Role of Altered Fractionation in H&N Cancers

1. Role of Altered fractionation in Head & Neck
carcinoma
Dr Rakesh Jadhav
Consultant radiation oncologist
HCG cancer centre
Vadodara

2. Head and Neck
Squamous Cell Carcinoma
• Accounts for about 3,00,373 cases worldwide*
• 1,45,353 estimated deaths per year worldwide
• World-wide 6th most common
• Most common cancer of males in India and the
fifth most common in females
*GLOBOCAN-IARC, 2012
Head and Neck Cancers in Developing Countries; April 2014 Volume 5 Issue 2 e0009

3. General Management Guidelines for H & N Cancers
AIM
Highest loco- regional control
Anatomical with functional Preservation
• Stage I / II disease - Single modality ( Surgery or RT )
• Stage III / IV disease – Combined modality
▪ Sx→ RT
▪ Sx →CT + RT
• When different modalities available, one with maximum chance of cure should
be used
• When different modalities have same results, one offering better quality of life,
with organ, function preservation and good cosmetic results should be used

4. Patterns of failure
• Loco regional failure 80 - 90 %
• Distant Mets &
Second Primary 10 - 20 %
Head & Neck Cancer

5. Biological Basis Fractionation
Repair of Sublethal Damage
Reassortment / Redistribution
Reoxygenation
Repopulation

6. ALTERED FRACTIONATION:
IMPORTANT FACTORS
• Total dose (D)
• Dose per fraction (d)
• Interval between fractions (t)
• Overall treatment time (T)
• Tumor type
• Acute reacting normal tissues
• Late reacting normal tissues

7. • Conventional fractionation
– Daily doses (d) of 1.8 to 2 Gy
– Dose per week of 9 to 10 Gy
– Total dose (D) of 60 to 70 Gy
• Hyperfractionation- Defined as keeping the same total
dose in the same overall time but delivering it in twice
as many fractions by the expedient of treating twice
per day.
– The number of fractions (N) is increased
– T is kept the same
– Dose per fraction (d) less than 1.8 Gy
– Two fractions per day (t)
Rationale: Spares late responding tissues
Accelerated Fractionation- Defined as the same total dose
delivered in half the overall time by the expedient of giving
two or more fractions each day.
Strategy is to reduce repopulation in rapidly proliferating
tumors.

8. Conventional
70 Gy - 35 fx - 7 wks
Moderately accelerated
72 Gy - 42 fx - 6 wks
Hyperfractionated
81.6 Gy - 68 fx - 7 wks

9. EORTC 22791
• A hyperfractionated schedule of 80.5 Gy delivered in 70 fractions
(1.15 Gy twice per day) over a period of 7 weeks was compared
with a conventional regimen of 70 Gy delivered in 35 fractions of 2
Gy over 7 weeks
• Local tumor control at 5 years was increased from 40% with the
conventional regimen to 59% with hyperfractionation, and this was
reflected in improved survival.
• There was no increase reported in late effects or complications. It
was concluded that hyperfractionation confers an unequivocal
advantage in the treatment of oropharyngeal cancer

10. Oropharyngeal Ca T2-3, N0-1
Years
LOCAL CONTROL SURVIVAL
Years
Horiot 1992
80.5 Gy - 70 fx - 7 wks control: 70 Gy - 35-40 fx - 7-8 wks
p = 0.02
p = 0.08
EORTC hyperfractionation trial in oropharynx cancer (N =
356)

11. DAHANCA(DANISH HEAD & NECK
CANCER COLLABERATIVE GROUP)
TRIALS
• ILLUSTRATES THE IMPORTANCE OF OVERALL TREATMENT
TIME.
• All three trials involved a total dose of 66 to 68 Gy. The first
trial was of a split course regimen that extended overall
total of 9.5 weeks. The 3-year local control was 32%.
• The second trial involved five fractions per week over a
treatment time of 6.5 weeks, with a 3-year local control of
52%.
• The third trial included six fractions per week, reducing the
overall treatment time to 5.5 weeks and improving the 3-
year local control to 62%.

13. DAHANCA 6: only glottic, (N = 694)
DAHANCA 7: all other sites, + nimorazole (N = 791)
Overgaard 2000
66-68 Gy - 33-34 fx - 6 wks control: 66-68 Gy - 33-34 fx - 7 wks
Actuarial 5-year rates
Local control
DAHANCA 6
DAHANCA 7
Nodal control
DAHANCA 6 + 7 .
Disease-specific survival
DAHANCA 6 + 7
Overall survival
Late effects (edema, fibrosis)
Moderately Accelerated
5 fx/wk 6 fx/wk
73% 81% p=0.04
56% 68% p=0.009
87% 89% n.s.
65% 72% p=0.04
n.s.
n.s.

14. Conclusions for HNSCC
• Hyperfractionation increases TCP and protects late
responding tissues
• Accelerated treatment increase TCP but also increases
acute toxicity
• In principle, tumors should be treated for an overall
treatment time that is as short as possible consistent with
acceptable acute morbidity, but with a dose per fraction that
does not compromise late responding normal tissues, or
total dose

15. HYPOFRACTIONATION
• SMALLER NUMBER OF LARGER DOSE FRACTIONS.
• RATIONALE:
• In the special case of prostate cancer, the ALPHA/BETA ratio is low,
in the region of 2 to 3—more similar to late-responding normal
tissues than to tumors. This essentially removes the basic rationale
for a multi-fraction regimen of 35 or more fractions.
• In Head and Neck cancer Hypo-fractionation is used in
-Early Glottic Larynx
-Palliative Settings

17. 5-year local control rates after radiotherapy were 76% for Arm A-1, 78% for Arm A-2,
91% for Arm B-1, and 92% for Arm B-2

20. Ultimate local control rates (including successful salvage treatment) were:
Overall 97.3 %, T1a 100 %, T1b 93.8 % and T2% 95.8 %.

25. Conclusions
We were able to reduce equipotent total fractions of SBRT from 15 to 5 without exceeding
protocol-defined acute/subacute toxicity limits. With limited follow-up, disease control appears comparable to standard
treatment. We continue to enroll to the 42.5 Gy/5 fx cohort and follow patients for late toxicity.

29. At our hospital we use a protocol that includes
Total dose 14.8Gy/4 fractions @ 3.7Gy /#/day over
4 days & repeat it after 3-4 weeks gap for total 3
cycles. (Total dose 44.4Gy/12#)
And in between the gap patient takes Tab.Gefitinib
250mg od.

30. Case 1
42 yr old male diagnosed case of Recurrent Adenocystic carcinoma Lt parotid gland with Lung mets
Received chemotherapy (Pacli+ Carbo)-→ Progressive disease→ Ref for Palliative RT

34. Case 2
50 yr Male diagnosed case of Ca Lt oropharynx with Lt level II N3 node→ Ref for
Palliative RT

38. FUTURE DIRECTIONS
• MORE KNOWLEDGE OF RADIOBIOLOGY CAN GIVE US INSIGHTS
TO THE APPROPRIATE USE OF FRACTIONATION IN THE
TREATMENT OF CANCER.
• MORE TRIALS USING BIOLOGICAL RESPONSE MODIFIERS
ALONG WITH RT CAN ENHANCE THE TUMOR CONTROL WITH
DECREASED NORMAL TISSUE TOXICITIES.

39. Thank you