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Prognostic Factors
The most important adverse prognostic factors for laryngeal cancers include increasing T stage and N
stage. Other prognostic factors may include sex, age, performance status, and a variety of pathologic
features of the tumor, including grade and depth of invasion.[5]
Prognosis for small laryngeal cancers that have not spread to lymph nodes is very good with cure rates of
75% to 95% depending on the site, tumor bulk,[6] and degree of infiltration. Although most
early lesions can be cured by either radiation therapy or surgery, radiation therapy may be reasonable to
preserve the voice, leaving surgery for salvage. Patients with a preradiation hemoglobin level higher than
13 g/dL have higher local control and survival rates than patients who are anemic.[7]
Locally advanced lesions are treated with combined modality treatment involving radiation
and chemotherapy with or without surgery, the aim of which is laryngeal preservation in appropriately
selected candidates.[8] Distant metastases are also common, even if the primary tumor is controlled.
Intermediate lesions have intermediate prognoses, depending on site, T stage, N stage, and performance
status. Therapy recommendations for patients with these lesions are based on a variety of complex
anatomic, clinical, and social factors, which should be individualized and discussed in multidisciplinary
consultation (surgery, radiation therapy, and dental and oral surgery) prior to prescribing therapy.
Faktor prognostic
Faktor prognostik samping yang paling penting bagi kanker laring termasuk
meningkatkan tahap T dan N panggung. Faktor prognostik lain mungkin termasuk
jenis kelamin, usia, status kinerja, dan berbagai fitur patologis tumor, termasuk
kelas dan kedalaman invasi.
Prognosis untuk kanker laring kecil yang belum menyebar ke kelenjar getah bening
sangat baik dengan tingkat kesembuhan 75% sampai 95% tergantung pada situs,
curah tumor, dan tingkat infiltrasi. Meskipun sebagian besar lesi dini dapat
disembuhkan dengan baik terapi radiasi atau operasi, terapi radiasi mungkin masuk
akal untuk melestarikan suara, meninggalkan operasi untuk penyelamatan. Pasien
dengan tingkat preradiation hemoglobin lebih tinggi dari 13 g / dL memiliki kontrol
dan kelangsungan hidup suku lokal lebih tinggi dibandingkan pasien yang
mengalami anemia.
Secara lokal lesi canggih diperlakukan dengan modalitas pengobatan gabungan
yang melibatkan radiasi dan kemoterapi dengan atau tanpa operasi, tujuan dari
yang pelestarian laring di kandidat terpilih dengan tepat. metastasis jauh juga
umum, bahkan jika tumor primer dikontrol.
lesi menengah memiliki prognosis menengah, tergantung pada situs, T panggung, N
panggung, dan status kinerja. rekomendasi terapi untuk pasien dengan lesi ini
didasarkan pada berbagai anatomi, klinik, dan sosial faktor yang kompleks, yang
harus individual dan dibahas dalam konsultasi multidisiplin (operasi, terapi radiasi,
dan operasi gigi dan mulut) sebelum meresepkan terapi.
Second primary tumors, often in the aerodigestive tract, have been reported in as many as 25% of
patients whose initial lesion is controlled. A study has shown that daily treatment of these patients with
moderate doses of isotretinoin (i.e., 13-cis-retinoic acid) for 1 year can significantly reduce
the incidence of second tumors.[9] No survival advantage has been demonstrated, partially because of
recurrence and death from the primary malignancy.
Patients treated for laryngeal cancers are at the highest risk of recurrence in the first 2 to 3 years.
Recurrences after 5 years are rare and usually represent new primary malignancies. Close, regular
follow-up is crucial to maximize the chance for salvage. Careful clinical examination and repetition of any
abnormal staging study are included in follow-up, along with attention to any treatment-related toxic effect
or complication.
Direct comparison of the results of radiation therapy versus endolaryngeal surgery (with or without laser)
has not been made for patients with early stage laryngeal cancer. The evidence is insufficient to show a
clear difference in the results between treatment options in regard to local control or OS. Retrospective
data suggests that in comparison with surgery, radiation therapy might cause less perturbation
of voice quality without a significant difference in patient perception.[6]
A direct comparison of chemotherapy followed by radiation therapy versus upfront surgery was made by
The Department of Veterans Affairs (VA) Laryngeal Cancer Study Group in a trial in which 332 patients
were randomly assigned to three cycles of chemotherapy (cisplatin and fluorouracil) and radiation therapy
or surgery and radiation therapy.[7] After two cycles of chemotherapy, the clinical tumor response was
complete in 31% of the patients, and there was a partial response in 54% of the patients. Survival was
similar in both arms; however, larynx preservation was possible in 64% of the patients in the
chemotherapy-followed-by-radiation therapy arm.
The VA study was followed up in a randomized study, RTOG 9111 (NCT00002496), in which the laryngeal
preservation arm of the VA study was compared with the concomitant chemoradiation and radiation-
alone arms, and the primary endpoint was laryngectomy-free survival (LFS).[3] The RTOG 9111 study
evaluated 547 patients with locally advanced laryngeal cancer who were enrolled between August 1992
and May 2000, with a median follow-up for surviving patients of 10.8 years (range, 0.0717 years). Three
regimens were compared, including induction chemotherapy plus radiation therapy, concomitant
chemoradiation, and radiation therapy alone. Both chemotherapy regimens improved LFS compared with
radiation therapy alone (induction chemotherapy vs. radiation therapy alone, hazard ratio [HR], 0.75; 95%
confidence interval [CI], 0.590.95; P = .02; concomitant chemotherapy vs. radiation therapy alone, HR,
0.78; 95% CI, 0.780.98; P = .03).
Concurrent radiation therapy plus cisplatin resulted in a statistically significantly higher percentage of
patients with an intact larynx at 10 years (67.5% for patients who had induction chemotherapy; 81.7% for
patients who had concomitant chemotherapy; and 63.8% for patients who received radiation alone); 80%
of laryngectomies were performed during the first 2 years (84 laryngectomies during year 1 and 35
laryngectomies during year 2).
Concomitant cisplatin with radiation therapy resulted in a 41% reduction in risk of locoregional failure
compared with radiation therapy alone (HR, 0.59; 95% CI, 0.430.82; P = .0015) and a 34% reduction in
risk compared with induction chemotherapy(HR, 0.66; 95% CI, 0.480.92; P = .004). Both chemotherapy
regimens had a lower incidence of distant metastases, although this did not reach statistical significance
compared with radiation therapy alone.
The 10-year cumulative rates of late toxicity (grades 35) were 30.6% for induction chemotherapy, 33.3%
for concomitant chemotherapy, and 38% for radiation alone, and were not significantly different between
the arms.
OS was not significantly different between the groups, although there was possibly a worse outcome in
the concomitant groups compared with the induction chemotherapy group (HR, 1.25; 95% CI, 0.98
1.61; P = .08). The OS rates were 58% (5 year) and 39% (10 year) for induction chemotherapy, 55% (5
year) and 28% (10 year) for concomitant chemoradiation, and 54% (5 year) and 32% (10 year) for
radiation alone. The number of deaths not attributed to larynx cancer or treatment were higher with
concomitant chemotherapy (30.8% vs. 20.8% with induction chemotherapy and 16.9% with radiation
alone), because after approximately 4.5 years, the survival curves began to separate and favor induction,
although the difference was not statistically significant.[3]
The risk of lymph node metastases in patients with stage I glottic cancer ranges from 0% to 2%, and for
more advanced disease, such as stage II and stage III glottic, the incidence is only 10% and 15%,
respectively. Thus, there is no need to treat glottic cancer cervical lymph nodes electively in patients with
stage I tumors and small stage II tumors. Elective neck radiation should be considered for T3 or T4 glottic
tumors or T1 to T4 supraglottic tumors.[8]
For patients with cancer of the subglottis, combined modality therapy is generally preferred for the
uncommon small lesions (i.e., stage I or stage II); however, radiation therapy alone may be used.
Patients who smoke during radiation therapy appear to have lower response rates and shorter survival
durations than those who do not;[9] therefore, patients should be counseled on smoking cessation before
beginning radiation therapy.
Risiko metastasis kelenjar getah bening pada pasien dengan stadium I glotis
rentang kanker dari 0% sampai 2%, dan untuk penyakit yang lebih maju, seperti
tahap II dan tahap III glotis, kejadian ini hanya 10% dan 15%, masing-masing.
Dengan demikian, tidak perlu untuk mengobati kanker glotis kelenjar getah bening
leher elektif pada pasien dengan saya tumor panggung dan tumor kecil tahap II.
radiasi leher elektif harus dipertimbangkan untuk T3 atau T4 tumor glotis atau T1
untuk T4 tumor supraglottic. [8]
Untuk pasien dengan kanker subglottis, terapi modalitas dikombinasikan umumnya
lebih disukai untuk lesi kecil jarang (yaitu, tahap I atau tahap II); Namun, terapi
radiasi saja dapat digunakan.
Pasien yang merokok selama terapi radiasi tampaknya memiliki tingkat respon yang
lebih rendah dan jangka waktu kelangsungan hidup lebih pendek dari mereka yang
tidak; [9] Oleh karena itu, pasien harus dikonseling pada berhenti merokok sebelum
memulai terapi radiasi.
Mengumpulkan bukti telah menunjukkan insiden tinggi (yaitu,> 30% -40%) dari
hipotiroidisme pada pasien yang telah menerima radiasi sinar eksternal untuk
seluruh kelenjar tiroid atau kelenjar pituitari. Tiroid pengujian persimpangan pasien
harus dipertimbangkan sebelum terapi dan sebagai bagian dari posttreatment
tindak lanjut. [10,11]
Supraglottis
Standard treatment options:
1. External-beam radiation therapy alone.
2. Supraglottic laryngectomy. Total laryngectomy may be reserved for patients
unable to tolerate potential respiratory complications of surgery or the supraglottic
laryngectomy.
Glottis
Standard treatment options:
1. Radiation therapy.[3-6]
2. Cordectomy for very carefully selected patients with limited and superficial T1
lesions.[7,8]
3. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic
considerations.
4. Endoscopic CO2 laser excision.[9]
Subglottis
Standard treatment options:
1. Lesions can be treated successfully by radiation therapy alone with preservation
of normal voice.
2. Surgery is reserved for failure of radiation therapy or for patients who cannot be
easily assessed for radiation therapy.
Supraglottis
Standard pilihan pengobatan:
1. External-beam terapi radiasi saja.
2. laryngectomy Supraglottic. Jumlah laryngectomy dapat dicadangkan untuk
pasien tidak dapat mentoleransi komplikasi pernapasan potensi pembedahan atau
laryngectomy supraglottic.
Celah suara
Standard pilihan pengobatan:
1. Terapi Radiasi. [3-6]
2. Cordectomy untuk pasien sangat hati-hati dipilih dengan lesi T1 terbatas dan
dangkal. [7,8]
3. parsial atau hemilaryngectomy atau total laryngectomy, tergantung pada
pertimbangan anatomi.
4. Endoskopi CO2 laser eksisi. [9]
Subglottis
Standard pilihan pengobatan:
1. Lesi dapat diobati berhasil dengan terapi radiasi saja dengan pelestarian suara
normal.
2. Pembedahan dicadangkan untuk kegagalan terapi radiasi atau untuk pasien yang
tidak dapat dengan mudah dinilai untuk terapi radiasi.
Glottis
Standard treatment options:
1. Radiation therapy.[1-4]
2. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic
considerations. Under certain circumstances, laser microsurgery may be
appropriate.[5]
Subglottis
Standard treatment options:
1. Lesions can be treated successfully by radiation therapy alone with preservation
of normal voice.[1]
2.Surgery is reserved for failure of radiation therapy or for patients in whom follow-
up is likely to be difficult.
Celah suara
Standard pilihan pengobatan:
1. Terapi Radiasi. [1-4]
2. sebagian atau hemilaryngectomy atau total laryngectomy, tergantung pada
pertimbangan anatomi. Dalam keadaan tertentu, Laser mikro mungkin tepat. [5]
Subglottis
Standard pilihan pengobatan:
1. Lesi dapat diobati berhasil dengan terapi radiasi saja dengan pelestarian suara
normal. [1]
2. Pembedahan dicadangkan untuk kegagalan terapi radiasi atau untuk pasien yang
tindak lanjut kemungkinan akan sulit.
An overall survival (OS) benefit was found for patients with positive margins and
extracapsular extensions based on a pooled analysis of the European Organization
for the Research and Treatment of Cancer (EORTC) 22931 [NCT00002555] and
RTOG-9501 studies.[6-9][Level of evidence: 1iiA] The addition of chemotherapy to
radiation therapy for other pathological risk factors is unclear. A postoperative
randomized trial (RTOG-0920 ) is evaluating the use of cetuximab with adjuvant
radiation therapy in the postoperative setting.[6-9][Level of evidence: 1iiA]
PORT Dengan atau Tanpa Kemoterapi
Tergantung pada temuan patologis setelah operasi utama, PORT atau kemoradiasi
pasca operasi digunakan dalam pengaturan ajuvan untuk temuan histologis berikut:
. Penyakit T4.
. invasi perineural.
. invasi Lymphovascular.
. margin positif atau margin kurang dari 5 mm.
. ekstensi ekstrakapsular dari kelenjar getah bening.
. Dua atau lebih terlibat kelenjar getah bening
Manfaat keseluruhan survival (OS) ditemukan untuk pasien dengan margin positif
dan ekstensi ekstrakapsular berdasarkan analisis dikumpulkan dari Organisasi Eropa
untuk Riset dan Perawatan Kanker (EORTC) 22.931 [NCT00002555] dan RTOG-9501
studi. [6-9 ] [Tingkat bukti: 1iiA] penambahan kemoterapi terapi radiasi untuk faktor
risiko patologis lainnya tidak jelas. Sebuah uji coba secara acak pasca operasi
(RTOG-0920) sedang mengevaluasi penggunaan cetuximab dengan terapi radiasi
adjuvant dalam pengaturan pasca operasi [6-9] [Tingkat bukti: 1iiA].
Glottis
Standard treatment options:
1. Chemotherapy administered concomitantly with radiation therapy can be
considered for patients who would require total laryngectomy for control of disease.
[1]
2. Induction chemotherapy followed by concomitant chemotherapy and radiation.
Laryngectomy is reserved for patients with less than a 50% response to
chemotherapy or who have persistent disease following radiation.[1-6]
3. Definitive radiation therapy alone with altered fractionation in patients who are
not candidates for concomitant chemotherapy and surgery (total laryngectomy) for
salvage of radiation failures.[7]
4. Surgery with or without PORT.[8]
Treatment options under clinical evaluation:
. Clinical trials exploring chemotherapy, radiosensitizers, or particle beam radiation
therapy.[9]
Celah suara
Standard pilihan pengobatan:
1. Kemoterapi diberikan sekaligus dengan terapi radiasi dapat dipertimbangkan
untuk pasien yang akan membutuhkan jumlah laryngectomy untuk pengendalian
penyakit. [1]
2. Induksi kemoterapi diikuti dengan kemoterapi bersamaan dan radiasi.
Laryngectomy dicadangkan untuk pasien dengan kurang dari respon 50% terhadap
kemoterapi atau yang memiliki penyakit persisten berikut radiasi. [1-6]
3. terapi radiasi definitif saja dengan fraksinasi diubah pada pasien yang tidak
kandidat untuk kemoterapi bersamaan dan operasi (Total laryngectomy) untuk
penyelamatan kegagalan radiasi. [7]
4. Operasi dengan atau tanpa PORT. [8]
Pilihan pengobatan di bawah evaluasi klinis: . Uji klinis menjelajahi kemoterapi,
radiosensitizers, atau partikel terapi radiasi sinar. [9]
Subglottis
Standard treatment options:
1. Laryngectomy plus isolated thyroidectomy and tracheoesophageal node
dissection usually followed by postoperative radiation therapy.[10]
2. Treatment by radiation therapy alone is indicated for patients who are not
candidates for surgery. Patients should be closely followed, and surgical salvage
should be planned for recurrences that are local or in the neck.
3. Definitive radiation therapy alone with altered fractionation in patients who are
not candidates for concomitant chemotherapy and surgery (total laryngectomy) for
salvage of radiation failures.[6,7]
4. Induction chemotherapy followed by concomitant chemotherapy and radiation.
Laryngectomy is reserved for patients with less than a 50% response to
chemotherapy or who have persistent disease after radiation.[6]
Subglottis
Standard pilihan pengobatan:
1. Laryngectomy ditambah terisolasi tiroidektomi dan trakeo diseksi biasanya diikuti
dengan terapi radiasi pasca operasi. [10]
2. Pengobatan dengan terapi radiasi saja diindikasikan untuk pasien yang tidak
kandidat untuk operasi. Pasien harus diikuti secara cermat, dan penyelamatan
bedah harus direncanakan untuk rekurensi yang lokal atau di leher.
3. Terapi definitif radiasi saja dengan fraksinasi diubah pada pasien yang tidak
kandidat untuk kemoterapi bersamaan dan operasi (Total laryngectomy) untuk
penyelamatan kegagalan radiasi. [6,7]
4. kemoterapi induksi diikuti dengan kemoterapi bersamaan dan radiasi.
Laryngectomy dicadangkan untuk pasien dengan kurang dari respon 50% terhadap
kemoterapi atau yang memiliki penyakit persisten setelah radiasi. [6]
Altered Fractionation
Radiation therapy alone with altered fractionation may be used for patients with locally advanced head
and neck cancer who are not candidates for chemotherapy. Altered fractionation radiation therapy yields a
higher locoregional control rate than standard fractionated radiation therapy for patients with stage III and
stage IV head and neck cancer. A long-term analysis of randomized trial RTOG-9003 included the
following four radiation therapy treatment arms:
1. Standard fractionated radiation therapy (SFX) to 70 Gy in 35 daily fractions for 7 weeks.
2. Hyperfractionated radiation therapy (HFX) to 81.6 Gy in 68 twice-daily fractions for 7 weeks.
3. Accelerated fractionated radiation therapy (AFX-S) to 67.2 Gy in 42 fractions for 6 weeks with a
2-week rest after 38.4 Gy.
4. Accelerated continuous fractionated radiation therapy (AFX-C) to 72 Gy in 42 fractions for 6
weeks.
Fraksinasi diubah
Terapi radiasi saja dengan fraksinasi diubah dapat digunakan untuk pasien dengan
stadium lanjut kanker kepala dan leher yang tidak kandidat untuk kemoterapi.
Diubah terapi radiasi fraksionasi menghasilkan tingkat kontrol locoregional lebih
tinggi dari terapi radiasi fraksinasi standar untuk pasien dengan stadium III dan
kepala stadium IV dan kanker leher. Sebuah analisis jangka panjang dari uji coba
secara acak RTOG-9003 termasuk empat radiasi kelompok pengobatan terapi
berikut:
1. Standar terapi radiasi fraksinasi (SFX) ke 70 Gy dalam 35 fraksi setiap hari
selama 7 minggu.
2. hyperfractionated terapi radiasi (HFX) untuk 81,6 Gy dalam 68 fraksi dua kali
sehari selama 7 minggu.
3. Percepatan difraksinasi terapi radiasi (AFX-S) untuk 67,2 Gy dalam 42 fraksi
selama 6 minggu dengan istirahat 2 minggu setelah 38,4 Gy.
4. Accelerated terus menerus fraksinasi terapi radiasi (AFX-C) untuk 72 Gy dalam 42
fraksi selama 6 minggu.
The three experimental arms were to be compared with SFX. Only the
HFX arm showed superior locoregional control and survival at 5 years compared with the SFX arm
(hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.621.00; P = .05). AFX-C was associated with
increased late toxicity compared with SFX.[14-19][Level of evidence: 1iiA]
In a meta-analysis of 15 randomized trials with a total of 6,515 patients and a median follow-up of 6 years
involving the assessment of HFX or AFX-S for patients with stage III and stage IV head and neck cancer,
there was a significant survival benefit with altered fractionated radiation therapy and a 3.4% absolute
benefit at 5 years (HR, 0.92; 95% CI, 0.860.97; P = .003). Altered fractionation improves locoregional
control, and the benefit is higher in younger patients. HFX demonstrated a greater survival benefit (8% at
5 years) than AFX-S (2% with AFX-S without total dose-reduction and 1.7% with total dose-reduction at 5
years, P = .02).[20][Level of evidence: 1iiA]
Tiga lengan eksperimental itu harus dibandingkan dengan SFX. Hanya lengan HFX
menunjukkan kontrol locoregional superior dan kelangsungan hidup pada 5 tahun
dibandingkan dengan lengan SFX (hazard ratio [HR], 0,79; 95% confidence interval
[CI], 0,62-1,00; P = 0,05). AFX-C dikaitkan dengan peningkatan toksisitas terlambat
dibandingkan dengan SFX [14-19] [Tingkat bukti: 1iiA].
Dalam meta-analisis dari 15 percobaan acak dengan total 6515 pasien dan median
tindak lanjut dari 6 tahun yang melibatkan penilaian HFX atau AFX-S untuk pasien
dengan stadium III dan kepala stadium IV dan kanker leher, ada yang signifikan
manfaat kelangsungan hidup dengan terapi radiasi difraksinasi diubah dan manfaat
mutlak 3,4% pada 5 tahun (HR, 0,92; 95% CI, 0,86-0,97; P = 0,003). Diubah
fraksinasi meningkatkan kontrol locoregional, dan manfaat lebih tinggi pada pasien
yang lebih muda. HFX menunjukkan manfaat kelangsungan hidup yang lebih besar
(8% pada 5 tahun) dari AFX-S (2% dengan AFX-S tanpa dosis total pengurangan dan
1,7% dengan total dosis-reduksi pada 5 tahun, P = 0,02). [20] [Tingkat bukti: 1iiA]
Celah suara
Standard pilihan pengobatan:
1. Kemoterapi diberikan sekaligus dengan terapi radiasi dapat dipertimbangkan
untuk pasien yang akan membutuhkan jumlah laryngectomy untuk pengendalian
penyakit, termasuk orang-orang dengan penyakit T4a nonbulky. [1]
2. Induksi kemoterapi diikuti dengan kemoterapi bersamaan dan radiasi.
Laryngectomy dicadangkan untuk pasien dengan kurang dari respon 50% terhadap
kemoterapi atau yang memiliki penyakit persisten berikut radiasi. [1-6]
3. terapi radiasi definitif saja pada pasien yang tidak kandidat untuk kemoterapi
bersamaan dan operasi (Total laryngectomy) untuk penyelamatan kegagalan
radiasi. [7]
4. Untuk pasien dengan penyakit T4 besar, jumlah laryngectomy dengan terapi
radiasi pasca operasi (PORT) dengan atau tanpa kemoterapi bersamaan
berdasarkan faktor risiko untuk penyakit patologis volume yang T4 besar. [8]
Subglottis
Standard treatment options:
1. Laryngectomy plus total thyroidectomy and bilateral tracheoesophageal node
dissection usually followed by postoperative radiation therapy.[10]
2. Treatment by radiation therapy alone is indicated for patients who are not
candidates for surgery.
Subglottis
Standard pilihan pengobatan:
1. Laryngectomy ditambah tiroidektomi total dan bilateral trakeo diseksi biasanya
diikuti dengan terapi radiasi pasca operasi. [10]
2. Pengobatan dengan terapi radiasi saja diindikasikan untuk pasien yang tidak
kandidat untuk operasi.
b
Metastases at level VII are considered regional lymph node metastases.
M0 No distant metastasis.
M1 Distant metastasis.
a
Reprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.:
AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.
Stage T N M
0 Tis N0 M0
I T1 N0 M0
II T2 N0 M0
III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
IVB T4b Any N M0
Any T N3 M0
IVC Any T Any N M1
a
Reprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.:
AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.