放射治療的演變 -放射生物、放射物理與治療儀器

季匡華教授國立陽明大學醫學系新光醫院腫瘤治療科主任

Radiotherapy: an overlooked modality

• Radiotherapy is the most overlooked cancer therapies.

• 100 cancer survivals, 50 principally from surgery, 45 from radiotherapy and 5 from others.

• Only 2% are spent on radiotherapy from total national insurance budget.

放射治療常用之游離輻射

放射劑量單位 SI Units

1Gy = 100cGy, 傳統常用分次劑量為 1.8Gy 或 2Gy,

即 180cGy 或 200cGy

現代直線加速器可產生高能 X-射線 +/- 高能電子束

Percent Depth DosePercent Depth Dose

% DD = Absorbed dose at A

Absorbed dose at Dmaxx 100 %

Dependence on composition of the irradiated medium.

Dependence on field size and shape.

Dependence on energy and depth.

Dependence on distance. ( increase with distance)

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高能 X-射線可治療較深層的腫瘤高能電子束治療較表淺的腫瘤

Photon beam profile Electron beam profile

Immobilization Device – Mask or Cast

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Four-field techniques are typically used in such sites as the abdomen or the

pelvis.

6MV 18MV

Variations in the dose gradient are achieved by differential weighting of each pair of

beams

Beam’s eye view

Wedges & Compensators

Skin sparing effect

Collimator

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Equipments In Radiation Oncology DepartmentEquipments In Radiation Oncology Department

Treatment Planning

2-D Planning System

3-D Planning System

Conformal Planning

Intensity Modulation Planning

Immobilization Device

Mask, Cast, Cradle, Invasive fixation frame

Total body noninvasive fixation device, Belly board

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• 傳統 2D 放療只能計算點及某些面 , 無法看到全面的構造 .

• 3D 隨形放療能透過 CTscan 看到以及計算全面的構造 . 但是照野內劑量仍是一視同任的 .

照野形狀 :多葉式準直儀Multi-leaf Collimator for Field Shaping

MLC 內建於机頭，每一葉片由獨立馬達軀動。照野形狀輸入電腦即快速將葉片拉到需要的形狀。

gantry 15

gantry 320gantry 270

gantry 220gantry 180gantry 70

每一角度皆有一畫素之組合，六個角度就組成一完整的 IMRT

Procedures of RadiotherapyImmobilization

Simulation

Defined targets and risk organs

Treatment Planning

Verification

Treatment

影像重建可看到靶區與重要器官的空間關係

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DKHC

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4-R’s In Radiobiology4-R’s In Radiobiology

1. Reoxygenation.

2. Repopulation.

3. Repair.

4. Radistribution.

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分次 治療 (Fractionation Scheme)

總量 , 分次量 , 照野大小 , 總治療時

分次治療的原則 (1)

• 分次治療最重要的目的是拉開腫瘤組織與正常組織放射耐受性間的差距

• 愈精細的機種，分次的次數就可以愈少 (5 次~10 次之間 )

• 愈小的腫瘤，分的次數可以愈少。 ( 加馬刀不適合治療 3 公分以上的腫瘤 , 因為只照一次 )

• 一般的放療每次約 200 雷德照射，依不同的情況，一療程分 25~35 次之間完成

分次治療的原則 (2)

• 生物效應是單次計量越高 , 生物效應加成的增加

• 例如 200 rad x 35 次約等於 250 rad x 25次 , 300 rad x 19 次 , 400 rad x 13 次 , 500 rad x 8 次 , 2000 rad x 1 次

• 惡性瘤不應該單次治療 , 一般分五次以上才合理 .( 因為供氧的關係 )

• 但治療超過 5 週 , 其實也有不利的邊照邊長的壞處

Wonder drug

• Hypofractionation schedule through new equipments have got more positive results than conventional fraction schedule.

• Radiation is a wonder drug for cancers that can be delivered to anywhere in the body with high dose to target, moderate dose to high risk and minimal dose to peripheral area by new equipments.

放射治療的定義、目的及一般通則• 定義 : 利用游離輻射線 (X- 射線、伽傌射線、高 能粒子束如電子及質子等 ) 照射腫瘤以殺 死癌細胞• 目的 :局部控制 (治愈或緩解治療 )、減少復發及

轉移

• 腫瘤區劑量愈高愈好、正常組織的劑量愈少愈好• 沒有照不死的癌細胞只怕劑量不夠(往往受限於正常組織的耐受劑量 )

• 可配合化療或手術使用以增加局部控制• 器官保留治療方法之一• 放療也可治療一些良性疾病

放射治療的重要性1. 與外科一樣，是屬於治癒性的治療手段。

化療、標靶基本上是非治癒性的。2. 在許多的情況下，可取代外科手術，做器

官保留的治療。3. 在許多的情況下，幫助降低外科的局部復

發率。4. 癌症病人 60 ％需要放射治療。

放療的適應症–首先要決定治療的性質–治愈性 (Curative intent):

• 第一線治療或器官保留治療 : eg: NPC, prostate cancer, head and neck cancer, esophageal cancer, lung cancer, anus cancer, cervix cancer, bladder cancer

• 手術前照射以縮小腫瘤以便開刀• pre-op: down staging• 手術後輔助性放療 ，增加局部控制。• 如手術邊沿不夠或有殘留癌細胞、淋巴管或血管浸潤，多顆局部淋巴結轉移

放療的適應症–緩解性 : 症狀控制、增加生活品質

•原則 : 「見好就收」

• Brain metastases, spinal cord compression, • SVC syndrome• tumor bleeding• obstruction (airway, esophagus, intestinal,

bile duct, trachea, bronchus… etc• cancer pain and bone pain.

•通常使用較大分次劑量，由 2.5Gy 至 5Gy 不等，總劑量由 20Gy 到 50Gy 上下

應該給多少劑量 ?

Depends on histology,

Radiosensitivity, size of tumor and treatment intent

Probability of Tumor Control

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Radiotherapy Unique in

1. Mathematically predictable.

2. Accurate medicine.

3. Surgically effective, but non-invasive.

Modern Curative RT Requires

1. Target volume of high dose must encompass the entire tumor.

2. Any microscopic extensions of disease must be covered with low to intermediate dose, but volume should be as small as possible.

3. Image-guide.

Why failure of Radiotherapy

1. Inadequate delineation of target.

2. Inadequate dose.

3. Moving targets.

4. Intrinsic radioresistance.

5. Acquired radioresistance.

Radiotherapy moving out from radiology to oncology since 1970, but now, moving more back to radiology.

Modern radiotherapy depends on more accurate radiology tools such as MRI, MRS, FDG-PET, choline PET, acetate PET, PET for cell proliferation, hypoxia, angiogenesis, apoptosis gene expression, etc.

Re-engaging Radiology and Radiotherapy

Radiology

Radiotherapy

Molecular Oncology

Wilhelm Roentgen Francois Baclesse

The Advent of PET/CT in Radiation Therapy Planning

1. Imaging of lesions not apparent on CT or MRI, such as unsuspected lymph node or distant metastases.

2. Prevention of futile irradiation of abnormalities that do not contain tumor, such as at atelectasis.

3. Imaging of biologically diverse tumor sub-volumes could potentially allow dose painting (different dose to different tumor regions)

4. Superior evaluation of tumor mass during or after chemotherapy.

5. Development of response adapted therapy in which changes to target volumes could potentially be make during a treatment course.

MVCT used to realign the internal target.

Image Guided Stereotactic RadiotherapyImage Guided Stereotactic Radiotherapy

Hodge W, Mehta MP.ActaOncol. 2006;45:890-6

Improved Targeting: GBM

• Relapses are local

• RT dose-response relationship

• Ideal for RT dose-escalation Local progression at 10 months

Distance from Edge of Initial Tumor (cm)

Incidence (% of All

Recurrences)

<1 60

1−2 19

2−3 18

>3 3

Walker MD: IJROBP. 1979;5; Hochberg FH: Neurology. 1980;30; Wallner KE: IJROBP. 1989;16.

GBM Higher Dose Improved Survival

SouhamiL, et al. IJROBP. 2004.

RT +/- SRS

Sur

viva

l Rat

e (%

)

Months

100

80

60

40

20

0

0 6 12 24 3018 36

RTSRS+RT

Median n Survival Time70 13.5 mo69 13.6 mo

P=0.64

1.0

0.8

0.6

0.4

0.2

0100

Surv

ival

Pro

babi

lity

Months to Death Since Surgery

0 20 40 60 80

RTBrx+RT

Median nSurvival Time69 13.2 mo71 13.8 mo

P=0.49

RT +/- Brachy

LaperriereNJ, et al. IJROBP. 1998

Where’s Waldo? Amino-Acid PET?

Malignant Glioma: T1 Contrast-enhanced volume: 4 mlMET-PET-defined volume: 72 ml

Courtesy: AncaGrosu, University of Freiburg, Germay

Equipments in Radiation Oncology DepartmentEquipments in Radiation Oncology Department

Treatment Machine

Linac

Cobalt machine

Gamma Knife

Brachytherapy

Low dose rate, high dose rate

Simulation Machine

Simulator

CT scanner

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高能治療機分類.壹 以物理性質區分

光子 photon

電子 electron

質子 proton

重離子 heavy ion

.貳 以体內外給予方式區分遠隔治療機 teletherapy

近接治療機 brachytherapy

近 20年來放療最重要的進步

• 強度調控• 影像導引

1900 1925 1950 1975 2000

•1895-Roentgen Discovered X-rays •1896-Cancer Treatment

•1928-dosimetry system•1951- 鈷六十

•1971-First Microprocessor (CPU)•1972-CT 發明

•1981-MRI 發明•1990-Digital Clinac

•1992-MLC 多葉片準直儀•1994- 加馬刀、光子刀

•1996-3D- 治療計畫•1997-Integrated System

•1998-IMRT 問世•2001-See and Treat•2003 – 影像導引 MRT

20世紀放射治療的發展里程碑

•2005 – 螺旋刀

高能治療機分類.參 依照野可變性原理區分

1. 以不可變固定圓形 (柱狀圓柱延伸管 ) 組合照野 加馬刀 Gammaknife 光子刀 X-ray knife 電腦刀 Cyber knife

2. 以可變小方形 ( 準直儀小葉片 ) 組合照野強度調控放療 IMRT螺旋刀 Tomotherapy諾力刀 Novalis

.肆 依是否具備影像導引功能區分 透視 X 光機 : 電腦刀 Cyberknife 組合式半 CT scan功能 (cone beam CT): 影像導引直線加速器 IGRT

全 CT scan功能 (MVCT): 螺旋刀 Tomotherapy

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1. 強度調控治療的小方塊愈細，劑量的隨形度愈好。( 一般 IMRT 由 1× 1 cm 到 0.5×0.5 cm ， tomotherapy 最細為 0.625×0.175 cm 。 )

2. 強度調控治療的入射角度愈多，劑量愈隨形、愈集中。 ( 一般 5-9 個角度， tomotherapy 為 51個角度。 )

3. 非強度調控的放射手術用 cone 來組合劑量，由0.4 公分直徑 ~1.8 公分直徑不等。

Cyberknife Cone

Thank You!

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