Transient neurological adverse effects following low dose radiation therapy for early stage testicular seminoma

Radiotherapy and Oncology 82 (2007) 137–144 www.thegreenjournal.com

Late effects

Transient neurological adverse effects following low dose radiation therapy for early stage testicular seminoma Marianne Brydøya,b,*, Anette Storsteinc, Olav Dahlb,a a Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway, bSection of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway, cDepartment of Neurology, Haukeland University Hospital, Bergen, Norway

Abstract Background and purpose: The aim of this study was to estimate the rate of neurological adverse effects following radiotherapy for testicular seminoma and to disclose possible dose-related effects. Patients and methods: All seminoma patients ðn ¼ 346Þ treated 1980–2001 at our department with radiotherapy as the only treatment modality following orchiectomy constitute the study group (median follow-up 10 years). Since 1980, clinical data including possible side effects have systematically been recorded in these patients. These records were used to identify men with possible neurological adverse effects. Univariate logistic regression was used to estimate doserelated effects. Results: Overall, 11 men (3.2%) with neurological symptoms probably related to radiotherapy were identified. Seven men treated with 25.2–36 Gray presented with sensory symptoms about 2 months following radiotherapy. These symptoms resolved in all but one after 1–3 months. The remaining four men (dose 36–40 Gray) had motor impairment which lasted at least one year, but none had persistent pareses at long-term follow-up. There was a statistically significant ðp ¼ 0:02Þ increase in rate of motor symptoms with higher dose. Conclusions: Although motor impairment is unlikely to occur at current standard doses for seminomas, physicians should be ware of the sensory symptoms these men may exhibit. c 2006 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 82 (2007) 137–144.



Keywords: Radiotherapy; Testicular cancer; Adverse effects; Neuropathy; Plexopathy

Neurological adverse effects following radiotherapy (RT) of the para-aortic and ipsilateral iliac lymph nodes for testicular cancer (TC) are considered rare. A syndrome characterised by lower motor neuron muscular weakness (flaccid pareses, amyotrophy, loss of deep reflexes) without sensory loss was first described in 1948 [14]. Although first ascribed to lesions of the anterior horn cells in the lumbosacral spinal cord, the lumbosacral nerve roots or plexus have later been suggested as more likely sites of injury. The neurological sequelae in published TC cases were with few exceptions progressive or stable [2,11,18,20,26, 27,29,30,33]. We have, however, also observed less severe neurological side effects among our seminoma patients treated with lower midplane doses [25.2–40 Gray (Gy)]. Some patients presented only transient sensory symptoms, and some had reversible pareses. Irradiation remains one of the standard treatment options following orchiectomy for early testicular seminoma [1]. Side effects are mainly gastrointestinal, renal, gonadal, haematological and secondary malignancies, while possible



neurological issues are less studied and not considered common [12]. The aim of this study was to estimate the rate of milder neurological side effects following low dose irradiation in seminoma patients and disclose any radiation dose-related effect.

Patients and methods Patients A total of 742 TC patients (410 seminomas and 332 nonseminomas) were evaluated and treated at our department from 1980 to 2001, representing all patients diagnosed with TC in Western Norway. Since 1980 the senior author (OD) has prospectively recorded stage, treatment, relapse and adverse effects at each follow-up visit in these patients. The majority were followed up as outpatients at our department. For those seen at other hospitals, we have received regular reports. The patients were scheduled to 10 years follow-up, and some were followed longer as part of a

0167-8140/$ - see front matter c 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2006.11.022

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survey for late effects [4]. They were histologically classified according to WHO [21] and staged by the Royal Marsden Hospital (RMH) staging system [22]. Prophylactic or therapeutic RT was given to 348 (47%) of these patients as the only treatment modality following orchiectomy, of which 346 patients with seminoma stages 1–2A were eligible for this study. One was excluded due to re-irradiation, and the other had stage 1 nonseminoma and refused surgery. We retrospectively reviewed the records of patients with neurological symptoms. One patient with vague sensory symptoms following RT presented with persisting pareses and pain in left leg eight years later. Although initially considered related to RT, he recently (15 years after RT) developed pareses at additional sites not directly explainable by RT and is thus not regarded as a case with adverse effect.

Treatment During the study period, we used L-fields, administered as two parallel-opposed AP and PA equally weighted fields (Fig. 1). The fields covered the para-aortic lymph nodes from the upper border of the 12th thoracic vertebrae (1980–1999) or 11th thoracic vertebrae (from 1999) to the lower margin of the 5th lumbar vertebrae. The caudal part of the ‘‘L’’ covered the presacral and ipsilateral iliac nodes.

Table 1 Standard radiation fractionation 1980–2001a Time period

Stage

Midplane dose

Fractionation

1980–1989

1 2A

36 Gy 40 Gy

2 Gy  18 2 Gy  20

1990–1996

1 2A

30.6 Gy 36–40 Gy

1:8 Gy  17 2 Gy  18–20

1996–2001

1 2A

25.2 Gy 27 Gy

1:8 Gy  14 1:8 Gy  15

a In the study group ðn ¼ 346Þ, 21 patients were treated with doses slightly deviant from standard and three of them received more than 40 Gray (Gy) (41–42 Gy).

The L-fields encompassed the conus medullaris, cauda equine, ipsilateral plexus, and parts of the contralateral plexus (Fig. 1). The standard fractionation was 1.8–2 Gy per fraction for five days a week with both fields treated each day by a megavoltage linear accelerator. The standard total dose varied from 40 to 25.2 Gy (Table 1). In 1980 to February 1991, an additional electron beam covering the inguinal nodes was given to patients if prior inguinal and/or scrotal surgery or infiltration of the scrotal wall or funicle was present. All treatment plans and therapy documentation of the men regarded to have neurological adverse effects were reexamined and disclosed no dosimetric errors.

Statistical analysis Univariate logistic regression was used to estimate doserelated effects on the occurrence of neurological symptoms (motor and sensory symptoms separately and combined). Graphs were based on predicted symptom probabilities from these regressions, using the statistical software R (The R Foundation for Statistical Computing, Vienna, Austria).

Ethics The Committee for Medical Research Ethics of the Western Health Region in Norway approved the study.

Results After a median follow-up of 10 years (range 4–22), we identified 11 patients (3.2%, 95% confidence interval [CI] 1.6–5.4%) with probable neurological adverse effects following RT among the 346 eligible men. By the clinical presentation they were divided into two groups: Group 1 presenting entirely sensory symptoms, most often transient ðn ¼ 7Þ, and group 2 featuring dominantly motor symptoms ðn ¼ 4Þ.

Group 1: Sensory symptoms only

Fig. 1. The L-fields and the relation to the lumbosacral nerve roots and plexus.

All the patients in group 1 had clinical stage 1 disease (Tables 2 and 3). No predisposing factors such as specific infections, hypertension, alcohol abuse or inflammatory disease were disclosed. Case S5 was however diagnosed with

M. Brydøy et al. / Radiotherapy and Oncology 82 (2007) 137–144

Table 2 Characteristics groups 1 and 2a Group 1 ðn ¼ 7Þ

Group 2 ðn ¼ 4Þ

Median

Range

Median

Range

Age at RT (years)

38

28–54

27.5

22–34

Midplane dose (Gy)

25.2

25.2–36

39.8

36–40

2

1–5

6.5

3–9

Duration

2 mo

1 mo–7 y

3.5 y

>1–3 yd

Follow-upe (years)

7.5

5.5–19

13.5

13–16.5

b

Latency (mo) c

a

RT, radiotherapy; mo, months; y, years; Gy, Gray. From ended radiotherapy to debut of sensory symptoms (Group 1) or pareses (Group 2). c Of sensory symptoms (Group 1) or pareses (Group 2). d See Table 4, exact duration is not known in all cases. e From ended radiotherapy. b

diabetes two years later. His blood sugar at orchiectomy is not known, but he had no glucosuria at that time. One patient (case S1) also had 36 Gy in 18 fractions towards his left groin by 13 MeV electrons due to prior ipsilateral surgery for inguinal hernia. Five of the men presented their symptoms at the first follow-up visit after completed RT, and the remaining two at the second or third visit. All had bilateral sensory symptoms. They typically complained of muscle tiredness and soreness in their lower extremities and/or sensory changes like hyperaesthesia and paraesthesia (Table 3), which were not limited to particular roots or nerves except for case S4 whose clinical picture differed slightly from the rest of the group. During a minor viral infection five months after RT, he noticed transient hyperaesthesia of the abdominal skin

139

corresponding to the radiation field. This was followed by numbness and paraesthesia in the lower lateral part of legs and three lateral toes bilaterally (S1 nerve root), though dominating on the left side, ipsilateral to the L-field. A lumbosacral computer tomography (CT) scan performed three years after symptom debut was normal. Blood samples analysed for sugar, iron status, cobalamin, protein and immunoglobulins as well as serum electrophoreses were normal. The symptoms gradually attenuated, but he still occasionally has minor symptoms after 7 years. In contrast, the symptoms lasted from one to less than 3 months in the remaining six. The attending oncologist performed a clinical neurological examination based on the patients given symptoms, but none of the patients in this group were referred to a neurologist. The examination was normal in four, of which one had already spontaneously improved. Among the remaining three patients, two had weak or absent tendon reflexes of the lower extremities (cases S2 and S7). Case S4 could provoke his symptoms by extending his knee while sitting in a slump position, but reflexes and sensation were normal.

Group 2: Motor symptoms, with or without sensory symptoms The patients in group 2 had stage 1 ðn ¼ 2Þ or 2 ðn ¼ 2Þ disease (Tables 2 and 4). None had a history of typical predisposing factors, but one (case M2) suffered from sciatica contralateral to the presented symptoms some years earlier, and one had mononucleosis ten months prior to the neurological symptoms (case M4). In addition, one had a substantial weight loss (20 kg) during and following treatment for TC (case M3). Whether this weight loss was accompanied by low levels of cobalamins, folic acid or serum proteins is not known, but he seemed well nourished when therapy commenced.

Table 3 Characteristics and symptoms presented by patients in Group 1a Case

Age at RT (y)

Midplane dose (Gy)

Latencyb

Symptoms

Duration

Follow-upc(y)

S1 S2 S3

40 38 49

36d 36e 36e

2 mo 2 mo <2 mo

<1 mo <2 mo <3 mo

19 16 11.5

S4

28

25.2d

5 mo

>7 yf

7.5

S5

54

25.2e

<2 mo

<2 mo

6.5

S6

35

25.2e

1 mo

4–6 w

5.5

S7

31

25.2e

6–7 w

Hyperaesthesia both legs Sore muscles both thighs. Tired when walking Felt that ‘‘legs would not bear him’’, and ‘‘leg muscles diminished’’. Tired Bilateral numbness and paraesthesia 3 lateral toes and laterally lower legs (dominating left side) following a minor viral infection. Gradual improvement, but still occasionally present in left leg. Legs felt heavy, sore leg muscles with some pain. Tired, minor muscle pain in upper-body Hyperaesthesia both legs, discomfort wearing trousers. Tiredness in legs, as if strained Discomfort and sore leg muscles (thighs, calves and buttocks), ‘‘as if run 3000 m’’

1 mo

6.5

a b c d e f

RT = radiotherapy; y, years; mo, months; w, weeks; Gy, Gray. From ended radiotherapy to debut of sensory symptoms. From ended radiotherapy. Left-sided L-field. Right-sided L-field. Still present at last follow-up.

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Neurological side effects of radiotherapy

Table 4 Characteristics and symptoms presented by patients in Group 2a Case

Age at RT (y)

Midplane dose (Gy)

Latencyb (mo)

Symptoms

Duration (y)

Follow-upc(y)

M1

26

40 (36)d,e

9

3

16.5

M2

34

36f

7

>3g

14

M3

29

40

f,h

3

>1 and <6

13

M4

22

39.6e

6

Weakness and coordination problems both legs. Sluggish and stumbling gait. Could not run. Initially sore muscles and slight numbness in legs. Gradually improved after 1 y Sore muscles in left calf. Could not walk on toes or heels. No sensory symptoms. Gradually improved from 9 mo and could run 100 m after 2 y. At 3 y still difficulties with heel-walking and visible muscular atrophy medially, anteriorly left lower leg. After 14 y normal power for several years, but persisting atrophy Could not run playing football, gradually weaker with problems climbing stairs. Weight loss 15–20 kg. No sensory or sphincter symptoms. Gradual improvement after 3–4 mo, exact time of full restitution unsure Sore muscles in legs (thighs and calves), legs felt ‘‘heavy’’ when walking uphill. Some difficulties with co-ordination (playing football). No sensory or sphincter symptoms. Gradually improved after 6 mo

2

13

a

RT, radiotherapy; y, years; mo, months; Gy, Gray. From ended radiotherapy to debut of pareses. c From ended radiotherapy. d Left-sided extended L-field including left scrotum (40 Gy), and 36 Gy to the mediastinum and left supraclavicular fossa (stage 2a with tumour cells in the resection margin of the funicle). e Left-sided L-field. f Right-sided L-field. g Exact time of recovery uncertain. In spite of persisting muscular atrophy, he had been well functioning for many years at last follow-up. h Right groin also irradiated, stage 1 anaplastic seminoma with tumour cells in the resection margin of the funicle. b

Table 5 Positive results of neurological examination in Group 2a Case c

M1

M2

M3d

M4

a b c d

Motorb

Sensoryb

Reflexes

Electrophysiological findings

Slight proximal (flexion and abduction in L hip) and distal (ankles) pareses. No atrophy, but slightly hypotonic left leg Slight distal pareses L (extension, ankle). Atrophy (visible first after 3 years)

Initially none. December 1983: Hypaesthesia of abdominal skin below Th10

Plantar flexor Patellar L: # Ankle jerks: #

Not performed

Distal hypaesthesia R (prior S1 sequella)

Ankle jerk R: 0 (prior S1 sequella)

Distal only: dysalgesia, dysaesthesia, vibration # - 0, joint position # Distal only, R > L: vibration #, joint position #

Plantar flexor Ankle jerk R: #

EMG, march 1988: MUP changes (neurogen type) in m. extensor digitorum brevis (L). Minor changes in m. tibialis anterior (L). November 1988: reinnervation potentials Not performed (did not meet)

General power loss (up to 4). Wide based and clumsy gait. Slight general atrophy Weakness of plantar flexion of both ankles, R > L

Plantar flexor Ankle jerks 0:#

Reduced motor and sensory NCV. Neurogenic MUP changes in proximal and distal muscle groups. No spontaneous activity, myokymia or fibrillation

L, left; R right; EMG, electromyography; MUP, motor unit potentials; NCV, nerve conduction velocity. Lower extremities when not indicated. This case also had slightly elevated cerebrospinal fluid (CSF) protein, 0.96 g/l (Normal value 0.15–0.52 g/l). Examined after improvement had commenced.

M. Brydøy et al. / Radiotherapy and Oncology 82 (2007) 137–144

10

15

20

25

cles (Table 4). Pain was not a prominent feature. The symptoms were bilateral in three and unilateral in one (case M2, contralateral to the L-field). One in particular could not climb stairs, and accidentally fell down on his knees when descending from a bus (case M3). All these patients were examined by a neurologist (Table 5). In addition to clear symptoms arising from the lumbosacral roots or nerves, case M1, who subsequently received RT towards the mediastinum, also exhibited slight symptoms pointing at an additional slight medullar lesion at the level of TH10 where the fields were jointed. Neurophysiologic testing was not performed in this patient.

5

Motor Symptoms (%)

141

0

Dose-related effects

25.2

30.6

36

38-40

Dose (Gy)

20 15 10 0

5

Neurological Symptoms (%)

25

Fig. 2. The occurrence of motor symptoms according to dose. The graph shows the predicted symptom probability based on univariate logistic regression ðp ¼ 0:02Þ and the shade illustrates the corresponding predicted 95% confidence interval. Crosses (x) represent the actual frequency at each dose in this material, with those receiving 38 Gy ðn ¼ 10Þ and 40 Gy ðn ¼ 26Þ considered together.

25.2

30.6

36

38-40

Dose (Gy) Fig. 3. The occurrence of neurological symptoms (motor and sensory combined) according to dose. The graph shows the predicted symptom probability based on univariate logistic regression ðp ¼ 0:2Þ and the shade illustrates the corresponding predicted 95% confidence interval. Crosses (x) represent the actual frequency at each dose in this material, with those receiving 38 Gy ðn ¼ 10Þ and 40 Gy ðn ¼ 26Þ considered together.

The motor symptoms started within nine months following RT in all and lasted at least one year. None had persisting pareses at long-term follow-up. Typical complaints were difficulties with running and coordination (playing football) and a feeling of sore leg mus-

None of our seminoma patients treated with doses less than 36 Gy developed motor symptoms. There was a statistically significant ðp ¼ 0:02Þ increase in rate of motor symptoms with dose (Fig. 2). However, we found no significant dose-effect for sensory symptoms alone or for sensory or motor symptoms together (Fig. 3).

Discussion The frequency of neurological symptoms regarded as adverse effects following RT was 3.2% (95% CI = 1.6–5.4%) among unselected patients treated by L-fields for early stage testicular seminoma in 1980–2001. We disclosed a dose-related effect for motor symptoms. This is the first description of the transitory sensory symptoms (group 1) following irradiation for testicular seminoma with current low standard doses. Noteworthy is also the reversal of pareses in all the cases with more pronounced motor symptoms (group 2), previously reported in a few single cases after pelvic and/or lumbar irradiation for various diagnoses [6,8,18,26,27,30]. The strength of this study is the long-term follow-up of an unselected group of seminoma patients. We believe we have captured all patients with motor impairment (group 2), and we found no other cause of the symptoms in this group. Probably, the sensory symptoms (group 1) were related to RT as the patients had similar complaints with comparable latencies and durations. However, the true frequency of sensory symptoms might be higher as some may not have mentioned these more vague symptoms spontaneously, and they were not routinely asked for. In addition to the presented cases, we are aware of three TC patients treated at our unit with neurological sequella following RT of which two developed a chronic lower motor neuron syndrome similar to that described by other authors [2,30]. They were, however, ineligible due to treatment by 60 CO in 1979, nonseminomatous histology or re-irradiation [29]. Established causes of plexopathy like diabetes, drugs, heredity, borrelia and herpes infections [34] were not apparent among our cases, although not serologically tested in all. Paraneoplasia is very unlikely, as none of these men were subsequently found to have active disease. Idiopathic lumbosacral plexopathy is usually accompanied by pain. With a stated incidence below 1:100,000 [31], it is rather

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unlikely to occur among the 346 patients in this series. Furthermore, RT is listed among aetiologies to be excluded for this diagnose [34]. Other differential diagnoses and possible contributing factors have also been considered. In group 1, the only potential contributing factor was a mild viral infection (case S4). In group 2, case M3 might have been exquisitely sensitive to radiation illustrated by intestinal side effects with a profound weight loss, and thus, a possible lack of essential nutritions. Case M4 had mononucleosis about ten months prior to the neurological symptoms, but radiculoplexopathy as a manifestation of Epstein-Barr virus infection seems to follow after only a few weeks interval and is commonly accompanied by pain [28]. Case M2 had right-sided sciatica some years prior to RT, contralateral to the relevant symptoms. This explains the loss of right side achilles jerk and slight sensory reduction consistent with S1 distribution. After radiotherapy, repeated electrophysiological testing showed new changes in the left L4–L5 domain, consistent with recent damage at this level. Although case M1 exhibited slight sensory symptoms pointing at an additional medullary lesion at TH10 where the fields were jointed (no overlap was evident from the dose plan), the findings in his legs were typical for a peripheral injury (roots or plexus), and could thus not be explained from a lesion at TH10. The post-irradiation lower motor neuron syndrome is considered rare and few authors comment on the frequency. We were only able to find one prior report on transient sensory symptoms following irradiation for TC [26]. Among 99 patients, neurological complications were reported in 12%, including pure sensory symptoms like paraesthesia and slight subjective weakness in 5%. Maier and colleagues reported pareses in 15 of 343 (4.4%) surviving TC patients [20]. Knap et al. recently reported late neurological complications in seven of 94 (7.4%) irradiated TC patients [17]. The symptoms appeared first after 10–20 years in six of their cases, highlighting the need for long-term follow-up. However, the patients in these three reports were treated more than 30 years ago, and received in most cases higher doses with different treatment set-ups (alternating anterior and posterior fields, cobalt units). More recently one case treated with RT (44 Gy midplane dose) and chemotherapy was reported by Esik et al., as probably a single case diagnosed with lower motor neuron disease among about 7000 treated TC patients [9]. In our cases, the dose to the medulla, lumbosacral roots and plexus is considered to be close to the midplane dose, due to the location of these structures and treatment with opposing megavoltage photon beams. Sensory symptoms occurred following 25.2 Gy in our series, which is lower than given to men with sensory symptoms in Schiodt and Kristensen’s report [26]. Pareses did not occur at doses below 36 Gy, and Fig. 2 therefore supports that motor impairment is unlikely to occur following today’s standard dose for early testicular seminoma. Prior indicated tolerance levels for pareses in irradiated TC patients correspond to 40– 54.5 Gy standard fractionation ð60 COÞ [20,26], and the calculated biologic spinal cord dose in the cases reported by Knap et al. was 52–62 Gy [17]. Thomas et al. included cases with various malignancies, and two received doses below 40 Gy ð60 COÞ [30].

Our observation of milder symptoms at lower doses than previously reported may be supported by electrophysiological studies demonstrating slowing of impulse conduction through irradiated segments of peripheral nerves and spinal cord in patients without symptoms treated with RT at conventional dosage schedules [7]. The clinical picture of group 1 cases has some similarities with transient radiation myelopathy of the upper spine [5,10,15,19] and what was reported by Schiodt et al. after irradiation for TC [26]. Symptoms were not defined to any dermatome or nerve (except case S4), and the latency and duration were similar or slightly shorter. We therefore postulate that the pathophysiology may be similar; a temporary interference with myelin synthesis leading to focal demyelination [15]. The typical latency may be explained by the normal survival period of myelin and recovery commences as the synthesis of myelin regain. A 5% risk of transient radiation myelopathy has been calculated following 34 Gy (standard 2 Gy/fraction) with mantle irradiation of Hodgkin lymphoma [13]. Identifying the principal site of injury in group 1 was not possible based on unspecific symptoms and sparse findings. However, data from rodents imply that in contrast to higher spinal segments, the lumbosacral roots are more radiosensitive than the lumbar spinal cord [3,32]. Selective lower motor neuron syndrome of the lower limbs has also been reported following prophylactic irradiation to the whole neuraxis in humans [24]. All group 2 cases showed characteristics of a lesion peripheral to the spinal cord, with a possible additional slight lesion of the spinal cord at the level of Th10 in case M1. Clinically, the findings were most consistent with injury of the lumbosacral plexus, but we cannot with certainty define the primary site within the lower motor neuron, since the neurophysiologic testing was not performed with a view to differentiate between root and plexus pathology. Radiculopathy being predominately, but not exclusively, motor has been supported by others with more extensive testing [2,30]. Various names like radiculoplexopathy and post-irradiation lumbosacral radiculopathy have been proposed as more accurate naming of the lower motor neuron syndrome [2,30]. The latency interval for patients in group 2 varied from 3 to 9 months compared to 3.5 months to 25 years in prior reported cases with pareses [18,26,27]. The striking feature in group 2 is the high rate of improvement. Apart from muscular atrophy in one, all were without symptoms after a median follow-up of 13.5 years. Though lasting more than one year in all, significant axonal damage is unlikely considering the clinical improvement in all cases. Thus, we find it most likely that demyelination caused the symptoms in group 2 as well. We are aware of only two similar TC cases with marked improvement (one seems reported twice) [18,26,27], and a few other cases irradiated by lumbar or pelvic fields [6,8,30]. Reversible brachial plexopathy is reported with various frequencies [23,25]. The patients in this study were treated with L-fields, while RT today mostly is limited to the para-aortic area [1]. If these symptoms arrive from injury within the roots or spinal cord, TC patients treated with RT are likely to

M. Brydøy et al. / Radiotherapy and Oncology 82 (2007) 137–144

continue to exhibit these adverse effects. If the lesions are within the plexus, these symptoms might be seen less frequently since only proximal parts of the plexus are encompassed by the para-aortic fields. The lowest dose applied in our patients was 25.2 Gy, while 20 Gy now seems sufficient for seminoma stage I [16]. This reduction in dose may also possibly reduce the incidence of neurological symptoms. Furthermore, RT is now less applied as one cycle of carboplatin and surveillance are considered equal options for cure in stage I Seminoma [1]. According to our analysis, it does not seem likely that those who choose RT are at risk of motor adverse effects, although sensory symptoms may possibly appear. These data may also be relevant for other patient groups treated with lumbar and/or pelvic irradiation at similar doses. In conclusion, there is a dose–response effect for neurological motor side effects after L-field radiation. With doses up to 40 Gy, the neurological symptoms generally are reversible. Although motor impairment is unlikely to occur following current standard radiotherapy for testicular seminoma, the clinicians treating these patients should be aware of the relation between neurological symptoms and low dose RT. The subtle neurological symptoms these patients may exhibit should be recognised as adverse effects, and the patients reassured of the benign course.

[7]

[8]

[9]

[10]

[11]

[12]

[13] [14] [15] [16]

Acknowledgements This study was supported by a grant from the Western Norway Regional Health Authority. Tore Wentzel-Larsen, Centre for Clinical Research, Haukeland University Hospital, is gratefully acknowledged for statistical assistance. We thank Jan I. Heggdal, Department of Oncology and Medical Physics, Haukeland University Hospital, for help in reexamining the treatment documentation in search for dosimetric errors. Finally, we thank Ellinor Moldeklev Hoff at the Photography and Drawing section, University of Bergen, for designing Fig. 1. * Corresponding author. Marianne Brydøy, Department of Oncology and Medical Physics, Haukeland University Hospital, 5021 Bergen, Norway. E-mail address: [email protected]

[17]

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[19]

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Received 6 July 2006; received in revised form 28 November 2006; accepted 30 November 2006; Available online 26 December 2006

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