Raza Hussain

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.

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.

Patterns of cancer cell sphere formation in primary cultures of human oral tongue squamous cell carcinoma and neck nodes

Recently a sub-population of cells with stem cell characteristics, reported to be associated with initiation, growth, spread and recurrence, has been identified in several solid tumors including oral tongue squamous cell carcinoma (OTSCC). The aim of our pilot study was to isolate CD44+ cancer stem cells from primary cultures of OTSCC and neck node Level I (node-I) biopsies, grow cell spheres and observe their characteristics in primary cultures. Parallel cultures of hyperplastic lesions of tongue (non-cancer) were set up as a control. Immunohistochemistry was used to detect CD44/CD24 expression and magnetic activated cell sorting to isolate CD44+ cell populations followed by primary cell culturing. Both OTSCC and node-I biopsies produced floating spheres in suspension, however those grown in hyperplastic and node-I primary cultures did not exhibit self-renewal properties. Lymph node metastatic OTSCC, express higher CD44/CD24 levels, produce cancer cell spheres in larger number and rapidly (24 hours) compared to node negative OTSCC (1 week) and non-cancer specimens (3 weeks). In addition, metastatic OTSCC have the capacity for proliferation for up to three generations in primary culture. This in vitro system will be used to study cancer stem cell behavior, therapeutic drug screening and optimization of radiation dose for elimination of resistant cancer cells.

Retrospective study of rare cutaneous malignant adnexal tumors of the head and neck in a tertiary care cancer hospital: a case series

BackgroundAdnexal tumors of the skin are a large and diverse group of benign and malignant neoplasms, which exhibit morphological differentiation toward one of the different types of adnexal epithelium present in normal skin and they pose a diagnostic challenge. The purpose of this study is to share our experience with these rare but aggressive tumors at a tertiary care cancer hospital in a developing country. A retrospective review of 11 patients diagnosed with rare adnexal tumors and their variants from January 2005 to December 2014, treated either surgically or non-surgically, was performed to describe the clinicopathological characteristics and outcome of the disease.Case presentationA total of 11 patients were diagnosed with adnexal carcinoma and its variants: a 34-year-old Sindhi man, a 59-year-old Punjabi woman, a 32-year-old woman from Khyber Pakhtunkhwa, a 43-year-old Punjabi woman, a 64-year-old Punjabi man, a 51-year-old man from Khyber Pakhtunkhwa, a 51-year-old Punjabi woman, a 74-year-old Punjabi woman, a 75-year-old Punjabi man, a 61-year-old man from Khyber Pakhtunkhwa, and a 53-year-old man from Khyber Pakhtunkhwa. The male to female ratio was 1.2:1. The histological variations were sebaceous differentiation (n = 4), microcystic adnexal carcinoma (n = 4), trichilemmal carcinoma (n = 1), pilomatrix carcinoma (n = 1), and hidradenocarcinoma (n = 1). The mean age at presentation was 54 years (range 32 to 75). The primary subsite of involvement was the scalp in nine patients followed by eyelids in two patients. Surgery was the primary treatment modality in almost all patients; postoperative radiotherapy (PORT) was offered to eight patients. The median dose of radiation was 45 Gy to the primary site. Indications for radiotherapy included close margins (n = 2), positive margins (n = 1), high grade histology (n = 4), and multifocal disease (n = 1). On follow-up, two patients presented with local, one regional and two patients developed distant metastasis.ConclusionsAdnexal carcinomas are rare tumors with diverse histological patterns and a tendency for locoregional and distant metastasis. Surgery should be the mainstay of treatment reserving radiotherapy for adjuvant, palliative, and re-treatment scenarios.

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.

Treatment Outcomes of Rare Retromolar Trigone Squamous Cell Carcinoma Using Combined Modalities

Background Retromolar trigone squamous cell carcinoma is relatively uncommon and due to its complex anatomy has always remained a challenge in terms of loco-regional control and survival. Surgery, radiotherapy, and chemotherapy as combined modalities have been used but high recurrence rates result in poor outcome. Methods We have retrospectively evaluated records of 62 patients treated in Head and Neck Oncology unit of Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC), Lahore, Pakistan from 2004 to 2014 who were included based on the criteria of histopathological proven squamous cell carcinoma of retromolar trigone (RMT) treated with radical intent. Diagnostic workup for all patients involved clinical examination, imaging modalities usually magnetic resonance imaging (MRI), computerized tomography (CT), Orthopantomogram (OPG), and chest x-ray (CXR) to evaluate regional and distant metastasis, respectively. Kaplan-Meier survival curves were used to depict survival. Results The study was comprised of 36 male and 26 female patients. Treatment modalities used are surgery only (n = 1), radiotherapy alone (n = 13), radiotherapy followed by surgery (n = 10), chemoradiotherapy (n = 16), induction chemotherapy followed by concurrent chemoradiotherapy (n = 19), induction chemotherapy followed by surgery, and radiotherapy (n = 2). Surgical interventions include wide local excisions (n = 6), marginal mandibulectomy (n = 4), and segmental mandibulectomy (n = 4). Surgical margins were clear in 54%, close in 38%, and involved in 8% of patients. AJCC 7th edition showed cT1 8%, cT2 22%, cT3 14%, and cT4 56% while pT1 2%, pT2 3%, and pT4 8%. During follow-up, 18% patients have come up with local recurrence, 22% showed persistent disease while 9% have presented with distant metastasis. The five-year and overall survivals are 38% and 22%, respectively. Conclusion Retromolar trigone involvement poses many vital structures at risk of involvement. Late presentation results in involvement of masticator space compromising both mouth opening and surgical outcomes. Surgery and radiotherapy have shown comparable results in disease control. Bone invasion has shown poor outcome in terms of loco-regional control and overall survival.

Depth of invasion (DOI) as a predictor of cervical nodal metastasis and local recurrence in early stage squamous cell carcinoma of oral tongue (ESSCOT)

Background The new AJCC staging system (8th edition) incorporates depth of invasion to stage oral cancers. It is a recognized predictor for neck nodal metastasis and local recurrence, the associated risk is not well defined. The aim of this study was to explore the risk of occult neck nodal metastasis and local recurrence in relation to depth in early stage squamous cell carcinoma of oral tongue. Methods We have evaluated records of 179 patients with early tongue cancer treated in our unit from 2006–2015 with a mean age of 57.92 ± 11.93 years. Treatment modalities used were surgery (26%), surgery followed by radiotherapy (64%) and chemo-radiation (10%). Neck dissection was ipsilateral in 94% and bilateral in 6% of the patients. Patients were grouped according to the AJCC cut off points in 8th edition for depth; group A: 1–5 mm (35%), group B: 6–10 mm (47%) and group C: > 10 mm (18%). Results Risk of local recurrence and nodal metastasis for Group A was 15% (10/63) and 23% (15/63), group B 20% (17/84) and 34% (29/84), and group C 40% (13/32) and 53% (17/32). Conclusions Depth more than 10 mm is associated with significantly increased risk of recurrence and nodal metastasis. Elective neck dissection should be a consideration for tumors having depth less than 5mm.

Clinicopathological Behavior and Oncological Outcomes of Malignant Parotid Tumors in a Pakistani Population

Introduction The incidence of salivary gland tumors is influenced by geographical and racial factors resulting in diverse histology. While salivary gland tumors account for a low proportion of head and neck cancers, most malignant tumors of the salivary gland are located in the parotid gland. The goals of this study are to describe the clinicopathological behavior of malignant parotid tumors and explore oncological outcomes related to survival in our Pakistani tertiary care cancer hospital. Methods We conducted a retrospective analysis of 209 patients diagnosed with malignant parotid tumors from 2004 to 2016. Data such as demographics, age, gender, histology, grade, clinical and pathological stage, surgical treatment types and adjuvant modalities used were analyzed using SPSS software version 20. We used Kaplan Meier curves to analyze survival data. Results The median patient age at diagnosis was 40 years, and the ratio of men to women was 1.2:1. Mucoepidermoid carcinoma was the most common histological variant (with a 50% incidence rate) followed by adenoid cystic carcinoma (13%), and adenocarcinoma (10%). Histology has further categorized these malignant tumors into low (34%), intermediate (28%), and high (21% ) grades. The American Joint Committee on Cancer, seventh edition, clinical staging was Stage I (21%), II (28%), III (15%), and IV (34%). The 5-year survival was 68%, and the 10-year survival was 45%. Conclusion Mucoepidermoid carcinoma is the most common malignant parotid histology in our patient population. Advanced age, increased T stage (size > 4 cm), high-grade histology, and cervical nodal involvement decrease overall survival. Open biopsies, piecemeal excisions, and delayed presentation for radiotherapy post-surgery may also have role in adverse outcomes in these malignancies.