Nasopharyngeal carcinoma (NPC)

Catholic University of Louvain, St - Luc University HospitalHead and Neck Oncology Programme

NPC 1Mar. 2006

Nasopharyngeal carcinoma (NPC)


NPC 2Mar. 2006

• Work-up procedure

• TNM staging

• Primary treatment

• Follow-up

• Treatment of recurrent and/orand/or metastatic metastatic disease

• References



NPC 3Mar. 2006

Standard clinical evaluation Evidence Option

l complete history of the diseasel weight and weight lossl fiberoptic examination of H&N mucosal neck examinationl evaluation of cranial nerves (I, II, III, IV, V, VI,

VIII, IX, XII)including audiometryl drawing of any lesionsl biopsy under local anesthesial endoscopy under general anesthesia with biopsies

if risk factors (tobacco and/or alcohol) and/or novisualization of primary tumor

l FNA of neck lymphnodes if primary not accessible for biopsy

Type CType CType CType CType C

Type CType CType C

Type C

Std.Std.Std.Std.Std.

Std.Std.Std.

Std.


NPC 4Mar. 2006

Advanced clinical evaluation Evidence Option

l ophtalmologic examinationl dental examination by oral surgeonl nutritional assessmentl others (if required)

Type CType CType CType C

Std.Std.Std.

Indiv.


NPC 5Mar. 2006

Laboratory tests Evidence Option

l hemogram, coagulation tests, liver enzymes, kidney function (including a creatinine clearance)

l serology: anti-VCA IgAl pituitary function: cortisol, TSH, free T4, LH,

FSH, GH, free testosterone and testosterone (male only), progesterone and oestradiol (femaleonly), prolactine, IGF-1

Type C

Type CType C

Std.

Std.Std.


NPC 6Mar. 2006

Imaging Evidence Option

l local: MRI ± CT scan1

l metastatic work-up: chest X-ray, thoracic andabdominal CT scan, bone scintigraphy

l additional examination depending on previousfindings

l PET scan

Type CType C

Type C

-

Std.Std.

Std.

Invest.1See guidelines for loco-regional imaging


NPC 7Mar. 2006

Pathology Evidence Option

l WHO classification1

l Immunohistochemistry for EBV (LMP1)Type CType C

Std.Std.

1See pathology guidelines


NPC 8Mar. 2006

• Work-up procedure• TNM staging• Primary treatment• Follow-up• Treatment of recurrent and/orand/or metastaticmetastatic disease• References



NPC 9Mar. 2006

Staging Evidence Option

l TNM classification (5th ed., 1997) Type C Std.l Who International Classification of Diseases for

Oncology (ICD-O 9 or ICD-O 10)Type C Std.


NPC 10Mar. 2006

•• TisTis: Carcinoma in situ: Carcinoma in situ•• T1: Tumor confined to the T1: Tumor confined to the nasopharynxnasopharynx•• T2: Tumor extends to soft tissues of T2: Tumor extends to soft tissues of oropharynx oropharynx and/or nasal and/or nasal fossafossa

T2a: without T2a: without parapharyngeal parapharyngeal extensionextensionT2b: with T2b: with parapharyngeal parapharyngeal extensionextension

•• T3: Tumor invades bony structures and/or T3: Tumor invades bony structures and/or paranasal paranasal sinusessinuses•• T4: Tumor with T4: Tumor with intracranial intracranial extension and/or involvement extension and/or involvement

of cranial nerves, of cranial nerves, infratemporal fossainfratemporal fossa, hypopharynx or orbit , hypopharynx or orbit

TNM/AJCC 1997 StagingTNM/AJCC 1997 Staging


NPC 11Mar. 2006


• N0: no regional node metastasis• Nx: regional nodes cannot be assessed• N1: unilateral metastasis in node(s), ≤ 6 cm, above the

supraclavicular fossa • N2: bilateral metastasis in node(s), ≤ 6 cm, above the

supraclavicular fossa• N3: metastasis in node(s)

N3a: > 6 cmN3b: extension to the supraclavicular fossa


NPC 12Mar. 2006


•• MX: Distant MX: Distant metastasis cannot bemetastasis cannot be assessedassessed•• M0: No distant M0: No distant metastasismetastasis•• M1: Distant M1: Distant metastasismetastasis


NPC 13Mar. 2006

• Work-up procedure• TNM staging• Primary treatment• Follow-up• Treatment of recurrent and/orand/or metastatic metastatic disease• References



NPC 14Mar. 2006

Primary treatment Evidence Option

l T1-N0-M0 / T2-N0-M0Ext. RxThBrachytherapy boost

l T1-T2, ≥ N1, M0 / T3-T4, any N, M0Ext RxTh+concomitant CH+adjuvant CHSurgery (RMND, RND or ERND unilateral or bilateral) for persitent N disease at 3 months

Type CType C

Type 2Type R

Std.Indiv.

StdStd.


NPC 15Mar. 2006

Primary treatment: RxTh regimen Evidence Option

l Target volumesBilateral levels II-V + RP nodes: prophylactic doseinvolved node(s) + NPharynx: curative dose

l Technique-conformal-IMRT radiotherapy

l Doseprophylactic dose: 50 Gycurative dose: T1, N1: 66 Gy

≥T2, ≥N2: 70 Gy5% dose reduction for UCNT(WHO 2-3)

l Fractionationdaily 2Gy/fraction

Type C

Type C

Type 3Type 3

Type CType CType CType R

Type C

Std.

Std.

Std.Invest.

Std.Std.Std.Std.

Std.


NPC 16Mar. 2006

Target Volumes: Target Volumes: nasopharynxnasopharynxLevel of evidence : type 3 / option : standardLevel of evidence : type 3 / option : standard

Stage Ipsilateral neck Controlateral neck

N0-N2 II-III-IV-V + RP ± sus. clav.1 II-III-IV-V + RP ± sus. clav.1

N3 II-III-IV-V +RP ± adjacent II-III-IV-V +RP ± sus. clav.1structures according to clinical

and radiological data1

1Supra-clavicular nodes when involvement of level IV and/or Vb


NPC 17Mar. 2006

Primary treatment: CH regimen Evidence Option

Intergroup study regimenl Concomitant: cddp 100 mg/m2 J1, J22, J43l Adjuvant: cddp 80 mg/m2 J71, J99, J127

5Fu 1 g/m2 J71-74, J99-102, J127-130

Type 2 Std.


NPC 18Mar. 2006




NPC 19Mar. 2006

Follow-up Evidence Option

l Clinical examination-fiberoptic and neck palpation every 3 months (first 2 years), every 6 months (years 3-5), then every year (> 5 years)-dental examination every 6 months

l Imaging-all T: MRI ± CT 2-3 months after end of RxTh-≥ T2: MRI ± CT every 6 months for 2 years

l Laboratory tests-serology: anti-VCA IgA at each clinical examination (if elevated before treatment)-thyroid and pituitary function: according to clinical findings

l Evolution of late toxicity (EORTC/RTOG) scale

Type C

Type C

Type C

Type C

Type C

Type C

Type C

Std.

Std.

Std.

Std.

Std.

Std.

Std.


NPC 20Mar. 2006

• Work-up procedure• TNM staging• Primary treatment• Follow-up• Treatment of recurrent and/orand/or metastaticmetastatic disease• References



NPC 21Mar. 2006

Salvage treatment for recurrent disease Evidence Option

l rT1-N0 / rT2-N0RxThSalvage surgeryChemotherapy

l T0-≥ rN1, M0Neck dissection

l rT3 / rT4, any rNChemotherapy

l MetastasisChemotherapy + RxThBest supportive care

Type 3Type 3Type 3

Type 3

Type 3

Type 3Type 3

Indiv.Indiv.Std.

Indiv.

Std.

Std.Indiv.


NPC 22Mar. 2006




NPC 23Mar. 2006

ReferencesReferences• Ahmad A, Stefani S. Distant metastases of nasopharyngeal carcinoma: a study of 256 male patients.

J Surg Oncol. 1986; 33: 194-197.• Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA,

Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 16(4):1310-7.

• AJCC Cancer StagingManual fifth edition. Lippincott Williams & Wilkins, Philadelphia, 1997• Ang KK, Peters LJ, Weber RS. Concomitant boost radiotherapy schedules in the treatment of

oropharynx and nasopharynx. Int J Radiat Oncol Biol Phys 1990; 19: 1339- 1345. • Chan AT, Teo PM, Leung TW, Leung SF, Lee WY, Yeo W, Choi PH, Johnson PJ. A prospective

randomized study of chemotherapy adjunctive to definitive radiotherapy in advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1995, 5;33(3):569-77.

• Chua DT, Sham JS, Choy D, Lorvidhaya V, Sumitsawan Y, Thongprasert S, Vootiprux V, Cheirsilpa A, Azhar T, Reksodiputro AH. Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group. Cancer. 1998 Dec 1;83(11):2270-83.


NPC 24Mar. 2006

ReferencesReferences• Cvitkovic E, Bachouchi M, Boussen H, Busson P, Rousselet G, Mahjoubi R, Flores P, Tursz T,

Armand JP, Azli N. Leukemoid reaction, bone marrow invasion, fever of unknown origin, andmetastatic pattern in the natural history of advanced undifferentiated carcinoma of nasopharyngealtype: a review of 255 consecutive cases. J Clin Oncol. 1993 Dec;11(12):2434-42.

• de-Vathaire F, Sancho-Garnier H, de-The H, Pieddeloup C, Schwaab G, Ho JH, Ellouz R, MicheauC, Cammoun M, Cachin Y, et al. Prognostic value of EBV markers in the clinical management ofnasopharyngeal carcinoma (NPC): a multicenter follow-up study. Int J Cancer 1988;42:176-81

• Fandi A et al. Nasopharyngeal Cancer: Epidemiology, Staging, and Treatment. Seminars in Oncology 1994, 21: 382-397.

• Geara FB, Sanguineti G, Tucker SL, et al.: Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of distant metastasis and survival. Radiother.Oncol. 43(1): 53-61, 1997.

• Kwong D, Sham J, Choy D. The effect of loco-regional control on distant metastatic dissemination in carcinoma of the nasopharynx: an analysis of 1301 patients. Int J Radiat Oncol Biol Phys 1994; 30: 1029-1036.

• Lee AW, Poon YF, Foo W, Law SC, Cheung FK, Chan DK, Tung SY, Thaw M, Ho JH. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure. Int J Radiat Oncol Biol Phys. 1992;23(2):261-70.

• Lee AW, Foo W, Law SC, Poon YF, Sze WM, O SK, Tung SY, Chappell R, Lau WH, Ho JH. Recurrent nasopharyngeal carcinoma: the puzzles of long latency. Int J Radiat Oncol Biol Phys. 1999 Apr 1;44(1):149-56.


NPC 25Mar. 2006

ReferencesReferences

• Lee AWM, Foo W, Law SC, Poon YF, Sze WM, O SK et al. Reirradiation for recurrentnasopharyngeal carcinoma: factors affecting the therapeutic ratio and ways for improvement. Int JRadiat Oncol Biol Phys 1997; 38: 43-52.

• Lee AW, Law SC, Hg SH et al. Retrospective analysis of nasopharyngeal carcinoma treated during 1976-1985: late complications following megavoltage irradiation. Br. J. Radiol. 66: 528-536, 1993.

• Liebowitz D. Nasopharyngeal Carcinoma: The Epstein-Barr Virus association. Seminars in Oncology 1994, 21: 376-381.

• Neel HB 3d, Taylor WF. New staging system for nasopharyngeal carcinoma. Long-term outcome. Arch Otolaryngol Head Neck Surg. 1989 Nov;115(11):1293-303.

• Qin DX, Hu YH, Yan JH, Xu GZ, Cai WM, Wu XL, Cao DX, Gu XZ. Analysis of 1379 patients with nasopharyngeal carcinoma treated by radiation. Cancer. 1988;61(6):1117-24.

• .Perez CA, Devineni VR, Marcial-Vega V, et al.: Carcinoma of the nasopharynx: factors affecting prognosis. Int J Rad Onc Biol Phys 23(2): 271-280, 1992.

• Sanguineti G, Geara FB, Garden AS, Tucker SL, Ang KK, Morrison WH. Carcinoma of thenasopharynx treated by radiotherapy alone: determinants of local and regional control. Int J Rad Onc Biol Phys 1997; 37: 985-996.


NPC 26Mar. 2006

ReferencesReferences

• Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin,epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. International Nasopharynx Cancer Study Group. VUMCA I trial. Int J Radiat Oncol Biol Phys. 1996 Jun 1;35(3):463-9.

• Tang SGJ, Lin FJ, Chen MS, Liaw CC, Leung WM, Hong JH. Prognostic factors of nasopharyngealcarcinoma: a multivariate analysis. Int J Biol Oncol Phys 1990; 19: 1143-1149.

• Teo PM, Leung SF, Lee WY, et al.: Intracavitary brachytherapy significantly enhances local control of early T-stage nasopharyngeal carcinoma: the existence of a dose-tumor-control relationship above conventional tumoricidal dose. Int. J. of Radiat. Oncol.Biol. Physics 46: 445,458, 2000.

• Wang CC. Accelerated hyperfractionation radiotherapy for cancer of the nasopharynx. Techniques and results. Cancer 1989; 63: 2461-67.

• World Health Organization. International Histological Classification of Tumours. Histologicaltyping of tumours of the upper respiratory tract and ear. Second Edition. Springer Verlag, 1991

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Nasopharyngeal carcinoma (NPC)