Presentation

1. ADAPTIVE RADIOTHERAPY
IN HEAD AND NECK CANCER
Speaker- Dr. Rituparna Biswas
Moderator- Dr. Suman Bhasker 16.11.2017

2. Line of presentation:
1.Introduction
2.What is Adaptive radiation therapy (ART)?
3.Dosimetric benefits of ART in Head and Neck
Cancer
4.Clinical benefits of ART in Head and Neck Cancer
5.Indications
6.Optimal timing for adaptive therapy
7.Other implications of ART

3. Goal of an optimized radiation therapy plan :
 To apply as much as possible radiation
dose to tumor volumes
• Maximum Tumour Control Probability
(TCP)
 To spare adjacent healthy tissue and
organs at risk
• Minimum Normal Tissue Complication
Probability (NTCP)
INCREASED THERAPEUTIC RATIO
INTRODUCTION

4. Over the years, the delivery of radiation therapy has improved with
innovations that have reduced toxicity without compromising
locoregional control.
Among these advances, the development of intensity modulated
radiation therapy (IMRT) has represented a major turning point in the
treatment of HNC patients.1
 IMRT is characterized by its highly conformal dose distribution with
improved ability to treat target volumes to therapeutic doses while
avoiding normal structures such as the salivary glands, larynx, spinal
cord, and oral cavity.
1Lee N, Xia P, Fischbein NJ, et al. Intensity modulated radiation therapy for head-and-neck
cancer: The UCSF experience focusing on target volume delineation. Int J Radiat Oncol Biol Phys.
2003;57(1):49-60.

5. Simulation CT Scan
 Is One CT Before Treatment Good
Enough For Planning and Entire
Treatment?

6.  Is One DVH Enough To
Accept The Plan and
proceed with the full
Treatment ?

7. Quantification of volumetric and geometric changes occurring during fractionated
radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator
system
Jerry L. Barker Jr, M.D., Adam S. Garden, M.D., K.Kian Ang, M.D., Ph.D., Jennifer C. O'Daniel, M.S., He Wang, Ph.D., Laurence E.
Court, Ph.D., William H. Morrison, M.D., David I. Rosenthal, M.D., K.S.Clifford Chao, M.D., Susan L. Tucker, Ph.D., Radhe Mohan,
Ph.D., Lei Dong, Ph.D Departments of *Radiation Oncology, †Radiation Physics, and ‡Biomathematics, The University of Texas M. D. Anderson Cancer Center, Houston, TX
July 15, 2004 Volume 59, Issue 4, Pages 960–970
 14 patients of head-and-neck cancer and having gross primary and/or cervical nodal
disease measuring at least 4 cm in maximal diameter.
 Treated with definitive external beam RT
 CT scans were acquired 3 times weekly during the entire course of RT, and both GTVs
(T & N) and normal tissues (parotid glands, spinal canal, mandible, and external contour)
were manually contoured on every axial slice.
 Volumetric and positional changes relative to a central bony reference (the center of
mass of the C2 vertebral body) were determined for each structure.

10. RESULTS
Conclusion:
Measurable anatomic changes occurred throughout fractionated external
beam RT for head-and neck cancers. These changes in the external contour,
shape, and location of the target and critical structures appeared to be
significant during the second half of treatment (after 3–4 weeks of treatment)
and could have potential dosimetric impact when highly conformal treatment
techniques are used. These data may, therefore, be useful in the
development of an adaptive RT scheme (periodic adjustment of the
conformal treatment plan) that takes into account such treatment-related
anatomic changes. In theory, such a strategy would maximize the therapeutic
ratio of RT.

11. Anatomical
modification
During
Radiation
Therapy

12.  A single plan designed before
treatment is insufficient to describe
the actual delivered doses, and often
leads to suboptimal treatment.

13. ADAPTATION

14. Abstract.
Adaptive radiation therapy is a closed-loop radiation treatment process where the
treatment plan can be modified using a systematic feedback of measurements.
Adaptive radiation therapy intends to improve radiation treatment by systematically
monitoring treatment variations and incorporating them to re-optimize the treatment
plan early on during the course of treatment. In this process, field margin and treatment
dose can be routinely customized to each individual patient to achieve a safe dose
escalation.
What is Adaptive radiation therapy?

15. What is Adaptive radiation therapy?

17. ART strategies:
1. Offline- between treatments
2. Online- immediately prior to a treatment, and in
3. Real-time- during a treatment

19. Workflow for
image - guided
adaptive RT

20. ART is technically challenging and labour-intensive
Daily re-planning?
Manual contouring:
• Time consuming
• subject to intra or
interobserver variations
(Geets et al. 2005)
Recent developments in deformable
image registration for atlas-based
autosegmentation proves to be an
effective method for adaptive RT (Lu et al.
2004; Wang et al. 2005; Chao et al. 2007;
Castadot et al. 2008; Zhang et al. 2007;
Nithiananthan et al. 2009).

21. Deformable image registration and automatic segmentation
One-to-one
mapping
between
points in the
two images

22. Atlas-based automatic segmentation-An atlas consists of an image and
corresponding contours (left). Contours are propagated from the atlas to a new image
(right) according to the results of DIR between the atlas and new image. In this example,
the atlas is the pCT and the new image is a CBCT of the same patient obtained in the
sixth week of treatment.

23. Dosimetric benefits of
ART in Head and Neck
Cancer

24. Dosimetric Effect of Anatomical Modifications During Radiation Therapy

25. Dosimetric Effect of Anatomical Modifications During Radiation Therapy

26. Conclusion: Implementation of adaptive
radiotherapy in head and neck cancer offers
benefits including improvement in tumor coverage
and decrease in dose to organs at risk. The tumor
volume reduction rate during treatment was
significantly correlated with disease-free survival
and overall survival.

27. Clinical benefits of ART
in Head and Neck
Cancer

28. Volume 36, Issue 11 November 2014 Pages 1541–1546
 Retrospective
 317 patients underwent IMRT with daily image- guidance
for newly diagnosed squamous cell carcinoma of the head
and neck to a median dose of 66 Gy (range, 60–74 Gy).
 Of these 51 (16%) underwent adaptive radiotherapy with
modification of the original IMRT midway during treatment
Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, California.

30. Adaptive replanning
 No standardized policy was in place to guide the selection of patients for
adaptive radiotherapy.
 Adaptive IMRT plan was implemented at a median dose of 40 Gy
(range, 10–58 Gy).

31. Results
Overall survival among patients treated with IMRT for head and neck cancer
according to whether adaptive radiotherapy (ART) was performed
2-year estimates
of overall survival
were 73% and
79% among
patients treated
with and without
ART, respectively
(p=0 .55).

32. Results
Local-regional control among patients treated with IMRT for head and neck cancer
according to whether ART was performed
2-year local-
regional control was
88% for patients
treated with ART
compared to 79%
for patients treated
without (p =0.01).

33. No difference in overall survival and distant
metastasis-free survival based on the matched-pair
analysis (p > .05, for both)
 No difference in acute and late toxicities.

34. Criticism
 Variability in patient populations
 No definite policy for adaptive radiotherapy existed
 Selection bias
 Retrospective
Conclusion. Although the use of routine
replanning is probably not necessary, their
findings do suggest a significant benefit in
appropriately selected patients.
This study is amongst the first to
suggest that the theoretical benefits
of adaptive replanning may be
associated with actual clinical
advantages for patients treated by
IMRT for head and neck cancer.

35. Int J Radiat Oncol Biol Phys. 2012 Jul 1; 83(3): 986–993.
Purpose: To present pilot toxicity and survival outcomes for a prospective trial
investigating adaptive radiotherapy (ART) for oropharyngeal squamous cell carcinoma.
Methods and Materials:
• 24 patients were enrolled; data for 22 of these patients were analyzed.
• Daily CT-guided setup and DIR permitted serial mapping of CTVs and avoidance
structures for ART planning.
The University of Texas M.D. Anderson Cancer Center, Houston, TX

36. Results:
• All patients required at least one replan (ART1) as specified by protocol
because of CTV and normal tissue changes; 8 patients (36%) required a
second replan (ART2).
• With a 31-month median follow-up (range; 13-45 months), there has been no
primary site failure and 1 nodal relapse, yielding 100% local and 95%
regional disease control at 2 years.
• Baseline tumor size correlated with absolute volumetric treatment response
(p =0.018).
• Parotid volumetric change correlated with duration of feeding tube placement
(p = 0.025).
• Acute toxicity was comparable to that observed with cIMRT.

37. Performance Status Scale for Head and
Neck Cancer (PSS-HN) results confirm
full preservation or functional
recovery of speech and eating function
across tested domains by 20 months.

38. Sialometry results are notable for
ongoing recovery of stimulated salivary
production after 1 year of followup,
despite persistent loss of unstimulated
salivary production.

39. Conclusion:
This is the first prospective evaluation of morbidity and
survival outcomes in patients with locally advanced
head-and-neck cancer treated with automated adaptive
replanning. ART can provide dosimetric benefit with only
one or two mid-treatment replanning events.

40. Int J Radiat Oncol Biol Phys. 2013 Jan 1;85(1):e47-54
129 patients with NPC were enrolled between June 2007 and August 2011 .
 43 patients received IMRT without replanning, while 86 patients received IMRT
replanning after CT images were retaken part way through therapy.
Chinese versions of the European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35
were completed before treatment began and at the end of treatment and at 1, 3, 6, and
12 months after the completion of treatment.
Overall survival (OS) data were compared using the Kaplan-Meier method.

41. 86 NPC patients treated with IMRT replanning (green) and 43 patients treated without
IMRT replanning (blue)
RESULTS

42. Results from the EORTC QLQ-C30:
The patients treated with IMRT with replanning had both statistically
and clinically significant improvements in most QoL scales, including
the global QoL, the 2 functional scales (role and social functioning),
and the 4 symptom scales (dyspnea, appetite, constipation, and
diarrhoea).
Results from the EORTC QLQ-H&N35:
Patients without replanning reported more complications, including
problems with speech, social contact, and teeth, as well as problems
with opening their mouths and problems with dry mouth and sticky
saliva.

43. November 1, 2015 Volume 93, Issue 3, Supplement,
Pages S211–S212
Purpose/Objective(s): This study explores the comparative safety and efficacy of adaptive
replanning for head and neck cancer intensity modulated radiotherapy (aIMRT) with
standard IMRT (sIMRT) as measured by clinical rather than dosimetric outcomes.
Materials/Methods: We identified all patients with stage III-IVB head and neck cancer
treated with definitive chemoradiation using IMRT at a single institution over a 5-year
period (2009-2014). Patients who exhibited either rapid disease regression and/or
significant weight loss that resulted in substantial geometric changes with target
volumes excessively encompassing skin or other uninvolved organs on daily CBCT
images by weeks 3 to 4 were adaptively replanned. Patient characteristics, disease
parameters, locoregional control, overall survival, and acute and late toxicity (CTCAE
version 4) were analyzed. Toxicity outcomes were compared by X2 tests; survival and
control rates were determined from Kaplan-Meier estimates.

44. Results: 203 patients (42.9% aIMRT, 57.1% sIMRT) were identified from our institutional
review board approved registry. Median follow-up was 20 months (range, 0.5-58.6 months),
median age 58 years, median KPS 90. The median radiation dose was 70 Gy for both
groups (range, 63-78 Gy), and all patients received chemotherapy. The majority of tumors
were oropharyngeal (84%) with larynx (11%) as the second most common site. Patients in
the aIMRT and sIMRT groups were well balanced for baseline patient, tumor, and treatment
characteristics with the notable exception that patients undergoing aIMRT had significantly
higher rates of N2b-3 disease (83% vs. 62%; P = .001) as well as group stage IVB disease
(17.2% vs. 3.4%; P = .0002). Despite more unfavorable disease characteristics in the aIMRT
group, no significant differences were observed in locoregional failure rates for sIMRT versus
aIMRT (5.2% vs. 9.2%; P= .24) or in 2-year overall survival (87.3% vs. 86.8%; P = .79), and
only 1 locoregional failure in the aIMRT group was marginal. Acute toxicity was comparable
for aIMRT versus sIMRT, respectively, including feeding tube use (39% vs. 37%; P = .77), >=
G2 mucositis (64% vs. 57%; P = .28), >=G2 dermatitis (44% vs. 43%; P Z .93). Late
swallowing dysfunction (aspiration, stricture, dysphagia) was higher in the aIMRT group
(17.2% vs. 7.8%; P= .04), as expected given the increased volume of pharyngeal
constrictors receiving prescription dose in N2b-3 disease, while late fibrosis and pain was
lower in the aIMRT group (4.6% vs. 12.1; P Z .05).
Conclusion: Adaptive IMRT yields excellent control and survival
rates comparable to standard IMRT without increasing the risk of
marginal failures. Despite more adverse disease characteristics in
the aIMRT patient group, similar acute and late toxicity profiles
suggest that image guided aIMRT may help offset the expected
increases in toxicity in patients with more locoregionally advanced
disease.

45. ART is labor-intensive and should be reserved
for those who are most likely to beneft.
Indications!!!!

46. Int. J. Radiation Oncology Biol. Phys., Vol. 80, No. 3, pp.
677–685, 2011
Methods and Materials: 23 sequential head and neck IMRT patients underwent serial CT scans during
their radiation course. After undergoing the planning CT scan, patients underwent planned rescans at 11,
22, and 33 fractions; a total of 89 scans with 129 unique CT plan combinations were thus analyzed.
Positional variability and anatomic changes during treatment were correlated with changes in dosimetric
parameters to target and avoidance structures between planning CT and subsequent scans.
Results: A total of 15/23 patients (65%) benefited from adaptive planning, either due to inadequate
dose to gross disease or to increased dose to organs at risk. Significant differences in primary and
nodal targets (planning target volume, gross tumor volume, and clinical tumor volume), parotid, and spinal
cord dosimetric parameters were noted throughout the treatment. Correlations were established between
these dosimetric changes and weight loss, fraction number, multiple skin separations, and change in
position of the skull, mandible, and cervical spine.

47. Identifcation of patients who benefit from ART
• Severe weight loss
• Significant reduction of the neck volume
• Advanced T stage
• An ill-fItting immobilization mask,
• Signifcant shrinking of palpable disease,
• Or an extended treatment break
Chen AM, Daly ME, Cui J, et al. Clinical outcomes among patients with head and neck cancer
treated by intensity-modulated radiotherapy with and without adaptive replanning. Head Neck.
2014;36(11):1541-1546.
Capelle L, Mackenzie M, Field C, Parliament M, Ghosh S, Scrimger S. Adaptive radiotherapy
using helical tomotherapy for head and neck cancer in defnitive and postoperative settings:
initial results. Clin Oncol. 2012;24:208–15.
Jensen AD, Nill S, Huber PE, Bendl R, Debus J, Munter MW. A clinical concept for
interfractional adaptive radiation therapy in the treatment of head and neck cancer. Int J
Radiat Oncol Biol Phys. 2012;82:590–6.
Lai YL, Yang SN, Liang JA, Wang YC, Yu CY, et al. Impact of body-mass factors on setup displacement in
patients with head and neck cancer treated with radiotherapy using daily on-line image guidance. Radiat
Oncol. 2014;9:19

48. Optimal timing for
adaptive therapy!!!

49. Conflicting reports!!!
Significant reduction of OAR volume after the 1st treatment week, while the largest
average tumor volume reduction occurred after the 5th week in patients with
oropharyngeal cancer undergoing IMRT with concurrent chemotherapy.
Ricchetti F, Wu B, McNutt T, Wong J, et al. Volumetric change of selected organs at risk during IMRT
for oropharyngeal cancer. Int J Radiat Oncol Biol Phys. 2011;80:161–8.
Average rates of volume reduction of the parotid and submandibular glands in the first
3 weeks of radiation therapy were larger than within the last 3 weeks of treatment.
Wang ZH, Yan C, Zhang ZY, et al. Radiation-induced volume changes in parotid and submandibular
glands in patients with head and neck cancer receiving postoperative radiotherapy: a longitudinal
study. Laryngoscope. 2009;119:1966–74
Significant reduction of CTV volume occured at week 2 but the largest parotid gland
volume reduction occurred at week 4.
Bhide SA, Davies M, Burke K, et al. Weekly volume and dosimetric changes during
chemoradiotherapy with intensitymodulated radiation therapy for head and neck cancer: a
prospective observational study. Int J Radiat Oncol Biol Phys. 2010;76:1360–8

50.  These conflicting reports suggest that the decision to re-plan
should be based on clinical judgment.
 Tumor response to treatment and the radiosensitivity of normal
tissues may vary from one patient to another.
 During the treatment, daily or weekly CT scans may identify
patients who require re-planning, but it is
 time-consuming and
 increases the radiation dose received by the patients

51. Other implications of ART
 May aid in outcome prediction for local control.
 To determine which patients may benefit from dose escalation during
treatment.
On multivariate analysis, it was demonstrated that a primary GTV
prior to treatment > 30 cc as well as tumor volume reduction rate <
50 % after treatment were prognostic for poor local control.
Yang SN, Liao CY, Chen SW, et al. Clinical implications of the tumor volume reduction rate in
head-and-neck cancer during definitive intensitymodulated radiotherapy for organ preservation.
Int J Radiat Oncol Biol Phys. 2011;79(4):1096-1103
Tumor volume reduction rate measured during ART in 59 patients
with oropharyngeal cancer was a signifcant prognostic factor for
local control on multivariate analysis.
Lee H, Ahn YC, Oh D,et al. Tumor volume reduction rate measured during adaptive defnitive
radiation therapy as a potential prognosticator of locoregional control in patients with
oropharyngeal cancer. Head Neck. 2014;36(4):499-504.

52. Current limitations to implementation of adaptative radiation therapy in routine practice

53. Conclusions
 Significant variations of the volume, shape and position of
tumors and OAR are frequently observed during the course of
radiation therapy for HNSCC.
 When these alterations produce significant dose changes
resulting in potential excessive dose to OAR or decrease the
dose to PTV, ART becomes necessary.

54. Take home message
 Multiple studies indicate the dosimetric benefits of ART when used in
selective subsets of patients, although clinical implications of this
remain unclear.
 ART still remains labor and resource intensive and future
improvements in ART, including automated replanning processes and
improved image guidance, will make ART a more economical option.
 Future prospective studies may resolve current ART limitations and
allow its routine adaptation in the clinic.