Radiation Therapy Workshop:Current knowledge on fraction size

Josep IsernHospital de la Santa Creu i Sant Pau, Barcelona

Current standard (outside prospective clinical trials):

1.8-2 Gy per fraction once-daily50-50.4Gy total doseIMRT highly preferred for most cases 5-6 weeks overall treatment time

FROM:NCIC SR-2

For preoperative RT

1.8-2 Gy per fraction once-daily50-50.4Gy total doseIMRT highly preferred for most cases 5-6 weeks overall treatment time

“several” weeks delay / rest

FROM:NCIC SR-2

1.8-2 Gy per fraction once-daily50-50.4Gy total doseIMRT highly preferred for most cases 5-6 weeks overall treatment time

“several” weeks delay / rest

definitive surgery

FROM:NCIC SR-2

1.8-2 Gy per fraction once-daily50-50.4Gy total doseIMRT highly preferred for most cases 5-6 weeks overall treatment time

“several” weeks delay / rest

definitive surgery

From AP data: boost ?¿?¿?

FROM:NCIC SR-2

If you want different results, do not do the same things

Current challenges in sarcoma radiation:

1. NO RADIATION

Current challenges in sarcoma radiation:

1. NO RADIATION2. FRACTION SIZE, DOSE and OVERALL TREATMENT

Current challenges in sarcoma radiation:

1. NO RADIATION2. FRACTION SIZE, DOSE and OVERALL TREATMENT3. COMBINED MODALITY REGIMENS

1. CONVENTIONAL CHEMOTHERAPY2. TARGETED AGENTS, IMMUNOLOGICAL …..

Current challenges in sarcoma radiation:

1. NO RADIATION2. FRACTION SIZE, DOSE and OVERALL TREATMENT3. COMBINED MODALITY REGIMENS

1. CONVENTIONAL CHEMOTHERAPY2. TARGETED AGENTS, IMMUNOLOGICAL …..

FRACTION SIZE

FRACTION SIZE,

Fraction size

.

Fraction size

However, no long-term follow up data on late functional sequelae are available from these 3 studies.

FRACTION SIZE

Fraction size

.

Fraction size

.By further reducing the fraction size from 3.5 Gy to 3 Gy, they were able to reduce the wound complication rate to 15%, while maintaining local control at 97% at 5 years follow up.

FRACTION SIZE, TOTAL DOSE and OVERALL TREATMENT

FRACTION SIZE, TOTAL DOSE and OVERALL TREATMENT

Fraction size

Fraction size

Phase II clinical trial: which may be on the lower level of acceptable local control.

Local controllocal

control

(%)

Local controllocal

control

(%)

Local controllocal

control

(%)

effect of

surgery

Local controllocal

control

(%)

effect of

surgery

“gain” by RT

Local controllocal

control

(%)

Local controllocal

control

(%)

Local controllocal

control

(%)

:

SOME RADIOBIOLOGICAL CONSIDERATIONS ARISE FROM THE RESULTS OF THE STUDIES PREVIOUSLY EXPOSED:

*

SOME RADIOBIOLOGICAL CONSIDERATIONS:

• Although the α/β ratio for the different sarcoma subtypes is unknown, it is possible that the value is below 10 Gy .

• One of the biological characteristics of sarcoma cells is their relatively low (-0.5 to 5.4) α/β ratio*. (most accepted 4 α/β ratio)

• This ratio, theoretically, may justify the use of larger-than-standard fractionation in order to achieve significant cell kill by RT.

*Joiner MC, Van der Kogel AJ. The linearquadratic approach to fractionation and calculation of isoeffect relationships. In: Steel GG, ed. Basic clinical radiobiology. New York,NY: Oxford University Press; 1997. pp. 106–12.

SOME RADIOBIOLOGICAL CONSIDERATIONS:

• BED DOSES.

*

SOME RADIOBIOLOGICAL CONSIDERATIONS:

Haas et alRadiother Oncol. 2016 April ; 119(1): 14–21.

.

A hypothetical local control probability curve, for simplification, calculated by: S = exp(− [αD + βD2]).

SOME RADIOBIOLOGICAL CONSIDERATIONS:

Haas et alRadiother Oncol. 2016 April ; 119(1): 14–21.

.

New approach....

• Ryan and colleagues reported on a series of 25 patients treated with the University of California Los Angeles:

• Hypofracctionated RT regimen (3.5Gy × 8) and dose-intense epirubicin and ifosfamide for three preoperative and three postoperative cycles

Results: • Local control: 88% (95% CI, 71–100%)• 95% pathologic necrosis rate of 40% (95% CI, 21–

59%).• The estimated 2-year rate for overall DFS was

62% (95%CI, 37–86%).• However, the regimen was too toxic, with 84%

predominantly hematologic grade 4 toxicities.• But, 20% wound complications actual rate who is

consistent with SR-2 Trial rates

• Investigators from the University of Calgary in Alberta, Canada, have published their experience with a “modified Eilber” protocol in 52 consecutive patients:

• Sequential intravenous doxorubicin for 3 days with 3 Gy × 10 (30 Gy) starting on the last day of chemotherapy.

Results

• They showed a 13.5% major wound complication rate and very good functional outcomes.

• No results about local control or survival

And adjuvant ?

• 21 elderly patients were treated with a short course of adjuvant RT

• Hypofractionated i regimen of 39–48 Gy in 13–16 fractions.( 3 G/fr)

Results:

• At a mean 26 months of follow-up.• Local control: 86 %• The hypofractionated radiation was well

tolerated with minimum long-term side effects.

CONCLUSIONS• Hypofractionated regimens delivered in eight

to 10 fractions, of 3-3,5 Gy, compared with conventional RT delivered in 25 fractions are the patient convenience of fewer treatments and associated reduced treatment cost.

• Although not yet proven, there are the potential appeals of increased treatment efficacy and/or decreased wound complication rates.