This ppt is for role of SBRT in head and neck cancer.

1. SBRT in Head and Neck
Cancer Workflow &
indication
Dr Rushi Panchal, MD
Consultant Radiation Oncologist
M S Patel Cancer Centre,
Shree Krishna Hospital,
Karamsad-Anand, Gujarat
Email id: rusp2582@gmail.com
Mob no: 09727757165

2. SBRT
• Extra cranial Radiosurgery
• Role in Primary case of Ca Lung/Prostate/Pancreas
• Role in oligo-metastatic disease of spine/lung/liver/adrenal
• Emerging data on head and neck cancer

3. SBRT in H&N Cancer
• Indications
• Efficacy
• Toxicity profile
• QoL
• Fractionation
• Target Definition
• Constrains
• Role of Cetuximab

4. Prospects in H & N Ca
• Salvage option for unresectable recurrent,
previously irradiated SHNC.
• Definitive treatment of 2nd
primary –
unresectable & heavily irradiated earlier.
• Palliative radiotherapy metastasis to head
and neck region from primary GI/Breast
Cancer.

5. SBRT as re-irradiation
• Rate of severe late toxicity of re-irradiation major
concern because of poor tolerance of previous irradiated
tissue.
• SBRT has become an attractive alternative for the
retreatment of patients with rSCCHN because of the
highly conformal dose distribution(high precision of
localization & delivery to target and small volume of
normal tissue irradiated) as compared to 3D/IMRT intern
causes less side effects, and delivered in the outpatient
setting over 1 to 2 weeks as opposed to 3D/IMRT that last
for 6-7week ( not be ethically compatible with expected
survival for most patient).

7. PH-I Study
•All patients were treated to the 80% isodose line, which
was intended to cover >90% of the target volume
•Critical structure constraints were as follows:
spinal cord maximum dose: <8 Gy; larynx: < 20 Gy;
mandible: < 20 Gy; parotid: variable; brainstem: <8 Gy; oral
cavity: variable
Heron et al. IJROBP 2009

8. In the present study, we found that in
the short term SBRT was feasible and
safe. The overall response
rate in this group of heavily pre-treated
patients was 28% (CR + PR).
No Grade 3 or 4 toxicities were noted
among our patients.
Metabolic response may
precede anatomic response
seen on CT good agreement
between PET and CT for the
assessment of CR and PD.
Heron et al. IJROBP 2009

9. Heron et al. IJROBP 2009

10. Heron et al. IJROBP 2009

11. Vargo et al, IJROBP 2015
•This ph I study evaluated the feasibility of dose escalation in
rSCCHN and met its accrual without dose-limiting toxicity at
8.8 Gy per fraction to 44 Gy in 5 fractions However, survival
and durable control remained suboptimal.
•Therapy began with a loading dose of cetuximab, 400
mg/m2, intravenous (IV) infusion over 120 minutes on day - 7
and then 250 mg/m2 on days 0 and +8 during the SBRT
course.

12. • Tumors <25 cc received 8.0 Gy per fraction for 5 fractions to 40 Gy;
tumours >25 cc received 8.8 Gy per fractions for 5 fractions to 44
Gy
• Prescription IDL were chosen to at least encompass 95% of the
PTV with no more than 20% of any PTV receiving doses >110% of
the prescribed dose, no more than 2% of any PTV receiving <93%
of the prescribed dose, and no more than 5% of any normal tissue
receiving doses in excess of 110% of the primary PTV dose.
• cumulative spinal cord dose not exceed 50 Gy at the equivalent
dose of 2 Gy per fraction, whereas the remaining normal tissues be
constrained as much as possible without compromising the target
volume on a case-by-case determination
Ph-II Study
Vargo et al, IJROBP 2015

13. • GTV-to-PTV expansion(3-5mm), PTV volumes were often reduced
from the skin to account for the dose build-up region in plan
optimization and, might elect to reduce the PTV expansion in
proximity to surrounding serial critical organs to prevent
circumferential treatment of adjacent critical organs.
• Daily image guidance is mandatory, with each fraction either by
cone beam CT or the 6-dimensional skull-based or X-sight tracking
system
Ph-II Study
Vargo et al, IJROBP 2015

14. 1-year local PFS was 60%
1-year locoregional PFS was 37%
1-year distant PFS was 71%
1- year PFS was 33%
median overall survival was 10m
1-year overall survival of 40%Vargo et al, IJROBP 2015

15. No grade IV toxicity present study
No carotid blow out syndrome
difference in oropharyngeal cancer patients( HPV +)
between the French trial (80%) and the presented study
(42%) may explain the slight survival differences
Vargo et al, IJROBP 2015

16. 62% patients reporting improved or stabilized overall QoL at the time of the
last survey compared to baseline, which suggests that SBRT plus
Cetuximab did not negatively impact QoL and helped in most patients
Vargo et al, IJROBP 2015

17. Vargo et al. radiotherapy and oncology 2012

18. Vargo et al. radiotherapy and oncology 2012

19. here-in demonstrate that QoL was preserved following SBRT re-irradiation, as
evidenced by progressive improvements in PR-QoL noted throughout the
duration of clinical follow-up across all domains in a validated PRQoL
assessment tool independent of age, use of cetuximab, tumor volume, and
interval since prior irradiation.
Vargo et al. radiotherapy and oncology 2012

20. • There were no significant differences in local control, distant control,
or overall survival by reirradiation interval, treatment platform
(cyberknife /Triology/ Truebeam), or second primary versus local
recurrence.
• Recurrent GTV (<25 cm3) was associated with significantly
improved locoregional PFS (1 year, 53%, and 22%, p 0.029%) and
overall survival (1 year, 70%, and 22%,p <0.01).
• Compared to our prior phase 1 dose escalation study, the
combination of 40 to 44 Gy over 5 fractions plus 3 doses of
Cetuximab translated into a 67% relative increase in median OS (10
vs. 6 months ) with acceptable toxicity.
• Short overall treatment time and low rates of acute toxicity which
allow patients with a generally poor prognosis to complete a
potentially aggressive salvage therapy without compromising QoL
Ph-II Study
Vargo et al, IJROBP 2015

21. Ph-II Study
• Compliance with the prescribed treatment course in this protocol
was 100% (with only 4% requiring treatment interruption both of
equivocal treatment association), which compares favourably to the
prior RTOG 9911 experience with conventional reirradiation plus
chemotherapy where RT was administered according to protocol in
only 46% with but 74% completing the prescribed 4 cycles of
cisplatin-paclitaxel.
• SBRT is safe , improved patient compliance & fewer treatment
related toxicity & 1 year PFS is similar to another retreatment
regimen.
Vargo et al, IJROBP 2015

22. prospective randomized phase 2 protocol that combines fractionated
SBRT (40-50 Gy) plus concurrent cetuximab with or without
concurrent radiation sensitizing docetaxel and 3 months of adjuvant
cetuximab with or without concurrent full-dose docetaxel in hopes of
improving outcomes in this challenging patient population of
unresectable locally recurrent previously irradiated SCCHN
(NCT02057107).

23. first report in the literature describing the use of SBRT as a definitive therapy for
selected patients with primary cancers of the head and neck who were not eligible
for or declined other treatment options
Siddiqui et al. IJROBP 2009

24. These patients had primary cancers in the lung (non–small-cell and small-
cell lung cancers), breast (invasive lobular and invasive ductal carcinomas),
renal cell carcinoma, gastric adenocarcinoma, and brain (glioblastoma
multiforme). Sites of metastatic disease in the head-and-neck region were
mandible, gingival mucosa, periorbital, maxillary, neck nodes, and scalp
(three lesions in the patient with glioblastoma).
Siddiqui et al. IJROBP 2009

25. Siddiqui et al. IJROBP 2009

26. Comet et al. IJROBP 2011

27. No grade 4 toxicities were observed
Four patients (10.3%) presented with grade 3 toxicities: mucositis, dysphagia,
induration, and fibrosis, 3 of whom had received cetuximab as the concomitant
treatment.
Eight patients (20.6%) experienced grade 2
10 (25.6%) grade 1 toxicities.
Altogether, 17 (43.6%) patients presented no toxicity
Only 2 patients with concomitant cetuximab experienced a skin rash
Comet et al. IJROBP 2011
Median overall survival
was 13.6 months.
One- and 2-year overall
survival rates were 58%
& and 24%.

28. • Treatment-related carotid blow-out syndrome was observed in 8
patients (17.8%), 7 (15.2% of whom died of bleeding from carotid.
• Bleeding was not statistically significantly related to tumor volume (p
=0.682), response to treatment (p = 1.00), sex (p = 0.698), or time
elapsed between SBRT and previous radiotherapy (p = 0.113).
However, when the dose received by the carotid artery was grouped
as <100% of the prescribed dose, a significant relation was
observed between the carotid artery dose and bleeding (p = 0.021).
None of the patients with carotid artery dose <100% experienced
carotid blow-out syndrome.
• Bleeding occurred only in patients whose carotid artery walls were
circumscribed by the tumor with a degree of >180 (p = 0.073).
Cengiz et al. IJROBP 2011

29. Yamazaki et al. radiotherapy and oncology 2015

30. Carotid blow out syndrome index
summation of number of risk factors;
carotid invasion >180 (yes = 1, no = 0)
presence of ulceration ( yes = 1, no = 0)
lymph node area irradiation (yes = 1, no = 0)
The Cox regression model revealed that the hazard ratios to the index
268 [95% confidence interval (CI) = 8.04–896, p = 0.002] for index (3)
31.2 (95% CI = 1.13–859, p = 0.04) for index (2)
4.68 (95% CI = 0.17– 129, p = 0.36) for index (1)
Yamazaki et al. radiotherapy and oncology 2015
Although the absence of these three risk factors
could be indicative of safer reirradiation, it does not necessarily
suggest 100% prevention of CBOS

31. Yamazaki et al. radiotherapy and oncology 2015

32. Yamazaki et al. radiotherapy and oncology 2015

33. Alternated day treatment is better: Sequentially 16% developed CBOS, whereas
only 12% patients who received treatment every alternate day (group II)
developed CBOS. Only 14% patients with CBOS survived in group I, whereas
50% in group II who developed CBOS survived.

34. mortality rate from CBS was 5.8% (22/381), and of the total number of
CBS patients, the mortality rate was 68.8% (22/32). The median survival
time after CBS was 0.1 month and the 1-year survival rate was 37.5%
Yamazaki et al. radiotherapy and oncology 2013

35. In multivariate analysis, only skin invasion
is identified as statistically significant
prognostic factor after CBS
Yamazaki et al. radiotherapy and oncology 2013

36. Yamazaki et al. radiotherapy and oncology 2013

37. -The 1-year survival rate for the skin invasion (-) group was 42%,
whereas no patient with active skin invasion survived beyond
4 months (0% at 1 year, p = 0.0049)
- Patients with necrosis/infection formation at CBS onset showed
17% of 1-year survival rate, whereas 67% of value was identified in
counterpart (p = 0.003)
Yamazaki et al. radiotherapy and oncology 2013

38. • patients treated 1.8–2-Gy daily fractions or 1.2-Gy twice daily
fractions rate of CBS was 1.3%.
• Patients treated with 1.5-Gy twice daily fractions over alternating
weeks or with delayed accelerated hyperfractionation received
concurrent chemotherapy, and the rate of CBS was 4.5% (p =
0.002).
• Intensity-modulated radiation therapy (IMRT) series reported
bleeding rates of 0–3%.
• 6.6% of CBS ratio in SBRT seems to be higher than conventional
Fraction.
• In conclusion, careful attention should be paid to the occurrence of
CBS if the tumor is located adjacent to the carotid artery. The
presence of skin invasion at CBS onset is ominous sign of lethal
consequences.
Yamazaki et al. radiotherapy and oncology 2013

39. Assessment of the impact of retrospectively adding margins/automated
PET volumes to the gross tumor volume (GTV) in patients with post-SBRT
recurrences.

40. Target Volume delineation
• Sharp dose fall-off and high dose per fraction of SBRT, accurate
tumor delineation and treatment planning are essential to
adequately cover tumors while avoiding excessive toxicity.
• Primary head and neck cancer, standard practice is to contour
regions of lymphatic drainage and large margins around the gross
tumor volume (GTV). For conventional hyperfractionated re-
irradiation of rSCCHN, many institutions have used margins of 6–10
mm around the GTV. However, there is no standard regarding the
use of such margins for hypofractionated techniques such as SBRT
for rSCCHN. Furthermore, the addition of margins has differed
greatly between institutions studying this technique: Roh – 2-3mm ,
Siddiqui – ‘‘slight’’ margin , Unger – 2-10mm , Cengiz – none.

41. Target Volume delineation
• A detailed description of our assessment of patterns of failure
following SBRT for rSCCHN can be found ,Pre-treatment planning
scans and GTVs were deformed to posttreatment follow-up scans
with Velocity A I™ (Velocity Medical Systems, Atlanta, GA), which
uses a modified B-spline deformable registration algorithm with a
mean error of 1–2 mm for noise-free Images. Use of deformable
registration to analyze patterns of failure.
• Recurrent tumors were categorized: In-field (>75% inside GTV),
Overlap (20–75% inside GTV), Marginal (<20% inside GTV but
closest edge within 1 cm of GTV), or Regional/Distant (more than 1
cm from GTV). In-field, Overlap, and Marginal failures were
considered local failures

42. Target Volume delineation

43. If internal
physiological
variations such as
respiration and
swallowing
movements were
anticipated, the
contour was
slightly overdrawn
especially in the
superior–inferior
direction and was
defined as the
internal target
volume (ITV).

45. For unresectable patients, especially in the intensity-modulated radiation
therapy (IMRT) era, conventional re-irradiation ± chemotherapy offers potential
for long-term salvage with LC rates >50% at 5-years combined with 2- to 5-year
OS >30%, but is often balanced with significant acute (grade >/=3: mucositis 5–
79%, dermatitis 16–46%, and neutropenia 18–26%) as well as late
toxicity (grade >/= 3 fibrosis 31–48%, trismus 9–24%, osteonecrosis 5–16%,
and carotid blowout 2–5%)
Yamazaki et al. radiotherapy and oncology 2011
(rSCCHN) with shorter treatment times (1–2 weeks), decreased toxicity
(toxicity grade > 3: 0–20%), and comparable LC/OS (2-year LC 31–41%,
2-year OS 14–50%) compared to conventional re-irradiation ±
chemotherapy
Salama JK, et al. Semin Oncol 2008

46. Take home message on SBRT
• SBRT was selected as the choice for reirradiation when the treating radiation
oncologist deemed full-dose re-treatment (i.e., >60 Gy) with either three-dimensional
or IMRT as challenging because of proximity to the spinal cord or other critical
structures
• Even if there is no demonstrated biological advantage (overcome the radioresistance
of recurrent tumor cells) using hypofractionation in recurrent HNC, there is a major
clinical advantage in keeping the overall treatment time ) short, improved therapeutic
ratio (local control/morbidity) in a population with a poor clinical prognosis.
• Combining with targeted therapies has the advantage of minimal acute toxicity, with
the exception of an acceptable skin rash for patients with short life expectancy
• The lack of hematologic or systemic toxicity permits the inclusion of patients in poor
general condition.
• Acute Mucositis was temporary and well managed with supportive care
• 5 Fraction protocol alternative day is better for toxicity than delivered daily(<10% vs.
20%)

47. Take home message on SBRT
• reirradiation with IMRT or conventionally fractionated SBRT is relatively safe with
regard to carotid blowout syndrome; however the risk of Grade 3 and 4 toxicities is
high . So, in patients with carotid arteries entrapped by the tumor, SBRT with
hypofractionation should be cautiously delivered. IMRT or conventionally fractionated
SBRT may be a better treatment option in these cases. Another possible approach is
to delineate the carotid artery and define it as an organ at risk to prevent hot spots of
>100 Gy (EQD 2) on significant carotid sheath volumes . Similarly, in the Turkish
study, all the patients who developed CBOS had received a maximal carotid artery
dose of >34 Gy.
• CT and/or Doppler ultrasound surveillance might be helpful to detect carotid
radionecrosis and indicate prophylactic intervention for preventing CBOS.
• At present, cases of recurrent head and neck cancers with carotid invasion of >180,
the presence of ulceration, and irradiation to areas of lymph nodes are not good
candidates for SBRT.
• SBRT for previously-irradiated, recurrent squamous cell carcinoma of the head and
neck (rSCCHN) have demonstrated control rates comparable to Conventional
radiotherapy with acceptable treatment- related toxicities.

48. Thank you