1701 ahnyc imrt lung

IMRT for Lung Cancer

Yong Chan Ahn, MD, PhD Dept. of Radiation Oncology

Samsung Medical Center Sungkyunkwan Univ. School of Medicine

HICARE, 2017

Types of IMRT

• LINAC-based: • MLC motion:

• Step & shoot • Dynamic

• Rotating gantry (VMAT)

• Tomotherapy-based: • Helical rotation

JTO, 2014

Clin Oncol, 2016

• Improved PTV coverage with IMRT. • Mixed results to OARs:

• IMRT reduces V20, heart and spinal cord doses • Variable V5 was variable

• Treatment time advantage in favor of VMAT over standard IMRT: VMAT (6.5 minutes) vs IMRT (11.1 minutes) vs Tomotherapy (15.9 minutes).

• Shorter treatment time reduces risk of intra-fractional movement and maximizes linear accelerator capacity.

Retrospective clinical studies (Tx and planning parameters)

Retrospective clinical studies (toxicity and outcomes)

Retrospective studies • Yom et al. (MDACC, Red, 2007):

– 68 NSCLC patients (85% stage III) treated with IMRT (2002~2005).

– 222 historical controls treated with 3DCRT (2000~2003).

– Reasons for IMRT: large treatment volume, failure to meet normal tissue dose constraints for 3DCRT, synchronous lung primary tumors, and poor baseline pulmonary function.

– Majority received 63 Gy in 35 fractions and concurrent platinum-based doublet chemotherapy.

– Despite larger GTV in IMRT (194 cc vs 142 cc), V20 was significantly lower, but V5 was larger than 3DCRT.

– Incidence of grade ≥3 TRP was significantly lower in IMRT (8% vs 22% at 6 months).

Retrospective studies • Liao et al. (MDACC, Red, 2010):

– 91 patients treated with 4DCT/IMRT (2004~2006).

– 318 historical controls receiving 3DCRT (1999~2004).

– Median 63 Gy using conventional fractionation.

– IMRT group contained greater proportion of patients who were older, current smokers, or staged with PET-CT (82% 4DCT IMRT vs 49% 3DCTRT).

– GTV was not reported.

– Reduced rate of TRP in IMRT group, with significantly lower V20 (34% vs 37%) and higher V5 (65% vs 57%).

– Similar LC and DM, but improvement in OS in IMRT group (median OS 1.40 years for 4DCT/IMRT and 0.85 year for 3DCRT).

Retrospective studies • Jiang et al. (MDACC, Red, 2012):

– Long-term outcome of 165 patients treated with 4DCT IMRT (76% stage III) +/- concurrent chemotherapy.

– Median 66 Gy in 33 Fxs and median GTV was 124.6 (4.3~730) cc.

– 11% developed grade ≥3 TRP at 6 months; one grade 3 pulmonary fibrosis at 18 months.

– 29 (18%) experienced grade 3 esophagitis and majority settled within 6 weeks; 4 developed esophageal stricture.

– Incidence and severity of toxicities were lower in IMRT patients than historical controls.

– With median 16.5 months FU, 2-year DFS and OS were 38% and 46%.

Retrospective studies • Sura et al. (MSKCC, Green, 2008):

– Assessed toxicity of IMRT in 55 stages Ib–IIIb (62% stage III) NSCLC patients (2001~2005).

– 60 Gy in 30 fractions with either sequential (53%) or concurrent (24%) chemotherapy.

– Mean GTV was 136 cc.

– With median follow-up of 12 months, 6 (11%) grade 3 pulmonary toxicity, and 2 (4%) grade 3 esophageal toxicity.

– 2-Yr OS was 58% with median survival of 25 months.

Retrospective studies • Govaert et al. (Green 2012):

– 71 stages IIb–IIIb NSCLC patients treated with IMRT (2008~2011).

– up to 66 Gy in 33 fractions with chemotherapy.

– Mean GTV volume was not reported.

– No grade 3/4 pulmonary or esophageal toxicity was observed, and no treatment-related deaths.

– With median follow-up of 12 months, median survival was 29.7 months and 2-Yr OS was 56%.

Retrospective studies • Uyterlinde et al (Clin Lung Ca, 2013) and Chen et al

(Green, 2013) (Netherlands Cancer Institute):

– Hypo-fractionated IMRT (66 Gy in 24 fractions) and concurrent chemotherapy.

– 35% developed grade >3 acute toxicity and 7% developed TRP.

– 6% (11/171) developed severe late esophageal toxicity (stenosis in 8 and fistula in 3), which was comparable to historical cohorts treated with 3DCRT.

– 2-Yr OS was 52%.

Prospective studies • Cannon et al. (JCO, 2013):

– Phase 1 dose escalating hypo-fractionated IMRT in NSCLC (79 patients based on TRP risk in 25 fractions).

– Patients with all stages of disease were recruited and 62% received neoadj or adj chemotherapy.

– All were PET staged, planned using 4D-CT and treated with helical tomotherapy.

– No grade 3 acute or late esophageal or lung toxicity up to 85.5 Gy/25 fractions.

2.28 Gy/Fx 2.53 Gy/Fx 2.77 Gy/Fx 3.0 Gy/Fx 3.22 Gy/Fx 3.42 Gy/Fx

Prospective studies • Cannon et al. (JCO, 2013):

– 6 grade 4/5 toxicities (massive hemoptysis and broncho-cavitary fistula) associated with central tumors, doses above 75 Gy, and specific 1~3 cc doses to proximal bronchial tree.

Prospective studies • RTOG 0617 study (Lancet Oncol, 2015):

– Phase 3 trial (60 Gy/30 Fxs vs 74 Gy/37 Fxs + conc paclitaxel/carboplatin, +/- cetuximab.

– Survival and LC disadvantage for high-dose arm.

– Under ½ of patients were treated with IMRT (46.5%: 46.1% in 60 Gy arm and 47.1% in 74 Gy arm).

P=0.0042

Population-based studies • Shirvani et al. (2001~2007 SEER DB, Lung Cancer, 2013):

– Year of diagnosis and treatment in dedicated center were the only independent predictors of IMRT use.

– Lung and esophageal toxicity was equal between IMRT and 3DCRT groups.

• Harris et al. (2002~2009 SEER DB, Red, 2014):

– Comparative effectiveness study on outcomes in stage III NSCLC for IMRT, 3DCRT, and 2DRT techniques.

– Nearly 7,000 patients

– IMRT was associated with similar toxicities and OS to 3DCRT.

– IMRT and 3DCRT showed advantage over 2DRT.

Conclusions • IMRT can achieve better dose conformality, avoid

OARs and lower treatment toxicity.

• Compared to 3DCRT, planning process and treatment delivery is time consuming and places strain on valuable resources.

• IMRT is best indicated when tumor volume is near to OAR or when treatment volumes are too large to treat to radical dose with 3DCRT.

• Further prospective data are needed to strengthen evidence base.

Advantages

• Ability to spare OARs.

• Better coverage of irregular shaped targets.

• Ability to dose escalate.

• Able to treat synchronous primary tumors and multiple targets simultaneously.

• Enables treatment of larger volumes to radical dose.

Disadvantages

• Increased contouring, planning, and QA time.

• Increased need to accurately delineate CTVs and involved nodes requiring treatment.

• Need for image guidance.

• Sharp dose gradient may lead to under-treatment of micro-metastatic disease.

• Potential interplay effects depending on fractionation and complexity of IMRT technique used.

• Low-dose radiotherapy bath.

Sem Rad Onc, 2016

IMRT or VMAT can spare more critical structures than 3DCRT in bulky stage III NSCLC tumor located near esophagus and heart.

• Little supporting clinical data:

– No randomized trial has compared conformal and IMRT,

– Few studies have reported late outcomes of IMRT,

– No evidence for improved control with increased dose.

• Best available evidence is level 3~4, and no ongoing phase II or III trials.

• Currently IMRT should be regarded as promising but unproven experimental therapy.

Sem Rad Onc, 2016

SMC experience

Selection of RT Technique

• RT technique selection was

individualized based on disease

extent and estimated toxicity

risks.

• IMRT was primarily offered if

DVH parameters were

unfavorable (if treated by 3D-

CRT):

– V20＞40%

– MLD＞25 Gy

– Spinal cord Dmax>50 Gy

• 3D-CRT: 3-4 portal, 4-10 MV

• IMRT: median 6 portals, 6 MV

Treatment Detail

• RT:

– Median 66 Gy in 33 Fxs

– Normal tissue constraints:

• Spinal cord: DMax<46 Gy

• Lung: V20<35%, V5<65%,

Mean<20 Gy

• Chemotherapy:

– Wkly docetaxel/paclitaxel + cis-

/carboplatin in 67 (87.0%)

– 3-wkly pemetrexed/etoposide +

cisplatin in 10 (13.0%)

Clinical characteristics

DVH parameters

Median PFS = 11.1 months

• IMRT has enabled to encompass larger disease extent

at high and homogenous radiation dose volume, which

could not have been achieved by 3D-CRT.

• Toxicities (esophagitis, pneumonitis) were not

increased though with IMRT group had more

unfavorable DVH parameters than 3D-CRT group.

• Early appearance of DM was most important factor in

PFS, which could be explained by high proportion of

adenocarcinoma histology and corresponding large

disease extent.

• OS might have been improved probably by effective

systemic treatment following progression (including

targeting agents).

Summary

• Frequent and early appearance of DM, associated

with adenocarcinoma histology, would require

modification of systemic Tx in concurrent &/or

salvage phases.

• RT technique selection guideline would be required.

Future Directions

• Beam angle optimization policy: • No beam (incident or existing)

passing though complete block is allowed.

• Only existing beam after passing through target is allowed to hit directional block.

Proton Therapy Center Samsung Medical Center

Example Case: Sq, cT2N3

Dose (Gy)

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Dose-volume Histogram (DVH)

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10

20

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90

100

0 10 20 30 40 50 60 70 80

Proton PTV

Proton Spinal Cord

Proton Both Lungs

IMRT PTV

IMRT Spinal Cord

IMRT Both Lungs

3DCRT PTV

3DCRT Spinal Cord

3DCRT Both Lungs

Tomo PTV

Tomo Spinal Cord

Tomo Both Lungs

Normal Tissue DVH

Lowest lung dose by IMPT

Excessive cord dose by 3D-CRT

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CTV DVH

IMPT

Tomo IMRT

3D-CRT

• Dosimetric study clearly showed more focal dose

distribution at lower toxicity risk by IMPT than

IMRT and 3D-CRT.

• RT technique selection guideline would be required

considering cost-effectiveness.

Future Directions

Fundamental Goals of RT

• To deliver high dose to tumor

• To safely limit dose to normal tissues

Different tools for same purpose!

Same tool for different purposes!

Thank you for attention!