Reactivity of monoclonal antibody 17.13. with human squamous cell carcinoma and its application to tumor diagnosis.

Monoclonal antibody 17.13., derived from a fusion of splenocytes of a BALB/c mouse immunized with a surgically resected poorly differentiated human laryngeal recurrent squamous cell carcinoma (SCC) with mouse Sp2/0 cells, is an IgM-K which recognizes a cytoplasmic component of basal cells. Tissue sections of malignant and normal squamous epithelium, tumors of nonsquamous origin, and normal and malignant cytological specimens were tested with an immunoperoxidase assay. Seventy-nine of 81 (98%) SCC of the head and neck, 26 of 26 (100%) SCC of the cervical and female gynecological tract, 29 of 30 (97%) SCC of the lung, 19 of 19 (100%) SCC of the oral cavity, and 17 of 17 (100%) SCC-involved neck lymph nodes reacted strongly. Various carcinomas from breast, colon, ovary, and others were unreactive. In normal squamous epithelial tissues, monoclonal antibody 17.13. reacts only with basal cells but not the cells above the basal layers. Normal tissues from heart, liver, spleen, kidney, bladder, colon, ovary, stomach, pancreas, breast, lung, prostate, thyroid, and lymph nodes were unreactive with the exception of myoepithelial cells. Monoclonal antibody 17.13. may be useful in the diagnosis and management of SCC.

p53 mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy.

Radiation resistant squamous cell carcinoma of the head and neck cell line JSQ-3 carries a mutant form of tumor suppressor gene p53. Treatment of these cells with an adenoviral vector containing wild-type p53 (Av1p53) was able to inhibit their growth in vitro and in vivo while having no effect on normal cells. More significantly, introduction of wtp53 also reduced the radiation-resistance level of this cell line in vitro, in a viral dose-dependent manner. Furthermore, this radiosensitization also carried over to the in vivo situation where the response of JSQ-3 cell-induced mouse xenografts to radiotherapy was markedly enhanced after treatment with Av1p53. Complete, long-term regression of the tumors for up to 162 days was observed when a single dose of Av1p53 was administered in combination with ionizing radiation, demonstrating the effectiveness of this combination of gene therapy and conventional radiotherapy. This sensitization of tumors to radiation therapy by replacement of wtp53 could significantly decrease the rate of recurrence after radiation treatment. Since radiation is one of the most prevalent forms of adjunctive therapy for a variety of cancers, these results have great relevance in moving toward an improved cancer therapy.

Iodine 125 suture implants in the management of advanced tumors in the neck attached to the carotid artery.

Between 1975 and 1982, 38 patients with locally advanced head and neck cancer attached to the carotid artery underwent surgical excision followed by iodine 125 vicryl suture implant in the neck. Most patients had neck masses that were greater than 6 cm and stage IV disease without clinically evident distant metastases. Twelve patients had received no previous therapy while 26 underwent an implant for recurrent disease. The local control rate in the implant volume was 79%. The local and regional control rate in all head and neck sites was 53%. The mean survival was 11 months. The overall complication rate was 26%. There was no significant correlation of local control or complications with the minimum total dose, volume implanted, individual 125I seed strength, or total seed strength. In patients with large masses attached to the carotid artery, surgical resection followed by a 125I implant for residual disease is a viable alternative to resection of the carotid artery.

125I vicryl suture implants as a surgical adjuvant in cancer of the head and neck.

Sixty-four intraoperative 125I seed implants using absorbable suture (Vicryl) carriers were performed in 53 patients with head and neck cancers at Stanford between 1975 and 1980. In previously untreated patients, local control in the implanted volume or in all head and neck sites was obtained in 79 and 71%, respectively. Five of these patients (40%) remained NED. Of 34 patients with recurrent carcinomas, local control was obtained in the implant volume in 20 (59%), while 38% had no recurrence post-implantation in any head and neck site. The incidence of complications is correlated with 125I radiation doses, total millicuries inserted, seed strength used, and tissue volume implanted for both untreated patients and those with local recurrences. Guidelines for the optimal use of the above 4 parameters are also presented. We conclude that 125I seed Vicryl intraoperative suture implants are an effective surgical adjuvant in the treatment of advanced, previously untreated or recurrent head and neck cancers.

Radiosurgery for skull base malignancies and nasopharyngeal carcinoma.

PURPOSE: Patients with skull base lesions present a challenging management problem because of intractable symptoms and limited therapeutic options. In 1989 we began treating selected patients with skull base lesions using linac stereotactic radiosurgery. In this study the efficacy and toxicity of this therapeutic modality is investigated. METHODS AND MATERIALS: Forty-seven patients with 59 malignant skull base lesions were treated with linac radiosurgery between 1989 and 1995. Eleven patients were treated for primary nasopharyngeal carcinoma using radiosurgery as a boost (7 Gy-16 Gy, median: 12 Gy) to the nasopharynx after a course of fractionated radiotherapy (64.8-70 Gy) without chemotherapy. Another 37 patients were treated for 48 skull base metastases or local recurrences from primary head and neck cancers. Eight of these patients had 12 locally recurrent nasopharyngeal carcinoma lesions occuring 6-96 months after standard radiotherapy, including one patient with nasopharyngeal carcinoma who developed a regional relapse after radiotherapy with a stereotactic boost. Lesion volumes by CT or MRI ranged from 0 to 51 cc (median: 8 cc). Radiation doses of 7.0 Gy-35.0 Gy (median: 20.0 Gy) were delivered to recurrent lesions, usually as a single fraction. RESULTS: All 11 patients who received radiosurgery as a nasopharyngeal boost after standard fractionated radiotherapy remain locally controlled (follow-up: 2-34 months, median: 18). However, one patient required a second radiosurgical treatment for regional relapse outside the initial radiosurgery volume. Thirty-three of 48 (69%) recurrent/metastatic lesions have been locally controlled, including 7 of 12 locally recurrent nasopharyngeal lesions. Follow-up for all patients with recurrent lesions ranged from 1 to 60 months (median: 9 months). Local control did not correlate with lesion size (p = 0.80), histology (p = 0.78), or radiosurgical dose (p = 0.44). Major complications developed after 5 of 59 treatments (8.4%), including three cranial nerve palsies, one CSF leak, and one trismus. Complications were not correlated with radiosurgical volume (p = 0.20), prior skull base irradiation (p = 0.90), or radiosurgery dose > 20 Gy (p = 0.49). CONCLUSION: Stereotactic radiosurgery is a reasonable treatment modality for patients with skull base malignancies, including patients with primary and recurrent nasopharyngeal carcinoma. The dose distribution obtained with stereotactic radiosurgery provides better homogeneity than an intracavitary implant when used as a boost for nasopharyngeal lesions, especially lesions which involve areas distant to the nasopharyngeal mucosa.

Iridium-192 interstitial implant and external beam radiation therapy in the management of squamous cell carcinomas of the tonsil and soft palate.

PURPOSE: To evaluate the results, techniques, indications and complications of interstitial brachytherapy in the management of squamous cell carcinomas of the tonsil and soft palate, we reviewed the Stanford University Medical School experience with this modality. METHODS AND MATERIALS: Between May 1975 and January 1990, 37 patients with squamous cell carcinomas of the Tonsillo-Palatine region were treated with a combination of external beam irradiation and a removable Iridium-192 interstitial implant. The mean age of these patients was 56. Twenty-two were males and 15 were females. The stage distribution included four patients with Stage I, 5 with Stage II, 10 with Stage III, and 18 with Stage IV cancers. Thirty-two percent (12/37) of these patients had T3 or T4 lesions. Forty-nine percent (18/37) had stage N2 or N3 cervical lymphadenopathy. All 37 patients received initial external beam irradiation to the primary, bilateral necks, and supraclavicular region (mean dose: 5400 cGy, range 4000-6600). Eighteen patients (49%) also received neck dissections. All 37 patients received an interstitial Irridium-192 implant using a combination intraoral swage and external looping technique. The mean dose was 2700 cGy (range 2000-4000 cGy) to an average volume of 24 cc (range 5-81). RESULTS: Local control was obtained in 95% (35/37) of the patients. Eighty-seven percent (32/37) of the patients have remained disease-free in the neck. Nine patients have developed second primary lesions, and one developed pulmonary metastasis. Fifteen patients have died (6 succumbed to their cancers, 6 to second primaries, 2 to intercurrent disease, 1 from an unknown cause). The actuarial freedom from relapse is 75%, and overall survival is 64% at 5 years, with a mean follow up of 43 months (range 5-110). Complications were limited to one case of osteoradionecrosis of the mandible and one tonsillar ulcer. Functional and esthetic integrity was preserved in most of these patients. CONCLUSION: Iridium-192 interstitial implant boost combined with external beam radiation therapy is a safe and effective therapy in the management of locally advanced carcinomas of the tonsil and soft palate.

Lymph node metastasis in maxillary sinus carcinoma.

PURPOSE: To evaluate the incidence and prognostic significance of lymph node metastasis in maxillary sinus carcinoma. METHODS AND MATERIALS: We reviewed the records of 97 patients treated for maxillary sinus carcinoma with radiotherapy at Stanford University and at the University of California, San Francisco between 1959 and 1996. Fifty-eight patients had squamous cell carcinoma (SCC), 4 had adenocarcinoma (ADE), 16 had undifferentiated carcinoma (UC), and 19 had adenoid cystic carcinoma (AC). Eight patients had T2, 36 had T3, and 53 had T4 tumors according to the 1997 AJCC staging system. Eleven patients had nodal involvement at diagnosis: 9 with SCC, 1 with UC, and 1 with AC. The most common sites of nodal involvement were ipsilateral level 1 and 2 lymph nodes. Thirty-six patients were treated with definitive radiotherapy alone, and 61 received a combination of surgical and radiation treatment. Thirty-six patients had neck irradiation, 25 of whom received elective neck irradiation (ENI) for N0 necks. The median follow-up for alive patients was 78 months. RESULTS: The median survival for all patients was 22 months (range: 2.4-356 months). The 5- and 10-year actuarial survivals were 34% and 31%, respectively. Ten patients relapsed in the neck, with a 5-year actuarial risk of nodal relapse of 12%. The 5-year risk of neck relapse was 14% for SCC, 25% for ADE, and 7% for both UC and ACC. The overall risk of nodal involvement at either diagnosis or on follow-up was 28% for SCC, 25% for ADE, 12% for UC, and 10% for AC. All patients with nodal involvement had T3-4, and none had T2 tumors. ENI effectively prevented nodal relapse in patients with SCC and N0 neck; the 5-year actuarial risk of nodal relapse was 20% for patients without ENI and 0% for those with elective neck therapy. There was no correlation between neck relapse and primary tumor control or tumor extension into areas containing a rich lymphatic network. The most common sites of nodal relapse were in the ipsilateral level 1-2 nodal regions (11/13). Patients with nodal relapse had a significantly higher risk of distant metastasis on both univariate (p = 0.02) and multivariate analysis (hazard ratio = 4.5, p = 0.006). The 5-year actuarial risk of distant relapse was 29% for patients with neck control versus 81% for patients with neck failure. There was also a trend for decreased survival with nodal relapse. The 5-year actuarial survival was 37% for patients with neck control and 0% for patients with neck relapse. CONCLUSION: The overall incidence of lymph node involvement at diagnosis in patients with maxillary sinus carcinoma was 9%. Following treatment, the 5-year risk of nodal relapse was 12%. SCC histology was associated with a high incidence of initial nodal involvement and nodal relapse. None of the patients presenting with SCC histology and N0 necks had nodal relapse after elective neck irradiation. Patients who had nodal relapse had a higher risk of distant metastasis and poorer survival. Therefore, our present policy is to consider elective neck irradiation in patients with T3-4 SCC of the maxillary sinus.

Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: impact on local control.

PURPOSE: Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy). RESULTS: All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases. CONCLUSIONS: Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.

Postoperative irradiation of minor salivary gland malignancies of the head and neck.

OBJECTIVES: (1) To review the Stanford experience with postoperative radiotherapy for minor salivary gland carcinomas of the head and neck. (2) To identify patterns of failure and prognostic factors for these tumors. MATERIALS AND METHODS: Fifty-four patients with localized tumors were treated with curative intent at Stanford University between 1966 and 1995. The 1992 AJCC staging for squamous cell carcinomas was used to retrospectively stage these patients. Thirteen percent had stage I, 22% stage II, 26% stage III, and 39% stage IV neoplasms. Thirty-two patients (59%) had adenoid cystic carcinoma, 15 (28%) had adenocarcinoma, and seven (13%) had mucoepidermoid carcinoma. Thirty (55%) had positive surgical margins and seven (13%) had cervical lymph node involvement at diagnosis. The median follow-up for alive patients was 7.8 years (range: 25 months-28.9 years). RESULTS: The 5- and 10-year actuarial local control rates were 91 and 88%, respectively. Advanced T-stage (T3-4), involved surgical margins, adenocarcinoma histology, and sinonasal and oropharyngeal primaries were associated with poorer local control. The 5- and 10-year actuarial freedom from distant metastasis were 86 and 81%, respectively. Advanced T-stage (T3-4), lymph node involvement at diagnosis, adenoid cystic and high-grade mucoepidermoid histology were associated with a higher risk of distant metastases. The 10-year cause-specific survival (CSS) and overall survival (OS) were 81 % and 63%, respectively. On multivariate analysis, prognostic factors affecting survival were T-stage (favoring T1-2), and N-stage (favoring NO). When T- and N-stage were combined to form the AJCC stage, the latter became the most significant factor for survival. The 10-year OS was 86% for stage I-II vs. 52% for stage III-IV tumors. Late treatment-related toxicity was low (3/54); most complications were mild and no cranial nerve damage was noted. CONCLUSIONS: Surgical resection and carefully planned post-operative radiation therapy for minor salivary gland tumors is well tolerated and effective with high local control rates. AJCC stage was the most significant predictor for survival and should be used for staging minor salivary gland carcinomas.

Unsuspected esophageal foreign bodies in adults with upper airway obstruction.

Esophageal foreign bodies rarely cause respiratory distress in adults. While it is well known that upper airway obstruction can occur with esophageal foreign bodies in children, the otorlaryngologic literature mentions little of this problem in older patients. Two adults with airway obstruction from unsuspected esophageal foreign bodies are described, with emphasis on the problems of diagnosis and management. The possibility of an unsuspected esophageal foreign body should be kept in mind during the evaluation of respiratory distress in an adult, especially in one who is a poor historian or has a history of a psychiatric disorder. Early endoscopic removal in the treatment of choice, although esophagotomy may be required.

MacFee incisions: dispelling the myth of cervical flap vascular inadequacy.

MacFee (double horizontal) incisions have often been criticized for transecting the dominant blood supply of the central bipedicled cervical flap. To assess the viability of this flap we reviewed our recent surgical data. Ninety-three patients who underwent 100 radical neck dissections were evaluated retrospectively for cervical skin viability after surgery. MacFee incisions were used in 50 of these; in the remaining 50 a variety of other incisions were used. With MacFee incisions no ischemic tissue loss resulted. By contrast, six patients (12%) in the comparison group experienced partial flap necrosis due to ischemia. Chi-square analysis shows this difference to be statistically significant (P less than 0.01). This study shows the bipedicled cervical flap to be durable, dependable, and sufficiently vascularized to prevent ischemic tissue loss, even when incisions were previously placed in the ipsilateral neck or antecedent radiation therapy was delivered.

Planned approach to the management of malignant invasion of the carotid artery.

A planned approach to the evaluation and management of patients with tumor involvement of the cervical carotid artery is presented. Preoperative arteriography and determination of carotid back-pressure permitted a rational approach in these high risk patients. One patient found to have an extremely low carotid back-pressure was advised not to undergo carotid resection. Six patients with satisfactory carotid back-pressure tolerated carotid resection and reconstruction.

Management of the clinically positive neck in organ preservation for advanced head and neck cancer.

BACKGROUND: To investigate clinicopathologic predictive criteria for the optimal management of neck metastases in patients with advanced head and neck cancers treated with combined chemoradiotherapy. METHODS: Prospective study, 48 patients. Mean length follow-up, 23 months. RESULTS: Neck stage predicted neck response to chemoradiotherapy; N3 necks showed more partial responses (P = 0.04), and N1 necks showed more complete responses (P = 0.12). Primary tumor site strongly predicted the pathologic response found on neck dissection in patients with a clinical partial response (cPR) following chemoradiotherapy. There was no difference in survival between patients with a clinical complete response (cCR) after chemoradiotherapy, and patients with a pathologic complete response (pCR) after neck dissection (P = 0.20); however, when grouped together, these patients survived longer than did patients with a pPR at neck dissection (P = 0.06). CONCLUSIONS: Clinical response to induction chemotherapy is a poor predictor of ultimate neck control. Induction chemotherapy followed by chemoradiotherapy, and planned neck dissection for patients with persistent cervical lymphadenopathy, provides good regional control.

Head and neck squamous cancers.

Head and neck squamous cancers are a heterogeneous group of neoplasms with varying etiologic factors, presenting symptoms, staging, treatment, and expected outcome. In this monograph, we discuss principles of management common to all sites as well as individual differences. The presenting symptoms of disease are reviewed, stressing the importance of early diagnosis. Accurate pathologic diagnosis can be improved on in difficult cases by newer immunohistochemical techniques. Following diagnosis, accurate clinical staging must be performed, and the evaluation of an unknown primary in the neck is described. We review general considerations for planning the treatment of head and neck cancer, and then discuss specific guidelines for individual sites, stressing the optimal integration of surgery and radiation therapy, particularly brachytherapy. Controversial management issues and new, innovative approaches are discussed. The conventional use of chemotherapy in head and neck cancer is for palliation of recurrent disease. In recent years, chemotherapy has been added to the primary treatment program in an induction role, as a radiosensitizer, as an adjunct following standard therapy, and for organ preservation. The current status of these roles is reviewed. This is a cancer for which there are known etiologic agents. Future efforts in this disease should be directed toward early detection and prevention.

Aminoglycoside ototoxicity in the human.

One hundred thirty-eight patient courses of tobramycin (tobra) and gentamicin (genta) were prospectively monitored for ototoxicity using weekly audiograms and electronystagmograms. Twice weekly drug serum levels and kidney function tests were determined. A pre, during, and post-therapy history was obtained and the results were analyzed to determine significant parameters of ototoxicity. Statistical analysis of the data was performed using SPSS on an IBM 370/3033 computer. Tobra showed less toxicity than genta but only the difference in vestibular toxicity was statistically significant. Significant associations with toxicity included the patient developing a high temperature, total dose, low hematocrit for tobra, high hematocrit for genta, high creatinine clearance with cochlear toxicity, high creatinine with nephrotoxicity, poor condition or critically ill, and duration of therapy greater than 10 days. Non-significant parameters included dose rate (mg/kg), serum levels, age, prior noise exposure, prior aminoglycosides, prior ear infections, non-aminoglycoside ototoxic drugs, underlying disease, or total number of high risks present. Ototoxicity was independent of nephrotoxicity.

Tracheoesophageal space abscess.

Two cases of a newly described complication of endotracheal intubation are presented with a discussion of the pathophysiology, clinical symptoms, and treatment evaluation. Treated late, bilateral arytenoid fixation associated with subglottic stenosis is the eventual outcome. Reconstructive efforts in one patient have allowed decannulation two years after onset of his disease following bilateral arytenoidectomy. No reconstructive efforts were attempted in the second patient because of her basic underlying disease process. Early recognition is important and exploratory laryngotracheal-fissure advocated for suspected cases in order to perhaps decrease the devastating consequences of late treatment.

Surgical management of recurrent nasopharyngeal carcinoma after radiation failure at the primary site.

Nine patients have undergone transpalatal resection of recurrent nasopharynx cancer 10 to 56 months following a full course of external beam irradiation. Seven patients were treated for cure, and two were treated palliatively because of nasal airway obstruction, recurrent epistaxis, and severe headaches. Of the patients treated for cure, five are living free of disease 6 to 48 months (mean, 22.2 months) after their surgery. Disease recurred in two patients at 5 and 7 months. Both underwent secondary procedures and are alive with disease at 25 months and 11 months, respectively. The mean hospital stay was 8.7 days (range, 2 to 30 days) for all patients. The average time to swallowing was 2 days (range, 1 to 3 days). Six patients required resection of their soft palate and a soft palate obturator; two patients had intact functioning soft palates without velopharyngeal insufficiency. Of the two patients treated for palliation, one patient died 1 year postoperatively and, although she received some benefit from the resection (diminished headaches), in retrospect, surgery was not worthwhile. The second patient is alive 3 years following her resection and remained symptom-free for 2 years.

Potential success of near-total laryngectomy despite postoperative radiation therapy.

Advanced laryngeal cancers frequently require total laryngectomy (TL). Some of these cancers, however, are suitable for near-total laryngectomy (NTL). We review our experience with NTL over a 14-year period and compare the functional results with those obtained over the same period using TL followed by tracheoesophageal puncture (TEP). One particular interest was the results achieved when surgery was preceded or followed by radiation therapy. From January 1980 through December 1994, 22 patients underwent NTL. The mean age of the 19 men (86.4%) and 3 women (13.6%) was 61.1 +/- 9.9 years. Follow-up ranged from 4 to 109 months, with a mean of 26.5 months. The local control rate was 90.9% (i.e., 20 of the 22 patients). Over the same time period, 11 TEPs were performed in 7 men (63.6%) and 4 women (36.4%) who had a mean age of 60.4 +/- 7.2 years. Compared with the TEP group, the patients in the NTL group had higher mean scores for swallowing, aspiration, and voice quality evaluations, although the differences were not statistically significant. Notably, 21 of 22 patients (95.5%) received preoperative or postoperative radiotherapy. Complications in the NTL group included aspiration, dilated shunt appendix, and inadequate tracheopharyngeal shunt function. Slight modifications of the NTL technique, including routine entrance into the vallecula in uninvolved larynges, the use of contralateral pyriform mucosa flaps, and the performance of an H-flap tracheostomy are described. The NTL is a sound oncologic procedure for tumors causing vocal cord fixation, and it can be successful even when postoperative radiotherapy is administered. The quality of speech, the ease of swallowing, and the incidence of aspiration are similar to those in patients who have had a TEP following TL.

Rhomboid flap principles and common variations.

The rhomboid flap was initially popularized by a Russian, Alexander Limberg, and modified by Claude Dufourmentel of Paris. Numerous variations on the flap have been proposed more recently by Webster and Gunter. This flap has found its way into the practice of most surgeons doing head and neck surgery, with its primary advantage being that it is an extremely simple flap operation to learn, with great versatility. The general principles and their clinical application are presented in order to increase proper utilization of the flap.

Trigeminal neurinomas.

Trigeminal neurinomas may produce atypical facial pain, loss of facial sensation, facial palsy, hearing loss, nystagmus, or vertigo, and thus may be confused with nasopharyngeal carcinomas or acoustic neurinomas. The diagnosis can be made by the clinical presentation together with radiographic features showing widening of the foramen ovale and/or smooth destruction of the anteromedial portion of the peterous apex. Tomography, pneumoencephalography, angiography, and other diagnostic procedures are sometimes helpful. Treatment is removal by transtemporal craniotomy and offers an excellent prognosis.