Nasopharynx Cancer. 1 Feb Presenters: Dr Raghav Murali-Ganesh (Radiation Oncology Registrar) Dr Peter Luk (Pathology Registrar)

Transcription

1 Nasopharynx Cancer 1 Feb 2016 Presenters: Dr Raghav Murali-Ganesh (Radiation Oncology Registrar) Dr Peter Luk (Pathology Registrar) Expert Panels Prof Mo Mo Tin Prof Michael Boyer Dr Raewyn Campbell Prof Ruta Gupta Chair Person Dr Hubert Low

2 Case, Mr. DC 75M from Hong Kong Presented with Left sided hearing loss, mild epistaxis and neck mass Previously well o/e Nasoendocopy Mass in lateral NP wall incl Foss of Rosenmuller, Torus and Eustachian tube orifice Does not cross midline or extend to oropharynx Left level 2b mass, mobile, contralateral neck clear

3 75M from HK Decreased hearing Epistaxis Neck lump Previously well

4

5

6

7

8

9

10

11 Case, Mr. DC Biopsy Non Keratinsing Nasopharyngeal carcinoma Undifferentiated type

12 Epidemiology West: per 100,000 Endemic areas China: Inuit: SE Asia: 8-12

13 Aetiology Epstein-Barr Virus Diet and environmental Nitrosamines from salt-cured food Salted fish Preserved/fermented food Chinese medicinal herbs Harissa Smoking

14 Neck mass Nasal obstruction Otitis media Lymph nodes 41% Present at diagnosis 75-90% Bilateral 50% Hearing loss/otalgia 27% Nasal bleeding/obstruction 21% Cranial nerve signs 8% Trismus 5%

15 Nodal disease Nodal disease is common and relates to type Nodal Mets at presentation 90% subclinical node +ve 70% clinically node +ve 50% bilateral node +ve By type Keratinising: 73% node +ve Non Keratinising (Endemic Chinese/Asian) : 92%

16 Diagnosis Diagnosis and Staging Hx + Examination Nasoendoscopy CT MRI EUA and Biopsy PET (10% distant metastases at diagnosis) Other Bloods Serum EBV DNA titre OPG

17 FNA

18 FNA

19 FNA

20 Biopsy

21 Biopsy

22 Biopsy

23 Biopsy

24 Pathology WHO I WHO II WHO III Other rarer histologies: Adenocarcinoma Plasmacytoma Melanoma Sarcomas

25 Keratinising SCC (20%) Squamous differentiation Keratin whorls, intercellular bridges Desmoplastic stroma

26 Non-keratinising, differentiated (30-40%) Interconnecting cords and trabeculae Pavement stone Well-defined cell borders EBV associated

27 Non-keratinising, undifferentiated (40-50%) Syncitial large cells Lymphocytic infiltrate (lymphoepithelioma) EBV associated

28

29 T3 N1 Stage III M0

30 T3 N1

31 Treatment Options Radiation +/- Chemotherapy Concurrent CXT (+/- Adjuvant chemotherapy) (+/- Induction chemotherapy)

32 Radiation Alone

33 MDACC series N= T-stage Histology N-stage Sanguineti et al, IJROBP, 1997

34 Concurrent CRT

35 INT 0099/RTOG N=193 Stage III/IV RT alone CRT + Adjuvant Chemo RT 70 Gy/35 Concurrent Cisplatin 100 mg/m2 weeks 1, 3, 5 Adjuvant 3 cycles Cisplatin 80 mg/m2 day 1 5-FU 1000 mg/m2 day 1-4 Al-Saraff et al, JCO, 1998

36 INT 0099/RTOG N=193 Stage III/IV RT alone CRT 78% 47% Stopped early due to significant benefit OS 69% 24% PFS Al-Saraff et al, JCO, 1998

37 INT 0099/RTOG N=193 Stage III/IV RT alone CRT Western population RT % CRT % Poor compliance with chemotherapy Poor outcomes with RT alone (OS 24%) - Compared with series evidence 40-50% Al-Saraff et al, JCO, 1998

38 Cochrane MA Baujat et al, Cochrane update Blanchard et al, Lancet Oncology 2015

39 Cochrane meta-analysis 19 RCTs 6.3% absolute survival benefit overall at 5 years Induction +/- Adjuvant Concurrent +/- Adjuvant 56% to 62% Adjuvant Blanchard et al, Lancet Oncology, 2015

40 Adjuvant 3 x RCTs of CRT vs RT alone: survival benefit 4 x RCTs of CRT + Adjuvant vs RT alone: survival benefit 3 x RCTs of RT + Adjuvant vs RT alone: no benefit

41 Adjuvant Chemotherapy For Adjuvant CXT Al Sarraf et al Trial, JCO 2008 Not for Adjuvant CXT Sun Yat Sen Univ trial, Lancet 2012

42 NCCN Response

43 Induction Chemotherapy Benefit maybe as much as adjuvant therapy however, not shown benefit over CRT alone (I.e Induction + RT alone) Induction + CRT is probably = CRT + Adjuvant Induction CXT is better tolerated than adjuvant CXT and potentially lowers distant failures hence this question exists Induction CXT is considered a potential option in NCCN guidelines

44 IMRT Benefits of IMRT Curving dose around optic structures Improved dose reduction to temporal lobe Salivary gland sparing for improved QOL

45 High Risk = 70 Gy/33 Intermediate Risk = 59.4 Gy/33 RTOG 0225, JCO, 2009

46 Late Toxicities Grade 3 = 20.3% Mostly: 24% 38% 22% 42% 20% 15% 4% 3% 1% 15% 21% 4% 19% 4% 28% 13% 3% 1% 1% 6% 3% 1% 3% 4% 7% Hearing impairment Dysphagia PEG-dependent = 4.2% RTOG 0225, JCO, 2009

47 Mr DC

48

49 Re-Irradiation Risk of late toxicities: Trismus Stricture Dysphagia requring gastrostomy Hearing loss Unilateral blindness Cranial neuropathy Temporal lobe necrosis Endocrinopathies Higher doses (>60Gy) are more effective than lower doses Other options include BCT and/or SRS or fsrt

50 Post treatment EBV levels predict outcome 1 week post radiotherapy, titres of EBV predict outcome of therapy If titres still detectable, poor prognostic marker

51 NRG HN 001 (HK and US centres)

52 Case Mr DC Underwent adjuvant CXT 5FU + Cis, 3 cycles Post treatment PET May 2013 Nil residual disease at primary Very low activity in left Level II LN Repeat PET Oct 2013 Nil disease at primary Left level II LN, more metabolically active

53 Case Biopsy of Post Nasal Space 19/11/13 Consistent with residual NPC Proceeded to undergo Salvage surgery, nasopharyngectomy + L neck dissection Jan mm poorly differentiated NPC Margin assessment difficult owing to artefact 1/13 left LN +ve, level IIb, 16mm node with 8mm ECE

54 Nasopharyngectomy

55 Nasopharyngectomy

56 Nasopharyngectomy

57 Nasopharyngectomy