Evidence Based Management GingivoBuccal Cancer

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Evidence Based Management Gingivo-Buccal Cancer

• Dr. A D Cruz
• Tata Memorial Hospital

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Oral Cancer Global Incidence

• 10th most common cancer
• 389,000 new cases annually (2000)
• 2/3rd in developing countries
• 200,000 deaths annually

• Stable or increased in last four
• decades
• Sharp increase in incidence in
• Germany, Denmark, Scotland,
• Central Eastern Europe
• Same increase in Japan, Australia,
• New Zealand USA ( non-whites)

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Oral Cancers
Oral cancer common cancer in India
Observations reported since late 19th century
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Cancer of the oral cavitySite Distribution
TONGUE FOM
GINGIVOBUCCAL COMPLEX BUCCAL MUCOSA RMT
LOWER GUM
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Biological Distinctions in Oral Cancer
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GINGIVOBUCCAL CANCER THE INDIAN ORAL CANCER
2275 PTS. (1997-99)
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Gingivo-Buccal Cancers
Areca nut is the fourth most common psychoactive
substance in the world (after caffeine, alcohol
and nicotine), the use extending to several
hundred million people.

Tobacco chewers (with cancer) 105 AGE AND
SEX MATCHED Tobacco chewers (no cancer )
71 RELATIVE RISK 12.5

GHOSH S. Eur J Surg Oncol, 1996
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Pre-malignant conditions n 2275 (97-99)
LEUKOPLAKIA - 8.5 (194)

• SMF -10.8(245)

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Oral Cancers Submucous fibrosis
Prevalence of tobacco use among oral submucous
fibrosis (OSF) cases
 Gupta PC et al. National Medical Journal of
India 11(3) 113-116, 1998.
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Oral Cancers Submucous fibrosis
Relative risk of oral submucous fibrosis by the
daily frequency of areca nut use - a case
control study from Government Dental College,
Nagpur
Hazare VK et al. National Medical Journal of
India. 11(6) 299, 1998.
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Chemoprevention
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Chemoprevention- Limitations

• Costly
• Side effects
• Long duration
• Lesion return on stoppage
• Exact agents not known (curcumin)

Encourage patient to stop habits Oral / Dental
Hygiene Good Diet
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Gingivo - buccal cancer
TREATMENT
Early Stage I II
Late Stage III IV
Operable III IVa
In Operable
Single modality treatment
IV c
IV b
Combined modality treatment
Low GC / Symptomatic Rx

• SX
• RT

Sx PORT / CT RT Radical RT
CT RT
Pall CT
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Gingivo buccal cancersGoals of treatment

• MAXIMIZING CURE RATES
• PRESERVING FUNCTION
• COSMESIS
• COST EFFECTIVE
• EXPEDITING CARE

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Gingivobuccal Cancers Factors Affecting Treatment

• TUMOR FACTORS
• T size, Location to bone, Type of lesion, Nodal
  disease
• PATIENT FACTORS
• Performance status, Persistence of habits,
  Preference
• PHYSICIAN FACTORS
• Availability of MULTIDISCIPLINARY TEAM EXPERTISE

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GINGIVO BUCCAL CANCERSEARLY T1/T2 CANCERS
SX RT
Cancer of the Oral Cavity Jatin P. Shah M J
Zelefsky
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Radiotherapy Carcinoma Buccal Mucosa
185 cases
2 years DFS - 48 RT 46 SX
Early Stage
Chaudhary, Seminars in Surgical Oncology 1989
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GINGIVO BUCCAL CANCERSEARLY T1/T2 CANCERS - RT

• BOTH EXTERNAL INTERSTITIAL NEEDED
• PROLONGED TREATMENT
• SIDE EFFECTS
• Xerostomia, Dental caries, ORN.
• CAN BE ONLY GIVEN ONCE
• Not suited for alveolar lesions
• Radiotherapy is chosen when surgery not possible
  / functional or cosmetic problems are
  anticipated

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GINGIVO BUCCAL CANCERSEARLY T1/T2 CANCERS -
Surgery

• SIMPLE
• EXPEDIOUS
• NO SIGNIFICANT FUNCTIONAL COSMETIC DEFECTS
• REPEATED PROCEDURE POSSIBLE
• COST EFFECTIVE
• CHOICE OF TREATMENT

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GB Cancers T1/T2 cancersSurgery ( margins)

• WIDE ADEQUATE MARGINS gt 5mm
• DEPTH BUCCINATOR MUSCLE
• Sieczka et al ( Roswell Park, Am J Otolaryngol
  2001)
• - 40 local failure T1 T2
• Post-op ADJUVANT NECESSARY

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Gingivo Buccal Cancers (T1 / T2)
M D Anderson Experience Jan 1974 Dec1998

• Worse than other head neck cancers stage
  matched
• Bad Prognostic factors muscle, Stenson duct
  involvement, ECS

Diaz, Head Neck April 2003
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GBS Cancers The TMH Experience (1997-99)

• Early Stage(I/II)
• n 207pts
• Median follow up 2.2 yrs
• DFS 2yrs 65.7
• 5yrs 50.33
• Local Rec. rate 21
• Salvage rate 37

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GINGIVO BUCCAL CANCERSEARLY T1/T2 CANCERS
SURG. v/s RT

• IS A RANDOMIZED TRIAL FEASIBLE?
• NO IT WOULD BE,
• UNETHICAL
• DIFFICULT OT ACCRUE PATIENTS

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Early GBS Cancers (T1/T2)Management of the Neck

• Low propensity to cervical metastasis
  lt10
• 7.2 Clinically N0 have occult metastasis
• (Nair, Cancer 1988)
• CAN WAIT WATCH UNLESS
• Poor follow up
• Cheek flap for surgical access

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Marginal Mandibulectomy for GBS CancersTMH
Experience

• Pradhan SA et al Indian J Cancer 1987 Control
  rate 79
• Pathak KA et al EJSO 2004
• 1994-2001 n83
• 2-year local control 79

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Marginal MandibulectomyContraindications

• Locoregional control influenced by soft tissue
  margins (plt0.01) - 127pts / 94 marginal
  mandibulectomies

OBrien C.J., Int J Oral Maxillofac Surg 2003
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GB Cancers Locally advancedT3, T4

• SURGERY FOLLOWED BY PORT
• RADIOTHERAPY WITH SALVAGE SURGERY
• NO RANDOMIZED CONTROL TRIALS

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Radiotherapy Carcinoma Buccal Mucosa
185 cases
Late Stage
2 years DFS - 5 RT 33 SX
Chaudhary, Seminars in Surgical Oncology 1989
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Gingivo Buccal Sulcus TumorsRadiotherapy

• 234 patients (Nair et al Cancer 1988)
• Stage I 85, Stage II 63, Stage III
  41, Stage IV -15
• Radium implant (28) Small Volume ext. RT (62
  Vs 64)
• Dismal Survival with RT in advanced stage poor
  surgical salvage
• Compared three groups S alone / S PORT / RT
  (no survival)
• Chhetri D.K., Otolaryngol Head Neck Surg 2000

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Adjuvant RT (RTOG 73.03)1973-1979 ( N277)

• 
  Pre-op POST
  OP RT
• LR CONTROL 48 65 p0.04
• SURVIVAL 33 38 pO.1,better trend
• COMPLICATIONS SAME

ORAL CAVITY (43) PREOP RT PORT SUBSET OAS
30 36 ANALYSIS LRC 43 52
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Radiotherapy in head and neck Cancers

• RTOG 73-03
• 277 PATIENTS - FOLLOW UP 9-15 yrs
• PRE OP RT POST OP RT
• 50.0 GY 60.0 GY

• LOCO REGIONAL CONTROL BETTER (p 0.04)
• NO DIFFERENCE IN ABSOLUTE SURVIVAL (p 0.15)
• COMPLICATIONS SAME (p - NS)

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Surgery PORT (1988 1994)
n-57 ( Sx RT) RT 45 68.4 (61.2 Gy) Poor
prognostic factors (Univariate) - Positive
Surgical Margin - Tumor invasion of cheek Poor
prognostic factors (Multivariate) - Tumor
invasion of skin (p0.0014)
Fu-min Fang et al Head Neck 1997
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GBS Cancers The TMH ExperiencePrognostic
factors -Late Stage ( III / IVa)

• Univariate Analysis
• Grade p0.002
• Cut margins p0.04
• Node positivity p0.000
• Perinodal extension p0.008
• Thickness gt 4mm p0.004
• Multivariate Analysis
• Node positivity p0.001, HR2.81, CI (1.5 5.2)
• Thickness gt4mm p0.002, HR1.8, CI (1.2 2.8)

n 624 DFS 2yrs 38.5
5yrs 13
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Surgery v/s Surgery PORT(1989 1993)

• N176 patients 115(S) 61(SR)
• LR control 11 48 III/IV
  (p0.001)
• 71 75 I/II (pNS)
• PROGNOSTIC FACTORS
• Margins
• Thickness
• Bone invasion
• Grade
• Nodal involvement
• RT BETTER IF BEFORE 30 DAYS
• - Dixit S, Vyas RK, Ann Surg Oncol. 1998

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GB Sulcus Cancers POST OP RTRCT

• 30 MONTHS FOLLOW UP
• DISEASE FREE SURVIVAL 38 v/s 68 ( p lt 0.005)

Mishra et al (1996 European Journal of Surgical
Oncology)
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RCT Role of RT

• Peters et al (1993) RISK GROUPS
• RCT
• N 240 LOW RISK HIGH RISK
• DOSE A DOSE B
  DOSE C
• 52 54 Gy/ 6wks 63Gy/ 7wks/35
  68.4Gy/7.5wks/35
• Interim Analysis
• Higher Recc
• 57.6Gy/ 6.5wks
• CONCLUSIONS
• A minimum of 57.6 Gy with boost of 63 Gy to sites
  of high risk and ECS, is essential
• Treatment should be started as soon as possible
• Dose escalation above 63 Gy does not appear to
  improve therapeutic ratio

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POST OP RT

• RISK FACTORS
• Oral cavity primary
• Margins close / positive
• Perineural invasion
• ? 2 positive lymph nodes

• Largest node gt 3 cms
• Performance status ? 2 WHO
• Delay gt 6 weeks

(Ang et al, 2001)
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Results

• Low risk / Intermediate risk had similar control
  survival
• They did better than high risk
• High risk had a trend towards better control when
  RT was given over 5 weeks

Ang et al, 2001
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POST OP CHEMORADSEORTC NEJM 2004

• Median follow up 60 months
• Progression free survival 47 v/s 36 (p 0.04)
• Overall survival 53 v/s 40 (p 0.02)
• Locoregional recurrences 18 v/s 31 (p 0.007)
• Toxicity GR?3 41 v/s 21 (p 0.001)

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POST OP CHEMORADSRTOG (9501) NEJM 2004

• Median follow up 60 months
• Locoregional control 82 v/s 72 (p 0.01)
• Disease free survival better (p 0.04)
• Overall survival similar (p 0.19)
• Acute toxicity GR?3 77 v/s 34 (p lt 0.001)

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Gingivo Buccal Cancers (T3 / T4)Prospective
Randomised Control Trial

• DFS 61 Vs 37 (p0.01)
• Local Recurrence less in first 6 months (p0.002)

Rao et al Am J Surg. 1994
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G B Cancers - T 3 / 4Management of nodes
1980 1989 - 527 patients
Extent of neck SD SOHD RND
Dissection (Level I )
(Level I III) (Level I V )
N0 N N0
N N0 N Nodes
95 71 141
42 67 111 Regional
11(12) 24(34) 7(5)
8(19) 2(3) 20(18) Recurrence
Pradhan S.A., DCruz A.K. Eur Arch
Otorhinolaryngol (1995) 252 143 - 145
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Recurrent Oral Tumors

• 38 patients who recurred after curative
  treatment
• Salvage better if -
• i) Initial tumor stage I / II Vs III / IV (
  p lt 0.001)
• ii) Recurring after 6 months ( p lt 0.005)
• iii) Surgery for salvage Vs RT / CT ( p lt
  0.001)
• iv) Stage of recurrence (N S)
• Overall Salvage rate 21
• Overall salvage rate whether 15 (Wheeler, 1990)
• Schwatz, Head Neck, Jan 2000

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Management of Advanced Unresectable Head and Neck
cancers

• Altered fractionation radiation
• Induction chemotherapy
• Alternating chemo-radiotherapy
• Concurrent CT RT

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Altered Fractionation RadiationRTOG 9303

• N1113 patients
• Four arms
• Standard fractionation
• Hyperfractionation
• Accelerated hyperfractionation with Split
• Accelerated fractionation with Concomitant boost
• Results
• Better locoregional control with
  Hyperfractionation (p0.045) Accelerated
  fractionation with Concomitant boost (p0.050)
• All three Altered fractionation group had
  increased acute toxicity and comparable late
  toxic effects
• Fu et al,Int J Radiat Oncol Biol Phys 2000

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GB cancers stage- IV B/C

• No conclusive evidence confirming the role of
  chemotherapy in palliation as compared to best
  supportive care

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Foscan study in advanced disease

• Objectives
• improvement in quality of life
• objective tumour response (complete and partial)
• toxicity, tolerability and safety
• one-year survival

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PDTAdvanced Cancers

• 147 patients assessed to date 109 M, 38 F
• 50 Caucasians, 50 Asians
• Clinical benefit
• 24 objective response
• 53 overall palliative benefit

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Overall study results
Palliation ( 122 patients.)
Overall palliative benefit 53 (64 patients)
43 patients were optimally treated 61 showed
overall palliative benefit
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VERRUCOUS CARCINOMA

• 5 of all SCC
• LOCALLY AGGRESSIVE
• DE-DIFFERENTIATION WITH RT (Medina 84)
• Recent studies DO NOT CONFIRM above
• (Tharp, Laryngoscope 1998 McCafferey 1998)
• Better results with SURGERY compared to RT

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Thank you
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Chemoradiation in Advanced Head Neck cancers

• Induction Chemotherapy
• Initial response rates 50 90 with
  Cisplatin-5FU based schedules
• However, multiple RCTs Failure to demonstrate
  a survival advantage with either Single /
  Multiagent Chemotherapy

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Chemoradiation in Advanced Head Neck cancers

• Alternating Chemoradiation
• 2 RCTs
• Complete response rates, Progression free
  survival and OAS significantly better for
  Alternation chemoradiation arm as compared to
  Radiation
• -Merlano, Cancer 1991 Merlano J Natl Cancer
  Inst 1996
• Concurrent Chemoradiation
• MACH-NC 63 RCTs, 10,000 patients
• 5 yr OAS benefit 8 (plt0.0001)
• -Pignon et al, Lancet 2000

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TMH RETROSPIVE REVIEW 3YRS 1997 1999

• Chart review of 2275 patients
• DFS
• Median followup
• No of patients with surgery /- RT
• Stages at presentation
• Reccurrence rates

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Adjuvant Chemotherapy for stage III / IV
Head Neck Contracts Program
Radiation 71 / 152 (Standard)
Induction CT Surgery RT 60 /140
(Induction)
Induction CT Surgery RT CT
(Maintenance) 67 /151
1978 -1982 462 patients (Median Follow-up 61
months)

• OS DFS similar (p0.86 p 0.16)
• DM less in maintenance group ( p0.025 p
  0.021)
• Time to 1st relapse increased ( p 0.032 p
  0.022)

Cancer 1980
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GBS Cancers The TMH Experience (1997-99)

• Late Stage(III/IVa)
• n 624
• Median follow up 1.91 yrs
• DFS 2yrs 38.5
• 5yrs 13
• OAS 2yrs 85
• 5yrs 78
• Overall recc rate 37
• Salvage rate 19