The Value Of ¹⁸F-FDG PET/CT In Different Phase Of Chemotherapy For Predicting The Prognosis Of Non-Hodgkin Lymphoma

[Objective]1.To investigate the clinical value of 18F-FDG PET/CTimaging for treatment evaluation of non-Hodgkin lymphoma.2.To assess the value of 18F-FDG PET/CT in different phase of chemotherapy for predicting the prognosis of non-Hodgkin lymphoma.[Materials and methods]1. Study objectiveForm May 2003 to February 2015, a total of 318 patients with already established diagnosis of non-Hodgkin lymphoma were enrolled in this study, including 205men and 113 women, aged from2 to 82 years old, with a mean age of 46 years old. These patients should meet the following facts:1) already established diagnosis of non-Hodgkin lymphoma according to the WHO standard.2) was observed with positive 18F-FDG PET/CT at NANFANG PET center or others.3) already take at least 2 cycles of chemotherapy of NHL.4) has complete clinical data and no other malignant tumor was observed during follow-up.There were 180 cases of DLBCL,51 cases of FL,32 cases of MCL,31 cases of MALT, and 24 cases of PTCL.197 cases of 18F-FDG PET/CT imaging before treatment were found among these patients.318 patients and patients of other pathological pattern of NHL were divided into 2 groups according to different phase of chemotherapy 18F-FDG PET/CT were performed. Among 160 cases of the interim phase group (2-4 cycles of chemotherapy),4 cases of 2 cycles,62 cases of 3 cycles, and 94 cases of 4 cycles, while 32 cases of 5 cycles,74 cases of 6 cycles,13 cases of 7 cycles and 39 cases of 8 cycles. The diagnosis of recurrent NHL and metastasis was established by pathologic examination, ulti-modality imaging and clinical follow-up for more than 18 months.2.Imaging modality and imaging agentThe examinations were carried out using a GE Discovery LS PET/CT scanner (GE, Healthcare, and Waukesha, WI). The positron emitter was produced using the cyclotron of PETtracer (GE,Healthcare, Waukesha, WI).The tracer 18F-FDG, was manufactured automated by the tracer synthesis system of FDG Microlab (GE,Healthcare, Waukesha, WI), with a radiochemical purity> 95%.3. Imaging methods and conditionsAll of the patients underwent PET/CT scans after fasting at least 6 hours prior to examination, detect blood sugar, weighed, measuring height are required before injection imaging agent.18F-FDG with the dose of 5.5MBq/kg was administrated intravenously via a T tube. After about 60 minutes of relaxed rest in a supine position in dark rooms without visual or acoustic stimulations, the patients were asked to void and were then placed into the PET/CT scanner for image acquisition. The image acquisition included non-enhanced CT scan and PET scan covered the range from the head to the middle thigh, if necessary, add to sweep the lower limbs,collection of 6 to 8 beds. Patients with suspected intracranial metastases should be collectedby the method of three-dimensional model of cerebral, emission scanning 3min/beds;for solitary pulmonary nodules less than 3cm conduct thin-section CT scans,thickness of 1.25mm.4. Image reconstruction and fusionPET images were reconstructed by using a standard iterative algorithm (ordered subset expectation maximization) with CT data being used for attenuation correction. The CT images were reconstructed by using a standard method.The thickness of each slice of PET and CT after reconstruction was 4.25mm. The acquired images of PET and CT were sent to theXeleris (GE Medical Systems) workstation for image registration and fusion.5. PET/CT Image analysisPET,CT and PET/CT images were interpreted independently by three experienced senior physicians of nuclear medicine and three experienced senior physicians of CT diagnosis. After visually examining all images on the workstation, the reviewers reached a final diagnosis basedmainly on fusion images of PET and CT. Any initialdifference of opinion was resolved by consensus. The following diagnostic criteria for recurrence and metastasis of NHLshould meet:(1)For the lymph node or region with F-FDG uptake higher than that of the blood pool and without density increasedsignificantly and calcification, no matter the size of the area it was diagnosed to be positive. (2)For the lymph node with 18F-FDG uptake lower than that of the blood pool or was similar to the blood pool, according to the CT diagnostic criteria, if the regional lymph short diameter<1.0cm, it was diagnosed to be negative,if the regional lymph nodes short diameter> 1.0cm, it was diagnosed to bepositive.[Clinical follow-up]a total of 318 patients with NHL were followed-up for a median number of 26.77 months (18～113 months). The diagnosis of recurrent tumor and metastasis was established by pathologic examination, ulti-modality imaging and clinical follow-up.Progression-free survival, PFS, is for the period from the first 18F-FDG PET/CT performed to the recurrence and metastasis of NHL was observed.[Results]1.18F-FDG PET/CTImage analysis1.1 NHLAmong 318 patients with NHL,210 were found negative 18F-FDG PET/CT while 108 were positive. There was no significant difference of positive finding rate of 18F-FDG PET/CT in the interim and the later phase groups (33.1% vs. 34.8%,x2=17.732, P> 0.05).1.2 DLBCLAmong 180 patients with DLBCL,121 were found negative 18F-FDG PET/CT while 59 were positive. There was no significant difference of positive finding rate of 18F-FDG PET/CT in the interim and the later phase groups (33.7% vs. 31.8%,x2=11.324, P>0.05).1.3 FL31 cases were found negative F-FDG PET/CT while 20 were positive among 51 patients with FL. The positive finding rate of F-FDG PET/CT in the interim phase group is 32.1% while that of 47.8% in the later phase group.1.4 MCLAmong 32 patients with MCL,22 cases were found negative 18F-FDG PET/CT while 10 were positive. The positive finding rate of F-FDG PET/CT in the interim phase group is 42.9% while that of 22.2% in the later phase group.1.5 MALTAmong 31 patients with MALT,22 cases were found negative 18F-FDG PET/CT while 9 were positive. The positive finding rate of 18F-FDG PET/CT in the interim phase group is 33.7% while that of 40.0% in the later phase group.1.6 PTCL14 cases were found negative 18F-FDG PET/CT while 10 were positive among 24 patients with FL. The positive finding rate of 18F-FDG PET/CT in the interim phase group is 40.0% while that of 42.9% in the later phase group.2. PFS analysis2.1 NHLAmong 318 patients with NHL, PFS of the those with the negative 18F-FDG PET/CT was much longer than that of the ones with positive 18F-FDG PET/CT (60.34 vs.22.85 months, P=0.000). PFS of the patients with the negative 18F-FDG PET/CT in the interim group was much longer than that of the ones with positive 18F-FDG PET/CT (48.03 vs.18.60 months, P=0.000).The similar result was observed in the PFS of the negative and positive F-FDG PET/CT in later phase group (62.83 vs.22.76 months, P=0.000). There was no significant difference of PFS of the negative 18F-FDG PET/CT between the interim and the later phase groups (42.03 vs.62.83 months, P=0.189), neither was that of the positive 18F-FDG PET/CT between the interim and later phase groups (18.60 vs.22.76 months, P=0.251).2.2 DLBCLAmong 180 patients with DLBCL, PFS of the those with the negative 18F-FDG PET/CT was much longer than that of the ones with positive 18F-FDG PET/CT (72.70 vs.13.62 months, P=0.000). PFS of the patients with the negative 18F-FDG PET/CT in the interim group was much longer than that of the ones with positive 18F-FDG PET/CT (50.13 vs.14.19 months, P=0.000). The similar result was observed in the PFS of the negative and positive 18F-FDG PET/CT in later phase group (59.81 vs. 21.23 months, P=0.000). There was no significant difference of PFS of the negative 18F-FDG PET/CT between the interim and the later phase groups (50.13 vs.59.81 months, P=0.847), neither was that of the positive 18F-FDG PET/CT between the interim and later phase groups (14.19 vs.21.23 months, P=0.117).2.3 FLPFS of the those with the negative 18F-FDG PET/CT was much longer than that of the ones with positive 18F-FDG PET/CT (45.26 vs.16.19 months, P=0.001) among 51 patients with NHL. PFS of the patients with the negative 18F-FDG PET/CT in the later phase group was much longer than that of the ones with positive 18F-FDG PET/CT (55.50 vs.13.55 months, P=0.000). But there was no significant difference of PFS of patients in the interim phase groupbetween negative F-FDG PET/CT between that of the ones with positive 18F-FDG PET/CT (31.66 vs.19.02 months, P=0.628).2.4 MCLAmong 32 patients with MCL, PFS of the those with the negative 18F-FDG PET/CT was much longer than that of the ones with positive 18F-FDG PET/CT (63.41 vs.10.50 months, P=0.000). PFS of the patients with the negative 18F-FDG PET/CT in the interim group was much longer than that of the ones with positive 18F-FDG PET/CT (31.86 vs.11.33 months, P=0.006). The similar result was observed in the PFS of the negative and positive F-FDG PET/CT in later phase group (66.52 vs.9.25 months, P=0.000). There was no significant difference of PFS of the negative 18F-FDG PET/CT between the interim and the later phase groups (31.86 vs.66.52 months, P=0.437), neither was that of the positive 18F-FDG PET/CT between the interim and later phase groups (11.33 vs.9.25 months, P=0.547).2.5 MALTAmong 31 patients with MCL, PFS of the those with the negative 18F-FDG PET/CT was much longer than that of the ones with positive 18F-FDG PET/CT (69.72 vs.15.74 months, P=0.000). PFS of the patients with the negative 18F-FDG PET/CT in the interim group was much longer than that of the ones with positive 18F-FDG PET/CT (33.54 vs.12.83 months, P=0.004). The similar result was observed in the PFS of the negative and positive 18F-FDG PET/CT in later phase group (57.67 vs.18.42 months, P=0.001). There was no significant difference of PFS of the negative F-FDG PET/CT between the interim and the later phase groups (33.54 vs.57.67 months, P=0.077), neither was that of the positive 18F-FDG PET/CT between the interim and later phase groups (12.83 vs.18.42 months, P=0.118).2.6 PTCLPFS of the those with the negative 18F-FDG PET/CT was not significant different to that of the ones with positive 18F-FDG PET/CT (27.19 vs.37.80 months, P=0.481) among 24 patients with NHL. There was no significant difference of PFS of patients in the interim phase groupbetween negative 18F-FDG PET/CT and positive 18F-FDG PET/CT (29.50 vs.55.50 months, P=0.688), neither was that of in the later phase group between between negative 18F-FDG PET/CT and positive 18F-FDG PET/CT (20.75 vs.22.33 months, P=0.176).3. PFS rate analysis3.1 NHLA whole PSF rate of 54.4% was observed among the 318 patients with NHL. Patients with the negative PET/CT have greater PFS rate than that of the positive 18F-FDG PET/CT (72.4% vs.19.4%, P=0.000). PFS rate of the patients with the negative PET/CT was greater than that of the positive 18F-FDG PET/CT in the interim group (72.0% vs.20.8%, P=0.000). The similar result was also observed in the PFS rate ofthe negative and positive 18F-FDG PET/CT in the later phase group (72.8% vs.18.2%, P=0.000).No different of PFS rate was found between the interim and the later phase groups (55.0% vs.53.8%, P=0.552). There were no significant difference of PFS rate of the negative 18F-FDG PET/CT between the interim and the later phase groups (72.0% vs.72.8%,P=0.189), neither was that of the positive 18F-FDG PET/CT between the interim and later phase groups (20.8% vs.18.2%, P=0.251).3.2 DLBCLA whole PSF rate of 53.3% was observed among the 180 patients with DLBCL. Patients with the negative PET/CT have greater PFS rate than that of the positive 18F-FDG PET/CT (72.7% vs.13.6%, P=0.000). PFS rate of the patients with the negative PET/CT was greater than that of the positive 18F-FDG PET/CT in the interim group (73.8% vs.12.9%, P=0.000). The similar result was also observed in the PFS rate ofthe negative and positive 18F-FDG PET/CT in the later phase group (71.7% vs.14.3%, P=0.000).No different of PFS rate was found between the interim and the later phase groups (53.3% vs.53.4%, P=0.565). There were no significant difference of PFS rate of the negative 18F-FDG PET/CT between the interim and the later phase groups (73.8% vs.71.7%, P=0.847), neither was that of the positive 18F-FDG PET/CT between the interim and later phase groups (12.9% vs.14.3%, P=0.117).3.3 FLA whole PSF rate of 51.0% was observed among the 51 patients with FL. Patients with the negative PET/CT have greater PFS rate than that of the positive 18F-FDG PET/CT (64.5% vs.30.0%, P=0.007). PFS rate of the patients with the negative PET/CT was greater than that ofthe positive 18F-FDG PET/CT in the later phase group (75.0% vs.27.3%, P=0.003). But similar result was not observed in the PFS rate ofthe negative and positive 18F-FDG PET/CT in the interim phase group (57.9% vs.33.3%, P=0.628).3.4 MCLA whole PSF rate of 50.0% was observed among the 32 patients with MCL. Patients with the negative PET/CT have greater PFS rate than that of the positive 18F-FDG PET/CT (68.2% vs.10.0%, P=0.000). PFS rate of the patients with the negative PET/CT was greater than that of the positive 18F-FDG PET/CT in the interim group (75.0% vs.16.7%, P=0.006). The similar result was also observed in the PFS rate ofthe negative and positive18F-FDG PET/CT in the later phase group (64.3% vs.0,P=0.000).No different of PFS rate was found between the interim and the later phase groups (50.0% vs.50.0%, P=0.440). There were no significant difference of PFS rate of the negative 18F-FDG PET/CT between the interim and the later phase groups (75.0% vs.64.3%, P=0.437, neither was that of the positive 18F-FDG PET/CT between the interim and later phase groups (16.7% vs.0, P=0.547).3.5 MALTA whole PSF rate of 67.7% was observed among the 31 patients with DLBCL. Patients with the negative PET/CT have greater PFS rate than that of the positive 18F-FDG PET/CT (90.9% vs.11.1%, P=0.000). PFS rate of the patients with the negative PET/CT was greater than that of the positive 18F-FDG PET/CT in the interim group (84.6% vs.0, P=0.000). The similar result was also observed in the PFS rate ofthe negative and positive 18F-FDG PET/CT in the later phase group (100% vs.16.7%, P=0.003).No different of PFS rate was found between the interim and the later phase groups (68.8% vs.67.7%,P=0.273). There were no significant difference of PFS rate of the negative 18F-FDG PET/CT between the interim and the later phase groups (84.6% vs.100%, P=0.017), neither was that of the positive 18F-FDG PET/CT between the interim and later phase groups (0 vs.16.7%, P=0.118).3.6 PTCLA whole PSF rate of 58.3% was observed among the 24 patients with FL. PFS rate of patients with the negative PET/CT was not greater than that of the positive 18F-FDG PET/CT (64.3% vs.50.0%, P=0.885). There were no significant difference of PFS rate between the patients with the negative PET/CT and the positive ones in the interim phase group (66.7% vs.75.0%, P=0.688). neither was that of the later phase group between the patients with the negative PET/CT and the positive ones (70.0 vs.50.0%, P=0.079).[conclusions]1. The present study demonstrated that18F-FDG PET/CT is useful for predicting the prognosis of the patients with NHL.18F-FDG PET/CT showed the similar value of predicting prognosis in the interim to that in the later phase of chemotherapy.2. Among the patients with DLBCL, who have the negative PET/CT imaging after chemotherapy may have greater PFS rate than those of the positive 18F-FDG PET/CT. On the other hand,18F-FDG PET/CT showed the similar value of predicting prognosis in the interim to that in the later phase of chemotherapy, which indicated 18F-FDG PET/CT can be performed in the interim phase of chemotherapy, not need to delay after the interim phase. Similar conclusions can be used in the patients with MCL, or MALT.3. Among the patients with FL, PFS rate of the patients with the negative PET/CT was found greater than that of the positive 18F-FDG PET/CT in the later phase group, but But similar result was not observed in the PFS rate ofthe negative and positive 18F-FDG PET/CT in the interim phase group, which indicated the value of 18F-FDG PET/CT for predicting the prognosisin the interim phase of chemotherapy is not as great as that of in the later phase group among the patients with FL according to the recent data.4. PTCL is more complex and more invasive and have worse prognosis than B-cell lymphomas. There are no effective therapeutic methods used in T-NHLs, comparing with those in B-cell lymphomas. According to the present study, we may guess that these could be reasons the veracity of 18F-FDG PET/CT for predicting the prognosis of PTCL is not as good as we expect. To expand the sample capacity of PTCL, and an extension of time for follow-up would be the barriers to break in our following research.