Investigation To The Value Of Pulmonary Perfusion Imaging And Clinical Physical Indicators In Predicting Radiation Pneumunitis

Part1Value of Clinical and Physical Indicators in Predicting Radiation PneumonitisObjective: to study the clinical and dosiology-related factors in radiation pneumonitis inlung cancer patients after radiotherapy.Materials and Methods: a retrospective analysis of the radiotherapy data on75lungcancer patients with visible lesions in the chest was conducted. Of the patients,13everreceived surgical therapy for their disease (three had residual lesions after surgery and10had cancer recurrence after surgery), and the other62were treated for the first time andhad not received chest radiotherapy before.61patients were diagnosed withnon-small-cell lung cancer (NSCLC) and the other14patients were diagnosed assmall-cell lung cancer (SCLC). Radiation pneumonitis was classified according toCommon Terminology Criteria for Adverse Events3.0, relevant factors fortreatment-related radiation pneumonitis grade II and above were analyzed, and one-wayand multi-way analyses were conducted.After a median follow-up of12months (7~36months), the radiotherapy dose for allpatients in the groups was≥50Gy, with the median dose being54Gy (50~70Gy). By thetime six months after the completion of radiotherapy,20%of the patients (15/75) gotradiation pneumonitis above grade2, and by12months after the completion ofradiotherapy, the incidence of radiation pneumonitis was28%(21/75). Analysis ofclinical factors, including age, gender, smoking history, with or without the complicationchronic obstructive pulmonary disease (COPD), TNM stage, pathology, whether or notthe patient previously received surgical therapy, whether the patient previously receivedconcurrent chemotherapy, whether the chemotherapy regimen contained Taxanes orGemcitabine, the gross target volume (GTV) and the radiotherapy dose, showed thatexcept pathology and the radiotherapy dose, other factors were not directly associatedwith occurrence of radiation pneumonitis. Among the pathological factors, the risk ofradiation pneumonitis in patients with SCLC was2.861times that in patients withNSCLC (P=0.017). The risk of radiation pneumonitis for the group with a totalradiotherapy dose≤60Gy was3.212times that in the group with a total radiotherapydose>60Gy (P=0.002), and the radiotherapy dose was significantly associated withoccurrence of radiation pneumonitis. One-way analysis of dosiology-related factorsincluding mean lung dose (MLD), V5, V10, V15, V20, V25, V30, V35，V405, V45,V50, V55and V60showed that MLD was not significantly associated with occurrence of radiation pneumonitis in this group, with P being0.10. Vd in low doseregion was related to occurrence of radiation pneumonitis, and the correlation betweenthe volume of V5and V25and the occurrence of radiation pneumonitis was statisticallysignificant, with the P value being0.035and0.034respectively; the incidence ofradiation pneumonitis in the group with V25≥25%was obviously higher than that in thegroup with V25<25%(P=0.04). In addition, the radiation volume in the low radiationdose groups V10, V15, V20and V30also seemed to be associated with occurrence ofthis disease, with a respective P value of0.063,0.071,0.052and0.061. Vd in the highdose region was not associated with occurrence of radiation pneumonitis. Logisticanalysis of such factors as smoking history, COPD, pathology, concurrent chemotherapyor not, radiation dose, GTV, MLD, V5, V10, V15, V20, V25and V30showed that V5and radiation dose group were the independent prognostic factor for radiationpneumonitis, with the P value being0.017and0.001respectively.Conclusions: Many clinical and dosiology-related factors affected occurrence ofradiation pneumonitis. The radiation volume in the low dose region and the totalradiation dose were independent prognostic factors. Occurrence of radiation pneumonitisis a complicated issue that requires consideration for various factors to establish atreatment plan.Part2Application of Pulmonary Perfusion Imaging in Calculating BiologicallyEquivalent Uniform Dose (EUD) to Predict Radiation PneumonitisObjective: this study investigated the best predictor factor for radiation pneumonitis byusing a combination of functional imaging and radiobiological parameters. Thebiologically equivalent uniform dose (EUD) was calculated based on pulmonary perfusionafter the radiation treatment planning system (TPS) was fused with the perfusion countvalue obtained by use of SPECT pulmonary perfusion imaging, and the value of EUD inpredicting the occurrence of radiation pneumonitis in lung cancer patients receivingradiotherapy was analyzed.Materials and Methods: this article conducted a prospective analysis of the clinical data offifty lung cancer patients with visible lesions in the chest who received radiotherapy. Noneof the patients received either surgical therapy or chest radiotherapy before. Of the50patients,42had non-small-cell lung cancer (NSCLC) and8had small-cell lung cancer(SCLC). All the patients took SPECT perfusion imaging before the radiotherapy, and theimaging agent used was technetium-99m (99mTc)-marked human serum macro-aggregated albumin. The obtained perfusion image data were transmitted to Philips Pinnacle3planningsystem, and the perfusion image and CT image were infused by using the Fusion function.The maximum nuclide uptake count was calculated by using the software of PhilipsPinnacle3planning system, and0~25%,26~50%,51~75%and76~100%of the maximumcount were used as the classification standards for lung function, according to which thenormal lung tissues were divided into four grades. The functional density value representedby perfusion count value was utilized to calculate EUD. Radiation pneumonitis wasclassified according to CTC3.0classification system.Results: mean EUD was13.16±5.75for lung on the100%side,17.2±5.64for lung tissueswith radiation pneumonitis and12.08±5.31for lung tissues without radiation pneumonitisrespectively, and the P value was0.000, indicating that the differences were statisticallysignificant. The95%confidence interval (95%CI) was2.51-7.74.Conclusions: the functional density value obtained by using perfusion count was wellcorresponding, and EUD calculated according to the count value was well representative ofthe biologically EUDs of lung tissues–the higher EUD, the greater the probability ofradiation penumonitis was.Part3Predictive Value of Cytokines in Radiation PneumonitisObjective: this study, through detection of pre-radiotherapy serum IL-6, ACE andICAM-1levels in lung cancer patients, investigated the correlation between suchindicators and occurrence of radiation-induced lung injury and explored the possibility ofusing such indicators as the susceptible predictors of radiation-induced lung injury.Materials and Methods: we conducted a retrospective analysis of the radiotherapy data on75lung cancer patients with visible lesions in chest, of whom,13ever received surgicaltherapy for their disease (three had residual lesions after surgery and10had cancerrecurrence after surgery), and the other62were treated for the first time and had notreceived chest radiotherapy before. Of the75patients,61were diagnosed withnon-small-cell lung cancer (NSCLC) and the other14were diagnosed as small-cell lungcancer (SCLC). Blood samples were collected before radiotherapy, and the separatedplasma was cryopreserved in a low-temperature refrigerator. ELISA kits were used todetect the levels of ICAM, ACE and IL-6. All the75patients were given three-dimensionconformal radiotherapy and clinically followed-up, and their radiation pneumonitis wasclassified according to CTCAE3.0to analyze the relationships of ICAM, ACE and IL-Lwith treatment-related radiation pneumonitis grade2and above. Results: After a median follow-up of12months (7~36months), the radiotherapy dose forall patients in the groups was≥50Gy, with the median dose being54Gy (50~70Gy). Bythe time six months after the completion of radiotherapy,20%of the patients (15/75) gotradiation pneumonitis above grade2, and by12months after the completion ofradiotherapy, the incidence of radiation pneumonitis was28%(21/75). In the group withradiation pneumonitis and the group without radiation pneumonitis, the mean serum IL-6level was51.11±14.46pg/ml and30.26±2.75pg/ml respectively, the mean serum ACElevel was56.93±19.38ng/ml and74.92±36.76ng/ml respectively, and the mean serumICAM level was140.09±25.66ng/ml and119.03±13.25ng/ml respectively. Differences inthe serum IL-6and ICAM levels in the group with radiation pneumonitis were notstatistically significant (P>0.05), while differences in the serum ACE levels werestatistically significant (P<0.05). When ACE90ng/ml before radiotherapy was used asthe judgment standard for occurrence of radiation pneumonitis,33.9%of the patientswith an ACE <90ng/ml developed radiation pneumonitis, and only6.25%of the otherpatients developed this disease (χ2=4.773, P=0.031). When ACE<90ng/ml beforeradiotherapy was used as the threshold for predicting occurrence of radiationpneumonitis, the sensitivity was95.2%, the specificity was27.8%, the positive predictivevalue (PPV) was33.9%, the negative predictive value (NPV) was93.8%, and theaccuracy was46.7%.Conclusions: ACE level before radiotherapy was associated with occurrence of radiationpneumonitis and of good value in predicting the occurrence of the disease. In addition,ACE>9090ng/ml was the optimum threshold for prediction of radiation pneumonitis.Serum IL-6and ICAM-1levels before radiotherapy were not apparently associated withoccurrence of radiation pneumonitis.