Suman Bhasker

Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial

BACKGROUND Several large randomised studies from western Europe and the USA have shown that accelerated fractionation of radiotherapy might be beneficial in the treatment of squamous-cell carcinoma of the head and neck (HNSCC). The aim of this study--the International Atomic Energy Agency (IAEA) ACC trial--was to determine whether accelerated fractionation could be applied in developing countries, where there are fewer therapeutic resources and where tumour burdens can be heavier. METHODS Between Jan 6, 1999, to March 31, 2004, nine centres from Asia, Europe, the Middle East, Africa, and South America recruited patients with HNSCC of the larynx, pharynx, and oral cavity who were eligible for curative radiotherapy. Patients were randomly assigned in this open-label trial to receive an accelerated regimen of six fractions of radiotherapy per week (n=458) or to receive a conventional radiotherapy regimen of five fractions per week (n=450), receiving a total dose of 66-70 Gy in 33-35 fractions. Patients were stratified by tumour localisation, T classification, histopathological grade, and institution. Randomisation was done by a central computer-generated balanced randomisation algorithm. The primary endpoint was locoregional control, analysed for all eligible patients, irrespective of whether or not they had completed the course of radiotherapy. This trial is registered with ClinicalTrials.gov, number NCT00120211. FINDINGS Six patients in the accelerated group and two in the conventional group were excluded from analyses because of withdrawal of consent or missing data. The planned total radiotherapy dose was received by 418 (92%) of the 452 eligible patients in the accelerated radiotherapy group and 413 (92%) of the 448 patients in the conventional radiotherapy group. Median treatment time was 40 days in the accelerated group and 47 days in the conventional group. The 5-year actuarial rate of locoregional control was 42% in the accelerated group versus 30% in the conventional group (hazard ratio [HR] 0.63, 95% CI 0.49-0.83; p=0.004). Acute morbidity in the form of confluent mucositis was noted in 45 patients in the accelerated group and 22 patients in the conventional group (2.15, 1.27-3.35); severe skin reactions were noted in 87 patients in the accelerated group and 50 patients in the conventional group (1.91, 1.31-2.79). There were no significant differences in late radiation side-effects. INTERPRETATION An accelerated schedule of radiotherapy for HNSCC was more effective than conventional fractionation, and since it does not require additional resources, might be a suitable new worldwide standard baseline treatment for radiotherapy of HNSCC. FUNDING International Atomic Energy Agency, Coordinated Research Project (IAEA-CRP E.3.30.18), the Danish Cancer Society, the Danish Strategic Research Council, and the Lundbeck Centre for Interventional Research in Radiation Oncology (CIRRO).

Outcome of surgery and post-operative radiotherapy for major salivary gland carcinoma: ten year experience from a single institute.

AIMS To determine the clinical characteristics, pathological features, local and distant failure patterns in patients with carcinoma of major salivary glands treated with surgery and postoperative radiotherapy (PORT). MATERIALS AND METHODS We retrospectively reviewed 106 cases of major salivary gland tumor seen at our centre (1998-2008). Sixty five cases of major salivary gland carcinoma were selected for analysis (exclusions: benign, palliative, non-carcinomas). The patient population treated by surgery and PORT was divided into two groups: 1) Patients who underwent surgery and immediate PORT (Primary PORT); 2) Patients with recurrent carcinoma who underwent at least two surgeries and received PORT in the immediate post-operative period of the last performed surgery (Recurrent PORT). Recurrence free survival (RFS) was assessed using the Kaplan-Meier method. RESULTS Median age was 35 years with a male: female ratio of 1.3:1. The majority of cancers were located in the parotid gland (86.2%) and the most common histology was mucoepidermoid carcinoma (43%). Thirty nine cases (60%) were primary while 26 (40%) were recurrent. Optimal surgery was performed in 59/65 patients (90.8%). 43 patients (66.2%) underwent neck dissection, of which 14 (32.5%) had nodal metastasis. Overall, 61 (93.8%) patients complied with the prescribed radiotherapy. Median dose of PORT was 60 Gy. Median follow-up was 13.1 months (range 2-70). Relapse free survival was 50.4% at 60 months. Some 12 cases (18.5%) recurred with a median time to recurrence of 16.9 months. CONCLUSIONS Surgery and PORT is an effective treatment for major salivary gland carcinoma with over 90% compliance and <20% recurrence. Early treatment with postoperative radiotherapy may increase the survival rate in major salivary gland carcinoma patients.

Aspiration pneumonia related deaths in head and neck cancer patients: a retrospective analysis of risk factors from a tertiary care centre in North India.

BACKGROUND Aspiration pneumonia is an important cause of death in head and neck cancer patients. This study therefore aimed to evaluate the risk factors associated with aspiration pneumonia in head and neck cancer patients. METHODS Hospital death records from 12 years (2000-2012) were reviewed to obtain the number of deaths. Treatment details and cause of death were analysed. Statistical analysis was performed to identify the risk factors for aspiration pneumonia. RESULTS The records revealed that aspiration pneumonia was the cause of death in 51 out of 85 patients. Primary tumour site (oropharynx and hypopharynx, odds ratio 3.3; 95 per cent confidence interval 1.17-9.4, p = 0.02) and advanced tumour stage (odds ratio 4.2, 95 per cent confidence interval 1.16-15.61, p = 0.02) had significant negative impacts on aspiration pneumonia related mortality. CONCLUSION Advanced pharyngeal cancer patients are at an increased risk of aspiration pneumonia related death. Investigations for the early detection of this condition are recommended in these high-risk patients.

Re-irradiation in head and neck cancers: an Indian tertiary cancer centre experience.

OBJECTIVE To explore the treatment outcomes of patients treated with re-irradiation for recurrent or second primary head and neck cancer. METHOD An analysis was performed of 79 head and neck cancer patients who underwent re-irradiation for second primaries or recurrent disease from January 1999 to December 2011. RESULTS Median time from previous radiation to re-irradiation for second primary or recurrence was 53.6 months (range, 2.7-454.7 months). Median age at diagnosis of first primary was 54 years. Median re-irradiation dose was 45 Gy (range, 45-60 Gy). Acute grade 3 or worse toxicity was seen in 30 per cent of patients. Median progression-free survival for recurrent disease was 15.0 months (95 per cent confidence interval, 8.33-21.66). The following factors had a statistically significant, positive impact on progression-free survival: patient age of less than 50 years (median progression-free survival was 29.43, vs 13.9 months for those aged 50 years or older; p = 0.004) and disease-free interval of 2 years or more (median progression-free survival was 51.66, vs 13.9 months for those with less than 2 years disease-free interval). CONCLUSION Re-irradiation of second primaries or recurrences of head and neck cancers with moderate radiation doses yields acceptable progression-free survival and morbidity rates.

Potential opportunities to reduce cervical cancer by addressing risk factors other than HPV

Cervical cancer is the most common cancer in developing world and 80% of global burden is reported from these nations. Human papillomavirus along with poverty, illiteracy/lower education level and standards, multi-parity, tobacco, malnutrition and poor genital hygiene may act synergistically to cause cervical cancer. Risk factor of cervical cancer may in itself be the reason for non-viability of cervical cancer vaccine program in this part of the world. Interventions to address these risk factors in addition to vaccination of girls before their sexual debut may hold promises of reducing the morbidity and mortality of female genital cancers.

Treatment of squamous cell carcinoma of external auditory canal: A tertiary cancer centre experience

OBJECTIVE Carcinoma of external auditory canal (EAC) is a rare disease with variable management strategies and prognosis. We aimed to analyze treatment modalities, prognostic factors and survival outcomes in patients of squamous cell carcinoma of EAC treated at our institution. METHODS Forty-three patients of squamous cell carcinoma of EAC were analyzed for clinical presentation, stage, surgical procedures and radiotherapy (RT) modalities employed. Stell and McCormick staging system was used for staging of the patients. Progression free survival (PFS) was estimated by the use of Kaplan-Meier product-limit method. Log rank test was used to assess the impact of prognostic variables on PFS. Multivariate analysis was performed using the Cox hazard regression model. p value of <0.05 was considered significant for all statistical analysis. RESULTS Median age was 56 years (range: 12-84 years). Male to female ratio was 31:12. Stage was T1, T2 and T3 in 2, 17 and 18 patients respectively. Sixteen patients underwent surgery. Thirty-six patients received RT (14 received definitive RT, 11 had post-operative RT and 11 had RT with palliative intent). Eight patients (16%) received chemotherapy (5 received concurrent with RT, 2 had adjuvant and 1 had neo-adjuvant chemotherapy). Nine patients (of 11 patients) achieved a complete response (CR) and 2 achieved a partial response (PR) after surgery plus post-operative RT. Nine patients and 5 patients respectively achieved CR and PR after definitive RT (with or without concurrent chemotherapy). Of the 11 patients who received palliative RT, 2 had very good objective response (>50%) and 7 patients had PR to palliative RT. After a median follow-up of 16 months, median PFS for the entire cohort was 14 months. Two-year PFS rates were 85.7%, 46.9% and 0% for patients treated with surgery and post-operative RT, definitive RT and palliative RT respectively. On univariate analysis, higher stage (p=0.05) and facial nerve palsy at presentation (p=0.0008) were significant predictors of inferior PFS. CONCLUSION Patients with carcinoma of EAC present mostly in advanced stage at our centre. Combined higher stage (T3) and facial nerve palsy at presentation portend poorer outcome. Combined modality treatment with surgery and radiotherapy should be advocated and palliative RT remains a reasonable treatment option in patients with advanced incurable disease.

Pediatric head and neck squamous cell carcinoma: Report of 12 cases and illustrated review of literature.

INTRODUCTION Head and neck carcinoma is a very rare entity in pediatric age group. We here present the demography, treatment and outcome of 12 pediatric patients. METHODOLOGY We retrieved the treatment charts of pediatric patients with a diagnosis of head and neck squamous cell carcinoma (PHNSCC). We also retrieved the published literature of pediatric HNSCC to present the treatment modalities being delivered across institutes. RESULTS We found 12 patients registered with a diagnosis of squamous cell carcinoma. Median age of the entire cohort was 17 years (Range: 8-20). Gender predilection was skewed in favor of male (male:female ratio-11:1). Oral tongue 3(25%) was the commonest sub site followed by soft palate 2(17%) gingiva 2 (17%), supra glottis larynx 2(17%) and one each of hard palate, buccal mucosa, floor of mouth (8.25% each). The most commonly employed modality of treatment was surgery in 6(50%). Radiation was used in seven cases: 7(Adjuvant-4, Radical-3). Two patients received radical chemo-radiation. Neo-adjuvant chemotherapy was used in two cases. Median follow up duration was 2 years (Range: 6 months to 8 years). One patient recurred 6 months post completion of radical chemo-radiation. The patient with recurrent disease had soft palate primary and had isolated local recurrence. The patient was salvaged with surgery and was disease free at the last follow up. At the last follow up all patients were surviving without disease. CONCLUSION The treatment and survival are not much different in pediatric patients compared to adult counterpart. However, in the absence of molecular profiling it is difficult to assess the cause of development of SCC in pediatric patients. A detailed study of underlying molecular pathway will further guide the future treatment.

A multimodality approach to sinonasal undifferentiated carcinoma: a single institute experience

BACKGROUND Sinonasal undifferentiated carcinoma is a rare aggressive tumour arising from the Schneiderian epithelium lining the sinonasal tract. Although considered the cornerstone of therapy, surgical resection can only be performed in a limited number of patients. This report describes the experience of treating sinonasal undifferentiated carcinoma with a multimodality approach. METHOD The treatment charts of sinonasal undifferentiated carcinoma patients treated at a tertiary care centre from 2004 to 2012 were retrospectively reviewed. RESULTS A total of 16 sinonasal undifferentiated carcinoma patients with a median age at diagnosis of 47.5 years (range 8-65 years) were included: 19 per cent had neck nodal metastasis at presentation. Four patients (25 per cent) underwent surgery: of these, two had post-operative radiotherapy, one had pre-operative radiotherapy and one had adjuvant chemotherapy alone. Six patients (38 per cent) received definitive radiotherapy: five had received neoadjuvant chemotherapy to reduce tumour size and help in radiotherapy planning, while four (25 per cent) received palliative radiotherapy. The median follow up was 10.4 months (range 1-42.5 months). The estimated median progression-free survival time was 29.3 months. One- and three-year progression-free survival rates were 77 per cent and 41 per cent, respectively. CONCLUSION Surgery is the best treatment option for sinonasal undifferentiated carcinoma, although most patients require post-operative radiotherapy for advanced disease and close tumour margins. Definitive radiotherapy with or without chemotherapy may be suitable for patients with inoperable locally advanced disease. Elective nodal irradiation to address the high nodal involvement rates should be considered to improve the survival rate.

Postoperative radiotherapy dose requirement in standard combined-modality practice for head and neck squamous cell carcinoma: Analysis of salient surgical and radiotherapy parameters in 2 cohorts

This study compared 2 sequential cohorts to identify the postoperative radiotherapy (PORT) dose requirement for head and neck squamous cell carcinoma (HNSCC).

A phase 2 randomized study to compare short course palliative radiotherapy with short course concurrent palliative chemotherapy plus radiotherapy in advanced and unresectable head and neck cancer.

BACKGROUND Treatment of unresectable HNSCC is not well defined and has a poor outcome. This study has been designed to address the unmet needs of such groups of patients with primary end points of (a) proportion of patients eligible for radical treatment in each arm (b) loco-regional disease control at 6months between two arms. MATERIALS AND METHODS Locally advanced and unresectable HNSCC patients (except Nasopharynx and Larynx) unfit for radical treatment were randomized to arm A [short course RT alone (4Gy/#/day for 5days)] or arm B [RT as arm A+concurrent cisplatin at 6mg/m(2)/day IV bolus for 5days]. Those with at least PR were taken for further RT to complete biological equivalent dose of 70Gy, in both the arms. In arm B, concurrent CDDP at a dose of 40mg/m(2)/week was administered. RESULTS 114 patients (57 in each arm) were randomized but 111 were analyzable. 15 (27.27%) patients in arm A and 28 (50%) patients in arm B had ⩾PR (p=0.01) however patients taken for FRT were 14 (25.45%) and 26 (46.42%) in arms A and B respectively (p=0.02). Locoregional control i.e. (CR+PR) at 6months was 16.36% in arm A versus 32.14% in arm B (p=0.15). Median PFS (arm A - 3.2months, arm B - 6.2months; p=0.02) and OS (arm A - 5.9months, arm B - 10.1months; p=0.03) was significantly more in arm B. There was relative improvement in quality of life for most parameters in arm B. CONCLUSION Concurrent low dose CTRT can be an effective treatment modality in advanced and incurable HNSCC. However, a larger phase III trial is required.