Transcript Hochvolttherapie bei Hauttumoren

Principles of Radiation Oncology
in (advanced stage) NSCLC
Stephan Bodis
Kantonsspital Aarau
The Tools for the Radiation Oncologist
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Sophisticated treatment machines
(dual energies, multileaf-collimator, 3 paired laser beams for
patient set-up, integrated CT, IMRT, stereotactic treatment)
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Tumor volume definition: CT-MRI-PET fusion imaging,
dedicated planing CT (lasersystem, large diameter)
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Treatment planing: Standardized dose prescription to tumor
(maximal) and to normal tissue (minimal), dose-volume
histogram for tumor and each organ at risk
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Treatment delivery: fix RT-field, moving RT-field (infield
movement = IMRT), image guidance, respiration correction
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Fractionated (daily) radiotherapy to a defined total dose
Integration of Molecular Biology
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Biology, Physics and Clinical Oncology
are the 3 pillars of Radiation Oncology
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Defined biologic model systems available:
> 20 years experience in classic radiobiology
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Molecular key targets for radiosensitization:
(search) for novel RT-sensitizers
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Stem cell research, human genome project,
microarray technology: Implications for clinical
radiation oncology
Life inside a LINAC Prototype
Ionizing Radiation: The physical tools
Photons:
- High energy X-rays (MV for LINAC)
- Skin sparing effect
- Dose decrease 2-5% /cm tissue
Electrons:
- Charged light particles
- No skin sparing effect, limited depth
- Steep dose decrease after a few cm‘s
- Charged heavy particles
- unique dose distribution (matterhorn
like – Bragg Peak)
Protons:
Imaging for RT Planing (incl. CT-MRI/PET)
Stage shift up to 30%
Preclinical research: Metabolic image guided RT
(mIGRT) with repeated FDG-PET during RT?
Intensity modulated RT (IMRT)
Voxel by voxel RT for complex volumes (high/low dose)
IMRT: Maximal dose in the tumor (red),
minimal dose in the adjacent normal tissue (blue)
Therapeutic Index of RT: Reason for
fractionated radiotherapy (daily low dose)
There is nothing magic about fractionation
Small fractions (daily dose) = high total dose
Large fractions (daily dose) = low total dose
Equivalent effect: 5 x 8 Gy = 30 x 2 Gy
(Various math. models for „effective dose“ (NSD, E/alpha)
E.g.: Large, radioresistant tumors with
radiosensitive adjacent normal tissue need a
small daily dose and high total dose
Radiotherapy in NSCLC
75 % of lung cancer patients need radiotherapy
Primary radical radiotherapy (Stage I – IIIB)
Adjuvant, radical radiotherapy (Stage IIB – IIIA)
Radical radiotherapy in local recurrence (Stage I – III)
Palliative radiotherapy (Any stage)
NSCLC Stage I/II
The role of radical radiotherapy
- Radical surgery: Gold-standard
Radical RT: 10-30% less effective (historic)
- Is „state of the art“ radical RT more effective ?
(e.g. CT-PET, stereotactic RT, IMRT, image guided RT, breathtriggered RT)
Assumption: better therapeutic index with smaller RTvolume, higher total dose, higher daily dose)
NSCLC Stage I/II
The role of adjuvant radiotherapy
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R0-resection: No proven benefit of adjuvant
radiotherapy
R1/R2-resection and no 2nd surgery: Postoperative
RT indicated (meta-analysis)
Small volume radiotherapy (involved field)
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Dose 50 to > 60 Gy (if 2 Gy/day and 5x/week)
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NSCLC Stage IIIA
The role of radiation oncology
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Multimodality therapy (patients should be
enrolled in international clinical trials)
Heterogeneous patient population: often lack of
subststaging (IIIA1/2; IIIA3; IIIA4 and biology)
Optimal RT is still controversial: IIIA1/2 adj. CT+
(RT), IIIA3 (?), IIIA4 (CT-RT?)
Historical toxicity of RT has to be re-considered
with current state of the art RT
NSCLC Stage IIIA
The role of radiation oncology
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Phase III trials: RT + Surgery OR Surgery + RT
vs. Surgery: same or worse OS, more toxicity
(NCI; LCSG-Weisenberger 1985, Dautzenberg 1999)
Benefit for preop. RT for Pancoast Tumors
(Paulson 1995)
Postop. phase III trials (EORTC, Villejuif)
S w/wo CT + RT vs. S w/wo CT: lower OS with
older trials using RT, same OS with recent trials;
more toxity - „reason“ for lower OS in metanalyis;
better LC with most recent studies)
NSCLC Stage IIIB
The role of radiation oncology
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Multimodality therapy (patients should be
enrolled in international clinical trials)
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Optimal combination and sequence is
controversial: Too many small studies
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Survival benefit of additional chemotherapy
modest: max 5% in 2 meta-analysis (2y, 5y OS)
(BMJ 1995 ; Auperin, Annals Onc. 2006)
NSCLC Stage IIIB
The role of radiation oncology
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Phase III trials: CT-RT vs. RT (data from 5 rand. trials):
CT-RT (2y OS of 14-26%) vs. RT (2 y OS 6% to 17%)
(e.g. leChevalier, Dillmann)
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Phase III trials: conc. CT-RT vs. sequential CT-RT
(3 rand. trials): concurrent CT better (modest gain in OS)
(e.g. Furuse, Curran)
median survial 17 months vs. 14 months, higher toxicity
(grade ¾ acute non-hem 40% vs. 0%!)
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Metaanalysis: a) conc. CT-RT vs. RT: OS at 2y. (25 / 21%)
conc. vs. seq. CT-RT: cc CT-RT better OS, more toxic deaths
(Auperin, Ann. Onc. 2006; Rowell Cochrane Library 2005
b)
NSCLC advance stage
palliative/elective local therapy
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Published RT-concepts: 10x3 or 5x4 Gy (3-4x/week)
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Immediate vs. deferred local RT in low symptom
patients: no difference (Falk, BMJ 2002)
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Elective whole brain RT for stage III NSCLC in CR
(PR/metabolic CR sufficient?)
Pre-clinical research: Potential molecular
targets for RT-sensitizers in lung cancer
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Radiobiology 2008