Positron emission tomography for radiation treatment planning in head and neck cancer

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1 Positron emission tomography for radiation treatment planning in head and neck cancer G.Frezza U.O. di Radioterapia Dipartimento di Oncologia AUSL di Bologna

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4 PET for radiation treatment planning in head and neck cancer Head and neck cancers affect 40/ males and 9/ women and represent nearly 4.5% of all tumors. Survival is good, at least in early stages, and has slightly improved in the last decade Local treatment plays an important role in the therapy of head and neck cancer Radiation therapy alone or combined with surgery and/or chemotherapy is emploied in the local treatment of most of these patients

5 PET for radiation treatment planning in head and neck cancer Radiotherapy process Staging Delineation of the target Treatment planning Treatment delivery Evaluation of the response and follow up

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7 Positron emission tomography for radiation treatment planning in head and neck cancer Staging Does every H&N patient need a PET/CT scan? Should PET-CT be performed in addition to, or instead of, CT and/or MRI scan? PET/CT has a sensitivity of 98%, a specificity of 92% and an accuracy of 92%, compared with 74%, 75% and 74% of CT scan respectively (Branstetter, Radiology 2005)

8 Positron emission tomography for radiation treatment planning in head and neck cancer Staging PET-CT alters TNM staging in approximately 30% of patients. This is predominantly in the upstaging of nodal disease and in the detection of distant metastases (Connell, Head and Neck 2007; Schwartz, IJROBP 2005) These data suggest that all patients, at least those with a high likelihood of additional regional or metastatic disease, should have a staging PET-CT, and that the altered staging should influence treatment decision, even if discordant with conventional imaging results

9 Delineation of the target CTV 54 CTV 66 PTV PTV CTV 54 Parotide dx Parotide sx CTV 54 Midollo spinale

10 Delineation of the target: Comparison of different imaging modalities Daisne et al., Radiology, 2004

11 Positron emission tomography for radiation treatment planning in head and neck cancer Delineation of the target ShouldwebeusingPET-CT scan in planning of radiotherapy in head and neck cancer? What is the evidence that it adds value? Significant variability in gross tumor volumes when using PET-CT to define them A delineation protocol for PET TC is required Default window setting ( SUV 0-10) SUV treshold>2,5 SUV treshold> 40% max.suv Burri et al., IJROBP 2008

12 Positron emission tomography for radiation treatment planning in head and neck cancer Delineation of the target FdG PET scan provides a more accurate definition of tumor and metastatic nodes than CT Significant variability exists in volumes obtained by using different SUV tresholds (SUV 40 better?) A combination of clinical examination, CT (or RM) and PET information should continue to be used for optimal treatment planning

13 Positron emission tomography for radiation treatment planning in head and neck cancer Delineation of the target The more accurate definition of the target allowed by PET CT SCAN helps to : Improve inter observer variability Reduce the risk of missing areas of GTV Spare critical organs from boost dose

14 Positron emission tomography for radiation treatment planning in head and neck cancer Delineation of the target Significant differences in GTV definition beetween PET TC scan and CT/MR GTV GTV CTV however is a clinical entity, and in H&N cancer is much larger than GTV Prescription dose to CTV is generally prescribed to a larger amount of tissue than GTV CTV GTV 7000 CGy Differences in GTV definition do not always have an impact on dose prescription to CTV CTV

15 Positron emission tomography for radiation treatment planning in head and neck cancer Dose escalation 61 Pts. With HNC treated with RT (3D CRT or IMRT) At a median f.u. of 22 mos. 9/61 pts (15%) had a LR In 8/9 pts the volume of the recurrence was within the PET-BTV Role of PET BTV in dose escalation

16 Positron emission tomography for radiation treatment planning in head and neck cancer Dose escalation

17 Positron emission tomography for radiation treatment planning in head and neck cancer Dose escalation 54 Gy 69 Gy T4N0 carcinoma of the nasopharynx Simultaneous integrated boost for dose escalation Boost volume: PET BTV 72.5 Gy?

18 Positron emission tomography for radiation treatment planning in head and neck cancer Biological characterization of the disease It has long been recognized that tumor hypoxia and its attendant radioresistence are assoiciated with poorer treatment outcomes Detection of hypoxia is important, particularly if specific therapies targeting hypoxia can subsequently be utilized The advantages of PET hypoxic imaging are that it is not invasive, permit visualization of both the primary and the nodes and can detect heterogeneous distribution of hypoxia 18F-Fluoromisonidazole is the most studied isotope for hypoxic imaging 18FdG PET scan 18F-FMISO PET scan

19 Positron emission tomography for radiation treatment planning in head and neck cancer Biological characterization of the disease The changes in spatial distribution of tumor hypoxia as detected in serial FMISO PET imaging can compromise the coverage of hypoxic tumor achievable with dose-painting IMRT. However even when changes occurr, dose painting can always increase the dose to hypoxic subvolumes Lin,Z., IJROBP 2008

20 Positron emission tomography for radiation treatment planning in head and neck cancer Biological characterization of the disease 18F-Fluoroazomycin-arabinoside (FAZA) is a new hypoxia tracer FAZA PET imaging can be used for a hypoxia directed IMRT approach in head and neck cancer The importance of hypoxia in the primary is supported by preliminary results from FAZA imaging in a phase III trial, with 0/18 hypoxic primaries treated with a Tirapazamine containing regimen failing locally, compared to 2/9 treated with CDDP (Rischin,R., IJROBP 2007)

21 Positron emission tomography for radiation treatment planning in head and neck cancer Assessment of treatment response

22 Positron emission tomography for radiation treatment planning in head and neck cancer Assessment of treatment response PET TC performed in 34 pts previously treated for malignancies of the skull base Positive predictive value: 46.2% The mucosal lining of the reconstructed skull base is a commom source for inflammatory pathologies which can lead to false positive PET scan

23 Positron emission tomography for radiation treatment planning in head and neck cancer Predictive value of treatment response 30 consecutive patients treated with RT for H&N cancer Before RT: recurrence of a previously treated nasopharyngeal ca. In the left orbit 2 ys disease free survival: 89% for metabolic complete responders; 57% for patients with persistent positive findings at PET TC (p <0,05) Connell, C.A., Head and Neck, mos after RT: complete metabolic response at PET CT scan 2 ys after RT: persistent abnormalities at MRI; no disease progression

24 PET for radiation treatment planning in head and neck cancer Conclusions PET CT scan is extremely useful in staging patients with H&N cancer, since it can alter the TNM stage up to 30% of patients PET CT scan is more accurate than CT/MRI in the definition of GTV and reduces interobserver variability PET CT scan helps in performing dose escalation (PET BTV) with IMRT PET CT scan with hypoxic imaging can be used for a hypoxia directed IMRT approach PET CT scan helps in assessing the response to treatment (residual abnormalities after radiation) and in predicting disease free survival after radiotherapy