Novel model integrating computed tomography-based image markers with genetic markers for discriminating radiation pneumonitis in patients with unresectable stage III non-small cell lung cancer receiving radiotherapy: a retrospective multi-center radiogenomics study.

BACKGROUND: Chemoradiotherapy is a critical treatment for patients with locally advanced and unresectable non-small cell lung cancer (NSCLC), and it is essential to identify high-risk patients as early as possible owing to the high incidence of radiation pneumonitis (RP). Increasing attention is being paid to the effects of endogenous factors for RP. This study aimed to investigate the value of computed tomography (CT)-based radiomics combined with genomics in analyzing the risk of grade ≥ 2 RP in unresectable stage III NSCLC. METHODS: In this retrospective multi-center observational study, 100 patients with unresectable stage III NSCLC who were treated with chemoradiotherapy were analyzed. Radiomics features of the entire lung were extracted from pre-radiotherapy CT images. The least absolute shrinkage and selection operator algorithm was used for optimal feature selection to calculate the Rad-score for predicting grade ≥ 2 RP. Genomic DNA was extracted from formalin-fixed paraffin-embedded pretreatment biopsy tissues. Univariate and multivariate logistic regression analyses were performed to identify predictors of RP for model development. The area under the receiver operating characteristic curve was used to evaluate the predictive capacity of the model. Statistical comparisons of the area under the curve values between different models were performed using the DeLong test. Calibration and decision curves were used to demonstrate discriminatory and clinical benefit ratios, respectively. RESULTS: The Rad-score was constructed from nine radiomic features to predict grade ≥ 2 RP. Multivariate analysis demonstrated that histology, Rad-score, and XRCC1 (rs25487) allele mutation were independent high-risk factors correlated with RP. The area under the curve of the integrated model combining clinical factors, radiomics, and genomics was significantly higher than that of any single model (0.827 versus 0.594, 0.738, or 0.641). Calibration and decision curve analyses confirmed the satisfactory clinical feasibility and utility of the nomogram. CONCLUSION: Histology, Rad-score, and XRCC1 (rs25487) allele mutation could predict grade ≥ 2 RP in patients with locally advanced unresectable NSCLC after chemoradiotherapy, and the integrated model combining clinical factors, radiomics, and genomics demonstrated the best predictive efficacy.

Compound Kushen Injection Reduces Severe Toxicity and Symptom Burden Associated With Curative Radiotherapy in Patients With Lung Cancer.

BACKGROUND: Radiotherapy (RT) causes adverse events for which there are no effective treatments. This study investigated the clinical benefits of compound Kushen injection (CKI) in managing radiation injury in patients with lung cancer. METHODS: A multicenter, open-label, randomized clinical trial randomly assigned patients with lung cancer to receive either CKI (20 mL/d for at least 4 weeks) integrated with curative RT (RT + CKI group; n=130) or RT alone (control group; n=130). The primary outcome was the incidence of grade ≥2 radiation-induced lung injury (RILI) in the lungs, esophagus, or heart. Secondary outcomes included patient-reported symptoms, quality of life, objective response rate (ORR), and toxic effects. RESULTS: During the 16-week trial, the RT + CKI group had a significantly lower incidence of grade ≥2 RT-related injury than the control group (12.3% [n=16] vs 23.1% [n=30]; P=.02). Compared with the control group, the RT + CKI group experienced a significant decrease in moderate-to-severe symptoms of fatigue, cough, and pain (P<.001 for the treatment and time interaction term); significantly less physical symptom interference (P=.01); and significantly better quality of life by the end of the trial (P<.05). No statistically significant difference in ORR was found. Adverse reactions associated with CKI were rare. CONCLUSIONS: This study demonstrated low toxicity of CKI and its effectiveness in patients with lung cancer in reducing the incidence of grade ≥2 RILI and symptom burden, improving patients' quality of life.

Pretreatment PET/CT imaging of angiogenesis based on 18F-RGD tracer uptake may predict antiangiogenic response.

PURPOSE: To explore the relationship between metabolic uptake of the 18F-ALF-NOTA-PRGD2 (18F-RGD) tracer on positron emission tomography/computerized tomography (PET/CT) and the antiangiogenic effect of apatinib in patients with solid malignancies. MATERIALS AND PATIENTS: Patients with measurable lesions scheduled for second- or third-line single-agent therapy with apatinib were eligible for this prospective clinical trial. All patients underwent 18F-RGD PET/CT examination before the start of treatment. Standardized uptake values (SUVs) of contoured tumor lesions were computed and compared using independent sample t-tests or the Mann-Whitney U test. Receiver-operating characteristic (ROC) curve analysis was used to determine accuracy in predicting response. Survival curves were compared using the Kaplan-Meier method. RESULTS: Of 38 patients who consented to study participation, 25 patients with 42 measurable lesions met the criteria for inclusion in this response assessment analysis. The median follow-up time was 3 months (range, 1-10 months), and the median progression-free survival (PFS) was 3 months (95% confidence interval, 1.04-4.96). The SUVpeak and SUVmean were significantly higher in responding tumors than in non-responding tumors (4.98 ± 2.34 vs 3.59 ± 1.44, p = 0.048; 3.71 ± 1.15 vs 2.95 ± 0.49, P = 0.036). SUVmax did not differ between responding tumors and non-responding tumors (6.58 ± 3.33 vs 4.74 ± 1.83, P = 0.078). An exploratory ROC curve analysis indicated that SUVmean [area under the ROC curve (AUC) = 0.700] was a better parameter than SUVpeak (AUC = 0.689) for predicting response. Using a threshold value of 3.82, high SUVmean at baseline was associated with improved PFS (5.0 vs. 3.4 months, log-rank P = 0.036). CONCLUSION: 18F-RGD uptake on PET/CT imaging pretreatment may predict the response to antiangiogenic therapy, with higher 18F-RGD uptake in tumors predicting a better response to apatinib therapy.

Recurrence/prognosis estimation using a molecularly positive surgical margin-based model calls for alternative curative strategies in pIIIA/N2 NSCLC.

Stage pIIIA/N2 non-small cell lung cancer (NSCLC) is primarily treated by complete surgical resection combined with neoadjuvant/adjuvant therapies. However, up to 40% of patients experience tumor recurrence. Here, we studied 119 stage pIIIA/N2 NSCLC patients who received complete surgery plus adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). The paired tumor and resection margin samples were analyzed using next-generation sequencing (NGS). Although all patients were classified as negative resection margins by histologic methods, NGS revealed that 47.1% of them had molecularly positive surgical margins. Patients who tested positive for NGS-detected residual tumors had significantly shorter disease-free survival (DFS) (P = 0.002). Additionally, metastatic lymph node ratio, erb-b2 receptor tyrosine kinase 2 (ERBB2) mutations, and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) mutations were also independently associated with DFS. We used these four features to construct a COX model that could effectively estimate recurrence risk and prognosis. Notably, mutational profiling through broad-panel NGS could more sensitively detect residual tumors than the conventional histologic methods. Adjuvant CT and adjuvant CRT exhibited no significant difference in eliminating locoregional recurrence risk for stage pIIIA/N2 NSCLC patients with molecularly positive surgical margins.

Case report: Cerebrospinal fluid-derived circulating tumor DNA diagnoses and guides the treatment of a lung adenocarcinoma case with leptomeningeal metastasis.

Leptomeningeal metastasis (LM) occurs in 3~5% of non-small cell lung cancer (NSCLC) patients. Diagnosis of patients with LM and disease monitoring remains challenging due to the low sensitivity and specificity of the commonly used approaches, such as cerebrospinal fluid (CSF) cytology and magnetic resonance imaging (MRI). Therefore, new approaches are necessary to improve the detection of LM. Recent studies have shown that circulating tumor DNA (ctDNA) in CSF can be used to detect and monitor LM, but whether it can serve as an early diagnostic biomarker prior to cytological and radiographic evidence of LM involvement requires further evaluation. Here we report a lung adenocarcinoma patient who had detectable oncogenic mutations in the CSF ctDNA prior to confirmation of LM by CSF cytology and MRI, highlighting the potential application of CSF ctDNA in early detection of LM.

Upfront brain radiotherapy improves intracranial progression-free survival but not overall survival in lung adenocarcinoma patients with brain metastases: a retrospective, single-institutional analysis from China.

Aims: The optimal timing of brain radiotherapy (BRT) for lung adenocarcinoma patients with brain metastases (BM) remains controversial. In this retrospective study, we performed a retrospective review to investigate the differential benefit of upfront versus deferred BRT for lung adenocarcinoma patients with BM. Methods: A total of 354 lung adenocarcinoma patients with BM treated in the Affiliated Cancer Hospital of Shandong University met the inclusion criteria for the study. Patients were divided into two groups: upfront BRT and deferred BRT. Intracranial progression-free survival (PFS) and overall survival (OS) were measured from the date of brain metastases. Subgroup analyses according to gene mutation status were also performed. Results: Among the entire cohort, the median intracranial PFS with upfront BRT (16.3 months) was longer than that with deferred BRT (11.3 months, p=0.001). However, the median OS did not differ significantly between patients who received upfront BRT and deferred BRT (27.6 and 31.5 months, respectively, p=0.813). Subgroup analyses indicated that upfront BRT yielded a significantly longer intracranial PFS than deferred BRT (p=0.003) for patients without EGFR (19 or 21) mutation. In both subgroups, the median OS showed no significant difference between upfront BRT and deferred BRT. Conclusion: This single-institutional retrospective study showed that in lung adenocarcinoma patients with brain metastases, upfront BRT was associated with a significantly longer intracranial PFS but not improvement in OS compared with deferred BRT. Considering the neurocognitive toxicities of BRT previously reported in the literature, deferred BRT might be considered as an acceptable therapeutic option for the treatment of patients with lung adenocarcinoma and BM.

Genomic alterations of whole exome sequencing in esophageal squamous cell carcinoma before and after radiotherapy.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer mortality, especially in China. Advances in technology have resulted in significant clinical gains in the treatment of ESCC, with more precise radiotherapy now considered an integral part of standard patient care, either alone or in combination with chemotherapy. Though, a better understanding of tumoral radiosensitivity is still needed in order to develop strategies and further personalize radiation treatments. METHODS: We carried out whole-exome sequencing (WES) on paired tumors collected before and after radiotherapy from 11 patients with ESCC. A comprehensive analysis was performed to compare the somatic mutations, the driver genes mutations, the copy number variations (CNVs), the mutational signatures, the tumor's clonal composition, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway between pre- and post-radiotherapy samples in this cohort. RESULTS: According to the analysis of WES results, more insertion/deletion mutations (indels) were discovered in the post-radiotherapy samples than in the pre-radiotherapy samples (Wilcoxon rank-sum test, P=0.014). The mutation rate of driver gene Ephrin-A2 (EPHA2) was significantly reduced after radiotherapy (Fisher's exact test, P=0.035). However, comparison between the pre- and post-radiotherapy groups reveals no significant differences in other content. CONCLUSIONS: Our study revealed the overall genomic profile of ESCC before and after radiotherapy and determined that a loss of EPHA2 mutations might make cancer cells resistance to radiotherapy.

Dosimetric evaluation of four whole brain radiation therapy approaches with hippocampus and inner ear avoidance and simultaneous integrated boost for limited brain metastases.

AIMS: To perform a dosimetric evaluation of four different simultaneous integrated boost whole brain radiotherapy modalities with hippocampus and inner ear avoidance in the treatment of limited brain metastases. METHODS: Computed tomography/magnetic resonance imaging data of 10 patients with limited (1-5) brain metastases were used to replan step-and-shoot intensity-modulated radiotherapy (sIMRT), dynamic intensity-modulated radiation therapy (dIMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (Tomo). The prescribed doses of 40-50 Gy in 10 fractions and 30 Gy in 10 fractions were simultaneously delivered to the metastatic lesions and the whole-brain volume, respectively. The hippocampal dose met the RTOG 0933 criteria for hippocampal avoidance (Dmax ≤17 Gy, D100% ≤10 Gy). The inner ear dose was restrained to Dmean ≤15 Gy. Target coverage (TC), homogeneity index (HI), conformity index (CI), maximum dose (Dmax), minimum dose (Dmin) and dose to organs at risk (OARs) were compared. RESULTS: All plans met the indicated dose restrictions. The mean percentage of planning target volume of metastases (PTVmets) coverage ranged from 97.1 to 99.4%. For planning target volume of brain (PTVbrain), Tomo provided the lowest average D2% (37.5 ± 2.8 Gy), the highest average D98% (25.2 ± 2.0 Gy), and the best TC (92.6% ± 2.1%) and CI (0.79 ± 0.06). The two fixed gantry IMRT modalities (step and shot, dynamic) provided similar PTVbrain dose homogeneity (both 0.76). Significant differences across the four approaches were observed for the maximum and minimum doses to the hippocampus and the maximum doses to the eyes, lens and optic nerves. CONCLUSION: All four radiotherapy modalities produced acceptable treatment plans with good avoidance of the hippocampus and inner ear. Tomo obtained satisfactory PTVbrain coverage and the best homogeneity index. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03414944 . Registered 29 January 2018.

Comparison of predictive powers of functional and anatomic dosimetric parameters for radiation-induced lung toxicity in locally advanced non-small cell lung cancer.

PURPOSE: To investigate the predictive value of the perfusion (Q) single-photon emission computed tomography (SPECT)-weighted dose-function histogram (DFH) obtained mid-treatment (mid-Tx) with radiotherapy (RT) for radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The study population consisted of NSCLC patients who were undergoing RT treatment and enrolled in prospective imaging studies. Q-SPECT was performed prior to and during RT (at ∼40-45 Gy). A baseline dose-volume histogram (DVH) and mid-Tx DVH based on simulation CT as well as a baseline DFH and mid-Tx DFH based on Q-SPECT were calculated. Only patients with stage III NSCLC and visible functional lung (FL) changes on the mid-Tx scan were eligible for this enriched analysis. RILT was graded according to a reported scale. RESULTS: Forty-two stage III NSCLC patients met the criteria for inclusion. The accumulative incidence of grade ≥2 RILT was 31% in this high-risk population. Significant differences in functional metrics such as functional lung volume FV5-FV20 at increments of 5 Gy and functional MLD (FMLD) were observed between patients with and without grade ≥2 RILT (p < 0.05). Similar results were also obtained for anatomical metrics from V5-V20 and MLD (p < 0.05). The areas under the receiver operating characteristic curves (AUCs) ranged from 0.724to 0.812 for baseline DVH parameters, from 0.745 to 0.830 for mid-Tx DVH parameters, from 0.764 to 0.878 for baseline DFH parameters, and from 0.767 to 0.891 for mid-Tx DFH parameters. Further principal components analysis showed that the AUCs were 0.814/0.817 and 0.790/0.857 for baseline/mid-Tx DVH and baseline/mid-Tx DFH, respectively. CONCLUSIONS: Mid-Tx DFH parameters based on Q-SPECT were significantly elevated in patients with grade ≥2 RILT in this study population. Among the metrics compared, mid-Tx DFH seemed to have better predictive accuracy, but this difference did not reach statistical difference.

To Explore a Representative Hypoxic Parameter to Predict the Treatment Response and Prognosis Obtained by [18F]FMISO-PET in Patients with Non-small Cell Lung Cancer.

PURPOSE: To explore a representative hypoxic parameter to predict the treatment response and prognosis for [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET)/X-ray computed tomography (CT) in patients with non-small cell lung cancer (NSCLC). PROCEDURES: Twenty-nine patients with NSCLC underwent FMISO-PET scans before chemoradiotherapy (CRT). The maximum standard uptake values (SUVmax) in the tumor, normal lung, aortic arch, and vertical ridge muscle were measured, and the tumor-to-lung (T/L) ratios, tumor-to-blood (T/B) ratios, ands tumor-to-muscle (T/M) ratios were calculated and analyzed. Fractional hypoxic volume (FHV) was expressed as percentage of hypoxic volume. RESULTS: SUVmax, T/L ratio, T/B ratio, and FHV were all significantly different between the responders and the non-responders (SUVmax, 2.07 ± 0.53 vs. 2.61 ± 0.69, P = 0.026; T/L ratio, 3.16 ± 0.85 vs. 4.09 ± 1.46, P = 0.047; T/B ratio, 1.27 ± 0.20 vs. 1.48 ± 0.32, P = 0.042; 38.92 ± 18.47 vs. 52.91 ± 11.29 %, P = 0.020). However, the T/M ratio was not significantly different between the two populations (1.46 ± 0.31 vs. 1.67 ± 0.33, P = 0.098). The correlation ratio between hypoxic parameters and treatment responses ranged from high to low as FHV (r = 0.412); SUVmax (r = 0.400); T/L ratio (r = 0.379), P < 0.05; and T/B ratio (r = 0.355), P = 0.059. According to the area under curve (AUC) to predict response, the hypoxic parameters were arranged as FHV (AUC = 0.748), SUVmax (AUC = 0.731), T/L ratio (AUC = 0.719), and T/B ratio (AUC = 0.705). Binary logistic regression analyses showed that FHV was the only independent predictor for treatment response with the P value of 0.038. In the progression-free survival (PFS) prediction, both FHV and SUVmax reached statistical significance by Kaplan-Meier plots (FHV, 46.99 %, P = 0.010; SUVmax, 1.99, P = 0.046) while only FHV was the independent prognostic factor in multivariate analysis by Cox proportional hazard model (P = 0.037). CONCLUSION: FHV may be a representative hypoxic parameter to predict the CRT response and PFS in patients with NSCLC.

To Find a Better Dosimetric Parameter in the Predicting of Radiation-Induced Lung Toxicity Individually: Ventilation, Perfusion or CT based.

This study aimed to find a better dosimetric parameter in predicting of radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) individually: ventilation(V), perfusion (Q) or computerized tomography (CT) based. V/Q single-photon emission computerized tomography (SPECT) was performed within 1 week prior to radiotherapy (RT). All V/Q imaging data was integrated into RT planning system, generating functional parameters based on V/Q SPECT. Fifty-seven NSCLC patients were enrolled in this prospective study. Fifteen (26.3%) patients underwent grade ≥2 RILT, the remaining forty-two (73.7%) patients didn't. Q-MLD, Q-V20, V-MLD, V-V20 of functional parameters correlated more significantly with the occurrence of RILT compared to V20, MLD of anatomical parameters (r = 0.630; r = 0.644; r = 0.617; r = 0.651 vs. r = 0.424; r = 0.520 p < 0.05, respectively). In patients with chronic obstructive pulmonary diseases (COPD), V functional parameters reflected significant advantage in predicting RILT; while in patients without COPD, Q functional parameters reflected significant advantage. Analogous results were existed in fractimal analysis of global pulmonary function test (PFT). In patients with central-type NSCLC, V parameters were better than Q parameters; while in patients with peripheral-type NSCLC, the results were inverse. Therefore, this study demonstrated that choosing a suitable dosimetric parameter individually can help us predict RILT accurately.

Late-Course Adaptive Adjustment Based on Metabolic Tumor Volume Changes during Radiotherapy May Reduce Radiation Toxicity in Patients with Non-Small Cell Lung Cancer.

To reduce the high risk of radiation toxicity and enhance the quality of life of patients with non-small cell lung cancer (NSCLC), we quantified the metabolic tumor volumes (MTVs) from baseline to the late-course of radiotherapy (RT) by fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET-CT) and discussed the potential benefit of late-course adaptive plans rather than original plans by dose volume histogram (DVH) comparisons. Seventeen patients with stage II-III NSCLC who were treated with definitive conventionally fractionated RT were eligible for this prospective study. FDG PET-CT scans were acquired within 1 week before RT (pre-RT) and at approximately two-thirds of the total dose during-RT (approximately 40 Gy). MTVs were taken as gross tumor volumes (GTVs) that included the primary tumor and any involved hilar or mediastinal lymph nodes. An original plan based on the baseline MTVs and adaptive plans based on observations during-RT MTVs were generated for each patient. The DVHs for lung, heart, esophagus and spinal cord were compared between the original plans and composite plans at 66 Gy. At the time of approximately 40 Gy during-RT, MTVs were significantly reduced in patients with NSCLC (pre-RT 136.2±82.3 ml vs. during-RT 64.7±68.0 ml, p = 0.001). The composite plan of the original plan at 40 Gy plus the adaptive plan at 26 Gy resulted in better DVHs for all the organs at risk that were evaluated compared to the original plan at 66 Gy (p<0.05), including V5, V10, V15, V20, V25, V30 and the mean dose of total lung, V10, V20, V30, V40, V50, V60 and the mean dose of heart, V35, V40, V50, V55, V60, the maximum dose and mean dose of the esophagus, and the maximum dose of the spinal-cord. PET-MTVs were reduced significantly at the time of approximately 40 Gy during-RT. Late course adaptive radiotherapy may be an effective way to reduce the dose volume to the organs at risk, thus reducing radiation toxicity in patients with NSCLC.

A Comparative Study of Noninvasive Hypoxia Imaging with 18F-Fluoroerythronitroimidazole and 18F-Fluoromisonidazole PET/CT in Patients with Lung Cancer.

PURPOSE: This is a clinical study to compare noninvasive hypoxia imaging using 18F-fluoroerythronitroimidazole (18F-FETNIM) and 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) in patients with inoperable stages III-IV lung cancer. METHODS: A total of forty-two patients with inoperable stages III-IV lung cancer underwent 18F-FETNIM PET/CT (n = 18) and 18F-FMISO PET/CT (n = 24) before chemo/radiation therapy. The standard uptake values (SUVs) of malignant and normal tissues depict 18F-FETNIM PET/CT and 18F-FMISO PET/CT uptake. Tumor-to-blood ratios (T/B) were used to quantify hypoxia. RESULTS: All patients with lung cancer underwent 18F-FETNIM PET/CT and 18F-FMISO PET/CT successfully. Compared to 18F-FMISO, 18F-FETNIM showed similar uptake in muscle, thyroid, spleen, pancreas, heart, lung and different uptake in blood, liver, and kidney. Significantly higher SUV and T/B ratio with 18F-FMISO (2.56±0.77, 1.98±0.54), as compared to 18F-FETNIM (2.12±0.56, 1.42±0.33) were seen in tumor, P = 0.022, <0.001. For the patients with different histopathological subtypes, no significant difference of SUV (or T/B ratio) was observed both in 18F-FMISO and 18F-FETNIM in tumor. A significantly different SUV (or T/B ratio) was detected between < = 2cm, 2~5cm, and >5cm groups in 18F-FMISO PET/CT, P = 0.015 (or P = 0.029), whereas no difference was detected in 18F-FMISO PET/CT, P = 0.446 (or P = 0.707). Both 18F-FETNIM and 18F-FMISO showed significantly higher SUVs (or T/B ratios) in stage IV than stage III, P = 0.021, 0.013 (or P = 0.032, 0.02). CONCLUSION: 18F-FMISO showed significantly higher uptake than 18F-FETNIM in tumor/non-tumor ratio and might be a better hypoxia tracer in lung cancer.

A Case Report of Local Recurrence Developing 24 Years After Mastectomy for Breast Cancer Recurrence From Breast Cancer After 24 Years.

INTRODUCTION: Breast cancer is a commonly diagnosed cancer, in which most patients' metastases (about 75%) occurred in 5 years after the initial diagnosis, especially in 3 years. Recrudescence exceeding 20 years is rarely reported in the past several decades.Case information: A 68-year-old female patient presented with breast cancer in which 3 focal increased 18F-fluorodeoxyglucose uptake in the right supraclavicular lymph node, the mediastinum and sternum were found on positron emission tomography and computed tomography. Then we learned that the patient had suffered from breast cancer and been given a right-sided mastectomy 24 years ago. Histopathology from the mediastinum revealed metastatic, moderately differentiated breast adenomatous cell carcinoma. CONCLUSION: We report this late recurrence of breast cancer 24 years following mastectomy, suggesting that possible recurrence of this disease with a 24-year latency period should be taken into consideration.

Noninvasive Evaluation of Metabolic Tumor Volume in Lewis Lung Carcinoma Tumor-Bearing C57BL/6 Mice with Micro-PET and the Radiotracers 18F-Alfatide and 18F-FDG: A Comparative Analysis.

PURPOSE: To explore the value of a new simple lyophilized kit for labeling PRGD2 peptide (18F-ALF-NOTA-PRGD2, denoted as 18F-alfatide) in the determination of metabolic tumor volume (MTV) with micro-PET in lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice verified by pathologic examination and compared with those using 18F-fluorodeoxyglucose (FDG) PET. METHODS: All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers 18F-alfatide and 18F-FDG within two days. 18F-alfatide metabolic tumor volume (VRGD) and 18F-FDG metabolic tumor volume (VFDG) were manually delineated slice by slice on PET images. Pathologic tumor volume (VPath) was measured in vitro after the xenografts were removed. RESULTS: A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent 18F-alfatide PET, and 35 of them underwent 18F-FDG PET and all underwent pathological examination. The mean ± standard deviation of VPath, VRGD, and VFDG were 0.59±0.32 cm3 (range,0.13~1.64 cm3), 0.61±0.37 cm3 (range,0.15~1.86 cm3), and 1.24±0.53 cm3 (range,0.17~2.20 cm3), respectively. VPath vs. VRGD, VPath vs. VFDG, and VRGD vs. VFDG comparisons were t = -0.145, P = 0.885, t = -6.239, P<0.001, and t = -5.661, P<0.001, respectively. No significant difference was found between VPath and VRGD. VFDG was much larger than VRGD and VPath. VRGD seemed more approximate to the pathologic gross tumor volume. Furthermore, VPath was more strongly correlated with VRGD (R = 0.964,P<0.001) than with VFDG (R = 0.584,P<0.001). CONCLUSIONS: 18F-alfatide PET provided a better estimation of gross tumor volume than 18F-FDG PET in LLC tumor-bearing C57BL/6 mice.

Gastric metastasis from small cell lung cancer: a case report.

Small cell lung cancer (SCLC) represents a group of highly malignant tumors that give rise to early and widespread metastases at the time of diagnosis. The preferential metastatic sites are the brain, liver, adrenal glands, bone, and bone marrow. However, metastases of the gastrointestinal system, especially the stomach, are rare; most cases of stomach metastasis are asymptomatic and, as a result, are usually only discovered at autopsy. We report a case of gastric metastasis originating from SCLC. The patient was a 66-year-old man admitted to our hospital due to abdominal pain. He underwent gastroscopy, with the pathological report of the tissue biopsy proving it to be a small cell cancer. Immunohistochemistry was positive for CD56, synaptophysin, and pan-cytokeratin. These results confirmed the diagnosis of gastric metastasis of a neuroendocrine small cell carcinoma from the lung.

Primary malignant melanoma of the esophagus with subtotal esophagectomy: a case report.

Primary malignant melanoma of the esophagus (PMME) is a rare disease, comprising 0.1-0.2% of all malignant esophageal neoplasms. The most common symptoms include progressive dysphagia, chest and back pain, choking feeling and weight loss. PMME cannot be definitely diagnosed from clinical symptoms or CT examination, but can be confirmed by histological examination or a pathological examination. Immunohistochemical examination with positive results of S-100 protein and human melanoma black 45 (HMB45) makes a definitive diagnosis. Esophagectomy is the standard treatment for localized PMME. But the prognosis is poor. Inoperableness, metastases and insensitiveness of radiotherapy and chemotherapy in advanced tumors have led to poor prognosis. Here, we report a case of a 61-year-old male with progressive dysphagia for 1 month. After barium X-ray test, chest and abdomen computed tomography examination, upper gastrointestinal endoscopy and biopsy, the patient accepted esophagectomy, then the pathologic and immunohistochemical examination conformed the diagnosis of PMME.

Primary clear cell carcinoma of nasal cavity: report of six cases and review of literature.

AIMS: This study is to retrospectively analyze the clinical and pathological data of six cases of primary nasal clear cell carcinoma in our hospital since 1992 and to review literatures on the clinical manifestations, pathological features, immunohistochemistry, diagnosis and treatment of the disease. METHODS: The pathological archives that were diagnosed as salivary gland nasal tumors in Shandong Cancer Hospital during 1992-2013 were reviewed. Careful review of sections was performed by two experienced pathologists. The samples were labeled using EnVision method. Immunostaining was performed using 3, 3'-diaminobenzidine reagent followed by counterstaining with hematoxylin. The immunohistochemical results were classified according to positive cells: no positive staining cells (-); positive cells <30% (+); positive cells between 30% and 50% (++); and positive cells >50% (+++). RESULTS: Among the 6 cases of primary nasal clear cell carcinoma in our hospital since 1992, 4 cases were diagnosed as clear cell carcinoma of nasal cavity after exclusion of other nasal cavity tumors with clear cells, and 2 cases were directly diagnosed as clear cell carcinoma of nasal cavity. Hyalinizing clear cell carcinoma of salivary gland (HCCC) tissues were mainly composed of polygonal epithelioid tumor cells arranged into the shapes of beehives, and separated by fibrous tissues containing rich thin-wall capillaries. The cytoplasm of HCCC cells was rich and translucent with some cells having multiple vacuoles. Reticular fiber staining showed that the tumor cells were arranged in shapes of beehives and separated by rich reticular fibers. HCCC tumor reacted differently on S-100 protein, glial fibrillary acidic protein, actin and vimentin. The ultrastructure of HCCC cells showed characteristics of ducts but no myoepithelial differentiation. CONCLUSIONS: This study demonstrates that correct diagnosis, timely surgical resection and postoperative radiotherapy are effective in treating nasal clear cell carcinoma.