Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease.

he purpose of this study was to evaluate the prognostic influence of various subtypes of tumour infiltrating lymphocytes (TIL) in head and neck cancer, in particular the potential influence of regulatory T cells (Treg) in relation to different treatment modalities was addressed. A total of 115 patients with squamous cell carcinoma of the oro- and hypopharynx were selected. A low-risk group of 62 patients with early disease was treated by primary surgery followed by external radiotherapy. A high-risk group of 53 inoperable patients with advanced disease was treated by primary radiochemotherapy. Two-hundred and forty biopsy samples were evaluated by use of the tissue-micro-array technique employing the following markers: CD3, CD4, CD8, CD20, CD68, FOXP3, Granzyme B. In the low-risk group high CD20+ infiltration was associated with a significantly better NED-survival rate (p=0.02). Contrary, among high-risk patients low CD20+ counts indicated significantly better survival (p=0.03). Additionally, in the low-risk group higher numbers of intraepithelial CD8+ TIL (>66.6 per thousand) led to improved NED-survival of 95% vs. 52% (p=0.005). The impact of TIL on prognosis in patients with head and neck cancer may be affected by type of treatment and stage of disease. This finding will influence future studies on the role of TIL in human cancers.

Imbalance between proliferation and apoptosis may be responsible for treatment failure after postoperative radiotherapy in squamous cell carcinoma of the oropharynx.

To assess the prognostic value of apoptosis, proliferation and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). Between 1985 and 1995, a total of 82 patients with 84 tumors were entered onto the study. Forty-two primary tumors (50%) involved the tonsils, 23 (27%) the soft palate, and 19 (23%) the base of the tongue. Median age was 52 years (range, 36-73 years). The pT- and pN-categories (UICC 1997) were: T1 (24), T2 (36), T3 (18), T4 (6), N0 (31), N1 (12), N2 (38), NX (8). Histologically clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given with 60 Gy in 6 weeks and single daily fractions of 2 Gy. The expression of the nuclear Ki-67 labeling index (LI) was investigated by immunostaining using the monoclonal antibody MIB 1 and apoptotic carcinoma cells were identified using the terminal deoxynucleotidyltransferase-(TdT)-mediated dUTP nick end labeling (TUNEL) technique. Median follow-up was 43 months (range, 14-132 months). Overall survival, disease-free survival, and locoregional tumor control rates were 59, 70 and 76% at 5 years. Median values for apoptotic index and Ki-67 labeling were 1.6% (range 0-4.7%), and 20% (range, 0-79%), respectively. Apoptotic index 47 days: 55%, P=0.03), Ki-67 LI (20%: 56%, P=0.006). A significant prognostic impact on locoregional control was noted for the duration of RT (P=0.01), tumor site (P=0.02), and the Ki-67 LI (P=0.02). A low apoptotic index together with higher proliferation rates led to unfavourable local control as low as 25% compared to the patients with higher apoptotic index (70-80%, P=0.009). An imbalance between apoptotic index and proliferation may identify patients with squamous cell carcinoma at high risk for local recurrence after surgery and postoperative RT. Prospective observation of these factors in clinical trials is warranted to further elucidate this phenomenon.

Neck dissection following radiochemotherapy of advanced head and neck cancer--for selected cases only?

PURPOSE: To address the value of neck dissection (ND) in patients with advanced head and neck cancer following primary radiochemotherapy and to specifically analyse its impact on locoregional tumour control, survival and toxicity. PATIENTS AND METHODS: Between 1987 and 1997 (9,335), a total of 142 patients (pts) were treated by primary radiochemotherapy (RCT) according to prospective protocols. There were 64 pts with involvement of the hypopharynx, 57 pts with oropharyngeal and 21 with oral cavity carcinoma. UICC (1997) stages included: 16 pts in stage III, 113 pts in stage IV A, 13 pts in stage IV B. All pts received platin-based RCT up to a median total dose of 70 Gy (range, 60-72 Gy). Six weeks after RCT, pts with complete response of the primary tumour (N=97) were offered a uni- or bilateral ND depending on the initially diagnosed nodal disease as part of a strict institutional policy. Fifty-six pts consented to ND and 41 refused. These two groups were analysed in terms of characteristics, local and regional tumour control, survival and long-term side effects. Median follow-up was 37 months (range, 22-124 months). RESULTS: Among the 56 pts receiving ND, a total of 13 (23%) was found to have residual tumour in the neck specimen. The rates of positive histology according to clinical N category after RCT were: yN0 (2/22[9%]), yN1 (2/10[20%]), yN2a-b (2/10[20%), yN2c-3 (7/14[54%]). Five-year overall survival and disease-specific survival rates for pts with ND were 44 and 55%, for pts without ND 42 and 47%, respectively (P=0.9). No difference was seen for long-term local and regional control between the two patient groups. Comparing the group of patients with and without ND, a trend towards higher subjective morbidity of grade 3 and 4 (LENT-SOMA), i.e. pain recording (24% vs. 17%), dysphagia (48% vs. 35%) and hoarseness (20% vs. 9%) was evident in patients with ND. CONCLUSION: No clear evidence for routine clinical use of ND after RCT in advanced head and neck tumours can be derived from these data. ND may be contemplated in selected cases with multiple residual nodes only.