Roberto Molinari

Salivary duct carcinoma : Clinical characteristics and treatment strategies

Salivary duct carcinoma (SDC) is a highly malignant tumor of the salivary gland.

Malignant Lymphomas of Waldeyer's Ring: Natural History and Survival after Radiotherapy

The natural history of 292 consecutive cases of reticulum cell sarcoma and lymphosarcoma of Waldeyers ring and the survival rate after radiotherapy are reported. In our institute since 1928 from 30 to 35% of pharyngeal neoplasms have been lymphomas, and of these 55% have been reticulum cell sarcomas, 21% lymphosarcomas, and 1% Hodgkins disease. This high incidence may probably be ascribed to the fact that in all malignant lymphomas, irrespective of the clinical presentation, a systematic biopsy of the whole Waldeyers ring was carried out. Pharyngeal lymphomas were confined to Waldeyers ring in 19·6% of cases, with initial spread to contiguous cervical nodes in 43·8%, to distant nodes in 24·2%, and to extranodal tissues in 12·4%. Lymphography showed abnormal retroperitoneal lymph nodes in 38·3% of cases. There was gastrointestinal involvement either initially or later in 17·6% of cases. High-energy radiation therapy to both sides of the neck was the treatment of choice for local and regional disease. It achieved a five-year survival rate of 41·9% in the group of 97 patients treated during the past decade. The incidence of relapse (recurrence and new manifestations) was highest in the first year after treatment.

Cisplatin in advanced salivary gland carcinoma. A phase II study of 25 patients.

A prospective Phase II study was carried out to test cisplatin (CDDP) as a single agent in salivary gland carcinomas. CDDP was administered (100 mg/m2) every 3 weeks to 25 consecutive patients with either recurrent or locally advanced salivary gland carcinoma. Six patients had received prior chemotherapy, and the other patients had had only surgery or radiation therapy or no treatment at all. The response rate was 18% (95% confidence interval [CI], 6% to 41%). Response duration was between 5 and 9 months. Median overall survival time was 14 months. CDDP is a moderately active drug in salivary gland carcinomas. It should be included in multidrug regimens to be tested in prospective studies, which are difficult to carry out due to the rarity of these tumors.

Retrospective comparison of conservative and radical neck dissection in laryngeal cancer.

A retrospective comparison of radical and conservative technique for neck dissection in cancer of the larynx was made, starting from analysis of 98 patients operated on with the conservative procedure (128 cervical neck fields at risk of recurrence) at the Istituto Nazionale Tumori of Milan. Furthermore, a series of 162 patients was selected from more than 500 radical neck dissections performed in the past to set up a series as comparable as possible as far as several parameters were concerned. No significant difference was found between radical and conservative neck dissection with regard to the incidence of recurrences in the operative field, either considering the whole series (2.5% versus 1.6%), or cases with histologically proven metastases (9.4% versus 4.5%). Conservative neck dissection seems as safe as radical neck dissection, at least within the limits set in the present study for the indication of the former procedure, ie, nonsuspect nodes or metastatic mobile nodes not greater than 2.5 cm.

LYMPHORETICULAR SARCOMAS WITH PRIMARY INVOLVEMENT OF WALDEYER'S RING. CLINICAL EVALUATION OF 225 CASES.

A total of 225 consecutive untreated patients with lymphoreticular sarcomas with primary involvement of Waldeyers ring was evaluated (151 without lymphography and 74 with lymphography). On admission, the anatomical distribution of the primary growth within Waldeyers ring was as follows: tonsil, 40%; nasopharynx, 27.5%; base of tongue, 2.7%; soft palate, 2.7%; oropharynx, 0.9%; other sites, 26.2%. In the group studied without lymphography, the disease was confined to Waldeyers ring in 22.5% of cases and had spread to the cervical nodes in 62.3% and to distant nodes in 15.2%. In the group studied more recently with lymphography, these figures were 13.5%, 41.9%, and 44.6%, respectively. At the time of initial evaluation, the lymphoma involved extranodal sites in only 24 of 225. In the 74 cases evaluated with lymphography, the mode of spread was studied by observing the first site of recurrence after radiotherapy. New manifestations occurred in most patients within 2 years from the end of treatment and preferentially in extranodal sites. The involvement of the gastointestinal tract, either at the time of admission or early in the follow‐up, was 20% in the group studied with lymphography. The possibility that a certain number of lymphoreticular sarcomas could arise concomitantly in Waldeyers ring and in the gastrointestinal tract is discussed.

Cancer of the nasopharynx

Nasopharyngeal cancer (NPC) is quite rare throughout Europe, accounting for an annual incidence rate below 1 per 100.000, whereas the highest risk area is South East Asia. A predominant occurrence in males is to be noted. NPC is an etiologically multifactorial disease, most probably involving viral, genetic and environmental factors. Carcinomas of the nasopharynx can be divided into two major histotypes: keratinizing squamous cell carcinomas (WHO-type 1) and non-keratinizing carcinomas (WHO-type 2). The histological type is a prognostic factor and it has a clear impact on the outcome of treatment. Standard therapeutic option for early stages of NPC is radiation, while an integration of radiation therapy and chemotherapy is indicated in more advanced stages.

Local Adoptive Immunotherapy of Advanced Head and Neck Tumors with Lak Cells and Interleukin-2

Since October 1987 a pilot phase I-II study on the effect of loco-regional injections of recombinant interleukin 2 (rIL-2) in association with LAK cells has been performed in advanced, recurrent head and neck cancer patients. Fourteen patients were treated with autologous LAKs and rIL-2 (Glaxo) given peritumorally and in the mastoid region (rIL-2 only in the latter site). LAKs (2-70 × 107) + rIL-2 were injected on the first day of therapy, followed by 9 daily injections of rIL-2 only. The total daily dose of rIL-2 was escalated from 2,400 to 1.8 × 106 IU. Clinical evaluation was performed 30 days from the onset of therapy; 3 partial (95%, 66% and 50% reduction) and 3 minor responses were seen in the evaluated patients. All the other patients with a progressive disease after the first cycle were shifted to palliative chemotherapy. The partial responses were found in patients with a tumor burden « 20 cm2. Cervical node metastasis did not respond to treatment. No relevant side effects occurred. These results indicate that loco-regional immunotherapy with rIL-2 and LAK cells can produce clinical responses in advanced head and neck cancer patients.

Short-term variation in labeling index as a predictor of radiotherapy response in human oral cavity carcinoma.

In vitro determination of [3H]thymidine labeling index (LI) was carried out on squamous cell carcinomas of the oral cavity from 52 patients before and during radiotherapy. Pretreatment LI values ranged from 0.01% to 50%. After administration of the first 10 Gy in five consecutive daily fractions, a decrease in LI was observed in 39 cases and an enhancement in 13 cases, with an overall median 70% decrease in the initial value. The type of variation induced by radiotherapy was not related to pretreatment LI except for tumors with a very low proliferative activity (LI less than or equal to 1.9%), which all showed a marked increase in LI. Pretreatment LI was not indicative of short- or long-term response to radiotherapy, whereas the variation induced on LI after 10 Gy was related to the clinical outcome. A variation in LI of more or less than 70% was not significantly associated (p = 0.077) with clinical objective response (respectively, 85 and 53%). However, all 8 patients who reached a complete regression, notwithstanding an enhancement or a slight decrease in LI, had a local recurrence within 19 months. Conversely, the probability of disease-free survival was 82% for the 11 patients whose tumors had a significant decrease in LI (greater than or equal to 70%) after the first 10 Gy.

Biological markers as indicators of pathological response to primary chemotherapy in oral-cavity cancers.

The predictive role in terms of pathological response and prognostic role of biomarkers such as GST‐π, p53, bcl‐2 and bax expression, immuno‐histochemically detected, and of the S‐phase cell fraction, autoradiographically determined as thymidine labeling index (TLI), were investigated within a prospective randomized phase III clinical trial on squamous‐cell carcinoma of the oral cavity, including surgery or primary chemotherapy (PCT), which foresaw the prospective determination of biological markers. Pathological response was defined as the achievement after PCT of a pathological complete remission or the presence of microresidual disease. The study was performed on tumors obtained from a series of 100 previously untreated patients with resectable T2–4N0–2M0 carcinoma. All biomarkers were unrelated, except for an inverse relation between TLI and GST‐π and a direct relation between bcl‐2 and bax expression. In patients treated with surgery alone, 3‐year disease‐free survival (DFS) appeared to be weakly, but not significantly, related only to GST‐π and p53 expression. In patients treated with PCT, pathological response and DFS were independent of p53 expression and cell proliferation. Conversely, low GST‐π and bax expression were indicative of pathological response but lost relevance as predictors of DFS, whereas absence of bcl‐2 was associated with high probability of 3‐year DFS in the overall series as well as in non‐responding patients. Within this latter sub‐set, all patients with bcl‐2‐positive tumors relapsed within 1 year of surgery, whereas a 60% probability of 3‐year DFS was observed for patients with bcl‐2‐negative tumors (p= 0.02). This interim analysis appears to indicate that some biofunctional markers can provide information on pathological response to PCT and could help in understanding treatment efficacy at a cellular level. Int. J. Cancer (Pred. Oncol.) 79:619–623, 1998.

Growth rate of head and neck tumors

Abstract The actual doubling time for 17 local recurrences of head and neck tumors was calculated by use of the method of Philippe and LeGal. The median value of 9.5 days placed them in the class of fast-growing tumors. Site and age did not seem to influence their growth; instead, they seemed to grow faster in females than in males. Comparison between doubling times of local recurrences and pulmonary metastases collected from the literature showed a statistically significant difference: pulmonary metastases grow slower.