Precision radiotherapy, also known as precision radiation therapy or targeted radiotherapy, is a cutting-edge approach in the field of radiation oncology that aims to deliver highly focused and accurate doses of radiation to cancerous cells while minimizing damage to surrounding healthy tissues.

1. Precision Radiotherapy: Tailoring
Treatment for Individualised Cancer
Care
Dr. Rituparna Biswas, MBBS (Hons), MD Radiotherapy,
Ex SR- AIIMS, New Delhi.
Assistant Professor- Radiation Oncology at Malda Medical College
(West Bengal)
Presented in a webinar arranged by M3 India and also available on their website.
Link: https://www.m3india.in/webinar/precision-radiotherapy-tailoring-treatment-for-individualised-cancer-care

2. Exploring:
 Radiomics,
 Immunotherapy Integration,
 Technological Advances,
 Adaptive Approaches in Precision Radiotherapy
 Future in Precision Radiotherapy:

3. • Cancer treatment is heading towards precision medicine driven by genetic
and biochemical markers rendering personalized treatment in cancer
• Precision radiotherapy, also known as precision radiation therapy or
targeted radiotherapy, is a cutting-edge approach in the field of radiation
oncology that aims to deliver highly focused and accurate doses of radiation
to cancerous cells while minimizing damage to surrounding healthy tissues.
• Need of the hour: To enhance treatment outcomes by customizing the
therapy to the individual patient's tumor profile.

4. Why do we need to
tailor Radiation
therapy as per
individual patient
characteristic?

5. • Personalized oncology works on the principle of identification of
subgroups of patients in particular disease types.
• Many biomarkers and gene mutations have been investigated to identify
the subgroups of the patients in various cancers and targeted drugs have
been identified for those subgroups.
• In recent years, technology-driven approach has also been tested in
various fields in precision oncology.
• One such is Radiomics.

6. Radiomics in Oncology
• Radiomics as a word was first used by Lambin et al. in 2012 in order to describe the
quantification of medical imaging data.
• Radiomics is a process to extract high throughput data from medical images like CT, PET, MRI
or SPECT by using advanced mathematical and statistical analysis of images.
• The Radiomics process explores the heterogeneity, irregularity and size parameters of the tumor
to calculate thousands of advanced features.

7. Process of Radiomics

8. Clinical Implications
 To increase precision in diagnosis,
 assessment of prognosis, and
 prediction of therapy response

9. Examples: Enabling Diagnosis
Texture features were computed from manually
segmented ROI identifying the normal peripheral zone
(blue) and cancer (red). Heat map images show clear
differences between healthy tissue and cancer.
• In a study of 147 men with biopsy-proven prostate
cancer, Wibmer et al* showed that Haralick texture
analysis has the potential to enable differentiation of
cancerous from noncancerous prostate tissue on both
T2W- MR images and ADC maps.
• In a follow-up study, these features were used to
automatically compute Gleason grade and were found to
enable discrimination between cancers with a Gleason
score of 6 (3+3) and those with a Gleason score of 7 of
more with 93% accuracy.
• Furthermore, these analyses could be used to distinguish
between two different forms of Gleason score 7 disease
(4+3 vs 3+4) with 92% accuracy .
*Wibmer A, Hricak H, Gondo T, et al. Haralick texture analysis of prostate MRI:
utility for differentiating non-cancerous prostate from prostate cancer and differentiating
prostate cancers with different Gleason scores. Eur Radiol 2015;25(10):2840–2850

10. Examples: Tumor Prognosis
• Numerous radiogenomic studies exist which shows a relationship between quantitative image features and gene
expression patterns in patients with cancer.
• In the first of these studies, the investigators compared semantic radiologist-defined features extracted from CECT
images in patients with HCC to gene expression patterns by using machine learning with a neural network. They
found that combinations of 28 imaging traits could be used to reconstruct 78% of the global gene expression
profiles, which in turn were linked to cell proliferation, liver synthetic function, and patient prognosis.
[Segal E, Sirlin CB, Ooi C, et al. Decoding global gene expression programs in liver cancer by noninvasive imaging. Nat Biotechnol 2007;25(6):675–680.]
• In a landmark article, Rose et al analyzed the pattern of enhancement on dynamic CE MRI in simulations,
phantoms, and 23 patients with glioma. They convincingly showed that complex measures of texture heterogeneity
could be used to distinguish high- and low-grade gliomas with much higher statistical power (P < .00005).
[Rose CJ, Mills SJ, O’Connor JP, et al. Quantifying spatial heterogeneity in dynamic contrast-enhanced MRI parameter maps. Magn Reson Med 2009;62(2):488–499.]

11. Examples: Treatment Selection
• In a seminal study, Kuo et al identified HCC imaging phenotypes that correlated
with a doxorubicin drug response gene expression program. Their results
suggested that radiogenomic analyses could be used to guide the selection of
therapy for individual tumors.
[Kuo MD, Gollub J, Sirlin CB, Ooi C, Chen X. Radiogenomic analysis to identify imaging phenotypes associated with drug
response gene expression programs in hepatocellular carcinoma. J Vasc Interv Radiol 2007;18(7):821–831.]
• More recently, a study of 58 women who underwent treatment for locally
advanced breast cancer suggested that texture analysis of dynamic CE MR
imaging could help predict response to neoadjuvant chemotherapy before its
initiation.
[Teruel JRHM, Heldahl MG, Goa PE, et al. Dynamic contrast-enhanced MRI texture analysis for pretreatment prediction of
clinical and pathological response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. NMR
Biomed 2014; 27(8):887–896.]

12. Potential in Precision Radiotherapy:
Enabling better-informed decisions for tailoring
Radiation treatment for a cancer patient as per
radiosensitivity information from radiogenomics.

13. iRT
• Radiotherapy (RT) is delivered for purposes of local control, but it can also
cause regression of tumor at remote and distant nonirradiated sites, which is
known as Abscopal effect.
• Considering the infrequency of the abscopal effect, it is essential to strategize
on enhancing the likelihood of its occurrence. This involves devising
methods to amplify the phenomenon, thereby expanding its beneficial impact
on the population.
• It is now widely accepted that RT can provoke a systemic immune response
which gives a strong rationale for the combination of RT and immunotherapy
(iRT).

15. CLINICAL PRACTICE
What We Currently Know: Investigations of Combined Radio-
Immunotherapy in patients with Advanced Malignancies

16. 1. Addition of Immunotherapy to Definitive Local Therapy
Turchan WT, Pitroda SP, Weichselbaum RR. Treatment of Cancer with Radio-Immunotherapy: What We Currently Know and What the
Future May Hold. Int J Mol Sci. 2021 Sep 3;22(17):9573. doi: 10.3390/ijms22179573. PMID: 34502479; PMCID: PMC8431248.

17. Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? Nat
Rev Clin Oncol. 2016 Aug;13(8):516-24. doi: 10.1038/nrclinonc.2016.30. Epub 2016 Mar 8. PMID: 26951040; PMCID: PMC6053911.
2. Combined Radio-Immunotherapy in Patients with Metastatic Disease

18. 3. Radiotherapy dose/fractionation for iRT
• The immune response induced by RT is “dose dependent”.
• In clinical practice, it seems that hypofractionated RT may show advances
and the combination of IO + SBRT may have more potential in the modality
of iRT .
• Still needs more clinical data.
Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? Nat
Rev Clin Oncol. 2016 Aug;13(8):516-24. doi: 10.1038/nrclinonc.2016.30. Epub 2016 Mar 8. PMID: 26951040; PMCID: PMC6053911.

19. 4. Next question is lesion selection for iRT
• Poleszczuk et al* described a mathematical model that incorporates physiologic information
about T-cell trafficking to estimate the distribution of focal therapy-activated T cells between
metastatic lesions. Their study showed that not all metastatic sites participate in systemic immune
surveillance equally and therefore the success in triggering the abscopal effect depends on the
selection of metastatic site to receive the treatment .
• Another approach: use multi-site RT to achieve systemic disease control
• Clinical trials also support IO may achieve better efficacy when patients with lower disease
burden and a reduction in tumor burden by comprehensive (but not single-site) RT may potentiate
IO.
*Poleszczuk, J. T. et al. Abscopal benefits of localized radiotherapy depend on activated T-cell trafficking and distribution between metastatic lesions.
Cancer Res. 76, 1009–1018 (2016).

20. 5. Selection of immunotherapy modality
• Still unknown.
• Considering that the most widely used ICI is PD-1 and CTLA-4 blockades,
a retrospective analysis of two single-institution prospective trials reported
that the PFS of anti-PD1 combined with SBRT for metastatic NSCLC was
significantly better than anti-CTLA4 combined with SBRT, although there
was no statistically significant difference in efficacy. *
• This area requires further exploration from additional clinical trials.
*Chen, D. et al. Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic
non-small cell lung cancer: retrospective analysis of two single-institution prospective trials. J.Immunother. Cancer 8, e000492 (2020)

21. • Data from clinical trials and retrospective studies indicate that
concurrent iRT may be more effective than sequential one.
• Nevertheless, due to relatively less clinical data, more studies are
needed to investigate the optimal timing.
6. The optimal timing for iRT

22. • There is significant concern for overlapping toxicities of iRT.
• Summarizing the available evidence to date, we observe that iRT may
result in grade 1 to 2 toxicity generally but the occurrence of toxicity
necessitating medical support (grade 3) or which is life threatening
(grade 4) is relatively rare.
• The currently available clinical trials suggest that iRT is likely to be well
tolerated with acceptable toxicity in patients with different tumor types
and there are many ongoing clinical trials to explore this issue.
7. The toxicity of iRT

23. Technological advances in radiation therapy
In addition to routine conventional external beam
radiotherapy with photon or electron beams and
brachytherapy, several specialized radiotherapy
techniques have been developed for dose delivery or
target localization.

24. The special dose delivery
techniques are:
• Conformal radiotherapy
• Intensity modulated radiotherapy (IMRT)
• Image guided radiotherapy (IGRT)
• Stereotactic irradiation
• Total body irradiation (TBI)
• Total skin electron irradiation (TSEI)
• Intraoperative radiotherapy (IORT)
Special target localization
techniques in radiotherapy are:
• Stereotaxy
• Image guided radiotherapy (IGRT)
• Respiratory gated radiotherapy
• Adaptive radiotherapy
• PET/CT/MRI/US fusion

25. • Conformal radiotherapy conforms or shapes the prescription dose volume
to the planning target volume (PTV) while at the same time keeping the
dose to specified organs at risk below their tolerance dose.
• The concept of conformal dose delivery has thus two main objectives:
 Maximized tumour control probability (TCP).
 Minimized normal tissue complication probability (NTCP).
CONFORMAL RADIOTHERAPY

26. Target localization is achieved through:
Anatomical imaging such as:
• Computerized tomography (CT)
• Magnetic resonance imaging (MRI)
• Single photon emission tomography (SPECT)
• Ultrasound (US)
Functional imaging such as:
• Positron emission tomography (PET)
• Functional magnetic resonance imaging (fMRI)
• Molecular imaging
CONFORMAL RADIOTHERAPY( Basic concepts)

27. Treatment planning is achieved through:
• Forward treatment planning techniques which design
uniform intensity beams shaped to the geometrical
projection of the target.
• Inverse treatment planning techniques which, in addition
to beam shaping, use intensity modulated beams to
improve target dose homogeneity and to spare organs at
risk.
CONFORMAL RADIOTHERAPY (Basic concepts)

28. Treatment planning process for 3-D CRT consists of 4 steps:
• Acquisition of anatomic information in the form of transverse (axial)
images.
• Determination of the planning target volume (PTV) by the radiation
oncologist by contouring the PTV on each individual axial image
(segmentation process).
• Design of radiation fields using the beam’s-eye-view option in the
treatment planning software.
• Optimization of the treatment plan through the design of optimal field
sizes, beam directions, beam energies, etc.
CONFORMAL RADIOTHERAPY (Three dimensional conformal Radiotherapy)

29. CONFORMAL RADIOTHERAPY
Intensity modulated radiotherapy
 Modern radiotherapy techniques based on computer controlled intensity modulation
systems have been developed during the past decade and currently represent the most
sophisticated 3-D conformal dose delivery process.
 .Non-uniform beam intensities (intensity modulation) can be used to improve dose
distributions by:
• Compensating for contour irregularities
• Compensating for tissue inhomogeneities
• Compensating for highly irregular target volumes
• Sparing organs at risk located in the vicinity of target volume.

30. Three techniques are currently available for IMRT dose delivery:
• Isocentric linac in conjunction with a MIMIC collimator.
• Tomotherapy unit.
• Isocentric linac in conjuction with a multileaf collimator.

31. IMRT treatments can be delivered with the MLC operating in one of three basic modes:
• Segmented MLC (SMLC) mode, often referred to as the step-and shoot mode, in which the intensity
modulated fields are delivered in the form of a sequence of small segments or subfields, each subfield
with a uniform intensity.
• Dynamic MLC (DMLC) mode, also referred to as the sliding window mode, in which the intensity
modulated fields are delivered in a dynamic fashion with the leaves of the MLC moving during the
irradiation of the patient.
• Intensity modulated arc therapy (IMAT) mode in which the sliding window approach is used as the
gantry rotates around a patient.

32. IMAGE GUIDED RADIOTHERAPY
• Imaging of patient anatomy on the treatment machine just prior
to each daily dose fraction provides an accurate knowledge of the
target location on a daily basis and helps with the daily patient
set-up on the therapy machine.
• This technique is known as the image guided radiotherapy
(IGRT) and has the potential of ensuring that the relative
positions of the target volume and some reference marker for
each fractional treatment are the same as in the treatment plan.

33. The IGRT systems currently commercially available are based on direct integration of:
• Kilovoltage or megavoltage imaging system and an isocentric Linac (cone beam CT).
• CT scanner and an isocentric linac.
• Megavoltage computerized tomography (MVCT) and a Tomotherapy machine
(miniature linac mounted on a CT-type gantry).
• 2-D or 3-D ultrasound system and an isocentric linac.
• On-line imaging with paired orthogonal planar imagers and a miniature linac mounted
on a robotic arm (Cyberknife).
IMAGE GUIDED RADIOTHERAPY

34. Integrated imaging systems based on kilovoltage cone beam CT

35. IMAGE GUIDED RADIOTHERAPY (The BAT system)
• The B-Mode Acquisition and Targeting (BAT) system is
based on 2-D ultrasound images acquired prior to dose
delivery. The images are used to realign the patient into the
appropriate position on the treatment table.
• The system consists of a cart-based ultrasound unit
positioned next to a linac treatment table and is used by the
radiotherapist to image the target volume prior to each
fraction of radiotherapy treatment.
Images of a patient with prostatic adenocarcinoma captured by BAT.
• BAT allows the determination of the degree of organ movement that has
taken place since the original CT treatment planning scan (top image).
• The patient is repositioned accordingly (bottom image).
• In this case, the patient was moved 0.1 cm to the left, 0.6 cm down, and
0.9 cm away from the linac.

36. Stereotactic irradiation comprises focal irradiation techniques
that use multiple, non-coplanar photon radiation beams and
deliver a prescribed dose of ionizing radiation to pre-selected
and stereotactically localized lesions.
Stereotactic external beam irradiation

37. Equipments used for stereotactic radiosurgery
• Stereotactic frame: defines a fixed coordinate system for an accurate localization and irradiation of the planning
target volume (PTV).

38. Stereotactic frame immobilization in
linac-based radiosurgery
• The immobilization of the stereotactic
frame during the treatment is achieved
with special brackets which attach the
frame to the linac couch, chair, or a
special floor stand.
• Direct couch mounting of the
stereotactic frame is less expensive,
safer for the patient, and more practical
than mounting onto a floor stand.

39. Equipments used for stereotactic radiosurgery
• Imaging equipment (CT, MRI and DSA) with which the structures, lesions and PTVs are visualized, defined and
localized.

40. Equipment used for stereotactic radiosurgery
• Target localization software: used in conjunction with the stereotactic
frame system and imaging equipment to determine the coordinates of the
target in the stereotactic reference system.
• Treatment planning system: calculates the 3-D dose distribution and
superimposes it onto the patient’s anatomical information.
• An appropriate radiation source and radiosurgical treatment technique.

41. Contemporary radiosurgery
is carried out mainly with
Gamma Knife machines, but
a significant number of
radiosurgical procedures is
also carried out with
modified isocentric linacs
and Cyberknife machines.

42. Linac-based radiosurgery falls into three main categories:
• Radiosurgery with modified isocentric linac
 Moving beam techniques
 Multiple non-coplanar converging arcs
 Dynamic rotation
 Conical rotation
 Multiple stationary beams in conjunction with miniature MLC
• Miniature linac mounted on robotic arm (CyberKnife)
• Miniature linac mounted on CT gantry (Tomotherapy)

44. Multiple non-coplanar converging arcs
technique:
• The target dose is delivered through
a series of gantry arcs, each arc with
a different stationary position of the
treatment couch or chair.
• The arc angles are usually smaller
than 180 degree to avoid parallel-
opposed beams in the plane of the
arc.
• Typical number of arcs used ranges
from 4 to 11.

45. Dynamic stereotactic radiosurgery
• The main features of the dynamic rotation is
the couch mounted frame approach and the
continual simultaneous rotation of the gantry
and couch during treatment.
• All points of beam entry lie in the upper
hemisphere on the patient’s head and all beam
exit points lie in the lower hemisphere.
• Even though all beams intersect in the target
volume at the linac isocentre and the gantry
travels almost a full circle (300o), there never
is a parallel-opposed beam situation to
degrade the steepness of the dose fall-off
outside the target volume.

46. Conical rotation:
• The patient rotates on a special treatment chair while the
gantry is stationary at a given angle off the vertical.
• Up to three gantry positions are used for a typical treatment,
resulting in conical circles for beam entry traces in the upper
hemisphere of the patient’s head and a conical irradiation
pattern.

47. Collimation for linac-based
radiosurgery
• Most linac based
radiosurgical techniques use
circular radiation beams
which are produced by
special collimators attached
to the head of the linac.

48. MicroMLC used in linac-based radiosurgery
• The use of microMLCs in conjunction with isocentric linacs enables a simple and efficient production of small
irregular fields in conformal radiosurgery.
• In contrast to the standard method used by the Gamma Knife and isocentric linacs which relies on multiple
isocentres (shots) to cover the full irregular target, the microMLC approach treats the whole irregular target with a
single isocentre.

49. Miniature linac on a robotic
arm (CyberKnife):
This radiosurgical technique uses:
• A miniature 6 MV linac instead of a
conventional isocentric linac mounted
on an industrial robotic manipulator.
• Non-invasive image guided target
localization, instead of the
conventional frame based stereotaxy.

50. New developments in linac-based radiosurgery:
• Fractionated radiotherapy which in contrast to radiosurgery is better suited for treatment of
many malignant disease.
• Irregular fields produced by microMLCs improve target dose homogeneity in contrast to
multiple isocentre technique practiced with a Gamma Knife.
• Very small radiation fields (of the order of millimetre in diameter) are available on linacs in
contrast to the minimum diametre of 4 mm available from a Gamma Knife in treatment of
functional disorders.
• Radiosurgery with relocatable frames and frameless radiosurgery are available with linacs.

51. TOTAL BODY IRRADIATION
• Megavoltage photon beams, either cobalt-60 gamma rays or megavoltage x rays are
used for this purpose.
• Usually, parallel-opposed irradiations are used by delivering each fractional dose in
two equal installments and switching the patient’s position between the two
installments.
• TBI treatment techniques are carried out with:
 Dedicated irradiators, i.e., treatment machines specially designed for total body
irradiation.
 Modified conventional megavoltage radiotherapy equipment:
 Treatment at extended source-surface distance (SSD)
 Treatment at standard SSD after the cobalt-60 machine collimator is removed.
 Treatment with a translational beam.
 Treatment with a sweeping beam.

52. A cobalt-60 machine dedicated for TBI.
The machine collimator has been removed to
obtain a large field for TBI irradiation at an SSD
of 230 cm.
Two linear accelerators mounted in such a
way that they produce two parallel-opposed
beams simultaneously.
Examples: Dedicated irradiators

53. Treatment at extended source-surface distance (SSD)
Modified conventional megavoltage radiotherapy equipment:
Treatment with a translational beam.

54. Sweeping beam technique with a column mounted linac.
Modified conventional megavoltage radiotherapy equipment:

55. Total skin electron irradiation (TSEI) is a special radiotherapeutic technique that aims to irradiate the patient’s
whole skin with the prescribed radiation dose while sparing all other organs from any appreciable radiation dose.
Since the skin is a superficial organ, the choice of electron beams for treatment of generalized skin malignancies
(most often mycosis fungoides) is obvious, even though superficial x rays were in the past used for this purpose.
TOTAL SKIN ELECTRON IRRADIATION

56. The TSEI techniques in use today may be grouped into
three main categories:
• Translational techniques, in which the patient is translated on a
stretcher through an electron beam of sufficient width to cover
the patient’s transverse dimensions.
• Large electron field techniques, in which a standing stationary
patient is treated at a large SSD with a single large electron
beam or a combination of large electron beams.
• Rotational techniques, in which the patient is standing on a
rotating platform in a large electron field.

57. • Intraoperative radiotherapy (IORT) is a special radiotherapeutic technique
that delivers in a single session a radiation dose of the order of 10 - 20 Gy
to a surgically exposed internal organ, tumour or tumour bed.
• IORT combines two conventional modalities of cancer treatment: surgery
and radiotherapy.
INTRAOPERATIVE RADIOTHERAPY

58. • A full implementation of image guided radiotherapy will lead to the concept of adaptive radiotherapy (ART).
• In ART the dose delivery for subsequent treatment fractions can be modified to compensate for inaccuracies in
dose delivery that cannot be corrected simply by adjusting the patient’s positioning like in the IGRT.
• The causes of these inaccuracies may include:
 Tumour shrinkage during the course of treatment.
 Patient loss of weight during the course of treatment.
 Increased hypoxia resulting during the course of treatment.
ADAPTIVE RADIOTHERAPY

59. ADAPTATION

60. 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?

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

62. ART is technically challenging and labour-intensive
Daily re-planning?
Manual contouring:
• Time consuming
• subject to intra or
interobserver variations
(Geets et al. 2005)
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).

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

64. 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.

65. Workflow for
image - guided
adaptive RT

67. RESPIRATORY GATED RADIOTHERAPY
• The quest for ever increasing tumour doses (dose escalation)
to increase the tumour control probability (TCP) and
simultaneously minimize the normal tissue complication
probability (NTCP) requires a move towards smaller margins
combined with an increased need to deal effectively with
organ motion during treatment.
• The next big challenge in IGRT comes from the natural and
unavoidable organ motion during treatment.

68. RESPIRATORY GATED RADIOTHERAPY
• To account for natural organ motion 4-D imaging
technology was developed.
• 4-D imaging technology allows viewing of volumetric
CT images changing over the fourth dimension: time.
• Examples of 4-D dose delivery techniques:
 Image guided radiosurgery, an elegant approach to dealing
with organ motion.
 Respiratory gating system (RGS), a special accessory added
to a linac to compensate automatically and instantly for the
effects of respiratory movement on external beam
radiotherapy to the chest and upper abdomen.

69. Future in Precision Radiotherapy:
1. Flash Therapy
2. Image-guided Radiotherapy Systems (MR guided LINAC)
3. Image-guided Radiotherapy Systems (PET CT guided LINAC)
4. PULSAR (Personalized, Ultra-fractionated, Stereotactic, Adaptive Radiotherapy)
5. AI in Radiotherapy
6. The Alpha DaRT Technology
7. Particle Radiotherapy

70. Flash Therapy is Biggest Technology Trend in Radiation
Oncology
• Rather than days or weeks of fractions of radiation given to a
patient, the entire massive dose is delivered all at once very
quickly in one fraction.
• Healthy tissues appear to recover pretty well, while the high
doses destroy the cancer cells very rapidly.
• If this proves to be safe and effective in clinical studies, it
will likely revolutionize radiation therapy.
• This also will make a lot more patient treatment slots
available on existing treatment systems.
A pre-clinical cat study of electron beam flash therapy to treat a
nasal tumor. The therapy was 4.5-6 MeV electrons, 25-41 Gy at
300 Gy per second. to treat the tumor in one fraction.
Flash Therapy

71. Image-guided Radiotherapy Systems
• MRI guided LINAC systems have become popular in the
past few years because they allow real-time imaging during
radiation delivery.
• It involves gating of the target volume within a user-specified
boundary, in which the beam is only on if the PTV falls
within the pre-defined boundary.
• AI is being integrated into MR-linacs to help rapidly alter
treatment plans with the patient on the table and help shorten
treatment times.
An example of real time imaging during a
prostate MRgRT treatment. The blue contour
depicts the prostate target tracking contour. The
red contour depicts the gated treatment
envelope boundary.

72. Image-guided Radiotherapy Systems
Reflexion X1 linac system.
• Biology-guided radiotherapy (BgRT) is a
new external beam radiotherapy delivery
modality combining PET-CT with a 6 MV linear
accelerator.
• The key innovation is continuous response of the
LINAC to outgoing tumor PET emissions with
beamlets of radiotherapy at subsecond latency.
This allows the deposited dose to track tumors in
real time.
• By transforming tumors into their own fiducials
after intravenous injection of a radiotracer, BgRT
has the potential to enable complete metastatic
ablation in a manner efficient for a single patient
and scalable to entire populations with metastatic
disease.

73. • PULSAR starts with a large
“pulse” of radiation therapy,
which we can then titrate, or
adjust, in subsequent doses
depending on how the tumor
responds between longer
treatment intervals.
• With this adaptive approach,
each treatment informs the
next, and as the tumor shrinks,
we can radiate an increasingly
smaller field, sparing healthy
tissue and reducing toxicity.
• PULSAR takes the precision
of SAbR to the next level.
PULSAR (Personalized, Ultra-fractionated, Stereotactic, Adaptive Radiotherapy)

74. AI in Radiotherapy
Applications of AI in the radiation therapy workflow.

75. The Alpha DaRT Technology
• Diffusing Alpha-emitters Radiation Therapy (‘Alpha DaRT’) is a
revolutionary new cancer treatment modality, which enables – for the
first time - the treatment of solid tumors by alpha particles.
• The basic idea is to insert into the tumor an array of implantable
seeds, whose surface is embedded with a low activity of radium 224.
Each seed continuously emits into the tumor, a chain of short-lived
alpha emitting atoms which spread by diffusion and convection over
several mm around it.
• The first trial, in Rabin Medical Center (Israel), focuses on recurrent skin and oral cavity squamous cell
carcinoma, and tumor size < 5 cm. So far, 15 of the enrolled patients have completed follow-up. Tumor
locations included the chin, ear, tongue, lip, nose, forehead, scalp and parotid skin areas. Treatment was
delivered based on a CT-simulation pre-treatment plan. DaRT seeds were inserted under local anesthesia using a
specially designed applicator. 2-4 weeks after implantation, the seeds were removed, and six weeks after
treatment CT was performed to assess the effect of treatment. Initial efficacy results for 15 subjects who have
reached the study endpoint, are highly promising: 11 subjects (11/15, 73%) had a CR and 4 (4/15, 27%) had PR
(substantial reduction in tumor volume). The treatment was shown to be safe for both the patient and medical
staff. Local side effects of the treatment were minimal.

76. Particle Radiotherapy

77. Conclusions
 Technological advancement in Radiotherapy has provided
state-of-the-art instrumentation that enables delivery of
radiotherapy with great precision to tumor lesions with
substantial reduced injury to normal tissues.
 Combination of radiotherapy and immunocheckpoint
blockade has shown promising results especially in
targeting metastatic tumors through abscopal response.
 Advancement in Radiogenomics will enable personalised
Radiotherapy in near future.