treatment time tobacco: twin terrors
TRANSCRIPT
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TREATMENT TIME & TOBACCO: TWIN TERRORS Of H&N Therapy
Anurag K. Singh, MDProfessor of Medicine
University at Buffalo School of MedicineProfessor of Oncology
Director of Radiation ResearchRoswell Park Cancer Institute
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CASE• 53 y/o man• T2N2cM0 Base of Tongue Cancer
• 40 pack years• HPV positive
• Smokes 1.5 ppd• Seen November 10• Because of work, wants to start on a wednesday
Can’t be changed
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OutlineTREATMENT TIME
• Historical Data• RPCI Experience pt 1
– 3‐4% per day over 50
• RPCI Experience pt 2– Preventing treatment prolongation works
TOBACCO• It is bad for you
– Bad during RT
• Quitting prior to RT
makes a BIGdifference
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OutlineTREATMENT TIME
• Historical Data• RPCI Experience pt 1
– 3‐4% per day over 50
• RPCI Experience pt 2– Preventing treatment prolongation works
TOBACCO• It is bad for you
– Bad during RT
• Quitting prior to RT
makes a BIGdifference
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Treatment Time is Important with RT alone
1. Suwinski, R., et al., Time factor in postoperative radiotherapy: a multivariate locoregional control analysis in 868 patients. Int J Radiat Oncol Biol Phys, 2003. 56(2): p. 399‐412.
2. Robertson, A.G., et al., Effect of gap length and position on results of treatment of cancer of the larynx in Scotland by radiotherapy: a linear quadratic analysis. Radiother Oncol, 1998. 48(2): p. 165‐73.
3. Hliniak, A., B. Maciejewski, and K.R. Trott, The influence of the number of fractions, overall treatment time and field size on the local control of cancer of the skin. Br J Radiol, 1983. 56(668): p. 596‐8.
4. Maciejewski, B., et al., Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: tumor dose‐response and repopulation. Int J Radiat Oncol Biol Phys, 1989. 16(3): p. 831‐43.
5. Robertson, C., et al., Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers. Int J Radiat Oncol Biol Phys, 1998. 40(2): p. 319‐29.
6. Kwong, D.L., et al., The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys, 1997. 39(3): p. 703‐10.
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Tx Time & Hgb with ChemoRTRades. IJROBP. 2008.
• 153 patients• Stage IV • Concurrent ChemoRT
– Definitive (70) or Post‐op (83)
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Prognostic FactorsRades. IJROBP. 2008.
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Prognostic FactorsRades. IJROBP. 2008.
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Prognostic FactorsRades. IJROBP. 2008.
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OutlineTREATMENT TIME
• Historical Data• RPCI Experience pt 1
– 3‐4% per day over 50
• RPCI Experience pt 2– Preventing treatment prolongation works
TOBACCO• It is bad for you
– Bad during RT
• Quitting prior to RT
makes a BIGdifference
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Am Jn Clin Oncol. 2009.
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RPCI Study #1• 2004‐2007• 78 patients• Mostly male• Oropharynx,
larynx most common
• Treatment– Chemotherapy
AND– IMRT
# patients %Total 78Median age
(range)62
(37-81)Sex
Male 56 72%Female 22 28%
Tumor SiteOropharynx 42 54%Larynx 28 36%Hypopharynx 4 5%Oral Cavity 4 5%
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RPCI Study #1• H&N Cancers
– Mostly advanced• 51% T3 or T4• 55% N2 or N3
T Stage # %1 11 14%2 27 35%3 32 41%4 8 10%
N Stage0 25 32%1 10 13%2a 5 6%2b 21 27%2c 13 17%3 4 5%
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RPCI Study #1• Median follow‐up was 12 months. • Fifteen of 78 (19%) patients experienced loco‐regional failure. – 6 primary site failures, – 5 nodal/ regional failures, and – 4 failures in both the primary site and regional lymph nodes.
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RPCI Study #1• Loco‐regional failure variables
– Age– Sex– Disease site– Stage
– Baseline hemoglobin– Treatment interruption > 1 week
* Statistically significant – meaning high level of correlation with loco-regional failures
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RPCI Study #1• Low hemoglobin
– 7/19 (37%) failures
• Normal hemoglobin– 8/59 (14%) failures
P = 0.042
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RPCI Study #1• Interruption > 1 week
– 6/13 (46%) failures
• Interruption < 1 week– 9/65 (14%) failures
P = 0.015
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RPCI Study #1 : SummaryMore loco‐regional failures in H&N with• Low hemoglobin
– Not easily / realistically correctable
• Treatment interruptions– Easily Correctable!… but will it matter?
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OutlineTREATMENT TIME
• Historical Data• RPCI Experience pt 1
– 3‐4% per day over 50
• RPCI Experience pt 2– Preventing treatment prolongation works
TOBACCO• It is bad for you
– Bad during RT
• Quitting prior to RT
makes a BIGdifference
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Head and Neck. 2012.
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RPCI Study #2• 2007‐2010• 62 patients• Mostly male• Oropharynx, larynx
most common • Treatment
– Chemotherapy AND
– IMRT• Avoid treatment
interruptions
# patients %Total 62Median age
(range)59
(38-82)Sex
Male 51 82%Female 11 18%
Tumor SiteOropharynx 37 66%Larynx 14 25%Hypopharynx 5 9%Oral Cavity 0 0%
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Treatment Time at RPCI2004‐2007
(n = 78)
2007‐2009
(n = 62)
Local Control
Median RT duration (days)
51 (39‐83)
46 (38‐67)
81 vs 95%,P=0.01
Duration < 56 days 64 58 90%Duration > 56 days 14 4 61%
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Optimal Treatment TimeStart on a Monday!Sun Mo Tu We Th Fr Sat
1 2 3 4 5
6 7 8 9 10
11 12 13 14 15
16 17 18 19 20
21 22 23 24 25
26 27 28 29 30
31 32 33 34 35
Sun Mo Tu We Th Fr Sat
1 2 3
4 5 6 7 8
9 10 11 12 13
14 15 16 17 18
19 20 21 22 23
24 25 26 27 28
29 30 31 32 33
34 35
Treatment time = 49 daysTreatment time = 47 days
Up to 6 fx/week if needed
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RPCI Study #2• IMRT Prescription
– Total dose 70 Gy– 2 Gy per fraction– 35 treatments.
• Treatment time– 35 fractions (35 days) – 6 weekends (12 days)– Total time 47 days
Sun Mo Tu We Th Fr Sat
1 2 3 4 5
6 7 8 9 10
11 12 13 14 15
16 17 18 19 20
21 22 23 24 25
26 27 28 29 30
31 32 33 34 35
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OutlineTREATMENT TIME
• Historical Data• RPCI Experience pt 1
– 3‐4% per day over 50
• RPCI Experience pt 2– Preventing treatment prolongation works
TOBACCO• It is bad for you
– Bad during RT
• Quitting prior to RT
makes a BIGdifference
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RTOG 0129 – Post Hoc Analysis• Retrospective Analysis• Randomized Trial
– Stage III and IV Oropharyngeal cancer– Accelerated fractionation vs Standard fractionation
• 2002‐2005• 721 patients
– 323 patients had HPV status known.Ang KK, New England Journal of Medicine. 2010; 363, 24-35
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RTOG 0129 – Post Hoc Analysis
Ang KK, New England Journal of Medicine. 2010; 363, 24-35
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RTOG 0129 – Post Hoc Analysis
Ang KK, New England Journal of Medicine. 2010; 363, 24-35
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OutlineTREATMENT TIME
• Historical Data• RPCI Experience pt 1
– 3‐4% per day over 50
• RPCI Experience pt 2– Preventing treatment prolongation works
TOBACCO• It is bad for you
– Bad during RT
• Quitting prior to RT
makes a BIGdifference
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Effect of Smoking on H&N Ca
• Retrospective Study 1989 ‐2006• 1871 patients• All H&N disease sites• All stages• Follow up time approximately 3 years.
Fortin et al. Int. J. Radiation Oncology Biol. Phys., Vol. 74, No. 4, pp. 1062–1069, 2009
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Effect of Smoking on H&N Ca
Fortin et al. Int. J. Radiation Oncology Biol. Phys., Vol. 74, No. 4, pp. 1062–1069, 2009
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Effect of Smoking on H&N Ca
Fortin et al. Int. J. Radiation Oncology Biol. Phys., Vol. 74, No. 4, pp. 1062–1069, 2009
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Smoking During RT Bad OutcomeChen. Int Jn Radiat Oncol Biol Phys. 2011.
• Retrospective Study, case matched (1999‐2008)
• 202 patients• “Former smoker”
– anyone who quit anytime prior to RT
• Squamous cell cancer of– Oral cavity– Pharynx (Naso ‐ , Oro ‐ , Hypo ‐ )
– Larynx• Median follow up
– 49 months
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Smoking During RT Bad Outcome
Chen et al. Int. J. Radiation Oncology Biol. Phys., Vol. 79, No. 2, pp. 414–419, 2011
Ove
rall
Surv
ival
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Smoking During RT Bad Outcome
Chen et al. Int. J. Radiation Oncology Biol. Phys., Vol. 79, No. 2, pp. 414–419, 2011
Loco
-reg
iona
l Con
trol
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Smoking + RT = bad idea.
23%
50%Active
58%
67%Active FormerFormer
55%69%Chen (2011)
55%80%Fortin (2009)
5 yr OS5 yr LRC
Int Jn of Rad Onc Biol Phys
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OutlineTREATMENT TIME
• Historical Data• RPCI Experience pt 1
– 3‐4% per day over 50
• RPCI Experience pt 2– Preventing treatment prolongation works
TOBACCO• It is bad for you
– Bad during RT
• Quitting prior to RT
makes a BIGdifference
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120 pts
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HPV+ Never/FormerHPV- Never/Former
HPV+ Active smoker HPV- Active smoker
p<0.01 p<0.28
90% OS in those who quit 30 days prior to starting RT.
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OutlineTREATMENT TIME
• Historical Data• RPCI Experience pt 1
– 3‐4% per day over 50
• RPCI Experience pt 2– Preventing treatment prolongation works
TOBACCO• It is bad for you
– Bad during RT
• Quitting prior to RT
makes a BIGdifference
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CASE• 53 y/o man• T2N2cM0 Base of Tongue Cancer
• 40 pack years• HPV positive
• Smokes 1.5 ppd• Seen November 10• Because of work, wants to start on a wednesday
Can’t be changed
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CASE• Smokes 1.5 ppd• Seen November 10
• Because of work, wants to start on a wednesday
Smoking Cessation
Start on a Monday
TX 6 fx/wk wknd/bid to cmplete in 47d