand (sCD40L) were measured in plasma. Patient compliance was checked by estimating drug and its metabolite levels (aspirin and clopidogrel) in plasma using liquid chromatography-mass spectrometry/mass spectrometry. Genomic DNA was extracted, amplified by polymerase chain reaction and subsequently sequenced to identify CYP450, P2Y 12, COX1 and GPVI gene polymorphisms. Results: Of the 207 patients, 32 were non-responders. The DAPT non-responsiveness was found in 15.5 per cent patients. The non-responsiveness showed a significant and an independent association with gender [odds ratio (OR)=0.18, 95% confidence interval (CI)=0.01-0.78, P=0.023], TxB2(OR=1.00, 95% CI=1.00-1.01, P=0.013), CYP2C19*2 G>A (OR=3.33, 95% CI=1.04-10.69, P=0.044) and GPVI T>C (OR=0.23, 95% CI=0.08-0.67, P=0.007) after adjusting the demographic, clinical and genetic confounding factors when assessed between non-responder and responder compliant patients. Interpretation & conclusions: The study showed a significant association of genetic polymorphisms (CYP2C19*2 G>A and GPVI T>C) with DAPT non-responsiveness in MI patients. The findings of this study need further validation in a large cohort of patients with clinical follow up.

Decline in seminal quality in Indian men over the last 37 years.

BACKGROUND: Since the first report of a decline in semen quality in 1974, there have been several reports of similar declines across populations. Despite some scattered reports of declining semen quality in the Indian sub-continent, comprehensive studies analyzing semen quality over the last few decades have not been undertaken. We undertook the present study to investigate the temporal trend in semen parameters in Indian populations over a period of 37 years (1979-2016). METHODS: Publications providing semen analysis details for fertile and infertile men from the Indian sub-continent were collected by a thorough literature search. Semen quality data for 6466 normal fertile or presumptive normal men (from 119 studies/data sets) and 7020 infertile men (from 63 studies/data sets) published between 1979 and 2016 were retrieved. We undertook systematic review and quantitative analysis of mean sperm count, motility, normal morphology and other available parameters. Data were analyzed to estimate semen parameters reference values for Indian men and to assess temporal trends in infertile, fertile and all subjects. RESULTS: Seminal quality shows a decreasing temporal trend and the decrease is higher in infertile than fertile males. In pooled analysis for all individuals, significant (p < 0.05 or < 0.001) declines in sperm concentration and normal morphology are observed; however, isolated analysis for each group shows declines without statistical significance. The mean (± SD) semen volume, sperm concentration, total motility, rapid linear progressive motility, normal sperm morphology and sperm viability for Indian fertile men are 2.88 ± 0.77 ml, 81.08 ± 29.21 million/ml, 66.37 ± 10.95%, 52.64 ± 15.78%, 56.68 ± 20.23% and 72.63 ± 8.31%, respectively, whereas in infertile these are 3.07 ± 1.27 ml, 37.94 ± 26.41 million/ml, 40.22 ± 13.76%, 26.79 ± 15.47%, 36.41 ± 21.66% and 55.25 ± 11.99%, respectively. The mean seminal parameter values were significantly lower (p < 0.001) in infertile as compared to fertile men, except semen volume. CONCLUSIONS: Semen parameters in Indian men have declined with time and the deterioration is quantitatively higher in the infertile group. The study also provides reference values for semen parameters in Indian men.

Oncostatin M upregulates HIF-1α in breast tumor associated macrophages independent of intracellular oxygen concentration.

AIMS: HIF is an important transcription-regulator for adaptation to cellular stress in cells of myeloid origin. Classically, expression and activity of HIF1-α is regulated by oxygen-concentration within cell. However, there exists an alternative regulatory mechanism affecting HIF1-α levels independent of oxygen concentration particularly in inflammatory cells like macrophages. Here we report the mechanism of HIF1-α upregulation in TAMs by Oncostatin-M (OSM) independent of cellular oxygen concentration. MAIN METHODS: THP-1 derived macrophages were treated with OSM. HIF1-α levels and interaction with pVHL were evaluated via immunoblot-analysis and Co-immunoprecipitation. Translocation of HIF1-α to nucleus was visualized using confocal-microscopy. Fold change in mRNA levels of ARG-1 and COX-2 was analyzed using RT-PCR. KEY FINDINGS: Current study demonstrates that OSM treatment to TAMs led to an increased expression of HIF1-α under normoxic conditions via activation of mTORC2. This HIF1-α upregulation was dependent on both de novo synthesis of HIF1-α and its enhanced stability due to disruption of its binding to pVHL. Furthermore, we evaluated that OSM not only enhances the expression of HIF1-α but also increases its localization to nucleus where it acts as a transcription factor regulating expression of genes like ARG-1 and COX-2. SIGNIFICANCE: Inflammation is a critical hallmark of cancer as tumor microenvironment is largely infiltrated with macrophages. These tumor associated macrophages (TAMs) display a M2 skewed phenotype. Many target genes of TAMs are HIF1-α responsive. These TAMs are involved in tumor progression, metastasis and angiogenesis. Targeting of HIF1-α/OSM can lead to devising of better therapeutic strategy against cancer.

Understanding molecular markers in recurrent oral squamous cell carcinoma treated with chemoradiation.

INTRODUCTION: Oral cancer accounts for approximately 2.1% of all cancers worldwide. In India, oral squamous cell carcinoma (OSCC) is the most common cancer with half a million new cases diagnosed every year. More than 50% of patients eventually develop local recurrence or metastasis usually within the first 2-years following completion of treatment. It is beneficial to analyze the prognostic significance of Cyclin D1, p53 and EGFR which are critical mediators in the pathogenesis of OSCC. The objective of this study was to assess the association of expression of these markers with recurrence and pattern of recurrence in OSCC patients undergoing chemoradiation. MATERIALS AND METHODS: A Total 290 OSCC cases of locally advanced stage (III, IV) oral cancer with World Health Organization (W.H.O.) performance status of grade 0/1 in the year 2009-2012 were enrolled in the study. Treatment response was assessed according to W.H.O. criteria. Cyclin D1, EGFR and p53 expression in tumor tissue was estimated by immunohistochemical (IHC) method and quantified as percentage positive nuclei. RESULTS: During the 2-years follow up, 56 (19.3%) patients recurred, out of which, 47 (83.9%) were locoregional and 9 (16.1%) distant sites. On correlating, χ2 test showed significant (P < 0.05 or P < 0.01 or P < 0.001) association of marker expressions (Cyclin D1, EGFR and p53) with recurrence. The strong positive expressions of all three markers showed significant association with early time of recurrence. The multivariate logistic regression analysis showed significant (P < 0.05 or P < 0.01 or P < 0.001) association of recurrence with primary site, differentiation, Cyclin D1 and p53 expressions indicating these as an independent predictors of recurrence in OSCC. The Cyclin D1, EGFR and p53 expressions also showed significant (P < 0.001) poor survivals (OS, DFS and RFS) in patients with positive/strong positive expressions than negative expression suggesting their prognosis in OSCC. CONCLUSION: Our results signifies that tumors over expressing Cyclin D1, EGFR and p53 are resistant to chemoradiation and are associated with increased risk of locoregional recurrence and metastasis in OSCC patients undergoing chemoradiation.

Macrophages promote matrix protrusive and invasive function of breast cancer cells via MIP-1ß dependent upregulation of MYO3A gene in breast cancer cells.

The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or "niche" interactions with local components. Tumor-associated-macrophages (TAMs) are the most abundant subpopulation of tumor stroma and represent a key component of tumor microenvironment. The dynamic interaction of cancer cells with neighboring TAMs actively drive cancer progression and metastatic transformation through intercellular signaling networks that need better elucidation. Thus, current study was planned for discerning paracrine communication networks operational between TAMs, and breast cancer cells with special reference to cancer cell invasion and dissemination to distant sites. Here, we report role of MIP-1ß in enhancing invasive potential of metastatic breast cancer MDA-MB-231 and MDA-MB-468 cells. In addition, the poorly metastatic MCF-7 cells were also rendered invasive by MIP-1ß. The MIP-1ß-driven cancer cell invasion was dependent on upregulated expression levels of MYO3A gene, which encodes an unconventional myosin super-family protein harboring a kinase domain. Ex ovo study employing Chick-embryo-model and in vivo Syngenic 4T1/BALB/c mice-model further corroborated aforementioned in vitro findings, thereby substantiating their physiological relevance. Concordantly, human breast cancer specimen exhibited significant association between mRNA expression levels of MIP-1ß and MYO3A. Both, MIP-1ß and MYO3A exhibited positive correlation with MMP9, an established molecular determinant of cancer cell invasion. Higher expression of these genes correlated with poor survival of breast cancer patients. Collectively, these results point toward so far undisclosed MIP-1ß/MYO3A axis being operational during metastasis, wherein macrophage-derived MIP-1ß potentiated cancer cell invasion and metastasis via up regulation of MYO3A gene within cancer cells. Our study exposes opportunities for devising potential anti-metastatic strategies for efficient clinical management of breast cancer.

IL-6 gene expression in adipose tissue of postmenopausal women and its association with metabolic risk factors.

Adipose tissue secretes various kinds of adipokines that controls the glucose and lipid metabolism in humans. The abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) both are associated with metabolic syndrome and insulin resistance. IL-6 is one of the adipokines, which promotes insulin resistance and dyslipidemia in humans. The association of adipokines with metabolic syndrome at protein levels are well documented. However, their association at gene expression level are lacking. The present study was design to investigate IL-6 mRNA expression in adipose tissues (VAT and SAT) and its correlation with metabolic risk factors and insulin resistance (HOMA) in post menopausal women. A total of 108 Asian North Indian post menopausal women, 54 without metabolic syndrome (controls) and 54 with metabolic syndrome (cases) were recruited and evaluated. Overnight fasting blood samples were collected at admission and abdominal visceral and subcutaneous adipose tissues were collected during open abdomen surgery. The results showed significantly (p < 0.05 or p < 0.01 or p < 0.001) higher mean SBP, glucose, insulin, HOMA, TG, VLDL and serum IL-6 while significantly (p < 0.001) lower HDL and estrogen in cases as compared to controls. In cases, the relative mean SAT IL-6 expression was also significantly (p < 0.05) higher as compared to VAT. Further, in cases, the VAT IL-6 expression showed significant (p < 0.05 or p < 0.001) and negative correlation with WC, WHR, glucose, HOMA, TC, LDL and estrogen while SAT IL-6 expression also showed significant (p < 0.05 or p < 0.01 or p < 0.001) and negative correlation with WC, WHR and estrogen. The Cox regression analysis found VAT IL-6 mRNA expression the significant (p < 0.05 or p < 0.01) an independent predictor of WC, HOMA, TC, LDL and estrogen while SAT IL-6 mRNA expression the significant (p < 0.01) an independent predictor of TG and VLDL. The study concluded that IL-6 expressions of both visceral and subcutaneous tissues may be associated with metabolic risk factors in postmenopausal Asian North Indian women.

Calcitonin gene- and parathyroid hormone-related peptides in normotensive and preeclamptic pregnancies: a nested case-control study.

PURPOSE: To identify whether CGRP and PTHrP serve as screening biomarkers for early detection of preeclampsia or even before the development of preeclampsia in early pregnancy. METHODS: It was a nested case-control study. The subjects were divided into normotensive (controls) and preeclamptic (cases) groups. Serum samples of 132 cases and 132 controls were collected during pregnancy at three different gestational periods and one sample post delivery, from within the cohort of pregnant women reporting to antenatal clinic. Circulating levels of CGRP and PTHrP were analyzed by enzyme-linked immunosorbent assay. RESULTS: Maternal serum concentrations of CGRP and PTHrP increased with the advancement of gestation age in both normotensive and preeclamptic pregnancies but the significantly less increased levels were observed in preeclamptic pregnancies as compared with normotensive pregnancies. In postpartum period level of CGRP significantly falls in both groups although level of PTHrP continues to increase even after delivery. Maternal serum CGRP and PTHrP concentrations were positively correlated with the infant's birth weights. CONCLUSION: Maternal circulating CGRP and PTHrP concentrations were significantly lower in women with preeclampsia, which may contribute to the development of preeclampsia.

Androgen receptor CAG repeats length polymorphism and the risk of polycystic ovarian syndrome (PCOS).

OBJECTIVE: Polycystic ovarian syndrome (PCOS) refers to an inheritable androgen excess disorder characterized by multiple small follicles located at the ovarian periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen receptor (AR) CAG numbers and AR function, led us to hypothesize that CAG length variations may affect PCOS risk. METHODS: CAG repeat region of 169 patients recruited following strictly defined Rotterdam (2003) inclusion criteria and that of 175 ethnically similar control samples, were analyzed. We also conducted a meta-analysis on the data taken from published studies, to generate a pooled estimate on 2194 cases and 2242 controls. RESULTS: CAG bi-allelic mean length was between 8.5 and 24.5 (mean = 17.43, SD = 2.43) repeats in the controls and between 11 and 24 (mean = 17.39, SD = 2.29) repeats in the cases, without any significant difference between the two groups. Further, comparison of bi-allelic mean and its frequency distribution in three categories (short, moderate and long alleles) did not show any significant difference between controls and various case subgroups. Frequency distribution of bi-allelic mean in two categories (extreme and moderate alleles) showed over-representation of extreme sized alleles in the cases with marginally significant value (50.3% vs. 61.5%, χ(2) = 4.41; P = 0.036), which turned insignificant upon applying Bonferroni correction for multiple comparisons. X-chromosome inactivation analysis showed no significant difference in the inactivation pattern of CAG alleles or in the comparison of weighed bi-allelic mean between cases and controls. Meta-analysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases. CONCLUSION: CAG bi-allelic mean length did not differ between controls and cases/case sub-groups nor did the allele distribution. Over-representation of short/extreme-sized alleles in the cases may be a chance finding without any true association with PCOS risk.

Strong impact of TGF-ß1 gene polymorphisms on breast cancer risk in Indian women: a case-control and population-based study.

INTRODUCTION: TGF-ß1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGF-ß1 signaling in breast cancer progression is well documented. Some TGF-ß1 polymorphisms influence its expression; however, their impact on breast cancer risk is not clear. METHODS: We analyzed 1222 samples in a candidate gene-based genetic association study on two distantly located and ethnically divergent case-control groups of Indian women, followed by a population-based genetic epidemiology study analyzing these polymorphisms in other Indian populations. The c.29C>T (Pro10Leu, rs1982073 or rs1800470) and c.74G>C (Arg25Pro, rs1800471) polymorphisms in the TGF-ß1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-ß1 were measured by ELISA. RESULTS: c.29C>T substitution increased breast cancer risk, irrespective of ethnicity and menopausal status. On the other hand, c.74G>C substitution reduced breast cancer risk significantly in the north Indian group (p = 0.0005) and only in the pre-menopausal women. The protective effect of c.74G>C polymorphism may be ethnicity-specific, as no association was seen in south Indian group. The polymorphic status of c.29C>T was comparable among Indo-Europeans, Dravidians, and Tibeto-Burmans. Interestingly, we found that Tibeto-Burmans lack polymorphism at c.74G>C locus as true for the Chinese populations. However, the Brahmins of Nepal (Indo-Europeans) showed polymorphism in 2.08% of alleles. Mean TGF-ß1 was significantly elevated in patients in comparison to controls (p<0.001). CONCLUSION: c.29C>T and c.74G>C polymorphisms in the TGF-ß1 gene significantly affect breast cancer risk, which correlates with elevated TGF-ß1 level in the patients. The c.29C>T locus is polymorphic across ethnically different populations, but c.74G>C locus is monomorphic in Tibeto-Burmans and polymorphic in other Indian populations.

Resistin gene expression in visceral adipose tissue of postmenopausal women and its association with insulin resistance.

AIM: The present study evaluates resistin mRNA expression in visceral adipose tissue (VAT) and its correlation with insulin resistance (homeostatic model assessment) in postmenopausal obese women. MATERIALS & METHODS: A total of 68 (nonobese = 34 and obese = 34) age-matched (49-70 years) postmenopausal women were recruited for the study. Fasting blood samples were collected at admission and abdominal VAT were obtained during surgery for gall bladder stones or hysterectomy. Physical parameters (age, height, weight and BMI) were measured. Biochemical parameters (plasma insulin, plasma glucose and serum resistin) were estimated by enzymatic methods. The VAT resistin mRNA expression was evaluated by real-time PCR. RESULTS: The relative mean (± standard deviation) VAT resistin mRNA expression in postmenopausal obese women lowered significantly by 20.4% compared with postmenopausal nonobese women (0.029 ± 0.011 vs 0.023 ± 0.013; p = 0.047). Furthermore, VAT resistin mRNA expression in postmenopausal obese women was downregulated by 0.69-fold when compared with age-matched postmenopausal nonobese women. Furthermore, the relative VAT resistin mRNA expression in postmenopausal obese women showed significant inverse association with insulin resistance (r = -0.48; p < 0.01) and serum resistin (r = -0.84; p < 0.001), while in postmenopausal nonobese women it did not show any association with both insulin resistance (r = 0.03; p > 0.05) and serum resistin (r = -0.03; p > 0.05). CONCLUSION: The VAT resistin mRNA expression in postmenopausal obese women is associated to insulin resistance.

Oral iron supplementation leads to oxidative imbalance in anemic women: a prospective study.

BACKGROUND & AIMS: This study was aimed to assess the desirable and undesirable effects of iron (100 mg/day as ferrous sulphate) and folic acid (500 µg/day) supplementation in iron deficient anemic women. METHODS: Iron and folic acid supplementations were given to 117 anemic women (mild = 55, moderate = 40, and severe = 22) and 60 age matched placebo treated (100 mg cane sugar) non-anemic controls for 100 days. Blood index values, oxidative stress parameters, antioxidant enzymes and vitamins were estimated as per standard protocols. RESULTS: Haemoglobin (Hb) levels along with antioxidant enzymes, namely catalase, superoxide dismutase (SOD), glutathione reductase (GSH-Rd), reduced glutathione (GSH) and total antioxidant capacity (TAC) were found significantly increased (P < 0.01) in anemic women after treatment. However, the glutathione peroxidase (GSH-Px) and antioxidant vitamins A, C and E were found significantly decreased (P < 0.01) in all treated groups. Lipid peroxide levels (LPO), protein carbonyl (PC), conjugated dienes (CD), lipid hydroperoxide (LOOH) and oxidized glutathione (GSSG) levels were found significantly increased (P < 0.01) after oral iron supplementation groups. Moreover, undesirable side effects of iron supplementation were observed maximally in mild as compared with moderate and severe anemic groups, whereas nausea, vomiting, systemic reactions were negligible in all treated subjects. CONCLUSION: Study found recommended dose of iron effective for improving Hb, but at the cost of increased oxidative stress (mild > moderate > severe). It is suggested that blind iron supplementation should be avoided and shall be provided on need basis.

Circadian variation in radiation-induced intestinal mucositis in patients with cervical carcinoma.

BACKGROUND: Mucositis, a radiotherapy-associated toxicity, is an important factor determining morbidity and treatment compliance. Gastrointestinal mucositis in patients undergoing radiotherapy may also depend on time of administration of radiation in addition to several other factors. The presence of any correlation between the severity of acute gastrointestinal mucositis in cervical carcinoma patients and the time of irradiation was prospectively evaluated. METHODS: A total of 229 patients with cervical carcinoma were randomized to morning (8:00-10:00 AM) and evening (6:00-8:00 PM) arms. The incidence of mucositis in the 2 arms was assessed and reported in terms of various grades of diarrhea. RESULTS: Overall (grade I-IV) as well as higher grade (III and IV) diarrhea was found to be significantly increased in the morning arm as compared with the evening arm (overall: 87.39 % vs 68.18 %, P < .01; higher grade: 14.29% vs 5.45%, P < .05). Other radiation-induced toxicity was also higher in the morning arm, but its occurrence in the 2 arms did not differ significantly (13.45% vs 12.73%, P > .05). After completion of treatment, patients' response to radiation in the 2 arms was similar (P > .05). CONCLUSIONS: The significant difference in the incidence of higher grade diarrhea between the morning and evening arms is indirect evidence of the influence of circadian rhythm on the intestinal mucosa of the human intestine. This knowledge may facilitate treating patients with decreased toxicity to the intestinal mucosa.

A prospective comparision of sequential chemoradiation vs concurrent chemoradiation in locally advanced oropharyngeal carcinomas.

PURPOSE: Induction chemotherapy has shown to provide consistent benefit for local control in primary treatment of advanced oropharyngeal cancer. The beneficial role of chemoradiation following induction chemotherapy over concurrent chemoradiation has not been evaluated. Present study evaluates the same prospectively. RESULTS: The response rate and acute toxicity (primary end points) in both the arms were found to be similar (p > 0.05) The points disease free survival and overall survival (secondary end points) were significantly (p < 0.05) better in treatment arm as compared to control arm. METHOD: Out of 135 patients of locally advanced oropharyngeal carcinoma, 105 patients were found eligible and randomized to treat either with induction chemotherapy consisting of 2-3 cycles of cisplatin and 5-Florouracil followed by low dose weekly cisplatin based chemoradiotherapy (treatment arm: n = 48) or chemoradiotherapy only (control arm: n = 57). The primary tumor and regional lymph drainage areas received 66-70 Gy in 6.5 to 7 weeks by fractionated dose schedule. CONCLUSION: Patients receiving chemoradiation following induction chemotherapy showed better response rates both in terms of complete response and disease free survival at two years than those receiving only concurrent chemoradiation but at the cost of manageable increase in toxicity.

Metastatic squamous cell carcinoma neck with occult primary: A retrospective analysis.

INTRODUCTION: Metastatic carcinoma in the lymph nodes of the neck from an unknown primary is relatively rare, accounting for about 3% of all head and neck cancers. Management of secondary neck of undetermined primary is controversial. MATERIALS AND METHODS: The case records of all the patients treated in the Department of Radiotherapy, Chatrapati Shahuji Maharaj Medical University, from Oct 1999 to Sep 2004, were studied and the patients with secondary neck without a known primary tumor were analyzed in detail to elucidate the outcome of various treatment modalities in various stages of the disease. One hundred and forty patients were found to be eligible for this analysis. Initial treatment could be divided into two categories: concurrent chemoradiation (n=76) and radiotherapy alone (n=64). RESULTS: The patients who had received radiotherapy alone (53.1%) had lesser complete response as compared to those who had received chemoradiotherapy (68.4%). The overall survival duration in patients of the radiotherapy treatment group ranged from 5 to 60 months, with an average (±SD) of 31.06 ± 21.01 months, while in the chemoradiotherapy treatment group it ranged from 6 to 60 months, with an average (±SD) of 39.42 ± 21.33 months. Both hematological and nonhematological toxicities, although higher in the chemoradiotherapy group, showed statistically insignificant differences. CONCLUSION: To the best of our knowledge, this is the only study evaluating the role of concurrent chemoradiation in cases of secondary neck with primary unknown. The improved response rates along with an increased survival (both disease free and overall) show the superiority of chemoradiotherapy in the management of such cases.