Utilizzo delle tecniche VMAT nei trattamenti del testa collo Marta Scorsetti M.D.

Transcription

1 Utilizzo delle tecniche VMAT nei trattamenti del testa collo Marta Scorsetti M.D. Radiotherapy and Radiosurgery Dpt. Istituto Clinico Humanitas, Milan, Italy.

2 Higher doses to the tumor Better sparing of normal tissues Improve local control rates Decreases Toxicity Positive impact on the quality of life and survival

3 Multimodality images CT/PET/MRI IGRT and adaptive RT Selectivity Accuracy Efficiency IMRT and VMAT Radiosurgery and SBRT

4 IGRT IGRT tools for verifying patient position and adapting treatment plans. accuracy and precision treatment time

5 IMRT also increases treatment delivery time by requiring a large number of beam directions and increases monitor units (MU) Time is of the essence! Is there a procedure that is better and more time efficient?

6 VMAT (Volumetric Modulated Arc Therapy) is a treatment planning and delivery platform using a single 360 gantry Arc : Time efficient Highly conformal dose distribution Superior dosimetric accuracy

7 RA (RapidArc) is a planning and delivery technique which aims to : Improve the degree of target coverage Improve OARs and healthy tissue sparing compared to other IMRT techniques Reduce significantly treatment time (beam on time) per fraction

8 Variable dose rate (0 600 MU/min) Variable gantry speed ( /sec) Variable MLC speed (0 2.5 cm/sec) Single or multiple arcs. Single or multiple isocentres Coplanar or noncoplanar arcs Any photon energy ADVANTAGES: Avoidance sectors Short delivery time Low MU per Gy Integrated IGRT Fast planning Simple QA procedures

9 WORK FLOW Multi-modality imaging (CT,PET,MRI,4D-PET/CT) QA Target and OAR delineation Inverse Treatment Planning

10 Head and Neck Cancer complex anatomy aggressive phenotype locally advanced stage Radiotherapy is an important treatment modality in these tumours as it offers an alternative treatment option to surgical resection which can cause unacceptable cosmetic disfigurement and functional impairment

11 2008 Head and neck cancer 20 comparative studies on head and neck cancer were included (one RCT and 19 case series) Nasopharyngeal carcinoma (4 studies) IMRT reduce salivary gland toxicity and improving quality of life This review shows evidence of reduced toxicity for various tumour sites by use of IMRT. Sinonasal cancer (3 studies) The Dry-eye findings syndrome regarding and local optic neuropathy control and can overall be substantially survival are decreased generally by IMRT inconclusive. Cancer of the oropharynx, hypopharynx, larynx, and oral cavity (13 studies) A significantly better recovery of salivary-gland function and grade 2-3 xerostomia less frequent after IMRT

12 2011 Xerostomia is the most common late side-effect of radiotherapy to the head and neck. 94 patients (pharyngeal squamous-cell carcinoma T1-4, N0-3, M0) were randomly assigned in a 1:1 ratio to parotid sparing IMRT or conventional radiotherapy (60-65Gy/30fr). CONCLUSIONS: Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamouscell carcinoma of the head and neck.

13 2004 The ability of IMRT to produce inhomogeneous dose distributions can be exploited to simultaneously treat the primary and elective target volumes (areas at risk of microscopic spread of disease) to different dose per fractions without increasing overall treatment time. SIB technique allows both volumes to be treated within one treatment plan. CONCLUSIONS: Dose level 2, 70.8 Gy in 30 fractions of 2.36 Gy, was defined as the MTD deliverable to the GTV using this accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing.

14 2011 The PTV coverage was similar between IMRT and VMAT with improved homogeneity when using two arcs with VMAT. Similarly there were no significant differences in the doses to the OARs, although the authors report a slightly lower mean dose (average of 2 Gy) to the parotid glands with the double arc VMAT plans compared with the single arc and IMRT plans. VMAT reduce treatment delivery time compared with conventional IMRT.

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16 2013 Methods: Five institutes generated IMRT and VMAT plans for five oropharyngeal cancer patients using either Pinnacle3 or Oncentra Masterplan to be delivered on Elekta linear accelerators. Results: Comparison of VMAT and IMRT plans within the same patient and institute showed significantly better sparing for almost all OARs with VMAT.

17 Dose distributions in a transverse slice for IMRT and VMAT plans prepared by the participating institutes A to E. OARs are depicted with a thick solid line: oral cavity (brown), parotid glands (orange) and spinal cord (blue). Conclusions: Independently of institution-specific optimization strategies, the quality of the VMAT plans including double arcs was superior to step-and-shoot IMRT plans including 5 9 beam ports, while the effective treatment delivery time was shortened by ~50% with VMAT (13:15 min vs 5:54 min).

18 2007 Intensity-modulated radiation therapy (IMRT) for head and neck tumors refers to a new approach that aims at increasing the radiation dose gradient between the target tissues and the surrounding normal tissues at risk, thus offering the prospect of increasing the locoregional control probability while decreasing the complication rate. As a prerequisite, IMRT requires a proper selection and delineation of target volumes. The promising results of IMRT are likely to be achieved when many treatment conditions are met: optimal selection and delineation of the target volumes and organs at risk, appropriate physical quality control of the irradiation, and accurate patient setup with the use of onboard imaging.

19 SELECTION AND DELINEATION OF THE TARGET VOLUMES As IMRT allows highly conformal dose distribution to target volumes of almost any shape, the adequate selection and delineation of these volumes become of critical importance. Guidelines for the delineation of the various node levels in the neck have also been proposed.

20 2003 Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groupsin Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck.

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22 Implementation of these guidelines in the daily practice of radiation oncology should contribute to reduced treatment variations from patient to patient and help to conduct multi-institutional clinical trials or retrospective studies. Lastly, although guidelines are designed to apply to the vast majority of patients, there will always be individual cases for which sound reasons preclude their use. More than ever, oncologic knowledge, experience and judgment are prerequisites for appropriate use of the recommendations proposed in this manuscript.

23 Another important issue regarding target volume delineation is the choice of the optimal imaging modality used for planning purposes. CT images are typically used because they allow dose calculation with corrections for tissue density inhomogeneity Contrast medium should be routinely used to allow a much better contrast between normal tissues and tumors Magnetic Resonance Imaging (MRI) has been shown to be superior to CT in reducing interobserver variability FDG-PET demonstrated higher accuracy in delineating GTV, with a statistically significant smaller target volume. Grègoire et al. The oncologist 2007

24 2012 Technical advances in imaging and in co-registration software provide the potential to substantially improve upon target definition for head and neck radiotherapy planning, both in terms of target selection and in target delineation. Identification of malignant lymph nodes with FDG-PET/CT. T4 squamous cell carcinoma of the base of tongue.

25 H&N TUMORS: Nasopharyngeal Carcinoma Because the nasopharynx is situated near numerous critical normal organs, that is, the brain stem and optic chiasm, IMRT is ideal in its attempt to deliver an adequate dose to the gross tumor while sparing these surrounding normal tissues.

26 2002 There is better coverage of the retropharynx, base of skull, and medial aspects of the nodal volumes IMRT provides better tumor target coverage with significantly better sparing of sensitive normal tissue structures in the treatment of locally advanced nasopharyngeal carcinoma.

27 2007 Patients and Methods: Between November 2001 and December 2003, 60 patients with T1-2bN0-1M0 NPC were randomly assigned to receive either IMRT or 2DRT. Primary end point was incidence of observer-rated severe xerostomia at 1 year after treatment.

28 Results: At 1 year after treatment, patients in IMRT arm had lower incidence of observer-rated severe xerostomia than patients in the 2DRT arm (39.3% v 82.1%; P.001). In conclusion, IMRT is superior to 2DRT in preserving parotid function and results in less severe delayed xerostomia in the treatment of early-stage NPC.

29 H&N TUMORS: Nasal and Paranasal Sinuses By their location, sinonasal tumors are surrounded by critical structures, including the frontal and temporal lobes of the brain, pituitary gland and brainstem, lacrimal glands, eyes, optic nerves, and chiasm. Conventional radiation therapy for sinonasal cancer resulted in significant ocular toxicity

30 2009 Methods and Materials: Between July 1998 and November 2006, 84 patients with sinonasal tumors were treated with IMRT to a median dose of 70 Gy in 35 fractions. Results: The median follow-up of living patients was 40 months (range, 8 106). On multivariate analysis, invasion of the cribriform plate was significantly associated with lower local control (p = ) and overall survival (p = ). Radiation-induced blindness was not observed. One patient developed Grade 3 radiation-induced retinopathy and neovascular glaucoma. Nonocular late radiationinduced toxicity comprised complete lacrimal duct stenosis in 1 patient and brain necrosis in 3 patients.

31 CONCLUSION The IMRT strategy provided an actuarial 5-year local control and overall survival rate of 70.7% and 58.5%, respectively. The low rates of late ocular toxicity demonstrate that IMRT could be considered as the treatment of choice for sinonasal tumors.

32 H&N TUMORS: Oropharyngeal Carcinoma For oropharyngeal cancer all series of IMRT outcome have reported outstanding locoregional control rates, in the range of 90% 98% Some of the most reliable information gained from clinical series of IMRT for HN cancer in general and oropharyngeal cancer in particular relates to the pattern of tumor recurrences relative to the targets and the locally delivered doses. Careful selection and delineation of the targets resulted in very few or no marginal or out-of-field recurrences.

33 2000 Purpose: This analysis demonstrates the spatial relationship of the region of recurrence to the previously treated dose distribution, allowing us to determine the adequacy of the target volume. Methods and Materials: 58 patients with head and neck cancer were treated with bilateral neck radiation (RT) using conformal or segmental IMRT techniques, while sparing a substantial portion of one parotid gland. The median RT doses to the gross tumor, the operative bed, and the subclinical disease PTVs were 70.4 Gy, 61.2 Gy, and 50.4 Gy respectively.

34 The recurrences were classified as 1) in-field in which 95% or more of the recurrence volume (Vrecur) was within the 95% isodose; 2) marginal in which 20% to 95% of Vrecur was within the 95% isodose; 3) outside in which less than 20% of Vrecur was within the 95% isodose. Results: median follow-up of 27 months (range 6 to 60 months) 10 patients relapsed in-field 2 patients developed marginal recurrences in the side of the neck at highest risk

35 Fig. 1. Lateral digitally reconstructed radiographs (DRRs) demonstrating the location of the recurrences involving the high neck in 4 patients. Recurrent tumor locations were determined on diagnostic CTs at the time of recurrence and transferred to the dataset of the CT scan performed at the time of RT planning (shown in red). The radiotherapy targets corresponding to the sites of recurrence contained subclinical disease. The CTVs treated to 50 Gy are displayed in green mesh. Patients A, C, and D had in-field recurrences, with 95% of the recurrence volume encompassed by the 95% isodose volume, and Patient B had a marginal recurrence. Conclusions: The majority of local-regional recurrences after conformal and segmental IMRT were in-field, in areas judged to be at high risk at the time of RT planning, including the GTV, the operative bed, and the first echelon nodes. These findings motivate studies of dose escalation to the highest risk regions.

36 2013 Backround: Radiotherapy techniques have evolved rapidly over the last decade with the introduction of Intensity Modulated RadioTherapy (IMRT) in different forms. It is not clear which of the IMRT techniques is superior in the treatment of head and neck cancer patients in terms of coverage of the planning target volumes (PTVs), sparing the organs at risk (OARs), dose to the normal tissue, number of monitor units needed and delivery time. The present paper aims to compare Step and Shoot (SS) IMRT, Sliding Window (SW) IMRT, RapidArc (RA) planned with Eclipse, Elekta VMAT planned with SmartArc (SA) and helical TomoHD (HT).

37 Methods: Target volumes and organs at risk (OARs) of five patients with oropharyngeal cancer were delineated on contrast enhanced CT-scans, then treatment plans were generated on five different IMRT systems. In 32 fractions, Gy and 56 Gy were planned to the therapeutic and prophylactic PTVs, respectively. For the PTVs and 26 OARs ICRU 83 reporting guidelines were followed. Conclusions: In the treatment of oropharyngeal cancer, we consider rotational IMRT techniques preferable to fixed gantry techniques due to faster fraction delivery and better sparing of OARs without a higher integral dose.

38 H&N TUMORS: Laryngeal Carcinoma IMRT can improve the target dose homogeneity in laryngeal and hypopharyngeal SCC while reducing the dose to normal tissues at risk Braaksma MM et al. Radiother Oncol 2003 Guerrero Urbano MT et al. Eur J Cancer Suppl 2005

39 2004 Patients and methods: Conventional radiotherapy (CRT) and IMRT plans were produced for six patients to treat the larynx (PTV1) and lymph nodes (PTV2) to 50 Gy (phase 1). A second plan was created to treat the PTV1 to 65 Gy and PTV2 to 50 Gy (phases 1 and 2). The potential to escalate the dose to both the larynx (to 67 Gy) and the nodes (to 56 Gy) was investigated for the IMRT plans.

40 A dose volume histogram showing data for a conventional and IMRT plan for a typical patient. The CRT plan data are shown as dotted lines and the IMRT is in solid lines. The IMRT data show a significant improvement in target coverage and dose inhomogeneity as well as improved cord sparing. Conclusions: IMRT offers improved target homogeneity and reduces irradiation of the spinal cord. This sparing of normal tissue structures is sufficient that significant dose escalation of both the larynx and lymph nodes may be possible.

41 2012 Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H).

42 The primary objective was to test the feasibility of delivering induction chemotherapy and modestly accelerated dose-escalated chemotherapy-imrt. Secondary objectives were to record acute and long-term toxicities, locoregional control, and progression free and overall survival

43 CONCLUSIONS Dose-escalated chemotherapy-imrt with moderate acceleration is safe, feasible, and seems to improve locoregional control rates for the treatment of laryngeal and hypopharyngeal cancers.

44 2012 Introduction: Cetuximab plus radiotherapy (RT) may be an effective alternative to chemoradiation in locally advanced head and neck squamous cell carcinoma (LASCCHN) patients. Materials and methods: 22 patients were submitted to IMRT-SIB plus cetuximab for radical intent in case of LASCCHN. None of the patients was suitable for chemotherapy because of important comorbidities. VMAT, by means of RapidArc, and SIB with two dose levels of Gy and Gy in 33 fractions were adopted.

45 Results: All but 2 patients completed treatment and achieved the minimum follow-up of 12 months after the end of the treatment. Skin toxicity N. % Mucositis N. % Dysphagia N. % G G G G G G G G G G G G Conclusion: The here reported toxicity data are promising and encouraging in regard to the adoption of moderate hypofractionation with VMAT-SIB techniques, when cetuximab is concomitantly administered.

46 DOSE ESCALATION 2013 Purpose: This study was designed to evaluate the feasibility of a dose-escalating radiotherapy treatment by using a SIB-IMRT approach in patients with early and moderately advanced head and neck cancers. Materials and methods: 57 patients with pharyngo-laryngeal T2N0 or T2N1, or laryngeal T3N0 SCC were included. The therapeutic PTVs were treated according to three consecutive dose levels, 69 Gy in 30 fractions of 2.3 Gy (dose level I), 72 Gy in 30 fractions of 2.4 Gy (dose level II) or 75 Gy in 30 fractions of 2.5 Gy (dose level III). The prophylactic PTVs received a dose of 55.5 Gy delivered in 30 fractions of 1.85 Gy.

47 Results: The 2-year loco-regional control was 82% for all 3 groups (79% dose level I, 88% dose level II, 79% dose level III). The 2-year overall survival was 89% for dose level I and II, and 95% for dose level III. Conclusions: This dose escalation SIB-IMRT protocol was safe and effective as the sole treatment of early and moderately advanced SCC of head and neck. No toxicity difference was observed between the groups.

48 ADAPTIVE RT 2012 Adaptive radiotherapy involves changes to the radiotherapy plan during treatment on the basis of patient-specific observations that were not taken into account during initial planning. Frequently the term adaptive radiotherapy is used to refer to different procedures used throughout the course of a treatment to account for anatomical and functional variations that can affect the dose distribution.

49 ADAPTIVE RT Volumetric and positional changes of organs at risk and target volumes are generally associated with progressive increase in the delivered dose compared with the planned dose, typically because of shrinkage of the gross target volume owing to tumour tissue loss (figure 1). The volumetric and positional changes of organs at risk and target volumes have also been shown to lead to increased mean doses to the ipsilateral and controlateral parotid glands, by 15% and 10%, respectively, and to small increases to the spinal cord and the oral cavity.

50 ADAPTIVE RT For the clinical target volume around the gross target volume, although planning studies show consistently that shrinkage of the gross target volume enables isodose reduction, implementation of this procedure is not recommended. The limited resolution of the imaging modalities raises the risk of underdosing to part of the surrounding normal tissues still infiltrated by tumour cells.

51 Technical implementation of IMRT adaptive planning is also challenging (figure 2).

52 2012 Purpose: Measuring parotid density changes in patients treated with IMRT for head neck cancer (HNC) and assessing correlation with treatment-related parameters. Patients and materials: 84 patients treated with IMRT for different HNC were pooled from three institutions. Parotid deformation and average Hounsfield number changes (DHU) were evaluated through diagnostic kvct images taken at the treatment start/end.

53 Fig. 1. Contour propagation algorithm; from left to right: parotid contour manually drawn on the first fraction KVCT; the same contour visualized on the last fraction KVCT;deformation field; deformed contour visualized on KVCT on the last fraction. Conclusions: Parotid density reduced in most patients during IMRT and this phenomenon was highly correlated with parotid deformation. The individual assessment of density changes was highly reliable just with diagnostic KvCT. Density changes should be considered as an additional objective measurement of early parotid radiation-induced modifications.

54 2013 Purpose: To evaluate feasibility of using deformable image co-registration in three-phase adaptive dosepainting-by-numbers (DPBN) for head-and-neck cancer and to report dosimetrical data and preliminary clinical results. Material and methods: 10 patients with non-metastatic head-and-neck cancer enrolled in this phase I clinical trial where treatment was adapted every ten fractions. 3 DPBN plans based on: a pretreatment 18[F]-FDG-PET scan (phase I: fractions 1 10), a per-treatment 18[F]-FDG-PET/CT scan acquired after 8 fractions (phase II: fractions 11 20) and a per-treatment 18[F]-FDG-PET/CT scan acquired after 18 fractions (phase III: fractions 21 30). Deformable image co-registration was used for automatic region-of-interest propagation and dose summation of the three treatment plans.

55 Fig. 1. Design of the three-phase adaptive dose-painting-by-numbers trial.

56 Dose distributions of the three treatment plans for a patient with a ct2cn1cm0 oropharyngeal cancer based on (a) 18[F]-FDG-PET/CT1, (b) 18[F]-FDG-PET/CT2, (c) 18[F]-FDG-PET/CT3, (d) summed on CT1 (anti-chronological), (e) summed on CT4 (chronologically). Conclusions: Three-phase adaptive 18[F]-FDG-PET-guided dose painting by numbers using currently available tools is feasible. Irradiation of smaller target volumes might have contributed to mild acute toxicity with no measurable decrease in tumor response.

57 RE-IRRADIATION 2013 Locoregional relapse is frequent after definitive radiotherapy (RT) or multimodal treatments, re-irradiation is only performed in few patients even in palliative settings like e.g. vertebral metastasis. This is most due to concern about potentially severe complications, especially when large volumes are exposed to re-irradiation. With technological advancements in treatment planning the interest in re-irradiation as a local treatment approach has been reinforced.

58 RE-IRRADIATION Therapy options for locoregional recurrences in previously irradiated head and neck patients are limited. Salvage surgery is the standard treatment for small relapses, but with locoregional spread, surgery alone is not sufficient. As normal tissue toxicity was significant after conventional RT, the introduction of SBRT in the re-irradiation of head and neck cancer patients has been pursued in the last years.

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60 In conclusion: SBRT in the re-irradiation situation for head and neck tumors is a promising salvage therapy modality with encouraging local control rates and justifiable toxicities. Severe late adverse events (grade 4 5 toxicities) have been reported in some studies but are less frequent than in patients re-treated with conventional techniques. Very high single fraction doses of Gy or higher should be avoided.

61 2012 Background: Thanks to new advanced techniques, as well as intensity modulated radiation therapy, it is possible to approach head and neck recurrences in selected patients. Volumetric Modulated Arc Therapy (VMAT) in its RapidArc format, permits to reduce significantly the time to deliver complex intensity modulated plans, allowing to treat hypofractionated regimes within a few minutes.

62 Materials and methods: 4 patients with local or regional recurrence of nasopharyngeal carcinoma. All patients were treated using TrueBeam with RapidArc technology and FFF beam for stereotactic hypofractionated re-irradiation. Fig. 1 Case 1: Direct comparison of PET/CT axial images before and 6 months after the SBRT re-treatment (30 Gy in 5 fractions), showing a complete response of nasophaynx recurrence.

63 Fig. 2 Case 2: Direct comparison of PET/CT images before and 6 months after the SBRT treatment (30 Gy in 5 fractions), showing (with white arrows) a complete response in the site of nasophaynx relapse. Conclusions: Our preliminary experience using TrueBeam with RapidArc technology and FFF beam for stereotactic hypofractionated re-irradiation of nasopharyngeal carcinoma was safe and effective in all 4 treated patients. Longer follow-up and a larger population of study is needed to confirm these promising results.

64 CONCLUSION Highly conformal dose distribution to target volumes Better sparing of sensitive normal tissue structures Reduce significantly treatment time (BOT) IGRT Volume delineation Adaptive VMAT Dose escalation studies SIB QUALITY OF LIFE

65 MEDICAL ONCOLOGIST RADIOLOGIST PATIENT SURGEON NURSES RADIATION ONCOLOGIST MULTIDISCIPLINARY APPROACH