Champ(Comprehensive and holistic management of pain) for cancer patients Radiation therapy for cancer pain management 熊佩韋 亞東醫院放射腫瘤科 Far Eastern Memorial Hospital New Taipei City, Taiwan
Outline Undertreatment of cancer pain A Tailored Approach of RT for Cancer pain Locally advanced disease Bone metastases Spinal cord compression Brain tumor Radiation induced pain flare Do no harm avoiding side effect
Outline Undertreatment of cancer pain A Tailored Approach of RT for Cancer pain Locally advanced disease bone metastases Spinal cord compression Brain tumor Radiation induced pain flare Do no harm avoiding side effect
Palliative Care An Extra Layer of Support Reduces symptom burden Reduces depression Improves quality of life May improve length of survival Increases patient and family satisfaction May decrease burnout among other providers
Prevalence of cancer pain systematic review of the past 40 years A major issue of healthcare systems worldwide Cancer pain prevalence after curative Tx: 33% on anticancer Tx: 59% Metastatic/advanced/terminal : 64% Beuken-van Everdingen et al. Ann Oncol 2007
Pain management index Cleeland CS, et al. NEJM, 1994
Undertreatment in cancer pain prospective study Pain Management Index ( PMI) 110 centers, 1801 in- and outpatients, dvanced/metastatic solid tumors centers specifically devoted to cancer and/or pain management 61% of cases, WHO-level III opioid potentially undertreated: 25.3% (9.8% 55.3% ) Apolone G, et al. Br J Cancer 2009
Prevalence of undertreatment cancer pain 2014 Updated systematic review: Greco,T. JCO. 2014
Outline Undertreatment of cancer pain A Tailored Approach of RT for Cancer pain Locally advanced disease Bone metastases Spinal cord compression Brain tumor Radiation induced pain flare Do no harm avoiding side effect
Palliative radiotherapy 緩和性 ( 治標性 ) 放射線治療 腦及脊髓 骨骼 呼吸道 泌尿道等部位的轉移性癌症或局部侵犯嚴重的原發性腫瘤, 常引起嚴重的疼痛 出血 阻塞等症狀, 放療能迅速有效的減輕這些症狀, 提高患者生活品質
Questions to palliative RT The most important question: To treat or not to treat? (based on previous discussions about goals, priorities, prognosis...) If treatment is appropriate: What dose/fractionation scheme? What technique?
RT of locally advanced status
RT +/- Chemo for unresectable oral cancer 13
晚期鼻咽癌的同步放化療緩解出血 頭痛等症狀 Concurrent chemoradiation(ccrt) of locally advanced NPC 100% 90% Tomo isodose curves NPC, ct4n3 80% 50% 14
有效改善肺上溝癌引起之肩臂疼痛 Relief of Pancoast syndrome http://www.nature.com/eye/ Pancoast Tumor seen on MRI Right Horner s syndrome: Pancoast syndrome: ptosis, miosis, anhidrosis 手臂肩膀疼痛 ( 最常見的初發症狀 ),Horner's syndrome, 及手部小肌肉的萎縮 Unresectable, good performance status CCRT Poor performance status or distant mets RT+/-C/T J Clin Oncol 2007 & 2008
亞東全球首例頑固性皮膚 T-cell 淋巴瘤的全身皮膚螺旋斷層放療 Helical Irradiation of the Total Skin (HITS) D1 D103 D232 BioMed Research International 2013 16
螺旋刀放療巧妙治療頑固頭皮鱗狀細胞癌 Tomotherapy of recurrent scalp SCC 84 y/o, male Recurrent squamous cell Ca Multiple surgical excision on the scalp Poor response to chemotherapy Palliate tomotherapy: good response and sparing critical organs Courtesy of An Liu, Ph.D.
RT of Bone metastasis
C. I. Ripamonti et al. Ann Oncol 2012
Indications for surery Bone metastasis Radiol Oncol 2009
RT for painful bone metastases An ASTRO evidence-based guideline Pain relief : 60% 80% Different RT regimens 3Gy x 10, 4Gy x 6, 4Gy x 5, 8Gy x 1 No significant differences: pain control and acute toxicity Repeat treatment rate: 8%, fractionated RT vs 20%, 8-Gy single dose Recommendation: All patients with painful bone metastases should be evaluated for external beam RT ; Dose: 8-Gy in single dose [I, A]. Higher doses, protracted fractionations: for selected cases [II, B]. Stereotactic body radiosurgery: for clinical trials [V, D]. Int J Radiat Oncol Biol Phys 2011
Uncomplicated bone metastases: painful bone metastases unassociated with impending or existing pathologic fracture or existing spinal cord or cauda equina compression.
RT of complicated bone mets Generally use longer dose/fractionation schemes More bone remineralization after longer dose/fractionation Reirradiation: feasible with avoiding critical organ injury
Metastatic Spinal cord compression (MSCC)
Metastatic Spinal Cord Compression Oncology emergency Pain in 90% of patients, usually precedes the Dx by days to months. local (back/ neck), radicular or both. Positive neurologic deficits : poor prognosis Early diagnosis and prompt therapy are powerful predictors of outcome
Immediate steroids after Dx Dexamethasone, the most frequently used Dose: moderate (16 mg/day) vs.high (36 96 mg/day) eventually preceded by a bolus of 10 100 mg iv usually tapered over 2 wks high-dose vs moderate dose? 16 mg/day more often prescription J Clin Oncol 2005
Treatment of MSCC surgery + RT or RT alone RT: usually the first line treatment back pain relief: 50% 58% of cases with an interesting rate of pain disappearing (30% 35% ) Optimal RT schedule: remains unknown Hypofractionated RT regimen can be considered More protracted RT regimens (e.g. 5 4Gy, 10 3 Gy) can be used in selected patients with a long life expectancy.
Recommendations of Tx for MSCC Early Dx/ prompt therapy: powerful predictors of outcome [I, A]. RT alone for the majority & surgery for selected cases [II, B]. Hypofractionated RT regimen can be the choice [I, A], while more protracted RT regimens can be used in selected pts with a long life expectancy [III, B]. Prescribe dexamethasone [II, A] at a medium dose [III, B]. Radioisotope treatment can be evaluated in selected pts with multiple osteoblastic bone metastases (esp.breast, lung)[ii, C]. Ann Oncol (2012) 23 (suppl 7)
A Score Predicting Posttreatment Ambulatory Status in 2096 Patients Irradiated for MSCC Rades D, Int J Radiat Oncol Biol Phys. 2008
Validation of a score predicting post-treatment ambulatory status after RT for MSCC: prospective trial Post-RT ambulatory rate 6-month OS of Group I, II and III: 11.3%, 46.4%, and 92.0% Conclusion: score 28: short course RT for palliation of pain score 29-37: consider adding laminectomy plus stabilization to RT score 38: RT alone provides excellent results Rades D, Int J Radiat Oncol Biol Phys. 2011
Pain flare during palliative bone RT Cancer Progression? RT?
Radiation induced pain flare A real phenomenon Definition: Increase worest pain scale>=2 increase analgesic dose>=25% Incidence:2%-44% (20-40%), but small numbers Occurs from 1-5 days post-rt No difference between different RT schemes Higher rates with SBRT up to 2/3 of patients?
Prophylaxis of RT-induced pain flare May discuss dexamethasone Double-blind randomized study, Methylprednisolone 5 mg/kg/d infusion day before RT vs Placebo (normal saline infusion) : 120 patients with vertebral body metastases All received 30 Gy in 10 fractions Pain flare: 6.6%, methylprednisolone vs 20%, placebo Yousef et al. JPSM. 2014 Phase II, dexamethasone 8 mg before RT (8Gy/1fx) and subsequent 3 days Dexamethasone appears to be effective in lessening pain flare Hird et al. Clin Oncol. 2009
Do no harm avoiding side effect 34
Goals of palliative RT Rapid & durable symptom relief Minimize side effects Minimize treatment time Courtesy of Joshua Jones, MD, MA
體外放射治療技術之演進 1960 二維定位放射治療 2D radiotherapy 第一代 1980 三維適形放射治療 3D conformal radiotherapy (3DCRT) 第二代 1990 強度調控放射治療 Intensity Modulated Radiotherapy (IMRT) 第三代 2000 影像導引放射治療 Image guided Radiotherapy ( IGRT) 第四代 低高高高損傷效率螺旋刀 劑量精確
Radiotherapy of brain mets 2D Whole Brain Treatment Field Stereotactic radiosurgery/radiotherapy 立體定位放射手術 / 立體定位放射治療
2014 年 直線加速器 Linac, 132 / 74 近接放療機 HDR Ir192, 41 / 41 23,000,000 人 RT Devices in 74 Hospitals 250 Board Certificated Radiation Oncologists 電腦刀加馬刀螺旋刀 Far Eastern Cyberknife, Memorial Hospital, 5 / Taiwan 5 Gamma 38 Knife, 9 / 8 Tomotherapy, 18/ 16
2006~2014 螺旋刀治療人次 缓和性 36.4% 960 亞東醫院雙導航螺旋刀中心 39
兒童第四腦室瘤螺旋刀放射治療 T1+C 2009/3 2009/3 before Tomo T2 2009/3 2 歲, 2009/3,during RT 7 歲, 2014/7, 64mo
第四腦室瘤治療後 MRI 系列變化 TIM +C 2009/6 1 mo post RT 2009/8 3 mo post RT 2009/12 7 mo post RT 2013/11 54 mo post RT 2014/12/31 67 mo post RT
巨大子宮頸癌導航螺旋刀放療後完全消失 Tomotherapy of Bulky cervical cancer 治療前 治療後 子宮 直腸 膀胱 子宮 直腸 膀胱 6x4.8x5.8 公分 63 歲女性停經後陰道出血及異常分泌物近 3 個月
導航螺旋刀有效降低鼻咽癌肋膜轉移之疼痛 48y/o, Male, NPC, ct4an2,mo post CCRT + adjuvant PF Distant mets ( liver and Bil pleura) 6 mo later Tomo 36 Gy Decreasing tumor volume: 75% (629 ml 158 ml) Effective pain relief No radiation peunomiotis Before RT: Fentanyl patch 75µg/hr Morphine 10 mg qid Diclofenac 100 mg bid Dextromethorphan 60 mg bid Neurontin 300 mg qid At the end of RT: Fentanyl patch 25µg/hr Meloxicam 15mg/d
47y/o, female IDC of left breast herbal medicines with PD in 2013 ct4cn3bm1 (Rt breast, pleura, bone), T:18cm Denosumab, Trastuzumab and paclitaxel since 2014/1 PD, extensive chest wall & skin mets 導航螺旋刀安全有效地治療乳癌大範圍胸腹壁病灶及疼痛 2014/1 2014/7 Tomotherapy 70.2Gy/39fx Before tomo 4 mo post tomo
多發性顱骨轉移之腦部迴避全顱骨螺旋刀放療 Total skull irradiation for skull mets with sparing of brain
螺旋刀放療改善骨痛但不傷害鄰近器官
螺旋刀放療改善症狀但不傷害鄰近器官
螺旋刀同次多目標放射治療 Total Metastases Irradiation (TMI) / Extended Oligometastases
Conclusion Be aware of issue of undertreatment Palliative RT is safe/effective for pain Palliative RT can tailor dosefractionation to individual patients Using optimal RT technique to minimize side effects 49