Abstract
Aims
To evaluate the efficacy and toxicity of concurrent chemoradiation in patients with head and neck cancers aged 65 and older.
Materials and methods
Thirty-two elderly patients were treated with radical chemoradiation. Twenty-six (81.3%) out of thirty-two patients had stage III–IV disease. Twenty-nine (90.6%) patients received concurrent weekly cisplatin or carboplatin, 3 (9.4%) patients received concurrent cetuximab or nimotuzumab. Total dose of radiotherapy ranged from 66 Gy to 70 Gy.
Results
Twenty-nine patients (90.6%) completed at least 5 cycles of concurrent chemotherapy. Twenty-four (77.6%) patients achieved complete response. Fourteen (45.2%) patients experienced grade 3 mucositis. None of our patients developed grade 3 or above hematological toxicity. Loco-regional control and overall survival at 2 year were 71.6% and 88.9%, respectively.
Conclusions
Chemoradiation in elderly patients with high precision radiotherapy is a feasible option.
1
Introduction
Head and neck cancers (HNC) constitute the fifth most common subsite of cancer worldwide, with an estimated annual global incidence of 533,100 cases . Majority of HNC occur in the fifth and sixth decades of life but as many as 24% patients are diagnosed in patients aged 70 years or older. Management of locoregionally advanced disease remains challenging, and an aggressive treatment approach is necessary to achieve cure . MACH-NC meta-analysis showed an absolute survival benefit of 6.5% favoring concurrent chemoradiation . Concurrent chemoradiotherapy is the standard of care in patients for organ preservation in stage III and IV oropharyngeal and laryngeal cancers, but the same has never been evaluated prospectively among elderly patients. This may drive elderly patients into receiving sub-optimal therapy on the pretext of their supposed lower ability to tolerate radical treatment. However, with technological advancement in the field of radiation oncology and the results of phase III PARSPORT trial emphasizing randomized evidence of reducing toxicities can actually increase the compliance of combined treatment . On the assumption of higher age and related comorbidities, almost all the randomized data excluded elderly patients (patients > 65 years of age) from receiving chemoradiation. So, we conducted this study to evaluate radical chemoradiation among elderly patients to evaluate tolerance, toxicity and efficacy.
2
Subjects and methods
Patients with histologically proven HNC, aged more than 65 years, Karnofsky performance status (KPS) > 70, who were treated with concurrent chemoradiation (CRT) at our center between April 2010 and October 2012, were included in this study. All patients gave informed consent for administering concurrent chemotherapy with radiation therapy. Baseline laboratory requirements for eligibility included a WBC count greater than 3000 cell/μL, an absolute neutrophil count greater than 1500 cell/μL, platelet count > 100,000 platelets/μL and serum creatinine < 1.5 mg/dL. Patients with co-morbid conditions adequately controlled with medical therapies were included.
Thirty-two patients were analyzed. Patient characteristics are shown in Table 1 . There were 27 males and 5 females with median age of 74 years (range, 65–87 years). KPS was 90 in 69% patients. All patients underwent complete staging workup with detailed clinical evaluation including endoscopies, contrast enhanced CT (CECT) scan of head and neck region, dental prophylaxis and dietary evaluation before initiation of treatment. Whole body PET-CECT was advocated only in those having N2c or higher nodal stage and with lower neck nodal positivity. Ultrasound abdomen and chest X-ray were undertaken for evaluating distant disease. Patients were staged by TNM criteria according to the AJCC 2007 staging system. All patients received radiation therapy with intensity modulated radiotherapy (IMRT) technique.
| Age | 74 year (median) |
| Range 65–87 years | |
| Male:female | 27:5 |
| KPS | |
| 90 | 22 (68.7%) |
| 80 | 8 (25.0%) |
| 70 | 2 (6.2%) |
| Comorbidity | |
| Diabetes | 3 (9.4%) |
| Hypertension | 10 (31.3%) |
| Coronary artery disease | 3 (9.4%) |
| Stroke | 1 (3.1%) |
| Stage | |
| II | 5 (15.6%) |
| III | 9 (28.1%) |
| IV | 18 (56.2%) |
| Site | |
| Oropharynx | 17 (53.1%) |
| Larynx | 6 (18.7%) |
| Hypopharynx | 9 (28.1%) |
| Dose | 68–70 Gy (range) |
| Concurrent chemotherapy | |
| Cisplatin | 16 (50.0%) |
| Carboplatin | 13 (40.6%) |
| Nimotuzumab/cetuximab | 3 (9.4%) |
| Overall treatment time | 49.4 days (range 44–65 days) |
Dietary intake was monitored by a trained dietician throughout the course of treatment. A diet of 2800 kcal, 2 g protein/kg/day and 0.5 g fats/kg/day were prescribed from the start of treatment. Patients were offered symptomatic and supportive care in the form of intravenous fluids, parenteral nutrition, nasogastric tube etc., as required during and following treatment. The requirement of percutaneous endoscopic gastrostomy (PEG) was discussed and applied as indicated. Patients having significant dysphagia at the outset were offered upfront before starting therapy while it was reserved as a salvage option during treatment if dysphagia led to > 10% weight loss.
2.1
Radiation therapy
Patients were immobilized in a commercially available custom-molded thermoplastic mask with fixation of head and shoulders. RT planning CECT was acquired with 3 mm slice thickness and zero interslice gap from the vertex to fourth thoracic vertebra with a flat table top configured to linear accelerator table top. The gross tumor volume (GTV) was defined as gross disease determined from CT, clinical information, endoscopic findings and PET-CECT/MRI, when available. Clinical target volumes (CTV1) were defined as the GTV plus areas containing potential microscopic disease, delineated by the treating physician. The GTV–CTV1 expansion was typically 1.5–2 cm, with a minimum of 5 mm except in areas with natural barriers to spread. CTV2 included neck node levels clinically uninvolved but at low risk of dissemination. Planning target volume (PTV1 around CTV1 and PTV2 around CTV2) generation was as per institutional protocol of 5 mm around CTV in all dimensions. Dose was prescribed at 2 Gy per fraction, 66–70 Gy to PTV1 and 54 Gy to PTV2.
All relevant organs at risk were assigned dose constraints. Spinal cord and brain stem: maximum dose (Dmax) < 45 Gy, mean dose (Dmean) < 35 Gy (spinal cord was contoured with a 5 mm radial margin as planning at risk volume-PRV); parotid (entire or partial) gland volume was spared to the maximum possible extent without compromising target coverage: Dmean < 26 Gy (partial volume outside the PTV was separately outlined for sparing and dose prescription; volume of entire gland was used for the purpose of analysis); optic nerve and chiasm: Dmax < 50 Gy; temporomandibular joint (TMJ): Dmax < 50 Gy; oral cavity outside the PTV (contouring included the mandible, maxillary bone and the oral vestibulum): Dmean < 35 Gy; cochlea: Dmean < 30 Gy.
IMRT planning was done on CMS XIO (ver 4.62) and CMS MONACO (ver 3.0) planning systems. Inverse planning using computerized optimization was used; algorithms used being superpositon and convolution in CMS XIO and Monte Carlo in CMS MONACO. The treatment plan used for each patient was based on an analysis of the volumetric dose, including DVH analysis of the PTV and critical normal structures. Radiation therapy was delivered using 6 MV photon beams on an Elekta linear accelerator (Elekta Synergy S and Elekta Infinity) with sliding window technique. The technical solution of choice, with 5, 7 or 9 coplanar beam arrangements, was used for most patients.
2.2
Chemotherapy
Twenty-nine (90.6%) patients received platinum-based chemotherapy. Of these, 16 patients received weekly cisplatin (35 mg/m 2 ) starting on day 1 of RT with a goal to achieve a cumulative cisplatinum dose of 200 mg/m 2 or higher during the treatment period. Thirteen patients with borderline serum creatinine level or glomerular filteration rate < 50 ml/min received weekly carboplatin (area under curve AUC 2). One patient received concurrent cetuximab and two received concurrent nimotuzumab (200 mg intravenous weekly with a loading dose of 400 mg/m 2 given one week prior to start of radiation therapy).
2.3
Response, toxicity evaluation and survival
Response was assessed 6–8 weeks after completion of treatment. RECIST criteria (version 1.1) were used to assess response . Acute toxicities were recorded weekly during the treatment period and were graded according to the National Cancer Institute Common toxicity criteria (CTC version 4), highlighting oral pain, oral mucositis, dysphagia and dry mouth and changes in blood counts. Loco-regional control and overall survival were estimated using Kaplan–Meier method.
2
Subjects and methods
Patients with histologically proven HNC, aged more than 65 years, Karnofsky performance status (KPS) > 70, who were treated with concurrent chemoradiation (CRT) at our center between April 2010 and October 2012, were included in this study. All patients gave informed consent for administering concurrent chemotherapy with radiation therapy. Baseline laboratory requirements for eligibility included a WBC count greater than 3000 cell/μL, an absolute neutrophil count greater than 1500 cell/μL, platelet count > 100,000 platelets/μL and serum creatinine < 1.5 mg/dL. Patients with co-morbid conditions adequately controlled with medical therapies were included.
Thirty-two patients were analyzed. Patient characteristics are shown in Table 1 . There were 27 males and 5 females with median age of 74 years (range, 65–87 years). KPS was 90 in 69% patients. All patients underwent complete staging workup with detailed clinical evaluation including endoscopies, contrast enhanced CT (CECT) scan of head and neck region, dental prophylaxis and dietary evaluation before initiation of treatment. Whole body PET-CECT was advocated only in those having N2c or higher nodal stage and with lower neck nodal positivity. Ultrasound abdomen and chest X-ray were undertaken for evaluating distant disease. Patients were staged by TNM criteria according to the AJCC 2007 staging system. All patients received radiation therapy with intensity modulated radiotherapy (IMRT) technique.
