Abstract
Objectives
Although concurrrent chemoradiation is increasingly used for patients with locally advanced head and neck cancer, many elderly patients receive radiation alone due to toxicity concerns. We evaluate acute and late toxicity among patients age ≥ 65 who received concurrent chemoradiation for head and neck cancer.
Design
Retrospective review.
Setting
Tertiary care center.
Participants
Between 6/2003 and 8/2011, 40 consecutive patients age ≥ 65 underwent combined chemoradiation for head and neck cancer. Ten patients were treated in the postoperative setting and 30 underwent definitive chemoradiation. Twenty-eight patients received concurrent platinum-based chemotherapy and 12 received concurrent weekly paclitaxel. Treatment plans were designed to provide a dose of 66–72 Gy at 2–2.12 Gy/fraction to > 95% of the gross tumor volume in the definitive setting or for positive margins and 60–66 Gy at 2 Gy/fraction post-operatively. Median follow-up was 23.2 months (range: 0–94.4 months).
Main outcomes measures
Acute skin and mucosal toxicity, unplanned treatment interruptions, and chronic treatment related toxicity including gastrostomy tube dependence as graded by the CTCAE v3.0.
Results
Eight patients (20%) required a radiation treatment break of ≥ 3 days. Thirteen (33%) required unplanned hospitalization during or immediately following treatment. No grade 4 + skin or mucosal toxicity was noted. Five patients remained PEG tube dependent at > 1 year. One patient developed non-healing mandibular osteoradionecrosis > 3 years following chemoradiation. The 2-year Kaplan–Meier estimate of overall survival was 55%.
Conclusion
Higher-than-expected rates of in-patient hospitalization with significant acute toxicity were noted in this cohort with a correspondingly high rate of radiation treatment breaks. Late toxicity rates were similar to those observed in historical controls with younger patients. Careful patient selection criteria should be employed for elderly patients considering concurrent chemoradiation for head and neck cancer.
1
Introduction
The management of locoregionally advanced head and neck cancer has evolved over the past two decades, with increasing use of organ preservation techniques. Combined modality approaches with radiation and concurrent chemotherapy have demonstrated improved local control as compared to radiotherapy alone in phase III trials . Concurrent chemoradiation (CRT) is also used in the post-operative setting for select patients with high-risk features including positive margins or nodal extracapsular extension, as defined by prospective trials by the Radiation Therapy Oncology Group (RTOG) and the European Organisation for Research and Treatment of Cancer (EORTC) . Between 2004 and 2008, patients over the age of 65 accounted for approximately 43% of all newly diagnosed cancers of the oral cavity and pharynx, with a median age at diagnosis of 62 . Although most large, phase III trials evaluating concurrent CRT for head and neck cancer have not specifically excluded the elderly, the median age of enrolled patients has consistently been under 60 , leaving inadequate prospective data regarding both the efficacy and toxicity of these approaches for older patients. Given the increased toxicity of combined modality approaches, significant concerns exist in using aggressive CRT regimens for elderly patients. Furthermore, the efficacy of concurrent CRT in the elderly is questionable following publication of a large meta-analysis suggesting decreasing benefit with advancing age . The present study evaluates acute and late toxicities for 40 consecutive head and neck cancer patients treated with concurrent CRT for head and neck cancer at a single institution.
2
Materials and methods
2.1
Patients
Following Institutional Review Board approval, the records for 41 consecutively treated patients age ≥ 65 treated with concurrent CRT for head and neck squamous cell carcinoma at the University of California, Davis were retrieved and reviewed. One patient who elected to stop therapy after two fractions for reasons unrelated to treatment toxicity was excluded, leaving 40 evaluable patients. Thirty patients were treated in the definitive setting and ten postoperatively. The median age was 69.6 years (range 65.0–81.5 years). The primary site was oropharynx in 15 (38%), larynx in 7 (18%), oral cavity in 6 (15%), hypopharynx in 5 (13%), unknown primary in 5 (13%), and nasopharynx in 2 (5%). The majority of patients had stage IVA (23) or IVB (6) disease. A total of 9 women and 31 men were included. All patients had a Karnofsky Performance Status (KPS) of 70 or higher. Thirteen never-smokers (defined as a lifetime smoking history of 5 or fewer pack-years) and twenty-seven former or current smokers were included. Median pack-year history among former or current smokers was 50 (range: 8–180 pack-years). Ten patients were actively smoking or had smoked within one month of radiotherapy. Full patient and disease characteristics are outlined in Table 1 .
| Patient Characteristics | Patients (%) |
|---|---|
| Age | 69.6 years (range 65.0–81.5 years) |
| Primary site | |
| Oropharynx | 15 (38%) |
| Oral Cavity | 6 (15%) |
| Hypopharynx | 5 (13%) |
| Larynx | 7 (18%) |
| Nasopharynx | 2 (5%) |
| Unknown Primary | 5 (13%) |
| Karnofsky Performance Status | |
| 70 | 2 (5%) |
| 80 | 15 (38%) |
| ≥ 90 | 23 (58%) |
| Smoking Status | |
| Never-smoker (≤ 5 PY) | 13 (33%) |
| Former smoker | 17 (43%) |
| Current smoker | 10 (25%) |
| Stage Group | |
| II | 2 (5%) |
| III | 8 (20%) |
| IVA | 23 (58%) |
| IVB | 6 (15%) |
| IVC | 1 (3%) |
| Treatment type | |
| Definitive | 30 (75%) |
| Post-operative | 10 (25%) |
| Chemotherapy | |
| Platinum-based | 28 (70%) |
| Weekly paclitaxel | 12 (30%) |
2.2
Radiotherapy
Treatment plans were designed to provide a dose of 66–72 Gy at 2–2.12 Gy/fraction to > 95% of the gross tumor volume (GTV) in the definitive setting or for positive margins and 60–66 Gy at 2 Gy/fraction in the post-operative setting. Twenty-six patients underwent static (7) or rotational (19) intensity-modulated radiotherapy, while the remaining 14 were treated with conventional fields. All patients underwent bilateral neck irradiation.
2.3
Chemotherapy
Twenty-eight patients (70%) received concurrent platinum-based chemotherapy while 12 (30%) received concurrent weekly paclitaxel. Platinum based regimens were as follows: cisplatin 100 mg/m 2 body surface area (BSA) day 1, 22, and 43 (4 patients), 50 mg/m 2 BSA weekly day 1, 8, 23, and 29 (18 patients); carboplatin 100 mg/m 2 BSA and paclitaxel 50 mg/m 2 BSA Q3 week (1 patient), and cisplatin 30 mg/m 2 BSA weekly with cetuximab 400 mg/m 2 BSA loading dose and 250 mg/m 2 BSA weekly concurrent with radiation (1 patient). One nasopharyngeal cancer patient also received 2 cycles of adjuvant carboplatin and paclitaxel.
2.4
Follow-up
Patients were evaluated by the treating radiation oncologist one or more times per week during radiotherapy. Acute toxicities were graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0. Following completion of treatment, patients were evaluated with a comprehensive history and physical examination including fiber optic nasopharyngolaryngoscopy every one to two months during the first year, every 3–6 months in years two and three, and annually thereafter. All endpoints were calculated from the date of completion of radiotherapy. Post-treatment imaging was at the discretion of the treating physicians.
2.5
Statistical analysis
Two-year estimates local-regional control (LRC), overall survival (OS), freedom from distant metastases (FFDM), and disease-free survival (DFS) were calculated by the Kaplan–Meier method . Impact of categorical variables on rate of radiotherapy interruptions and risk of hospitalization was evaluated with Fisher’s exact test with 2 tailed p-values. Mean age between patients with and without treatment interruptions, and between hospitalized and non-hospitalized patients was compared with the unpaired T test. The impact of categorical variables on LRC, DFS, FFDM, and OS was calculated with the log-rank test, while the impact of continuous variables was calculated with a Cox model. Statistical calculations were performed with StatView (SAS Institute, Cary, NC) and GraphPad (GraphPad Software, Inc. La Jolla, CA) software.
2
Materials and methods
2.1
Patients
Following Institutional Review Board approval, the records for 41 consecutively treated patients age ≥ 65 treated with concurrent CRT for head and neck squamous cell carcinoma at the University of California, Davis were retrieved and reviewed. One patient who elected to stop therapy after two fractions for reasons unrelated to treatment toxicity was excluded, leaving 40 evaluable patients. Thirty patients were treated in the definitive setting and ten postoperatively. The median age was 69.6 years (range 65.0–81.5 years). The primary site was oropharynx in 15 (38%), larynx in 7 (18%), oral cavity in 6 (15%), hypopharynx in 5 (13%), unknown primary in 5 (13%), and nasopharynx in 2 (5%). The majority of patients had stage IVA (23) or IVB (6) disease. A total of 9 women and 31 men were included. All patients had a Karnofsky Performance Status (KPS) of 70 or higher. Thirteen never-smokers (defined as a lifetime smoking history of 5 or fewer pack-years) and twenty-seven former or current smokers were included. Median pack-year history among former or current smokers was 50 (range: 8–180 pack-years). Ten patients were actively smoking or had smoked within one month of radiotherapy. Full patient and disease characteristics are outlined in Table 1 .
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