Pencil Beam Scanning (PBS) in Radiotherapy of Malignant Lymphomas - - PowerPoint PPT Presentation

Pencil Beam Scanning (PBS) in Radiotherapy

• f Malignant Lymphomas
• J. Kubeš

PTC Prague, Czech Rep.

Dose 40- 50%

40% dose

Photons 60 Gy

Why proton beam therapy

Why protons ?

• Have Br

Bragg peak and th they stop

• p in

in th the tis tissue

• Radio

iobiological effec ectiven eness is is sim imila ilar

Bragg's peak is energy-dependent. This energy can be precisely regulated

Photons Protons

Better dose distribution in the body

2,400 X-rays of the skull

Proton therapy technology

• First clinical use – 1953
• Technology sophisticated from 2011

Cyclotron Magnetic optics Gantry

Pencil beam scanning

Technology available from 2011 A fundamental change in proton technology

• Better dose distribution
• Greater and more complicated targets
• Smaller neutron contamination

Equipment

Proton beam

• Cyclotron IBA

Proteus 5

• 230 MeV

nominal beam energy

Imaging

• 2x MRI
• 2x CT
• PET/CT

IGRT

• Verisuite
• VisionRT
• Robotic couch
• DynR

Clinical oncology Urology ORL Cooperation with:

• Czech and Slovakia comprehensive cancer centers
• Charles University, Czech Technical University, Academy of

Science

Malignant lymphomas

Malignant lymphomas 1) Comprehensive and extensive target volumes 2) Young patients 3) High curability rate 4) Late and very late effects of photon techniques

3D CRT – heart dose! IMRT - lung dose, breast dose!

Schellong et al., 2010; Hull et al., 2003; Heidenreich et al., 2003; Brusamolino et al., 2006; Harbron et al., 2013

• Cardiotoxicity - RIHD
• Ischemic heart disease
• Pneumotoxicity
• Secondary cancer

Better tool – PBS(?)

Cardiotoxicity

Hahn E. described 44 cardiac events in 125 HL patients. Risk was correlated with heart dose and heart vessels dose.

Popuation study 2,168 women Treatment 1958-2001 Heart Dmean = 4.7 Gy Risk increases with 7.4% per Gy Without threshold. Darby et al., 2013

Malignant lymphomas

Secondary malignancies

• Cellai et al. IJROBP (2001) described 14.9%

incidence of SM in 20 years.

In a lifetime approximately 42 of 100 people will be diagnosed with cancer. Approximately one cancer (star) per 100 people could result from a single exposure to 0.1 Sv of low-LET radiation above background.

Cardiotoxicity and secondary malignancies are significant complications of radiotherapy of lymphomas

• Probability is dose-dependent
• Proton radiation can significantly reduce

doses to the heart and integral dose

Which malignant lymphomas?

1

Maximum utilization of proton beam features:

• Sharp dose gradient
• Stopping at a defined depth
• Significant reduction of dose

Significant dosimetric benefit

• Hodgkin lymphoma/NHL
• Mediastinal forms
• Residual mediastinal mass
• Women, 25 years old, Hodgkin

lymphoma st. IIBE Residual PET + mediastinal

Malignant Lymphomas

PROTON THERAPY FOR THE MANAGEMENT OF HODGKIN AND NON-HOGKIN LYMPHOMAS INVOLVING THE MEDIASTINUM: GUIDELINES FROM THE INTERNATIONAL LYMPHOMA RADIATION ONCOLOGY GROUP (ILROG) Bouthaina Shbib Dabaja, Bradford S. Hoppe, John P. Plastaras, Wayne Newhauser, Katerina Rosolova, Stella Flampouri, Radhe Mohan, N. George Mikhaeel, Youlia Kirova, Karin Dieckmann, Lena Specht, Joachim Yahalom.

Problem - movement

Criteria gamma 3mm, 3% γ<1 [%] γ<1,5 [%] Average gamma Max gamma Gating 98.56 100 0.39 1.27 Without gating 67.88 88.52 0.76 2.00

Effects of movement

Motion management

• Repainting
• Gating
• Tumor tracking
• Deep inspiration

breathold

Movement still present! Promising, but technology still not available! Movement up to 1 cm! Stopping of movement, possible solution

Motion management - DIBH – Dyn‘R

Reproducibility

Fusion of two DIBH CT scans (HL, IS RT)

• 3 patients - CT in the upper or lower part of deep inspiration
• Comparison of differences in WET for 5 points for each CT series
• Calculation in Python

Robustness of deep inspiration

PET/CT check of dose distribution

• Activation of tissue
• PET/CT immediately after fraction (in 10 min)
• Spatial control
• Detection of activation outside of the target volume

CALCULATED

REAL

“Virtual” dose distribution “In vivo” dose control

10 20 30 40 2013 2014 2015 2016

Number of Lymphoma patients

Clinical experiences at PTC Prague

• 2013 - 2014 – 4D CT and

repainting

• 2015 – DIBH (in combination

with repainting, if necessary)

Proton Radiotherapy for Mediastinal Hodgkin Lymphoma: Single Institution Experience

Dědečková et al., 10th ISHL, Cologne, 2016

Characteristics of patient group (n=35)

Males/Females [pts.] 10/25 Age at the time of RT median [years] 27 (13-59 ) RT volume [pts.] Involved field 9 Residual disease 11 Involved site 15 Follow-up median [months] 9.9 (2.6-36.4) RT on PET neg/PET positive disease [pts.] 25/10 RT in DIBH/FB [pts.] 17/18 Median dose [GyE] 30 (19.8-44) All patients were irradiated via pencil beam scanning (PBS) technique

Dědečková et al., 10th ISHL, Cologne, 2016

Dosimetric parameters (n=35)

PTV volume [cm3] 1,207.6 (442.8-2,252.8) Heart Dmean [Gy] 6.6 (0.9-20.7) Lungs bilat. Dmean [Gy] 4.9 (2.4-9.2) Lungs bilat. V5 [%] 30 (12-59.8) Lungs bilat. V20 [%] 22.3 (7.9-44.8) L mammary gland Dmean [Gy] 1.3 (0-6.8) R mammary gland Dmean [Gy] 0.9 (0-2.5) L mammary gland V4 [%] 11.6 (1.4-48.2) R mammary gland V4 [%] 10.2 (1.7-19.4) Oesophageus Dmean [Gy] 17.3 (0-30.8) Spinal Cord Dmax 2% [Gy] 5.2 (0-21)

Dědečková et al., 10th ISHL, Cologne, 2016

• Pharyngeal mucositis

– grade 2: 9% – grade 1: 63%

• Leucopenia

– grade 3: 3% – grade 2: 6% – Radiodermatitis

• grade 2: 3%
• grade 1: 40%
• Pleuritic pain

– grade 1: 3%

Acute toxicity (CTCAE v4.0)

NO CASE of radiation pneumonitis or Lhermitt´s syndrome NO PATIENT required growth factors

• r

hemosubstitution during RT Dědečková et al., 10th ISHL, Cologne, 2016

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 5 10 15 20 25 30 35 40

Relaps probability

Time (months)

Time to relaps (Kaplan Meier)

Total observed Total failed Total censored 35 2 33

Treatment results

• 35 patients (100%) achieved

local control

• 2 pts (6%) progressed out
• f the target volume (distal

regions)

• 34

pts (97%) are in complete remission (1 pt after alo-SCT)

• 1 pt (3%) has progressive

disease on salvage therapy

Dědečková et al., 10th ISHL, Cologne, 2016

– Promising and safe option for a majority of patients – Low acute toxicity profile and a potential to decrease the risk of significant late toxicity – Should be considered in all HL patients indicated for mediastinal RT ( first of all, young patients with long life expectancy) or re-irradiation

Summary on protons for mediastinal Hodgkin lymphoma

Female, 44 years

• Hodgkin lymphoma, NS, st. IIB, dg. 5/2016,

1 Risk factor

• Initial involvement: mediastinal mass

72x28 mm, pretracheal mass 39x30 mm, mediastinal lymf nodes 18 mm, left axilar and supraclavicular lymph nodes

• 2x escal. BEACOPP+2x ABVD
• Metabolic CR 9/2016
• 10/2016 RT IS 30 Gy/15fr
• Last follow up: 3/2018
• CR
• without toxicity

Case 1 – Media iastin inal Hodgkin Lymphoma

Organ at risk Parameter Dose Gy PTV Dmean 27,85 Lung (R+L) Dmean 4.96 Heart Dmean 3,17 Spinal cord Dmax 1.7 Breast R Dmean 1.61 Breast L Dmean 1.17

Standard case – significant reduction

• f heart dose, lung dose, reduction
• f breast dose

Male, 23 years

• Hodgkin lymphoma, NS, st. IIB, dg. 11/2017, 2 Risk factors
• Initial involvement: mediastinal mass 72x28 mm, including

lower mediastinum precordialy, supraclavicular and neck lymph nodes

• 2x ABVD
• Interim PET/CT – negative
• 2x ABVD
• 5/2018 RT IS 30 Gy/15fr
• Last follow up: 9/2018
• episode of asymptomatic radiation pnemonitis
• CR based on PET/CT 8/2018

Case 2 – Media iastin inal Hodgkin Lymphoma

Organ at risk Parameter Dose Gy PTV Dmean 28.32 Lung (R+L) Dmean 5.26 Heart Dmean 5.8 Spinal cord Dmax 13.8 Esophageus Dmean 13.15

Most suitable case for protons -– significant reduction of heart dose, lung dose

Male, 69 years

• Non Hodgkin B-lymphoma, DLBCL, dg. 12.10.2017, st.IIAS, -

Initial involvement: liver hilus, spleen

• stp 6X r-CHOP+2X R
• PR on PET/CT (PET+ liver involvement, CR spleen)
• 7/2018 RT to PET+ residual disease 36 Gy/18fr

Case 3 – Subdia iaphragmatical Non-Hodgkin Lym ymphoma

Organ at risk Parameter Dose Gy PTV Dmean 33.5 Liver Dmean 6.42 Kidney R Dmean 8.85 Kidney L Dmean 3.57 Spinal cord Dmax 26.6

Feasible with protons -– significant reduction of liver, kidney, abdominal cavity dose

Female, 26 years

• Non Hodgkin B-lymphoma, DLBCL, CD 20+, aaIPI 2 (LDH, PS), RF

(mediastinal bulk, Ki67 80%, sTK) dg. 3/2017, st.IIA,

• Initial involvement – mediastinal mass 142x88x197 mm, lymph nodes

mediastinal

• stp. 2x R-PACEBO from 3/2017,
• restaging after 2.cyklus – PR
• R-IVAM from 5/2017
• R-HAM priming from 27.6.2017, sběr PSC,
• 3x R-PACEBO
• Trnsplantation of PBSC 14.8.2017
• PET/CT 24.11.20107: persistent/progressive disease in mediastinal mass
• Radiotherapy to the PET+ residual disease 50 Gy/25fr – 1/2018
• Allo-SCT – 3/2018
• 9/2018 – PR-CR

Case 4 – Media iastin inal Non-Hodgkin Lym ymphoma, , hig ighly ly pretreaed

Organ at risk Parameter Dose Gy PTV Dmean 37.25 Lung (R+L) Dmean 8.74 Heart Dmean 15.5 Spinal cord Dmax 0.05 Esophageus Dmean 17.2

Refractory, bulky mediastinal disease – almost impossible to treat to such doses with photons. Probably CR after alo-SCT

Male, 37 years

• Non Hodgkin T-lymphoblastic lymphoma, st.IVB,
• Several lines of chemotherapy
• Allo-SCT including TBI
• PET + residual disease in mediastinum and pleural cavity
• Radiotherapy to the PET+ residual disease 36 Gy/18 fr – 8/2013
• 5/2016 – CR, without significant toxicity

Case 5 –Non-Hodgkin Lym ymphoma, , hig ighly pretreaed, , ple leural in invole lement

Organ at risk Parameter Dose Gy PTV Dmean Lung (R+L) Dmean Heart Dmean Spinal cord Dmax Esophageus Dmean

Refractory disease, pleural involvement, after TBI – considered like palliative treatment, 3 years after CR

Conclusion

Demografické parametry

• Adaptive radiotherapy with PBS for Head and neck

cancer is feasible approach with low toxicity rate and promising effectivity

• PBS radiotherapy with gating in DIBH is feasible

approach for malignant lymphomas with significantly better dosimetry than photon radiotherapy

Thank you for attention!