Laryngeal cancer

60-65% of cancers are glottis, 30-35% are supraglottic and about 5% occur in the subglottis.

Majority of lesions are squamous cell carcinomas arising from the tissues covering the structures of the larynx.

Tobacco and alcohol exposure of the dominant risk factors.

Predisposes patients with swallowing problems associated with malnutrition and aspiration.

Early stage disease can be treated with radiation alone.

Intermediate to early-advanced disease can be treated with localized radiation therapy with wider field radiation and concurrent chemotherapy to maximize local control.

Laryngectomy and postoperative radiation reserved for aggressive malignancies that invade cartilage or the tongue or severely impair voice or swallowing function.

68% 2-year survival for patients treated with chemotherapy and radiation and is the same as those treated with laryngectomy.

Patients present predominantly with local or locoregional involvement as opposed to distant metastasis.

Great majority of patients will be treated with curative intent.

Tobacco-associated disease and its incidence in the United States and most developed countries is declining due to lower smoking rates.

Complete staging consists of nasopharygolaryngoscopy to delineate the extent of the primary tumor, and bronchoscopy and esophagoscopy are performed frequently to exclude the possibility of metachronous primary tumors of the aerodigestive tract.

To determine the severity/spread of the laryngeal cancer and the level of vocal fold function, indirect laryngoscopies using mirrors, endoscopies (rigid or flexible) may be performed.

In very advanced cases tracheostomy may be performed, since initiation of radiotherapy can be associated with life threatening edema of the airway.

In the presence of impaired nutrition parenteral or gastrostomy tube feelings are considered.

Initial imaging consists of computed tomography or MRI scanning of the neck and chest.

Baseline swallowing function is assessed to guide long-term therapy for speech and swallowing.

VA Laryngeal Cancer Study randomized subjects to surgery or sequential chemotherapy and radiotherapy: Equivalent survival was reported between the two arms, with approximately two-thirds of subjects in the experimental arm avoiding a laryngectomy.

Sequential chemoradiotherapy is an accepted standard of care for laryngeal cancer.

RTOG 91-11 was a Phase III randomized trial in patients with larynx cancer and compared concurrent chemoradiotherapy (cisplatin 100 mg/m2 every three weeks with single-daily fractionated radiotherapy) or radiotherapy alone: The five-year results of this study support the benefit of concurrent chemoradiotherapy with respect to larynx preservation, locoregional control, and disease-free survival.

In patients who are candidates for laryngectomy, comparing cisplatin/5-FU with or without docetaxel (TPF) revealed TPF improved larynx preservation, progression-free survival, and organ function.

T4 tumors are large volume cancers that can extend through cartilage and invade secondary structures so that function cannot be preserved by surgery.

In T4 tumors radiotherapy is less effective when cartilage destruction is present.

It is reasonable to attempt chemoradiotherapy in T4 patients.

Initial steps include staging and ascertaining whether a curative, organ-preservation approach is appropriate.

A curative, organ-preservation approach for many patients consist of concurrent chemoradiotherapy of cisplatin and single-daily fractionated radiotherapy.

Higher rate of local recurrence for patients treated with radiation and chemotherapy than for those treated with laryngectomy, but there is a lower rate of distant metastases in the former group.

The Radiation Therapy Oncology Group (RTOG) 91-11 trial compared concurrent cis-platinum based chemotherapy and radiotherapy with sequential cis-platinum plus 5-FU therapy and the former treatment was associated with a statistically superior larynx preservation rate for cancer of the larynx.

In the above study long-term survival beyond 4.5 years showed a separation of survival curves in favor of induction chemotherapy.

Induction chemotherapy predominantly improved systemic control, while concomitant chemoradiation exerts its major effect by improving local regional control.

Patients who respond to induction chemotherapy are most likely subsequently to respond to radiotherapy and to have an excellent prognosis.

The 2 year larynx preservation rate was 88% and 75%, respectively for the above study, and at 5 years laryngectomy free survival rates were similar at 45% in the sequential group and 47% in the concurrent chemotherapy and radiation group.

The GORTEC 2000-01 trial demonstrated that the larynx preservation rate can be improved by adding docetaxel to platinum and 5-FU (TPF) with a 3 year larynx preservation rate of 70% with TPF compared to platinum and 5-FU alone at 58% (Pointreau Y et al).

In a phase 3 study comparing radiotherapy with radiotherapy plus cetuximab in patients with locally advanced squamous cell carcinoma of the larynx, the larynx preservation rate was higher in the combination group at 2 years, 92% versus 83%, respectively and at 3 years 88% versus 80%, respectively (Bonner JA et al).

Bioradiotherapy and concurrent cetuximab is superior to single modality radiation in carcinoma of the larynx, but has not been directly compared with induction or concurrent chemoradiation.

To date no nonsurgical approach has provided a superior survival effect to that seen with total laryngectomy followed by postoperative radiation (2010).

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