A phase I clinical trial of recombinant human tumor necrosis factor given daily for five days.

A phase I trial of human recombinant tumor necrosis factor (rH-TNF) has been carried out in patients with advanced solid tumors. Sixty-six courses of the drug were given by 1 h IV infusion, daily for 5 days to 33 patients at doses of 5, 10, 20, 30, 45, 60, and 80 x 10(4) U/m2/day. All patients received isotonic saline (up to 21/day) and either indomethacin or ketoprofen. Acute toxicity resembled that seen with the phase I study of a single dose (5). Dose limiting toxicity was acute, rapidly reversible, hepatic dysfunction and hypotension. Hypertension during drug infusion and dyspnea were marked in some patients. There was one complete and one minor response, both in patients with renal cell carcinoma. The dose of 80 x 10(4) U/m2/day x 5 was poorly tolerated and the recommended starting dose for phase II studies is 60 x 10(4) U/m2/day x 5. Caution is recommended in treating patients with pre-existing hepatic function abnormalities, hypertension, hypotension or significant obstructive airway disease.

Squamous cell carcinoma of the pyriform sinus.

At the Roswell Park Memorial Institute, 111 patients were treated for squamous cell carcinoma of the pyriform sinus over a 15-year period. Treatment modalities included surgery, radiation therapy, or a combination of both. A retrospective study was carried out to determine how these treatments, used singly or in combination, affected the cure rate. TNM clinical staging and recurrence patterns were studied, and a high tendency for distant metastases was documented. The five-year survival figure in this study was 29% (28/97).

Nonsimultaneous bilateral radical neck dissection.

From January 1963 to December 1977, 63 patients underwent a therapeutic second (staged) neck dissection at our institute. The mean interval between the first neck dissection and the second neck dissection was 13.2 months; 58.7% of the second neck dissections were performed between 6 and 12 months after the first. Forty-six patients had histologically positive and 17 patients had histologically negative nodes in the first neck clearance; 57 patients had histologically positive and 6 patients had histologically negative nodes in the second neck clearance. Forty-two of the 63 patients had bilateral nodal disease, while 2 patients had no disease in either side of the neck. Fifty-four percent of the patients had postoperative complications; 30% developed immediate postoperative edema, and 14% had wound infection. The overall three-year and five-year survival rates were 60% and 38%, respectively. Patients who had bilateral histologically positive nodes had a 16% five-year survival rate, while those who had histologically positive nodes in one side of the neck only had a 26% five-year survival rate.

Reconstruction of massive orbito-maxillary-cheek defects.

The problem of soft-tissue reconstruction in patients who must undergo radical resection of the maxilla, orbit, and cheek is discussed. This problem is greatly complicated by previous radiation therapy or by the need for postoperative radiation therapy. Restoration of oral competence is of primary importance and usually cannot be satisfactorily accomplished with prosthetic appliances when a stable support base is lacking. An orderly reconstructive plan with a high success rate is of the utmost help to the surgeon facing this problem. A multistaged procedure utilizing a deltopectoral flap that has been successful in 7 patients is presented.

Chemotherapy for advanced and recurrent squamous cell carcinoma of the head and neck with high and low dose cis-diamminedichloroplatinum.

Cis-diamminedichloroplatinum (cis-DDP) in both a high dose regimen of 120 mg/M2 every three weeks with pretherapy hydration and mannitol diuresis and a low dose regimen of 20 mg/M2 daily for five days and cycled every three weeks have effective antitumor activity in approximately one third of patients. Its toxicity in both regimens appears to limit the number of cycles of administration and the duration of response. Further trials with dose schedules intermediate between the present high and low dose schedules are needed to provide a suitable and effective one day regimen every three to four weeks that can be given on an outpatient basis and on a long-term basis.

Management of "localized" oral cancer.

We have outlined the clinical manifestations of "localized" malignant lesions of the intraoral cavity, their clinical behavior after intraoral excision, and their control rate employing intraoral excision as primary therapy. We must keep in mind that these small "localized" cancers are potential "killers" and the five year mortality from disease in our series was 25 per cent. This mortality may decrease with (1) more careful selection when patients are included in the "localized" lesion group and (2) earlier use of composite procedures in questionable cases.

Significance of site and nodal metastases in squamous cell carcinoma of the epiglottis.

One hundred twelve patients treated by surgery alone for squamous cell carcinoma of the epiglottis were retrospectively reviewed. The results showed: (1) 27 per cent of patients with N0 disease had microscopic nodal metastases; (2) 35 to 47 per cent of patients with N0 and N1 disease and histologically positive nodes (micrometastases) in the initial neck dissection developed contralateral nodal metastases; (3) 36.9 per cent of the patients who had nodal micrometastases (histologically positive) survived five years, as contrasted with 94.5 per cent of those who did not have node involvement; (4) 53.2 per cent of the patients who had nodal metastases in one neck and 16 per cent of those who had metastases in both necks survived five years; (5) when the primary tumor in the epiglottis was located in the midline or there was bilateral supraglottic involvement, 18 to 50 per cent of patients developed contralateral ("second") neck nodal metastases; (6) performing early elective contralateral ("second") neck dissection shortly after recovery from the initial surgery may improve survival of patients in whom either the "first" neck dissection showed microscopic nodal metastases and/or the primary tumor was located either in midline or there was bilateral supraglottic involvement.

Modified radical neck dissection for metastatic carcinoma of the thyroid. A reappraisal.

From January 1958 through December 1983, 56 modified radical neck dissections were performed on 47 patients with metastases to the cervical nodes from differentiated carcinomas of the thyroid. In nine patients, a second modified radical neck dissection was performed either simultaneously or at a later date. Lymph node clearance was performed on all but one surgical specimen. The number of nodes in each specimen ranged from 10 to 96, and the number of involved nodes ranged from 1 to 20. Thirty-eight of the 56 neck specimens contained four or more positive nodes. Seventeen patients were followed for 10 to 26 years, 18 patients for 5 to 9 years, and 5 patients for less than 5 years. Seven other patients died, three from other causes and four from lung metastases. There were no recurrences in the neck sides that would have been cleared if standard radical neck dissection had been performed. This reappraisal with long-term follow-up supports our initial impression that a modified radical neck dissection sparing the spinal accessory nerve, the sternocleidomastoid muscle, the internal jugular vein, or any combination thereof is an effective procedure for differentiated cancer of the thyroid, with preservation of good shoulder function and improvement in the cosmetic appearance of the neck.

Total glossectomy.

Forty-five patients had a "total" glossectomy for initial advanced tongue carcinoma or for recurrent carcinoma. Forty percent of the patients (18) had a total laryngectomy at the time of glossectomy. Forty-nine percent of the patients (22) had either a lateral or anterior mandibulectomy at the time of glossectomy. Seventy-one percent of the patients (15 of 21) who had an intact larynx and 12.5 percent who had laryngectomy (3 of 24) had some degree of useful speech. Thirty-one percent of the patients (14 of 45) had no problems in deglutition whereas 53 percent of the patients (24) needed a nasogastric tube, 4 patients inserted the feeding tube themselves, 2 had a cervical esophagostomy, and 1 had a special prosthesis for feeding purposes. Thirty-seven percent of the patients (10 of 27) had considerable aspiration problems. Twenty-two percent (6 patients) needed a laryngectomy, and 7.5 percent (2 patients) needed a cervical esophagostomy to prevent further problems. Seven and one-half percent of the patients (2) succumbed to serious pulmonary infection. In this study, total glossectomy had a salvage rate of 65 percent at 6 months postoperatively, 27.5 percent at 1 year, 25 percent at 2 years, 25 percent at 3 years, 20 percent at 5 years, and 10 percent at 10 years.

Suppressive therapy of thyroid nodules in patients with previous radiotherapy to the head and neck.

This is a prospective, randomized study of 431 patients with palpable thyroid nodules who had previous radiotherapy for benign disorders of the head and neck area to determine the response of the thyroid nodules to suppressive therapy and the incidence of thyroid cancer in patients who could not be suppressed and had surgery. A complete response was achieved within 6 months in 18.3 percent of the patients, and in an additional 26 percent of patients between 7 and 12 months postoperatively. Twenty percent of the patients showed complete disappearance of nodules after 1 to 2 years of suppressive therapy. Twenty-two percent who underwent surgery showed carcinoma. If suppressive therapy is to be used, a trial of 1 year rather than 3 or 6 months, as often recommended, may be appropriate.

Major head and neck reconstruction using the deltopectoral flap. A 20 year experience.

Six hundred seventy-eight deltopectoral flaps were raised in 604 patients, 125 of which were delayed and 215 of which were used in previously irradiated beds. The rate of major flap necrosis was 16.9 percent and the overall rate of complications, 51.4 percent. Delay in creating the deltopectoral flap had no influence on the risk of complications and necrosis, whereas the use of the flap in a previously irradiated bed was associated with a significantly increased risk of major flap necrosis. The least flap loss occurred when the deltopectoral flap was used without tubulation for skin coverage only. Complications and flap necrosis occurred most frequently when flaps were tubulated in a reversed manner or used for lining of major portions of or for total oropharyngeal and hypopharyngeal reconstruction. The deltopectoral flap remains a useful, reliable, and versatile regional flap that can be used alone or in combination with other flaps in selected circumstances for major head and neck reconstruction.

Immunologic patterns of regional lymph nodes in squamous cell carcinoma of the floor of the mouth. Prognostic significance.

Histologic specimens from 43 patients with squamous cell carcinoma of the floor of the mouth treated exclusively by surgery were studied with special attention paid to the reactivity of regional lymph nodes. The lymph nodes were classified into four microscopic patterns of immune response: lymphocyte predominance for sinus histiocytosis, germinal center predominance, unstimulated, and lymphocyte depletion. No nodes of the lymphocyte depletion pattern were found. Correlations were then made between the patterns and survival rate at 5 year follow-up. The results showed that those patients with lymph nodes that demonstrated lymphocyte predominance had a better survival rate than patients with germinal center predominance and the unstimulated patterns. These correlations were independent of stage and metastatic nodal status and the differences were statistically significant (p less than 0.5). Morphologic assessment of immunologic activity in lymph nodes that drain carcinoma of the floor of the mouth appears to be of significant prognostic value.

Correlation between prognosis and degree of lymph node involvement in carcinoma of the oral cavity.

Accurate histologic determination of lymph node metastasis is most important in predicting prognosis in patients who undergo radical neck dissection. In this study of 340 determinate patients, the five year survival was 75 per cent when lymph nodes were histologically negative, 49 per cent when one lymph node was positive, 30 per cent when two lymph nodes were positive, and 13 per cent when three or more nodes were positive. Other factors useful in predicting prognosis are, to some extent, the level of lymph node metastasis in the neck, and the presence or absence of capsule penetration and soft tissue involvement. Those patients with metastasis to three or more lymph nodes had a five year survival of 13 per cent and belong to a high risk group. In this high risk group among those who died, the incidence of recurrence in the neck was 72 per cent, and the incidence of distant metastasis was 70 per cent. When autopsy was performed, more still were found to have distant metastasis, 75 to 80 per cent. Most of these high risk patients already have systemic dissemination of cancer at the time of their initial therapy; therefore, the addition of a systemic form of adjuvant therapy, such as chemotherapy and/or immunotherapy, is justified.

Nasopharyngeal carcinoma: results of treatment over a 27 year period, 1950 through 1977.

In a retrospective study, 107 patients with squamous cell carcinoma of the nasopharynx were reviewed. One hundred six patients were treated primarily by radiation therapy and only one by surgery. The overall 5 year survival rate free of disease was 29 percent. Possible prognostic factors of age, sex, cancer stage, histopathology, and treatment were studied. The younger patients did significantly better. Patient's sex and clinical stage were not significant factors in this study. The patients with lymphoepitheliomas, anaplastic carcinomas, and those with poorly differentiated cell types did significantly better than those with more differentiated lesions. Fifty-five patients received irradiation therapy of 6,000 rads by external ports alone, and 51 patients received radiation therapy of 6,000 rads by external ports supplemented by 1,500 rads using an intracavitary radium applicator. The higher survival rate with the use of the supplementary dosage was only suggestively significant.

Metastatic patterns in squamous cell cancer of the head and neck.

This retrospective study on 832 head and neck cancer patients who died between 1961 and 1985 was carried out to determine the incidence and sites of distant metastases. All patients were staged prior to definitive treatment and were autopsied. The overall incidence of distant metastases was 47 percent. The hypopharynx had the highest incidence of distant metastases (60 percent), followed by the base of the tongue (53 percent) and the anterior tongue (50 percent). Of the 387 patients with distant metastases, 91 percent died with uncontrolled tumor either at the primary site or in the neck. The lung was the most common site of distant metastases (80 percent), followed by the mediastinal nodes (34 percent), the liver (31 percent), and bone (31 percent). Overall, 6 percent of the patients had stage I disease, 20 percent had stage II disease, 32 percent had stage III disease, and 43 percent had stage IV disease. The highest incidence of distant metastases was found in those patients with stage IV disease (193 of 350 patients, 55 percent). We believe that the initial stage of disease does appear to be related to the ultimate development of the distant metastases.

Management of advanced glottic carcinomas.

One hundred twenty-eight patients with T3 or T4 glottic cancers were treated by initial surgery; 59 had a total laryngectomy and 69 had total laryngectomy with regional node dissection. Fifty-eight percent of the total laryngectomy group and forty-nine percent of the total laryngectomy with neck dissection group remained free of disease for 5 or more years. Forty-seven percent (60 of 128 patients) treated surgically developed regional recurrences requiring further treatment. Nine patients had evidence of widespread metastases, leaving 51 suitable for salvage radiotherapy. Twenty-three percent (12 of 51 patients) were salvaged with radiotherapy given for postoperative recurrences. Twenty-five patients received an initial 6,600 rads to larynx and neck with curative intent, 28 percent of whom remained free of disease for 5 or more years. Seventeen percent of patients were salvaged with one laryngectomy for persistent or recurring tumors. Initial total laryngectomy gave better survival figures for advanced glottic carcinoma.

Surgical management of squamous cell carcinoma of the floor of the mouth.

Treatment failure and survival in 209 patients with squamous cell carcinoma of the floor of the mouth treated with surgery as the single curative modality are reported. Fifty percent of the patients had stage III and IV disease. The primary tumor was excised with 1 to 2 cm margins and the mandible was resected in 73 percent of the patients; 77 percent underwent radical neck dissection. No cures were observed in 11 patients with involved surgical margins on permanent section. For 198 patients with uninvolved margins, determinate survival at 5 years for all stages was 49 percent and 69, 64, 46, and 26 percent for stages I through IV (p less than 0.01). The most common sites of initial and ultimate treatment failure were the neck (42 of 72 patients) and distant metastases (33 of 53 patients), respectively. Treatment of the neck is identified as an unresolved problem in the management of early stage disease. Recent improvements in survival for stage III and IV disease are accounted for, in part, by adequate surgical resection.

Radiotracer uptake in medullary carcinoma of the thyroid.

A patient with pathologically confirmed medullary carcinoma of the thyroid with lymph node metastases was noted to show uptake of radiothallium, radiopertechnetate, and radioiodine. A perchlorate washout test was markedly positive, indicating that the uptake was largely due to trapping.

Carotid artery hemorrhage and ligation in head and neck cancer.

During a 20-year period, 77 patients who underwent ligation of the common or internal carotid artery were analyzed for the site, side of hemorrhage and/or ligation, with incidence of rebleed, previous treatment (surgery and/or radiation therapy), the type of incision utilized for resection, the incidence of preoperative and intraoperative hypotension and hemiplegia. The immediate mortality and subsequent follow-up of the patients were also noted.