Abstract
Hypothesis
Patients with advanced laryngeal cancer sometimes desire organ preservation protocols even if it portends a worse outcome.
Background
To assess outcomes of patients with T4 laryngeal cancer treated with chemoradiation therapy.
Methods
Case series with chart review at a tertiary university hospital. Twenty-four patients with T4 laryngeal cancer all declined total laryngectomy with adjuvant radiation as the primary treatment modality and alternatively received concurrent chemoradiation therapy. The primary outcome was overall survival. Secondary outcomes were rates of tracheotomy dependence, gastric tube dependence, and need for salvage laryngectomy.
Results
All patients had T4 laryngeal disease, 71% had cartilage invasion and 59% had regional metastasis to the neck. Kaplan–Meier analysis determined 2-year and 5-year overall survival to be 64% and 59% respectively. The locoregional recurrence rate was 25%. The distant metastasis rate was 21%. The rate of salvage laryngectomy was 17%, which occurred at a mean of 56.5 months after the original diagnosis. The rate of tracheotomy dependence was 33% while gastric tube dependence was 25%.
Conclusion
Advanced T4 laryngeal cancer, particularly with cartilage invasion, remains a surgical disease best treated with total laryngectomy and adjuvant radiation. This data may help guide patients and practitioners considering concurrent chemoradiation therapy for definitive treatment of advanced laryngeal cancer.
1
Introduction
The American Cancer Society estimates that 13,560 new cases of laryngeal cancer will be diagnosed in 2015, directly accounting for 3640 deaths . The majority of these diagnoses will present at an early stage with disease confined to the larynx and normal vocal cord mobility (T1–T2 disease). Treatment modalities for early stage laryngeal cancer are either primary radiotherapy or endoscopic resection, both of which aim to preserve laryngeal function and share similar survival and functional outcomes .
Advanced stage laryngeal cancer is defined by vocal cord fixation (T3), disease extending beyond the larynx (T4), regional metastasis, or distant metastasis. Historically, resectable disease was addressed with a total laryngectomy and adjuvant radiotherapy. The laryngectomy procedure and its voice rehabilitation process carry a significant social and psychological burden on the patient . While the long-term overall quality of life between laryngectomy versus chemoradiation therapy has been shown to be equal, many patients struggle to accept the social ramifications and figurative disturbances that accompany the laryngectomy . Today, patients have an unprecedented amount of autonomy, even in the setting of cancer treatment decisions. A recent study assessed patient preference with realistic clinical vignettes of laryngectomy pathways versus chemoradiation pathways. Of the 114 surveyed participants, they found 62% preferred chemoradiation over laryngectomy when both treatment arms did not have significant complications .
In 1991, a landmark study by the Department of Veterans Affairs (VA) changed the paradigm of treating laryngeal cancer . In this randomized study a control arm (total laryngectomy and adjuvant radiotherapy) was compared to an experimental arm (induction chemotherapy with radiation therapy) and found no difference in survival rate after two years (68% for both groups). They also found that 64% of patients in the experimental arm kept their larynx after a median follow-up of 33 months. In 2003, the Radiation Therapy Oncology Group Trial 91-11 (RTOG 91-11) demonstrated that in regard to laryngeal preservation concomitant chemoradiation therapy was superior to induction chemotherapy or radiation alone (88%, 72%, and 67% respectively) . The RTOG 91-11 trial included patients with T2, T3, and “low-volume” T4 laryngeal disease. The “low-volume” T4 designation in the RTOG 91-11 trial and the higher rate of local recurrence for T4 disease in the experimental arm in the VA trial has led the majority of clinicians to still advocate for total laryngectomy in the setting of T4 laryngeal disease with cartilage involvement.
Our institutional practice is to counsel all laryngeal cancer patients on the risks and benefits of both operative and non-operative treatment modalities. If there is advanced local disease, particularly thyroid or cricoid cartilage invasion, a total laryngectomy with adjuvant radiotherapy is recommend. Adjuvant chemotherapy is reserved for high-risk features on surgical pathology. Despite this recommendation a subset of patients with T4 laryngeal disease are reluctant to undergo a laryngectomy and thus choose concurrent chemoradiation therapy as their primary treatment modality. The goal of this study was to evaluate the overall survival of patients with T4 laryngeal cancer who declined total laryngectomy and were treated primarily with concurrent chemoradiation. Secondarily we report the rates of salvage laryngectomy, tracheotomy dependence, gastric tube dependence, pharyngoesophageal dilations, and treatment morbidity.
2
Materials and methods
This is an IRB-approved case series with retrospective chart review of 24 patients treated at University Hospitals Case Medical Center in Cleveland, OH from January 1998 through August 2012. All patients were diagnosed with advanced stage glottic or supraglottic squamous cell carcinoma. Work-up included clinical examination, direct laryngoscopy, bronchoscopy, esophagoscopy, and computed tomography. All patients had local disease consistent with T4 status. Patients were excluded if they had previously been treated for a head and neck malignancy. All patients declined total laryngectomy and were subsequently treated with concurrent chemoradiation as the definitive treatment modality. The institutional chemotherapy protocol consists of two cycles of cisplatin and 5-flurouracil. Patients deemed medically unfit to tolerate this regimen received alternative agents, often with carboplatin or cetuximab. All patients completed a full course of standard fractionated radiotherapy delivered 5 days a week for 7 weeks (35 fractions). The target dosage for the primary tumor was 70–72 Gy. Bilateral necks (levels 2–4) were also included in the radiation field.
Overall patient survival at 2-years and 5-years was analyzed and a Kaplan–Meier survival curve was created. Patients who were lost to follow-up were censored at the time of their last known visit or medical encounter. Categorical variables are summarized with frequency counts and percentages. Statistical analysis for the categorical variables was calculated using a chi-square contingency table with a significance cutoff p -value <0.05. Continuous variables are reported as means, standard deviations (SD) and ranges. A Student’s t -test with p -values <0.05 was used to determine statistical significance.
2
Materials and methods
This is an IRB-approved case series with retrospective chart review of 24 patients treated at University Hospitals Case Medical Center in Cleveland, OH from January 1998 through August 2012. All patients were diagnosed with advanced stage glottic or supraglottic squamous cell carcinoma. Work-up included clinical examination, direct laryngoscopy, bronchoscopy, esophagoscopy, and computed tomography. All patients had local disease consistent with T4 status. Patients were excluded if they had previously been treated for a head and neck malignancy. All patients declined total laryngectomy and were subsequently treated with concurrent chemoradiation as the definitive treatment modality. The institutional chemotherapy protocol consists of two cycles of cisplatin and 5-flurouracil. Patients deemed medically unfit to tolerate this regimen received alternative agents, often with carboplatin or cetuximab. All patients completed a full course of standard fractionated radiotherapy delivered 5 days a week for 7 weeks (35 fractions). The target dosage for the primary tumor was 70–72 Gy. Bilateral necks (levels 2–4) were also included in the radiation field.
Overall patient survival at 2-years and 5-years was analyzed and a Kaplan–Meier survival curve was created. Patients who were lost to follow-up were censored at the time of their last known visit or medical encounter. Categorical variables are summarized with frequency counts and percentages. Statistical analysis for the categorical variables was calculated using a chi-square contingency table with a significance cutoff p -value <0.05. Continuous variables are reported as means, standard deviations (SD) and ranges. A Student’s t -test with p -values <0.05 was used to determine statistical significance.
3
Results
Twenty-four patients met inclusion criteria and were included in this study. Their demographics and tumor characteristics are summarized in Table 1 . The mean patient age was 60.5 years old (range 44–83). Females accounted for 42% of the patients. Six patients (25%) were African-American. All patients presented with T4 laryngeal squamous cell carcinoma according to the 2010 American Joint Committee on Cancer (AJCC) criteria. Half of the patients were diagnosed with supraglottic cancer and half were diagnosed with glottic cancer. Seventeen patients (71%) had cartilage invasion upon diagnosis. Fourteen patients (59%) had either clinical or radiographic evidence of regional metastasis to the neck at the time of diagnosis. The mean follow-up was 43.0 months (SD 26.5).
| Number n = 24 | Percentage or Standard deviation | |
|---|---|---|
| Mean age (years) | 60.5 | ±11.2 |
| Sex | ||
| Male | 14 | 58% |
| Female | 10 | 42% |
| Site | ||
| Glottic | 12 | 50% |
| Supraglottic | 12 | 50% |
| Cartilage invasion | 17 | 71% |
| N stage | ||
| N0 | 10 | 42% |
| N1 | 4 | 17% |
| N2B | 3 | 13% |
| N2C | 7 | 29% |
| Chemotherapy | ||
| Cisplatin/5-FU | 13 | 54% |
| Carboplatin | 4 | 17% |
| Cetuximab | 4 | 17% |
| Taxotere/bevacizumab | 1 | 4% |
| Taxotere/erlotinib | 1 | 4% |
| Unknown | 1 | 4% |
| Radiation dose (Gy) | 70.6 | ±2.6 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
