J.P. Agarwal

Epidemiology of lung cancer in India: Focus on the differences between non-smokers and smokers: A single-centre experience

CONTEXT Lung cancer has varied epidemiology depending on the geographic region. Globally, there have been important changes in incidence trends amongst men and women, histology, and incidence in non-smokers. Indian epidemiological data on lung cancer is scarce. AIMS We set out to study the epidemiological patterns and clinical profile of lung cancer in India. MATERIALS AND METHODS We interviewed patients discussed in the thoracic oncology multidisciplinary meetings between 2008 and 2009. Demographic data, smoking history, place of residence, histology, stage at presentation, and treatment details were collected. Data was entered and analyzed in SPSS. RESULTS There were 489 patients, with a median age of 56 years, of which 255 (52%) were non-smokers and 234 (48%) were smokers. One hundred and thirty-three patients had consumed smokeless tobacco. The male-to-female ratio was 3.5:1. Sixty-nine patients (14.1%) were incorrectly diagnosed and treated with anti-tuberculosis treatment, which delayed the diagnosis of lung cancer by four months. Eight percent of patients had small-cell carcinoma; of the 92% patients with non-small-cell carcinoma (NSCLC), the most common histology was adenocarcinoma (43.8%), followed by squamous cell (26.2%), large cell (2.1%) and other (8.3%). Eighteen percent of patients were diagnosed by cytology, therefore were diagnosed as NSCLC, without further histologic subtyping. Most patients (43%) were in Stage III at presentation. Lung followed by bone were the common sites of metastases. The majority of the patients (49%) received palliative chemotherapy. Among definitive therapy, concurrent chemo-radiation (13%) was offered more frequently than surgery (6%). CONCLUSION Considerably higher numbers of Indian patients with lung cancer are non-smokers, compared to the West. The global trend of rise in adenocarcinoma is paralleled in India. Non-tobacco-related risk factors need further investigation.

Analysis of prognostic factors in 1180 patients with oral cavity primary cancer treated with definitive or adjuvant radiotherapy

INTRODUCTION The present study identifies the prognostic factors influencing oral cancers in a large cohort of patients treated at a single institute. MATERIALS AND METHODS This is an audit of 1180 patients treated from 1990 to 2004 in the service setting with prospective data collection. Patients were treated with radical radiotherapy or were planned for surgery and post operative radiotherapy (PORT). None of the patients received postoperative concurrent chemoradiation. For analysis, patients were divided into Group 1 and Group 2 based on the oral cavity subsite. RESULTS Of the entire cohort, 810 patients had tumors of the Gingivo-alveolo-buccal complex, lip and hard palate (Group 1) and 370 patients had primaries in tongue and floor of mouth (Group 2). Three year locoregional control for the entire cohort was 58%. The three year local control (LC), locoregional control (LRC) and disease free survival (DFS) for PORT group were 74%, 65% and 60%, respectively, with pathological nodal status, perinodal extension and cut margin status showing statistical significance (P <0.001). In the definitive radiotherapy group, the three year LC, LRC and DFS were 34%, 31% and 30%, respectively, with age, T stage, nodal status and stage being significant. Group 1 patients showed significantly better LC, LRC and DFS than Group 2 patients for the entire cohort. CONCLUSION The results indicate superior outcomes with PORT particularly in advanced stages of oral cancer and inferior outcomes in tongue and floor of mouth subsites. There is scope for improving outcomes by adopting treatment intensification strategies.

Intraoral adenoid cystic carcinoma: prognostic factors and outcome.

Intraoral (oral cavity and oropharynx) adenoid cystic carcinomas are uncommon cancers characterized by slow evolution, protracted clinical course, multiple and/or delayed recurrences, and late distant metastases. The molecular biology behind this enigmatic disease remains poorly characterized. To analyze and correlate prognostic factors with outcome in intraoral adenoid cystic carcinoma. Medical records of 76 patients with intraoral adenoid cystic carcinoma treated with definitive loco-regional therapy at the institute between 1992 and 2004 were retrospectively reviewed and analyzed.Majority (85.5%) of the patients had advanced stage disease. Seventy-four patients underwent surgery, of which 51 (68.9%) received adjuvant radiotherapy. The median dose of radiation was 56 Gy (range 44-66 Gy). Two patients with medical co-morbidities received radical radiotherapy. Perineural invasion, margin positivity and nodal positivity were present in 24 (32.4%); 27 (36.4%); and 15 (19.7%) patients, respectively. Ten (13.1%) patients developed local recurrence and 6 (7.8%) distant metastases. With a median follow-up of 20 months (range 1-137 months), the 5-year Kaplan-Meier estimates of local control and disease-free survival were 57.9% and 47.1%, respectively. On uni-variate analysis, perineural invasion (p=0.003), oropharyngeal primary (p=0.033), and advanced T-stage (p=0.047) were associated with increased local recurrences. Perineural invasion (p=0.05) and primary site (p=0.042) also predicted disease-free survival. On multivariate analysis, both perineural invasion and primary site retained significance for local control (p=0.007, p=0.011) and disease-free survival (p=0.018, p=0.014), respectively. Intraoral adenoid cystic carcinoma is an uncommon disease with an enigmatic clinical course. Perineural invasion, site of primary, and T-stage significantly impact upon local control and disease-free survival. The role of adjuvant radiotherapy remains controversial. Larger prospective studies with mature follow-up are needed to define the optimal treatment of intraoral adenoid cystic carcinoma.

Neoadjuvant chemotherapy followed by surgery in very locally advanced technically unresectable oral cavity cancers

BACKGROUND The median survival of technically unresectable oral-cavity cancers (T4a and T4b) with non surgical therapy is 2-12 months. We hypothesized that neoadjuvant chemotherapy (NACT) could reduce the tumour size and result in successful resection and ultimately improved outcomes. We present a retrospective analysis of consecutive patients who received NACT at our centre between January 2008 and August 2012. PATIENTS AND METHODS All patients with technically unresectable oral cancers were assessed in a multidisciplinary clinic and received 2 cycles of NACT. After 2 cycles, patients were reassessed and planned for either surgery with subsequent CTRT or nonsurgical therapy including CT-RT, RT or palliation. SPSS version 16 was used for analysis of locoregional control and overall survival (OS). Univariate and multivariate analysis was done for factors affecting the OS. RESULTS 721 patients with stage IV oral-cavity cancer received NACT. 310 patients (43%) had sufficient reduction in tumour size and underwent surgical resection. Of the remaining patients, 167 received chemoradiation, 3 radical radiation and 241 palliative treatment alone The locoregional control rate at 24 months was 20.6% for the overall cohort, 32% in patients undergoing surgery and 15% in patients undergoing non surgical treatment (p=0.0001). The median estimated OS in patients undergoing surgery was 19.6 months (95% CI, 9.59-25.21 months) and 8.16 months (95%, CI 7.57-8.76) in patients treated with non surgical treatment (p=0.0001). CONCLUSION In our analysis, NACT led to successful resection and improved overall survival in a significant proportion of technically unresectable oral-cancer patients.

Delay in seeking specialized care for oral cancers: Experience from a tertiary cancer center

OBJECTIVE Advanced oral cancers are a challenge for treatment, as they require complex procedures for excision and reconstruction. Despite being occurring at a visible site and can be detected easily, many patients present in advanced stages with large tumors. Timely intervention is important in improving survival and quality of life in these patients. The aim of the present study was to find out the causes of delay in seeking specialist care in advanced oral cancer patients. MATERIALS AND METHODS A prospective questionnaire based study was done on 201 consecutive advanced oral squamous cancer patients who underwent surgery at our hospital. All patients had either cancer of gingivobuccal complex (GBC) or tongue and had tumors of size more than 4 cm (T3/T4) and were treatment naοve at presentation. RESULTS Even though most patients observed abnormal lesions in their mouth, majority delayed the decision to visit a physician early. A significant percentage of patients (50%) also reported a delayed diagnosis by the primary care physician before being referred to a tertiary care center for definitive treatment. The average total duration from symptoms to treatment was 7 months. CONCLUSION The main reasons of this delay in receiving treatment were due to patients themselves (primary delay) or due to time taken by the primary physician to diagnose the condition (secondary delay). Oral self-examination can be helpful in detecting oral cancers early.

Radiotherapeutic management of locally advanced head and neck cancer

Head and neck cancer management has undergone several paradigm shifts for several relevant reasons. From the dismal experience with the use of radiotherapy as the sole modality in the treatment of this group of patients with advanced disease, radiotherapy has been evaluated as an adjuvant for the same group of patients who had undergone successful surgery. Although there is no level 1 evidence to support postoperative adjuvant radiation, several studies have demonstrated that adjuvant radiotherapy reduces the local failures and, thereby, improves survival. Predictors of recurrence after surgical resection are: positive margins of resection; extranodal spread in involved nodes; perineural invasion; and presence of two or more involved regional lymph nodes. Realization of the advantages of a combination of chemotherapy with radiotherapy has had a major impact on the management of these cancers. There is emerging evidence for the use of adjuvant concurrent chemoradiotherapy in the group with high-risk features. Multiple organ conservation strategies in the management of locally advanced head and neck cancers have evolved over the years. However, the meta-analyses of impact of chemotherapy in various settings reveal that concomitant chemoradiotherapy is superior to any of the other regimens. Increasing use of computed tomography, magnetic resonance imaging and positron emission tomography scan images has resulted in better visualization of target volumes and critical structures. Delineation of these structures is of paramount importance and has resulted in a profound change in conformal treatment planning. Better understanding of the physical aspects of delivery of radiotherapy and the advent of modern treatment planning systems have led to the development of conformal techniques. Although the benefit of these techniques on survival have yet to be demonstrated, there is evidence to suggest that they reduce treatment-related toxicities significantly and facilitate dose escalation. Increased knowledge of radiobiology has led to the development of various altered fractionation regimens in the management of locally advanced head and neck cancers. Discovery of cell-cycle kinetics and signal transduction pathways has led to the unearthing of several potential targets for targeted therapy. The epidermal growth factor recepter gene has emerged as the most promising target. The role of biological radiation response modifiers is evolving. All of these approaches to improve the therapeutic gain would be incomplete without evaluating their effect on the quality of life of these patients.

Stereotactic Conformal Radiotherapy in Non-small Cell Lung Cancer — An Overview

Stereotactic conformal radiotherapy is an established technique in treating cranial lesions and has made significant inroads in the treatment of extracranial sites as well. Early stage non-small cell lung cancer is one such site. This overview assesses the results that have been achieved with stereotactic conformal radiotherapy in non-small cell lung cancer so far and compares its efficacy with surgical and other non-surgical modalities.

Management and clinical outcome of sinonasal teratocarcinosarcoma: single institution experience.

PURPOSE To study the outcome of patients with sinonasal teratocarcinosarcoma treated at a single institution. METHODS We reviewed the medical records of 22 patients with histopathologically proven sinonasal teratocarcinosarcoma diagnosed during the period 1993-2007. Treatment was completed in 16 patients. RESULTS Fourteen patients underwent surgery (six received craniofacial resection, four open surgery and four endoscopic resection); this was followed by radiation therapy with or without chemotherapy in 11 patients. Two patients received chemoradiation as the definitive treatment. At median follow up in surviving patients of 34 months (range one to 180 months), only five were controlled. Disease recurred in 11 patients, with a median time to recurrence of seven months. The two-year disease-free survival rate and the overall survival rate were 28 and 46 per cent, respectively. CONCLUSION Sinonasal teratocarcinosarcoma appears to be an aggressive disease, with the majority of patients suffering locoregional failure. Multimodality treatment, in the form of a combination of surgery, radiation therapy and chemotherapy, appears to be the optimal approach.

Radiation recall dermatitis with gatifloxacin: a review of literature.

Radiation recall dermatitis (RRD) is a hypersensitivity skin reaction at the previously irradiated site after the administration of certain pharmacologic agent, which recovers on stopping the medication. RRD is a well‐recognized phenomenon with the use of chemotherapeutic agents; however, only a few cases have been reported with noncytotoxic antibiotics, despite their common use in patients with cancer. We report here a case of RRD with the use of gatifloxacin and describe the time dose factors of radiation exposure, characteristics of skin reactions, management and response and our reasons to label this case as RRD. We also discuss published work regarding proposed mechanisms, histological features, radiation dose threshold and response to rechallange with the RRD‐triggering drug. If RRD is to be characterized unequivocally, all the potential areas of confusion must be clarified like radiosensitization, nonhealing of acute reactions and skin‐related adverse effects of the RRD‐triggering drug. With the same objective, we further discussed radiosensitization and photosensitizing potential of fluoroquinolones. Gatifloxacin, although devoid of photosensitivity reactions, may cause idiosyncratic hypersensitivity reaction to cause RRD and should be considered as a potential cause of RRD. Given the potential severity of the reaction and increasing use of gatifloxacin, it is important to be aware of this phenomenon.

Systematic Review and Meta-analysis of Conventionally Fractionated Concurrent Chemoradiotherapy versus Altered Fractionation Radiotherapy Alone in the Definitive Management of Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

AIMS Treatment intensification either by using concurrent chemoradiotherapy (CCRT) or altered fractionation radiotherapy (AFRT) improves outcomes of locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The superiority of one approach over the other, however, remains to be firmly established. The aim of the present study was to compare outcomes of CCRT versus AFRT in the definitive non-surgical management of locoregionally advanced HNSCC for evidence-based decision making. MATERIALS AND METHODS An electronic search of Medline via PubMed was conducted with no language, year, or publication status restrictions. The Cochrane Central Register of Controlled Trials (CENTRAL) and Database of Abstracts of Reviews of Effectiveness (DARE) were also searched electronically. Only randomised controlled trials assigning HNSCC patients randomly to conventionally fractionated CCRT or AFRT alone were included. Data were extracted independently by two reviewers and pooled using the Cochrane methodology for meta-analysis and expressed as a hazard ratio with 95% confidence intervals. Overall survival was the primary outcome of interest, whereas disease-free survival, locoregional control and toxicity were secondary end points. RESULTS Five randomised controlled trials (involving 1117 patients and 627 deaths) directly comparing conventionally fractionated CCRT with AFRT alone were included. The risk of bias in included studies was low for efficacy outcomes, but high for toxicity outcomes. The overall pooled hazard ratio of death was 0.73 (95% confidence interval = 0.62-0.86), which significantly favoured conventionally fractionated CCRT over AFRT alone (P < 0.0001). Similarly, disease-free survival (hazard ratio = 0.79, 95% confidence interval = 0.68-0.92; P = 0.002) and locoregional control (hazard ratio = 0.71, 95% confidence interval = 0.59-0.84; P < 0.0001) were significantly improved with CCRT. There were no significant differences in the incidence of severe acute toxicity (dermatitis and mucositis) between the two approaches of treatment intensification. Late xerostomia was significantly increased with CCRT. Significant haematological toxicity and nephrotoxicity were seen exclusively with chemotherapy. CONCLUSION There is moderate quality evidence that conventionally fractionated CCRT improves survival outcomes compared with AFRT alone in the definitive radiotherapeutic management of locoregionally advanced HNSCC. No form of acceleration can potentially compensate fully for the lack of concurrent chemotherapy.