Pencil Beam Scanning (PBS) in Radiotherapy of Malignant Lymphomas J. Kubeš PTC Prague, Czech Rep.
Why proton beam therapy Why protons? - Have Bragg peak and they stop in the tissue - Radiobiological effectiveness is similar Bragg's peak is energy-dependent. This energy can be precisely regulated Better dose distribution in the body Dose 40-50% Photons Protons Photons 60 Gy 40% dose 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 IGRT - Verisuite - VisionRT - Robotic couch - DynR Imaging - 2x MRI - 2x CT - PET/CT 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 - Cardiotoxicity - RIHD - Ischemic heart disease - Pneumotoxicity - Secondary cancer 3D CRT heart dose! IMRT - lung dose, breast dose! Better tool PBS(?) Schellong et al., 2010; Hull et al., 2003; Heidenreich et al., 2003; Brusamolino et al., 2006; Harbron et al., 2013
Cardiotoxicity Hahn E. described 44 cardiac events in 125 HL patients. Risk was correlated with heart dose and heart vessels dose. Darby et al., 2013 Popuation study 2,168 women Treatment 1958-2001 Heart Dmean = 4.7 Gy Risk increases with 7.4% per Gy Without threshold.
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
1 Which malignant lymphomas? 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
Effects of 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
Motion management Repainting Gating Tumor tracking Deep inspiration breathold Movement up to 1 cm! Movement still present! Promising, but technology still not available! Stopping of movement, possible solution
Motion management - DIBH Dyn R
Reproducibility Fusion of two DIBH CT scans (HL, IS RT)
Robustness of deep inspiration 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
PET/CT check of dose distribution Virtual dose distribution CALCULATED In vivo dose control REAL Activation of tissue PET/CT immediately after fraction (in 10 min) Spatial control Detection of activation outside of the target volume
Clinical experiences at PTC Prague 40 30 20 10 0 Number of Lymphoma patients 2013 2014 2015 2016 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
Acute toxicity (CTCAE v4.0) 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% NO CASE of radiation pneumonitis or Lhermitt s syndrome NO PATIENT required growth factors or hemosubstitution during RT Dědečková et al., 10th ISHL, Cologne, 2016
Relaps probability Treatment results 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Time to relaps (Kaplan Meier) 0 0 5 10 15 20 25 30 35 40 Time (months) Total observed Total failed Total censored 35 2 33 35 patients (100%) achieved local control 2 pts (6%) progressed out of 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
Summary on protons for mediastinal Hodgkin lymphoma 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
Case 1 Mediastinal Hodgkin Lymphoma Female, 44 years - Hodgkin lymphoma, NS, st. IIB, dg. 5/2016, 1 Risk factor PTV Dmean 27,85 - Initial involvement: Lung (R+L) mediastinal Dmean mass 4.96 72x28 mm, Heartpretracheal Dmean mass 39x30 3,17 mm, mediastinal Spinal cord lymf Dmax nodes 18 mm, left 1.7 axilar and Breast supraclavicular R Dmean lymph nodes 1.61-2x escal. BEACOPP+2x ABVD Breast L Dmean 1.17 - Metabolic CR 9/2016-10/2016 RT IS 30 Gy/15fr Organ at risk Parameter Dose Gy Standard case significant reduction of heart dose, lung dose, reduction of breast dose - Last follow up: 3/2018 - CR - without toxicity
Case 2 Mediastinal Hodgkin Lymphoma Male, 23 years - Hodgkin lymphoma, Organ at risk NS, Parameter st. IIB, dg. 11/2017, Dose Gy 2 Risk factors - Initial involvement: PTV mediastinal Dmean mass 72x28 28.32 mm, including lower mediastinum Lung (R+L) precordialy, Dmean supraclavicular 5.26 and neck lymph nodes Heart Dmean 5.8-2x ABVD Spinal cord Dmax 13.8 - Interim PET/CT Esophageus negative Dmean 13.15-2x ABVD - 5/2018 RT IS 30 Gy/15fr Most suitable case for protons - significant reduction of heart dose, lung dose - Last follow up: 9/2018 - episode of asymptomatic radiation pnemonitis - CR based on PET/CT 8/2018
Case 3 Subdiaphragmatical Non-Hodgkin Lymphoma Organ at risk Parameter Dose Gy Male, 69 years PTV Dmean 33.5 - Non Hodgkin B-lymphoma, DLBCL, dg. 12.10.2017, st.iias, - Liver Dmean 6.42 Initial involvement: liver hilus, spleen - stp 6X r-chop+2x Kidney R R Dmean 8.85 - PR on PET/CT Kidney(PET+ L liver Dmean involvement, 3.57 CR spleen) - 7/2018 RT Spinal to PET+ cordresidual Dmax disease 36 Gy/18fr 26.6 Feasible with protons - significant reduction of liver, kidney, abdominal cavity dose
Female, 26 Organ yearsat risk Parameter Dose Gy - Non Hodgkin PTV B-lymphoma, Dmean DLBCL, CD 20+, 37.25 aaipi 2 (LDH, PS), RF (mediastinal bulk, Ki67 80%, stk) dg. 3/2017, st.iia, Lung (R+L) Dmean 8.74 - Initial involvement mediastinal mass 142x88x197 mm, lymph nodes mediastinal Heart Dmean 15.5 - - stp. 2x Spinal R-PACEBO cord from Dmax 3/2017, 0.05 - restaging Esophageus after 2.cyklus Dmean PR 17.2 - R-IVAM from 5/2017 - R-HAM priming from 27.6.2017, sběr PSC, - 3x R-PACEBO - TrnsplantationRefractory, of PBSC 14.8.2017 bulky mediastinal - 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 Mediastinal Non-Hodgkin Lymphoma, highly pretreaed disease almost impossible to treat to such doses with photons. Probably CR after alo-sct
Case 5 Non-Hodgkin Lymphoma, highly pretreaed, pleural involement Organ at risk Parameter Dose Gy PTV Dmean Male, 37 years - Non Hodgkin Lung (R+L) T-lymphoblastic Dmeanlymphoma, st.ivb, - SeveralHeart lines of chemotherapy Dmean - Allo-SCT including TBI - PET + residual Spinal cord disease in Dmax mediastinum and pleural cavity Esophageus Dmean - Radiotherapy to the PET+ residual disease 36 Gy/18 fr 8/2013-5/2016 CR, without significant toxicity Refractory disease, pleural involvement, after TBI considered like palliative treatment, 3 years after CR
Conclusion Adaptive radiotherapy with PBS for Head and neck cancer is feasible approach with low toxicity rate and promising effectivity Demografické parametry PBS radiotherapy with gating in DIBH is feasible approach for malignant lymphomas with significantly better dosimetry than photon radiotherapy
Thank you for attention!