Recurrent Head & Neck Cancer and Nasopharyngeal cancer

- Rec Nasopharynx with ONLY local recurrence need treatment with Surgery/ RT

- High precision RT do have benefit in terms of toxicity

- Small Vol disease, Persistent local disease, treated with high dose (>50Gy), rT1-2

disease have better prognosis

- Prognostication is possible for recurrent disease treated with RT

- In favorable group, SBRT in recurrent localized nasopharynx provide relative long

term LC & survival

Carcinoma nasopharynx

• Localized NPX is treated with CT-RT: 66Gy/30# to primary & involved nodes and 54-60Gy/30# to uninvolved nodes

• Response assessment if done before 5 wks, <50% will be residual on biopsy• Majority (>70%) responds at 10-12 wks

• PET scan & endoscopy/ biopsy at 10-12 wks done for response assessment

Still- • 7-20% of NPX pt will have residual disease after CT-RT at 10-12 wks• Another group: local recurrence after CT-RT

• Pts with persistent disease at 12 wks had significantly lower LC rate (40 %), regional & distant metastasis-free rate (47 %), OS (54 %).

• They need additional treatment

Yu KH, et al. Head Neck. 2005;27(5):397–405.

Recurrent/ persistent Ca nasopharynxTwo distinct group

At 10-12 wks response assessment

Recurrent disease after CT-RT

Persistent only at Nasopharynx

Persistent NPX & LN

Recurrence only at Nasopharynx

RecurrenceNPX & LN Distant mets

Local Rx

Surgery- NasopharengectomyRT- IMRT OR SBRT/ fSRSPDTChemotherapy

Chemotherapy

Long term Follow up of Ca Nasopharynx (n=610)

Failure= 192/610 (31%)Local Failure ONLY= 52%Distance metastasis=27%

Death= 156/610Cause of death:Local Relapse only= 44%Distance mets= 28%

Local control after relapse improves survival

Sun JA et al, Asian Pacific J 2007

Management of ONLY local recurrence

- Surgery

- Nasopharengectomy- Re-RT:

- IMRT

- SBRT

- Intracavitary Brachytherapy

- Gold seed implant- Photodynamic therapy- Systemic therapy

No randomized study between diff techniquesNeed to depend only on prospective single centre reports

Surgery for Rec Nasopharynx

- ONLY few prospective reports - Skull base/ bone erosion & carotid artery erosion not considered for surgery- 5-Yr OS: 40-60%- 20% palatal fistula

Riaz N et al Radiat Oncol 2014

Concordance index= 0.68.

Normogram for prognostication of LRC after RT

Rec / residual Nasopharynx: 2-Yr LRC ≅70%

Liu et al. Radiation Oncology 2013

SBRT: persistent Nasopharyngeal Ca

N=35 ptsLocally recurrent NPC treated using FSRT with CKGTV= 2.6-64.0 ml (median, 7.9 ml)RT doses=24 to 45 Gy (median, 33 Gy) in 3 or 5#

At 5-Yr FU:- OS= 60%- LFFS= 79%- DPFS=74%- CR after CK=23 pt- Severe late toxicity (Grade 4 or 5)=5 pt

Only T stage at recurrence was an independent prognostic factor for OS

Yao Y et al, Radiat Oncol 2009

Rec Ca Naso: Ph II study with CK

N=136 NPC pts Residual lesions after RT (median, 70.0 Gy). Median time to FSRT =24.5 daysTumor vol =13.4 cm3FSRT dose =8.0-32.0Gy (median, 19.5 Gy)

Results:•5-Yr LFFS=92.5%•5-Yr FFDM=77%•5-Yr OS=76.2%•5-Yr DFS=73.6%•Late toxicity= 19 pt.

T stage at diagnosis & age: significant prognostic factor for OS & DFS

SBRT: Residual Nasopharyngeal Ca (n=136)

Liu et al. Radiation Oncology 2013

Riaz N et al Radiat Oncol 2014

July 1996 -April 2011, n=257 Median prior RT dose= 65 Gy Median time between RT = 32.4 months.Salvage surg= 157 (44%) & Conc RT= 172 (67%)Median re-RT dose = 59.4 Gy; IMRT=201 (78%) Median FU= 32.6 mo2-Yr LRC= 47% & OS= 43%,

Independent prognostic factor:1.Recurrent stage (P = 0.005)2.Non-oral cavity subsite (P < 0.001)3.Absent organ dysfunction (P < 0.001) 4.Salvage surgery (P < 0.001)5.Dose >50 Gy (P = 0.006)

Re-RT in Rec Nasopharynx (n=257)

Best group for Re-RT: Non oral cavity site small vol disease treated with salvage surgery & treated with Re-RT dose >50Gy

Scoring depends upon:1.Stage2.Volume3.Time to rec4.Persistent/ Rec

GroupsPoor: Score >0.5Intermediate: <0.5

Prognostication of Rec Naso ca treated with SBRT

Scoring done for Rec Ca Nasopharynx

Chua DT et al, BMC Cancer 2009

Prognostic scoring of Rec Naso ca treated with SBRT

Survival probability after SBRT depends upon prognostic group

Chua DT et al, BMC Cancer 2009

Outcome depends upon:1.Stage at Rec2.Residual Volume

Radiotherapy Techniques: Pros & Cons

Higher dose/Fr - Higher BED - Greater toxicity probability

High precision RT: - Better target coverage - Less spillage - Less dose to OARs

Impact of PTV margin on OAR dosage

Asselen B et al, Radiother Oncol 2002

•Oropharyngeal tumours accrued.

•Margin of 0, 3, 6, 9 cm given to CTV.

•IMRT planned with different PTV margin.

•NTCP for xerostomia applied.

•Reducing PTV margin from 6 to 3 mm reduces

NTCP for xerostomia by 20%.

Reducing PTV margin reduces NTCP

SBRT Conf RT P-value

n 24 27

Method CK Conf RT

Dose 30Gy/5#/1wk 56Gy/28#/5wk

2-Yr LC 82% 80% P=0.6

2-Yr Dis specific Sur

64% 47% P=0.4

Late Toxicity (Gr-3)

21% 48% P=0.04

Serious late Toxicity

12.5% 14.8% P=0.8

Ozygit G et al, IJROBP 2010

Retrospective analysis: Survival function similar between SBRT & CRT SBRT is safer in terms of toxicity

Retrospective analysisRecurrent Nasopharynx (n=51)Median FU: 2 yrs

Comparison of CRT Vs SBRT

IMSRT have better OAR sparing and HI parameter

Factors influencing outcome with SBRT

- Dose

- Volume

- T Stage at recurrence

- Time gap between recurrence

- Persistent vs recurrent disease

Re-RT in H&N Cancer: LC & Dose effect: Pittspurg Exp

Rwigema et al. Am J Clic Oncol 2011

Up to 50Gy/5# is feasible with SBRTHigher dose is associated with better LC & 2&3-Yr Survival

Re-RT in H&N Cancer: LC & Volume effect: Pittsburg Exp

Rwigema et al. Am J Clic Oncol 2011

Lower vol persistent/ recurrent disease responds better with SBRT

Median follow-up was 20.3 months.

Gr-1 Gr-2 P-value

Disease Persistent recurrent

n 34 56

Method CK Non-co Arc

Dose 18Gy/3# 48Gy/6#

CR 66% 63%

3-Yr LFFS 89% 75%% P=0.037

3-Yr Dis specific Sur

80% 46% P=0.04

3-Yr PFS 72% 43% P=0.048

Toxicity Gr3 8% 25% P=0.05

Yu S et al. IJROBP 2007

Rec Naso Ca: Persistent Vs Recurrent (n=90)

Persistent Nasopharyngeal Ca responds better with SBRT

Yu S et al. IJROBP 2007

Rec Naso Ca: Vol effect (n=90)

Low Vol Nasopharyngeal Ca responds better with SBRT

Failure pattern after SBRT in Rec Naso Ca (n=90)

Wang et al. Head & Neck Oncology 2012

Rec Volume contouring with PET scan (n=45)

With PET scan contouring: 5 mm margin covers the Recurrent Vol

Wang K et al. Radiat Oncol 2013

Wang et al. Head & Neck Oncology 2012

Failure after SBRT: Patterns

Re-RT with SBRT: Toxicities

- Brain necrosis: temporal lobe

-Cranial Nr palsy

-Severe haemorrhage

-Bone & skin necrosis

-Carotid blow out syndrome

Incidence: 5-8%

N= 484 re-irradiation sessions 2000-2010 with CKIncidence= 32 (8.4%) Median survival time =0.1 mo & 1-Ys OS= 37.5%

Factors:1.Elder age2.Skin invasion3.Necrosis/infection

Carotid blowout syndrome

Re-RT in tumor is located adjacent carotid artery need attention

Yamazaki H et al Radiat Oncol 2013

Group=1: •Daily SBRT•N=43•CBS= 7•Median OS= 11 mo

Prevention of Carotid blowout syndrome (Re-RT=75)

Reduce CBS:•Alternate day SBRT•Carotid contact <180deg•Max Carotid dose <34Gy•Skin intact•No infection•Low Vol rec disease

Group=2•Alternate day SBRT•N=32•CBS= 4•Median OS= 23 mo

Yazici et al. Radiation Oncology 2013

Dosimetric studyNode negative H& N cancer (Ca Tonsil) (T3 N0M0)

IMRT: 46 Gy/23#PTV: Primary+ Level I-IV bilateral LN

IMRT boost: 24 Gy/6#PTV: Primary

HDR brachy: 24 Gy/6#PTV: Primary

CK boost: 24 Gy/6#PTV: Primary

Comparison between boost plans:1)Target Coverage2)OAR dose (spinal cord & parotid dose)

(n=11)

- No difference in maximum spinal cord dose and mean

parotid doses between HDR & CK boost plans

- In IMRT plan, higher ipsi-lateral parotid dose

Comparison of three plans (Dose: 24 Gy/6#)

IMRT boost HDR boost CK boost

Spinal cord Dmax (Gy) 7.4 1.2 1.5

Ipsi-lateral parotid Mean dose (Gy)

8.3 3.1 2.1

Conta-lateral parotid Mean dose (Gy)

3.7 1.4 1.7

(n=11)Dutta et al; CK Society meeting San Francisco 2010

Infra-temporal fossa recurrence Infra-temporal fossa recurrence

60 yr old from Kolkata

K/C/O Ca R buccal mucosa Treated with surgery, adj RT

Post RT 1 year recurrence in R ITF region

RE-RT with CyberKnife: 30 Gy/5#/1 wk

Post RT 6 month FU: Controlled disease

Excellent radiological & clinical response

Infra-temporal fossa recurrence (36 mo FU) Infra-temporal fossa recurrence (36 mo FU)

Take home message- Rec Nasopharynx with ONLY local recurrence need treatment with Surgery/ RT

- High precision RT do have benefit in terms of toxicity

- Small Vol disease, Persistent local disease, treated with high dose (>50Gy), rT1-2

disease have better prognosis

- Prognostication is possible for recurrent disease treated with RT

- In favorable group, SBRT in recurrent localized nasopharynx provide relative long

term LC & survival

- However, distant metastasis may offset the impact of local treatment

- Need prospective randomized studies to ascertain role of different modalities

Thank youduttadeb07@gmail.com