Application Of¹⁸F-FMISO PET/CT To The Clinical Practice Of Nasopharyngeal Carcinoma

[Objectives] To evaluate the hypoxia status of primary tumor and metastasis lymph nodes of nasopharyngeal carcinoma (NPC), and the relationship between hypoxia and stage, tumor volume.[Materials and methods]Between May2011and Jan.2012,16patients who was diagnosed as NPC, stage Ⅱ-Ⅳ were enrolled. Nasopharyngeal and cervical MRI,18F-FMISO PET/CT and18F-FDG PET/CT were performed one week before treatment. There was at least one day between each PET scan. Tumor muscle ratio (TMR) and hypoxia volume (HV) were measured. HV was defined as the subvolume of primary tumor and metastatic lymph node where TMR was more than1.3.[Results] TMR of primary tumor, metastatic lymph nodes was1.91±0.56and1.85±0.90, respectively. HV of primary site and metastatic lymph node was1.95(0-25.70)ml,0.1(0-71.6)ml, respectively.93.8%of primary tumors and75%of metastatic lymph nodes were hypoxia to different extents. TMR, HV of primary tumor correlated with the volume of primary tumor. Similarly, TMR, HV of metastatic lymph nodes correlated with the stage and volume of them. SUVmax, TMR of primary tumors4h post injection (p.i.) was better than that2h p.i.(p=0.03, p=0.0003). TMR of metastatic lymph nodes4h p.i. had the same trend (p=0.05).[Conclusions] TMR4h p.i. was a practical index to evaluate the hypoxia conditions in primary tumor and metastatic lymph nodes for NPC. Most primary tumors and metastatic lymph nodes were hypoxia. The extent of hypoxia correlated with tumor volume and stage. [Objectives] To evaluate the role of18F-FMISO PET/CT in predicting response to chemoradiotherapy for NPC.[Materials and methods]Between May2011and Jan.2012,13patients who were diagnosed as NPC, stage Ⅱ-Ⅳb were enrolled into the study. MRI of nasopharynx and neck,18F-FMISO PET/CT and18F-FDG PET/CT were performed a week before treatment. All patients received two cycles of induction chemotherapy and concurrent chemoradiation with a total dose of66-70.4Gy in30-32fractions. A second18F-FMISO PET/CT was performed two weeks post-induction chemotherapy and a third one was performed at the10th fraction radiotherapy. MRI was done two weeks post-induction chemotherapy and at the25th fraction of radiotherapy, to evaluate the regression of tumor, according to RECIST1.1criteria. The relationship between TMR, HV and tumor regression rate was analyzed.[Results] After induction chemotherapy,53.8%of patients were PR and46.2%were SD. After the25th fraction,66.7%of them were PR and33.3%of them were CR. Post-chemotherapy TMR for the primary tumor significantly decreased, compared with pre-treatment TMR (p=0.002), so as the mid-radiotherapy TMR. Post-chemotherapy total HV was significantly lower than that of pretreatment (p=0.008), so as mid-radiotherapy one (p=0.013). Pretreatment, post-chemotherapy and mid-radiotherapy TMR of primary tumor strongly correlated with tumor regression rate at the25th fraction of radiotherapy (p=-0.758,-0.777,-0.666). The pretreatment TMR of primary tumor was significantly higher in PR patients than CR patients(2.04±0.55vs.1.35±0.11, p=0.009). In addition, pretreatment HV of primary tumor correlated with tumor regression rate at the25th fraction of radiotherapy (p=-0.825). Pretreatment SUVmax of primary tumor and metastatic lymph nodes of FDG PET/CT correlated with TMR of FMISO PET/CT (p=0.753,0.845). Moreover, there was also a strong negative correlation between pretreatment SUVmax of primary tumor of FDG PET/CT and tumor regression at the end of radiotherapy (p=-0.768).[Conclusions] Induction chemotherapy could reoxygenate primary tumor, reduced hypoxia volume of primary tumors and metastatic lymph nodes. Pretreatment, post-chemotherapy and mid-radiotherapy TMR of primary tumor correlated with tumor regression rate during radiotherapy, had a potential value of predicting radiosensitivity. Pretreatment SUVmax of primary tumor of FDG PET/CT correlated with TMR of FMISO PET/CT, which was also a potential predictor of radiosensitivity. [Objectives] To evaluate the feasibility of18F-FMISO PET/CT guided simultaneous integrated boost Intensity-Modulated Radiotherapy for NPC.[Materials and methods] This study enrolled8patients who fulfilled the following criteria:pathologically diagnosed as NPC, stage Ⅱ-IVb, with primary tumor or lymph nodes hypoxia before radiotherapy. Pre-radiotherapy and mid-radiotherapy18F-FMISO PET/CT scans were co-registered. High uptake subvolume (TMR≥1.1,1.2and1.3) were contoured within tumor region and the overlapping volume between pre-radiotherapy and mid-radiotherapy was measured. The stability coefficient was defined as the ratio of overlapping volume to the pre-treatment volume.5patients with a higher hypoxia volume were included into the planning study.18F-FMISO PET/CT scans and TPS CT were co-registered using the same immobilization methods. Regions of elevated18F-FMISO uptake (TMR≥1.3)within the GTV were defined as GTVh and targeted for an simultaneous boost. A total dose of77Gy,84Gy,87.5Gy was delivered to GTVh in different plans. Paired t test was used to compare the dosimetric differences between IMRT plan with or without boost.[Results] The stability coefficient was individualized and ranged from0-44%. We were able to deliver a boost of77Gy to87.5Gy to the GTVh, meanwhile make the dose of normal structures within the constraints, besides that the mean dose and V30of parotid slightly exceed the constraints.[Conclusions] The stability of hypoxia volume between pre-radiotherapy and mid-radiotherapy scan varied from patient to patient. In some patients, the hypoxia volume was relatively stable. It was technically and dosimetrically practical to deliver a modest boost (110%-125%) to the hypoxia volume of NPC.