possibilities and perils of re-rt

1. RETREATMENT AFTER RADIOTHERAPY:
THE POSSIBILITIES AND THE PERILS
Presented By- Dr. Rashmi Yadav
Moderated By- Dr. Ayush Garg

2. HISTORY OF RE-IRRADIATION
• 1918 - 1931 Patients of Cervix were Re-irradiated for the first time, but no survival
benefit was observed.
• 1940 - 1956 Patients of Nasopharynx were re-irradiated with EBRT /Brachy or bot.
Some survival advantage but side effects like soft tissue necrosis
and ORN were observed.
• 1965 Karmer- Summarized factors to be considered during Re-RT
a) The natural history of the tumor
b) Tumor extent, the normal tissue tolerance
c) Details of previous treatment
d) Present objectives of the proposed Re-RT
e) Any chances of geographical miss
f) Radio-resistance of tumor.
He Concluded:
Re-RT has a definite role
but only in selected
patients.

3. CAUSES OF RECURRENCE
1. Continued life style
2. Genetic predisposition
3. Treatment induced second malignancies

5. FACTOR’S EFFECTING RE-IRRADIATION
• The single-most important factor in planning re-irradiation is the ability using these
techniques to determine the doses to various tissues in the irradiated volume.
• Tolerance, and these may include residual tissue injury present (the presence of
residual stem or corrective cell depletion still present in the tissue);
• The interval between the two courses of radiation which will determine the extent of
tissue regeneration;
• The volume of tissue required to undergo re-irradiation;
• Fractionation schedule used in before course

6. • It is important to first calculate the expected dose received from the previous
course of radiation to all normal structures in the volume expected to be
irradiated (calculation should be for late effects, i.e., Biological equivalent dose
(BED) for 3 Gy fraction size or BED 3gy) before prescribing a fresh course of
radiation therapy.
• In the re-irradiated volume also, the normal tissues can be divided into early
reacting (skin, mucosa, lung, and intestine) and late reacting (muscle,
connective tissue, vasculature, brain, spinal cord, brainstem, lungs, heart,
bladder, and kidney).

7. WHEN CONSIDERING RETREATMENT WITH
RADIATION FACTORS MUST BE TAKEN INTO
ACCOUNT
1. The dose and volume treated during the initial radiotherapy and the extent to
which the re- treatment fields overlap with the initial fields
2. Whether chemotherapy was added to the initial radiotherapy
3. The time interval that has elapsed since the initial radiotherapy
4. The tissues and organs involved because they differ markedly in their ability to
recover
5. Highly conformal techniques, such as stereotactic radiosurgery, stereotactic body
radio- therapy (SBRT), or brachytherapy, are most appropriate.
6. Whether there are alternative options to radiation that could be considered

10. CONCEPT OF BED, EQD2 & RELATIVE EFFECTIVENESS
• RE : Relative Effectiveness
• BED: Biological Effective dose
• EQD2: 2 Gy Equivalent dose
BED = nd 1 + d
α/β
EQD2 = BED/ RE
RE = 1 + d
α/β

15. EARLY- AND LATE-RESPONDING
TISSUES

19. ORGANS RE-RT & TOLERANCE
Brain
Spinal cord
Head and Neck
Breast
Lungs
Rectum
Blood vessels
Bone metastasis
Recurrent Vaginal metastasis

20. BRAIN
• Data mainly relates to temporal lobe injury.
• Re-irradiation of brain is a viable alternative compared to surgery without any negative
impact on QOL.
• No standard recommendation or imaging modality to be used.
• PRV of the OARs to be given – 3 mm.
• Radiation modalities:
1. Brachytherapy with Au & I 125 (40 – 64 Gy)
2. Radiosurgery –SRS (13-20 Gy)
3. Hypo-fractionated SRT (20 -50 Gy)
4. Conventional fractionation (35 -45 Gy)
• No correlation between the time of Re-RT & necrosis

21. RE-RT OF BRAIN

22. BRAINSTEM
• At risk of being radiated during re-irradiation of tumor involving
nasopharynx and brain tumors.
• The tolerance to cumulative dose increases further with increase in
interval between the primary radiation and re-irradiation.

23. SPINAL CORD
• Major dose-limiting organ
• When initial radiation therapy is delivered in conventional 2 gy per day
fractions, the consensus is that the incidence of myelopathy is less than 1%
for total doses of 50 to 55 gy,
• Up to 5% for total doses of 55 to 60 gy.
• The authors conclude that sbrt is both safe and effective in the
palliative/retreatment setting.
• Clinical data are very sparse in terms of toxicity and tolerance of spinal cord
re-irradiation.

24. • The most important side effect is myelopathy.
• Many primitive Re-RT effects of spinal cord showed myelopathy.
• If Initial RT of 46 Gy @ 2 Gy/# was given, it might be followed by
a) 23 -24 Gy @ 2Gy/#, 1-2 yrs after initial RT.
b) 24 Gy in 3#s with SBRT without unacceptable toxicities.
• Risk of myelopathy increases if :
1. Cumulative dose increases (max <70 Gy)
2. Time interval < 6 months.
SBRT
Sahagal et al. provided a
recommendation of
presumably safe
stereotactic Re-RT doses
after initial conventional
RT
1. Thecal sac point max
EQD2 – 20-25 Gy
2. Total max EQD2 – 70
RE-RT OF SPINAL CORD

26. HEAD AND NECK IRRADIATION
• The target volume and field size is the most significant factor in
determining tissue tolerance; elective volume irradiation is not
recommended
• Prominent late sequelae of re-irradiation to the head and neck
region include soft-tissue fibrosis, carotid blowouts (discussed
further), cartilage necrosis, osteoradionecrosis (ORN) especially
of the mandible, and arytenoid edema.

27. RE-RT IN HEAD & NECK TUMORS
• The OS of pts with H&N tumors is increasing with newer modalities of
t/t.
• CTRT in Re-RT schedule is not tolerated , therefore must be avoided.
• For best results:
1. Target volumes should be kept tight.
2. Elective nodal irradiation should be avoided to minimize severe toxicity.
• Re-RT doses of 50-60 Gy is effective than lower doses.
• A total cumulative dose upto 116 Gy in both the courses is acceptable.
• Higher modalities like IMRT, IGRT or Brachytherapy is better for Re-RT.

28. AORTA AND GREAT VESSELS
• New techniques such as IMRT or SRT have helped achieve these dose
targets while sparing the organs at risk in the thorax.
• The carotid blowout syndrome (CBOS) is a much-discussed side effect of
radiation, especially in HNC radiotherapy.

29. RE-RT AND BLOOD VESSELS
• High dose Re-RT identified large arteries as OARs.
• Studies showed that large artery toxicities developed in 25% of pts who received a
cumulative dose of >/=120 Gy.
• CBOS: Carotid Blow Out Syndrome, is seen in pts after 4-5 mts of Re-RT.
• To assess the risk of CBOs an index was developed called CBOS index which
includes:(with 0-3 points)
1. Carotid invasion >180 degrees.
2. Presence of ulceration,
3. LN area Re-RT.

31. LUNGS
• Radiation pneumonitis is a common side effect of irradiation to
the lung
• Due to limited survival after relapse and re-irradiation of lung
tumors, there are sparse data on re-irradiation.

32. RE-RT IN LUNGS
• Large pt data is not available but with the available small studies the authors conclude that
such Re-RT resulted in a symptomatic benefit in most patients but at a cost of substantial
toxicity.
• Most patients succumbed to their disease before the serious late effect of lung fibrosis
could be expressed.
• Proton therapy, characterized by a well-defined localized high-dose region, would seem to
be the logical way to approach Re-RT of recurrent lung cancer.
• When protons are not available, a highly conformal technique such as SBRT may give
improved results.
• Data of Trachea, Bronchi & oesophagus are lacking.

33. HEART
• The cardiac tolerance dose was defined as the dose causing at
least 50% function loss (ED50).

34. RE-RT IN BREAST
• For prior BCS pts – 5 to 10% of pt have recurrence after 10yrs of BCS+WBRT
• Salvage mastectomy is the std of care for IBRT with a LRR – 10%.
• But pts who are not fit for mastectomy or refusing for the Sx we can offer BCS +
Re-RT of breast with a LRR- 40%.
• For prior MRM pts -25% of pts have recurrence at 10 yrs after prior course.
• Re-RT can be offered by:
1. Electron beam (CR seen in 40-75% pts).
2. Photon beam
3. IORT
4. Brachytherapy- LDR, HDR, PDR (brachytherapy offers the best LRC &OS with
good cosmosis than others with CR rate of 80%)
Durable LRC ins more often
achieved in pts with axillary nodal
involvement only and Re-Rt
improves LRC and should be
applied wherever feasible.

39. RE-RT IN VAGINAL METASTASIS
• Studies concluded that Re-RT for late recurrence in vagina after previous Rt for
cervix ca, is a valuable option in selected Pts.
• Small tumor volume and brachytherapy give best results.
• Radiotherapy has been an accepted form of treatment for decades, but when there
is recurrent or persistent disease after a full course of radiation, the best option is
radical surgery, which can result in a 5-year survival rate in excess of 60% (Rubin et
al.).
• When this is not possible, Re-RT has been used in the past as an alternate, but both
local control and survival rates were poor, although there was a significant rate of
complications.

41. RE-RT IN BONE METASTASIS
• Available chemical data support the Re-Rt of sites of bone pain after
Initial RT, particularly when this follows an initial period of response
• Pts who respond to initial RT to bone usually respond to Re-RT to
bone.

42. CONCLUSION
• In the present day, the possibility of re-irradiation has increased due
to the availability of image guidance, IMRT, etc., but at the same time
the risk-benefit ratio should be considered before deciding on the
treatment.
• The performance status and availability and feasibility of other less
toxic treatment alternatives should also be taken into consideration
• The knowledge of previous radiation field, portals, dose per fraction,
technique, dose distribution, and exact dose of critical organs are
important determinants in prescribing dose and volume for re-
irradiation
• Many acutely reacting tissues such as skin and mucosa usually
recover early after first dose of radiation and tolerate re-irradiation

43. SUMMARY
• Of patients presenting at major cancer centers in the Western World, 10%
present with a second cancer.
• If the radiation tolerance of a given organ or tissue was exceeded by the
initial treatment to the extent that function is lost, or is in process of being
lost, then retreatment cannot be contemplated safely.
• If the normal tissue tolerance was not exceeded by the initial treatment,
some reirradiation at a later date is safe, varying very much with the tissue
or organ involved and depending on other factors.
• In general, early-responding tissues recover and tolerate retreatment better
than late-responding tissues, but there are exceptions.

44. • Radiation-induced skin damage recovers well, with restoration of
almost full radiation tolerance. Recovery is slower after larger doses.
• Poorer retreatment tolerance for fibrosis.
• Retreatment with reduced doses is possible in both lung and spinal
cord. There is much data for spinal cord in both rodents and
monkeys.
• Kidney and bladder are not capable of recovery from late functional
damage.

45. • Most clinical studies involve small numbers of patients, variable doses, and
various time intervals between the initial treatment and reirradiation.
• Reirradiation is possible in various sites with reduced doses and with a high price
in terms of morbidity.
• Most data are for head and neck. Reirradiation with 50 to 60 Gy within a few years
of the initial treatment improves local control and possibly survival, but with severe
toxicity and functional sequelae.
• Studies using IMRT or, better still, pro- tons to reduce the volume of normal tissue
exposed, as well as hyperfractionation to spare normal tissues, may be called for
in the future, but no data are available at the present time.

46. THANK YOU