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Although reactive oxygen species (ROS)-mediated tumor treatments are predominant in clinical applications, ROS-induced protective autophagy promotes cell survival, especially in hypoxic tumors. Herein, X-ray triggered nitrite (NO2 - ) is used for hypoxic prostate cancer therapy by inhibiting autophagy and inducing nitrosative stress based on an electrophilic zeolitic imidazole framework (ZIF-82-PVP). After internalization of pH-responsive ZIF-82-PVP nanoparticles, electrophilic ligands and Zn2+ are delivered into cancer cells. Electrophilic ligands can not only consume GSH under hypoxia but also capture low-energy electrons derived from X-rays to generate NO2 - , which inhibits autophagy and further elevates lethal nitrosative stress levels. In addition, dissociated Zn2+ specifically limits the migration and invasion of prostate cancer cells through ion interference. In vitro and in vivo results indicate that ZIF-82-PVP nanoparticles under X-ray irradiation can effectively promote the apoptosis of hypoxic prostate cancer cells. Overall, this nitrosative stress-mediated tumor therapy strategy provides a novel approach targeting hypoxic tumors.

In high-Z element enhanced radiotherapy strategies, the clinical potential of metal-based nanocomposites is always reduced by the serious side effects of leaked heavy metal ions. In this study, we demonstrate a novel anticancer strategy to realize controllable cytotoxicity of metal elements with the aid of high-energy radiation, based on a design of chelator-modified barium peroxide nanoparticles (GL-BaO2 NPs). Free Ba2+ is a potassium channel inhibitor that inhibits cell proliferation. The chelator modification can strongly bind leaked free Ba2+, thus reducing its unwanted side effects in normal tissues. However, under X-ray radiation in tumor regions, the produced hydroxyl radicals will break the chemical structures of chelators. Consequently, the released Ba2+ can access the membrane without a barrier and contribute to tumor treatment. More importantly, the sensitization of Ba in the lattice of barium peroxide will directly transform peroxide groups into reactive hydroxyl radicals, which further guarantees the decomposition of chelators as well as the efficient killing of cells. This strategy, which we termed ion interference therapy, demonstrates a universal paradigm by employing the biological effects of metal ions in tumor treatment, revealing its industrial potential for radiotherapy enhancement.

Background: This study aims to establish lung biologically effective dose (BED)–based uniform dosimetric constraints for minimizing the risk of symptomatic radiation pneumonitis (SRP) from stereotactic body radiation therapy (SBRT) using variable fractionations in patients with lung tumors.Materials and Methods: A total of 102 patients with primary or oligometastatic lung tumors treated with SBRT in our institution were enrolled into this study. The associations between the clinical and dosimetric parameters and the incidences of SRP were analyzed using univariate and multivariate Cox regression hazard models. The receiver operating characteristic (ROC) curve was generated to evaluate the predictive performance of lung BED on the SRP risk compared with the physical dose.Results: SRP occurred in 11 patients (10.8%). In univariate analysis, the mean lung dose (p = 0.002), V5 (p = 0.005), V20 (p < 0.001), and the percentage of non-target normal lung volume receiving more than a BED of 5–170 Gy (VBED5−170, p < 0.05) were associated with SRP. Multivariate logistic regression analysis showed that there existed a significant statistical correlation between SRP and VBED70 (p < 0.001), which performed better than V5 or V20 on the ROC curves, resulting in an optimal cut-off value of lung VBED70 of 2.22%.Conclusions: This retrospective study indicated that non-target lung BED may better predict SRP from patients with SBRT-treated lung cancer. Limiting the lung VBED70 below 2.22% may be favorable to reduce the incidence of SRP, which warranted further prospective validation.

Multiple paclitaxel-based regimens are widely used in chemoradiation therapy against esophageal cancer, including regimens combining paclitaxel with fluorouracil, cisplatin, and carboplatin. However, which among these 3 regimens provides the best prognosis with minimum adverse events is still unknown.To compare the efficacy and adverse events of fluorouracil, cisplatin, and carboplatin in definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC).This randomized clinical trial of patients with ESCC was conducted in 11 treatment centers in China. Eligible patients were aged 18 to 75 years and had histologically confirmed ESCC stages IIa to IVa with no prior treatment, Eastern Cooperative Oncology Group performance status of 2 or lower, and adequate organ functions. The study was conducted between July 2015 and February 2018, and the cutoff date for data analysis was August 31, 2020.Patients with locally advanced ESCC were randomly assigned (1:1:1) to groups combining paclitaxel treatment with fluorouracil, cisplatin, or carboplatin. Patients in the cisplatin group were treated with 2 cycles of concurrent chemoradiotherapy followed by 2 cycles of consolidation chemotherapy with monthly paclitaxel plus cisplatin. For the fluorouracil group, patients were administered 6 cycles of weekly paclitaxel plus fluorouracil in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus fluorouracil in consolidation chemotherapy. Patients in the carboplatin group were treated with 6 cycles of weekly paclitaxel plus carboplatin in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus carboplatin in consolidation chemotherapy. All patients received radiotherapy of 61.2 Gy delivered in 34 fractions.The primary end point was overall survival (OS). The secondary end points were progression-free survival and adverse events.Overall, 321 patients (median [IQR] age, 64 years [59-69 years]; 248 [77.3%] men) with ESCC from 11 centers were randomized into fluorouracil, cisplatin, or carboplatin groups between July 2015 and February 2018. Over a median (IQR) follow-up time of surviving patients of 46.0 months (36.6-53.0 months), the 3-year OS rates were 57.2% in the fluorouracil group, 60.1% in the cisplatin group, and 56.5% in the carboplatin group, respectively (fluorouracil vs cisplatin: HR, 1.06; 95% CI, 0.71-1.60; P = .77; fluorouracil vs carboplatin: HR, 0.94; 95% CI, 0.63-1.40; P = .77). The cisplatin group had significantly higher incidences of acute grade 3 or 4 neutropenia (69 events [60.8%] vs 19 [17.8%] for fluorouracil and 37 [34.6%] carboplatin; P .001), thrombocytopenia (14 events [13.1%] vs 4 [3.7%] for fluorouracil and 5 [4.7%] for carboplatin; P = .01), anemia (50 events above grade 2 [46.7%] vs 25 [23.4%] for fluorouracil and 37 [34.6%] for carboplatin; P = .35), fatigue (11 events [10.3%] vs 2 [1.9%] for fluorouracil and 1 [0.9%] carboplatin; P = .007), and vomiting (17 events above grade 2 [15.9%] vs 3 [2.8%] for fluorouracil and 5 [4.7%] for carboplatin; P .001) than the other 2 groups.In this randomized clinical trial, paclitaxel plus fluorouracil did not show OS superiority over paclitaxel plus cisplatin or paclitaxel plus carboplatin regimens in definitive chemoradiation in patients with locally advanced ESCC. Higher rates of hematologic and gastrointestinal toxic effects were reported in the cisplatin group compared with those in the fluorouracil or carboplatin groups.ClinicalTrials.gov Identifier: NCT02459457.

Oxidative damage, which mainly includes cell membrane lipid peroxidation (LPO) and DNA damage, plays a vital role in tumor therapy. Unfortunately, the overproduction of polyamines in tumor tissues inhibits cell membrane LPO and promotes DNA repair, leading to the limited oxidative damage efficacy. Herein, we propose an innovative polyamine-activated carbonyl stress strategy based on the MIL-100 @PAO@PVP (MPP) nanoplatform that successfully overcomes the drawbacks of oxidative damage therapy and achieves excellent chemodynamic therapy (CDT)-induced oxidative damage efficacy. Once endocytozed by tumor cells, the loaded plasma amine oxidase (PAO) on MPP can rapidly deplete polyamines at the tumor site to produce a large amount of highly toxic acrolein and H2O2. The produced H2O2 enhances the MIL-100-driven CDT efficiency to promote cell membrane and DNA damage. Furthermore, the depletion of polyamines further reduces the stability of the cell membrane and DNA. More importantly, the reactive product, acrolein, induces carbonyl stress to further increase DNA damage, inhibit the expression of GPx4 and DNA repair proteins, and significantly enhance CDT-induced oxidative damage. Overall, this strategy not only efficiently overcomes the drawbacks of oxidative damage but also provides a new strategy for tumor treatment.

X-ray-induced photodynamic therapy (X-PDT) has high depth of penetration and has considerable potential for applications in cancer therapy. Scintillators and heavy metals have been adopted to absorb X-rays and transmit the energy to photosensitizers. However, the low efficiency of converting X-rays to reactive oxygen species (ROS) presents a challenge for the use of X-PDT to cure cancer. In this study, a new method based on LiLuF4:Ce@SiO2@Ag3PO4@Pt(IV) nanoparticles (LAPNP) is presented that could be used to enhance the curative effects of X-PDT. To make full use of the fluorescence produced by nanoscintillators (LiLuF4:Ce), a cisplatin prodrug Pt(IV) was utilized as a sacrificial electron acceptor to increase the yield of hydroxyl radicals (·OH) by increasing the separation of electrons and holes in photosensitizers (Ag3PO4). Additionally, cisplatin is produced upon the acceptance of electrons by Pt(IV) and further enhances the damage caused by ·OH. Via two-step amplification, the potential of LAPNP to enhance the effects of X-PDT has been demonstrated.

The "partial matching" between upconversion nanoparticle (UCNP) emission and absorption by photosensitizers (PSs) often leads to a theoretically reduced therapeutic efficiency in UC-based photodynamic therapy (PDT) strategies in which the chosen PSs have limited capabilities and are unable to utilize all the near-infrared-upconverted light. In this study, needle-like SnWO4 nanocrystals (SWs) with a broad UV-vis absorption region were synthesized to solve the problem. After covalent conjugation with UCNPs, all the UCNP-emitted light was effectively absorbed by SWs, triggering the type-I PDT process to activate ROS maxima. The unique nanostructure of the as-formed UCNP-SnWO4 nanohybrids (USWs) also enhanced the receiving light intensities of SW, which further boosted the antitumor efficacy. Meanwhile, the strong X-ray attenuation capacity of both tungsten and tin elements qualified the USWs as excellent radio-sensitizers for radiotherapy (RT) enhancement, which played a complementary role with PDT treatment because PDT-mediated induction arrested the cells in the G0-G1 cell cycle phase, and RT was more damaging toward cells in the G2/M phase. The remarkably enhanced UC-PDT/RT efficiency of USWs was next validated in vitro and in vivo, and the combined NIR light and ionizing irradiation treatment completely suppressed tumor growth, revealing its great potential as an efficient anticancer therapeutic agent against solid tumors.

The conversion of bulk water to confined water in biological tissues has been proposed to benefit the treatments of diseases. However, regulating the states of water in vivo is still a challenge. Herein, we constructed nanocatalysts (BiOCl) containing abundant superficial vacancies to confine water in situ and investigated the potential utilization in cancer radiotherapy. Vacancies absorbed bulk water, transformed its structure and converted it to confined water. Enhanced reactivity of confined water increased the efficiency of water radiolysis and the yield of hydroxyl radicals (·OH) from radiation exposure. The results validated the feasibility of water-confinement-based radiosensitization strategy. These findings not only provide a method of constructing confined water in vivo, but also present the potentials of confined water for biological applications.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) and Radiofrequency ablation (RFA) are two important treatment options for medically inoperable patients with stage I non-small cell lung cancer (NSCLC). Here we performed a systemic review and pooled analysis to compare clinical outcomes of these two techniques. METHODS: A comprehensive literature search for published trials from 2001 to 2012 was undertaken. Pooled analyses were performed to obtain overall survival (OS), local tumor control rates (LCR), and the adverse events. Regression analysis was conducted considering each study's proportions of stage IA and age. RESULTS: Thirty-one studies on SBRT (2767 patients) and 13 studies on RFA (328 patients) were eligible. LCR (95% confidence interval) at 1, 2, 3 and 5 years for RFA was 77% (70 – 85%), 48% (37 – 58%), 55% (47 – 62%), and 42% (30 – 54%) respectively, which was significantly lower than that for SBRT 97 % (96 – 98%), 92% (91 – 94%), 88% (86 – 90%), and 86% (85 – 88%) (P.05). The most frequent complication of RFA was pneumothorax, occurring in 31% of patients, while that for SBRT (≥grade 3) was radiation pneumonitis, occurring in 2% of patients. CONCLUSIONS: Comparing to RFA, SBRT seems to have higher LCR, but similar OS. More studies with larger sample sizes are warranted to validate such findings.

4564 Background: Paclitaxel (PTX) is effective in concurrent chemoradiation (CCR) against esophageal squamous cell carcinoma (ESCC). Which regimen, among cisplatin (DDP) (TP), carboplatin (CBP) (TC) or 5-Fu (TF) in combination with PTX concurrent with radiotherapy, provides best prognosis with minimum adverse events (AEs) is still unknown. Methods: The study compared two pairs of regimens: TF vs. TP and TF vs. TC concurrent with radiotherapy. Patients with histologically confirmed ESCC (clinical stage II, III or IVa) 20 were randomized into the three groups. Patients in TP group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with TP (DDP 25 mg/m2/d, d1-3, PTX 175 mg/m2, d1, q28d). Patients in TF group were treated with 6 cycles of TF (5-Fu 300 mg/m2, civ 96h, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TF (5-FU 1800 mg/m2, civ 72h, PTX 175 mg/m2, d1, q28d) in consolidation chemotherapy. Patients in TC group were treated with 6 cycles of TC (CBP AUC = 2, d1, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TC (CBP AUC = 5, d1, PTX 175 mg/m2 d1, q28d) in consolidation chemotherapy. The radiotherapy dose in all groups was 61.2 Gy delivered in 34 fractions. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS) and adverse events. Results: Between July 2015 and January 2018, 321 ESCC patients in 11 centers were enrolled. Median follow-up of patients who survived was 36.3 months (IQR 27.9–45.2). The 3-yr OS was 58.2% in TF group and 59.5% in both TP and TC group. (TF vs. TP, HR 0.935, 95% CI 0.627-1.417; TF vs. TC, HR 0.881, 95% CI 0.578-1.342; P = 0.839). No significant differences were found in 3-yr PFS between TF, TP and TC groups [48.3% vs. 45.5%(TP) or 48.3% (TC). P = 0.820]. TP group had a significant higher incidence of acute Grade 3/4 neutropenia [60.7% vs. 16.8%(TF) or 32.7%(TC)], thrombocytopenia [13.1% vs. 2.8%(TF) or 4.7%(TC)], anemia [5.6% vs. 1.9%(TF) or 3.7% (TC)], fatigue [10.3% vs. 1.9%(TF) or 0.9%(TC)] and vomiting [5.6% vs. 0%(TF) or 0.9%(TC))]than other two groups ( P< 0.05). TF group had a significant higher incidence of Grade 3/4/5 esophagitis [11.2% vs. 0.9%(TP) or 4.7%(TC))]and pneumonitis [4.6% vs. 0%(TP) or 1.9% (TC)]than other two groups ( P< 0.05). Conclusions: No statistical differences were found in OS and PFS among TF, TP and TC groups. TC might be an option used in CCR in ESCC patients with mild of side effects compared with other two groups, although it did not significantly prolong OS. Clinical trial information: NCT02459457 .

To retrospectively analyze the computed tomography (CT) features in patients with pre-invasive lesions and early-stage lung adenocarcinoma and to explore the correlation between tumor morphological changes and pathological diagnoses. CT morphological characteristics in 2106 patients with pre-invasive (stage 0) and early-stage (stage I) lung adenocarcinoma were analyzed; lesions were confirmed by surgical pathology. Based on the morphological characteristics, the lesions were divided into eight types: I (cotton ball, ground-glass nodules), II (solid fill), III (granular), IV (dendriform), V (bubble-like lucencies), VI (alveolate or honeycomb), VII (scar-like), and VIII (notched or umbilication). The different distributions of eight morphological types in pathological types of the lesions and subtypes of invasive adenocarcinoma were analyzed by chi-squared or Fisher’s exact test. Correlation between the percentage of ground-glass opacity in the lesions and pathology types were analyzed by two-tailed Pearson’s test. A negative correlation was observed between the pathological types and proportion of ground-glass component in the lesions (p

The objective of this study was to investigate the correlation between dual-energy computed tomography (DECT)-based iodine quantitation and fluorine-18 fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging for response evaluation of lung cancers to treatment.In this prospective study, a total of 32 pairs of DECT and F-FDG PET/CT imaging acquired consecutively from 13 patients with primary or metastatic lung cancers receiving either radiotherapy alone or chemoradiotherapy were analyzed. Imaging examinations were performed before, immediately, and no later than 6 months after treatment for response evaluation. Iodine-related parameters including the total iodine uptake (TIU) and vital volume (VIV) from DECT and metabolic metrics such as the standardized uptake value normalized to lean body mass (SULpeak), metabolic tumor volume (MTV), and the total lesion glycolysis (TLG) from F-FDG-PET/CT were generated and measured by semiautomatic approaches. Dual-energy CT and PET/CT metrics were calculated and followed up with comparison with response evaluation criteria in solid tumors (RECIST).Analysis of pretreatment imaging data revealed a strong correlation between DECT metrics (RECIST, TIU, and VIV) and F-FDG PET/CT metrics (MTV, TLG) with coefficients of R ranging from 0.86 to 0.90 (P0.01). With the delivery of treatment, all measured DECT and PET/CT metrics significantly decreased whereas the descending amplitude in RECIST was significantly smaller than that of the remaining parameters (P0.05). During follow-up examinations, both metrics followed a similar changing pattern. Overall, strong consistency was found between RECIST, TIU, VIV and SULpeak, MTV, TLG (R covers 0.78-0.96, P0.05).Semiautomatic iodine-related quantitation in DECT correlated well with metabolism-based measurements in F-FDG PET/CT, suggesting that DECT-based iodine quantitation might be a feasible substitute for assessment of lung cancer response to chemoradiotherapy/radiotherapy with comparison with F-FDG PET/CT.

Due to the inherent heterogeneity in histology, biological behavior, and anatomical location, small adenocarcinoma may have various imaging manifestations which results in the common phenomenon of “same diseases with distinct imaging features” and “distinct diseases with same imaging features.” To decode the complicated imaging puzzles and facilitate differential diagnosis, we summarize CT imaging findings of small adenocarcinoma into ten patterns that are discussed with related to pathological features in this chapter.

Anatomy is the cornerstone of modern medicine. Pulmonary alveoli in pulmonary lobule are regarded as the origin of the lung adenocarcinoma. The pulmonary vasculatures, as the blood supply system, exert a pillar-like role in the course of initiation, development, and progression of lung adenocarcinoma. Imaging analysis of lung cancer should include five basic categories: location, quantitation, qualitation, shape description, and staging determination. For fulfillment of these purposes, mastery of the normal anatomy and variants of the lung as well as mediastinal structures, especially lymph nodes, carries significant clinical relevance.

There is currently an attempt to establish a categorization system for ground-glass nodules to guide the management and prognosis of pulmonary adenocarcinoma, based on multidisciplinary consensus. Ground-glass lesions can present as part of various pathologic entities, including tumors, infections, focal hemorrhage, and focal interstitial fibrosis. Imaging features from a single CT examination are not sufficient for a definitive diagnosis of the lesions. Comparative studies with routine imaging follow-up are helpful for differentiation, particularly when a patient’s clinical status is considered. Rich vasculature within and/or around ground-glass nodules (GGNs) can form the characteristic “CTA-TA” sign during enhancement CT imaging. As a significant point of distinction and one of several key differentiation points between AIS and AAH, the CTA-TA sign will be discussed in detail in this chapter.

Part-solid ground-glass nodule (pGGN) refers to a nodular lesion encompassing both a ground-glass component and a centrally or eccentrically solid component. CT examination can be suggestive of pathologic diagnoses considering the possible correlation between ground-glass components and lepidic patterns and between solid components and invasive components. If signs including spiculation, lobulation, pleural indentation, and vascular involvement are seen, the likelihood of malignancy dramatically increases. If the size of the invasive area represented by solid component is within 5 mm, a diagnosis of minimally invasive adenocarcinoma (MIA) should be rendered; otherwise lepidic-predominant adenocarcinoma (LPA) should be suspected. The presence and development of solid components in pGGNs indicate the disease progression.

Lobectomy remains the standard treatment for early-stage non-small cell lung cancer (NSCLC). However, due to medical comorbidities (such as severe diabetes, severe hypertension, and chronic obstructive pulmonary disease), some patients may not tolerate surgical procedures. For this fragile patient population, stereotactic ablation radiotherapy (SABR) provides a noninvasive but radical treatment option with limited impact on quality of life and acceptable efficacy. In contrast with conventional radiotherapy, SABR is characterized by delivering a high biological effective dose in several fractionations (

A solid pulmonary nodule (SPN) is a single, spherical, well-circumscribed radiographic opacity of less than 3 cm diameter with a component predominant in solid material. SPNs may display an average attenuation of 20–60 HU or higher. In CT images, various signs including deep lobulation, spiculation, pleural indentation, and the CTA-TA sign may be seen in many nodules with malignant potential. An SPN of 5 mm diameter continuously growing in an invasive pattern is highly suspicious for transformation from minimally invasive adenocarcinoma (MIA) to invasive adenocarcinoma (IAC). The variants of IAC have several imaging features and show a very strong correlation with the KRAS mutation, resulting in poor responsiveness to tyrosine kinase inhibitors and an unfavorable prognosis.

Tumor development and progression correlate with the ability of the tumor to induce vascular development in the microenvironment. The nutritional supply is limited at the avascular stage, and the tumor remains in a state of dormancy or growth inertia; tumor cell apoptosis and proliferation maintain a dynamic balance. Angiogenic switch activation and subsequent angiogenesis are critical biological events that signal the initiation of tumor progression as dormancy ends. Besides the perfusion of nutrition to the tumor, neovessels have the paracrine function via endothelial cells and secrete various growth factors to stimulate vascular proliferation and accelerate tumor differentiation and invasion. Angiogenesis improves blood supply to the tumor and reflects a change in biological behavior: specifically, a transition from a dormant status to an active one or from low-grade malignancy to intermediate- or high-grade malignancy. Hence, the early detection and scrutiny of novel vessels related to tumors are vital for the assessment of disease progression and making decisions about proper medical intervention. In this chapter, tumor dormancy, angiogenic switch, angiogenesis, and the characterization of neovasculature will be discussed.

With low-dose CT screening of lung cancer, the detection rate of multiple primary lung cancer (MPLC) significantly increased. Temporally, MPLC can be either synchronous or metachronous; spatially it can be distributed in the same lobe or same lung or bilaterally without specific preference. Radiographically, each single lesion in MPLC may have characteristic imaging features of solitary lung cancer. And all lesions may be in the same developmental stage or sequential stages. For instance, in a patient with MPLC, AAH, AIS, MIA, and IAC may coexist, causing a variety of imaging presentations and challenges in the differentiation of MPLC from diseases with multinodular presentations, such as intrapulmonary metastases, tuberculosis, or other infectious pulmonary disorders. Due to distinct treatment management and prognosis of MPLC, physicians and radiologists should be adequately aware of this particular entity.

Chest radiography remains the traditional and basic imaging modality for assessment of pulmonary nodules for many decades, while CT has been proven as the most valuable, reliable, and necessary examination for nodules less than 10 mm. While employing CT for medical examination, radiologists should implement reasonable measures to protect patients from unnecessary radiation exposure. Evidence has shown that low-dose CT (LDCT) could be used as lung cancer screening with high sensitivity and accuracy at an affordable radiation burden compared to chest radiography. To effectively implement CT-based lung cancer screening, radiologists and clinicians should be well aware of guidelines related to screening and management of pulmonary nodules released by organizations.

While conventional ultrasound and laboratory testing can differentiate most thyroid conditions and malignancies, spectral dual-energy computed tomography (DECT) provides molecular data potentially useful in differential diagnosis of small, complex, and partially obscured hemorrhaged nodules with recent bleeding. To demonstrate that Gemstone Spectral Imaging (GSI) analysis of DECT data differentiates challenging benign thyroid nodule conditions in patients with intranodular hemorrhages. A retrospective study was conducted of 30 intranodular hemorrhage patients from 2010 to 2013, including 18 that underwent surgery and provided thyroid tissues for prospective histological analysis. Iodine and water content were determined in patient CT scans and ex vivo tissue specimen scans by reconstruction of raw CT data at 65 keV (optimal contrast). Slope of spectral curve (λ HU), effective atomic number (Z eff), and final pathological diagnosis were recorded. Iodine content, water content, Z eff, and λ HU significantly varied by region (intranodular hemorrhage, solid thyroid nodule, and adjacent margins) in patients and tissue specimens (P

Combination therapy is a promising cancer treatment strategy that is usually based on the utilization of complicated nanostructures with multiple components functioning as photo-thermal energy transducers, photo-sensitizers, or dose intensifiers for photothermal therapy (PTT), photodynamic therapy (PDT), or radiation therapy (RT). In this study, ultrathin tungsten oxide nanowires (W18O49) were synthesized using a solvothermal approach and examined as a multifunctional theranostic nanoplatform. In vitro and in vivo analyses demonstrated that these nanowires could induce extensive heat- and singlet oxygen-mediated damage to cancer cells under 980 nm near infrared (NIR)-laser excitation. They were also shown to function as radiation dose intensifying agents that enhance irradiative energy deposition locally and selectively during radiation therapy. Compared to NIR-induced PTT/PDT and RT alone, W18O49-based synergistic tri-modal therapy eradicated xenograft tumors and no recurrence was observed within a 9-month follow up. Moreover, the strong X-ray attenuation ability of the tungsten element (Z = 74, 4.438 cm2·g–1, 100 KeV) qualified these nanowires as excellent contrast agents in X-ray-based imaging, such as diagnostic computed tomography (CT) and cone-beam CT for image-guided radiation therapy. Toxicity studies demonstrated minimal adverse effects on the hematologic system and major organs of mice within one month. In conclusion, these nanowires have shown significant potential for cancer therapy with inherent image guidance and synergistic effects from phototherapy and radiation therapy, which warrants further investigation.

In 2011, the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society proposed a new classification for lung adenocarcinomas. The new classification system fully affirmed the role of preoperative computed tomography (CT) examinations in the diagnosis of early-staged lung cancer; the data provided by studies using the new classification system indicate that the lymph node metastasis rates for adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are extremely low and that patients are expected to have 100% or nearly 100% disease-specific survival following complete resections (1). With the rapid development of multidetector spiral CT (MDCT) and video-assisted thoracoscopic surgery (VATS), not only can small pulmonary nodules be detected clearly but also more and more patients with small nodules that are highly suspicious of lung cancer can be cured with minimally invasive surgery. Atypical adenomatous hyperplasia (AAH), AIS, and MIA often present as pure ground-glass nodules (pGGNs) or mixed ground-glass nodules (mGGNs) containing small amounts of solid elements that are detected on CT images; the diameter of such nodules is often less than 10 mm, and early intervention can improve the prognoses of patients with these lesions. However, it is widely known that these lesions, which are small in volume and low in density, can be extremely difficult to accurately position during surgery and in surgically resected specimens, leading to problems for both thoracic surgeons and pathologists. In addition, it is much more difficult for pathologists to localize all lesions without CT-guided fine-needle localization when two or more GGNs are present in the same lobe. In such cases, the localization of all the GGNs is crucial because the pathologic diagnosis (including gene mutations) of each nodule could help to guide subsequent treatments (1, 2). The aim of this study was to analyze the value of CT-guided fine-needle positioning of lesions that presented as GGNs on CT images under constant, moderate mechanical aeration of the surgical specimens. To the best of our knowledge, this is the first study describing needle localization of small lung nodules in postoperative specimens.

Clinically applied chemotherapy and radiotherapy is sometimes not effective due to the limited dose acting on DNA chains resident in the nuclei of cancerous cells. Herein, we develop a new theranostic technique of "intranuclear radiosensitization" aimed at directly damaging the DNA within the nucleus by a remarkable synergetic chemo-/radiotherapeutic effect based on intranuclear chemodrug-sensitized radiation enhancement. To achieve this goal, a sub-50 nm nuclear-targeting rattle-structured upconversion core/mesoporous silica nanotheranostic system was firstly constructed to directly transport the radiosensitizing drug Mitomycin C (MMC) into the nucleus for substantially enhanced synergetic chemo-/radiotherapy and simultaneous magnetic/upconversion luminescent (MR/UCL) bimodal imaging, which can lead to efficient cancer treatment as well as multi-drug resistance circumvention in vitro and in vivo. We hope the technique of intranuclear radiosensitization along with the design of nuclear-targeting nanotheranostics will contribute greatly to the development of cancer theranostics as well as to the improvement of the overall therapeutic effectiveness.

Immunocompromised patients are subject to a variety of infectious pathogens involving lungs. Imaging examination of pulmonary conditions could provide valuable information for differentiation diagnosis, treatment assessment as well as prognostic prediction. Imaging manifestations of immunocompromise-related pulmonary diseases could be either pathogen-specific or -non-specific. It is particularly fundamental to recognize these imaging characteristics at suspicion of opportunistic infections in such patients. In this article, we attempt to present a review to refresh and update our knowledge of imaging features of pulmonary infectious diseases in immunocompromised patients.

The "partial matching" between upconversion nanoparticle (UCNP) emission and absorption by photosensitizers (PSs) often leads to a theoretically reduced therapeutic efficiency in UC-based photodynamic therapy (PDT) strategies in which the chosen PSs have limited capabilities and are unable to utilize all the near-infrared-upconverted light. In this study, needle-like SnWO

Purpose This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.

Multimodal bio-imaging has attracted great attention for early and accurate diagnosis of tumors, which, however, suffers from the intractable issues such as complicated multi-step syntheses for composite nanostructures and interferences among different modalities like fluorescence quenching by MRI contrast agents (e.g., magnetic iron oxide NPs). Herein, the first example of T2-weighted MR imaging of Ho3+-doped upconversion nanoparticles (UCNPs) is presented, which, very attractively, could also be simultaneously used for upconversion luminesence (UCL) and CT imaging, thus enabling high performance multi-modal MRI/UCL/CT imagings in single UCNPs. The new finding of T2-MRI contrast enhancement by integrated sensitizer (Yb3+) and activator (Ho3+) in UCNPs favors accurate MR diagnosis of brain tumor and provides a new strategy for acquiring T2-MRI/optical imaging without fluorescence quenching. Unlike other multi-phased composite nanostructures for multimodality imaging, this Ho3+-doped UCNPs are featured with simplicity of synthesis and highly efficient multimodal MRI/UCL/CT imaging without fluorescence quenching, thus simplify nanostructure and probe preparation and enable win–win multimodality imaging.

4055 Background: Paclitaxel (PTX) is effective in concurrent chemoradiation (CCR) against esophageal squamous cell carcinoma (ESCC) . Which regimen, among cisplatin (DDP) (TP), carboplatin (CBP) (TC) or 5-Fu (TF) in combination with PTX concurrent with radiotherapy, provides best prognosis with minimum adverse events (AEs) is still unknown. Methods: The study compared two pairs of regimens: TF vs. TP and TF vs. TC concurrent with radiotherapy. Patients with histologically confirmed ESCC (clinical stage II, III or IVa) were randomized into the three groups. Patients in TP group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with TP (DDP 25 mg/m2/d, d1-3, PTX 175 mg/m2, d1, q28d). Patients in TF group were treated with 6 cycles of TF (5-Fu 300 mg/m2, civ 96h, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TF (5-FU 1800 mg/m2, civ 72h, PTX 175 mg/m2, d1, q28d) in consolidation chemotherapy. Patients in TC group were treated with 6 cycles of TC (CBP AUC = 2, d1, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TC (CBP AUC = 5, d1, PTX 175 mg/m2 d1, q28d) in consolidation chemotherapy. The radiotherapy dose in all groups was 61.2 Gy delivered in 34 fractions. The primary endpoint was overall survival and the secondary endpoints were progression-free survival and adverse events. Results: Between July 2015 and January 2018, 321 ESCC patients in 11 centers were enrolled. TP group had a significant higher incidence of acute grade 3/4 neutropenia (59.7% vs. 16.8%(TF) or 32.4%(TC)), thrombocytopenia (12.7% vs. 3.5%(TF) or 6.2%(TC)), anemia (6.4% vs. 4.4%(TF) or 4.4%(TC)), fatigue (10.0% vs. 0.9%(TF) or 0.9%(TC)) and vomiting (5.5% vs. 0%(TF) or 0.9%(TC)) than other two groups ( P < 0.05). TF group had a significant higher incidence of grade 3/4/5 esophagitis (13.1% vs. 1.8%(TP) or 5.3%(TC)) and pneumonitis (4.4% vs. 0%(TP) or 1.8%(TC)) than other two groups ( P < 0.05). One patient in TF group died of acute pneumonitis. One patient in TF group and one in TC group died of acute esophagitis. Conclusions: TP and TF regimen showed different severe AEs in CCR in ESCC patients and TC showed mild AEs. Clinical trial information: NCT02459457.

OBJECTIVE: To explore the CT characteristics of small lung nodules and improve the diagnosis of pulmonary ground-glass nodules less than 10 mm in size. METHODS: We retrospectively analyzed CT images of 161 pulmonary nodules (less than 10 mm in size) with spiculation, lobulation, vacuoles, and pleural indentation and compared these images with pathological results or follow-up CT images. The relationships between the ground-glass nodules (GGNs) and blood vessels were observed. The GGN-vessel relationship was divided into four types, Type I (pass-by), Type II (pass-through), Type III (distorted/dilated), Type IV (complicated). The vessels traveling through a GGN were divided into three categories, category A (arteries), category B (veins), category C (arteries and veins). RESULTS: 161 GGNs were divided into three groups (benign group, pre-invasive group, and adenocarcinoma group) according to their pathological diagnosis. Significant differences in density of nodules were observed among the three different groups (p < 0.05). Significant differences in the shape (round/round-like or not) of the nodules were observed between the benign group and the pre-invasive group and between the pre-invasive group and the adenocarcinoma group (p < 0.05). No significant differences in the presence of vacuoles were observed between the benign group and the pre-invasive group or between the pre-invasive group and the adenocarcinoma group (p ＞0.05), but a significant difference was observed between the benign group and the adenocarcinoma group (p < 0.05). The differences in the vascularization of the lesions among the three groups were statistically significant (p < 0.05). No significant differences or correlations were observed between vascular categories and GGN groups (p > 0.05). CONCLUSION: For subcentimeter nodules, mixed GGNs with vacuoles, well-defined border, combined with Type III or Type IV GGN-vessel relationship may strongly suggest malignant. ADVANCES IN KNOWLEDGE: Previous studies mainly focused on CT diagnosis of pulmonary nodules (≤ 3 cm in diameter), but this study focused on ground-glass nodules less than 10 mm in diameter, which had not been fully studied. For subcentimeter nodules, mixed GGNs with vacuoles, well-defined border, especially the GGN-vessel relationship manifest as Type III (distorted/dilated) or Type IV (complicated) may strongly suggest malignant.

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.

Objective To investigate the relationships between pulmonary ground-glass nodules (GGN) and blood vessels and their diagnostic values in differentiating GGNs. Methods Multi-detector spiral CT imaging of 108 GGNs was retrospectively reviewed. The spatial relationships between GGNs and supplying blood vessels were categorized into four types: I, vessels passing by GGNs; II, intact vessels passing through GGNs; III, distorted, dilated or tortuous vessels seen within GGNs; IV, more complicated vasculature other than described above. Relationship types were correlated to pathologic and/or clinical findings of GGNs. Results Of 108 GGNs, 10 were benign, 24 preinvasive nodulesand 74adenocarcinomasthatwerepathologicallyproven. Types I, II, III and IV vascular relationships were observed in 9, 58, 21 and 20 GGNs, respectively. Type II relationship was the dominating relationship for each GGN group, but significant differences were shown among them. Correlation analysis showed strong correlation between invasive adenocarcinoma and type III and IV relationships. Subgroup analysis indicated that type III was more commonly seen in IAC with comparison to type IV more likely seen in MIA. Conclusion Different GGNs have different relationships with vessels. Understanding and recognising characteristic GGN-vessel relationships may help identify which GGNs are more likely to be malignant. Key Points  Multi-detector CT offers new information about groundglass nodules  In particular we can now study their relationship with vessels

OBJECTIVE The objective of this study was to investigate the feasibility of using monochromatic spectral computed tomography (CT) imaging to assess fatty infiltration in liver. MATERIALS With spectral CT imaging, phantoms with known fat concentrations were studied for scanning parameter optimization, then 52 patients enrolled into 4 groups (healthy, mild, moderate, and severe fatty infiltration) received abdominal scanning. Based on reconstructed monochromatic images, hepatic attenuation was analyzed, and dual-energy subtraction imaging (DESI) was created for quantifying fat infiltration. RESULTS Corresponding to various hepatic fat infiltrations, 4 characteristic CT attenuation curve patterns were described. In DESI images, only fat and fatty components appeared bright. For livers without abnormal fat deposition, isolated bright pixels were visualized (% area = 0.5% ± 0.3%). With hepatic fat accumulation increasing, more bright pixels appeared in subtraction images with percentages of total liver area involved in 2.5%, 6.7%, and 13.4% of mild, moderate, and severe fat infiltration cases, respectively (P < 0.05). The corresponding CT values were as follows: 1.33, 2.53, 8.69, and 16.4 Hounsfield units (P < 0.01), which correlated with the % DESI area values (r = 0.9811). CONCLUSIONS Spectral CT imaging is a promising method to quantitatively assess hepatic fat content and fatty infiltration with advantages compared with conventional CT imaging.