Chapter 41

Treatment of the Elderly Head and Neck Cancer Patient

Jean-Claude Horiot and Matti S. Aapro

Abstract Elderly patients represent at least 40% of head and neck squamous cell carcinoma (HNSCC). These patients often receive inadequate treatment, either exceeding their tolerance capability or exposing them to a lesser chance of cure because of undertreatment. Customizing treatment to the individual patient is the key for avoiding such pitfalls. This paper analyses the literature on optimal management of elderly patients with HNSCC, from the diagnostic procedures with a comprehensive geriatric assessment (CGA) of co-morbidities to the specific recommendations for surgery, radiotherapy, and chemotherapy. Keywords Head and neck Cancer Elderly Geriatric Diagnostic Treatment Surgery Radiotherapy Chemotherapy

excluding patients over 65 or 70 years of age, thus leaving us with no evidence-based guidelines and a few often ill-defined recommendations for older patients age groups. This lack of evidence stresses the need for prospective studies with reliable assessment of patients co-morbidities aiming at well-defined treatment schedules including individually customized variations according to patients condition. Several conflicting facts need some clarification: it seems logical to accept the statement that the number and severity of co-morbidities increase with age and interfere with the choice of treatment and disease outcome. However, every year, more reports claim that head and neck cancer patients should be treated regardless of age when their general condition is satisfactory. Unfortunately, there is an epidemiologic evidence that most elderly patients do not benefit of the same chance of access to proper oncologic management as younger patients.

Introduction
The concept of elderly patient is highly questionable and definitely not closely linked to civil age. The median age for the diagnosis of invasive head and neck cancers is of about 60 years. More than 40% of head and neck cancers occur in patients older than 65 years [1]. Hence, the management of so-called elderly patients with head and neck cancer represents a very common situation in our daily practice. This incidence of elderly people with head and neck cancer squamous cell carcinoma (HNSCC) will further grow in the next decade due to several independent parameters: the constant increase of life expectancy in most industrialized countries, the limited efficacy of tobacco and alcohol prevention campaigns and growing female incidence, and finally the medical awareness to provide a better quality of care to the geriatric population. Unfortunately, as for other cancer types, most research trials have been using an upper age limit
J.-C. Horiot (*) Clinique de Genolier, Institut Multidisciplinaire dOncologie, 5 Route du Muids, Genolier CH-1272, Vaud, Switzerland e-mail: JCHORIOT@genolier.net

The Specificity of the Elderly Head and Neck Cancer Patient

By definition, the elderly patient with HNSCC has been exposed for a longer time to the main epidemiological features of such diseases: heavy tobacco and/or alcohol addictions with resulting co-morbidities, chronic obstructive broncho-pneumonitis, infection with various degrees or cardio-respiratory insufficiencies, liver steatosis and cirrhosis, poor oral hygiene and dental condition, fungal infections, malnutrition, weight loss, frailty, low-performance status, Wernickes encephalopathy, and associated neurological disorders. However, the degree of severity and combinations of co-morbidities widely differ from a patient to another. They should not constitute a contra-indication to curative treatment unless they would expose the patient to a shorter life expectancy than the spontaneous evolution of the malignant tumor. Moreover, a number of these co-morbidities are either ignored or insufficiently controlled at the time of the diagnosis of cancer. The identification, systematic evaluation, and, whenever possible, correction of such conditions
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should be done before starting the treatment of head and neck malignancies to give the patient the best chance for tolerance and ultimate benefit. Sometimes, however, the elderly head and neck cancer patient may just present with a perfect general condition and be biologically younger than most people in the same age group. Such patients should also be clearly identified and offered the same management as for younger patients.

Upper Age and Outcome in Curatively Treated Head and Neck Cancer Patients
The more solid data come from prospective research trials including patients older than 65 years with reliable data on acute and late morbidity as well as disease outcome, compared per age group. Under those conditions, the eligible patient population presents with a similar range of patients health conditions, disease stages, and management. In 1996, Pignon et al. [2] reported 1,589 patients with head and neck cancers enrolled in EORTC trials with follow-up on radiotherapy toxicity and survival. Patients over 65 years represented more than 20% of the sample. Survival and toxicity were examined in different age ranges from 50 to 75 years and over. There was no significant difference in survival between age groups. A trend test was performed to assess correlation between age and acute toxicity. There was no significant difference in acute objective mucosal reactions (p = 0.1) and in weight loss >10% (p = 0.4). In contrast, older patients had more severe (grade 3 and 4) functional acute toxicity (p < 0.001) than younger patients. The probability of late toxicity occurrence in relation to time was evaluated with the KaplanMeier method and the logrank test. Eighteen percent of patients were free of late effects at 5 years, the logrank test showing no significant difference between ages (p = 0.9). In conclusion, chronological age was considered irrelevant for therapeutic decisions. As a consequence, the recommendation was made to delete the upper age limit from the eligibility criteria in every EORTC on-going and new protocol of radiotherapy in head and neck cancer. In 2004, a report on the compliance to this recommendation in subsequent protocols was made by Horiot [3] during the 2004 SIOG (International Society of Geriatric Oncology) meeting in San Francisco and later published [4]. Six EORTC head and neck trials (including 574 patients) were activated after 1996. Two had an upper limit at 75 years and four no upper age limit (EORTC protocols 22954, 24954, 22962, and 24001). Only 15% of these 574 patients were aged 65 or more: Unfortunately, only one patient was older than 75. Despite of a satisfactory compliance from protocol writers, the recruitment of older patients was disappointing. The reasons for that low recruitment are probably multifactorial:

resistance to change, insufficient information of doctors and patients, and need for specific protocol design for adequate selection of elderly patients. Another probably relates to the increasing number of treatment schedules involving concomitant radio-chemotherapy regimens, obviously more toxic than radiotherapy alone. Literature reports on the outcome of treatment for head and neck cancer patients aged 80 years were very rare up until a few years ago. Several reports on this upper age group were recently published. Similar prognosis regardless of age after radiotherapy of head and neck cancers, including small subsets of patients over 80 years of age, has been reported by Metges [5], Schofield [6], and Zachariah [7]. Italiano [8] reports a series of 316 patients treated by surgery and/or radiotherapy and concludes that the outcome is similar to that of younger patients. However, this is an historical retrospective analysis of a regional database with selection biases and wide treatment variations. Ortholan [9] reports 260 patients over 80 years of age with oropharyngeal cancers. Two hundred patients received a locoregional treatment with a curative intent (surgery and/or radiotherapy), 29 with a palliative intent, and 31 did not receive a LR treatment. The median disease-specific survival (DSS) was 29 months. In multivariate analysis, the independent prognostic factors for DSS were stage (HR = 0.42 [0.240.72]), age (HR = 0.43 [0.240.75]), and performance status (HR = 0.50 [0.270.95]). The median overall survival (OS) was 14 months. In multivariate analysis, the independent prognostic factors for OS were age (HR = 0.52 [0.350.79]), stage (HR = 0.56 [0.380.84]), tumor differentiation (HR = 0.60 [0.330.93]), and performance status (HR = 0.6 [0.370.97]). In patients treated with a curative intent, treatment adapted to age was not associated with a decreased overall survival or DSS as compared with the standard treatment. However, prophylactic lymph node treatment in stage III tumors decreased the rate of nodal recurrence from 38 to 6% (p = 0.01). Impact of age at diagnosis on prognosis and treatment in laryngeal cancer was recently reviewed in 945 patients with laryngeal cancer treated from 1978 to 2004 in the UppsalaOrebro region in Sweden [10]: There were no significant differences in the clinical features between the age groups. Overall survival (OS) and DSS were worse among the oldest, although a significant proportion was cured. Relapse risk was lower among the oldest (12%) compared with the youngest (23%). However, the risk of never becoming tumor-free was 25% among the oldest versus 7% in the youngest. The authors conclude that although elderly patients with laryngeal carcinoma cope well with treatment, undertreatment may determine the outcome more than age. Although specific prospective trials are still badly missing, recent literature reports all stress that older age groups are of increasing relevance in HNSCC and need reliable and comprehensive pretreatment evaluations. This patient

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population also require the activation of prospective trials on adapted strategies and dose reductions whenever justified by risk factors induced by co-morbidities.

Multidisciplinary Diagnosis and Pretreatment Assessment in Geriatric Patients Definitions, Geriatric Scales, and Geriatric Evaluation Focused on Head and Neck Cancer Patients. Selection of Patients for Radical Treatment
The inclusion of a specific geriatric assessment in the multidisciplinary work-up of the cancer patient is a pre-requisite to give the best chance to the well-fit patient to receive the same treatment as a younger patient and to plan the appropriate changes in treatment strategies for patients with co-morbidities. The comprehensive geriatric assessment (CGA) [11, 12] is a multidisciplinary evaluation of functional, cognitive and psychological status, co-morbidities, nutritional status and medications, family, relatives, and social support. Functional status explores patients ability to fulfill usual daily activities. Objective performance measurements include the timed up and go test and the 6-min walk and grip test. Optimally, the geriatrician coordinates these evaluations and collect the data needed to complete the scoring scale. CGA is now a well-documented tool to predict morbidity and mortality in elderly patients with cancer [1315]. Repeated measurements during treatment and follow-up can reliably quantify the changes of patients condition with time. Practical algorithms have been published to assist clinicians in selecting patients for standard treatment versus modified schemes [15]. The severity of a single co-morbidity is of more relevance than the number of co-morbidities. The weight of such combinations is taken into account in the Adult Comorbidity Evaluation 27 (ACE-27) [16]. Nutritional evaluation, ultrasound screening of carotid arteries, identification of tobacco and alcohol addictions and assistance for stopping it, detection and treatment of depression, assessment of renal function measured by isotopic clearance methods are part of the pretreatment assessment of elderly head and neck cancer patients. Fatigue is a very common symptom, often of multifactorial origin. Its causes must be understood and whenever possible corrected before the starting of treatment since the deterioration of general condition and exhaustion of patient resources are the major reasons for noncompliance and/or early treatment interruption in curative management of elderly cancer patients.

There are, however, practical obstacles to organize a full-scale multidisciplinary CGA: Sometimes because of insufficient expertise or availability of some of the involved disciplines (including the geriatrician!), but mostly because of the lack of coordination to ensure a smooth and timely planning of the consultations and specific work-up of each consultant. That situation may result in suboptimal coordination and customization of treatment strategy. Obviously, multidisciplinary hospitals and/or cancer institutes usually offer the best conditions to set-up this rather heavy multidisciplinary work-up and management of the elderly cancer patient.

Preparation of the Patient to Treatment

Denutrition or malnutrition is present in about 20% of cancer patients. This figure is probably underestimated in geriatric head and neck cancer patients due to a reduced oral intake because of pain, difficulty in swallowing, and inappetence. Moreover, elderly people often do not complain of loss of appetite. Fluid intake is frequently suboptimal resulting in various degrees of dehydration, electrolyte imbalance sometimes associated with impaired renal function. The nutritional status of elderly patients should be systematically evaluated [17] at the time of the initial work-up since rapid deterioration may occur early in the course of radiotherapy and is a common observation when delivering concomitant radiochemotherapy. Missing this point would expose the patient to a high risk of poor treatment tolerance, treatment interruption, and/or dose reduction with a loss of chance of cure. Minor denutrition conditions should be dealt with dietetic counseling, oral nutritional supplements, and regular follow-up of oral intake during and after treatment. Artificial nutrition should be planned before treatment when oral intake is of less than 60% of needs and/or when severe mucosal and general side effects of treatment are expected. Percutaneous endoscopic gastrostomy (PEG) should be preferred to naso-gastric feeding tubes which may become a cause of discomfort upon the appearance of severe acute mucosal reactions. With proper prospective management, the need for parenteral nutrition remains rare, except for situations of severe malnutrition with poor digestive function, preexisting to cancer diagnosis. A systematic evaluation of the denture and periodontal tissues is mandatory in every head and neck cancer patient. It is even more important in the elderly patient in whom the probability of deterioration of dental condition is usually higher than in the younger patients. The clinical and radiological dental work-up should take place as early as possible to allow healing of dental extractions when needed without increasing the delay between diagnosis and treatment.

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When radiation therapy is planned, teeth in good condition will be preserved. Daily fluoride topical applications and oral hygiene will prevent postradiation dental caries [18]. Customized dental gutters will be manufactured to enable lifetime daily topical fluoride gel applications. Oral hygiene recommendations and compliance to fluoride applications should be initiated and checked during radiotherapy. The use of very high fluoride toothpaste contents (about 1,300 ppm) is an alternative method when customized gutters are poorly tolerated, e.g., when acute mucosal reactions occur. Keeping good dental status and hygiene is an essential component of maintaining a good nutritional intake. Edentulous patients also need to be evaluated to detect the presence of hidden risks (sharp extractions edges, residual roots, impacted wisdom teeths, etc.) and to check the condition of removable dental prosthesis. Elderly patients are often left alone to deal with the constraints of disease diagnostic and therapeutic procedures. This may sometimes result in inappropriate patient understanding and adhesion to therapeutic recommendations, thus leading refusal or poor compliance to treatment. Adequate management of the elderly cancer patient, including specific advice and support on head and neck cancer treatment, must be organized in the frame of the geriatric oncology team, with, whenever needed, the availability of psycho-social workers and psycho-oncologists. This includes the information of patients and relatives as well as the assistance for proper organization of patient venues (transportation and timing) for the duration of ambulatory treatments.

Management of the Elderly Cancer Patient Curative Aim

Surgical Management of the Elderly Patient Predictive factors for complications in surgically treated elderly patients with HNSCC have been analyzed by Sanabria [19] in 242 patients over 70 years of age. Co-morbidities were present in 87.6% of patients and 56.6% presented with complications (44.6% local and 28.5% systemic). Male sex, bilateral neck dissection, presence of two or more co-morbidities, reconstruction procedures, and clinical stage IV were associated with a high risk of postoperative complications. The authors propose a predictive index based upon preoperative variables which, in their series, shows a 84% sensitivity and 41% specificity. As expected, the main limitation to surgical indications in the elderly cancer patients is the number and severities of

co-morbidities, interfering with the risks of general anesthesia, and perioperative period. In most cases, mild cardiovascular co-morbidities can be corrected and should not interfere with the treatment choice. Conservative surgical techniques should be preferred whenever possible. Reconstructive surgery with flaps is seldom considered in older patients since higher complications rates are reported in patients of more than 70 years of age [20]. Moreover, older patients are known to be less compliant to feeding and phonatory rehabilitation procedures than younger patients [21]. Radiotherapy alone or radio-chemotherapy when feasible should be preferred to mutilating surgery in moderately advanced and advanced laryngeal and hypopharyngeal carcinomas. Conservative surgical procedures either by cervicotomy or by transoral resections [22] can be considered in the management of limited carcinomas of oral cavity, oropharynx, and larynx especially when the need for postoperative radiotherapy is unlikely. Early vocal cord cancers can be either treated surgically (usually by microsurgical carbon dioxide laser techniques) or by radiotherapy alone although the quality of voice seems superior with radiotherapy. Difficult access to radiotherapy facilities and shorter treatment with surgery may be good arguments in favor of surgery. Functional neck node surgery, whenever indicated, can be usually performed regardless of age except for major medical contra-indications. Recommendations on the surgical management of elderly patients with cancer have been issued by experts of the International Society of Geriatric Oncology [23]. In most cases, however, surgery will be combined to radiation therapy, mostly postoperatively. The quality of surgical techniques and pathology report are essential to optimal radiotherapy planning and to reduce the risk of late complications from combined treatment. With modern radio-surgical techniques, the risk of carotid artery rupture has become very low. However, the risk of carotid stenosis and cerebrovascular stroke is not negligible after neck dissection and radiotherapy, reported sometimes as high as 3040% [24, 25]. An effective prevention of such risk is made by identifying and treating patients with risk factors (tobacco addiction, hypertension, dyslipidemia, and ultrasound screening of carotid arteries before and after treatment). Modern radiotherapy techniques have almost eliminated the dose hot spots that could result, for instance, from overlapping the upper and lower neck nodal target volumes.

Radiotherapy The consistency of geriatric assessment recommendations to patients receiving radiotherapy was discussed by Falandry [26]. However, although general statements apply to HNSCC patients, no comments is made regarding the specificity of

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head and neck radiotherapy. By definition, radiotherapy to HNSCC is a local-regional treatment. Small tumors from almost any head and neck site, adequately irradiated with well-controlled target volumes to the primary site and first nodal level, produce moderate mucosal side effects and provide high cure rates. Hence, age should not interfere at all with the indication of curative radiotherapy. Larger primary tumors, usually associated with various degrees of nodal spread, will need a more aggressive treatment on larger tumor and nodal target volumes with more toxic mucosal acute side effects that will interfere with patient nutrition and treatment tolerance. The difficulties met with radiotherapy to elderly patients will be potentialized in these moderately advanced and advanced HNSCC. Techniques of external megavoltage radiotherapy have considerably progressed over the past decade allowing high accuracy to conform target volumes to effectively irradiate volumes and enable a better sparing of normal tissues. Intensity-modulated radiotherapy technique (IMRT) is now the reference radiotherapy technique to treat head and neck cancers. Brachytherapy also benefited from imaging progress but remains less frequently used probably because it requires a more specific expertise and is performed under general anesthesia. As a result, acute tolerance has markedly improved while the incidence and severity of late normal tissue damage decreased. The benefit from innovative radiotherapy techniques is essential to offer head and neck cancer geriatric patients, the best chance of a good tolerance to curative radiotherapy. Acute tolerance is improved by minimizing skin and mucosal reactions. The main benefit seems however arise from the reduction of the incidence and severity of late effects, mainly fibrosis (by multiplication of portals) and xerostomia by sparing whenever possible the contra-lateral salivary glands [27]. Unfortunately, IMRT is not available in every radiotherapy department. When present, not all patients can benefit of it for reasons of cost, availability, and experience. Even when novel techniques are available, the geriatric population may be excluded from their use, either by the absence of specific protocol recommendations or worst, as being considered as a low priority. Most of the literature on radiotherapy toxicity in elderly patients is gathered from the reports of series treated with standard radiotherapy which still provide a biased message to contraindicate radiotherapy or lower total doses, thus reducing the chance of cure of these patients. Socioeconomic and psychological issues may interfere with the medical decision as well as the patient acceptance or refusal to radiotherapy. The distance between patient home and treatment site may not be consistent with a protracted ambulatory treatment. Access to local hosting facilities for elderly people for the duration of their treatment is rare and sometimes unaffordable. Hospital admission may be either

impossible because of priorities given to other patients or refused by the patient. Daily transportation for long distances may generate psychological lassitude and physical fatigue that may jeopardize treatment delivery and outcome by early stopping or increased overall treatment time. In some cases, a dose/fractionation compromise is proposed to patients, by reducing the number of fractions and increasing the dose per fraction. This concept called hypofractionation, when equivalent biologic tumor doses are delivered, always results in increased late normal tissue damage, sequelae, and complications. Head and neck hypofractionated radiotherapy with a lower biological tumor dose exposes the patient to a poorer outcome and should be reserved for palliation only. Prevention of nutritional deterioration is essential when irradiating large volumes of oral cavity, oropharyngeal, and hypopharyngeal mucosa. As said earlier, a PEG should be performed before starting treatment and be progressively used to compensate reduced oral intake due to the progression of mucosal reactions. Oral hygiene recommendations, preventive treatment of bacterial and fungal infections, should almost systematically be activated.

Radiotherapy and Chemotherapy Up until the advent of platinum compounds, there was no or little interest in combining radiotherapy and chemotherapy in head and neck cancers. The additional toxicity of chemotherapy was then a major argument to contra-indicate its use in frail and/or elderly patients. The results of randomized trials and meta analyses [28] then demonstrated that cisplatinum-based schemes and radiotherapy could significantly improve the outcome compared to radiotherapy alone, the main benefit being observed after concomitant radio-chemotherapy at the cost of an increased (mostly acute) toxicity. Postoperative concomitant radio-chemotherapy has become standard management of moderately advanced and advanced head and neck cancers carrying a significant locoregional failure risk [29]. Of course, these randomized trials excluded almost all frail and elderly patients. The revival of the interest of induction chemotherapy was raised by trials on laryngeal preservations [30, 31] and more recently by the local-regional and survival benefit of neoadjuvant Taxanes [32]. Moreover, a noncytotoxic moleculartargeted therapy [anti-epidermal growth factor receptor (anti-EGFR) cetuximab] combined with radiotherapy also produced a significant locoregional and survival benefit in moderately advanced head and neck cancers. These progresses, although not applicable in all patients, have urged to reconsider the indications of chemotherapy in the elderly patients. The main severe toxicities of cisplatinum-based chemotherapy consist of renal failure with potassium and magnesium

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losses, nausea and vomiting, peripheral neuropathies, and hearing impairment. Adequate hydration is not always feasible in older patients. Dose reductions based only on the patients age should not be done when treatment is given with a curative aim. Attention should be given about the results provided by the CockcroftGault method to calculate creatinine clearance which often underestimates renal function in elderly patients [33]. Combined platinum-based chemoradiotherapy regimens, used in healthy nonelderly patients, substantially increase the incidence of severe acute [34, 35] and late adverse events [36, 37]. Hence, they should be prescribed with care in fit elderly patients only. Cisplatin is the preferred platinum agent and is associated with higher tumor response rates than carboplatin [38], which because of a better toxicity profile is often reserved for patients unable to tolerate cisplatin. The usefulness of the addition of 5-FU to platinum compounds is still debated in younger patients because its advantages are not obvious while inconveniences (cardiotoxicity and increased mucosal toxicity) are well documented. Hence, although it can be safely delivered to elderly patients in good general condition [39], it is preferable in most cases to prescribe a single platinum compound. Taxanes (Paclitaxel and Docetaxel) metabolism can be affected in patients with impaired liver function, a significant decrease in total paclitaxel clearance being observed with increasing age [40]. This may contra-indicate the use of taxanes in patients with severe alcoholic-induced liver dysfunction. The sequential combinations of cisplatin and taxanes increase the incidence and severity of peripheral neuropathies. Combinations of cisplatin, fluorouracil, and taxanes, now widely used for induction chemotherapy, can produce a large range of acute severe toxicities: Grade 4 neutropenia and febrile agranulocytosis, sepsis, and severe mucositis. Thus, the combination of these three therapies must be avoided or prescribed only to elderly patients without any co-morbidity. Careful patient selection of elderly patients allows induction chemotherapy with cisplatin and docetaxel as shown in 44 patients over 65 years of age with stage III and IV head and neck cancers using a 3-week course [41]: The overall response rate was 88%, with grade 34 neutropenia in 75% and febrile neutropenia in 4%.

lower toxicity than most cytotoxic drugs and seem an attractive alternative combination with radiotherapy in older and/or frail patients. The first randomized trial comparing radiotherapy and cetuximab to radiotherapy alone [42] concluded to a 30% reduction in the risk of disease progression and 11% increase in the 3-year PFS rate survival in favor of the experimental arm. There was no upper age limit in the eligibility criteria. Acute mucosal reactions were similar in both arms. The main acute cetuximab toxicity consists of acneiform rash (17%) occurring predominantly in the facial and cervical areas. Of interest, this rapidly reversible side effect seems to be associated with a better chance for improved survival; grade 24 acne/rash being associated with a 51% reduction in the risk of death compared to that of patients with a 01 grade of acne/rash [43]. This rather acceptable toxicity profile seems attractive for including cetuximab in the radiotherapy management of elderly head and neck cancer patients. In the original randomized trial, the median age is 57, suggesting a very low percentage of elderly patients entered in this study. Although not formally established on a nonselected elderly population, the addition of cetuximab to curative radiotherapy for elderly patients seems to be safe. Several trials are underway to evaluate the combination of cetuximab and radiotherapy in the management of other cancers, esophageal, and non-small cell lung cancers in elderly patients. Moreover, the addition of an intratumoral EGFR antisense oligonucleotide gene therapy (EGFR AS) is underway in untreated locally advanced HNSCC who either elderly (i.e., 70 years or older) or cisplatin ineligible [44].

Radiotherapy, Chemotherapy, and Molecular-Targeted Therapies The EXTREME phase III trial [45, 46] undertaken in recurrent and/or metastatic head and neck cancers, adding cetuximab to standard first-line platinum-based chemotherapy, produced statistically and clinically significant benefits, in terms of prolonged survival, and improved tumor response, compared with the traditional approach of combination chemotherapy. Of interest, 77 patients (10% of the whole sample) were over 65 years of age. The next logical step in healthy patients is to investigate the role of cetuximab in combination with definitive chemoradiotherapy in locally advanced disease. The on-going phase III RTOG 0522 trial, comparing a chemoradiotherapy regimen of accelerated concurrent radiotherapy plus cisplatin with the same chemoradiotherapy regimen plus cetuximab, should provide the answer. Presently, it is prematurate to propose this combined scheme to elderly fit head and neck cancer patients outside of a research trial.

Radiotherapy and Molecular-Targeted Therapies About 90% of head and neck cancer cells over-express the epidermal growth factor receptor (EGFR), which correlates to the malignant phenotype leading to reduced apoptosis, high proliferation rate, angiogenesis, and metastatic invasiveness. Agents blocking this malignant phenotype have a

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587 4. Horiot JC. Radiation therapy and the geriatric oncology patient. J Clin Oncol. 2007;25(14):19305. 5. Metges JP, Eschwge F, de Crevoisier R, et al. Radiotherapy in head and neck cancer in the elderly: a challenge. Crit Rev Oncol Hematol. 2000;34:195203. 6. Schofield CP, Sykes AJ, Slevin NJ, et al. Radiotherapy for head and neck cancer in elderly patients. Radiother Oncol. 2003;69:3742. 7. Zachariah B, Balducci L, Verkattaramanabalaji GV, et al. Radiotherapy for cancers aged 80 and older. A study of effectiveness and side effects. Int J Radiat Oncol Biol Phys. 1997; 39:11259. 8. Italiano A, Ortholan C, Dassonville O, et al. Head and neck squamous cell carcinoma in patients aged > or = 80 years: patterns of care and survival. Cancer. 2008;113:31608. 9. Ortholan C, Lusinchi A, Italiano A, et al. Oral cavity squamous cell carcinoma in 260 patients aged 80 years or more. Radiother Oncol. 2009;93:51623. 10. Reizenstein JA, Bergstrm SN, Holmberg L, et al. Impact of age at diagnosis on prognosis and treatment in laryngeal cancer. Head Neck. 2009;32:10628. 11. Extermann M. Studies of comprehensive geriatric assessment in patients with cancer. Cancer Control. 2003;10:4638. 12. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25:182431. 13. Repetto L, Fratino L, Audisio RA, et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol. 2002;20: 494502. 14. Extermann M, Aapro M, Bernabei R, et al. Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol. 2005;55:24152. 15. Rodin MB, Mobile SG. A practical approach to geriatric assessment in patients with cancer. J Clin Oncol. 2007;25:193644. 16. Sanabria A, Carvalho AL, Vartanian JG, et al. Comorbidity is a prognostic factor in elderly patients with head and neck cancer. Ann Surg Oncol. 2007;14:144957. 17. Tran M, Raynard B, Bataillard A, Duguet A, Garabige V, Lallemand Y, et al. Standards, Options and Recommendations 2005 for a good practice in enteral nutrition in oncology (summary report). Bull Cancer. 2006;93:71522. 18. Horiot JC, Schraub S, Bone MC, et al. Dental preservation in patients irradiated for head and neck tumours: a 10 year experience with topical fluoride and a randomized trial between two fluoridation methods. Radiother Oncol. 1983;1:7782. 19. Sanabria A, Carvalho AL, Melo R, et al. Predictive factors for complications in elderly patients who underwent oncologic surgery. Head Neck. 2008;30(2):1707. 20. Pompei S, Tedesco M, Pozzi M, et al. Age as a risk factor in cervico-facial reconstruction. J Exp Clin Cancer Res. 1999;18: 20912. 21. Ashley J, Duggan M, Sutcliffe N. Speech, language and swallowing disorders in older adult. Clin Geriartr Med. 2006;22:291310. 22. Werner JA, Dunne AA, Folz BJ, et al. Transoral laser microsurgery in carcinomas of the oral cavity, pharynx and larynx. Cancer Control. 2002;9:37986. 23. Audisio RA, Bozzetti F, Gennari R, et al. The surgical management of elderly cancer patients: recommendations of the SIOG surgical task force. Eur J Cancer. 2004;40:92638. 24. Dubec JJ, Munk PL, Tsang V, et al. Carotid artery stenosis in patients who have undergone radiotherapy for head and neck malignancies. Br J Radiol. 1998;71:8725. 25. Brown PD, Foote RL, McLaughlin MP, et al. A historical prospective cohort study of carotid artery stenosis after radiotherapy for

Recommendations Elderly head and neck cancer patients should benefit of the same diagnostic investigations and multidisciplinary decision process than younger patients. Elderly patients should access to a CGA (comprehensive geriatric assessment) to identify, quantify, and whenever possible treat co-morbidities. Elderly patients should be exposed to more aggressive management than they are currently receiving. This management should be closer to that currently received by younger patients. Patients should receive the most intensive and appropriate treatment thought to be safe and effective according to their biological age and co-morbidities. The aim should be to maximize the overall survival while minimizing the toxicity to achieve the greatest patient benefit. Socioeconomic and psychological issues should be dealt with to facilitate access, acceptance, and compliance to treatment. The maintenance of a proper dietetic input and balance should be planned and controlled before during and after treatment using preferably PEG whenever an insufficient oral intake is foreseen. Lighter radiotherapy (and chemotherapy) schedules should be preferred to supportive care only, unless survival expectancy is very short. The inclusion of fit elderly patients in research protocols should be encouraged regardless of age. Specific protocols should be designed for elderly patients with co-morbidities in order to collect evidence-based data on optimal management of these patients. CGA should be involved in trial design and clinical practice to document how to tailor treatment to a patient population of growing incidence.

References
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