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Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.
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Objective:Patients are breathing freely during adjuvant proton pencil beam radiotherapy after breast conserving surgery. Fluctuation of the thorax may affect the position of the end of the proton beam flow, which needs to be precisely evaluated on a millimeter scale.Methods:For 20 patients with breast cancer treated with proton radiotherapy after breast conserving surgery, PET-CT scan was performed approximately 10 min after the end of proton radiotherapy. The images of PET-CT were processed for ROI determination and sampling line (profile) extraction on a Raystation RV workstation to calculate the actual difference between the predicted and real radioactivity from the same spatial location as obtained by PET acquisition R50. Then, the differences in the spatial location between the actual process of proton irradiation and the planned process were obtained. Depth difference values for each pair of sampling lines were presented. Results:For 20 patients with breast cancer with a median follow-up of 22 months (range 12 - 46 months), all patients survived at the last follow-up, and no radiation pneumonitis was observed during the follow-up period. Among the verification results of 21 cases, the depth difference of evenly distributed was (-0.75±1.89) mm in the primary field and (-0.82±2.06) mm in the secondary field; The depth difference of sequential treatment was (1.81±1.87) mm in the primary field and (1.32±1.74) mm in the secondary field; The depth difference of synchronous addition in the primary field was (-1.47±1.44) mm, and the depth difference in the secondary field was (-1.48±2.11) mm.Conclusion:The results of off-line PET-CT in vivo biological verification show that the accuracy of the dose boundary cut-off was within 3 mm in breast cancer patients, which meets the clinical and physician requirement for the precision in breast cancer treatment.
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Objective:To test the usefulness of PET-range verification (RV) method for proton radiation accuracy verification in poly (methyl methacrylate) (PMMA) phantom using off-line PET/CT scanning.Methods:Proton irradiation dose of 2 Gy and 4 Gy were delivered in PMMA phantom. Given the difference of clinical target volume (CTV), 7 subgroups with different depth (5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0 cm) were set for each dose (14 radiation plans or radiation fields). PET/CT scan was performed 10 min after irradiation of 48-221 MeV proton beam. A co-registration between CT from treatment planning system and PET/CT was performed, as well as the smoothing and normalization of PET/CT data. The region of interest (ROI) and profile lines were drawn with the Raystation PET-RV software. The predictive induced radioactivity and the measured induced radioactivity profile lines were analyzed to evaluate the Δ R50, namely, the error at the position corresponding to 50% of the maximum predictive induced radioactivity at the end of both curves. Results:The size of each ROI was 5.0 cm×5.0 cm×2.5 cm. Profile lines were evenly distributed with the interval of 3 mm, and totally 289 pairs of profile lines were drew. The 2 Gy- and 4 Gy-dose groups yielded similar mean depth errors (Δ R50 between 1 mm and -1 mm with a standard deviation <1 mm). Conclusions:The off-line PET/CT scanning of PMMA phantom reveals a good agreement between predicted and measured PET data, with error of ±1 mm. The PET-RV method can be extended to clinical cases′ verification in human body treatment with further investigation.
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Objective@#To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation.@*Methods@#Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation.@*Results@#Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed.@*Conclusions@#IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.
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Background and purpose: Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) can be used for magnetic resonance imaging systemic examination, especially in examing the metastatic lesions, lymph node and bone diseases, and the imaging result is similar with PET. This study aimed to evaluate the application value of magnetic resonance DWIBS and positron emission tomography with computed tomography (PET/CT) on malignant metastatic diseases. Methods: Thirty-six patients confirmed with malignant tumors accompanying metastasis by the pathology of operation or biopsy underwent both DWIBS imaging and PET/CT, chi-square test and Kappa test were used for comparing the detection results of metastasis by these 2 imaging methods. Results:Among the 36 malignant tumor patients with 238 metastatic lesions, 218 (91.6%, 218/238) lesions in DWIBS and 209 (87.8%, 209/238) lesions in PET/CT were detected, with 200 lesions detected by the two methods simultaneously, and the concordance rate was 88.7%(211/238);but there was no statistical signiifcance between this two methods (χ2=1.843, P=0.157). Kappa test showed a fair concordance rate between DWIBS and PET/CT (P=0.000).There were different significance between DWIBS and PET/CT in detecting metastatic lesions of brain and bone (P=0.005 and 0.031);But there was no signiifcant differences (P=0.309 and 1.000) in detecting metastatic lesions of lymph nodes and liver. Conclusion:DWIBS could detect metastatic lesions effectively, and there is ifne consistency with PET/CT. DWIBS is more sensitive than PET/CT in detecting metastatic lesions of brain and bone, so DWIBS could be chosed for screening metastatic lesions according to the characteristics of different primary tumors.
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Background and purpose: 18F-FDG has been considered to be of limited value for the detection of bladder lesions because of interference by the 18F-FDG excreted in urine. Delayed pelvic images with“diluted and iflled bladder”use a method of 18F-FDG PET/CT with delayed images after oral hydration so as to increase the detection rate of 18F-lfuorodeoxyglucose(FDG) PET/CT imaging for the lesions of bladder. Methods:48 patients with bladder lesions(35 patients with bladder primary tumor and 13 patients with metastatic tumor) underwent 18F-FDG PET/CT detection and were required oral hydration of 1200-1800 mL water, urination frequently, holding urine when the more scan began. Lesions conifrmed by histopathology, MRI, CT or clinical follow-up at least 1 year. Results:89%(43/48) of patients were obtained good clearance and the urine SUVmax declined from 33.14(9-66.80)to 3.23(1.35-5.65) signiifcantly and the statistical difference was signiifcant (t=8.703, P<0.01). The interval time between two scan was 2 h approximately. At the same time, the SUVmax of bladder lesion was 2.8-25.0. Detection sensitivity, speciifcity and accuracy were 90.47%(19/21), 81.48%(22/27)and 85.41%(41/48), respectively. Conclusion: 18F-FDG activity in the bladder signiifcantly decreased in most patients with“diluted and iflled bladder”. The PET/CT scan can highly detect lesions of bladder tissues. Our method with high accuracy and better endurance could be applied to detect the lesions in bladder.
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Background and purpose:Tumor suppressor gene P53 has long been studied in tumors, including breast cancer. More studies focused on the relationship between P53 and prognosis of breast cancer and found that P53 overexpression suggested a bad prognosis. However, the effect of P53 on early stage postmenopausal patients with ER-positive breast cancer has not been clariifed yet. This study was to investigate the role of P53 plays in aromatase inhibitor (AI) resistance among early stage postmenopausal patients with ER-positive breast cancer patients. Methods:A total number of 293 operable breast cancer patients who received surgical treatment during Jul. 2000 to Jul. 2006 in Fudan University Shanghai Cancer Center were enrolled into this study. All patients received AI treatment. The SPSS 12.0 software was used to estimate the survival rate. Univariate and multivariate analysis were also performed via above software. Results:The median follow-up time is 72 months (6-140 months). The 5 year disease free survival (DFS) of P53 positive and negative were 78%and 89%. The results showed that P53 overexpression (HR=1.729, 95%CI:1.038-2.880, P=0.035), pathological stage (HR=2.270, 95%CI:1.399-3.681, P=0.001);histological grade (HR=2.328, 95%CI:1.312-4.133, P=0.004); age (HR=1.988, 95%CI:1.511-2.617, P<0.005) were still the independent risk factors of recurrence and metastasis in breast cancer patients treated with AI. Conclusion:P53 overexpression correlated strongly with AI resistance in early stage postmenopausal patients with ER-positive breast cancer patients who were treated with AI and conifrmed the relevance of previously described prognostic factors. It is reasonable to take P53 expression into account when we evaluate the risk of breast cancer patients and decide the anti-cancer treatment strategy.
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Background and purpose:Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) can be used for MR imaging systemic examination, especially the lymph node and bone diseases can be clear, and the imaging result is similar with PET. The aim of this study was to compare the value of clinical application in the diagnosis of malignant metastatic osteopathic between DWIBS and bone scintigraphy mapping. Methods:Thirty-six specimens conifrmed with malignant tumors by the pathology of operation or biopsy underwent both DWIBS imaging and bone scintigraphy mapping, chi-square test was used for comparing the detection results of bone metastasis by this two imaging methods. Results:Thirty (165 positions in all) of 36 malignant tumor patients were conifrmed as having bone metastasis, compared that 26 patients (143 positions) with DWIBS method and 23 patients (132 positions) with bone scintigraphy mapping were detected, but there was no statistical signiifcance between this two imaging methods (χ2=1.002, P=0.506). The sensitivity, positive predictive value (PPV) and accuracy of the detection rate of bone metastasis were similar in DWIBS and bone scintigraphy, with 86.7%, 96.3%, 86.1%and 76.7%, 88.5%, 72.2%, respectively;but the speciifcity and negative predictive value (NPV) in DWIBS (83.3%and 55.6%) was higher than that of in bone scintigraphy (50.0%and 30.0%). The detection rates of different bone metastasis with DWIBS and bone scintigraphy were 86.7%(143/165) and 80.0%(132/165), and it was no signiifcant difference (χ2=2.640, P=0.104);DWIBS method was better than bone scintigraphy in the detection of osseous metastasis on pelvis and limbs long bone, and there was different signiifcant (χ2=6.783 and 7.636, P=0.023 and 0.016). Conclusion:DWIBS could detect bone metastatic lesions effectively, and there is ifne consistency with bone scintigraphy. Therefore, DWIBS is to hope to be extended and applicated clinically.
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Background and purpose: One of the main mechanism of chemotherapy is inducing tuomr apoptosis. Molecular imaging can allow noninvasively and dynamically monitor tumor apoptosis in vivo, and help to drug screening and therapeutic evaluation. The purpose of this study was to evaluate the feasibility of 18F-SFB-Annexin B1 in detecting apoptosis at an early phase after chemotheraphy. Methods:Annexin B1 was labeled with 18F using SFB as a chelating agent. Tissue distribution of 18F-SFB-Annexin B1 was studied in healthy mice by the dissection method. W256 tumor-bearing rats were injected with 18F-SFB-Annexin B1 intravenously at 24 h after the treatment of cyclophosphamide (CTX 200 mg/kg) or saline. Then imaging was acquired at 1, 2, 3, and 4 h postinjection on a PET/CT, and the tumor-to-muscle ratio of SUVmax (T/M) and the AI from TUNEL testing were compared. Results: 18F-SFB-Annexin B1 had a radiochemical pruity (RCP)>95%. Biodistribution of this probe showed a predominant uptake in the kidney, then was liver, spleen, and myocardium, rapid clearance from blood and urinary was observed. The radios of T/M were 4.38±0.56, 6.75±1.16, 6.44±1.12, 4.81±0.17, respectively at 1, 2, 3, 4 h post injection of the chemotherapy group, much higher than that of the saline group (2.35±0.14, 2.99±0.55, 3.04±0.41, 2.33±0.47, respectively). The differences between the two groups were significant (F=23.790, 16.913, 14.046, 77.517, respectively, all P<0.05). TUNEL staining revealed that chemotherapy treatment significantly increased the percentage of apoptosis cells with an AI of (21.00±0.04)%in the chemotherapy group, higher than that in the saline group (8.58±0.01)%, the difference was significant (F=21.539, P<0.05). The radios of T/M were significantly correlated with the values of AI (r=0.91, P<0.05). Conclusion: 18F-SFB-Annexin B1 can be used to apoptosis imaging and early therapeutic evaluation in vivo because it can reflect apoptosis at an early stage after chemotheraphy.
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Background and purpose:Neoadjuvant chemotherapy with docetaxel was gaining more attention in the treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). The prediction of the sensitivity to neoadjuvant chemotherapy with docetaxel could enable clinicians to individualize treatment protocols for NPC. Recently we found that 99mTc-MIBI imaging in NPC could predict tumor response to chemotherapy with cisplatin plus 5-FU. However, there was no study to support similar findings in NPC patients receiving chemotherapy containing docetaxel. This study was to evaluate the value of double-phase 99mTc-MIBI SPECT/CT in predicting response to neoadjuvant chemotherapy with docetaxel-based regimen for nasopharyngeal carcinoma. Methods:Thirty-one nasopharyngeal carcinoma patients participated in this prospective study. Before treatment, early and delayed single-photon emission computed tomography/compute tomography (SPECT/CT) images were obtained instantly and 2 hours after an intravenous injection of 25-30 mCi 99mTc-MIBI. All patients received neoadjuvant chemotherapy consisting of docetaxel, cisplatin plus 5-FU for two cycles. The relationships between efficacy of neoadjuvant chemotherapy and the early uptake ratio, late uptake ratio and washout rate of 99mTc-MIBI were evaluated.Results:According to the MRI, the early uptake of 99mTc-MIBI (2.67±0.83) in the lesions which were sensitive to chemotherapy was significantly higher compared with that (1.69±0.46) in the insensitive lesions(P=0.003). The difference of the late uptake between the sensitive(1.46±0.39) and the insensitive (1.06±0.62) was also statistically significant (P=0.026). However, the washout rate of 99mTc-MIBI was not significantly different between the two groups (P=0.23). Through ROC curve analysis, the AUC for early uptake of 99mTc-MIBI and late uptake were 0.84. The sensitivity, specificity, positive predictive value and negative predictive value were 74.2%, 87.5%, 95.8%and 46.7%for early uptake when the cut off value of 1.97 was used. Conclusion:The uptake of 99mTc-MIBI in both early phase and late phase could predict the efficacy of neoadjuvant chemotherapy with docetaxel-based regimen.