rttithlrecurrent tumor in the larynx and hypopharynx...
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Department of ORL, Head and Neck Surgery andDepartment of ORL, Head and Neck Surgery andDiagnostic Interventional and Pediatric RadiologyDiagnostic Interventional and Pediatric RadiologyDiagnostic, Interventional and Pediatric Radiology, Diagnostic, Interventional and Pediatric Radiology, University Hospital Bern, SwitzerlandUniversity Hospital Bern, Switzerland
R t T i th LR t T i th LRecurrent Tumor in the LarynxRecurrent Tumor in the Larynxand Hypopharynx after (Chemo)radiation:and Hypopharynx after (Chemo)radiation:
Clinical and Histopathological AspectsClinical and Histopathological Aspects
P Zbaeren H ThoenyP Zbaeren H ThoenyP. Zbaeren, H. ThoenyP. Zbaeren, H. Thoeny
Background
With the onset of new chemotherapy regimens, py gnew treatment strategies for advanced carcinomas were developed: combined chemoradiotherapy, concomitant
ti lor sequential
Currently, many T3 and even T4 carcinomas are initiallyCurrently, many T3 and even T4 carcinomas are initially treated by chemoradiotherapy while primary total laryngectomies are becoming rare
As recurrent laryngeal carcinomas are increasingly being treated by voice preservation salvage surgery a precisetreated by voice-preservation salvage surgery, a precise diagnostic work-up is currently mandatory.
Spirano et al Head Neck 2002
Yiotakis et al Ortolaryngol Head Neck Surg 2003
Questions
Do tissue changes - observed on imaging studies or during endoscopies - correspond to sequelaeor during endoscopies - correspond to sequelae
of (chemo)radiation or are they due to tumor recurrence?tumor recurrence?
How is the reliability of imaging studies and endoscopies in the assessment of recurrent
disease extent?
Grading system for radiation reactions
Chandler JR Ann Otol Rhinol Laryngol 1979
Endoscopic findings
Endoscopic findings
Definition Chondroradionecrosis
Histologic characteristicsHistologic characteristics
► Lack of perichondrium► Lack of perichondrium
►Cartilage erosion►Cartilage erosion
►Severe inflammation►Severe inflammationAbscesses
►Destroyed cartilage with sequestrationwith sequestration
Imaging findings of radionecrosis
Cricoarytenoid sclerosis
Anterior dislocation and sloughing of the arytenoidsAnterior dislocation and sloughing of the arytenoids
P f b bblPresence of gas bubbles
Fragmentation and collapse of cartilages
Hermans et al Am J. Neurolradiol 1998
Imaging findings of radionecrosis
Radionecrosis versus recurrent disease
Patients
Radiation or radiochemotherapy 341
Symptoms suggestive of tumor recurrence
92recurrence
Tumor recurrence found by imagingTumor recurrence found by imaging studies and endoscopy with biopsy
72
No tumor recurrence 20
Zbaeren et al Otolaryngol Head Neck Surg 2006
Patients
Study group
20 patients with symptoms suggestive20 patients with symptoms suggestive of recurrence but without evidence of recurrence on initial imaging studiesrecurrence on initial imaging studies
and endoscopy
Methods
Retrospective studyRetrospective study
Analysis of clinico-pathologic findings, a ys s o c co pat o og c d gs,diagnostic work-up and treatment modalities
Tumor staging according the UICC 1997 classificationthe UICC 1997 classification
Laryngectomy specimes were analyzed on whole organ slices
Symptoms
Increase of dysphonia with progessive dyspnoea 20
Respitarory distress needing tracheotmy 12
Severe dysphagia 4
Acute laryngeal hemorrhage 2
Pharyngocutaneous fistula 1
L t fi t l 1Laryngocutaneous fistula 1
Imaging findings
CT scan 40CT scan 40
MR imaging 11
Fi di T iti f 3Findings True positive for recurrence 3
False positive 1False positive 1
True negative 13True negative 13
False negative 3False negative 3
True negative for recurrenceTrue negative for recurrence
Results Imaging studies
14.10.01 13.01.02
True positive for recurrence
True negative for recurrence
Endoscopic findings and biopsies
Endoscopies with biopsies 40
Marked edema with severe occlusionof airways needing a tracheotomy 12
Denuded bone or cartilage or sequesters 5
Ulceration without denuded bone or cartilage 2
Pathologic tissue suggesting tumor recurrence 2
Results Biopsies
Biopsies performed during 40 endoscopies 40
Positive biopsies (during 2nd or 3rd endoscopy) 4Positive biopsies (during 2nd or 3rd endoscopy) 4
Negative biopsies 36
Reccurences in laryngectomy specimens 6y g y p
Incidence of chondroradionecrosis
Chondroradionecrosis in laryngectomy specimens
10
Cartilage sequester 2
(Patients with tracheotomies)2
Frank fragmentation of cartilage
(Patients with tracheotomies)3
Total 17Total 17
Summary
In case of recurrent or progressive symptomsIn case of recurrent or progressive symptoms such as hoarseness, dysphagia and dyspnea, repeated imaging studies and endoscopiesrepeated imaging studies and endoscopies must be performed, as
in about 22% of cases it may be difficult to differentiate between persistent or recurrentdifferentiate between persistent or recurrent tumor and severe radiation effects
In a few cases a total laryngectomy must be performed despite repeated negative biopsiesperformed despite repeated negative biopsies
Questions
Do tissue changes - observed on imaging studies or during endoscopies - correspond to sequelaeor during endoscopies - correspond to sequelae
of (chemo)radiation or are they due to tumor recurrence?tumor recurrence?
How is the reliability of imaging studies and endoscopies in the assessment of recurrent
disease extent?
To understand the difficulty in assessingTo understand the difficulty in assessing the extent of recurrent carcinoma, one
must know the histologicmust know the histologic characteristics and tumor spread of
recurrent carcinomasrecurrent carcinomas
Histologic characteristics and tumor spread of recurrent glottic carcinomasecu e t g ott c ca c o as
Aim of the studyy
T l th tt f t dTo analyze the pattern of tumor spread
To compare the growth patternTo compare the growth pattern of pr T3 / pr T4 (n=21) carcinoma with that of de novo“ p T3 / p T4 carcinoma (n=52)of „de novo p T3 / p T4 carcinoma (n=52)
Zbaeren et al Head Neck 2007
Patients
Initial (chemo)radiation ofcT1 /cT2 N0 glottic carcinoma 168cT1 /cT2 N0 glottic carcinoma 168
Recurrence 32(19%)Recurrence 32(19%)
Total or classical partialTotal or classical partial salvage laryngectomy 29
pr T1 / pr T2 8pr T1 / pr T2 8pr T3 / pr T4 21
Results
Multicentric foci
Salvage Laryngectomy17/21 (81%)
„De novo“ Laryngectomy15/52 (23%)( ) ( )
Results
Dissociated tumor cellsDissociated tumor cells
Salvage Laryngectomy16/21 (76%)
„De novo“ Laryngectomy15/52 (33%)15/52 (33%)
Results
Subglottic and supraglottic tumor extensions
Results
Perineural infiltration
Salvage Laryngectomy17/21 (81%)17/21 (81%)
„De novo“ Laryngectomy„ y g y28/52 (54%)
Results
Pattern of cartilage infiltrationSalvage Laryngectomy „De novo“
Laryngectomy
Summary
Recurrent glottic carcinomas present withRecurrent glottic carcinomas present with multiple tumor foci dispersed in different
regions of the larynxregions of the larynx
Assessment of recurrent tumor extent
H i th li bilit f tiHow is the reliability of preoperative imaging studies and clinical and
d i i ti i th tendoscopic examination in the assessment of the extent and staging of
t l l i ?recurrent laryngeal carcinomas?
Assessment of recurrent tumor extent
Aim of the study
T l th f th
Aim of the study
To analyze the accuracy of the preoperative imaging studies and endoscop in the assessment ofendoscopy in the assessment of recurrent laryngeal carcinomas
Patients
R di ti di h th 241Radiation or radiochemotherapy 241
Tumor recurrence 60
Excluded from the study 18Excluded from the study 18
no appropriate histology 9
no appropriate imaging studies 9no appropriate imaging studies 9
Included in the study 42
Patients N = 42
Initial TInitial TT1a 9
T1b 5
T2 18
T3 10
Initial tumor locationInitial tumor locationGlottic level 15
Supraglottic level 8Supraglottic level 8
Glottosupraglottic levels 8
Glottosubglottic levels 5Glottosubglottic levels 5
Transglottic 6
Patients N = 42
Treatment of rec rrent t morTreatment of recurrent tumor
Total laryngectomy 37
Supraglottic laryngectomy 3p g y g y
Supracricoid laryngectomy 2Supracricoid laryngectomy 2
Methods
Retrospective studyRetrospective study
The laryngectomy specimens were analyzed onThe laryngectomy specimens were analyzed on axial whole-organ slices
The CT scans (n=25) or MR imaging (n=17) i d b t i d di l i twere reviewed by two experienced radiologists
Th d i d i i fi diThe endoscopic and imaging findings were compared with histologic findings
Methods
The follo ing items ere anal edThe following items were analyzed
► T t i di t th l l► Tumor extension according to the levels
► Contralateral tumor spread► Contralateral tumor spread
► Cartilage infiltration
► Preepiglottic space
► Paraglottic space
► T l ifi ti► crT classification
Results
Histopathologic analysis
Glottic carcinoma 2
Supraglottic carcinoma 7
Glottosupraglottic carcinoma 4Glottosupraglottic carcinoma 4
Glottosubglottic carcinoma 7
Transglottic carcinoma 22
Contralateral tumor spread 36Contralateral tumor spread 36
Results
Histopathologic analysis
Preepiglottic space 16
Tumor involvement of the
Preepiglottic space 16
Paraglottic space 29
Thyroid cartilage 25
Cricoid cartilage 17Cricoid cartilage 17
Arytenoid cartilage 16
Results
Imaging findings
Accuracy Sensitivity Specificity
Preepiglottic space 83 59 100Preepiglottic space 83 59 100
Paraglottic space 60 73 25
Thyroid cartilage 64 48 88
Cricoid cartilage 65 47 80g 65 47 80
Arytenoid cartilage 86 62 95
C t l t l t dContralateral tumor spread 52 50 67
Tumor at this level?
Results
Endoscopic findings
correctover- under-
correctestimated estimated
Involved levels 22 (52%) 4 1522 (52%) 4 15
Contralateral tumor spread
22 (52%)tumor spread
Results
crT pT
T1 1 3T1 1 3
T2 6 4
T3 27 13
T4 7 22
Accuracy 50%y
Overclassification 3
Underclassification 18Underclassification 18
Discussion
Recurrent tumor assessment is difficult forRecurrent tumor assessment is difficult for the following reasons:
► T ft di ti th i► Tumor may recur after radiation therapy in multicentric foci, undetectable by imaging studies
► Residual inflammation changes associated with radiation therapy
► Tumor recurrence may be localized submucosally – invisible during endoscopyy g py
► Differentiation between radionecrosis and tumor recurrence often not obvious
Zbären Head and Neck 2007Zbären Otolaryngol Head Neck 2007
recurrence often not obvious
Discussion
Comparison with assessment of de novo
C i idTh id
Comparison with assessment of de novo laryngeal carcinoma
De novoRe-
current
Cricoid
De novoRe-
current
Thyroid
MRICT
current
MRICT
current
83
88
100
92
47
65
62
83
95
72
48
64
Sensitivity
Accuracy
90
83
87
100
80
47
97
62
56
95
88
48
Specificity
Sensitivity
Becker Radiology 1995; 194: 661 -669 Zbären Cancer 1996; 77: 1263-73
Summary
In many cases, the assessment of tumor t i i i t ith b dextension is inaccurate either by endoscopy or
by imaging studies
The assessment of recurrent laryngealThe assessment of recurrent laryngeal carcinoma is much more difficult than the assessment of «de novo» carcinoma either byassessment of «de novo» carcinoma either by endoscopy or by imaging studies
New imaging modalities
PET - CT
For all negative PET scans (n=27), the Teerhard 2001
PET CT
g ( ),biopsies taken were negative and no recurrence was seen for at least 1 year thereafterthereafter
In 7 patients PET did not confirm the recurrence, which was suspected clinically and by CT scan
Périé 2007
clinically and by CT scan
Terhaard CH. Head Neck 2001Périé S. Otolaryngol Head Neck Surg 2007
New imaging modalities
Male 60 yearsPET - CTMale 60 years
2000 cT2 glottic - supraglottic carcinoma treated by chemoraditherapychemoraditherapy
2007 Pain and progressive dysphagia
New imaging modalities
Diffusion - weighted MRI
Male 54 years
1991 cT2 glottic carcinoma treated by radiation
1999 recurrent disease rT3 treated by
supracricoid larygectomy
2007 progressive dysphonia and dyspnoe
b=1000 ADC map
New imaging modalities
Female 52 yearsDiffusion - weighted MRIFemale 52 years
2004 cT2 hypopharyngeal carcinoma treated by CO2 - laser - resection and adjuvant radiationj
2007 Pain and dysphagie
New imaging modalities
Institutional experienceInstitutional experience
Diffusion - weighted MRI 12
true positive findings 5
f l iti fi di 1false positive findings 1
true negative findings 6
Conclusions
CT scan and conventional MR imaging cannot differentiate between recurrence and tissue changes
due to (chemo) radiotherapy in many casesdue to (chemo) radiotherapy in many cases
M d di ti d liti h PET CTModern diagnostic modalities such as PET - CT and diffusion - weighted MR imaging are
promising diagnostic toolspromising diagnostic tools
To impro e the q alit of ork pTo improve the quality of work - upprospective studies are needed
Endoscopic findings
Patients
Radiation or radiochemotherapy 341ad at o o ad oc e ot e apy 3
L l i 237Laryngeal carcinomas 237Hypopharyngeal carcinomas 104
T1/T2 272T3/T4 69
Conclusions
To improve the assessment of recurrent plaryngeal carcinomas,
prospective studies comparing the p p p gendoscopic and imaging findings with whole-organ sections of laryngectomy g y g y
specimens should be performed
Patients
Radiation or radiochemotherapy 341ad at o o ad oc e ot e apy 3
L l i 237Laryngeal carcinomas 237Hypopharyngeal carcinomas 104
T1/T2 272T3/T4 69
Background
T1 d T2 l l d h h l iT1 and T2 laryngeal and hypopharyngeal carcinomas can be managed either by organ-sparing surgery or by radical radiotherapyradical radiotherapy
With the onset of new chemotherapy regimens, y gnew treatment strategies for advanced carcinomas were developed: combined chemoradiotherapy, concomitant
ti lor sequential
Currently many T3 and even T4 carcinomas are initiallyCurrently, many T3 and even T4 carcinomas are initially treated by chemoradiotherapy while primary total laryngectomies are becoming rarey g g
Background
Salvage surgery after irradiation was historically id d t b ibl l ith t t l l tconsidered to be possible only with total laryngectomy,
wherefore the knowledge of an exact tumor extension was not requiredwas not required.
As recurrent laryngeal carcinomas are increasingly beingAs recurrent laryngeal carcinomas are increasingly being treated by voice-preservation salvage surgery, a precise diagnostic work-up is currently mandatory.diagnostic work up is currently mandatory.
Spirano et al Head Neck 2002
Yiotakis et al Ortolaryngol Head Neck Surg 2003
Conclusions
All patients with symptoms suggestive of tumor recurrence but negative on initial work-up presentedrecurrence but negative on initial work-up presented
finally with documented radionecrosis or Chandler IV radiation reaction
Recurrent carcinoma is not always visible on endoscopy. Therefore biopsies
b f l timay be false negative
Patients
Surgical treatment Total laryngectomy 10Surgical treatment Total laryngectomy 10
Tracheotomy 10Tracheotomy 10
Results Biopsies
Biopsies performed during 40 endoscopies 40
Positive biopsies (during 2nd or 3rd endoscopy) 4p ( g py)
Negative biopsies 36
Total laryngectomy with positive biopsies 4
Total laryngectomy despite repeated negative biopsies
6
Radionecrosis versus recurrent disease
Aim of the study
To analyze the incidence and diagnostic difficultiesand diagnostic difficulties of chondroradionecrosisafter (chemo)radiotherapy
Zbaeren et al Otolaryngol Head Neck Surg 2006
Incidence of chondroradionecrosis
Chondroradionecrosis in laryngectomy specimens
10+2
Cartilage sequester 2
(Patients with tracheotomies)2
Frank fragmentation of cartilage
(Patients with tracheotomies)3
Total 17/341 (5%)Total 17/341 (5%)
Results Endoscopic findings
fMarked edema with severe occlusion of airways
Patients
Surgical treatment Total laryngectomy 10Surgical treatment Total laryngectomy 10
Total laryngectomy with positive biopsies 4y g y p p
Total laryngectomy despite repeated negative biopsies
6biopsies