Chemotherapy in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma is a unique disease entity among head and neck cancers due to its epidemiology and clinical behavior. Non-keratinizing or undifferentiated carcinoma is the most common histological type in endemic areas. Radiotherapy is the treatment for early-stage disease. With the widespread use of IMRT, loco-regional control has improved significantly in locally advanced diseases. But distant metastasis continues to be the most common pattern of failure. To address this issue, chemotherapy has been incorporated into radiotherapy in various settings; as concurrent, induction, and adjuvant. The initial trials of concurrent chemotherapy incorporated adjuvant chemotherapy also and the magnitude of benefit contributed by each treatment was not clear. Later trials proved that adjuvant chemotherapy was not beneficial. Induction chemotherapy when added to concurrent chemoradiation resulted in improvement in Failure Free Survival, Overall Survival, and Distant Metastasis Free Survival. Thus, induction chemotherapy followed by concurrent chemoradiation became the standard of care for locally advanced disease (stage III and IVA). The role of chemotherapy in stage II disease is still evolving. Metastatic nasopharyngeal carcinoma is treated by platinum doublet chemotherapy, Cisplatin-gemcitabine is the standard regimen

Human Papillomavirus Associated Oropharyngeal Carcinoma-Diagnosis and Management

Head and neck squamous cell carcinomas arise from the mucosa of the upper aerodigestive tract and is often driven by risk factors like tobacco and alcohol consumption. Most of the time patients present with locally advanced stages and the outcome is poor, despite recent advances in multi-modality treatment. The epidemiology of the disease has changed over the last decade with the introduction of a separate clinical entity; Human Papillomavirus (HPV) associated head and neck cancer. The tumorigenesis is different from that of tobacco and alcohol-driven malignancies. These tumors have a better response to treatment owing to their inherent genetic makeup and carry an excellent prognosis. The current school of thought is to reduce the long-term morbidities associated with various treatment modalities, as these patients tend to survive longer. The best management of HPV-associated oropharyngeal cancer is under active investigation

Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium

Objective: To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. Design: Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. Setting: General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). Participants: 1 124 897 men and women (mean age 53.4 years at baseline). Main outcome measures: Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. Results: 49 184 cardiovascular deaths (40 791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and less than 15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). Conclusions: Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians

Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged ≥45 Years in Asia: A Pooled Analysis of 21 Cohorts

Background:Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest.Methods and Findings:We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan-accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37-1.51) and 1.48-fold (1.38-1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%-17.2%) and 3.3% (2.6%-4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000-1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: A 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y.Conclusions:Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented.Please see later in the article for the Editors' Summary. © 2014 Zheng et al

Long-term outcome of surgical excision of leukoplakia in a screening intervention trial, Kerala, India

Oral cancer is often preceeded by precancerous lesions and conditions, such as leukoplakia, erythroplakia and oral submucous fibrosis. One of the approaches for control of oral cancer is to detect oral precancerous lesions early in the development and prevent their malignant transformation to invasive cancer either by chemoprevention or by surgical excision of the lesions with concurrent control of tobacco and alcohol use and other specific etiological factors. However, the value of specific approaches, such as surgery in long-term control of lesions and prevention of malignant transformation is not known. We describe our experience with cold knife surgical excision of oral leukoplakia diagnosed in the context of a community-based oral cancer cluster randomized oral cancer screening trial in Kerala, jointly organized by the Regional Cancer Centre, Trivandrum and the International Agency for Research on Cancer of the WHO, Lyon. France. During the period from January 1997 to December 2002, 111 subjects underwent surgical excision- Thirteen patients were found to have malignancy on histopathology and were not considered for further analysis. At the last follow-up, 9 (13%) patients could not be traced and 19 (27%) patients died due to causes other than oral cancer. Of the remaining 70 cases, 48 (68-6%) were remaining disease free with no evidence of recurrence or new lesions, 16 (16.9%) developed new leukoplakic lesions, (one patient developed recurrence as well), three (4.2%) developed recurrence. Recurrence was more common among those who continued the habits, but this was not statistically significant. There were four (5 7%) cases of malignant transformation during the mean follow-up period of 8-1 years. The superiority of surgical excision over other modalities of management of leukoplakia could not be established in the present study

Role of Organ Preservation in Locally Advanced Hypopharyngeal Carcinoma

Hypopharyngeal carcinoma is relatively rare and has the worst prognosis of all head and neck cancers. Initially, surgery followed by postoperative radiation was the standard of care for locally advanced disease. In the recent years, various organ sparing approaches have evolved. There are mainly two schools of thought regarding larynx preservation in hypopharyngeal cancers which include either induction chemotherapy followed by response assessment for radical radiotherapy or concurrent chemoradiation. An ongoing trial is comparing the effectiveness between these two established approaches. The role of anti-EGFR therapy and immunotherapy is still being evaluated. Despite all the advancements in treatment, hypopharyngeal cancers are still associated with poor treatment outcomes

Setup uncertainties and PTV margins at different anatomical levels in intensity modulated radiotherapy for nasopharyngeal cancer

AimTo determine the systematic error (∑), random error (σ) and derive PTV margin at different levels of the target volumes in Nasopharyngeal Cancer (NPC).Materials and methodsA retrospective offline review was done for patients who underwent IMRT for NPC from June 2015 to May 2016 at our institution.Alternate day kV images were matched with digitally reconstructed radiographs to know the setup errors. All radiographs were matched at three levels – the clivus, third cervical (C3) and sixth cervical (C6) vertebra. The shifts in positions along the vertical, longitudinal and lateral axes were noted and the ∑ and σ at three levels were calculated. PTV margins were derived using van Herk's formula.ResultsTwenty patients and 300 pairs of orthogonal portal films were reviewed. The ∑ for the clivus, C3 and C6 along vertical, longitudinal and lateral directions were 1.6 vs. 1.8 vs. 2[[ce:hsp sp="0.25"/]]mm; 1.2 vs. 1.4 vs. 1.4[[ce:hsp sp="0.25"/]]mm and 0.9 vs. 1.6 and 2.3[[ce:hsp sp="0.25"/]]mm, respectively. Similarly, the random errors were 1.1 vs. 1.4 vs. 1.8[[ce:hsp sp="0.25"/]]mm; 1.1 vs. 1.2 vs. 1.2[[ce:hsp sp="0.25"/]]mm and 1.2 vs. 1.3 vs. 1.6[[ce:hsp sp="0.25"/]]mm. The PTV margin at the clivus was 4.4[[ce:hsp sp="0.25"/]]mm along the vertical, 4[[ce:hsp sp="0.25"/]]mm along the longitudinal direction and 3.2[[ce:hsp sp="0.25"/]]m in the lateral direction. At the C3 level, it was 5.5[[ce:hsp sp="0.25"/]]mm in the vertical, 5[[ce:hsp sp="0.25"/]]mm in the lateral direction and 4.4[[ce:hsp sp="0.25"/]]mm in the longitudinal direction. At the C6 level, it was 6.4[[ce:hsp sp="0.25"/]]mm in the vertical, 6.9[[ce:hsp sp="0.25"/]]mm in the lateral direction and 4.4[[ce:hsp sp="0.25"/]]mm in the longitudinal direction.ConclusionA differential margin along different levels of target may be necessary to adequately cover the target