Seed implantation for other body sites

COULD PERMANENT LDR BRACHYTHERAPY BE USED IN OTHER BODY SITES? Alfredo Polo MD, PhD Brachytherapy and Intraoperative Radiotherapy Unit Radiation Oncology Department. University Hospital Ramon y Cajal Madrid (Spain)

IMAGE-GUIDEDBRACHYTHERAPY AND SEED IMPLANTATION

IMAGE GUIDANCE TUMOUR IMAGE-GUIDED PHYSICALCOORDINATES BRACHYTHERAPY OPTIMIZATION RADIOBIOLOGY PREDICTIVE ASSAYS

Volume-based dose prescription

Technological Radiobiological framework framework BRACHYTHERAPY RELOADED Personalized treatments

Technological Radiobiological Personalised framework framework treatmentsHigh precision Geometric Molec. biol. IGBT issues Radiobiology Functional Imaging issues imaging Workﬂow Hypofractionation IDA templates

Imaging for tumor diagnosisImaging for IOP tumor localizationImaging for IOP dose planningOn-board imaging (navigation)

CT - BASED NAVIGATIONNicolau S. Un système de réalité augmenteé pour guider les opérations de foie en radiologie interventionnelle. These.

PREPLANNED BRACHYTHERAPYNicolau S. Un système de réalité augmenteé pour guider les opérations de foie en radiologie interventionnelle. These.

RADIOLOGY INTERVENTIONALSIDE SIDE• Link to PACS - RIS • Surgical simulation• View, acquire, processimages during intervention • IOP navigation• Cone beam CT • IOP dose calculation• Advanced US • Augmented reality• Digital endoscopy • Positioning

Seeds - Perfect implementation of IGBT• Single fraction treatment• No repositioning - Perfect tracking• IOP imaging, planning and optimization• IOP navigation (on-board imaging) and augmented reality• IOP dose delivery• Treatment completed in 1-2h

RADIOBIOLOGICAL AND PHYSICAL ASPECTS

HDR vs. LDR

MONTE CARLO AIDED 3D DOSE CALCULATION 0,10 0,08Dose (5cm)/Dose (1cm) 0,07 0,05 0,03 0,02 Attenuation and scattering Inverse-square law only 0 0 100 200 300 400 Gamma-ray energy (Kev)

Gradients and margins

TO TARGET

Deﬁning adequate margins in brachytherapy Margin Clonogen densityHerk M, et al. The probability ofcorrect target dosage: dose-population histograms for derivingtreatment margins in radiotherapy.IJRO 2000; 47: 1121-1135 GTVAntolak JA, et al. Planning targetvolumes for radiotherapy: howmuch margin is needed? IJRO1999; 44: 1165-1170 CTV Distance from edge

Target deﬁnition (Prostate) 100 % residual tumor 83 Davis, B. J. 1999 The radial 67 distance of extraprostaticextension of prostate carcinoma: 50 implications for prostatebrachytherapy 02/01/2008 23:17 Aged 81 728 33 No EIC 17 0 0 0,5 1 1,5 2,0 2,5 3,0 3,5 4 4,5 5 Distance from prostate capsule (mm)

Target deﬁnition (Breast) Holland 1985 Faverly 2001 Tumor @ 2cm50 50 4740 42 40 42 39 3930 30 2820 22 20 17 18 No T< T<10 10 10 EIC 2cm 2cm 12 0 0 0 0 1 cm 2 cm 3 cm 4 cm H85 F01 H90 M93 G92 Holland R et al. Cancer 1985; 56: 979-90 H85: Holland 1985, F01: Faverly 2001, H90: Holland Faverlyy D et al. Cancer 2001; 91: 647-59 1990, M93: Morimoto 1993, G92: Gump 1992

Target deﬁnition (Lung) 100 % residual tumorGiraud P, et al. 75Evaluation ofmicroscopic tumorextension in non-smallcell lung cancer for 50three dimensionalconformalradiotherapy planning. 25IJRO 2000; 48:1015-1024 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Distance from tumor edge (mm)

Impact of margin on tumor coverage 0 cm margin 1 cm margin 2 cm margin 3 cm margin 100 DoseHerk M, et al. The probability ofcorrect target dosage: dose- 75population histograms forderiving treatment margins inradiotherapy. IJRO 2000; 47: 501121-1135 25 0 0 10 20 30 40 50 60 70 80 90 100 Clonogens

Dose geographic miss dose failure 0 0 Volume

TECHNICAL ASPECTS

BT vs. Other high precision techniques

PROS CONS Multipurpose Integral dose CK Precise dose delivery Cost Tracking Precise dose delivery CostProtons Integral dose Tracking Tracking Reproducibility BT IOP adaptive Invasive Integral dose Selected indications

REVIEW OF THE LITERATURE

Number of Number of MeSH terms Title [Ti] terms publications publications Central nervoussystem neoplasm + 591 Seed 19 BrachytherapyLung neoplasms + 404 Seed 6 BrachytherapyBreast neoplasms + 587 Seed 5 BrachytherapyLiver neoplasms + Different search 104 0 - 10 Brachytherapy criteria Sarcoma + 299 Seed 0 Brachytherapy

Seed implantation for CNS malignancies

Techniques• External beam - based stereotactic irradiation• Catheter - based HDR brachytherapy (IOP vs. PostOP)• Seed (LDR) implantation (IOP vs. PostOP)

Courtesy Mayﬁeld Clinic

Courtesy Stanford University

of KPSs at the time of implant was as follows: 50 — 4%; 70 —18.7%; 80 —24%; 90 —36%; 100 —17.3%. Neuro- Classes V and VI because of the low patient numbers logic function was defined by (1) the ability to work/ main- entered, an approach seen in other studies (1). The propor- tenance of normal activities of daily living and (2) a mental tional distribution of patients per class in our analysis is status assessment. Fifty-seven patients (77%) were able- similar to that seen in the RTOG study, with combined bodied; 14 patients (18.9%) were engaged in limited or no Classes IV and V representing approximately 60% of pa- activities. Fifty-three patients (73.6%) had a normal mental tients in each study (I-125 implant 59.8%; RTOG Results status at diagnosis, with 19 (26.4%), an abnormal. For 59 58%). The stratification of the brachytherapy patients using the patients (81.9%), symptom duration preceding consultation RPA criteria revealed a significant difference in 2-year was 3 months whereas in 13 (18.1%), it was 3 months. survival between classes, with the best survival in Classes Fifteen patients (20.3%) underwent biopsy of the lesion I/II and the worst survival in Classes V/ VI (Fig. 1). This alone, whereas 59 (79.7%) had partial or total resection of reflects the class survival trend which is seen in the RTOG the primary tumor. All such biopsy patients received a analysis. This result for the implants did not achieve statis- minimum of 54 Gy adjuvantly by EBRT. Pathological ex- tical significance but was suggestive (p 0.1). Although amination of the MG specimens showed that 22 patients direct statistical comparison between the two studies wasology ● Biology ● Physics Volume 45, Number 3, 1999 anaplastic astrocytoma (AA) while 53 patients (29.3%) had (70.7%) had glioblastoma multiforme (GBM). Of the 75 Table 5. Selectedimplanted,brachytherapy in the data to complete the patients studies of 3 patients lacked initial Table 4. Comparison of 2-year survival by RPA class: management of malignant gliomas implanted MG patients versus RTOG RPA data base RTOG class criteria; 72 patients were therefore considered in the present study. Median I-125 implant patients RTOG MG data base A number of No. of follow-up intervals were defined for the survival Author/Referencestudy. We looked atDiagnosis from (Mth) diagnosis present patients the time primary S MST S MST Class (%) CI (months) (%) CI (months) to the time of analysis for (1) all patients: 13.5 months Zamorano et al. (18, 19) 50 AA NR (range 2– 80); (2) 44 AA GBM for patients: 29 months (range 70 – 16 I/II 68* 29.5, 86.5 37* I 76 68.7, 83.3 58.6 Fernandez et80);(6) for GBM 40 al. (3) patients:AA months (range 2–79); and 12.6 31 II 68 51.6, 83.6 37.4 18 GBM 23 for all surviving patients at the time of analysis: 35 months III 74 12.5, 80.5 31 III 35 27.6, 42.2 17.9 Sneed et al. (16) 52 AA 36 IV 34 17.2, 55.1 16 IV 15 12.0, 18.0 11.1 (range 3– 80). 159 GBM 19 V/VI 29† 7.5, 32.6 11† V 6 4.0, 8.0 8.9 Gutin et al. (3) Survival estimates were obtained using157 wk 29 AA the Kaplan-Meier VI 4 1.8, 6.2 4.6 ients receiving standard method. Comparison of survival at 2 years between prog- 34 GBM 88 wkRTOG RPA classes. Lucas et al. nostic classes and with the previously reported RTOG re- (17) 7 AA 23 MG malignant glioma; S 2-year survival; MST median 6 Two-sided 95% confidence intervals GBM 10 survival time; CI 95% confidence interval. sults was performed. * Results combined for prognostic classes I and II. NR notwere calculatedweeks; mth months. values of the implant reached; wk for the 2-year survival † Results combined for prognostic classes V and VI; 2-yr S @ patients but could not be determined for the median survival 23 months.VI, overall survival for to the results for then the other hand, there longer survivals than noneligible patients. Of note, Florell etfor Class I/II patients al. (20) found the results for this favorable subset to be in vival in months, for {Videtic et al., 1999, Int J Radiat Oncol Biol Phys, 45, 687-92} the range of that reported in previous brachytherapy studies. The first substantial confirmation of the inferred benefits superior for the im- of CNS implants in the primary management of MG cameerparts. Of interest, the from the published abstract of the Brain Tumor Trial Co- implant was seen for operative Group Trial No. 8701 (11). This study random-with 25% improvement ized MG patients to boost with the brachytherapy implant or .9 months) and a more no boost. Survival was found to be significantly longer for at 2 years (29% vs. the implanted patients, which would suggest that patients le difference between selection alone was not the only factor influencing survival.group. Unfortunately, this group has not yet formally published ts were alive (40.3%) their results to update their initial report.r actuarial overall sur- Recently a randomized trial was published by the group %. The 5-year overall from the Princess Margaret Hospital and affiliated Toronto

Level of evidence• Level II evidence (Randomized trials): contradictory• Level III evidence suggesting beneﬁt from Brachytherapy

Seed implantation for lung cancer

Ariel, IM et al. The use of interstitial radon seeds and needles in inoperable lung cancer. Cancer 1949; 2: 581-586

Techniques• External beam - based stereotactic irradiation• Catheter - based HDR brachytherapy (IOP vs. Closed)• Seed (LDR) implantation (IOP vs. Closed)

* Case provided courtesy of St. Joseph’s Hospital, Phoenix, Arizona (USA)

Pre-treatment (1.5 mm slices) 15 weeks post-treatment (5 mm slices)* Case provided courtesy of St. Joseph’s Hospital, Phoenix, Arizona (USA)

{Martinez-Monge et al., 2008, Lung Cancer, 61, 209-13}

{Stewart et al., 2009, Brachytherapy, 8, 63-9}

Results• Sublobar resection with brachytherapy (IOP)• Paraspinal tumor resection (IOP)• Selected T1 - T2 (Closed technique *)* Competitive with other conformal techniques

Sublobar resection with brachytherapy {Stewart et al., 2009, Brachytherapy, 8, 63-9}

Paraspinal tumor resection with brachytherapy {Stewart et al., 2009, Brachytherapy, 8, 63-9}

Seed implantation for breast cancer (Partial Breast Irradiation)

1930 circa

Techniques• External beam - based Partial Breast Irradiation• Catheter - based HDR brachytherapy (IOP vs. PostOP)• Ballon - based HDR brachytherapy (IOP vs. PostOP)• Seed (LDR) implantation (PostOP)

Source: own material

Courtesy Douglas Arthur

{Jansen et al., 2007, Int J Radiat Oncol Biol Phys, 67, 1052-8}

{Pignol et al., 2006, Int J Radiat Oncol Biol Phys, 64, 176-81}

Level of evidence• Level II evidence for PBI using EBRT, Multicatheter and Balloon• NO Level II evidence for the use of seeds• Phase I - II feasibility studies• Preliminary results for prospective series

Seed implantation for liver cancer - mets

Techniques• Stereotactic Body Radiotherapy (SBRT)• Catheter - based HDR brachytherapy (IOP vs. Exclusive)• Seed (LDR) implantation (Exclusive)

Results: Liver metastases• SBRT: • 2y “in-ﬁeld” local control 92% {Rusthoven et al., 2009, J Clin Oncol, 27, 1572-8} • 1y local control 71% {Lee et al., 2009, J Clin Oncol, 27, 1585-91}• Brachytherapy: • 1y local control 72% {Pech et al., 2008, Strahlenther Onkol, 184, 302-6} • 2y local control 89% {Wieners et al., 2009, Cardiovasc Intervent Radiol, 32, 937-45}

Level of evidence• SBRT: Phase I - II studies• Brachytherapy: Phase I - II feasibility studies• Preliminary good results comparable to surgical series

Seed implantation for soft tissue sarcoma

Seed implantation for pelvic relapses

CONCLUSIONS

Seeds have always a missionSeeds are the way to achieve the objectiveSeeds are a good implementation of IGBTSeeds could be cost-efﬁcient

Seed implantation for other body sites

by Alfredo Polo

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