brain cancer.docx

Support Care Cancer (2012) 20:1425–1434DOI 10.1007/s00520-011-1225-6

ORIGINAL ARTICLE

Acute stress in patients with brain cancerduring primary careSimone Goebel & Hans Strenge & H. Maximilian Mehdorn

Received: 13 January 2011 / Accepted: 21 June 2011 / Published online: 30 June 2011# Springer-Verlag 2011

AbstractPurpose This study investigated whether diagnosis andneurosurgical removal of a brain tumour induced AcuteStress Disorder (ASD) in adults. We also aimed to identifyfactors associated with the development of ASD in thisspecific patient group and setting.Methods Forty-seven consecutive patients with intracranialneoplasms completed a variety of self-report questionnairesand underwent a structured clinical interview (SCID) withinthe first 4 weeks after tumour detection on average 1 weekafter neurosurgical treatment. Moreover, the Diagnostic andStatistical Manual of Mental Disorders, 4th edition (DSM-IV),A1 and A2 criterion and thus the characteristics of thetraumatic event were explored in detail.Results ASD symptoms were common. Twenty-three per-cent of the patients met stringent criteria of ASD andanother 4% suffered from subsyndromal ASD. Predisposingfactors previously reported in literature with the exceptionof previous trauma could not be identified in this study(e.g., sex, age, intelligence).Conclusion It has been critically discussed whether thediagnosis of ASD is appropriate in cancer patients due tothe often future-related nature of cancer-related traumaticevents. The diagnosis of ASD was justified in the vast

S. Goebel (*) : H. M. MehdornDepartment of Neurosurgery,University Hospital Schleswig-Holstein,Arnold-Heller-Str. 3,24105 Kiel, Germany

e-mail: [email protected]

H. StrengeDepartment of Medical Psychology and Medical Sociology,University Hospital Schleswig-Holstein,Diesterwegstr. 10-12,24113 Kiel, Germany

majority of affected patients due to the specific, acute andpast traumatic experiences in concordance with the DSMand International Statistical Classification of Diseases andRelated Health Problems (ICD) trauma definitions. Thus,ASD is a common and relevant psychiatric comorbidity inpatients with brain tumours. Our data highlight both theneed for the routine psychological assessment as well as ofpsychosocial support in this early treatment phase.

Keywords Intracranial tumour . Acute stress . Mentaldisorder . Patients . Primary care

Introduction

During the past years, researchers have stressed thespecific needs and burdens of patients with braintumours (BT) (e.g., [1–4]). These include the oftendeflating prognosis, rapid deterioration of neurologicalfunctioning (e.g., paralysis, sensory impairment) as wellas physiological and biological effects specific to braintumours such as seizures, personality changes or impairmentsin the areas of language and cognition [5]. Altogether, patientswith BT rank among those cancer patients suffering from thehighest psychosocial burden [6, 7]. Patients often suffer fromanxiety, depression, or elevated levels of distress [1, 3, 8, 9].This is of high clinical relevance, as mood disorders areassociated with a decrease in Health-Related Quality of Lifeand presumably even a shorter time of survival [4, 8]. Thus,it has been stressed that diagnosis and treatment of emotionaldistress is crucial for patients with brain cancer [3, 10].However, at the same time, information and psychosocialsupport are still more difficult to assess for patients with BTcompared to other cancer patients [11]. Recent research hasdemonstrated an ongoing and profound neglect of brain

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tumour patients regarding both research and treatment ofpsychosocial comorbidity [12].

To date, there are only few studies assessing the psycho-

logical state of this patient group during the early treatmentphase [1, 9]. Moreover, most studies solely relied on self-report screening instruments despite the fact that for thecomprehensive assessment of psychological sequelae ofcancer, these should be supplemented by a structured clinicalinterview [13]. One recent study [14] demonstrated that morethan one third of patients with an intracranial tumour sufferedfrom a psychiatric disorder as assessed via the StructuredClinical Interview for Diagnostic and Statistical Manual ofMental Disorders, 4th edition (DSM-IV) (American Psychi-atric Association, 1994) (SCID-IV; [15, 16]). Acute StressDisorder (ASD) was with a prevalence of 19% the mostprominent psychiatric sequela for patients.

Traumatic stress is a specific area of possible psychiatric

morbidity in cancer patients. Traditionally, only extraordi-narily threatening experiences beyond the normal range ofexperiences were considered to be potentially traumatic.The DSM-IV, however, focuses on the subjective andindividual psychological responses in potentially traumaticsituations. Therefore, a person needs to be exposed to, orwitness, an event that involves actual or threatened death,or a threat to the physical integrity of oneself or others(criterion A1), and he or she needs to react with intensefear, helplessness, or horror (criterion A2). Moreover, theDSM-IV recognizes, for the first time, that traumatic stressreactions may be precipitated by life-threatening illness.This development has contributed to greater focus on theissue of stress reactions following cancer (e.g., [17]). ASDwas introduced in the DSM-IV to describe psychologicalstress reactions within the initial month after experiencing atraumatic event with the aim of identifying those

individ-uals who would subsequently develop Posttraumatic StressDisorder (PTSD). To date, only few studies have prospec-tively assessed the incidence of ASD in adult cancerpatients [18–20]. These studies demonstrated that a consid-erable proportion of cancer patients suffer from ASD withinthe first weeks after tumour diagnosis.

This study focuses for the first time on the question

whether diagnosis and neurosurgical treatment of braintumours might cause significant acute psychological stressreactions. We also aimed to identify factors associated with thedevelopment of ASD in this specific patient group and setting.

Materials and methods

Subjects

During a recruiting phase of 18 months, 109 possibleeligible participants hospitalized at the Department of

Support Care Cancer (2012) 20:1425–1434

Neurosurgery, University Hospital Schleswig-Holstein,Kiel were identified by the attending physician. Ofthose, eight (7%) declined to participate due to eitherfatigue (n= 3) or high emotional distress (n=5). Anothersix patients (6%) could not be seen due to organiza-tional problems (e.g., discharge ahead of schedule).Twenty-four (22%) patients met at least one of thefollowing exclusion criteria: age below 18 or over80 years, history of cancer, concomitant neurologicaldiseases, previous life-threatening illness, a history ofsignificant brain impairment, severe medical complica-tions, or a Karnofsky index below 50 indicating a non-satisfactory medical condition. Moreover, aphasic dis-orders as diagnosed via the German Golden Standardfor Assessment of Aphasia (Aachener Aphasie Test[AAT]; [21]) as well as severe cognitive disabilities asindicated by scores below 24 in the Mini Mental StateExamination (MMSE; [22]) served as exclusion criteria.Of the remaining 68 patients, 21 patients (31%) had notreceived the diagnosis within the last 28 days and weretherefore excluded. The resulting sample consists of 47patients with brain cancer (WHO° II, III or IV).Participants were consecutively interviewed after surgery.Written, informed consent was obtained from eligiblepatients. All participants were right-handed. First language ofall patients was German. Participants and non-participants didnot differ in terms of age, gender, and tumour stage (p>0.2).None of the patients had started chemotherapy or radiother-apy at the time of testing.

Procedure

This study has been approved by the appropriate ethicscommittee and performed in accordance with the ethicalstandard laid down in the 1964 Declaration of Helsinki.Patients were tested within 3 to 11 days after neurosur-gical removal of the tumour during in-patient stay (Mx=5.83; SD=1.72). All examinations fell within the first 28 daysafter the subjects received the diagnosis due to thedetection of the neoplasms via CT or MRT (range 11–28 days, Mx=19.04; SD=5.60). At the beginning of theexamination, it was established whether a patient met theinclusion criteria. If so, aim and requirements of thestudy were detailed and patients gave written consent toparticipate in the study. This was followed by anextensive exploration and anamnesis. Afterwards, thestructured clinical interviews were completed followedby self-report measures. The procedure took from 75 to150 min. Depending on the physical state of the patientsas well as available appointments, 40 (85%) of theincluded patients also underwent an extensive standardizedneuropsychological assessment as described below. This wasscheduled during a second visit.


Assessment

Psychological measures

ASD symptomatology was assessed with both clinician andself-report measures.

Structured Clinical Interview for DSM-IV (SCID [15, 16])The SCID is a widely used structured clinical interview for theassessment of mental disorders according to the DSM-IVcriteria. We used the modules for assessment of cancer-relatedASD and lifetime PTSD. In addition to the A criterion asdescribed above, the diagnostic criteria for ASD consist ofdissociation (e.g., emotional numbing, derealization, ordepersonalization), reexperiencing symptoms including intru-sions or flashbacks, marked avoidance, significant anxietyand/or increased arousal as well as evidence of significantstress or impairment. Probes were added to the interview todetermine whether each symptom was attributable to physicalcausation (e.g., deficits in sleeping or concentration). If so,the symptom was not scored in the SCID.

Clinician Administered PTSD Scale (CAPS; [23, 24]) TheCAPS is a structured clinical interview that is based onDSM-IV criteria for PTSD and possesses sound reliabil-ity, sensitivity and validity [25]. The CAPS includesdetailed questions regarding the nature of the traumaticevent and thus enabling the substantiated assessment ofthe A1 and A2 criterion. The CAPS also enables theassessment of PTSD symptomatology and its severity aswell as consequences. However, since we focused onASD, this part of the CAPS was not included.

Acute Stress Disorder Scale (ASDS; [26, 27]) The ASDSconsists of 19 items, in which participants are asked to rate theintensity of symptoms associated with acute stress disorders.Items can be rated from 1 to 5. Symptoms of derealization anddepersonalization are assessed by five items, four items eachassess intrusion and avoidance and six items ask for symptomsof hyperarousal. The ASDS possesses good validity,

reliabil-ity, sensitivity and specificity for identification of acutelytraumatized individuals at risk for developing PTSD [27].

Cambridge Depersonalisation Scale State (CDSS; [28, 29])The Cambridge Depersonalisation Scale State Version(copies available on request) is a 22-item scale derivedfrom the Cambridge Depersonalisation Trait Scale.Respondents are asked to rate the current intensity ofsymptoms relevant to depersonalisation and derealizationon a visual analogue scale ranging from 0% to 100%.

Impact of Event Scale—Revised (IES-R; [30, 31]) The IES-R aims to assess symptoms of intrusion, avoidance, and

1

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hyperarousal over the past 7 days. It consists of 22 items. Scalescores are formed for the three subscales, which reflect intrusion(seven items), avoidance (eight items), and hyperarousal (sevenitems). Items are scored 0, 1, 3, or 5. It has been used innumerous studies on trauma and has excellent reliability andvalidity. The term “distressing event” was replaced by the term“diagnosis of the neoplasm”. For statistical analysis, the sum ofintrusion, avoidance, and hyperarousal was used with a cut-offscore of or above 30 to indicate at least moderate symptom-atology as proposed by Creamer and colleagues [32].

Posttraumatic Stress Diagnostic Scale (PDS, [33]) Thisself-report measure yields a PTSD diagnosis, a measure ofseverity and a list of traumatic experiences. Participantswere only presented with the list of 13 possible traumaticexperiences and had to rate for each whether they hadexperienced it any time before. Dependent measure was thenumber of reported previous traumatic experiences.

Hospital Anxiety and Depression Scale (HADS; [34, 35])The HADS is a widely used questionnaire to assesssymptoms of anxiety and depression in patients withsomatic complaints with satisfying reliability andvalidity. It consists of 14 items, seven per subscale.Items are scored 0, 1, 2, or 3.

Additional measures

Demographic data were obtained by using a semi-structuredinterview. Medical charts were reviewed to obtain informationabout disease stage and treatment characteristics. Patients’awareness of the diagnosis as well as characteristics of thetraumatic experience were assessed via a semi-structuredinterview. Premorbid intelligence was estimated by a formulausing educational and socio-demographic data [36], similar tothe formula of Barona and Chastian [37].1

Cognitive functioning was assessed via a comprehensiveneuropsychological test battery which was composedaccording to the procedures drawn by Taphoorn and Klein[5]. Digit Span (Forward and Backwards; [38]) served as anindicator of verbal short-term and working memory. Forassessment of visuo-motor speed, we used the Trail-MakingTest (TMT)-A. The TMT-B additionally assesses processesof divided attention and executive functioning [39]. AGerman version of the Controlled Oral Word AdministrationTest COWAT [40] using the letters “L”-“B”-“S” was chosenfor assessment of lexical fluency. Visuo-perception was

Premorbid IQ is calculated as follows: 82.08+0.22×age + level ofeducation + level of occupation + level of media use. For each of thelast three predictors, one out of a different number of possibleconstants is selected according to detailed criteria.

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assessed via the ability of object recognition, using the subtestObject Decision from the Visual Object and Space PerceptionBattery [41]. Visuo-construction was assessed via the Rey–Osterrieth Complex Figure (ROCF; [42]). The delayed recallof the ROCF serves as indicator for non-intentionalvisual memory. Assessment of anterograde verbal mem-


from 95 to 133 (Mx=114.8; Sx=9.4). All patients reportedgood or very good satisfaction with their social support(one 4-scaled question during exploration: very good, good,sufficient, not sufficient). Table 1 provides more details.

Table 1 Demographic and medical characteristics (n=47)

ory was performed by the Buschke Selective RemainingTest BSRT [43] consisting of 12 items using a delayedrecall interval of 20 min.

Statistical analysis

Statistical analyses were performed using the StatisticalPackage for the Social Sciences (SPSS) version 14.0.Descriptive statistics were used to characterize the demograph-ic and psychosocial characteristics of the study sample, theprevalence of ASD and the characteristics of the cancer-relatedtraumatic events. Neuropsychological test results were con-verted to z-scores. This allows for the standardisation of thedifferent classification systems used in clinical Neuropsychol-ogy and thus for the comparison of different test results. Theoriginal distribution is transformed into one with a mean ofzero and a standard deviation of 1. Thus, z-scores quantify theoriginal scores in terms of the number of standard deviations(SD) that each score differs from the mean of the distribution.Patients scoring 1.5 SD below the mean (i.e., patients with z-scores of ≤−1.5) were classified as impaired in each regardingtest. Associations between variables including diagnosis ofASD were calculated using Spearman’s correlation coeffi-cients. χ2 tests were used to analyze differences in thedistribution of categorial variables between groups. For allother group comparisons, Mann–Whitney U-tests were used.Two-tailed significance tests were conducted using a signifi-cance level of p<0.05. Retrospective power analyses were

performed with G*power (see Ref. [44]) in order to facilitatethe interpretation of statically non-significant results with

Variable

Marital statusMarriedPartnershipWidowedSingle

ChildrenNoneYounger than 18 yearsOlder than 18 years

Educational levelElementary schoolJunior high SchoolHigh school certificate/university degree

Employment status

Currently employedRetiredHousekeeper/unemployed

Post-surgery histopathologic classification

GlioblastomaAstrocytomaOligoastrocytomaOligodendroglioma

Tumour-lateralization

RightLeft

Tumour size in cm (maximal dimension)

RangeMx (SD)

n

35

17

12

1920

10

2214

2621

1.0–6.33.5 (1.5)

4 9

8 1727 58

8 17

35 75

2 4

56

––

5545

36

3819

6

105

2111

112

234

a

%

75

215

26

4043

21

47

291113

5545

respect to the sample size. Sensitivity describes the truepositive rate, i.e., the proportion of patients suffering fromASD who were correctly identified via the screeninginstruments (sensitivity=true positive/(true positive+falsenegative)). Concordantly, specificity describes the truenegative rate and thus the proportion of patients without ASDwith a negative test result in the screening questionnaires(specificity=true negative/(true negative+false positive).

Adjacent oedemaYes 26No 21

Tumour-localization (mainly affected cerebral lobe)Frontal 17Temporal 9Parietal 18Occipital 3

Initial symptoms/reason for seeking medical consulta

Epileptic seizure 17 36

Results

Demographic and medical sample characteristics

Twenty-four (51%) of the 47 patients were male and 23female. The median age of sample was 51.7 (SD=13.7)with a range from 21 to 79. Estimated premorbid IQ ranged

Motoric/sensoric symptomsVertigo/nauseaHeadacheLanguage/cognition/personalityVision disordersNone (incidental findings)

Multiple ratings possible

114

239


Prevalence of cancer-related ASD and resultsof accompanying measures

Eleven patients (23%) fulfilled all DSM-IV criteria forASD according to SCID and CAPS. Another two patients(4%) suffered from subsyndromal ASD. For classificationof subsyndromal ASD, we followed the instructions ofSchützwohl and Maercker [45], who suggested thisclassification as adequate if all but one DSM-IV criteriaare fulfilled. These 13 patients were grouped for furtheranalysis as patients suffering from (full or subsyndromal)ASD. Table 2 gives an overview about the classification ofpatients according to the screening instruments.

Fulfilment of individual diagnostic criteria

Twenty-seven patients (57%) fulfilled both the A1 and A2criterion and thus experienced the situation as traumatic(Table 3). The results regarding the A criterion from SCIDand CAPS were identical. The focus of the ASD diagnosis asformulated in the DSM-IV lies explicitly on the B criterion for

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related traumatic events yielded the following results: 11patients (85%) described receiving the diagnosis as atraumatic experience; one patient (8%) described death-anxiety after diagnosis as traumatizing. The remaining patientdescribed future-related fears (fear of functional loss).

Fulfilment of ASD diagnosis and results of other diagnosticmeasures

Comparison of patients who fulfil or do not fulfil criteriafor ASD provided the following results: The formerachieved higher test scores in the ASDS, the CDSS wellas the IES-R (p < 0.01). The same is true for thefrequencies of patients who were classified as impairedby each of the instruments (p<0.01). Moreover, Patientswith ASD were more likely to suffer from clinical relevantanxiety (HADS >11; p=0.01), but not depression (p=0.18).However, patients with ASD scored higher in both theanxiety and the depression score of the HADS (p<0.01).

Intercorrelations between measures

which therefore detailed frequencies are displayed in Table 3.Correlations between HADS scores and all measures of

Characteristics of tumour-related traumatic events

The majority of patients (n=38; 81%) experienced thediscovery of the neoplasm as unexpected and frighteningand reported relevant emotional burden after the diagnosis.Receipt of diagnosis was the most frequently distressingevent. However, 16 patients (34%) described future-orientedfears as most distressful (Table 4). Thus, these patientsreported that fears regarding an event in the future (e.g.,surgery-related anxiety during the preoperative phase) hadbeen most distressing.

The separate analysis of the 13 patients suffering from full

or subsyndromal ASD regarding the characteristics of cancer-

Table 2 Number and percentage of patients meeting the respectivecut-off scores in the applied self-report measures (n=47)

traumatic stress were small but significant (Rho<0.3; p<0.05), whilst all measures of traumatic stress showed atleast medium intercorrelations (Rho>0.3; p<0.05).

Neuropsychological data

None of the psychological test scores was correlated with any ofthe neuropsychological test scores (p>0.2). The only exceptionyielded the depression score of the HADS: This was correlatednegatively with both immediate and delayed free recall inverbal semantic memory (r=0.358 and 0.386, respectively;p<0.05). The total sample was impaired in the areas ofvisuo-motor speed, visuo-construction, as well as verbal andfigural memory. Moreover, about half of the includedpatients were considerably impaired in those domains. Fordetails, see Table 5. Comparison between patients with orwithout full or subsyndromal ASD showed no differences

Cut-off score Patients meeting thecut-off score

regarding the frequency of impaired patients (p>0.2) in any ofthe cognitive measures. The same is true, if the z-converted

n % raw scores were compared between both groups (p>0.2).

ASDSCDSS I ES- R ∑I+A+H

9

HADS AnxietyHADS Depression ≥56

≥70≥30≥11≥11

810167

1721341519

Influencing variables

Demographic data

All dependent measures were analyzed for both frequency

ASDS Acute Stress Disorder Scale, CDSS Cambridge Depersonaliza-tion Scale – State, IES-R Impact of Event Scale (sum of the threescales intrusion, avoidance, and hyperarousal), HADS HospitalAnxiety and Depression Scale

(proportion of patients classified as impaired) and intensity(raw scores) with regard to the following demographicvariables: gender, age, premorbid IQ, living in a stablerelationship, being wage-earners, having (young) children.

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Table 3 ASD cluster andsymptoms endorsed by patients

Cancer-related ASD symptoms


(n=47)

Number of criteria that need to

be fulfilled for diagnosis ofASD

A Traumatic event, subjective reaction (CAPS and SCID) (2)a

A1 Traumatic eventA2 Subjective reaction

B Dissociative symptoms (SCID) (3)a

B1 Numbing, detachment, absence of emotional responsivenessB2 Reduced awareness of surroundingsB3 DerealizationB4 DepersonalizationB5 Dissociative amnesia

C Intrusion (SCID)D Avoidance (SCID)E Anxiety/arousal (SCID)

27322713161915104

2517

57685726344032219

5336

None of these variables was associated with psychologicalmorbidity (p>0.15). Retrospective power analyses revealedlow statistical power for the conducted tests, ranging from0.07 to 0.39.

Medical data

The following medical factors were examined with regardto their relation to frequency as well as intensity ofpsychological symptomatology. None of the followingfactors was associated with any of the dependent measures:WHO stage, extend of tumour resection, acute onset oftumour symptomatology, tumour size, oedema, tumourlateralization/localization, Karnofsky index (p>0.2). Again,retrospective power analyses revealed low statistical power

not experienced one or more traumatic event did notdiffer with regard to any of the dependent measures (p>0.2) with exception of the tendency for a significantdifference in the CDSS (p=0.066). Number of previoustraumatic events was not correlated with any of thedependent measures with exception of the CDSS (r=0.316; p=0.03). Diagnosis of life time PTSD was fulfilledin eight patients (17%). None of those participantshowever reported persistent PTSD symptoms within thelast 4 weeks prior to the tumour diagnosis. Of thissubgroup, 50% (n= 4) fulfilled diagnostic criteria forASD. For patients without lifetime PTSD, the same wastrue for seven of 39 patients (18%). The χ2 test revealed atendency towards a significant difference regarding thesefrequencies (p=0.051).

for the conducted tests, ranging from 0.15 to 0.29.Clinical identification of acute stress

Previous exposure to traumatic eventsFor implementation in daily practice, the application of a

Based on the SCID and PDS, 19 (40%) of our patientsreported experiencing at least one traumatic event prior todetection of the brain tumour. Patients who respectively had

Table 4 Type and frequency of brain-tumour-related traumatic events

Cancer-specific traumatic eventsa

Detection of the neoplasm/receiving the diagnosisFear of functional lossFear of having cancer and going to die

structured clinical interview as well as of a variety ofsupplemental questionnaires might not be feasible. Thus,we evaluated the capability of the applied screeninginstruments for the detection of full or subsyndromal ASDas diagnosed via the SCID. The IES-R showed with 77%the highest sensitivity (correctly identified ASD cases) anda good specificity (82% true negative classifications). TheCDSS showed a sensitivity of 62% and a specificity of 87%whereas the ASDS identified 54% of the ASD casescorrectly with a specificity of 97%. Sensitivity of bothHADS subscales for detecting ASD was below 50% andthus non-sufficient.

Fear of surgery Emo tional burden of the family

n %

a

20 43

(n=47)

n %

27 578 176 13

21

42

a

Major epileptic seizure 2 4

DiscussionNone 1 2

In this study, acute traumatic stress in patients with brainMost distressful event (open question), one answer per patient

cancer during primary care was examined for the first time.

Support Care Cancer (2012) 20:1425–1434 1431

Table 5 Neuropsychological measures (z-scores) of the whole sample (n=40) as well as for patients with (n=11) or without (n=29) full orsubsyndromal ASD

All With ASD Without ASD

Mx (SD) % impaired Mx (SD) % impaired Mx (SD) % impaired

Digits ForwardDigits BackwardsTMT-ATMT-B

−0.454 (1.176)−0.945 (0.977)−01.664 (2.986)−2.341 (3.119)

15354562

−0.645 (1.077)−1.266 (1.203)−1.581 (3.001)−2.456 (3.093)

15463969

−0.381 (1.202)−0.822 (0.927)−1.701 (2.443)−2.297 (3.228)

15324759

COWAT: Letters 0.310 (1.182) 0.041 (1.147) 0.413 (1.172)VOSP: object decisionROCF—copy

−0.588 (1.388)−2.023 (2.163)

2358

−0.358 (1.096)−1.702 (1.053)

2446

−0.676 (1.432)−2.146 (2.303)

2162

ROCF—recall 0.179 (0.913) −0.114 (0.394) 0.291 (0.918)BSRT: supraspanBSRT: average recallBSRT: delayed recallBSRT: recognition

−0.568 (1.013)−1.226 (1.425)−1.324 (1.331)−2.171 (2.394)

15505055

−0.429 (0.882)−1.189 (1.597)−1.534 (1.546)−1.758 (1.421)

15555555

−0.621 (1.040)−1.240 (1.423)−1.366 (1.324)−2.329 (2.486)

15484855

Digits Forward and Backwards digit span from the Wechsler Memory Scale—Revised, TMT Trail-Making Test A and B, COWAT Controlled OralWord Association Test (lexical verbal fluency), VOSP Visual Object and Space Perception Battery, ROCF: Rey − Osterrieth Complex Figure Test,BSRT Buschke Selective Reminding Test

We used a prospective approach and a variety of assessmentinstruments.

The findings of this study indicate that a considerableproportion of patients with a brain tumour suffers fromclinical relevant ASD symptomatology within the first4 weeks after detection of the neoplasm: 28% of oursample suffered from full or subsyndromal ASD. However,57% of the patients described the situation as traumatic andfulfilled the DSM-IV A criterion. Moreover, the majority ofour sample reported relevant emotional burden after thediagnosis and fulfilled at least one ASD criterion. Thus, itwas demonstrated that acute stress reactions are a frequentand relevant mental comorbidity for patients with braincancer during primary care. In a previous study from ourgroup, 19% of 26 patients with intracranial tumourssuffered from ASD. The difference in the prevalencebetween the two studies was likely influenced by the factthat about one quarter of the patients from the previousstudy did not meet the time criterion (duration sincediagnosis >1 month) and thus ASD could not be diagnosed.However, as both sample sizes are small, this cannot beanswered on the basis of the existing data.

When interpreting these results, some additional

factorshave to be taken into account: (1) A great number ofpatients was excluded due to severe cognitive, aphasic, orphysical disabilities. Thus, we assessed only those patientsthat were least impaired by the disease and therefore mightbe less affected than others (e.g., [10]). (2) Moreover, innone of our patients peri- or postoperative complicationsoccurred which might put an additional burden on patients.

8 9 7

5 9 4

Additionally, five patients declined to participate because ofhigh psychological burden and marked avoidance. Thus,again patients with most severe emotional burden mighthave been not included. (3) We included only those patientswho received the diagnosis of the neoplasm within the last28 days. Different biases might hence result: The samplemight, on the one hand, include a higher proportion ofmedically severely endangered patients who have to beoperated immediately in order to avoid life-threateningconditions resulting in higher psychological distress. On theother hand, patients who were diagnosed within the last28 days could be less traumatized by the diagnosis,resulting in less avoidance behaviour and simply imme-diately following the medical referral for neurosurgicaltreatment. (4) Moreover, our patients were tested whilestill recovering from brain surgery during in-patient stay.This might have inflated responses as they were still in apotentially stressful setting. These possible biases couldbe reduced if patients were recruited from an MRT centrerather than the neurosurgical unit.

In our study, we found no associations between cognitivemeasures and measures of traumatic stress. Moreover,group comparisons between patients with or without ASDshowed no differences with regard to the neuropsycholog-ical profile. Regarding cognitive performance in ASD,previous research has linked deficits in the areas of memory,high-level attentional resources, executive function andworking memory with ASD in non-medical subjects [46,47]. There are different possible explanations for thisdiscrepancy, including the high rate of cognitive deficits

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in our patients (and in patients without ASD inparticular), the small sample size and the small numberof patients with ASD, resulting in diminished statisticalpower for group comparisons. There are only few studiesassessing cognitive functioning in ASD to date. Recently,the link between cognition and PTSD has been ques-tioned [48]. Thus, this issue warrants further clarification.

A multitude of factors has been associated with thedevelopment of ASD amongst which rank gender, education/intelligence, or age (e.g., [19, 49]). These could not bereplicated by our data. Only previous exposure to traumaticevents and lifetime PTSD were marginally associated withASD. This is important for clinical practice as our dataindicates that it might be difficult to predict acute stressresponses in this acute setting via objective data.However, this should be assessed in future studies withlarger sample sizes. This point is not only stressed by thesmall n of our study but also by the retrospective poweranalyses as well as the sample sizes of n>80 in the citedstudies. It should also be noted that patients in this studywere assessed within a week from receiving brain surgeryand were still inpatients. This may further explain why thecurrent findings contrast to other ASD cancer studies inthe literature which have documented socio-demographicfactors being associated with ASD.

It has been critically discussed whether the diagnosisof ASD is appropriate in cancer patients due to the oftenfuture-related nature of cancer-related traumatic events(e.g., [20]). In our sample, all but one ASD-patients (> 93%)reported specific, acute and past traumatic experiences inconcordance with the DSM and International StatisticalClassification of Diseases and Related Health Problems(ICD) trauma definitions. Thus, for the majority of patientsidentified as ASD cases in this study, ASD can be considereda valid and appropriate diagnosis. This is supported by thefact that there were no indicators for organically inducedtraumatic stress responses as demonstrated by the followingfactors: First, no patient suffered from dissociation who

didnot fulfil the DSM-IV A criterion as established via acomprehensive psychological interview. Second, none ofthe medical factors including tumour localization showedany relation to ASD symptomatology. Third, cognitiveperformance was not correlated with acute stress. Thus,diagnosis and treatment of traumatic stress in this patientgroup should be accounted for in the same manner as hasbeen proposed for other cancer populations (e.g., [17]).

In all screening instruments for traumatic stress (ASDS,

CDSS, IES-R), patients with ASD scored significantlyhigher than patients without ASD which had to be expectedwith regard to the validity of self-report instrumentscomprising items primarily related to trauma symptoms.Regarding the routine assessment of acute stress in braincancer patients however, only the IES-R showed con-


vincing properties with regard to both sensitivity andspecificity. Interestingly, of all applied instruments theIES-R also identified the highest proportion of patientsas suffering from clinically relevant psychological morbidityindependent of specific traumatic stress responses. This isconsistent with previous research which has recommended theIES-R or the IES [36, 50] as screening tool for theidentification of relevant but unspecific emotional burdenin early stages of physical diseases [51, 52]. Regarding theself-report measures specifically designed for assessment ofacute traumatic stress symptoms (ASDS, CDSS), lesspatients met the ASD cut-off scores compared to theSCID-ASD module. Usually however, self-report measurestend to inflate prevalence rates (e.g., [53]). Both the ASDSand the CDSS are relatively new screening instrumentsand until now, only few studies have assessed theirpsychometric properties. Thus, it might be that theseinstruments possess a high specificity but a lowersensitivity. However, the discrepancy to previous studiesmight also be due to the specifics of brain tumourpatients and/or the neurosurgical setting, which howeverwould have to be answered in future studies.

Some limitations of the current study should becarefully considered. First, the small sample size meansthat the study outcomes are preliminary, as non-significantoutcomes may be due to power issues. Second, no measure ofpatients current functional well-being, including health-related quality of life was included which would havestrengthened the study design.

The following clinical conclusions can be drawn fromour paper: Acute stress is an important topic in aconsiderable proportion of patients with brain cancer. Nopredictors were identified which would allow for theprediction of ASD. Thus, the routine assessment of ASDis indicated. However, as sensitivity of ASD-specificscreening instruments was low in our study and even theIES-R as most suitable screening instrument for ASDidentified only about three quarters of ASD patientscorrectly, to date there is no appropriate screeninginstrument for ASD in brain cancer patients. One recentstudy [54] demonstrated that the Distress Thermometer(DT; [55]), a single-item rapid screening measure, waswell suited for the routine identification of brain cancerpatients suffering from psychiatric morbidity as assessedvia the SCID. The DT has been specifically validated forpatients with brain cancer and exhibited excellent psychometricproperties for application in this population [54]. Thus, futureresearch could assess the ability of the DT to detect traumaticstress in patients with brain cancer. Moreover, future studiesshould also assess the incidence of PTSD in brain cancerpatients as well as the ability of ASD to identify patients atrisk for developing subsequent PTSD. This is of high clinicalrelevance as the negative impact of traumatic stress on


Quality of Life as well as on emotional, social, andoccupational functioning is serious (e.g., [56]). Finally,research findings should result in the development of targetedinterventions for patients with brain cancer.

Conflict of interest This study was not funded. The authors havefull control of all primary data and agree to allow the journal to reviewthe data if requested. There are no conflict of interests and no financialdisclosures by any of the authors.

References

1. Goebel S, Stark A, Kaup L, von Harscher M, Mehdorn HM(2011) Distress in patients with newly diagnosed brain tumours.Psychooncology. doi:10.1002/pon.1858

2. Gustafsson M, Edvardsson T, Ahlström G (2006) The relationship

between function, quality of life and coping in patients withlow-grade gliomas. Support Care Cancer 14:1205–1212

3. Keir ST, Calhoun-Eagan RD, Swartz JJ, Saleh OA, FriedmanHS (2008) Screening for distress in patients with brain cancerusing the nccn's rapid screening measure. Psychooncology17:621–625

4. Kvale EA, Murthy R, Taylor R, Lee JY, Nabors LB (2009)Distress and quality of life in primary high-grade brain tumorpatients. Support Care Cancer 17:793–799

5. Taphoorn MJ, Klein M (2004) Cognitive deficits in adult patients

with brain tumours. Lancet Neurol 3:159–1686. Hinz A, Krauss O, Hauss JP, Höckel M, Kortmann RD,

Stolzenburg JU, Schwarz R (2009) Anxiety and depression incancer patients compared with the general population. Eur JCancer Care 19:522–529

7. Zabora JR, BrintzenhofeSzoc KM, Curbow B, Hooker C,Piantadosi S (2001) The prevalence of psychological distress bycancer site. Psycho-Oncology 10:19–28

8. Mainio A, Hakko H, Timonen M, Niemelä A, Koivukangas J,Räsänen P (2005) Depression in relation to survival amongneurosurgical patients with primary brain tumor: a 5-year follow-upstudy. Neurosurgery 56:1234–1242

9. Pringle A-A, Taylor R, Whittle IR (1999) Anxiety and depression

in patients with an intracranial neoplasm before and after tumoursurgery. Br J Neurosurg 13:46–51

10. Janda M, Steginga S, Langbecker D, Dunn J, Walker D, Eakin E

(2007) Quality of life among patients with a brain tumour andtheir carers. J Psychosom Res 63:617–623

11. Davies E, Higginson IJ (2003) Communication, information and

support for adults with malignant cerebral glioma: a systematicliterature review. Support Care Cancer 11:21–29

12. Pace A, Metro G, Fabi A (2010) Supportive care in neurooncology.

Curr Opin Oncol Aug 11:S1531–1703X13. Trask PC (2004) Assessment of depression in cancer patients. J

Natl Cancer Inst Monogr 32:80–9214. Goebel S, von Harscher M, Mehdorn HM (2010) Comorbid

mental disorders and psychosocial distress in patients with braintumours and their spouses in the early treatment phase. SupportCare Cancer. doi:10.1007/s00520-010-1021-8

15. First MB, Spitzer RL, Gibbon M, Williams JBW (1996)Structured clinical interview for DSM-IV Axis I disorders —clinician version. American Psychiatric Press, New York

16. Wittchen HU, Zaudig M, Fydrich T (1997) Skid. Strukturiertes

interview für DSM IV. Achse I und II. Handanweisung. Hogrefe,Göttingen

80

374

1433

17. Kangas M, Henry JL, Bryant RA (2002) Posttraumatic stressdisorder following cancer: a conceptual and empirical review. ClinPsychol Rev 22:499–524

18. Kangas M, Henry JL, Bryant RA (2005) The relationship betweenacute stress disorder and posttraumatic stress disorder followingcancer. J Consult Clin Psychol 73:360–364

19. McGarvey EL, Canterbury RL, Koopman C, Clavet GJ, Cohen R,Largay K, Spiegler D (1998) Acute stress disorder followingdiagnosis of cancer. Int J Rehab Health 4:1–15

20. Mehnert A, Koch U (2007) Prevalence of acute and post-traumaticstress disorder and comorbid mental disorders in breast cancerpatients during primary cancer care: a prospective study. Psycho-Oncology 16:181–188

21. Huber W, Poeck K, Weninger D, Willmes K (1983) Der AachenerAphasie Test (AAT). Hogrefe, Göttingen

22. Folstein MF, Folstein SE, McHugh PR (1975) "Mini-mental-state": A practical method for grading the cognitive state ofpatients for the clinician. J Psychiatr Res 12:189–198

23. Blake DD, Nagey LM, Kaloupek DG, Klauminzer G, CharneyDS, Keane TM (1990) A clinician rating scale for assessingcurrent and lifetime PTSD: The CAPS-1. Behav Ther 13:187–188

24. Schnyder U, Moergeli H (2002) German version of clinician-administered PTSD scale. J Traumatic Stress 15:487–492

25. Weathers FW, Keane TM, Davidson JR (2001) Clinician-administered PTSD scale: a review of the first 10 years ofresearch. Depress Anxiety 13:132–156

26. Bryant RA, Moulds ML, Guthrie RM (2000) Acute stress disorderscale: a self-report measure of acute stress disorder. PsycholAssess 12:61–68

27. Helfricht S, Landolt MA, Moergeli H, Hepp U, Wegener D,Schnyder U (2009) Psychometric evaluation and validation ofthe german version of the acute stress disorder scale acrosstwo distinct trauma populations. J Traumatic Stress 22:476–

28. Michal M, Sann U, Niebecker M, Lazanowsky C, Kernhof K,Aurich S, Overbeck G, Sierra M, Berrios GE (2004) Themeasurement of the depersonalisation–derealisation-syndromewith the German version of the Cambridge DepersonalisationScale (CDS). Psychother Psychosom Med Psychol 54:367–

29. Sierra M, Berrios GE (2000) The Cambridge DepersonalizationScale: a new instrument for the measurement of depersonalization.Psychiatry Res 93:153–164

30. Maercker A, Schützwohl M (1998) Erfassung von psychischenbelastungsfolgen: Die impact of event skala — revidierte version(IES-R). Diagnostica 44:130–141

31. Weiss DS, Marmar CR (1996) The impact of event scale—revised.In: Wilson JP, Keane TM (eds) Assessing psychological traumaand PTSD. Guildford Press, New York

32. Creamer M, Bell R, Failla S (2003) Psychometric properties of theimpact of event scale—revised. Behav Res Ther 41:1489–1496

33. Foa EB (1997) Posttraumatic stress diagnostic scale (PDS).Pearson, San Antonio

34. Herrmann C, Buss U, Snaith RP (1995) HADS-D—HospitalAnxiety and Depression Scale—deutsche version: Ein fragebogenzur erfassung von angst und depressivität in der somatischenmedizin Huber, Bern

35. Zigmond AS, Snaith RP (1983) The Hospital Anxiety andDepression Scale. Acta Psychiatr Scand 67:361–370

36. Leplow B, Friege L (1998) Eine sozialformel zur schätzung derprämorbiden intelligenz. Zeitschr Klin Psychol 27:1–8

37. Barona A, Chastian RL (1986) An improved estimate ofpremorbid IQ for blacks and whites on the WAIS-R. Int J ClinNeuropsychol 8:169–173

38. Wechsler D (1987) Wechsler Memory Scale—Revised. ThePsychological Corporation, San Antonio

235

1434

39. Tombaugh TN (2004) Trail Making Test A and B: Normative data

stratified by age and education. Arch Clin Neuropsychol 19:203–214

40. Benton AL, Kd H (1989) Multilingual aphasia examination. AJA

Associates, Iowa City41. Warrington EK, James M (1992) Testbatterie für visuelle objekt-

und raumwahrnehmung (vosp). Thames Valley Test Company,Bury St Edmunds

42. Osterrieth PA (1944) Le test de copie d'une figure complexe. Arch

Psychol 30:206–35643. Buschke H, Fuld PA (1974) Evaluation of storage, retention, and

retrieval in disordered memory and learning. Neurology 11:1019–1025

44. Faul F, Erdfelder E, Buchner A, Lang A-G (2007) Statisticalpoweranalyses using g*power 3.1: tests for correlation andregression analyses. Behav Res Methods 41:1149–1160

45. Schützwohl M, Maercker A (1999) Effects of varying diagnostic

criteria for posttraumatic stress disorder are endorsing the conceptof partial PTSD. J Traumatic Stress 12:155–165

46. Lagarde G, Doyon J, Brunet A (2010) Memory and executive

dysfunctions associated with acute posttraumatic stress disorder.Psychiatry Res 177:144–149

47. Quin S, Hermans EJ, van Marle HJ, Luo J, Fernandez G (2009)

Acute psychological stress reduces working memory-relatedactivity in the dorsolateral prefrontal cortex. Biol Psychiatry66:25–32


48. Danckwerts A, Leathen J (2003) Questioning the link betweenptsd and cognitive dysfunction. Neuropsychol Rev 13:221–

49. Kangas M, Henry JL, Bryant RA (2007) Correlates of acute stressdisorder in cancer patients. J Traumatic Stress 20:325–334

50. Horowitz M, Wilner N, Alvarez W (1979) Impact of event scale: ameasure of subjective stress. Psychosom Med 41:209–218

51. Carpenter KM, Fowler JM, Maxwell GL, Andersen BL (2010)Direct and buffering effects of social support amonggynecologic cancer survivors. Ann Behav Med. doi:10.1007/s12160-010-9160-1

52. Tedstone JE, Tarrier N (2003) Posttraumatic stress disorderfollowing medical illness and treatment. Clin Psychol Rev23:409–448

53. Mitchell AJ (2010) Short screening tools for cancer-relateddistress: a review and diagnostic validity meta-analysis. J NatlCompr Cancer Netw 8:487–494

54. Goebel S, Mehdorn HM (in press) The measure of psychologicaldistress in patients with intracranial tumours: The nccn distressthermometer. J Neurooncol

55. NCCN (2003) Distress management clinical practice guidelines. JNatl Compr Cancer Netw 1:344–374

56. Davidson JR (2000) Trauma: the impact of post-traumatic stressdisorder. J Psychopharmacol 14(2Suppl1):S5–S12

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