Yukio Inuyama

Prognostic factors influencing relapse of squamous cell carcinoma of the maxillary sinus

In 95 surgically staged patients with squamous cell carcinoma of the maxillary sinus, multivariate regression analyses were employed to identify prognostic factors. Possible prognostic factors for local control were TNM stage and type of surgical procedures: T2 or T3 tumors and use of total maxillectomy showed better local control rates (P < 0.01). High radiation doses of 40 Gy or more also seemed to be of prognostic significance: P < 0.2 for 40 to 60 Gy, and P < 0.1 for 60 Gy or more. The risk of cervical relapse increased when the cheek or alveolus was grossly involved (P < 0.2). However, since cervical relapse frequently accompanied uncontrollable primary recurrence or distant spread, and since cervical relapse alone was frequently salvaged by radical neck dissection, prophylactic irradiation to the neck is not recommended. Sex, age, nodal state, addition of chemotherapy, total doses of bleomycin or 5‐fluorouracil (5‐FU), or intra‐arterial administration of chemotherapeutic agents did not appear to be of prognostic significance.

Computed tomography of malignant tumors of the nasal cavity and paranasal sinuses

Staging of malignant tumors of the nasal cavity and paranasal sinuses by computed tomography (CT) was studied in a total of 49 patients, 33 with squamous cell carcinoma and 16 with tumors of other histologic types. Involved sites by the tumor were studied, and clinical staging was made using CT findings alone according to AJC classification for maxillary sinus tumors. Surgical findings for comparison were available for most cases. Of 33 squamous cell carcinomas and of 16 tumors with other histologic types, the maxillary sinus was the site of origin in 29 and eight, respectively. Of these 37 maxillary sinus tumors, 11 were staged T3, 26 T4, and none was staged T1 or T2. None of these tumors were down staged, and one T3 was upstaged after surgical procedures, although all sinuses were not explored in some cases. Sinusitis due to obstruction was indistinguishable from the tumor without bone destruction. And the determination of the site of origin was difficult in some cases. Despite these, CT should be used for pretreatment evaluation of the tumors of these sites.

Improved survival of patients with nasopharyngeal squamous cell carcinoma

One hundred and one patients with nasopharyngeal squamous cell carcinoma (NPC) were treated with irradiation. The UICC TNM staging system (1978) was used: 6 patients were T1N0, 10 T2N0, 5 T3N0, 13 T4N0, 11 T1N+, 18 T2N+, 19 T3N+ and 19 T4N+. Since 1978, 34 patients were examined with computed tomography (CT) at first presentation. Fourteen (41%) of the 34 tumors were upstaged based on the CT findings alone. The technique of radiation therapy was markedly changed around 1978. The fields to the primary site and neck were enlarged. Two-year relapse-free survival was significantly better for the post-CT era than pre-CT era. This was mainly because of improved local-recurrence-free survival, and cervical-relapse-free survival. Improved local-recurrence-free survival, however, was appreciated in only T3 + T4 patients; there was no difference in T1 + T2 patients. It is suggested that merely enlarging radiation fields or increasing radiation doses could not be curative for some subpopulations. In order to increase local control rates further, we have started to use intracavitary irradiation with an after-loading technique as a boost. Preliminary results are encouraging.

Patterns of relapse of squamous cell carcinoma of the maxillary sinus

Ninety‐five M0 patients with squamous cell carcinoma of the maxillary sinus were treated mainly with combined surgery, radiation and chemotherapy. They were staged surgically according to the American Joint Committee TNM classification: 3 were T2N0, 55 T3N0, 27 T4N0 and 10 T3–4N1–3 patients. Relapse developed in 66 patients (69%): one (33%), 35 (64%), 22 (81%) and 8 (80%), respectively. All patients experienced relapse within 2 years after diagnosis. Local recurrence developed during the course of disease in 52 (79%) of the 66 patients who relapsed. Three patients with cervical relapse and one with local recurrence were successfully salvaged with rescue surgery. Local control achieved in 39 (41%) of the 95 patients: 2 (67%), 28 (51%), 7 (26%) and 3 (30%) in T2N0, T3N0, T4N0 and T3–4N1–3 patients, respectively. Autopsy findings of 17 patients are presented. An impact of computed tomography on staging of maxillary sinus tumors is discussed.

Maxillary squamous cell carcinomas staged by computed tomography

In 72 patients with maxillary squamous cell carcinoma, computed tomography (CT) alone was used for T-staging according to the AJC classification. Five, 31, and 36 tumors were diagnosed as T2, T3, T4, respectively. In N0 patients with a minimum follow-up of 2 years, local control rates for T2, T3, and T4 tumors were 33% (1/3), 64% (16/25) and 38% (9/24), respectively. Addition of maxillectomy to treatment seemed to have improved the local prognoses in T3 and T4 tumors. High radiation doses of 60 Gy or more seemed to be beneficial for patients with T3 tumors and without maxillectomy. CT will be of great help in classifying tumors objectively. But more importantly, it will reveal resectability and dictate treatment of choice by delineating the tumor extent precisely.

Local control of squamous cell carcinoma of the mobile tongue: an experience of different modalities

From 1966 through 1983, 163 patients with squamous cell carcinoma of the mobile tongue were treated. Fifty-two patients were staged as T1N0, 77 as T2N0, 14 as T2N+, 8 as T3N0, 7 as T3N+, and 5 as T4. The follow-ups were complete. Treatment modalities varied considerably during that period, because of increasing difficulty to use radioactive sources by regulations. All T3N+ and T4 patients died shortly after treatment. Five year absolute survivals for the T1N0, T2N0, T2N+, and T3N0 patients were 87%, 60%, 27% and 63%, respectively. Local recurrence free survivals at 5 years for the T1N0, T2N0, T2N+, and T3N0 patients were 72, 48, 58, and 88%, respectively. Local recurrence free survivals seemed to be better with Ra-226 needling +/- external irradiation (EXT) than other modalities. Because many patients with local recurrence were salvaged, ultimate local-disease-free survivals should also be considered. They were 96 and 70% at 5 years for the T1N0 patients treated with Ra-226 +/- EXT, and with surgery +/- EXT, respectively; the corresponding figures for the T2N0 patients were 83 and 64%. For these reasons, Ra-226 needling may be preferable to other modalities as initial treatment. Although cervical failures did not develop after 2 years of treatment, late local recurrences were rather common, even after 5 years. Long-term follow-up is mandatory for the management of the patients, and analyzing and comparing the results.

Neoadjuvant chemotherapy in maxillary sinus carcinoma with cisplatinum and peplomycin intraarterial infusion.

The purpose of this paper is to present our preliminary assessment of a new multimodal treatment including neoadjuvant chemotherapy with cisplatinum and peplomycin for maxillary sinus carcinoma. Fifteen patients with squamous cell carcinoma of the maxillary sinus carcinoma seen at Keio University Hospital, with Stage III and IV disease, were enrolled in this trial between January 1982 and January 1985. Regimen of chemotherapy was as follows: day 1, 50 mg/m2 of cisplatinum, intraarterial infusion over 2 hr, days 2-6, peplomycin at a dose of 5 mg/day, intraarterial infusion over 5 hr. Routinely, radiotherapy of 40 Gy by Linac was given to the primary site, concomitantly combined with 5-fluorouracil intraarterial injections only during the first 10 days, 2 weeks after the end of initial chemotherapy. Additional treatment was performed according to the extent of residual tumor. Response to initial chemotherapy revealed that complete response was achieved in 7 and partial response in 6 out of 15 patients with a response rate of 87%. Nine patients required no surgical intervention while 6 underwent a surgical resection. Median follow-up in this group of patients is 20 months. Thirty-month survival rate calculated by Kaplan-Meiers method was 83%. Chemotherapy toxicity was mild in most cases. This pilot study does not provide conclusive survival information, but the results obtained are encouraging.

Treatment of Non-Hodgkin Lymphomas in the Nasal Cavities and Paranasal Sinuses a Failure Analysis

Twenty-five patients with sinonasal lymphoma were treated mainly with irradiation. All were non-Hodgkin lymphomas of diffuse type. Twenty patients had stage IA, 2 had stage IB, 1 stage IIA, 1 stage IIIA, and 1 stage IVA disease. Relapse developed in 16 (64%) of the 25 patients, with a failure rate of 64 per cent in the stage I patients (14/22). Most patients with failures had distant spread of the disease with or without local recurrence. Only one patient had local recurrence alone at the first relapse. Histologic classification according to the new working formulation seemed to be a reliable prognostic indicator for relapse: failure rates for low, intermediate, and high grade lymphomas were 0 per cent (0/2), 46 per cent (6/13), and 100 per cent (10/10), respectively. Computed tomography was valuable for planning of radiation therapy and for follow-up.

Combination Chemotherapy With Cisplatin and Peplomycin in Squamous Cell Carcinoma of the Head and Neck

Ninety-three patients with head and neck cancer were treated with combined cisplatin-peplomycin chemotherapy (CP therapy). Cisplatin (CDDP) 50 mg/m2 i.v. (intravenous) or i.a. (intraarterial) over 2 hr was given with hydration and mannitol diuresis on day 1. From day 2 through day 6, peplomycin (PEP) 5 mg/day was administered by 5-hr i.v. or i.a. infusion, or 24-hr continuous hypodermic injection. Of 85 who were evaluable, there were 22 complete responses or CR (26%) and 36 partial responses or PR (42%), with an overall response rate of 68%. Concerning of the route of administration, i.a. infusion obtained the higher CR and overall response rates than i.v. infusion. Effectiveness was clearly greater in previously untreated cases than in cases that had received some previous therapeutic modality. Looking at response in relation to the number of the courses, at least 2 courses of CP therapy are required. Side effects were recognized in 68 out of 87 evaluable cases (78%). Nausea and vomiting were the most common (62%). Renal toxicity was observed in 24% and was mostly transient. From the above results, it is considered that the CP therapy is effective, not only for the palliative treatment of advanced and recurrent cancer of the head and neck, but also as neo-adjuvant chemotherapy of stage III and IV cases.

Clinical trials on UFT in the treatment of head and neck cancer.

A new anticancer agent, UFT which is a mixture of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 1:4 was administered orally at a dose of 600 mg/day every day. Forty-three patients were evaluable. Eight patients achieved a complete response and eight achieved a partial response with an overall response rate of 37.2%. In terms of response by histology, a response rate was 32.4% (11/34) in cases of squamous cell carcinoma and 75% (3/4) in cases of adenocarcinoma. A response rate by primary site was 57.1% in the nose and paranasal sinuses, 50.0% in the oropharynx and 30.0% in the oral cavity. A response rate was 36.1% in patients with prior treatment and 42.9% in patients with no prior treatment, but there was no statistical significance. Eight of 43 patients developed toxic effects. Most of them were mild such as anorexia, nausea, and stomatitis, but in one case of maxillary sinus carcinoma, severe bone marrow suppression was observed. UFT is a considerably effective and useful drug in the treatment of head and neck cancer. It is possible to increase cure rate by examining various usages of UFT.