Critical Reviews in Oncology / Hematology
Volume 74, Issue 2 , Pages 79-86, May 2010

Lhermitte's sign: Review with special emphasis in oncology practice☆

  • Cengiz Gemici

      Affiliations

    • Corresponding Author InformationTel.: +90 532 5780702; fax: +90 216 3273374.

Dr. Lutfi Kirdar Kartal Education and Research Hospital, Department of Oncology, Barajyolu cad. Adiguzel Sitesi K-Blok Daire, 20 Yukari Dudullu, Umraniye, Istanbul, Turkey

Accepted 30 April 2009. published online 03 June 2009.

Article Outline

Abstract 

Lhermitte's sign (LS) is characterized by electric shock like sensation, spreading along the spine in a cervico-caudal direction and also into both arms and legs, which is felt upon forward flexion of the neck. It is a myelopathy resulting from damage to sensory axons at the dorsal columns of the cervical or thoracic spinal cord and a well-known clinical sign in neurology practice. Patients with cancer may present with LS due to various causes either related to the tumor itself or to its treatment. Spinal cord tumors, radiotherapy and chemotherapy are possible causes of LS observed in oncology practice. While LS is observed with a frequency of 3.6–13% in large patient groups receiving radiotherapy for head and neck and thoracic malignancies, the true incidence of chemotherapy and spinal cord tumor induced LS is unknown with only few reported cases in the literature. In the present article, various pathologies causing Lhermitte's sign are reviewed with special emphasis on the implications of this sign in oncology practice.

Keywords: Lhermitte's sign, Myelopathy, Chemotherapy, Radiotherapy, Cancer, Neurotoxicity

 

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1. Introduction 

Lhermitte's sign (LS) is a rare nonspecific neurologic complication arising from involvement of spinal cord and can be associated with various conditions. It is characterized by an unpleasant sensation or pain in form of electric discharge spreading down the spine and limbs with neck flexion. In fact it is rather a symptom than a sign and it can be stimulated by certain maneuvers like Valsalva, bending of the head, coughing. This sign was first reported by Marie and Chatelin in 1917, during the First World War [1]. They described ‘pins and needles’ type sensations traveling the spine which were induced by forward flexion of the head in soldiers who had suffered cranial trauma [1]. Although first observed and reported by Marie and Chatelin, LS was defined in detail and introduced to the neurology literature by Jean Lhermitte, as a clinical entity like the Babinski's sign [2], [3]. Beside traumatic lesions of the head and spinal cord which were initially identified as the cause of this sign, Lhermitte was the first to report it in a patient with multiple sclerosis (MS) [2], [3]. He emphasized the importance of this sign in the early diagnosis of multiple sclerosis. He contributed to the pathogenesis of this sign and published several papers. He suggested that this symptom was due to the irritation of the spinal cord resulting in axonal demyelination with preservation of axonal continuity at the cervical level of the spinal cord. He also showed the existence of this sign in other diseases that could affect the spinal cord, like pernicious anemia [3].

Besides being a well-known clinical sign in neurology practice, LS is also encountered in oncology practice in association with various oncologic pathologies involving the spinal cord.

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2. Methods 

2.1. Search strategy and selection criteria 

Data for this review were identified by searches of PubMed using the search terms “Lhermitte's sign”, “Lhermitte's”, “Lhermitte” “myelopathy” and “neurotoxicity”, and using references from relevant articles. One abstract from Proceedings of American Society of Clinical Oncology published in 1995 was included as it was directly related to the subject. Papers published until the end of 2008 were included.

The study was not funded by any source.

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3. LS in neurology and neurosurgery practice 

3.1. Pathophysiology 

The exact pathophysiology of LS is not known. Any event causing damage, irritation or compression of myelinated sensory axons in dorsal columns of the spinal cord at cervical or rarely thoracic level can give rise to this sign. The characteristic electric-like sensation of the sign, which spreads down the spine to the arms and legs, is triggered by the flexion of the neck. How neck flexion causes generation and transmission of electric-like sensory discharges is unclear; but it is presumed that neck flexion causes a mechanical stimulation of the damaged myelinated axons by lengthening and deforming the affected area of the cervical spinal cord [4], [5]. LS is not specific to any disease and can be present in a variety of clinical conditions. Among different causes, demyelination, trauma, spinal cord injuries and compression, spinal cord tumors, metabolic and toxic conditions, infections, vitamin deficiency states, inflammatory diseases can be cited.

Although the pathologic process takes place in dorsal part of the cervical spinal cord, and can usually be localized by radiological imaging, electrophysiologic studies and clinical observation, the exact mechanism by which LS occurs is unclear. This special type of spinal cord toxicity in most of the clinical situations described above develops due to the interference with the synthesis and turnover of myelin resulting in segmental demyelination at the dorsal columns of the cervical spinal cord [4], [6]. It may disappear gradually without any sequelae, when the oligodendrocytes recover from the damaging cause and resume the myelin synthesis [6], [7].

Among the possible causes vitamin B12 deficiency is the most important one, since LS is a frequent finding during the course of this vitamin deficiency and its pathophysiology is well known.

Vitamin B12 is involved in myelin synthesis and repair and, its deficiency results in a systemic disease that often affects the nervous system [8], [9], [10], [11]. Subacute combined degeneration of the spinal cord is one of the most prevalent clinical manifestations of vitamin B12 deficiency. Neuropathological findings are diffuse multifocal pattern of axonal loss and demyelination at the cervical and thoracic spinal cord levels. Dorsal columns followed by anterolateral and anterior tracts of the spinal cord are mostly affected.

Multiple sclerosis, radiotherapy and chemotherapy may also induce LS by a demyelination related mechanism similar to Vitamin B12 deficiency.

3.2. Imaging and radiologic findings 

The evidence supporting the role of a pathologic process at the dorsal columns of the cervical spinal cord comes from electrophysiologic studies and radiological investigation of the brain and spinal cord of the affected patients [5], [12], [13], [14], [15]. In vitamin B12 deficiency and subacute combined degeneration of the spinal cord, magnetic resonance imaging (MRI) show increased T2-weighted signal, decreased T1-weighted signal, with contrast enhancement of the posterior and lateral columns of the spinal cord, mainly at the cervical and upper thoracic segments [13]. MRI may even be useful in assessing the response to vitamin B12 replacement therapy. The symptoms, however may precede any imaging abnormality [13], [16]. MRI in patients with multiple sclerosis discloses a strong association between LS and the presence of demyelinated plaques at the posterior part of the cervical spinal cord [12]. In one report, 22 patients among 28 presenting with LS, had abnormal findings on cervical MRI, and the authors concluded that a lesion at the posterior part of the cervical spinal cord was responsible for LS in multiple sclerosis [12]. Miller et al. [14] in a review comprising noncompressive spinal cord syndromes, observed a lesion at the posterior part of the cervical spinal cord on MRI in 11 out of 13 patients presenting with LS. Beside radiological findings, further evidence supporting the role of posterior cervical spinal cord involvement comes from the association of LS with compressive lesions of cervical spinal cord, with tumors involving posterior part of cervical spinal cord or with mechanical stimulation of the posterior part of the cervical spinal cord during surgery [17], [18], [19], [20], [21]. Neurophysiological studies conducted by Nordin et al. in the presence of LS, also suggested the involvement of posterior columns at the cervical spinal cord level [5]. Imaging with positron emission tomography (PET) may also provide additional information, not only on the location of the involved area of the spinal cord but also on the pathophysiology of the symptom, even when MRI is not informative although a sensitive tool in the detection of demyelination of posterior columns of the spinal cord [6], [22]. Esik et al. demonstrated increased 18-Fluorodeoxyglucose (FDG) uptake in the irradiated spinal cord segment in two patients with long standing radiation related LS [6], [22]. FDG uptake differs in different organs depending on the functional status of the organs. The spinal cord in contrast to the brain has a very low FDG accumulation because of considerable proportion of white matter. There is normally low glucose consumption and blood perfusion. However in case of LS, there is increased metabolism and perfusion at the involved site of the spinal cord which is very much like the situation in the brain. Esik et al. suppose that an elevated FDG uptake in the irradiated spinal cord segment in the presence of long standing LS may be related to inflammatory process or another phenomena involving an augmented energy requirement [6], [22].

3.3. Incidence of LS in neurology and neurosurgery practice 

Multiple sclerosis [23], [24], [25], head and neck injuries [1], [17], [18], [26], [27], [28], [29], vitamin B12 deficiency, subacute and combined degeneration of the spinal cord [8], [9], [10], [11], herpes zoster infection [30], Behcet's disease [31], [32], systemic lupus erythematosus [33], nitrous oxide abuse [34], [35], [36], and cavernous angioma of the cervical spinal cord [37], congenital partial aplasia of the posterior arch of the atlas [20], are the most important ones encountered in neurology and neurosurgery practice.

LS, although first described in patients with head traumas, is not so common after head and neck traumas and is usually reported in the literature as case reports. Among these neurologic pathologies, LS is most frequently observed in patients with multiple sclerosis. It is present in about one-third of these patients [23], [38]. In one review comprising 300 MS patients, 41% of the questioned patients reported to have LS during the course of their illness [24], and in most of them it was an isolated symptom during the first years of the disease [24]. Lhermitte himself stated that the symptom may occur early in the course of disease and the presence of the symptom in an otherwise healthy person may suggest the diagnosis of MS [2], [3].

Apart from MS, LS is also a common finding during the course of vitamin B12 deficiency and subacute combined degeneration of the spinal cord [8], [9], [10], [11]. Gautier-Smith observed LS in one-fourth of their patients which presented with subacute combined degeneration of the spinal cord [11].

Patients with a history of chronic exposure or abuse of nitrous oxide, particularly healthcare professionals, also experience a myeloneuropathy accompanied by LS. In addition to many other neurological problems encountered, affected individuals often present with LS [34], [35], [36]. The neurological pathology in nitrous oxide related LS is similar to subacute combined degeneration of the spinal cord, and it is presumed that nitrous oxide interferes with the action of vitamin B12 in the nervous system [35]. LS cases associated with other neurological conditions are rare and limited to individual case reports.

Cancer patients may present with LS due to various causes either related to the tumor itself or to its treatment. Spinal cord tumors, radiotherapy and chemotherapy are possible causes of LS observed in oncology practice.

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4. LS in oncology practice 

Although first described as a neurological sign occurring with head and neck traumas [1], [17], [18], [26], [27], [28], [29], multiple sclerosis [12], [23], [24], [25], and thus mainly encountered in neurology and neurosurgery practice, LS later became a well-known neurological sign in oncology practice (Table 1).

Table 1. Frequency of LS in different conditions.
ConditionFrequencyComment
Multiple sclerosis [23], [24], [25]Common, in one-third of patientsHelpful in diagnosis
Vitamin B12 deficiency [8], [9], [10], [11]Common, in one-fourth of patients with subacute combined degeneration of spinal cordPathophysiology is quite clear
Head and neck trauma [17], [18], [26], [27], [28], [29]Rare, individual case reportsLhermitte's sign was first described in association with this condition
Herpes zoster infection [30]Rare, individual case reports
Behcet's disease [31], [32]Rare, individual case report
Systemic lupus erythematosus [33]Rare, individual case reports
Nitrous oxide abuse [34], [35], [36]RarePathophysiology similar to vitamin B12 deficiency
Cavernous angioma of the spinal cord [37]Rare, individual case reports
Radiotherapy related LS [6], [41], [42], [43], [69]Common after head and neck radiation treatmentObserved with radiation fields covering cervical and thoracic spinal cord segments
Chemotherapy related LS [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62]RareUnderreporting may explain rarity; mostly associated with cisplatin and oxaliplatin
Bone marrow transplantation [63]Rare, individual case reportsMultiple factors may be responsible
Spinal cord tumors [19], [21], [67], [68]RarePrimary or metastatic tumors

4.1. Radiotherapy related LS, incidence and pathophysiology 

Radiation causes spinal cord toxicity in two different forms: a transient and reversible myelopathy characterized by LS, which appears soon after or within 6 months, following the completion of radiation treatment [39]; a permanent and irreversible myelopathy, which is characterized by a Brown-Séquard like transverse myelitis, which appears one year or later after the completion of radiation treatment [39]. While delayed radiation myelopathy is the most fearful complication and causes permanent paralysis, transient radiation myelopathy is a self-limited sensory disturbance in the form of LS and resolves spontaneously without any sequelae. Demyelination of the ascending sensory neurons is the cause of LS developing as a result of radiotherapy [39]. Radiation causes injury to the myelin forming oligodendroglial cells and results in temporary demyelination [7], [40]. When oligodenroglial cells recover and myelin synthesis is restored, LS disappears.

Both types of radiation myelotoxicity and LS may develop following radiotherapy, especially of head and neck and thoracic neoplasmes. LS developing in the context of transient radiation myelopathy is not rare and its incidence was reported to be between 3.6% and 13% in large patient groups receiving radiotherapy for head and neck and thoracic malignancies [6]. In one study, nasopharyngeal carcinoma patients treated primarily by radiotherapy, LS was observed in 121 out of 1171 patients (10.3%) [41]. The authors examined the risk factors for the development of LS. While no significant correlation was found between the development of LS and neither sex or tumor stage, interestingly the incidence was significantly lower for patients who had also received chemotherapy compared to patients receiving only radiotherapy. The incidence was also lower for patients older than 60 years than for those younger than 60 years [41].

In another report, 1112 patients treated for various head and neck malignancies, Fein et al. [42] found a 3.6% incidence of LS. The mean time to the development of LS after radiotherapy was 3 months, and the mean duration of symptoms was 6 months. Among the risk factors evaluated, total radiation doses above 50Gy to the cervical spinal cord, and daily radiation fraction doses above 2Gy was found to be significant for the development of LS [42]. None of the patients with LS developed later delayed radiation myelopathy. Thus LS appearing in the context of transient radiation myelopathy is not associated with chronic progressive myelitis, however delayed radiation myelopathy which is irreversible and results in paralysis may be preceded by LS [6]. LS that predated delayed radiation myelopathy is observed later in onset than the usual latency period of LS observed in transient radiation myelopathy [6], [42]. A dual mechanism of injury has been postulated to contribute to the pathogenesis of delayed radiation myelopathy [39]. One is related with endothelial cell injury leading to microvascular dysfunction resulting in hemorrhagic necrosis and infarction of the irradiated segment of the spinal cord, and the second is related to cellular damage to oligodendroglial cells leading to marked demyelination. Risk for delayed radiation myelopathy increases with the increase in the volume of irradiated segment of the spinal cord, with the increase in the total dose of radiation received by the irradiated part of the spinal cord, and with the increase in the dose per fraction of the radiation delivered [39]. Due to devastating result of delayed radiation myelopathy, radiation oncologists take every precaution to avoid delayed radiation myelopathy. At present the maximum dose considered safe for spinal cord tolerance and for the prevention of delayed radiation myelopathy is 45–50Gy delivered in 1.8–2Gy daily fractions. When the spinal cord dose is kept below 50Gy, the incidence of delayed radiation myelitis is very low. Marcus and Million observed only two cases of delayed radiation myelopathy among 1112 patients treated for head and neck malignancies with various radiation doses [43].

Spinal cord tumors, either primary or metastatic were rarely reported in the literature as the cause of LS [19], [21]. Chemotherapy associated LS is also rare.

The rarity of this sign in association with chemotherapy may be related to the lack of knowledge about this sign and lack of reporting, or considering the classical symptoms of LS as a component of sensory neuropathy of the administered chemotherapeutic agents, which is the commonest neurotoxicity related to the chemotherapy.

4.2. Chemotherapy related LS, incidence and pathophysiology 

Neurologic side effects are common complications of widely used chemotherapeutic agents. These side effects encountered during chemotherapy can cause discontinuation of treatment or dose modification. Chemotherapy related neurotoxicity can substantially impair the patient's quality of life. Among the many chemotherapeutic agents, taxanes, platinum compounds and vinca alkaloids are the most important ones associated with neurotoxicity [44], [45], [46], [47], [48]. Chemotherapeutic agents can be toxic either at the central nervous system or at the peripheral nervous system. They can cause different forms of neurotoxicity depending on the site of involvement. The chemotherapy induced neurotoxicity can be acute, subacute or chronic [44], [45], [46], [47], [48]. It is usually cumulative and dose dependent. Chemotherapy related neurotoxicity is potentially reversible and resolves gradually after termination of treatment [44], [45], [46], [47], [48]. Preexisting diabetes mellitus, chronic alcoholism, other disorders predisposing to neuropathies or administration of concurrent neurotoxic drugs increase the risk of neurotoxicity associated with chemotherapy. Neurotoxicities encountered with chemotherapeutics include, peripheral neuropathy, cerebellar toxicity, encephalopathy, cerebrovascular events, neuropsychiatric symptoms, autonomic neuropathy, cranial nerve palsies, ototoxicity, retinal toxicity and spinal cord toxicity which also includes LS [44], [45], [46], [47], [48]. Peripheral sensory neuropathy is the most common type of neurotoxicity observed in the clinic and results from either damage to dorsal root ganglia, or axonal degeneration, or demyelination. This neuropathy manifests itself as paresthesias in the fingers, the toes and the feet, loss of deep tendon reflexes and vibration sense.

Chemotherapy induced LS is very rare. Cisplatin is the most common chemotherapeutic agent reported in association with this sign [49], [50], [51], [52], [53], [54]. The definitive pathology of chemotherapy related LS is not known, but the chemotherapeutic agents associated with this sign are potentially neurotoxic and mostly give rise to peripheral sensory neuropathy through a demyelination related mechanism [48], [55], [56], [57], [58]. Postmortem examination of a patient heavily treated with cisplatin showed marked degeneration of dorsal columns with substantial axonal loss in dorsal roots while ventral roots were spared from this effect [59]. The central nervous system and the spinal cord appear to be spared from toxic effects of the chemotherapeutics because of poor passage of these drugs through the blood–brain barrier. The rarity of chemotherapy associated LS is probably due to the protection of the spinal cord from the neurotoxic effect of these agents by this barrier, which is not present in peripheral nerves and dorsal root ganglia. Another possible explanation for the rarity of LS associated with chemotherapy may be the lack of reporting due to the lack of knowledge about LS among medical oncologists. They may mistakenly consider LS, as if it is the characteristic neurotoxicity of the applied chemotherapeutic agent, which most of the time is the peripheral sensory neuropathy and is frequently present together with LS. Another reason for the reported rarity of this sign may also be lack of questioning the patients receiving neurotoxic chemotherapy about the presence of this sign by the treating oncologist.

There are only few reports of LS published in the English medical literature associated with chemotherapeutic agents other than cisplatin. These chemotherapeutic agents include: docetaxel [55], [56], oxaliplatin [57], [58], [60], [61], carboplatin [62], busulfan and cyclophosphamide [63].

Isolated myelopathy in the form of LS is rare with chemotherapy. Most of the patients with chemotherapy induced LS, experience also the classical neurotoxicity, principally the peripheral sensory neuropathy, related with that agent [50], [51], [52], [53], [54], [55], [56], [57], [58], [61]. Although previous treatment with a neurotoxic chemotherapeutic agent may predispose to the development of LS during treatment with another neurotoxic chemotherapeutic agent [58], [62], interestingly there is no increase in the incidence of LS with concomitant administration of head and neck radiotherapy and chemotherapy [41], [64]. This may be attributed to the administration of corticosteroids for antiemetic prophylaxis during chemotherapy. There is no study in the literature that either vitamin B12 deficiency or replacement of vitamins can increase or decrease the incidence of LS associated with chemotherapy or radiotherapy. Chemotherapy associated LS usually appears after a certain cumulative dose and with a latency period of several weeks to months following the completion of chemotherapy, similar to the cases observed with radiotherapy [49], [50], [51], [52], [56], [57].

4.3. Bone marrow transplantation and LS 

High dose chemotherapy together with total body irradiation is often used as the preparative therapy before bone marrow transplantation. Various neurological complications may arise in patients undergoing bone marrow transplantation such as central nervous system infections, encephalopathies, cerebrovascular complications, cerebellar syndromes and others [65], [66]. Neurological complications involving spinal cord have been reported very rarely in bone marrow transplant recipients [63], [65]. LS is a very rare event after bone marrow transplantation with only several cases published in the English medical literature. It has been proposed that a demyelination related mechanism in the posterior columns of the spinal cord is responsible from bone marrow transplantation related LS, since histopathological evidence of demyelination with histiocytic infiltration of the posterior columns of the spinal cord have been previously reported in three patients [63]. Development of LS appears to depend on multiple factors. Among these the type of preparative therapy, the type of graft versus host disease prophylaxis, and the use of allogenic or autologous transplant can be counted. Contribution of radiotherapy, chemotherapy, infection, autoimmunity, toxic and metabolic factors is uncertain [63]. Bone marrow transplantation related LS appears after a latency period of several months and resolves spontaneously similar to radiation and most chemotherapy related LS cases, without necessitating any specific treatment.

4.4. Spinal cord tumors and LS 

Although very rare, primary or metastatic spinal cord tumors both have been reported to be associated with LS [19], [21], [67], [68]. Spinal tumors located at cervical or thoracic levels may cause LS due to the distortion of the sensory axons of the dorsal columns of the spinal cord. LS may develop even before the onset of other tumor related symptoms [21], [67]. The actual prevalence of LS in primary or metastatic spinal cord tumors is unknown. Presence of LS may be a presenting symptom of malignant cervical or thoracic spinal cord compression from either primary or metastatic tumors. Ventafridda et al., in a small series of 20 consecutive patients with epidural spinal cord compression due to metastatic tumor deposits at thoracic spinal cord level, observed 3 patients presenting with LS [21]. LS disappears after decompressive laminectomy and tumor resection [21]. Epidural spinal cord compression is a frequent and disabling complication of cancer. It is important to diagnose and treat this complication early in order to prevent lasting paraplegia. LS in a disseminated cancer patient may herald the presence of epidural spinal cord compression. The treating oncologist should hold this possibility in mind in order to intervene on time.

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5. Treatment 

There is no specific treatment. Corticosteroids may be beneficial [40]. LS appearing in the context of transient radiation myelopathy is not associated with chronic progressive myelitis, but delayed radiation myelopathy which is irreversible and results in paralysis, may be preceded by LS [6]. LS that predates delayed radiation myelopathy is observed later in onset than the usual latency period of the LS observed in transient radiation myelopathy [6], [42].

Patients experiencing LS related with transient radiation myelopathy should be managed conservatively [6], [42], [69]. A soft neck collar may be beneficial in minimizing the flexion of the spine and thus the unpleasant sensation felt by neck flexion. Corticosteroids may be beneficial [6], [40], [42], [69]. There is no effective treatment for delayed radiation myelopathy. Corticosteroids may reduce inflammation and may delay progression of myelitis [39]. Combined heparin and warfarin treatment may provide some clinical and radiological improvement [70]. Hyperbaric oxygen treatment has been reported to be beneficial in a patient with delayed radiation myelopathy not responding to steroid therapy [71].

Chemotherapy associated LS resolves completely in time without leaving any sequelae and same measures apply for the treatment of chemotherapy associated LS [52], [55], [56], [57], [58].

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6. Discussion 

The sensation of a sudden electrical impulse that shoots down the back and into the limbs when the neck is flexed has been known as Lhermitte's sign or Barber's Chair sign. This sign is not specific to any disease and indicates a lesion in the cervical spinal cord. Many different conditions, pathologies and treatments can give rise to this sign, and thus, it may be encountered in different medical disciplines and may be perceived differently in diverse clinical settings. For example, presence of it may suggest multiple sclerosis or vitamin B12 deficiency for a neurologist, or may indicate a spinal cord tumor, a head and neck or spinal cord trauma, or a spinal cord compression for a neurosurgeon, or it may indicate radiation or chemotherapy toxicity at spinal cord level for an oncologists. Therefore, it may have specific implications for different clinical settings. For a radiation oncologist, it is a widely known, relatively common early sign and it is benign and reversible. A differential diagnosis should be done in order to exclude delayed radiation myelopathy, which is an irreversible and dreadful condition. For a medical oncologist, it may be easily confused with the other neurological complications of the treatment. Thus, its differential diagnosis may be important in terms of identifying the side effects of new chemotherapeutic agents and for their adverse event surveillance studies. For a neurosurgeon, it may be an early sign of a spinal tumor.

Although very unpleasant for the patient, LS is transient and self-limited sign mostly resolving spontaneously without necessitating a specific treatment. A soft neck collar and sometimes steroids may help to lessen this unpleasant sensation. However, correct differential diagnosis is mandatory.

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Conflict of interest 

None.

Contribution of authors: The study was conducted by a single author, so all the work needed to be done was performed by Cengiz Gemici MD.

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Reviewers 

Prof. Esat Mahmut Ozsahin, Senior Consultant, Centre Hospitalier Universitaire Vaudois CHUV, Department of Radiation Oncology, Bugnon 46, CH-1011 Lausanne, Switzerland.

Prof. Jean-Charles Soria, Institut Gustave Roussy, Department of Medicine, 39, rue Camille, Desmoulins Villejuif, Cedex 94805, France.

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Dr Cengiz Gemici is a radiation oncologist at the Department of Radiation Oncology, Dr Lutfi Kirdar Kartal Education and Research Hospital, Istanbul Turkey. He received his M.D. in 1990 at the University of Marmara, Istanbul and completed his residency at S.S.K Okmeydani Hospital, Department of Radiation Oncology, between 1990 and 1994. He later worked as a resident first at the Department of Radiation Oncology and then at the Department of Medical Oncology, Tenon Hospital, Paris, France, between 1994 and 1998. He obtained his Medical Oncology specialty diploma from University of Paris XI, Paris-Sud Medical Faculty, Paris, France. He is a member of ASTRO and ASCO. Chemotherapy and radiation interactions and treatment with combination chemoradiotherapy in different types of tumors is his main area of interest.

☆ The study has not been presented elsewhere, either as a whole or in part.

PII: S1040-8428(09)00100-0

doi:10.1016/j.critrevonc.2009.04.009

Critical Reviews in Oncology / Hematology
Volume 74, Issue 2 , Pages 79-86, May 2010

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