Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab

Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers     

Evaluating the Cost-Effectiveness of Hydrogel Rectal Spacer in Prostate Cancer Radiation Therapy

Purpose

A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT).

Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease

Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

Evaluation of polymerase chain reaction and adenosine deaminase assay for the diagnosis of tuberculous effusions in children.

AIM: To evaluate and compare the utility of polymerase chain reaction (PCR) for the diagnosis of tuberculous effusions in children. METHODS: PCR, adenosine deaminase (ADA) activity and absolute lymphocyte count (ALC) were evaluated in the fluid of 31 tuberculous (20 pleural, 8 ascites and 3 pericardial) and 24 non-tuberculous (10 transudtative ascites, 8 empyema thoracis, 3 malignant pleural and 3 pyopericardium) effusions. RESULTS: Fluid PCR for Mycobacterium tuberculosis was positive in 74% of tuberculous effusions, whereas it was falsely positive in 13% of the non-tuberculous group. The mean fluid ADA and ALC values were significantly higher in tuberculous effusions than in non-tuberculous effusions (p<0.001). The sensitivity and specificity of PCR, ADA (> or =38 IU/l) and ALC (> or =275/mm3) were 74% and 88%, 81% and 75%, and 90% and 83%, respectively, in diagnosing tuberculous effusions. The sensitivity of PCR, ADA and ALC was 100%, 100% and 88%, respectively, for confirmed tuberculous effusions. When the two tests were combined (either/or positive), the sensitivity increased (90-100%) at the expense of specificity. When both the tests were positive, then the specificity markedly increased (92-96%), but sensitivity of the tests decreased. CONCLUSION: Fluid PCR alone should not be relied on as a single test; rather, combined analysis with either ADA or ALC could be more useful in the diagnosis of tuberculous effusions in children.     

Implantation of parathyroid carcinoma along fine needle aspiration track

Introduction Fine needle aspiration cytology is not a commonly employed diagnostic modality in the diagnosis of parathyroid tumors.Case report A 28 year old lady being followed-up for 5 years after en bloc resection of a parathyroid carcinoma presented with a nodule in the lower neck, away from the parathyroidectomy scar. The 1 cm isolated nodule was located in the muscular and subcutaneous plane and corresponded to the needle track of FNA performed on a neck nodule before the parathyroidectomy. On evaluation, she had mild hypercalcemia and high normal serum parathyroid hormone levels. FNAC and histology including immunohistochemistry for Chromogranin A after local excision of the nodule confirmed the nodule to be a recurrent parathyroid carcinoma along the needle track.Discussion To the best of the authors’ knowledge, this is only the second case of needle track implantation after FNA in parathyroid carcinoma reported to date. This case highlights the risk of engraftment of parathyroid tissue after FNA and cautions against the use of FNA as a preoperative diagnostic modality for the evaluation of parathyroid lesions.Drs. Agarwal and Dhingra have contributed equally, as joint first authors.     

Total thyroidectomy for differentiated thyroid cancer: primary compared with completion thyroidectomy.

OBJECTIVE: To analyse morbidity after completion total thyroidectomy compared with primary total thyroidectomy in a specialist thyroid surgery centre. DESIGN: Retrospective study. SETTING: Tertiary referral hospital, India. PATIENTS: Medical records of 143 patients who had total thyroidectomy between January 1990 and December 1999. 95 had primary thyroidectomies and 48 were completion thyroidectomies. MAIN OUTCOME MEASURES: Complication rate in both groups. RESULTS: The groups were comparable in respect of clinicopathological variables. Residual tumour was found in 19/48 (40%). After completion thyroidectomy, transient hypoparathyroidism and transient recurrent laryngeal nerve palsy were recorded in 8/48 (17%) and 2/48 (4%), respectively. No permanent hypoparathyroidism or permanent recurrent laryngeal nerve palsy was recorded in the completion thyroidectomy group. CONCLUSIONS: Completion thyroidectomy can be done with acceptable morbidity in a specialist thyroid surgery centre. Fear of increased morbidity after the procedure should not deter surgeon from doing this operation or referring the patients to a specialist centre.