Trattamenti stereo-RT e radiochirurgici come opzioni standard di trattamento: stato dell’arte in base a linee guida internazionali

Trattamenti stereo-RT e radiochirurgici
come opzioni standard di trattamento:
stato dell’arte in base a linee guida
internazionali
Silvia Chiesa, Alessandra Castelluccia, Barbara Diletto, Domenico Marchesano

Materials and MethodsMaterials and Methods

come opzioni standard di trattamento nei
tumori cerebrali primitivi:
internazionali

Enthusiasm for SRS
in low grade gliomas
has wanted due to
insufficient evidence
for therapeutic
advantage
No Evidence

At the diagnosis
SRS
GTV or CTV < 40mm
15-24 Gy (SRS) + 60 Gy (EBRT)
Conclusions:Conclusions: Stereotactic
radiosurgery followed by
EBRT and BCNU does not
improve the outcome in
patients
with GBM nor does it
change the general quality
of life or cognitive
functioning.
Randomized
RTOG 93-05

At the diagnosis
FSRT
CTV < 60mm
50 Gy (EBRT) +
20/28 Gy (FSRT) a 5/7 Gy/die
Conclusions:Conclusions: This first, multi-
institutional FSRT boost trial for
GBM was feasible and well tolerated.
There is no significant survival
benefit using this dose-intense RT
regimen. Subset analysis revealed a
trend toward improved outcome for
GTR patients suggesting that
patients with minimal disease
burden may benefit from this form of
accelerated RT.
Phase II
p=0.24
RTOG 00-23

REIRRADIAZIONE
Retrospective Studies

District Level I/
Category 1
Level II/
Category 2A
Level II/
Category 2B
Primary
Brain Tumors
None
-Adult Medulloblastoma and
Sopratentorial PNET:
residual/recurrent
-Gliomas: reirradiation in
selected patients
SummarySummary

come opzioni standard di trattamento nel
Metastasi Cerebrali/Vertebrali:
internazionali

PFS OS
CH + WBRTCH + WBRT
CH + WBRTCH + WBRT
WBRTWBRT
WBRTWBRT
p=0,02 p<.01
Category 1
WBRT: 36Gy in 12fr
GTR + WBRT vs
WBRT alone:
1 randomized study

Category 1
GTR + WBRT vs
GTR alone:
1 randomized study
p<,001 p<,001 p=,03

WBRT + SRS
should be
standard
treatment for
patients with a
single
unresectable
brain metastases
and considered
for patients with
two or three
brain metastases
WBRT 37,5Gy in 15fr
SRS 15-24Gy
SRS + WBRT vs
WBRT alone:
2 randomized studies
-RTOG 95-08
- Kondziolka et al, IJROBP 1999; 45:427-434
Category 1

SRS 18-25Gy
WBRT 30Gy in 10fr
+WBRT
-Did not improve
survival
-Reduce rate of new
mts
SRS alone vs
SRS +WBRT
1 randomized study
Category 1

+WBRT
-Did not improve
survival
-Reduce rate of new
mts

Level II-2-3
No Evidence
Level II-3
Retrospectives studies

District Level I/
Category 1
Level II/
Category 2A
Level II/
Category 2B
Brain/Spinal
Metastases
-1-3 lesions:
GTR + WBRT
-single lesion:
SRS + WBRT
-2-3 lesions: SRS + WBRT
-1-3 lesions: SRS alone
- Multiple lesions: SRS
- Recurrence or progression: SRS
-Spinal lesions at recurrence or in
case of intractabil pain
SummarySummary

Ongoing Trials
• RTOGRTOG
- RTOG 0671/0574- A Phase III Randomized Trial of the Role of Whole
Brain Radiation Therapy in Addition to Radiosurgery in the Management of
Patients with One to Three Cerebral Metastases
- RTOG 1270/NCCTG N107C – A Phase III Trial of Post-Surgical
Stereotactic Radiosurgery (SRS) Compared With Whole Brain Radiotherapy
(WBRT) for Resected Metastatic Brain Disease.
- RTOG 0631- A Phase II/III Study of Image Guided Stereotactic
Radiosurgery for Localized (1-3) Spine Metastasis: Phase II Results.
• EORTCEORTC: None: None

Trattamenti stereo-RT e
radiochirurgici come opzioni
standard di trattamento nelle lesioni
benigne intracraniche:
internazionali

PATIENT SELECTION
Large tumor
sympoms related to mass
Elderly, minimal symptoms
incidentally discovered tumors and no grow
Growth (size and location) SRS
SURGERY
OBSERVATION
SRS

District Level I Level II /
category 2a
Level II/
category 2b
Level III
Intracranial
benign lesions
None
-Primary Spinal
Cord Tumors:
recurrence
-Meningiomas:
small, residual,
recurrent
•Vestibular
schwannoma
•Pituitary
adenoma:
residual, recurrent
•Ependymoma: as
boos after EBRT
•AVM: small
•Trigeminal neuralgia: if
surgery not possible
SummarySummary

Trattamenti stereo-RT come opzioni
standard di trattamento nei tumori
polmonari NSCLC:
internazionali

SABR & LUNG CANCER :
WHEN? HOW?
WHY?

Early stage (I/II, N0):
• Medically inoperable
• High surgical risk
(eg. age 75 years or older, poor lung function)
Locoregional recurrence
Limited lung metastases
WHEN?

• early stage - medically inoperable
Eligibility Criteria
Stage I or II disease based on 1 of the following tumor node metastasis
(TNM) stage criteria
•T1, N0, M0
•T2 (≤ 5 cm), N0, M0
•T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only)
•No primary tumor of any T-stage within or touching the zone of the
proximal bronchial tree* NOTE: *Defined as a volume 2 cm in all directions
around the proximal bronchial tree
Deemed medically inoperable based on pulmonary function for
surgical resection of NSCLC secondary to an underlying physiological
problem
RTOG 0236 Protocol Information
A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients with Medically Inoperable Stage I/II Non-Small Cell Lung Cancer
Patients receive 3 fractions of stereotactic body radiotherapy over 8-14 days (18 Gy x 3fr, 54
Gy total) in the absence of disease progression or unacceptable toxicity.
The primary endpoint of this study was local control.
Secondary endpoints included disease free survival, overall survival, and toxicity.

SABR & LUNG CANCER
JAMA. 2010 March 17; 303(11): 1070–1076.
Timmerman R,; Paulus R,; Galvin J,; et al.
Results
Local control
•3-year primary tumor control rate: 97.6% (95%
CI, 84.3%-99.7%).
•median overall survival : 48.1 months (95% CI,
29.6 months to not reached)
Toxicity
•grade 3 adverse events : 12.7% (95% CI, 9.6%-
15.8%)
4.5%)
•No grade 5 adverse events were reported
•Disease-free survival
at 3 years : 48.3%
•Overall survival at 3
years : 55.8%

SABR & LUNG CANCER
JAMA. 2010 March 17; 303(11): 1070–1076.
Timmerman R,; Paulus R,; Galvin J,; et al.
•Disease-free survival
at 3 years : 48.3%
•Overall survival at 3
years : 55.8%
Results
Local control
•3-year primary tumor control rate: 97.6% (95%
CI, 84.3%-99.7%).
•median overall survival : 48.1 months (95% CI,
29.6 months to not reached)
Toxicity
15.8%)
4.5%)
•No grade 5 adverse events were reported

• early stage - medically inoperable/refused

• early stage - medically inoperable/refused
Toxicity
• Sixteen patients (28%) experienced grade
3 toxicity
• 1 pt had grade 4 dyspnea at 36 months
• No patient was lethally affected by SBRT
• Fourteen patients (25%) had no
pulmonary adverse effects

Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1060-70.
• early stage - high risk patients

Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1060-70.
Shirvani S.M. et al.

WHEN?
Category 2A

V5
Risk-adapted SBRT fractionation
schemes were based on PTV size
and degree of overlap between
areas from conventionally
fractionated RT and SBRT

•Limited lung metastases
1-3 lung metastases, < 7 cm.
Dose escalation : 48 - 60 Gy/ 3fr
The primary end point was local control.
Secondary end points included toxicity and survival.
3/38 pt
Median survival was 19 months.

.
Category 2A
1-3 lung metastases, < 7 cm.
Dose escalation : 48 - 60 Gy/ 3fr

SABR & LUNG CANCER:
Fractionation schedule
• Local control
J Thorac Oncol. 2007 Jul;2(7 Suppl 3):S94-100.
Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, Niibe Y, Karasawa K, Hayakawa K, Takai
Y, Kimura T, Takeda A, Ouchi A, Hareyama M, Kokubo M,Hara R, Itami J, Yamada K, Araki T.
METHODS:
This is a retrospective study to review 257 patients with
stage I NSCLC (median age, 74 years: 164 T1N0M0, 93
T2N0M0) were treated with HypoFXSRT alone at 14
institutions. Stereotactic three-dimensional treatment
was performed using noncoplanar dynamic arcs or
multiple static ports. A total dose of 18 to 75 Gy at the
isocenter was administered in one to 22 fractions. The
median calculated biological effective dose (BED) was
111 Gy (range, 57-180 Gy) based on alpha/beta = 10.
Overall
survival
rate in
operable
patients
Local
control
rate
BED≥100
improves
LC and OS

Toxicity
•No side effects: 105/219 pt
•Grade ≥ 3 radiation
pneumonitis: 6/219pt
•Rib fractures: 4/219 pt
•Chronic toracic pain
syndromes: 3/219 pt

Fractionation schedule
• Toxicity
BED3
<210 Gy reduce the risk of death by approximately 75%
Senthi S et al. Outcomes of stereotactic ablative radiotherapy for central lung tumours: a systematic review.Radiother Oncol. 2013 Mar;106(3):276-82

ONGOING TRIALS
RTOG 0813
Phase I/II study of SBRT for early stage
centrally located NSCLC in medically
inoperable patients
RTOG 0915
A Randomized Phase II Study Comparing 2 Stereotactic Body Radiation
Therapy (SBRT) Schedules for Medically Inoperable Patients with Stage I
Peripheral Non-Small Cell Lung Cancer
RTOG 0618
A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the
Treatment of Patients with Operable Stage I/II Non-Small Cell Lung Cancer
This study is ongoing, but not recruiting participants
Active, not recruiting
Active, not recruiting

District Level I/
Category 1
Level II/
Category 2A
Level II/
Category 2B
Lung NSCLC
None
•Early stage (I/II, N0):
Medically inoperable
High surgical risk
•Locoregional recurrence
None
SummarySummary

standard di trattamento nell’
Epatocarcinoma:
internazionali

: Transaterial bland embolization (TAE), Transarterial
Chemoembolization (TACE) and radioembolization with
Yttrium-90 microsperes

At IUSCC…
Percutaneus
ethanol injection
Radiofrequency
ablation
TACE SBRT
(At time of
trasplant)
2-year Local
Control rate
70-85%
Lesion <3cm = 85-98%
Lesion >3cm = ≤ 80%
60-70%
Median tumor
(3,2 cm)=
90%

standard di trattamento nelle
Metastasi epatiche:
internazionali

• 69 Patients with 174 metstatic liver lesions
• Median toral dose of 48 Gy
• Dose for fraction = 2 – 6 Gy
• 69 Patients with 174 metstatic liver lesions
• Median toral dose of 48 Gy
• Dose for fraction = 2 – 6 Gy
RESULTS
10-months Overall infiel Local
Control
76%
20-months Overall infiel Local
Control
57%
Median Overall Survival time 14.5 months
6-m0nths Progression-Free
Survival
46%
12-m0nths Progression-Free
Survival
24%
Patients developed grade ≥ 3
toxicity
0

Adenocarcinoma Pancreatico:
internazionali

PRO
6-months Overall Local Control =
91 %
12-months Overall Local Control =
84%
• Retrospective study
• 77 Patients
• Unresectable
• SBRT = 25 Gy in 1 Fraction

CONS
6-months late grade ≥2 toxicity =
11 %
12-months late grade ≥2 toxicity =
25%
• Retrospective study
• 77 Patients
• Unresectable
• SBRT = 25 Gy in 1 Fraction

Adenocarcinoma Prostatico:
internazionali

Summary
District Level I/
Category 1
Level II/
Category 2A
Level II/
Category 2B
Level III
Category 3
Primary Brain
Tumors
None
-Adult Medulloblastoma and
Sopratentorial PNET:
residual/recurrent
-Gliomas: reirradiation in selected patients
Brain/Spinal
Metastases
-1-3 lesions:
GTR + WBRT
-single lesion:
SRS + WBRT
-2-3 lesions: SRS + WBRT
-1-3 lesions: SRS alone
- Multiple lesions: SRS
-Spinal lesions at recurrence or in
case of intractabile pain
Intracranial
Benign Lesions
-Meningiomi: residual7recurrent
• Vestibular schwannoma
•Pituitary adenoma
•Ependimomi: as boost after EBRT
•AVM: small
•Trigeminal neuralgia: if surgery not
possible
Lung None
•Early stage (I/II, N0):
Medically inoperable
High surgical risk
•Locoregional recurrence
None
Abdomen None -None
HCC: unresectable, locally advanced,
recurrence
Pancreatic Adenocarcioma: unresectable,
advanced
Liver metastases
Prostate None -None
Low risk
Localized
None

Trattamenti stereo-RT e radiochirurgici come opzioni standard di trattamento: stato dell’arte in base a linee guida internazionali

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