Abdul R. Fakih

Elective versus therapeutic neck dissection in early carcinoma of the oral tongue

A prospective, randomized trial was carried out to assess the value of elective versus therapeutic neck dissection in early squamous cell carcinoma of the oral tongue. Disease-free survival (median follow-up 20 months) was 52 percent versus 63 percent in patients who underwent hemiglossectomy alone and those who underwent hemiglossectomy and radical neck dissection, respectively (difference not statistically significant). Patients with a tumor depth of less than 4 mm did significantly better than those with a tumor depth of greater than 4 mm; they were also more likely to have uninvolved nodes at elective radical neck dissection compared with those with a tumor depth of greater than 4 mm. However, when the survival rates of patients in the two treatment groups were compared with respect to a tumor depth of 4 mm, there was no significant difference between the hemiglossectomy and the hemiglossectomy and radical neck dissection groups. A policy of interval elective radical neck dissection only in those with a tumor depth of greater than 4 mm may optimize cure rates and avoid neck dissection in those unlikely to develop neck recurrence.

Prognostic factors in head and neck soft tissue sarcomas

Soft tissue sarcomas of head and neck constitute a heterogeneous group of rare malignant tumors occurring at rare sites. The purpose of this retrospective study is to evaluate the pathologic features, treatment modalities, outcome, patterns of failure, survival, and other prognostic factors.

Human gamma delta T cells recognize heat shock protein-60 on oral tumor cells.

In the present investigations, γδ T cells were isolated from the peripheral blood of oral cancer patients and analyzed for their immunophenotype and cytotoxic potential. Flow‐cytometric analysis revealed a dominant population expressing Vγ9 and Vδ2 T‐cell receptors. In a 4‐hr 51Cr‐release assay, activated γδ T cells showed specific cytotoxicity against Daudi Burkitts lymphoma cells and fresh oral tumor cells. Cold target competition assays demonstrated that γδ T cells recognize a common ligand on Daudi and oral tumor cells. Expression of heat shock protein 60 (hsp60) molecules was detected on the surface of Daudi as well as oral tumor cells by flow cytometry and immunoprecipitation of surface biotinylated cells by anti‐hsp60 monoclonal antibody (MAb). Such MAbs brought about a significant inhibition of cytotoxicity of γδ T cells against Daudi and oral tumor cells. The results suggest that γδ T cells isolated from the peripheral blood of oral cancer patients have the ability to lyse oral tumor cells. The lysis of oral tumor cells occurs via recognition of hsp60 on the surface of oral tumor cells. Int. J. Cancer 80:709–714, 1999.

Limiting dilution analysis of proliferating and cytotoxic lymphocytes in the peripheral blood and tumours of oral cancer patients

Frequencies of proliferating and cytotoxic lymphocytes from the peripheral blood and tumour tissue of oral cancer patients and healthy individuals were monitored using limiting dilution analysis. Significantly lower precursor frequencies of proliferating lymphocytes were observed in the peripheral blood and tumour tissue of oral cancer patients. A high frequency of natural killer (NK) cells but low cytotoxic T lymphocytes (CTL) was observed in the peripheral blood compartment of oral cancer patients as compared to healthy individuals. A marked reduction in both NK and CTL frequencies in the tumour tissue compared to the peripheral blood was observed. In the tumour tissues, increased percentages of activated CD4+ lymphocytes as compared to CD8+ lymphocytes were observed. Our results suggest that impaired proliferative and cytotoxic potential of tumour infiltrating lymphocytes may play an important role in the escape of tumour cells from the immune system.

Perioperative chemotherapy in patients with oral cancer

In the final report of a prospective, randomized controlled clinical trial, we report the results of using adjuvant perioperative chemotherapy in patients with oral cancer. Our study is based on the hypothesis of Goldie and Coldman. A total of 135 patients with alveolobuccal carcinoma, classified as clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The patients in the test arm of the study received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The patients in the control arm underwent observation. This analysis at 24 months showed a disease-free survival rate of 61% in the test arm versus 37% in the control arm, which is statistically highly significant (P < 0.01). Analysis of the recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P = 0.002). Our study provided further clinical evidence in support of the concepts of Goldie and Coldman that the timing of chemotherapeutic drugs is critical for a successful end result.

Modulatory effect of cytokines on natural killer and antibody dependent cellular cytotoxicity directed to squamous cell carcinoma targets by lymphocytes from oral cancer patients.

Cells from solid tumours are generally poor targets for natural killer (NK) cytotoxicity and antibody dependent cellular cytotoxicity (ADCC). In this paper, we have analysed NK cytotoxicity and ADCC mediated by peripheral blood mononuclear cells from healthy individuals and oral cancer patients before and after modulation with recombinant interleukin-2 (rIL-2), on target cells derived from two squamous cell carcinoma (SCC) cell lines prior to and after treatment with recombinant interferon-alpha (rIFN alpha). Target SCC cell directed monoclonal antibody 3F8E3 was used in ADCC. The results showed that the unmodulated SCC cells were poor targets for NK and ADCC compared to standard targets (K562 cells and chicken red blood cells, respectively). Modulation of targets alone with rIFN alpha showed moderate increase in their susceptibility while rIL-2 treated effectors could significantly lyse even unmodulated targets. Combined treatment of targets with rIFN alpha and effectors with rIL-2 showed additive enhancement in NK and ADCC activity against SCC cells. Lymphocytes from treated patients with recurrent disease could not efficiently lyse SCC targets even after combined modulation.