Jedi Wisdom for Lung Cancer Radiotherapy: May the Force Be With You

Transcription

1 Jedi Wisdom for Lung Cancer Radiotherapy: May the Force Be With You SHAUN LOEWEN MD PhD FRCPC Assistant Professor, University of Manitoba Radiation Oncologist, CancerCare Manitoba

2 Disclosure Relationship with commercial interests Grant/Research Funding: Varian Medical Systems 2

3 Mitigating Potential Bias Universal descriptions of radiotherapy delivery techniques are used rather than trademark/marketing terms 3

4 Star Wars Analogy Radiation Oncologist = Jedi Master? Radiation Oncologist (def n): Doctor who specializes in using ionizing radiation to fight cancer 4

5 Star Wars Analogy Radiation Oncologist = Jedi Master? Radiation Jedi Master Oncologist (def n): (def n): A wise Doctor noble who practitioner specializes skilled in using ionizing the ways of The Force radiation who opposes, to fight often cancer in combat, the evils of the Dark Side 5

6 Learning Objectives List the indications for radiation and potential benefits of treatment for lung cancer patients Recognize common toxicities associated with thoracic radiation after treatment Review a new emerging radiation treatment for lung cancer with stereotactic body radiotherapy 6

7 Major Types of Lung Cancer Non-small cell lung cancer (85%) Adenocarcinoma (40%) Squamous cell carcinoma (30%) Large cell carcinoma (10%) Others: Neuroendocrine tumours, carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements, carcinoid, etc. Small cell lung cancer (15%) Mesothelioma (1%) 7

8 Mesothelioma Roles for surgery, chemotherapy, and radiotherapy dependent on disease or patient factors Extensive pleural involvement requires large radiotherapy treatment volumes Toxicity concerns to lungs, esophagus, liver, spinal cord, and heart 8

9 RT and Mesothelioma Adjuvant radiotherapy after extrapleural pneumonectomy Gy to hemithorax improved LC, but toxicity still a concern even with modern RT delivery Palliation of pain, dyspnea, superior vena cava obstruction, and dysphagia Prescription doses vary Prophylactic radiotherapy of incisional tracts 21 Gy in 3 fractions lowers seeding incidence 9

10 Small Cell Lung Cancer (SCLC) Combination chemotherapy with cisplatin and etoposide forms the mainstay of treatment Traditionally a two-tiered staging system Limited stage: one hemithorax, regional mediastinal and/or ipsilateral supraclavicular lymph nodes AND encompassed within a safe radiation treatment plan Extensive stage: Overt metastasis, malignant pleural effusion, or non-regional lymph node involvement 10

11 Limited Stage SCLC Concurrent chemoradiation recommended 45 Gy in 30 fractions BID (15 treatment days) 40 Gy in 15 fractions 50 Gy in 25 fractions Prophylactic cranial irradiation (PCI) for good PR or CR after primary treatment 25 Gy in 10 fractions to the whole brain RT and PCI improve survival outcomes and PCI lowers incidence of brain mets by 1/2 11

12 Extensive Stage SCLC 4-6 cycles of platinum-based chemotherapy is standard care Prophylactic cranial irradiation (PCI) for PR or CR after primary treatment Thoracic RT not routinely used, but may be considered if CR at distant sites and good PR within the thorax PCI improve survival outcomes and lowers incidence of brain mets 12

13 Non-small Cell Lung Cancer (NSCLC) Leading cause of death in Canada (20,200 deaths/yr) ~20,000 cases of NSCLC/yr 20% Stage I or II (early stage) Treatment: Surgery preferred 5yr OS: 60-80% (IA/B) 25% Stage I/II s inoperable radiotherapy (66Gy/33fx) 5yr OS: 20-30% (T1N0) and 10-20% (T2N0, TxN1) 5yr LC: 30-50% 13

14 Locally advanced NSCLC Concurrent chemoradiation preferred, but sequential chemo RT an option Phase II dose escalation trials showed promising results of improved local controls RTOG 0617 final results reported in 2013 Phase III trial comparing 60 Gy to 74 Gy chemoradiotherapy ± cetuximab for stage III NSCLC 60 Gy arm was superior in terms of OS and LRC Cetuximab data awaiting further follow-up 14

15 Trimodality Therapy? INT 0139 (Lancet 2009) compared induction chemort followed by surgery vs. chemo RT alone in IIIA(pN2) NSCLC; both arms received consolidation chemo Surgery arm favoured with improved PFS, but no difference in 5yr OS (20-27%) and MS (~23 mo) Weaknesses: must be resectable at initial staging, more deaths with pneumonectomy, patients with progression after induction chemort delayed boost chemort 15

16 Special Cases INT 0160 (2007) and JCOG 9806 (2008): Two Phase II trial with T3-4N0-1 NSCLC in superior sulcus treated with chemort (45 Gy) restaging surgery chemo x 2c. If progression at restaging, completed chemort to 63 Gy chemo x 2c. 5 yr OS ~ 50% establishing this approach as standard of care for superior sulcus tumours 16

17 Locally advanced NSCLC Patient selection factors for high dose RT ECOG 2 Adequate lung function FEV1 > 1 L DLCO > 50% Early or controlled congestive heart failure Technical factors for high dose RT Radiotherapy plan can be safely administered with acceptable toxicity 17

18 Post-operative RT in NSCLC CONTROVERTIAL In general, if resected N0/1 no role (survival detriment demonstrated) Data for post-operative RT for patients with N2 disease is conflicting PORT meta-analyses showed no benefit SEER and ANITA subset analyses suggest survival benefit of 5-7% at 5 years 18

19 Post-operative RT in NSCLC Indications: pn2 after surgery Positive margin (R1) Unresected nodal disease ECE Results from European phase III Lung ART trial highly anticipated Decision for post-op (C)RT is individualized 19

20 Palliative Radiotherapy May be offered if patient unsuitable for high dose radiotherapy Palliative thoracic RT indicated for chest pain due to tumour invasion, dysphagia, persistent hemoptysis, SVCO, symptomatic bronchial obstruction causing dyspnea Palliative RT for diffuse brain mets and painful bone mets 20

21 Radiotherapy Side Effects (SUB)ACUTE EFFECTS Fatigue Slight cough Shortness of breath Radiation pneumonitis Skin dermatitis Esophagitis LATE EFFECTS Pulmonary fibrosis Rib fractures Esophageal strictures Pericarditis Coronary artery disease Brachial plexopathy L hermitte s syndrome 2 º malignancy 21

22 Radiation Pneumonitis Occurs with any lung radiation Risk is determined by the amount of lung receiving a threshold dose Presents with fever, persistent cough, and dyspnea Onset 6 weeks to 6 months after RT Treated with high dose steroids with long taper If severe, can be life threatening Mild radiation pneumonitis is common (20-30%) 22

23 Esophagitis Usually starts in 3 rd week and resolves 2-4 weeks after completing radiotherapy Feels like heart burn, but patients may experience a sharp, burning pain when swallowing Management Soft foods, non-spicy diet, avoid alcohol and excessively cold/hot foods Magic Mouthwash (1:1:1 lidocaine, Maalox, Benadryl) Occasionally liquid morphine or nystatin required 23

24 Pericarditis Classic symptoms: Substernal or left precordial chest pain with radiation to the back Pain is relieved by sitting up and bending forward Worse pain when lying down or with deep inspiration Classic signs: Friction rub on auscultation Pericardial effusion/tamponade: low BP, distant heart sounds, elevated JVP Treatment: Aspirin, NSAIDs (first line); steroids, colchicine, pericardiocentesis 24

25 What is SBRT? Highly precise/conformal, high dose radiation therapy given in 3-10 fractions Based on 4 technological advances: Improved Immobilization Improved Imaging and Targeting Improved Planning Improved Treatment Delivery 25

26 What is SBRT? Stereotactic Use of coordinate system to accurately locate tumours in three-dimensional space 26

27 What is SBRT? Stereotactic Use of coordinate system to accurately locate tumours in three-dimensional space Body Performed outside the brain Radiation Therapy or Radiotherapy Use of X-rays to kill cancer cells 27

28 SABR Stereotactic Ablative (Body) Radiotherapy 28

29 Prospective SBRT Trial Outcomes 3 yr LC 80-98% 3 yr CSS 75-90% 3 yr OS 45-72% 29

30 Radiation Comparison SBRT Conventional RT Dose (Gy) Time frame (wks) <2 6 Treatments 4 30 Dose per day (Gy) 12 2 EQD2 (Gy)

31 Advanced Immobilization 31

32 Advances in Imaging and Targeting Coronal 3D-CT image Internal gross tumour volume (IGTV) Gross tumour volume (GTV) Coronal 4D-CT image Maximal intensity projection (MIP) shows all possible tumour positions throughout the respiratory cycle 32

33 Computer-assisted Planning 33

34 Cone Beam CT and Image Guidance Cone Beam CT (CBCT) performed prior to treatment Match CBCT with Planning CT Cone Beam CT Planning CT Planning CT Cone Beam CT

35 Advanced Treatment Delivery 35

36 Lung SBRT: Which patients are candidates? Non-small cell lung cancers 5-6 cm No nodal involvement Patients who are poor surgical candidates Case-by-case basis Suspicious solitary lung nodules Bilateral Stage I NSCLCs 1-3 small lung metastases 36

37 Surgery vs. Radiotherapy Advantages Limitations 3 yr Local Control Outcomes Lobectomy Gold standard; pathological staging/nodal resection performed Invasive; Requires healthy patients with good lung function; post-op morbidity Wedge Resection Suitable for patients with poor lung function and/or multiple tumours Invasive; risk of recurrence compared to lobectomy Conventional RT Inoperable patients w/ good lung function; non-invasive; suitable for nodepositive NSCLC Tumour can only be in one lung; local control is poor Lung SBRT Inoperable patients with severe COPD and/or multiple tumours; noninvasive Limited long-term toxicity and outcome data; node-negative patients only; tumour 6 cm ~94% ~80% 30-70% 80-98% 5-yr OS 65-75% 5-yr OS 20-30% 3-yr OS: 60-85% 37

38 Lung SBRT Toxicities ACUTE EFFECTS Slight cough Shortness of breath MSK discomfort Radiation pneumonitis Skin dermatitis Esophagitis LATE EFFECTS Chronic chest wall pain Rib fractures Airway stenosis/fistula Esophageal strictures Severe skin toxicities Brachial plexopathy Pericarditis Massive hemoptysis 2 º malignancy 142/2587 (5.5%) patients had grade 3 late toxicities 1 1 Olsen et al. IJROBP 2011; 81(4):e

39 Future Directions in Radiotherapy Continual advancements in technology 4D and real-time imaging while receiving treatment 4D planning and radiation delivery expected within 10 years Reduced treatment toxicity Local therapies for selected metastatic patients SBRT for small lesions in spine, liver, adrenal gland, pancreas, kidney, or para-aortic lymph nodes Gammaknife/SRS for brain mets 39

40 Summary Radiotherapy has many roles in the treatment of lung cancer Early recognition and management of radiotherapy side effects may lead to better patient experiences Lung SBRT is now the new standard for inoperable early stage lung cancer 40