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Managment Of N+Neck

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1. Management of the neck in head and neck cancer involves addressing clinically negative (N0) and positive (N+) lymph nodes. 2. For N0 necks, elective neck dissection may decrease recurrence rates for high-risk primary sites. For N+ necks, selective neck dissection is adequate for early stage single node involvement without extracapsular spread. 3. Post-operative radiotherapy improves local control for N+ necks with adverse features like multiple nodes, extracapsular spread or positive margins. Concurrent chemoradiotherapy is preferred for advanced N2/N3 disease.

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Management of the Neck (N 0 and N + ) Dr. A D’Cruz Tata Memorial Hospital
Cervical Metastasis Single most important prognostic factor 50% decrease in survival Paradigm shift in the management in last 20 years Treatment usually influenced by choice of treatment for primary
Management of the neck Surgery Should the N 0 neck be addressed What should be the extent of dissection N 0 What should be the extent of dissection for the N + neck When & what adjuvant treatment is indicated after neck dissection
1. Should the neck be addressed in a N0 neck? No debate - T3,T4 - Cheek flap - Site Glottis (low risk) BOT, PFS, SGL (high risk) Debate T1,T2 oral cavity, which can be treated per orally
END v/s Observe END Trend towards better survival Single surgery ? Diversion of lymphatics Observe No compromise on survival Sx avoided in upto 80% Low salvage rates “ It must be shown that neck dissection performed for clinically palpable metastases (cN+) is less successful than a similar operation for involved but not palpable nodes (cN0 but pN+)”
N0 Current Management Policies – I Mathematical Models Weiss et al A patient with a N0 neck status should be observed if the probability of occult cervical metastasis is less than 20% If the probability is greater than 20%, treatment of the neck is warranted (quality adjusted survival) Arch Otolaryngol H & N Surg. 1994;120:699 -702
N 0 Current Management Policies - II Historical evidence Site % nodal metastases T1 T2 T3 Oral tongue 14 30 47 Floor of mouth 11 29 43 RMT 11.5 37 54 Lindberg et al, Byers et al, Shah et al.
Author (n) DFS OAS Haddadin - p = 0.01 * (137) Lydiatt ns ns (156) Yuen p < 0.05 * - (63) Piedbois(1991) - p < 0.04 (233) * in favour of elective neck dissection N0 Current Management Policies - III Retrospective
Author (n) DFS OAS Vandenbrouck (1980) ns ns (75) Fakih (1989) ns ns (70) Kligerman (1994) p = 0.04 * - (67) * in favour of elective neck dissection N 0 Current Management Policies - IV Trials – Prospective
Tongue cancer Retrospective analysis (1997 – 2001) 359 patients Observe Operate (200 patients) (159 patients) SOHD (89) MND (70) Previously untreated pts Per oral excisions
Tumor characteristics Observe Operate T Stage T1 118(59%) 69(43.4%) T2 82(41%) 90(56.6%) Grade I 48(24%) 30(18.9%) II 132(66%) 109(68.6%) III 20(10%) 20(12.6%) PNI No 181(90.5%) 145(91.2%) Yes 19(9.5%) 14(8.8%) Thickness <=3 39(19.5%) 13(8.2%) 4-9 115(57.5%) 89(56%) >=10 37(18.5%) 52(32.7%) Cut margin +ve 7(3.5%) 4(2.5%) -ve 184(92%) 146(91.8%) close 9(4.5%) 9(5.7%)
Status at last follow -up Observe Operate Disease free 131(65.5%) 117(73.6%) Alive with Disease 38(19%) 25(15.7%) Died of Disease 8(4%) 5(3.1%) Died of other cause 6(3%) 1(0.6%) Lost to follow-up 17(8.5%) 11(6.9%)
Views on management of N0 neck Questionnaire Werning et al, Random survey of 763 otolaryngologists To determine the variability of Mx of the N0 neck 13% Observe 66% END 19% Radiotherapy to neck Arch Otolaryngol Head Neck Surg 2003
2. Extent of neck dissection (N0 neck) Location: Oral BOT Hypopharynx Larynx Level of : I-III II-III II-IV II-IV Neck SOHD ( I – III) - Oral cavity Lateral neck (II – IV) - Oropharynx, Larynx, Hypopharynx - Lindberg, Byers, Shah
SOHD (Oral Cavity) Recurrences in dissected neck [Primary controlled; 2 YR follow up] Path Surgery only Sx + RT Staging Medina 1 Byers 2 Medina 1 Byers 2 N0 0 / 51 7/130(5%) 1/29(3.45%) 2/24(8%) N1 - 1/10(10%) 1/3 0/8 Multiple 0 / 1 5/21(24%) 2/16(12.5%) 6/14(15%) Nodes 1 Hawai 1991 , 2 Head & Neck 11; 1989
Lateral Neck Dissection – Reccurences in dissected neck [Primary controlled; 2 YR follow up] Path Staging Surgery only Sx + RT Medina 1 Byers 2 Medina 1 Byers 2 N0 0 / 15(0) 10/130(8) 1/19(5.2) 1/126(1) N1 - 0/4(0) 0/3(0) 0/17(0) Multiple - - 0 /6(0) 3/20(15) Nodes 1 University of Oklahoma experience , 2 Am J Surg 1986;150: 414-421
Critical Assessment of SOHD 94 Patients / 107 SOHD’s Spiro Am J surgery 1998 94 Patients / 107 SOHD’s 24 Clinical N + 83 Clinical N - 26 Path +ve 17 Path +ve 64 Path -ve 4 (15%) Neck Fail 3 (5%) Neck Fail 5 (29%) Neck Fail
ORAL SCC T2 – T4 N0) RCT (148 patients) Rec 5Yr Survival Comp MND 19 63% 41% SOHD 16 67% 25% p0.7150 p0.043 Am J Surg 1998 Brazilian H & N group
3. What should be the extent of dissection for the N + neck “ IS SELECTIVE NECK DISSECTION A VALID PROCEDURE FOR N+ NECK?”
Management of the neck Crile 1906, Martin 1950
Management of the neck Bocca 1984 Laryngoscope 843 Cases Byers 1985 Am J Surg 967 Cases Anderson 1994 Am J Surg 366 Cases RND 63% 12% MRND 71% 8% p (NS) 5 year Survival Neck Failure MND = RND Same control  Less Morbid
Level V Metastases Overall 3 % Hypopharynx 7 % Oropharynx 6 % Oral Cavity 1 % Larynx 2 % Davidson et al, Am J Surg, Oct. 93. N = 1277
SND in N+ Neck Kowalski 1993 164 / 95 +ve Kolli 2000 69 / 39 +ve Traynor 1996 29 patients +ve Safe
Therapeutic Neck Dissection – 25 Yr Review Median follow up – 4.3yrs SND MND RND (61) (54) (61) Regional Control 2(3.3%) 3(5.6%) 3(4.9%) ( p = NS) DFS at 2yrs 80% 64% 64% Comparable - K. Muzzafar, Laryngoscope: 2003
SND in N+ Neck Anderson (106 patients/ 129 necks) Oral Cavity 42 (39.6%) Oropharynx 37 (34.9%) Larynx 20 (18.9%) Hypopharynx 7 ( 6.6%) T0 1 (0.9%) T1 9 (8.5%) T2 28 (26.4%) T3 36 (34.0%) T4 32 (30.2%) Post Op RT 71.7% N1 58(54.7%) N2a 5(4.7%) N2b 28(26.4%) N2c 14(13.2%) N3 1(0.9%) ECS 30(34%) Regional failures 9 (5.7%) 6 within fields Archives 2002
SND in N+ Neck Medina & Byers ; Head & Neck 1989 114 patients node +ve - 91(79.8%) pathologic evidence of mets N1 / No ECS Surgery Only - 10% recc Multiple / ECS - 24% SX + RT - 15%
SND in N+ Neck Only in pts without massive adenopathy No nodal fixation Obvious gross ECS No prior neck surgery / RT
AHNS - Procedures Studied Selective neck dissection Total thyroidectomy Parotidectomy Endoscopic laryngeal surgery
Evidence-Based Review Thorough, systematic review of literature Each relevant paper reviewed by explicit guidelines and assigned a ‘level of evidence’ All papers compiled and topic is assigned ‘grade of recommendation’
Results Expert opinion 5 D Case series (no control group) 4 C Case control studies 3 Cohort studies, Low quality RCT 2b B Meta-analysis of cohort studies 2a High quality RCT 1b A Meta-analysis of RCT’s 1a Study Design Level of Evidence Grade of Recommendation
4. Adjuvant treatment after neck dissection PROGNOSTIC IMPLICATIONS Extracapsular spread Johnson (Arch 1981) < 40% Survival Steinhart 1994 – ECS 28% v/s NO ECS 70% Carter (Am J Surg 1985) – “ Macroscopic ECS worse than Microscopic” Desmoplastic stromal pattern 284 Patients (no RT) – 7 fold increase in regional recurrences OLSEN (Archives 1994) Number of lymph nodes O’BRIEN ( Am J Surg 1986) - No. of nodes Recurrences KALNINS (Am J Surg 1977) N0 75%, 1 node 49%, 3 nodes 30%, >3 13% Level of Lymph nodes Lower nodes have worse prognosis Spiro Am J Surg 1974, Tulenko Am J Surg 1966, Mendelson 1976
RCT – Role of RT in management of Neck 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
POST OP RT RISK FACTORS: Oral cavity primary Margins close / positive Perineural invasion  2 positive lymph nodes Largest node > 3 cms Performance status  2 [WHO] Delay > 6 weeks ( Ang et al, 2001 ) RCT – 213 patients Low risk n = 31 Intermediate risk n = 31 High risk n = 151 NO ADJUVANT RT 57.6 Gy/ 6.5 weeks n = 76 63 Gy / 5 weeks n = 75 63 Gy / 7weeks
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 NO DATA about the ROLE FOR RT with A SINGLE NODE Ang et al, 2001 Results
Management of Neck - Single node, NO ECS Rec. SURGERY 11% 5/47 SURGERY + PORT 0% 0/21 [Retrospective] Barkley Am j Surg 1972
Single node ECS -Ve M D Anderson Data
POST OP CHEMORADS EORTC – 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) Curative post surgery 167 RT [66 Gy / 6.5 weeks] 167 CT / RT [100mg Cispat/m2 T3;T4;Node +ve &T1/T2 adverse factors
POST OP CHEMORADS RTOG (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 < 0.001) Curative surgery 231 RT [60 – 66 Gy ] 228 RT + Cisplat [100mg/m2, Day 1,22,43]  2 nodes; ECS; +ve margins
Management of the neck RT / Chemo-Rads Should the N0 neck be radiated Do we need chemo-rads for an N1 neck How is an N2 / N3 node ideally managed with chemo-rads Does an N2 / N3 node influence the choice of treatment of the primary
2. Do we need chemo-rads for an N1 neck No proof that N1 node with T1 / T2 primary needs to be treated with chemo-rads Daily Fractionated RT = Chemo-rads 92% control at 3 years for <3cms node with daily RT * Mendelhall, Int J Radiation Onco 1986
3. How is an N2 / N3 node ideally managed with chemo-rads SIZE CONTROL 1.5 – 2.0 88% - 92% 2.5 – 3.0 74% 3.5 – 6.0 70% >7.0 0% Menderhall, In J. Rad Oncol 1984 (110 patients) McComs & Fletcher – Am J. Roentgenol 1957 Berkley & Fletcher – Am J. of Surgery 1972 RT + NECK DISSECTION
N2/N3 nodes: Planned Neck dissection ADVANTAGES 30% of specimens have occult metastasis Better regional control rates Poor salvage rates if picked up later (14-22%) DISADVANTAGES Unnecessary surgery in 70% of cases Better imaging like PET Complication rates - Menderhall 1986, Peters 1996
CHEMORADIOTHERAPY:N2/N3 Node 69 of 237 patients treated on CT/RT protocols 35% of neck specimens pathologically positive 26% total complications 10% wound complications CONCLUSIONS: Feasible Acceptable complication rates May be overtreatment in 65-70% of patients STENSON et al, Archives 2000
CT RT – RCT (LAVERTU et al , Head Neck 1997) 2 cycles Cisplat + 5 FU + RT Assessed at 50 – 55 Gy Non responders Responders Progressive disease 65 – 72 Gy SURGERY Persistent CR Planned adenopathy No dissection dissection (17) 3/12 relapsed (35) 8/17+ve – 1 relapsed (25%) 4/18+ve no relapsed NO SIGNIFICANT COMPLICATIONS  NOT STATISTICALLY SIGNIFICANT
N2/N3 nodes Oro/laryngopharynx Early disease - RT Locally advanced - Chemorads/RT Sx+PORT Small Primary Large Neck Node - ? ? T4 T3 II T2 I T1 N3 N2 N1 N0
Node excision followed by RT T1/T2 lesions of the PFS, Oropharynx, SGL N2/N3 operable adenopathy Schema Appropriate nodal debulking Radical RT to neck and primary (66-70Gy;7 wks)
SPLIT THERAPY - COMPARISON OF STUDIES WITH SURGERY FOLLOWED BY RT LR- Local Recurrence; RR- Regional Recurrence, OAS- Overall Survival; DFS- Disease free Survival DSS – Disease specific survival T/N criteria T1-2, N1-3 T1-3, N2-3 T1-3N2-3 T1-3N2-3 T1-2N2-3 T1-2N2-3 Survival statistics Median survival 19mths DSS at 2yrs-49% 5yr OAS-55% 3yrOAS-37%, DFS-60% 73% alive at 60mth 5yr OAS-60% 5yr DFS-59.4% RR 4% 15% 11% 8% Nil 13% LR 9% 28% 28% - 20% 7% No. of pts. 65 32 35 24 15 52 Trial Design Retrospective Retrospective/ Prospective Retrospective Retrospective Retrospective Retrospective Prospective Author/ Institute French Head And Neck Study group 2 Smeele Byers Allal Verschur TMH
4. Does an N2 / N3 node influence the choice of treatment of the primary Concurrent CTRT- 9303 RTOG N Stage Cisplat+5FU RT-Concurrent RT alone -RT [N=173] Cisplat [N=172] [N=173] N0 87(50) 86(50) 87(50) N1 38(22) 39(23) 32(18) N2a 02(01) 07(04) 03(02) N2b 17(10) 13(08) 13(8) N2c 26(05) 23(13) 36(21) N3 03(02) 04(02) 02(01) 87(50) 86(50) 87(50) 38(22) 39(23) 32(18)
Management of the neck Surgery N Stage N 0 N 2 -3 Neck Treatment N 1 SND / Wait & Watch MND / RND SND / MND Histology of LN pN 2 – 3 ECS pN1 pNO Further Treatment ? RT RT / ? CT / RT None
Management of the neck * Except T1 glottis, Bracytherapy alone treating primaries RT CT / RT N 0 N 1 N 2 -3 N Stage Neck Treatment Histology of LN Elective neck * Irradiation Neck RT Neck RT No residual tumor on completion of treatment Observe Residual tumor on completion Neck dissection Imaging Neck dissection Residual tumor No residual tumor on completion Observe END 4 – 6 weeks
Thank you
Management of Neck N 2b (Multiple levels) Failures with multiple nodes RT + neck better < 6cms 50Gy + Neck > 6cms 60Gy + neck Mendenhall 1986, Int J Radiation Oncology
Cervical Metastasis Chemotherapy Debatable role VA trial (N2 / N3) [ 46 / 166 patients ] 61% did not receive a ‘CR’ 33% unresectable at salvage surgery Responders 60 - 70 % survival Non responders 20 - 30% survival
Dagum - - - 58% 5yrs Actuarial Survival (48) Wang 9.8 9.8 - 67% DFS (71) Narayan 19.2 17.3 15.3 38% 5yrs OAS (52) SPLIT THERAPY - Comparison of results of studies with RT followed by Surgery LR RR DM Survival Statistics LR- Local Recurrence RR- Regional Recurrence DM- Distant Metastasis; OAS- Overall Survival
3. How is an N2 / N3 node ideally managed with chemo-rads Radio-curability proportional to volume of tumor Occult 4500 rad 1 cms 6000 ” 3 cms 7000 ” 6 cms 8000 ” McComs & Fletcher – Am J. Roentgenol 1957 Berkley & Fletcher – Am J. of Surgery 1972 RT + NECK DISSECTION
Management of the neck Surgery N Stage N 0 N 2 -3 Neck Treatment N 1 SND / Wait & Watch MND / RND SND / MND Histology of LN pN 2 – 3 ECS pN1 pNO Further Treatment ? RT RT / ? CT / RT None
Patterns of recurrence Site Observe Operate Primary 9(4.5%) 18(11.3%) Neck 94(47%) 9(5.7%) Neck+primary 3(1.5%) 1(0.6%) 2nd Primary 1(0.5%) 2(1.3%)
Patterns of recurrence 59.5% recurrences - Within 6 months Median time to recurrence - 6.18 months Observe Ipsilateral – 91, Contralateral – 1, Bilateral – 2 Recurrences-Nodal Stage Total recurrences = 94 N1 47(50%) N2a 14(14.9%) N2b 22(23.4%) N2c 4(4.3%) N3 7(7.4%) ECS 55(58.5%)
Adjuvant radiotherapy- Is it a confounding factor? Observe Operate 21/200 55/159 C/M +ve 3 5 Poor diff 6 12 PNI 7 6 T size 5 12 +ve nodes - 20

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Managment Of N+Neck

  • 1. Management of the Neck (N 0 and N + ) Dr. A D’Cruz Tata Memorial Hospital
  • 2. Cervical Metastasis Single most important prognostic factor 50% decrease in survival Paradigm shift in the management in last 20 years Treatment usually influenced by choice of treatment for primary
  • 3. Management of the neck Surgery Should the N 0 neck be addressed What should be the extent of dissection N 0 What should be the extent of dissection for the N + neck When & what adjuvant treatment is indicated after neck dissection
  • 4. 1. Should the neck be addressed in a N0 neck? No debate - T3,T4 - Cheek flap - Site Glottis (low risk) BOT, PFS, SGL (high risk) Debate T1,T2 oral cavity, which can be treated per orally
  • 5. END v/s Observe END Trend towards better survival Single surgery ? Diversion of lymphatics Observe No compromise on survival Sx avoided in upto 80% Low salvage rates “ It must be shown that neck dissection performed for clinically palpable metastases (cN+) is less successful than a similar operation for involved but not palpable nodes (cN0 but pN+)”
  • 6. N0 Current Management Policies – I Mathematical Models Weiss et al A patient with a N0 neck status should be observed if the probability of occult cervical metastasis is less than 20% If the probability is greater than 20%, treatment of the neck is warranted (quality adjusted survival) Arch Otolaryngol H & N Surg. 1994;120:699 -702
  • 7. N 0 Current Management Policies - II Historical evidence Site % nodal metastases T1 T2 T3 Oral tongue 14 30 47 Floor of mouth 11 29 43 RMT 11.5 37 54 Lindberg et al, Byers et al, Shah et al.
  • 8. Author (n) DFS OAS Haddadin - p = 0.01 * (137) Lydiatt ns ns (156) Yuen p < 0.05 * - (63) Piedbois(1991) - p < 0.04 (233) * in favour of elective neck dissection N0 Current Management Policies - III Retrospective
  • 9. Author (n) DFS OAS Vandenbrouck (1980) ns ns (75) Fakih (1989) ns ns (70) Kligerman (1994) p = 0.04 * - (67) * in favour of elective neck dissection N 0 Current Management Policies - IV Trials – Prospective
  • 10. Tongue cancer Retrospective analysis (1997 – 2001) 359 patients Observe Operate (200 patients) (159 patients) SOHD (89) MND (70) Previously untreated pts Per oral excisions
  • 11. Tumor characteristics Observe Operate T Stage T1 118(59%) 69(43.4%) T2 82(41%) 90(56.6%) Grade I 48(24%) 30(18.9%) II 132(66%) 109(68.6%) III 20(10%) 20(12.6%) PNI No 181(90.5%) 145(91.2%) Yes 19(9.5%) 14(8.8%) Thickness <=3 39(19.5%) 13(8.2%) 4-9 115(57.5%) 89(56%) >=10 37(18.5%) 52(32.7%) Cut margin +ve 7(3.5%) 4(2.5%) -ve 184(92%) 146(91.8%) close 9(4.5%) 9(5.7%)
  • 12. Status at last follow -up Observe Operate Disease free 131(65.5%) 117(73.6%) Alive with Disease 38(19%) 25(15.7%) Died of Disease 8(4%) 5(3.1%) Died of other cause 6(3%) 1(0.6%) Lost to follow-up 17(8.5%) 11(6.9%)
  • 13. Views on management of N0 neck Questionnaire Werning et al, Random survey of 763 otolaryngologists To determine the variability of Mx of the N0 neck 13% Observe 66% END 19% Radiotherapy to neck Arch Otolaryngol Head Neck Surg 2003
  • 14. 2. Extent of neck dissection (N0 neck) Location: Oral BOT Hypopharynx Larynx Level of : I-III II-III II-IV II-IV Neck SOHD ( I – III) - Oral cavity Lateral neck (II – IV) - Oropharynx, Larynx, Hypopharynx - Lindberg, Byers, Shah
  • 15. SOHD (Oral Cavity) Recurrences in dissected neck [Primary controlled; 2 YR follow up] Path Surgery only Sx + RT Staging Medina 1 Byers 2 Medina 1 Byers 2 N0 0 / 51 7/130(5%) 1/29(3.45%) 2/24(8%) N1 - 1/10(10%) 1/3 0/8 Multiple 0 / 1 5/21(24%) 2/16(12.5%) 6/14(15%) Nodes 1 Hawai 1991 , 2 Head & Neck 11; 1989
  • 16. Lateral Neck Dissection – Reccurences in dissected neck [Primary controlled; 2 YR follow up] Path Staging Surgery only Sx + RT Medina 1 Byers 2 Medina 1 Byers 2 N0 0 / 15(0) 10/130(8) 1/19(5.2) 1/126(1) N1 - 0/4(0) 0/3(0) 0/17(0) Multiple - - 0 /6(0) 3/20(15) Nodes 1 University of Oklahoma experience , 2 Am J Surg 1986;150: 414-421
  • 17. Critical Assessment of SOHD 94 Patients / 107 SOHD’s Spiro Am J surgery 1998 94 Patients / 107 SOHD’s 24 Clinical N + 83 Clinical N - 26 Path +ve 17 Path +ve 64 Path -ve 4 (15%) Neck Fail 3 (5%) Neck Fail 5 (29%) Neck Fail
  • 18. ORAL SCC T2 – T4 N0) RCT (148 patients) Rec 5Yr Survival Comp MND 19 63% 41% SOHD 16 67% 25% p0.7150 p0.043 Am J Surg 1998 Brazilian H & N group
  • 19. 3. What should be the extent of dissection for the N + neck “ IS SELECTIVE NECK DISSECTION A VALID PROCEDURE FOR N+ NECK?”
  • 20. Management of the neck Crile 1906, Martin 1950
  • 21. Management of the neck Bocca 1984 Laryngoscope 843 Cases Byers 1985 Am J Surg 967 Cases Anderson 1994 Am J Surg 366 Cases RND 63% 12% MRND 71% 8% p (NS) 5 year Survival Neck Failure MND = RND Same control  Less Morbid
  • 22. Level V Metastases Overall 3 % Hypopharynx 7 % Oropharynx 6 % Oral Cavity 1 % Larynx 2 % Davidson et al, Am J Surg, Oct. 93. N = 1277
  • 23. SND in N+ Neck Kowalski 1993 164 / 95 +ve Kolli 2000 69 / 39 +ve Traynor 1996 29 patients +ve Safe
  • 24. Therapeutic Neck Dissection – 25 Yr Review Median follow up – 4.3yrs SND MND RND (61) (54) (61) Regional Control 2(3.3%) 3(5.6%) 3(4.9%) ( p = NS) DFS at 2yrs 80% 64% 64% Comparable - K. Muzzafar, Laryngoscope: 2003
  • 25. SND in N+ Neck Anderson (106 patients/ 129 necks) Oral Cavity 42 (39.6%) Oropharynx 37 (34.9%) Larynx 20 (18.9%) Hypopharynx 7 ( 6.6%) T0 1 (0.9%) T1 9 (8.5%) T2 28 (26.4%) T3 36 (34.0%) T4 32 (30.2%) Post Op RT 71.7% N1 58(54.7%) N2a 5(4.7%) N2b 28(26.4%) N2c 14(13.2%) N3 1(0.9%) ECS 30(34%) Regional failures 9 (5.7%) 6 within fields Archives 2002
  • 26. SND in N+ Neck Medina & Byers ; Head & Neck 1989 114 patients node +ve - 91(79.8%) pathologic evidence of mets N1 / No ECS Surgery Only - 10% recc Multiple / ECS - 24% SX + RT - 15%
  • 27. SND in N+ Neck Only in pts without massive adenopathy No nodal fixation Obvious gross ECS No prior neck surgery / RT
  • 28. AHNS - Procedures Studied Selective neck dissection Total thyroidectomy Parotidectomy Endoscopic laryngeal surgery
  • 29. Evidence-Based Review Thorough, systematic review of literature Each relevant paper reviewed by explicit guidelines and assigned a ‘level of evidence’ All papers compiled and topic is assigned ‘grade of recommendation’
  • 30. Results Expert opinion 5 D Case series (no control group) 4 C Case control studies 3 Cohort studies, Low quality RCT 2b B Meta-analysis of cohort studies 2a High quality RCT 1b A Meta-analysis of RCT’s 1a Study Design Level of Evidence Grade of Recommendation
  • 31. 4. Adjuvant treatment after neck dissection PROGNOSTIC IMPLICATIONS Extracapsular spread Johnson (Arch 1981) < 40% Survival Steinhart 1994 – ECS 28% v/s NO ECS 70% Carter (Am J Surg 1985) – “ Macroscopic ECS worse than Microscopic” Desmoplastic stromal pattern 284 Patients (no RT) – 7 fold increase in regional recurrences OLSEN (Archives 1994) Number of lymph nodes O’BRIEN ( Am J Surg 1986) - No. of nodes Recurrences KALNINS (Am J Surg 1977) N0 75%, 1 node 49%, 3 nodes 30%, >3 13% Level of Lymph nodes Lower nodes have worse prognosis Spiro Am J Surg 1974, Tulenko Am J Surg 1966, Mendelson 1976
  • 32. RCT – Role of RT in management of Neck 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
  • 33. POST OP RT RISK FACTORS: Oral cavity primary Margins close / positive Perineural invasion  2 positive lymph nodes Largest node > 3 cms Performance status  2 [WHO] Delay > 6 weeks ( Ang et al, 2001 ) RCT – 213 patients Low risk n = 31 Intermediate risk n = 31 High risk n = 151 NO ADJUVANT RT 57.6 Gy/ 6.5 weeks n = 76 63 Gy / 5 weeks n = 75 63 Gy / 7weeks
  • 34. 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 NO DATA about the ROLE FOR RT with A SINGLE NODE Ang et al, 2001 Results
  • 35. Management of Neck - Single node, NO ECS Rec. SURGERY 11% 5/47 SURGERY + PORT 0% 0/21 [Retrospective] Barkley Am j Surg 1972
  • 36. Single node ECS -Ve M D Anderson Data
  • 37. POST OP CHEMORADS EORTC – 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) Curative post surgery 167 RT [66 Gy / 6.5 weeks] 167 CT / RT [100mg Cispat/m2 T3;T4;Node +ve &T1/T2 adverse factors
  • 38. POST OP CHEMORADS RTOG (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 < 0.001) Curative surgery 231 RT [60 – 66 Gy ] 228 RT + Cisplat [100mg/m2, Day 1,22,43]  2 nodes; ECS; +ve margins
  • 39. Management of the neck RT / Chemo-Rads Should the N0 neck be radiated Do we need chemo-rads for an N1 neck How is an N2 / N3 node ideally managed with chemo-rads Does an N2 / N3 node influence the choice of treatment of the primary
  • 40. 2. Do we need chemo-rads for an N1 neck No proof that N1 node with T1 / T2 primary needs to be treated with chemo-rads Daily Fractionated RT = Chemo-rads 92% control at 3 years for <3cms node with daily RT * Mendelhall, Int J Radiation Onco 1986
  • 41. 3. How is an N2 / N3 node ideally managed with chemo-rads SIZE CONTROL 1.5 – 2.0 88% - 92% 2.5 – 3.0 74% 3.5 – 6.0 70% >7.0 0% Menderhall, In J. Rad Oncol 1984 (110 patients) McComs & Fletcher – Am J. Roentgenol 1957 Berkley & Fletcher – Am J. of Surgery 1972 RT + NECK DISSECTION
  • 42. N2/N3 nodes: Planned Neck dissection ADVANTAGES 30% of specimens have occult metastasis Better regional control rates Poor salvage rates if picked up later (14-22%) DISADVANTAGES Unnecessary surgery in 70% of cases Better imaging like PET Complication rates - Menderhall 1986, Peters 1996
  • 43. CHEMORADIOTHERAPY:N2/N3 Node 69 of 237 patients treated on CT/RT protocols 35% of neck specimens pathologically positive 26% total complications 10% wound complications CONCLUSIONS: Feasible Acceptable complication rates May be overtreatment in 65-70% of patients STENSON et al, Archives 2000
  • 44. CT RT – RCT (LAVERTU et al , Head Neck 1997) 2 cycles Cisplat + 5 FU + RT Assessed at 50 – 55 Gy Non responders Responders Progressive disease 65 – 72 Gy SURGERY Persistent CR Planned adenopathy No dissection dissection (17) 3/12 relapsed (35) 8/17+ve – 1 relapsed (25%) 4/18+ve no relapsed NO SIGNIFICANT COMPLICATIONS  NOT STATISTICALLY SIGNIFICANT
  • 45. N2/N3 nodes Oro/laryngopharynx Early disease - RT Locally advanced - Chemorads/RT Sx+PORT Small Primary Large Neck Node - ? ? T4 T3 II T2 I T1 N3 N2 N1 N0
  • 46. Node excision followed by RT T1/T2 lesions of the PFS, Oropharynx, SGL N2/N3 operable adenopathy Schema Appropriate nodal debulking Radical RT to neck and primary (66-70Gy;7 wks)
  • 47. SPLIT THERAPY - COMPARISON OF STUDIES WITH SURGERY FOLLOWED BY RT LR- Local Recurrence; RR- Regional Recurrence, OAS- Overall Survival; DFS- Disease free Survival DSS – Disease specific survival T/N criteria T1-2, N1-3 T1-3, N2-3 T1-3N2-3 T1-3N2-3 T1-2N2-3 T1-2N2-3 Survival statistics Median survival 19mths DSS at 2yrs-49% 5yr OAS-55% 3yrOAS-37%, DFS-60% 73% alive at 60mth 5yr OAS-60% 5yr DFS-59.4% RR 4% 15% 11% 8% Nil 13% LR 9% 28% 28% - 20% 7% No. of pts. 65 32 35 24 15 52 Trial Design Retrospective Retrospective/ Prospective Retrospective Retrospective Retrospective Retrospective Prospective Author/ Institute French Head And Neck Study group 2 Smeele Byers Allal Verschur TMH
  • 48. 4. Does an N2 / N3 node influence the choice of treatment of the primary Concurrent CTRT- 9303 RTOG N Stage Cisplat+5FU RT-Concurrent RT alone -RT [N=173] Cisplat [N=172] [N=173] N0 87(50) 86(50) 87(50) N1 38(22) 39(23) 32(18) N2a 02(01) 07(04) 03(02) N2b 17(10) 13(08) 13(8) N2c 26(05) 23(13) 36(21) N3 03(02) 04(02) 02(01) 87(50) 86(50) 87(50) 38(22) 39(23) 32(18)
  • 49. Management of the neck Surgery N Stage N 0 N 2 -3 Neck Treatment N 1 SND / Wait & Watch MND / RND SND / MND Histology of LN pN 2 – 3 ECS pN1 pNO Further Treatment ? RT RT / ? CT / RT None
  • 50. Management of the neck * Except T1 glottis, Bracytherapy alone treating primaries RT CT / RT N 0 N 1 N 2 -3 N Stage Neck Treatment Histology of LN Elective neck * Irradiation Neck RT Neck RT No residual tumor on completion of treatment Observe Residual tumor on completion Neck dissection Imaging Neck dissection Residual tumor No residual tumor on completion Observe END 4 – 6 weeks
  • 52. Management of Neck N 2b (Multiple levels) Failures with multiple nodes RT + neck better < 6cms 50Gy + Neck > 6cms 60Gy + neck Mendenhall 1986, Int J Radiation Oncology
  • 53. Cervical Metastasis Chemotherapy Debatable role VA trial (N2 / N3) [ 46 / 166 patients ] 61% did not receive a ‘CR’ 33% unresectable at salvage surgery Responders 60 - 70 % survival Non responders 20 - 30% survival
  • 54. Dagum - - - 58% 5yrs Actuarial Survival (48) Wang 9.8 9.8 - 67% DFS (71) Narayan 19.2 17.3 15.3 38% 5yrs OAS (52) SPLIT THERAPY - Comparison of results of studies with RT followed by Surgery LR RR DM Survival Statistics LR- Local Recurrence RR- Regional Recurrence DM- Distant Metastasis; OAS- Overall Survival
  • 55. 3. How is an N2 / N3 node ideally managed with chemo-rads Radio-curability proportional to volume of tumor Occult 4500 rad 1 cms 6000 ” 3 cms 7000 ” 6 cms 8000 ” McComs & Fletcher – Am J. Roentgenol 1957 Berkley & Fletcher – Am J. of Surgery 1972 RT + NECK DISSECTION
  • 56. Management of the neck Surgery N Stage N 0 N 2 -3 Neck Treatment N 1 SND / Wait & Watch MND / RND SND / MND Histology of LN pN 2 – 3 ECS pN1 pNO Further Treatment ? RT RT / ? CT / RT None
  • 57. Patterns of recurrence Site Observe Operate Primary 9(4.5%) 18(11.3%) Neck 94(47%) 9(5.7%) Neck+primary 3(1.5%) 1(0.6%) 2nd Primary 1(0.5%) 2(1.3%)
  • 58. Patterns of recurrence 59.5% recurrences - Within 6 months Median time to recurrence - 6.18 months Observe Ipsilateral – 91, Contralateral – 1, Bilateral – 2 Recurrences-Nodal Stage Total recurrences = 94 N1 47(50%) N2a 14(14.9%) N2b 22(23.4%) N2c 4(4.3%) N3 7(7.4%) ECS 55(58.5%)
  • 59. Adjuvant radiotherapy- Is it a confounding factor? Observe Operate 21/200 55/159 C/M +ve 3 5 Poor diff 6 12 PNI 7 6 T size 5 12 +ve nodes - 20