Background We performed a prospective, randomized study in patients with previously untreated advanced (Stage III or IV) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation therapy with those of conventional laryngectomy and postoperative radiation. Methods Three hundred thirty-two patients were randomly assigned to receive either three cycles of chemotherapy (cisplatin and fluorouracil) and radiation therapy or surgery and radiation therapy. The clinical tumor response was assessed after two cycles of chemotherapy, and patients with a response received a third cycle followed by definitive radiation therapy (6600 to 7600 cGy). Patients in whom ther was no tumor response or who had locally recurrent cancers after chemotherapy and radiation therapy underwent salvage laryngectomy. Results After two cycles of chemotherapy, the clinical tumor response was complete in 31 percent of the patients and partial in 54 percent. After a median follow-up of 33 months, the estimated 2-year survival was 68 percent (95 percent confidence interval, 60 to 76 percent) for both treatment groups (P = 0.9846). Patterns of recurrence differed significantly between the two groups, with more local recurrences (P = 0.0005) and fewer distant metastases (P = 0.016) in the chemotherapy group than in the surgery group. A total of 59 patients in the chemotherapy group (36 percent) required total laryngectomy. The larynx was preserved in 64 percent of the patients overall and 64 percent of the patients who were alive and free of disease. Conclusions These preliminary results suggest a new role for chemotherapy in patients with advanced laryngeal cancer and indicate that a treatment strategy involving induction chemotherapy and definitive radiation therapy can be effective in preserving the larynx in a high percentage of patients, without compromising overall survival.

Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer

Head and neck cancer.

Head and neck cancer

Occult (silent) gastroesophageal reflux disease (GER, GERD) is believed to be an important etiologic factor in the development of many inflammatory and neoplastic disorders of the upper aerodigestive tract. In order ot test this hypothesis, a human study and an animal study were performed. The human study consisted primarily of applying a new diagnostic technique (double-probe pH monitoring) to a population of otolaryngology patients with GERD to determine the incidence of overt and occult GERD. The animal study consisted of experiments to evaluate the potential damaging effects of intermittent GER on the larynx. Two hundred twenty-five consecutive patients with otolaryngologic disorders having suspected GERD evaluated from 1985 through 1988 are reported. Ambulatory 24-hour intraesophageal pH monitoring was performed in 197; of those, 81% underwent double-probe pH monitoring, with the second pH probe being placed in the hypopharynx at the laryngeal inlet. Seventy percent of the patients also underwent barium esophagography with videofluoroscopy. The patient population was divided into seven diagnostic subgroups: carcinoma of the larynx (n = 31), laryngeal and tracheal stenosis (n = 33), reflux laryngitis (n = 61), globus pharyngeus (n = 27), dysphagia (n = 25), chronic cough (n = 30), and a group with miscellaneous disorders (n = 18). The most common symptoms were hoarseness (71%), cough (51%), globus (47%), and throat clearing (42%). Only 43% of the patients had gastrointestinal symptoms (heartburn or acid regurgitation). Thus, by traditional symptomatology, GER was occult or silent in the majority of the study population. Twenty-eight patients (12%) refused or could not tolerate pH monitoring. Of the patients undergoing diagnostic pH monitoring, 62% had abnormal esophageal pH studies, and 30% demonstrated reflux into the pharynx. The results of diagnostic pH monitoring for each of the subgroups were as follows (percentage with abnormal studies): carcinoma (71%), stenosis (78%), reflux laryngitis (60%), globus (58%), dysphagia (45%), chronic cough (52%), and miscellaneous (13%). The highest yield of abnormal pharyngeal reflux was in the carcinoma group and the stenosis group (58% and 56%, respectively). By comparison, the diagnostic barium esophagogram with videofluoroscopy was frequently negative. The results were as follows: esophagitis (18%), reflux (9%), esophageal dysmotility (12%), and stricture (3%). All of the study patients were treated with antireflux therapy. Follow-up was available on 68% of the patients and the mean follow-up period was 11.6 +/- 12.7 months.(ABSTRACT TRUNCATED AT 400 WORDS)

The Otolaryngologic Manifestations of Gastroesophageal Reflux Disease (GERD): A Clinical Investigation of 225 Patients Using Ambulatory 24‐Hour pH Monitoring and an Experimental Investigation of the Role of Acid and Pepsin in the Development of Laryngeal Injury

Background Patients with head-and-neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors Retinoids have proved efficacious in the treatment of premalignant oral lesions and are promising agents for the prevention of epithelial carcinogenesis Methods We prospectively studied 103 patients who were disease-free after primary treatment for squamous-cell cancers of the larynx, pharynx, or oral cavity After completion of surgery or radiotherapy (or both), these patients were randomly assigned to receive either isotretinoin (13-cis-retinoic acid) (50 to 100 mg per square meter of body-surface area per day) or placebo, to be taken daily for 12 months Results There were no significant differences between the two groups in the number of local, regional, or distant recurrences of the primary cancers However, the isotretinoin group had significantly fewer second primary tumors After a median follow-up of 32 months, only 2 patients (4

https://www.nejm.org/doi/pdf/10.1056/NEJM199009203231205

Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck.

This report describes the experimental design and initial results of an ongoing clinical investigation of voice disorders. Its major focus is the development and use of quantitative measures to provide objective descriptions of conditions referred to as "vocal hyperfunction." The experimental design for this project is based on a descriptive theoretical framework, which holds that there are different types and stages of hyperfunctionally related voice disorders. Data consist of indirect measures derived from noninvasive aerodynamic and acoustic recordings including (a) parameters derived from inverse filtered approximations of the glottal air flow waveform; (b) estimates of transglottal pressure, average glottal air flow, glottal resistance and vocal efficiency; and (c) measures of vocal intensity and fundamental frequency. Initial results (based on comparisons among 15 voice patients and 45 normal speakers) support major assumptions that underlie the theoretical framework, and indicate that the measurement approach being utilized is capable of differentiating hyperfunctional from normal voices and hyperfunctional conditions from one another. Organic manifestations of vocal hyperfunction (nodules, polyps, contact ulcers) are accompanied by abnormally high values for the glottal waveform parameters of AC flow and maximum flow declination rate, suggesting increased potential for vocal fold trauma due to high vocal fold closure velocities and collision forces. In contrast, nonorganic manifestations of hyperfunction (functional disorders) tend to be associated with abnormally high levels of unmodulated DC flow, without high values for AC flow and maximum flow declination rate, suggesting reduced potential for vocal fold trauma. Measures also suggest different underlying mechanisms for nodules and polyps as compared to contact ulcers. Results are discussed relative to predictions based on the theoretical framework for vocal hyperfunction.

Objective Assessment of Vocal Hyperfunction: An Experimental Framework and Initial Results

Stenosis of the larynx and/or trachea presents perplexing problems. No one technique has proved totally satisfactory in the management of all varieties of stenosis. Recent reports have described the successful use of the CO2 laser in the endoscopic management of stenosis of the larynx and trachea. Failures of this technique need emphasis to assure appropriate selection of therapeutic method. Retrospectively, 49 cases of laryngeal stenosis, 6 cases of tracheal stenosis and 5 cases of combined laryngeal and tracheal stenosis were studied (total 60 patients) following treatment at the Boston University Affiliated Hospitals. Follow-up ranged from 1 to 8 years. Multiple procedures were required in 35 laryngeal patients. Of the laryngeal patients 39 were successfully managed (average number of procedures in successful cases 2.18). Of 11 tracheal patients with combined laryngeal and tracheal procedures, 3 were successfully managed (average number of procedures in successful cases 6). Failures in laryngeal stenosis included four patients in whom an adequate airway was not established though voice was present while maintaining tracheostomies. Thirteen patients failing endoscopic management required open surgery with good result. Factors associated with poor result or failure include circumferential scarring with cicatricial contracture, scarring wider than 1 cm in vertical dimension, tracheomalacia and loss of cartilage, previous history of severe bacterial infection associated with tracheostomy, and posterior laryngeal inlet scarring with arytenoid fixation. In these circumstances, multiple procedures, more extensive alternative open surgical techniques, or maintenance of tracheostomy were necessary. In successful cases only three or fewer procedures on average were required. The factors associated with failure or success of endoscopic methods in the management of laryngotracheal stenosis, including use of the CO2 laser and soft Silastic stents, are analyzed.

Predictive factors of success or failure in the endoscopic management of laryngeal and tracheal stenosis.

The sequence of histological change induced by CO2 laser irradiation was discussed in terms of two factors: the physiomechanical factor and the physiochemical factor. At sufficiently high heat energy levels, the immediate findings are characterized by crater formation resulting from rapid vaporization of the water and ejection of the solid component. In the immediate vicinity of the crater edge, the maximum tissue temperature rise is 65 degrees C above the 32 degrees C ambient tissue temperature and it decreases to the primary tissue temperature within a distance of 2 mm. The healing process of CO2 laser induced lesions proceeds with minimal delay. The lymphatic and vascular channels are occluded in the marginal area of coagulation resulting in a marked hemostatic effect. This sealing effect increases the margin of safety in preventing possible dissemination of tumor cells. By selecting the appropriate power, time, and focus cone angle, precise destruction of preselected areas of tissue can be achieved with an extraordinary hemostatic effect without damaging the underlying tissue. These advantages are especially helpful in function-preserving surgery.

Laser surgery in otolaryngology: interaction of co2 laser and soft tissue

Recurrent respiratory papillomatosis is most common in childhood but it affects all age groups; it represents a diathesis of the aerodigestive tract so that lesions amy develop at various sites - the nares, lips, pharynx, nasopharynx, larynx, tracheobronchial tree, approximately one-third of patients for one year or more; since relapses amy occasionally occur 2 to 20 years later, cure can never be assumed. At the present time, management is directed towards total ablation of all visble papilloma consistent with preservation of the airway and voice; reduction of the tumor burden to minimal proportions is thought to allow the maximum opportunity for remission. As the host-papilloma relationship is unraveled, it may be possible in the future to provoke an immune response so that remissions can be predicted and produced consistently.

Recurrent Respiratory Papillomatosis: Management with the CO2 Laser

Forty patients with advanced head and neck cancer were treated with combined Cis-platinum-Bleomycin chemotherapy. Cis-diammine dichloroplatinum (DDP) 120 mg/m2 iv was given after prehydration, with mannitol diuresis on Day 1. On Day 3, an initial loading dose of Bleomycin 15 mg/m2 was given by rapid iv push followed by continuous 24 hour intravenous infusion of Bleomycin 15 mg/m2 Day 3 through Day 10. DDP 120 mg/m2 iv was administered again on Day 22. The patients were evaluated for tumor response and resectability between Day 29 to Day 35. Of 39 patients who were evaluable, there were 8 complete responses or CR (20%) and 22 partial responses or PR (56%), for a major response rate of 76%. Nineteen patients had surgery (14 patients whose lesions were initially inoperable and 5 patients who were initially operable). Chemotherapy toxicity in 40 patients included alopecia (40), vomiting (39), mucositis (11), skin rash (10), fever (17), weight loss of more than 5 lbs. (25), WBC less than 3,000 (2), platelets less than 100,000 (1), peak serum creatinine of 2 mg% (3), severe-hearing loss (1), hypersensitivity reaction (2). Surgical complication in 19 patients were pharyngocutaneous fistulae (2), wound dehiscence (1), meningitis and brain abscess (1). There was one death secondary to nephrotoxicity. This particular combination chemotherapy when given as initial treatment, appears very effective in reduction of tumor bulk. Long-term follow-up and randomization is necessary to determine effect upon survival.

https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%28197907%2944%3A1%3C19%3A%3AAID-CNCR2820440104%3E3.0.CO%3B2-R

Charles W. Vaughan

Papers

Objective Assessment of Vocal Hyperfunction: An Experimental Framework and Initial Results

Predictive factors of success or failure in the endoscopic management of laryngeal and tracheal stenosis.

Laser surgery in otolaryngology: interaction of co2 laser and soft tissue

Recurrent Respiratory Papillomatosis: Management with the CO2 Laser

Induction chemotherapy in advanced squamous head and neck carcinoma with high‐dose cis‐platinum and bleomycin infusion