Hassan Iqbal

Gemcitabine And Cisplatin Followed by Chemo-Radiation for Advanced Nasopharyngeal Carcinoma

Concurrent chemo-radiation (CRT) has been established as the standard of care for non-metastatic loco- regionally advanced nasopharyngeal carcinoma (NPC) but recently the addition of induction chemotherapy in the already established regimen has presented an attractive multidisciplinary approach. This retrospective study was carried out to evaluate the efficacy of induction chemotherapy (IC) followed by CRT for the management of loco-regionally advanced NPC. Between July 2005 and September 2010, 99 patients were treated with cisplatin based IC followed by CRT. Induction chemotherapy included a 2 drug combination; intravenous gemcitabine 1000 mg/m2 on day 1 and 8 and cisplatin 75 mg/m2 on day 1 only. Radiotherapy (RT) was given as a phase treatment to a total dose of 70 Gy in 35 fractions. Concurrent cisplatin (75 mg/m2) was administered to all patients on days 1, 22 and 43. All patients were evaluated for tumor response and adverse effects after IC and 6 weeks after the completion of the treatment protocol. Statistical analysis was performed using SPSS version 17 and Kaplan Meier estimates were applied to project survival. Median follow-up duration was 20 months. The 5-year overall survival (OS), loco regional control (LRC) and relapse free survival (RFS) rates were 71%, 73% and 50%respectively. Acute grade 4 toxicity related to induction chemotherapy and concurrent chemo-radiation was 4% and 2% respectively, with only 3 toxicity-related hospital admissions. We conclude that induction gemcitabine and cisplatin followed by chemo-radiation is a safe and effective regimen in management of nasopharyngeal carcinoma, meriting further investigation in randomized clinical trials.

Ten Year Experience with Surgery and Radiation in the Management of Malignant Major Salivary Gland Tumors

BACKGROUND Despite being rare in incidence, malignant tumors of major salivary glands show diverse histological variation. There are limited data on major salivary gland tumor management and outcome from Pakistan. The objective of this study was to share our experience with management of malignant tumors of major salivary glands. MATERIALS AND METHODS Patients who received treatment at Shaukat Khanum Cancer Hospital and Research Center from July 2002 to June 2011 with an underlying diagnosis of a major salivary gland malignancy were included. Patient characteristics and treatment modalities were assessed. Local, regional and distant failures were determined. Disease free survival (DFS) and overall survival (OS) were calculated using Kaplan Meier curves and the Log rank test was used to determine statistical significance. Univariate and multivariate analyses were performed using Cox proportional hazard regression. RESULTS The parotid gland was the primary site of origin in 104 (80%) patients. Mucoepidermoid carcinoma (43%) and adenoid cystic carcinoma (24%) were the most common histological types. Surgery followed by adjuvant radiation remained the mainstay treatment modality with 81 (62%) patients. Nineteen (15%) patients were treated with surgery alone and 30 (23%) patients with locally advanced surgically inoperable tumors received radiation only. Forty one (32%) patients failed the treatment (local 12, regional 11, locoregional 5, distant 13). The expected 5 year DFS and OS were 65% and 74% respectively. On multivariate analysis, grade was the only independent predictor of DFS and nodal involvement was the only independent predictor of overall survival. CONCLUSIONS Employing existing standards of treatment, comparable survival can be achieved in Pakistani population with major salivary gland malignancies as elsehwere in the world.

TriCurin, a novel formulation of curcumin, epicatechin gallate, and resveratrol, inhibits the tumorigenicity of human papillomavirus-positive head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and epicatechin gallate from green tea. Cell viability, clonogenic survival, and tumorsphere formation were inhibited and significant apoptosis was induced by TriCurin in UMSCC47 and UPCI:SCC090 HPV-positive HNSCC cells. Moreover, TriCurin decreased HPV16E6 and HPV16E7 and increased p53 levels. In a pre-clinical animal model of HPV-positive HNSCC, intra-tumoral injection of TriCurin significantly inhibited tumor growth by 85.5% compared to vehicle group (P < 0.05, n = 7). Our results demonstrate that TriCurin is a potent anti-tumor agent for HPV-positive HNSCC. Further development of TriCurin as a novel anti-cancer therapeutic to manage the HPV-positive HNSCC population is warranted.

Regional Failures after Selective Neck Dissection in Previously Untreated Squamous Cell Carcinoma of Oral Cavity

Aim. To share experience with regional failures after selective neck dissection in both node negative and positive previously untreated patients diagnosed with squamous cell carcinoma of the oral cavity. Patients and Methods. Data of 219 patients who underwent SND at Shaukat Khanum Cancer Hospital from 2003 to 2010 were retrospectively reviewed. Patient characteristics, treatment modalities, and regional failures were assessed. Expected 5-year regional control was calculated and prognostic factors were determined. Results. Median follow-up was 29 (9–109) months. Common sites were anterior tongue in 159 and buccal mucosa in 22 patients. Pathological nodal stage was N0 in 114, N1 in 32, N2b in 67, and N2c in 5 patients. Fourteen (6%) patients failed in clinically node negative neck while 8 (4%) failed in clinically node positive patients. Out of 22 total regional failures, primary tumor origin was from tongue in 16 (73%) patients. Expected 5-year regional control was 95% and 81% for N0 and N+ disease, respectively (P < 0.0001). Only 13% patients with well differentiated, T1 tumors in cN0 neck were pathologically node positive. Conclusions. Selective neck dissection yields acceptable results for regional management of oral squamous cell carcinoma. Wait and see policy may be effective in a selected subgroup of patients.

Image guided surgery in the management of head and neck cancer

Complete resection of head and neck tumors relies on palpation and visual inspection. Achieving a negative margin in remote locations in the head and neck region, especially in close proximity to critical structures, is often difficult to achieve. Positive resection margins in head and neck cancer are at high risk to develop recurrent disease and associated with poor prognosis. Near-infrared fluorescence-guided optical imaging is an emerging technology with the potential to move the surgical field forward and facilitate surgeons to visualize tumors in real-time intra-operatively. In this review, our focus is to discuss the recent advances and the potential application of near infrared (NIR) fluorescent-guided surgery in the management of head and neck cancer.

Five-Year Follow-Up of Concomitant Accelerated Hypofractionated Radiation in Advanced Squamous Cell Carcinoma of the Buccal Mucosa: A Retrospective Cohort Study

In resource limited settings, induction chemotherapy with Gemcitabine and Cisplatinum and concurrent hypofractionated chemoradiation for locally advanced carcinoma of buccal mucosa (BMSCC) are a cost effective option but remain under reported. The objective of this study was to report long term survival outcome after concurrent hypofractionated radiotherapy in locally advanced BMSCC. Between February 2005 and 2009, 63 patients received treatment. Induction chemotherapy (IC) regimen consisted of two drugs: Gemcitabine and Cisplatin. All patients received 55 Gy of radiation in 20 fractions with concurrent single agent Cisplatin (75 mg/m2). Five-year overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were determined. Based on AJCC staging, 7 (11%) patients were stage III, 31 (49%) stage IV a, and 25 (40%) stage IVb at presentation. After IC, 8 (18%) patients had complete radiological response, 33 (73%) had partial response, and 4 (9%) had stable disease. After concurrent hypofractionated chemoradiation, thirty-nine (62%) patients were complete responders and 24 (38%) had stable disease. With a minimum follow-up of 60 months, 5-year OS, DFS, and PFS were 30%, 49%, and 30%, respectively. In locally advanced buccal mucosa squamous cell carcinoma, concurrent hypofractionated chemoradiation results in acceptable survival and regimen related toxicity.

Survival outcome of malignant minor salivary tumors in Pakistani population

Objective: Malignant tumors of minor salivary glands (MSG) are rare. Survival outcome in Pakistani population with malignant MSG tumors remains to be defined. The objective of this study was to report the clinical presentation, treatment modalities, and survival outcome of radically treated malignant tumors of MSG in Pakistani population. Materials and Methods: Between April 2003 and March 2011, 45 patients with malignant tumors of MSG were treated at Shaukat Khanum Cancer Hospital and included in the study. Patient characteristics and treatment modalities were assessed and local, regional, and distant failures determined. Relapse-free (RFS) and overall survival (OS) was calculated using Kaplan-Meier curves, and log-rank test was used to determine significance. Results: Median age was 40 (17-83) years. Male to female ratio was 1.25:1. Most common site was hard palate in 31 (69%) patients. Adenoid cystic carcinoma (51%) was the most common histological diagnosis. Nine patients (20%) underwent surgery as the only treatment modality, six patients received (13%) radiotherapy alone, and 30 patients (67%) had surgery followed by adjuvant radiotherapy. Eight patients developed recurrence (four local, two regional, one locoregional, and one distant). The 5-year actuarial overall OS and RFS was 77 and 66%, respectively. Age, T-stage, and treatment modality were significant for RFS, whereas T-stage and treatment modality were significant factors for OS. Conclusion: Surgery as single modality or combined with radiation therapy resulted in acceptable survival in Pakistani population with malignant minor salivary tumors.

Capecitabine for treating head and neck cancer.

ABSTRACT Introduction: With an increasing incidence, over half a million cases of head and neck cancer (HNC) are diagnosed annually worldwide. Various chemotherapeutic agents are utilized to achieve adequate locoregional control. Cisplatin, fluorouracil (FU), and taxanes are often used to treat HNC but these regimens have shown high toxicity and poor patient compliance. Capecitabine is an orally administered prodrug that is preferentially converted to FU in tumor cells in comparison to normal cells. Area covered: In this review, the authors evaluate the role of capecitabine in radical and palliative settings either alone or in combination with other chemotherapeutic drugs in the management of HNC. In addition, metabolic conversion, pharmacokinetics, pharmacodynamics, and toxicity profile of capecitabine are discussed. Expert opinion: Various phase II trials conducted on capecitabine in the management of recurrent HNC have shown comparable results and tolerable toxic effects especially in pre-treated fragile patients. Capecitabine, used in induction or concurrent settings in the radical management of locoregionally advanced HNC, have also shown promising results. Randomized trials are needed to validate the role of capecitabine in the management of HNC.

Impact and prognostic value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography scan in the evaluation of residual head and neck cancer: Single-center experience from Pakistan

Background: Overview of clinical impact of positron emission tomography-computed tomography (PET-CT) scans in patients with head and neck carcinomas at our center. Methods: Retrospective review of posttreatment 18F-fluorodeoxyglucose (18F-FDG) PET-CT scans in patients with head and neck carcinomas with risk of residual disease. Clinical outcome served as the reference standard. Results: This study included 93 patients (65.6% males, mean age: 48.8 years ± 17.2 standard deviation) with squamous cell carcinoma as most frequent histopathology (91.4%). PET-CT scans were performed on average 6 months posttreatment. Diagnostic accuracy, positive predictive value, and negative predictive value of PET-CT for disease were found to be 88%, 88%, and 92%, respectively. A median follow-up of 24 months was available for 91 patients. Kaplan–Meier curves showed significantly higher disease-free survival with negative PET-CT as compared to positive PET-CT (P = 0.01) and maximum standardized uptake values of <5.0 (P = 0.01). Conclusion: FDG PET-CT has diagnostic and prognostic implications in treated patient of head and neck cancers.

Temporal trends in outcome of oral squamous cell cancer in a resource-limited setting.

Aims and background Improving survival has been documented for oral squamous cell carcinoma in recent years. It is a common malignancy in Pakistan but survival outcomes have not been reported. The objective of this study was to determine survival and identify independent predictors in patients with oral squamous cell cancer in 2 different time periods. Methods A retrospective review of patients who received treatment between 2003 and 2012 was performed. Patients were divided into two 5 year groups: group 1 (2003-2007) (n = 628) and group 2 (2008-2012) (n = 920). Demographics, risk factors, treatment approaches, and outcomes were compared. Disease-free and overall survival were calculated. Cox proportional hazard model was used to determine independent predictors of survival. Results A significant difference was present for ethnicity and grade and clinical T and N stage of tumors, with earlier presentation in group 2. More patients underwent surgery (p = 0.001) and had radical treatment intent (p<0.0001) in recent years. Induction chemotherapy (p<0.0001) and palliative chemotherapy (p<0.0001) were used more frequently. No significant difference in disease-free survival was observed but overall 5-year survival improved significantly (23% vs 42%) (p<0.0001). Use of palliative chemotherapy reduced risk of death significantly (hazard ratio [HR] 0.1, confidence interval [CI] 0.02-0.4, p = 0.003), while pathologic nodal positivity significantly increased the risk (HR 2.5, CI 1-5.9, p = 0.03). Conclusions These results from a single cancer hospital demonstrate improvement in overall survival secondary to early detection, better patient selection, and use of palliative chemotherapy in the later period.