Elsevier

Radiotherapy and Oncology

Volume 101, Issue 3, December 2011, Pages 369-375
Radiotherapy and Oncology

Hypoxic PET in treatment planning
Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: Potential for guiding intensity modulated radiation therapy in overcoming hypoxia-induced treatment resistance

https://doi.org/10.1016/j.radonc.2011.07.029Get rights and content

Abstract

Background and purpose

Positron emission tomography (PET) imaging with [F-18] fluoromisonidazole (FMISO) has been validated as a hypoxic tracer [1], [2]. Head and neck cancer exhibits hypoxia, inducing aggressive biologic traits that impart resistance to treatment. Delivery of modestly higher radiation doses to tumors with stable areas of chronic hypoxia can improve tumor control [3]. Advanced radiation treatment planning (RTP) and delivery techniques such as intensity modulated radiation therapy (IMRT) can deliver higher doses to a small volume without increasing morbidity. We investigated the utility of co-registered FMISO-PET and CT images to develop clinically feasible RTPs with higher tumor control probabilities (TCP).

Materials and methods

FMISO-PET images were used to determine hypoxic sub-volumes for boost planning. Example plans were generated for 10 of the patients in the study who exhibited significant hypoxia. We created an IMRT plan for each patient with a simultaneous integrated boost (SIB) to the hypoxic sub-volumes. We also varied the boost for two patients.

Result

A significant (mean 17%, median 15%) improvement in TCP is predicted when the modest additional boost dose to the hypoxic sub-volume is included.

Conclusion

Combined FMISO-PET imaging and IMRT planning permit delivery of higher doses to hypoxic regions, increasing the predicted TCP (mean 17%) without increasing expected complications.

Section snippets

Patients

A total of 102 patients with head and neck squamous cell cancer (HNSCC) were enrolled in a FMISO-PET imaging study of patients with newly diagnosed cancer between April 1994 and August 2007 as part of on-going research protocols. Ten of these patients were randomly selected for inclusion in this sub-analysis. These 10 patients had an average ⩾119 weeks of clinical follow up. They were recruited from the University of Washington Medical Center, Harborview Medical Center, and the Veterans

Results

Significant hypoxia was identified in all 10 patients in this subanalysis, as shown in Table 1. Data for doses to targets and critical structures in radiotherapy plans with and without the boost dose for the 10 cases included in this report are given in Table 2, Table 3. In all cases the IMRT planning technique permitted the dose escalation without exceeding the clinically acceptable limits for the critical structures. Contralateral parotid glands were spared, except in cases where the primary

Discussion

By inducing resistance to treatment, tumor hypoxia “protects” cancer cells, either as a direct effect (due to lack of molecular oxygen that dampens radiation toxicity) or an indirect effect due to the induction of aggressive phenotypes. Dose escalation to hypoxic sub-volumes with conventional photon radiation has been investigated in clinical radiation oncology practice to overcome this cure-limiting effect [14], [17], [37], [38]. In current clinical practice, boost treatment (beyond that

Conflict of interest

The authors confirm that there are no conflicts of interests, financial or otherwise, in conducting this research with FMISO-PET imaging and radiation therapy planning.

Acknowledgments

We would like to thank Paul Kinahan and all nuclear medicine technologists, radiochemists, and physicists in the division of Nuclear Medicine at the University of Washington Medical Center for their help in PET imaging. We would also like to thank Drs. Upendra Parvathaneni and Jay Liao for their contributions to head and neck planning. This study was supported by NIH Grants P01 CA42045 and S10 RR17229.

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