Radiation therapy can cause complications and side effects. Common early side effects include mucositis, dermatitis, and hair loss affecting areas receiving radiation. Late effects include xerostomia, osteoradionecrosis, brain necrosis, myelitis, fibrosis, and endocrine changes. Trismus, a limited opening of the mouth, is a complication for head and neck cancers. Physiotherapists can help with trismus management and pulmonary rehabilitation. Precautions and symptom management strategies are needed depending on the radiation site and timeline.

1. 放射治療的併發症
謝 忱 希 醫師
亞東紀念醫院 放射腫瘤科 主治醫師
國立陽明大學 傳統醫藥研究所醫學博士
哈佛 麻省總醫院 Francis H. Burr 質子治療中心 研究

2. 腫瘤的分類
上皮癌(Carcinoma) 肉瘤(Sarcoma)
外胚層 原始中胚層, 外胚層的
Schwann cells, 血管的內皮
胚胎來源 內襯(endothelial lining)和間
皮(mesothelium)。
黏膜層(mucosa) 黏膜下層(submucosa)的結
組織學 締組織(connective tissue)
腺癌、鱗狀細胞癌、移行細 種類很複雜
病理學 胞癌、小細胞癌、分化不良
癌等等。
佔大多數的癌症。 發生率卻不到所有癌症的1%。
發生率

3. 常見癌症治療方式

4. 何謂放射治療(以下簡稱RT)
• 使用放射線治療疾病
• 廣泛用於惡性腫瘤
(癌症)，良性腫瘤，
預防冠狀動脈再阻塞，
抗排斥等
Rontgen discovers x-rays in 1895

5. ＲT 給予方式
• 遠隔治療(Teletherapy) ：
– 使用離開身體之射源
• 近接治療(Brachytherapy)：
– 使用接近或在體內之射源

6. 遠隔治療(Teletherapy)
• 俗稱外電
• 機器：
1.鈷六十治療機(Co-60)
2.直線加速器(Linear
accelerator)：可放出
光子(photon)或電子
(electron)射束
3.導航螺旋刀
4.質子(proton)及中子
(neutron)

7. 體外放射治療技術之演進
2000’
影像導引
放射治療
1990’
強度調控 Image guided
Radiotherapy
放射治療 ( IGRT)
1980’
三維適形 Intensity Modulated
•
•
•
•
低高高高
1960’ 放射治療 Radiotherapy 損效劑精
(IMRT) 傷率量確
二維定位 3D conformal 第三代
放射治療 radiotherapy
(3DCRT) 導航螺旋刀
2D radiotherapy 第二代
第一代
銳速刀
第四代

8. 傳統放射線治療

9. Linear accelerator

11. 肺癌: 治療前 肺癌: 治療後
IMRT + 化學治療

12. RapidArcTM
• 體積弧形放射治療。
• 利用直線加速器旋轉一次(360度)或多次(小於360度)
傳送一個的三度空間(3D)劑量分布。
• 縮短治療所需時間。

13. Volumetric Modulated Arc Therapy;
VMAT
• 整合IMRT及IGRT功能的技術設備

14. Tomotherapy

15. Clinical trends in Radiation Therapy
• Increased treatment precision and accuracy
– Image Guided delivery (3D)

18. Proton therapy
Swanson EL, et al. Int J Radiat Oncol Biol Phys 2012 Jan 21. [Epub ahead of print]

19. IMRT vs IMPT – Dose distribution
IMRT IMPT IMRT IMPT
Taheri-Kadkhoda Z, et al. Radiat Oncol. 2008 Jan 24;3:4.

20. • 特性：
1.光子治療較深層之腫瘤
2.電子治療較淺層之腫瘤
3.鈷六十可治療深層之腫瘤，但是皮膚反應較
大
4.質子可使正常組織劑量降至最低

21. 近接治療(Brachytherapy)-射源
• 俗稱: 內電
• 射源
– 銥-192 (Ir-192)
– 金-198 (Au-198)
– 碘-125 (I-125)
– 銫-137 (Cs-137)

22. 近接治療(Brachytherapy)
--方式
• Interstitial implant(組織間插種)：
如插針或植入同位素顆粒
• Intracavity/Intraluminal(腔內治療)：
– 如：Cx Ca 放裝置入 vagina or uterus
– 如：Bronchogenic Ca 放裝置入 Bronchus
– 如：NPC 放裝置入 Nasopharynx

23. Brachytherapy

24. Brachytherapy

25. 放射治療之原理
1.利用放射線殺死腫瘤細胞，使其走向凋亡
（apoptosis)
2.正常組織細胞則可在受損之後修復

26. 為何 RT 要分多次給予
1.腫瘤細胞在細胞週期
的 G2/M phase 最易
被放射線殺死，故分
次後可使非G2/M
phase 之細胞走入
G2/M phase 而被殺死
2.正常組織細胞在兩次
照射之間，將有機會
修復

27. 放射治療的劑量
•單位: 雷得 (rad, cGy), 葛雷 (Gy)
100雷得=1葛雷。
•通常一天一次給予180-200 雷得。
或一天兩次給予110-120 雷得。
•緊急或緩和治療時一天一次給予300-400雷得。

28. RT之角色
1.Radical intent(根治性):
如 NPC, Cx Ca等
2.Adjuvant / Neoadjuvant intent(輔助性):
術前或術後之輔助性治療
3.Palliative intent(緩和性):
for metastasis or symptom relieve
4.Emergent RT:
如 tumor bleeding, obstruction, spinal cord
compression or SCV syndrome etc.

29. 放射增敏劑與放射保護劑
• 使用放射增敏劑 (radiosensitizer):
如 5-FU, IUdR, Misonizazole 等，使腫瘤對放
射治療更敏感
• 使用放射保護劑 (radioprotector):
如 Amifostine (WR2721) 等，以減少正常組織
之傷害

30. 放射治療之流程
Tomo plan
Pinnacle
plan

31. 治療計劃方向
1.使腫瘤得到足夠劑量
2.儘量減少正常組織劑量
3.Critical organ tolerance:
 Spinal cord: 45Gy
 Brain: 50Gy
 Optic nerve: 54Gy
 Lens: 2Gy
 Liver: 30Gy
 Kidney: 23Gy

32. RT reactions
• 早期反應（前六個月）
– Mucositis: oral & intestine
– Dermatitis
– Hair loss

33. Mucositis
Ulceration
Mucositis

34. Dermatitis
Grade 1
Grade 4

35. Radiation pneumonitis
Chest computed tomography (CT) post The dose distribution of radiotherapy
intubation in the MICU shows interstitial pattern designed for tomotherapy.
with traction
Bronchiectasis consolidation and fibrosis in the
bilateral lung fields.
Shueng PW, et al, Radiat Oncol. 2009 Dec 31;4:71.

36. • 晚期反應（六個月之後）
– Xerostomia, loss of
taste
– osteoradionecrosis
– brain necrosis
– spinal cord myelitis
– trismus
– skin fibrosis
– hypopituitarysm
– hypothyroidism

37. 放射治療的副作用及處理
• 與照射部位有關
• 頭頸癌照射:
第一至三次:想嘔吐--喝運動飲料
口乾舌燥--用蒸氣吸入器
脖子和喉嚨腫脹--會自消
第八至十次:喉頭異物感--吃高蛋白食物
口水黏稠--蘇打水漱口
第十二至十五次:喉嚨吞就痛及口腔黏膜炎--吃軟且
溫和之高蛋白,蘇打水漱口
第二十至二十五次:痰多喉嚨癢--多喝水吸蒸器,勿用
力咳嗽
第二十八至三十次:食之無味--吃維他命B12二月恢復
耳朵積水--看耳鼻喉科

38. 放射治療的副作用及處理
• 腦部照射後掉髮會再慢慢長出
• 婦癌照射:
第一至三次:想嘔吐,吃不下,下腹脹--吃止吐及助消
化藥
第五至十次:分泌物多或帶血--要沖洗
第十一至十五次:頻尿,陰癢--多喝水不憋尿保持乾燥
第十六次至結束:腹瀉,腸蠕動快,體力差--吃止瀉藥
或適度點滴
• 乳癌照射: 注意破皮
• 飲食方面: 要均衡,忌:菸,酒,辛辣,刺激性食物

39. PT 可能可著力的的範圍
• Trismus
• Pulmonary function training
• …….

40. Trismus
• The prevalence of trismus in head and neck
cancer
– 5% to 58.5%.[1-6]
• Reported incidences of trismus in NPC after
radiotherapy
– 5% of 17%.[4,7-11]
1. Steelman R, et al. Mo Dent J 1986:66: 21–23.
2. Thomas F, et al. Int J Radiat Oncol Biol Phys 1988:15: 1097–1102.
3. Yeh SA, et al. Int J Radiat Oncol Biol Phys. 2005;62:672-679.
4. Qin DX, et al. Cancer.1988;61:1117-1124.
5. Chen M, et al. Chin J Cancer. 2001;20:651-653.
6. Dijkstra et al. Oral Oncol. 2004;40:879-889.
7. Huang SC. Int J Radiat Oncol Biol Phys 1980;6:401–407.
8. Haghbin M, et al. Am J Clin Oncol 1985;8:384–392.
9. Hoppe RT et al. Cancer 1976;37:2605–2612.
10. Mesic JB, et al. Int J Radiat Oncol Biol Phys 1981;7:447–453.
11. Tuan JK, et al. Radiother Oncol. 2012 Jan 24. [Epub ahead of print]

41. Definition of trismsus
• It has been defined as a mouth-opening capacity from <20 mm up to 40
mm.[1]
• A mouth opening of 35 mm or less should be regarded as indicative of
trismus for head and neck oncology patients.[2]
• The SOMA [3]
– Grade 2: 1.0 cm to 2.0 cm
– Grade 3: 0.5 cm to 1 cm
– Grade 4: <0.5 cm
• Trismus also can be defined as a mouth-opening size <30 mm [4]
– Normal: size >30 mm
– Moderate trismus: 20-30 mm
– Severe trismus: <10 mm.
1. Dijkstra PU et al.Oral Oncol. 2004;40:879-889.
.
2 Dijkstra PU, et al. Int J Oral Maxillofac Surg 2006;35:337–342
3. LENT SOMA tables. Radiother Oncol. 1995;35:17-60.
4. Sakai S, et al. Cancer. 1988;62:2114-2117.3.

42. Definition of trismsus
• Chen YY, et al [1]
– Grade 1: 20-30 mm.
– Grade 2: 1.0 cm to 2.0 cm
– Grade 3: 0.5 cm to 1 cm
– Grade 4: <0.5 cm
• CTCAE v4.02
– Grade 1: Decreased ROM (range of motion) without impaired eating.
– Grade 2: Decreased ROM requiring small bites, soft foods or purees
– Grade 3: Decreased ROM with inability to adequately aliment or
hydrate orally
1. Chen YY, et al. Cancer. 2011;117(13):2910-6.

43. Measurement of trismsu
• Maximal interincisal distance or opening
(MID/MIO)
– Measures with calipers
Wang CJ et al. Laryngoscope. 2005 Aug;115(8):1458-60.

44. Risk factors
• The mean maximum interincisal opening (MIO)
– MIO <35 mm> mean: 51 mm.[2]
• The trismus patients also had significantly
– Larger tumors (p=0.0437),[2]
– Advanced T status (P=0.0001) [1]
– Young age (P=0.0001),[1]
– Physical function before start of treatment (p=0.0344), [2]
– Received a higher total tumor radiation dose (p=0.0418).[2]
1. Ozyar E, et al. Radiother Oncol. 2005;77(1):73-6.
2. Johnson J, et al. Med Sci Monit. 2010 Jun;16(6):CR278-82.

45. Risk factors
• The severity of trismus is dependent on
– the configuration of the radiation field,
– the radiation source
– the radiation dose. [1-3]
1. Vissink A, et al. Crit Rev Oral Biol Med 2003;14:199–212.
2. Goldstein M, et al Oral Surg Oral Med Oral Pathol Endod 1999;88:365–73.
3. Wollin M, et al. Med Phys 1976;3:113–6.

46. Structure
Masseter
Temporalis
Med. Pterygoid
Lat. Pterygoid
Mandibular condyle

47. Muscle, tissue for trismsus
• Patients with NPC and oropharyngeal
carcinoma are prone to suffer trismus after
RT
– They are at great risk of receiving high
radiation doses to the TMJ structure.[1,2,3]
1. Chen YY, et al. Cancer. 2011;117(13):2910-6.
2. Goldstein M, et al. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:365–373
3. Steelman R, MO Dent J1986;66:21–3.

48. Muscle, tissue for trismsus
• Direct RT effect on masticator muscles (N=35)
– Medial pterygoid 11 (31%)
– Lateral pterygoid 16 (45%)
– Masticator 5 (14%)
– Temporalis 4 (11%)
– Total=19 (54%)
• Masticator muscle atrophy secondary to V3 nerve palsy
– 1 (3%)
• RT-related mandibular abnormality
– Temporomandibular joint deformity 5 (14%)
– Ramus osteoradionecrosis 5 (14%)
– Total=8 (23%)
Bhatia KS, et al. Eur Radiol. 2009;19(11):2586-93.

49. Jaw-stretching devices
Lund TW, et al . Quintessence Int 1993;24:275-279

50. Can exercises improve the
trismus?

51. A mobilization regimen to prevent mandibular
hypomobility in irradiated patients:
An analysis and comparison of two techniques
• Group 1:
– A control (no exercise)
• Group 2:
– Buchbinder techniques.
• Group 3:
– Santos techniques.
Grandi G, et al. Med Oral Patol Oral Cir Bucal. 2007 1;12(2):E105-9

52. Buchbinder technique
• Instructions - exercises buccal opening recommendations: The
exercises will have to be made 6 times to the day
• - To open mouth maximum that to obtain
– count 3 seconds with open mouth and to close - to make this 10
times;
• - Chin for the right side
– count 3 seconds in this position and to come back ploughs the
normal position - to make this 10 times;
• - Chin for the left side
– count 3 seconds in this position and to come back ploughs the
normal position - to make this 10 times;
• - Onward chin
– count 3 seconds in this position and to come back toward the
normal position - to make this 10 times.

53. Santos techniques
• The exercises will always have to be carried through in the same
schedule, 3 times per day, after breackfast, lunch and dinner.
• - To open mouth maximum
– count 3 seconds with open mouth and to close - to make this 5 times
• - Chin for the right side,
– count 3 seconds in this position and to come back toward the normal
position - to make this 5 times
• - Chin for the left side, to count 3 seconds in this position and to
come back toward the normal position - to make this 5 times
• - Onward chin, to count 3 seconds in this position and to come back
toward the normal position - to make this 5 times.
• Immediately after to make the exercises, chews 2 tablets of gum
to chew (trydentr) per 15 minutes.
• These exercises have to be maked every day while you are having
radiotherapy

54. No statistically significant differences

56. Mobilization regimens for the prevention of jaw
hypomobility in the radiated patient: a
comparison of three techniques
• Three groups of patients • The initial average
– Unassisted exercise maximum incisal opening
– Mandibular mobilization (MIO)
with stacked tongue – 21.6 mm.
depressors combined with • At week 6 and thereafter,
unassisted exercise,
the net increase in MIO
– Therabite System combined
with unassisted exercise. – Group 1: 6.0 mm (+/- 1.8)
– Group 2: 4.4 mm (+/- 2.1)
– Group 3: 13.6 mm (+/- 1.6)
• There was no statistical
difference between groups 1
and 2.
Buchbinder D, et al. J Oral Maxillofac Surg. 1993;51:863–7

57. A Randomized Preventive Rehabilitation Trial in Advanced Head
and Neck Cancer Patients Treated with Chemoradiotherapy:
Feasibility, Compliance, and Short-term Effects
• The S rehabilitation • The stretch exercise of the E
rehabilitation
– Range-of-motion – A passive and slow opening
exercises of the mouth
• using the Thera-Bite device.
– Three strengthening
– The strengthening exercise
exercises. consisted of swallowing
• the effortful swallow, with the tongue elevated to
the Masako maneuver, the palate
and the super- • Maintaining mouth opening
at 50% of its maximum,
supraglottic swallow. (training the suprahyoid
muscles)
van der Molen L, et al. Dysphagia. 2011 Jun;26(2):155-70

58. Instructions Standard Rehabilitation

59. Instructions Standard Rehabilitation

60. Instructions Standard Rehabilitation

61. Instructions Standard Rehabilitation

62. Instructions TheraBite® Rehabilitation

63. Instructions TheraBite® Rehabilitation

64. Instructions TheraBite® Rehabilitation

65. A Randomized Preventive Rehabilitation Trial in Advanced
Head and Neck Cancer Patients
Treated with Chemoradiotherapy:
Feasibility, Compliance, and Short-term Effects
• Comparing the pre- and post-treatment maximum mouth
opening (MIO)
– a significant decrease over time was found (from 50 to 47 mm,
respectively; p < 0.01).
– Not in occurrence of trismus (MIO<35 mm; from 5 to 7 patients; p
= 0.70).
van der Molen L, et al. Dysphagia. 2011 Jun;26(2):155-70

66. Can exercises improve the trismus?
• Patients who applied the exercises described
by compared to those who did not exercise
– A trend toward better results. [1,2,3]
1. Grandi G, et al. Med Oral Patol Oral Cir Bucal. 2007 1;12(2):E105-9..
2. Buchbinder D, et al. J Oral Maxillofac Surg. 1993;51:863–7.
3. van der Molen L, et al. Dysphagia. 2011 Jun;26(2):155-70

67. Can exercises improve the
pulmonary capacity and
improve survival?

68. Exercise Testing, 6-MmWalk,andStair
Climb in the Evaluation of Patients at High
Risk for Pulmonary Resection
• Patients with an FEV1 < 1.60 L
– ↑ risk of surgical morbidity and mortality and
require additional preoperative testing.
• FEV1% < 45 % and FEV1%PPO < 40 %
– identify a subset at even higher risk.
• A 6-min walk (6MWT) distance of 1,000 feet
and a stair climb of > 44 steps
– As threshold values to determine surgical
morbidity and mortality requires further
prospective evaluation.
Holden DA, et al. Chest 1992;102;1774-1779

69. 6 MW > 400 m:
a useful prognostic factor for survival in patients
with advanced non-small cell lung cancer.
• NSCLC stage IIIA, IIIB, or IV, ECOG-PS 0 to 2 and with a life
expectancy of at least 4 months were included.
• Six-Minute Walk
– Instructs to cover as much distance as possible
• participants walked up and down a 30-m hallway for the allotted 6
minutes.
• Patients were instructed to walk at their own pace and were advised to
slow down or stop as needed.
• Resume walking as soon as they felt they were able to do so.
– At the end of 6 minutes
• The distance covered was measured by the instructor.
– Dyspnea was measured by the Borg scale, oxygen saturation and
pulse rate were assessed at the start and end of 6MW.
Kasymjanova G, et al. J Thorac Oncol. 2009;4: 602–607

70. 6MW > 400 m:
a useful prognostic factor for survival in patients
with advanced non-small cell lung cancer.
Survival curve during the initial 6MW test
Patients who walked > 400 m (n = 35) and who
walked < 400 m (n = 29).
Walked > 400 m
Kasymjanova G, et al. J Thorac Oncol. 2009;4: 602–607

71. A 6-MW 400 m identified lung cancer
patients with less toxicity after radiation
therapy
• A prospective trial to study radiation
therapy–induced lung injury
– A pre-RT 6MWT was performed in 41 patients.
– The predictive capacities of pre-RT 6MWT
• Forced expiratory volume in 1 s (FEV1)
• Single-breath diffusing capacity for carbon
monoxide (DLCO) for the development of RTLI
were assessed with receiver operating curve (ROC)
techniques.
Miller KL, et al. Int J Rad Oncol Biol Phys 2005;62:1009 –1013

72. A 6-MW 400 m identified lung cancer patients
with less toxicity after radiation therapy
Miller KL, et al. Int J Rad Oncol Biol Phys 2005;62:1009 –1013

73. Can exercises improve the pulmonary
capacity and improve survival?
• 6 MWT could be a useful prognostic factor
for cancer patients under different
modalities treatment.
Holden DA, et al. Chest 1992;102;1774-1779
Kasymjanova G, et al. J Thorac Oncol. 2009;4: 602–607
Miller KL, et al. Int J Rad Oncol Biol Phys 2005;62:1009 –1013

74. • Physical therapists have roles to improve
the side effects caused by radiotherapy.

75. Thank you for your attention!