Arif Jamshed

Objectives: Oral cancer (OC) poses a growing health concern in Pakistan, emerging as the second‐most diagnosed cancer in the country. The escalating incidence and mortality rates of OC place considerable strain on the health system. This study aims to delineate the factors contributing to the elevated incidence of OC in Pakistan. Methods: A hospital‐based case–control study involving 688 participants above 18 years old was conducted. Participants were evaluated for reported OC risk factors. Results: Findings indicate a heightened susceptibility among men (71.5%) to develop OC in Pakistan. Factors contributing to OC include advancing age (AOR 1.12, 95% CI 1.13–1.18, p = 0.001), low SES (61.4%), and limited education. Significant risk was associated with chewing tobacco (niswar) AOR 6.83, 95% CI 2.67–17.45, p = 0.001), areca nut (AOR 4.99, 95% CI 1.51–16.45, p = 0.001), and pan (AOR 7.90, 95% C1 3.19–19.59, p = 0.001). Parental consanguinity increased OC incidence (AOR 4.72, 95% CI 1.12–4.14, p = 0.02). Physical activity had no association with OC (AOR 0.41, 95% CI 0.23–0.75, p = 0.004). Excessive sunlight exposure appeared to be associated with OC (AOR 0.15; 95% CI: 0.08–0.28, p ‐value: 0.001). At the same time, cigarette smoking and alcohol are not significant factors for the development of OC in Pakistan. Conclusion: The study underscores the elevated prevalence of OC among Pakistani men, attributable in part to lower literacy rates and inadequate access to healthcare facilities. The implementation of targeted prevention strategies informed by these epidemiological insights is essential for mitigating the burden of OC in the region.

Purpose Oropharyngeal mucositis is a common complication of anticancer therapy. This study aimed to determine the effectiveness and safety of intralesional corticosteroid therapy (ICT) in the management of persistent mucositis. Methods A retrospective chart review of patients who underwent ICT in the oral cavity to manage oral mucositis managed with basic oral care and preventive modalities and persisting at least 6 weeks after head and neck radiation or chemoradiation therapy completion between November 2017 and September 2023 was performed. Bio-demographic data, cancer and anticancer therapy characteristics, medical history, and mucositis-related variables were extracted from electronic medical records. Results Among the 34 participants, 22 (64.7%) were male. Twenty (58.8%) participants received radiotherapy; the rest received chemoradiation therapy. Before the ICT, the median mucositis lesion surface area was 225 mm² (range 9–2025 mm²), and 22 (64.7%) patients had grade III mucositis. Post-intervention, the median size was reduced to 0 mm² (range 0–1600 mm²). Clinically effective response (≥ 75% size and symptom reduction) was observed in 28 (82.4%) participants over a median of 26 days (7–60 days). Within this cohort, complete healing of the lesion was seen in 18 (64.3%) subjects. Overall, 25 (73.5%) participants experienced a downgradation in the mucositis stage. Local complications from injections were found in two (5.7%) participants. A correlation was found between clinically effective relief and absence of trismus (p = .03) and smaller pre-procedure surface area (p = .009). Conclusion The ICT represents a viable option in managing non-healing, persistent radiation, and chemoradiation-induced oral mucositis. The modality was well tolerated and had no systemic complications.

6027 Background: The current standard of treatment in locally advanced nasopharyngeal cancer is concurrent chemoradiation, however recent addition of induction chemotherapy in the already established regimen has presented an attractive alternative approach. We report on survival with induction Gemcitabine and Cisplatin (GC) followed by chemoradiation (CRT) in the treatment of advanced nasopharyngeal carcinoma. Methods: Between 2005 and 2015, 300 patients (M 70%: F 30%) with histologically confirmed nasopharyngeal carcinoma. Histological subtypes WHO I 4% (13) and WHO III 96% (287). AJCC (7^th edition) stage was Stage III 28% (85) and Stage IV 72% (215) patients. IC 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 was given as a phase treatment to a total dose of 70 Gy in 35 fractions. Concurrent three weekly cisplatin (75 mg/m²) was administered to all patients. Results: Median follow up time was 30 months. The 5-year overall survival (OS), loco regional control (LRC) and relapse free survival (RFS) rates were 70% (95% CI 6.43 – 7.52), 69% (95% CI 6.52 – 7.64) and 52% (95% CI 5.25 – 6.34) respectively. One hundred and seven patients failed treatment; local or loco-regional 39% (42), regional 16% (17) and distant 45% (48). Conclusions: We conclude that induction gemcitabine and cisplatin followed by chemo-radiation is an effective regimen in management of nasopharyngeal carcinoma, meriting further investigation in randomized clinical trials.

To determine the outcome in patients with early squamous cell carcinoma of oral tongue, and the impact of various prognostic factors on survival. The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised records of patients treated for squamous cell carcinoma of early stage tongue between March 2003 and October 2009. Various factors, including demographics, risk factors, stage, and grade of the tumour were determined. Kaplan Meier curves were plotted to determine the 5-year overall survival, relapse-free survival, local control, regional control, and loco-regional control. A total of 137 patients with early oral tongue tumours were treated. With a median follow-up of 46 months, the overall survival of T1, T2 early tongue tumour was 73% and 64%. The incidence of occult metastasis was 30%. The overall survival for Stage I/II and III/IV was 78% and 50% (p=0.002). Patterns of failures included; local 19 (13%), regional 22 (16%), loco-regional 4 (3%) and distant 5 (4%) respectively. The 5-year local control, regional control, loco-regional control was 86%, 82% and 72%. The only significant predictor of overall survival was clinical and pathological N stage in T1 patients, and surgical procedure, grade, pathological N stage in T2 cases. Treatment of early squamous cell carcinoma of oral tongue effectively achieved local control and disease-free survival. Nodal stage was the most important prognostic factor in terms of survival and recurrence.

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 55Gy of radiation in 20 fractions with concurrent single agent Cisplatin (75mg/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.

Objectives: Breast conservative therapy (BCT) is an established method of treating early stage invasive breast cancer. Survival after BCT in Pakistani population has not been reported. This study was carried out to report locoregional control and overall survival (OS) after BCT for invasive breast cancer and analyze prognostic factors in Pakistani population. Materials and Methods: Patients who received BCT between 1997 and 2009 were included in the study. Patients' follow-up, demographics, prognostic variables and treatment modalities were assessed. Data were analyzed for locoregional and distant relapse and estimated 10-year locoregional recurrence free survival (LRRFS) and OS was calculated using Kaplan Meier curves. To determine the significance of prognostic variables, univariate and multivariate analysis was performed. Results: A total of 902 patients underwent BCT. Median age was 42 (17-82) years and the median follow-up was 51 (1.4-187) months. There were 484 (53.6) poorly differentiated and 194 (21.5) triple negative tumors. T3/T4 tumors were found in 128 (14.1) patients and 441 (44.8) patients had nodal involvement. Among adverse events, 58 (6.3) locoregional failures, 152 (16.8) distant failures and 155 (17.1) deaths were observed. Estimated 10 years LRRFS- was 88% while OS was 70%. On multivariate analysis, tumor size and nodal involvement were independent predictors of locoregional recurrence-free and OS. In addition, hormonal therapy significantly affected OS. Conclusion: BCT has acceptable long-term results in Pakistani women. Tumor size and nodal involvement are independent predictors of survival.

Retrieval of 12 lymph node groups. The LNR groups were based on interquartile range. Clinicopathological and treatment outcomes were compared. Expected 5 year disease free and overall survival was calculated. Cox proportional hazard model was used to determine independent predictors. More patients in <12 lymph nodes removed group had low tumors (<5 cm from anal verge) (75.5% versus 60.7%) (P=0.03) and underwent abdominoperineal resection (59.1% versus 42.9%) (P=0.02). Overall survival (OS) and disease free survival (DFS) was not different [(56% and 52% (P=0.7)] [(50% and 57% (P=0.5)]. LNR<0.15 was independent predictor of DFS while LNR ratio<0.12 for OS on multivariate analysis. LNR and not number of retrieved nodes impacts survival in younger patients with predominance of anorectal tumors after C-XRT. A specific LNR cutoff remains to be defined.

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.

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.