Thoracic Cancer Patients Research Articles

Does deformation of immobilization devices impact treatment accuracy in thoracic cancer radiotherapy?

Immobilization devices are essential for maintaining accurate and repeatable patient positioning in radiotherapy. This study aimed to evaluate the setup errors and dosimetric deviation induced by the deformation of immobilization devices in thoracic cancer radiotherapy using CT-linac. A retrospective analysis was conducted on 40 thoracic cancer patients who underwent radiotherapy, using vacuum cushion (VC) and thermoplastic mask (TM) for immobilization. A total of 206 weekly Fan-beam CT (FBCT) images (4-7 per patient) were analyzed to manually delineate immobilization devices and assess their geometric deformations against setup errors. Dosimetric deviations between the clinical plan (CT-plan) and the delivered plan (FBCT-plan) were compared for planning target volume (PTV) and organs at risk (OARs). Correlations between dose variations and setup errors were analyzed in lateral (LAT), longitudinal (LNG), and vertical (VRT) axes. The conformity of the VC (Nup) and TM (Ndown) with the patient in simulation CT exhibited moderate to strong correlations with VRT setup errors (Ndown: r=-0.484, p<0.01;Nup: r=-0.697, p<0.01). However, intra-fraction deformation of immobilization devices (in FBCT) showed no significant correlation with setup errors. In the dosimetric analysis of OARs, lung dose parameters (Dmean, V5, V20) and heart Dmean exhibited a consistent absolute difference with increasing setup errors. Dose variation decreased significantly when errors exceeded 5 mm, particularly in the VRT direction for most PTV indices, with the exception of CI and HI. Spinal cord Dmax variation correlated significantly with setup accuracy along the LNG axis, but not along other axes. The conformity of immobilization devices in simulation CT exhibits a stronger correlation with setup accuracy than the deformation of these devices in intra-fraction FBCT. FBCT is recommended for improving treatment precision through dosimetric assessment and planning adjustments.

Perioperative gum-chewing training prevents a decrease in tongue pressure after esophagectomy in thoracic esophageal cancer patients: a nonrandomized trial

Tongue pressure (TP) decreases significantly after esophagectomy in esophageal cancer patients (ECPs). Meanwhile, 2 weeks of gum-chewing training (GCT) significantly increased TP in healthy university students. We examined whether perioperative GCT would decrease the proportion of patients exhibiting a decline in TP at 2 weeks postoperatively, and prevent postoperative complications, in thoracic ECPs (TECPs). This was a single-center interventional study, and nonrandomized study with a historical control group (HCG). TECPs who underwent first-stage radical esophagectomy were recruited. Thirty-two patients of 40 in the gum-chewing group (GCG) were completed perioperative GCT in 3 times daily. Propensity score matching was performed with covariates related to TP including preoperative age, sex, body mass index, and the repetitive saliva swallowing test result, and yielded a matched cohort of 25 case pairs. Eleven GCG patients [44.0%] exhibited significantly lower TP at 2 weeks postoperatively than before esophagectomy was significantly fewer than that of 19 patients [76.0%] in the HCG. The median number of fever days (> 38 °C) in the 2 weeks after esophagectomy in the GCG was significantly fewer than those in the HCG. Perioperative GCT may prevent postoperative TP decline and postoperative dysphagia-related complications after esophagectomy.

EP.05B.03 Evaluating the Risk of Pneumonitis from G-CSF in Thoracic Cancer Patients with Pre-Existing ILD

EP.05B.03 Evaluating the Risk of Pneumonitis from G-CSF in Thoracic Cancer Patients with Pre-Existing ILD

Lung adenocarcinoma size as a predictor of distant metastasis: A CT scan-based measurement.

Previous studies have associated tumor size with metastasis and prognosis in lung carcinoma; however, a precise cut-off for predicting distant metastasis in lung adenocarcinoma remains unclear. The aim of this study was to determine the cut-off point for predicting distant metastasis in lung adenocarcinoma. A cross-sectional study was conducted at Dr. Moewardi Hospital, Surakarta, Indonesia, from January 2022 to September 2023. Total sampling was employed, involving patients over 18 years old with a confirmed diagnosis of lung adenocarcinoma based on lung computed tomography (CT) scan findings, who had not yet received chemotherapy and had confirmed metastasis outside the lung. The study's dependent variable was the incidence of distant metastasis, while the independent variable was lung adenocarcinoma size. Two experienced thoracic radiologists measured lung adenocarcinoma size by assessing the longest axis using chest multi-slice computed tomography (MSCT) in the lung window setting. Receiver operating characteristic (ROC) curve analysis determined the optimal tumor size cut-off for predicting distant metastasis. Of 956 thoracic cancer patients, 108 were diagnosed with lung adenocarcinoma. After applying the inclusion and exclusion criteria, 89 patients were eligible. In the present study, tumor size predicted 68.1% of distant metastasis cases, with a cut-off point of 7.25 cm, yielding a sensitivity of 61.9% and a specificity of 61.5%. Tumors >7.25 cm had a 2.60-fold higher risk of distant metastasis compared to smaller tumors, with larger tumors more likely to spread to various sites. In conclusion, lung adenocarcinomas larger than 7.25 cm have a 2.60-fold increased risk of distant metastasis, making tumor size a crucial predictive factor. The study provides valuable insights for radiologists and can improve diagnosis accuracy and treatment planning by emphasizing tumor size as a key factor in managing lung adenocarcinoma.

Innovative regression model-based decision support tool for optimizing radiotherapy techniques in thoracic esophageal cancer.

Modern radiotherapy exemplified by intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), has transformed esophageal cancer treatment. Facing challenges in treating thoracic esophageal cancer near vital organs, this study introduces a regression model-based decision support tool for the optimal selection of radiotherapy techniques. We enrolled 106 patients diagnosed with locally advanced thoracic esophageal cancer in this study and designed individualized IMRT and VMAT radiotherapy plans for each patient. Detailed dosimetric analysis was performed to evaluate the differences in dose distribution between the two radiotherapy techniques across various thoracic regions. Single-factor and multifactorial logistic regression analyses were employed to establish predictive models (P1 and P2) and factors such as TLV/PTV ratio. These models were used to predict the compliance and potential advantages of IMRT and VMAT plans. External validation was performed in a validation group of 30 patients. Using predictive models, we developed a data-driven decision support tool. For upper thoracic cases, VMAT plans were recommended; for middle/lower thoracic cases, the tool guided VMAT/IMRT choices based on TLV/PTV ratio. Models P1 and P2 assessed IMRT and VMAT compliance. In validation, the tool showed high specificity (90.91%) and sensitivity (78.95%), differentiating IMRT and VMAT plans. Balanced performance in compliance assessment demonstrated tool reliability. In summary, our regression model-based decision support tool provides practical guidance for selecting optimal radiotherapy techniques for thoracic esophageal cancer patients. Despite a limited sample size, the tool demonstrates potential clinical benefits, alleviating manual planning burdens and ensuring precise, individualized treatment decisions for patients.

Variations in Perioperative Thromboprophylaxis Practices: Do the Guidelines Need a Closer Look?

BackgroundIn 2022, the American Association for Thoracic Surgery (AATS) and the European Society of Thoracic Surgeons (ESTS) published joint guidelines regarding the timing, duration, and choice of agent for perioperative venous thromboembolism prophylaxis for thoracic cancer patients. Now, 1 year after their release, we looked to assess practices and general adherence to these recommendations. MethodsWe conducted a survey among board-certified/board-eligible thoracic surgeons in the United States, between July and October 2023. ResultsA total of 103 board-certified thoracic surgeons responded to the survey. Over half of the surgeons reported using preoperative chemical thromboprophylaxis routinely for lobectomy/sublobar resections (56.3%), pneumonectomy/extended lung resections (64.1%), and esophagectomy (67%). Over two thirds of thoracic surgeons limited the duration of postoperative chemical thromboprophylaxis to the patient’s length of hospital stay and never administered chemoprophylaxis post-discharge. Among surgeons who always continued chemical thromboprophylaxis post-discharge, low-molecular-weight heparin (LMWH) was the most commonly used agent (>70%), followed by direct oral anticoagulants (13.8%-16.7%). Only 33.3% of surgeons prescribing post-discharge chemical thromboprophylaxis after lobectomy/sublobar resections continued prophylaxis up to 4 weeks postoperatively. ConclusionsContrary to the 2022 joint AATS/ESTS guidelines, the majority of surveyed thoracic surgeons in the United States do not routinely prescribe postoperative thromboprophylaxis after lung and esophageal cancer resections. The dogma of routine extended thromboprophylaxis must be reevaluated as modern minimally invasive thoracic surgery allows for very earlier ambulation and enhanced recovery. There is a need for randomized controlled trials exploring the utility of extended thromboprophylaxis and newer agents such as direct oral anticoagulants.

Risk and prognosis of secondary lung cancer after radiation therapy for thoracic malignancies.

Radiation therapy (RT) may increase the risk of second cancer. This study aimed to determine the association between exposure to radiotherapy for the treatment of thoracic cancer (TC) and subsequent secondary lung cancer (SLC). The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for TC. Univariate Cox regression analyses and multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SLC. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and SLC-related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis. In a total of 329 129 observations, 147 847 of whom had been treated with RT. And 6799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients (adjusted HR, 1.25; 95% CI, 1.19-1.32; P < 0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT(P). The incidence risk of SLC in TC patients who received radiotherapy was significantly higher than the US general population (SIR, 1.19; 95% CI, 1.14-1.23; P < 0.050). Radiotherapy for TC was associated with higher risks of developing SLC compared with patients unexposed to radiotherapy.

Daily Caffeine Consumption May Increase the Risk of Acute Kidney Injury Related to Platinum-Salt Chemotherapy in Thoracic Cancer Patients: A Translational Study.

Although their efficacy has been well-established in Oncology, the use of platinum salts remains limited due to the occurrence of acute kidney injury (AKI). Caffeine has been suggested as a potential pathophysiological actor of platinum-salt-induced AKI, through its hemodynamic effects. This work aims to study the association between caffeine consumption and the risk of platinum-salt-induced AKI, based on both clinical and experimental data. The clinical study involved a single-center prospective cohort study including all consecutive thoracic cancer patients receiving a first-line platinum-salt (cisplatin or carboplatin) chemotherapy between January 2017 and December 2018. The association between daily caffeine consumption (assessed by a validated auto-questionnaire) and the risk of platinum-salt induced AKI or death was estimated by cause-specific Cox proportional hazards models adjusted for several known confounders. Cellular viability, relative renal NGAL expression and/or BUN levels were assessed in models of renal tubular cells and mice co-exposed to cisplatin and increasing doses of caffeine. Overall, 108 patients were included (mean age 61.7 years, 65% men, 80% tobacco users), among whom 34 (31.5%) experienced a platinum-salt-induced AKI (67% Grade 1) over a 6-month median follow-up. The group of high-caffeine consumption (≥386 mg/day) had a two-fold higher hazard of AKI (adjusted HR [95% CI], 2.19 [1.05; 4.57]), without any significant association with mortality. These results are consistent with experimental data confirming enhanced cisplatin-related nephrotoxicity in the presence of increasing doses of caffeine, in both in vitro and in vivo models. Overall, this study suggests a potentially deleterious effect of high doses of daily caffeine consumption on the risk of platinum-salt-related AKI, in both clinical and experimental settings.

Prospective Observational Study of COVID-19 Vaccination in Patients with Thoracic Malignancies: Adverse Events, Breakthrough Infections and Survival Outcomes.

Due to the devastating COVID-19 pandemic, a preventive tool in the form of vaccination was introduced. Thoracic cancer patients had one of the highest rates of morbidity and mortality due to COVID-19 disease, but the lack of data about the safety and effectiveness of vaccines in this population triggered studies like ours to explore these parameters in a cancer population. Out of 98 patients with thoracic malignancies vaccinated per protocol, 60-75% experienced some adverse events (AE) after their first or second vaccination, most of them were mild and did not interfere with their daily activities. Out of 17 severe AEs reported, all but one were resolved shortly after vaccination. No significant differences were noted considering AE occurrence between different cancer therapies received after the first or second vaccination dose, p = 0.767 and p = 0.441, respectively. There were 37 breakthrough infections either after the first (1), second (13) or third (23) vaccine dose. One patient died as a direct consequence of COVID-19 infection and respiratory failure, and another after disease progression with simultaneous severe infection. Eight patients had moderate disease courses, received antiviral therapies and survived without consequences. Vaccination did not affect the time to disease progression or death from underlying cancer.

Simultaneous evaluation of brain metastasis and thoracic cancer using semiconductor 11C-methionine PET/CT imaging.

To investigate the potential of whole-body digital 11C-methionine (MET) PET/CT imaging for simultaneous evaluation of thoracic cancer patients suspected of local recurrence (LR) after stereotactic radiosurgery (SRS) for brain metastasis. A total of 45 lung or breast cancer patients suspected of LR after SRS were investigated using brain and whole-body MET-PET/CT scans. We compared the tumor-to-normal ratio (TNR) and maximum standardized uptake values (SUVmax) between patients with LR and radiation necrosis (RN) and performed receiver operating characteristic (ROC) analyses. We also investigated associations among extracranial recurrence, intracranial recurrence, primary site, and initial treatment type. A total of 44 LR and 14 RN lesions were analyzed. In the ROC analyses for differentiating LR from RN, TNR showed higher area under the curve (AUC) (0.82) than SUVmax (0.79), and the cutoff TNR value (2.12) was higher than current cutoff values of conventional PET systems. The whole-body scans detected extracranial recurrences in 31.1% of the patients. Recurrence rates were not significantly correlated with existence of intracranial recurrence or primary site, but patients who underwent non-surgical treatment (consisting of stage III/ IV patients according to the Union for International Cancer Control TNM classification or small-cell lung cancer patients) showed significantly higher recurrence than the surgically treated patients (68.8% vs. 10.3%, p = 0.0001). In digital MET-PET/CT imaging, TNR was a more useful parameter to differentiate LR from RN than SUVmax, and the cutoff value was higher than those with conventional PET systems. Additional whole-body scans could detect extracranial recurrence and would be especially useful for advanced thoracic cancer patients who underwent non-surgical treatment.

Rosmarinic Acid Alleviates Radiation-Induced Pulmonary Fibrosis by Downregulating the tRNA N7-Methylguanosine Modification-Regulated Fibroblast-to-Myofibroblast Transition Through the Exosome Pathway.

Radiation-induced pulmonary fibrosis (RIPF) is a common complication after radiotherapy in thoracic cancer patients, and effective treatment methods are lacking. The purpose of this study was to investigate the protective effect of rosmarinic acid (RA) on RIPF in mice as well as the mechanism involved. m7G-tRNA-seq and tRNA-seq analyses were conducted to identify m7G-modified tRNAs. Western blotting, immunohistochemistry, northwestern blotting, northern blotting, immunofluorescence, wound-healing assays and EdU experiments were performed to explore the molecular mechanism by which RA regulates fibroblast-to-myofibroblast transformation (FMT) by affecting the exosomes of lung epithelial cells. Ribo-seq and mRNA-seq analyses were used to explore the underlying target mRNAs. Seahorse assays and immunoprecipitation were carried out to elucidate the effects of RA on glycolysis and FMT processes via the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) acetylation. We found that RA had an antifibrotic effect on the lung tissues of RIPF model mice and inhibited the progression of FMT through exosomes derived from lung epithelial cells. Mechanistically, RA reduced the transcription and translation efficiency of sphingosine kinase 1 in lung fibroblasts by decreasing N7-methylguanosine modification of tRNA, downregulating the expression of tRNAs in irradiated lung epithelial cell-derived exosomes, and inhibiting the interaction between sphingosine kinase 1 and the N-acetyltransferase 10 protein in fibroblasts. Furthermore, the acetylation and cytoplasmic translocation of PFKFB3 were reduced by exosomes derived from irradiated lung epithelial cells, which following RA intervention. This suppression of the FMT process, which is triggered by glycolysis, and ultimately decelerating the progression of RIPF. These findings suggest that RA is a potential therapeutic agent for RIPF.

Results of combined and chemoradiation treatment of patients with thoracic esophageal cancer according to the data of the regional cancer center

Background. esophageal cancer (ec) is one of the most aggressive malignancies of the gastrointestinal tract. chemoradiation therapy is the standard of care for locally advanced ec.The purpose of the study was to evaluate the efficacy of chemoradiation therapy given alone and in combination with surgery in patients with thoracic esophageal cancer.Material and Methods. From January 1, 2012 to december 31, 2021, a total of 940 patients with thoracic esophageal cancer were registered in the regional cancer registry, of which 178 patients were selected for concurrent chemoradiotherapy (CRT) at clinical stages I–III. thirty seven thoracic esophageal cancer patients who received CRT and required treatment interruption due to complications were not included in our analysis. The final analysis included 141 patients.Results. 37 (20.7 %) patients were unable to complete treatment due to intolerance and the development of severe complications of CRT. Hematological toxicity of grade 3-4 was noted in 21 patients (14.8 %). Non-hematological complications of grade 2-4 were noted in 109 patients (77.3 %). The 5-year relapse-free survival rates in patients undergoing and non-undergoing to surgery were 23.0 and 25.0 %, respectively (p=0.018). Overall 5-year survival rates were 24 and 27 %, respectively (p=0.020). The rate of pathological complete response (pcR) was 43.5 % (in 20 of 46 patients who underwent surgery after CRT). The median survival time in patients with clinical complete response (ccR) was 24.0 months and the median survival time in patients with pcR was 29.0 months. The 3-year survival rates were 21 and 45 %, respectively (p=0.050).Conclusion. The combination of chemoradiotherapy and surgery in patients with thoracic esophageal cancer demonstrated an increase in overall survival in our study. if there is a complete clinical response to CRT and contraindications for surgery or the patient’s refusal to undergo surgery, it is advisable to use the “wait &amp; watch” tactic.

Whole Liver Radiotherapy for Multiple Liver Metastases in Thoracic Malignancies

Liver metastases (LM) are common in advanced thoracic cancer patients with dismal oncological outcomes. Even in the modern era of novel systemic therapy, LM led to a 21% increased mortality risk compared with those without. Options for progressive multiple LM after systemic therapy are limited. Therefore, a different treatment modality is urgently needed to overcome such a predicament. Herein, we renovate the classical whole liver radiotherapy (WLRT) and evaluate its efficacy and safety in treating thoracic cancer patients with progressive multiple LM. Patients with lung or thymic cancer who had multiple LM treated by WLRT between 2018 and 2022 were enrolled. Radiotherapy (RT) was delivered with a median dose of 24 Gy (range 8-25 Gy) in 8 fractions (range 1-16) at the discretion of treating physicians. Overall survival (OS) and cumulative incidence of intrahepatic progression were calculated from the completion of WLRT till death or progression by Kaplan-Meier and competing risk analyses, respectively. Twenty-four patients were enrolled in this retrospective study. Eleven patients (46%) had lung adenocarcinoma, of which nine patients had oncogenic mutations. Six patients (25%) had small cell lung cancer (SCLC), four patients (17%) had thymic squamous cell carcinoma (SqCC), two patients (8%) had lung SqCC, and one patient (4%) had mixed histology. Eighteen patients (75%) were under systemic therapy treatment before the diagnosis of LM, and fifteen (63%) received LM biopsy. The median time from the diagnosis of LM to WLRT was 7.5 months (range, 0.5-33.9 months). Eleven patients (46%) had concurrent RT and systemic therapy. With a median follow-up of 3.1 months, the 3-, 6- and 12-month OS were 57%, 38%, and 15%, respectively. After adjusting death as a competing risk, the cumulative incidence of LM progression at 3, 6, and 12 months were 10%, 19%, and 44%, respectively. Within three months after the completion of RT, one patient (4%) had grade 5 radiation-induced liver disease (RILD), one patient (4%) had grade 4 abnormal liver function test (LFT), three patients (13%) had grade 3 abnormal LFT, and twelve patients (50%) had ≤ grade 2 abnormal LFT. The patient who had Gr.5 RILD expired 51 days after the completion of RT with 24 Gy in 8 fractions concurrently with topotecan. He had primary SCLC with viral hepatitis B. His LFT was around the normal upper limit before WLRT. WLRT provided favorable intrahepatic control with acceptable radiation-related toxicities and could be considered a treatment option for patients with progressive LM under systemic therapy. Further investigation with a larger cohort is warranted to identify patients at a high risk of developing severe RILD.

Exploration of AI-Assisted On-Board Perfusion Imaging Technique on Patients Undergoing Thoraxradiotherapy

Pulmonary function of lung cancer patients can significantly change along the radiation therapy (RT) course. Scholars have synthesized lung function maps from computed tomography (CT) images. Still, there is lack of study exploring the feasibility of generating lung perfusion information from cone-beam CT (CBCT). Our study aims to fill up this gap in the body of literatures. One-hundred-and-six pairs of planning CT and CBCT images of thoracic cancer patients from XX hospital were collected retrospectively. All CT images were registered to CBCT with a deformable algorithm, and referred as deformed planning CT (dCT). A 2D convolutional neural network (CNN) model built with cycle generative adversarial network (cycle-GAN) was trained to correct CBCT image artifacts and HU value discrepancies. The corrected CBCT was named enhanced CBCT (eCBCT) in this study. All CBCT, eCBCT and dCT images were then input to a pre-trained CT-to-perfusion deep learning (DL) model to synthesize perfusion images (PI), namely PICBCT, PIeCBCT and PIdCT respectively. For model training, 80 image pairs were assigned to the training set while others to the testing set. dCT and PIdCT were respectively regarded as the ground truth in two consecutive models. One extra validation case acquired with SPECT perfusion scan was collected for model performance test. Quantitative evaluation was done between the ground truth and the synthesized images. Peak signal-to-noise ratio (PSNR) and mean absolute error (MAE) were computed to assess efficacy of CBCT enhancement. Correlation (R) and Dice similarity coefficient (DSC) were used to evaluate voxel-wise and function-wise concurrence in CBCT-derived perfusion mapping. In CBCT enhancement, [eCBCT-dCT] pairs demonstrated higher agreement than [CBCT-dCT] pairs. Quantitatively, PSNR and MAE were improved from 21.10±1.60 to 24.08±1.76, and 68.99±13.51 to 47.06±11.31 (p<0.01), respectively. For perfusion translation, higher correlation was demonstrated in both voxel-wise and function-wise evaluation within [PIeCBCT-PIdCT] than [PICBCT-PIdCT]. R correlation increased from 0.84±0.09 to 0.89±0.06 (p<0.01), whereas DSC in high-functional regions increased from 0.77±0.06 to 0.82±0.05 (p<0.01). In the validation case, strong correlation was observed between SPECT perfusion scan and PIeCBCT, with R increasing from 0.57 to 0.65 when compared to PICBCT. We proposed a novel DL framework that synthesized perfusion images from fractionally acquired CBCT. Our framework met the clinical needs in providing real-time lung perfusion maps. It can be used to track the continuously changing pulmonary function status throughout the RT course using routinely scanned CBCT, without additional imaging modalities. The framework can facilitate functionally guided adaptive radiation therapy by providing immediate pulmonary function information.

Assessment of short-term effects of thoracic radiotherapy on the cardiovascular parasympathetic and sympathetic nervous systems.

Prior research suggests that cardiovascular autonomic dysfunction might be an early marker of cardiotoxicity induced by antitumor treatment and act as an early predictor of cardiovascular disease-related morbidity and mortality. The impact of thoracic radiotherapy on the parasympathetic and sympathetic nervous systems, however, remains unclear. Therefore, this study aimed to evaluate the short-term effects of thoracic radiotherapy on the autonomic nervous system, using deceleration capacity (DC), acceleration capacity (AC) of heart rate, and heart rate variability (HRV) as assessment tools. A 5 min electrocardiogram was collected from 58 thoracic cancer patients before and after thoracic radiotherapy for DC, AC, and HRV analysis. HRV parameters employed included the standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low frequency power (LF), high frequency power (HF), total power (TP), and the LF to HF ratio. Some patients also received systemic therapies alongside radiotherapy; thus, patients were subdivided into a radiotherapy-only group (28 cases) and a combined radiotherapy and systemic therapies group (30 cases) for additional subgroup analysis. Thoracic radiotherapy resulted in a significant reduction in DC (8.5 [5.0, 14.2] vs. 5.3 [3.5, 9.4], p = 0.002) and HRV parameters SDNN (9.9 [7.03, 16.0] vs. 8.2 [6.0, 12.4], p = 0.003), RMSSD (9.9 [6.9, 17.5] vs. 7.7 [4.8, 14.3], p = 0.009), LF (29 [10, 135] vs. 24 [15, 50], p = 0.005), HF (35 [12, 101] vs. 16 [9, 46], p = 0.002), TP (74 [41, 273] vs. 50 [33, 118], p < 0.001), and a significant increase in AC (-8.2 [-14.8, -4.9] vs. -5.8 [-10.1, -3.3], p = 0.003) and mean heart rate (79.8 ± 12.6 vs. 83.9 ± 13.6, p = 0.010). Subgroup analysis indicated similar trends in mean heart rate, DC, AC, and HRV parameters (SDNN, RMSSD, LF, HF, TP) in both the radiotherapy group and the combined treatment group post-radiotherapy. No statistically significant difference was noted in the changes observed in DC, AC, and HRV between the two groups pre- and post-radiotherapy. Thoracic radiotherapy may induce cardiovascular autonomic dysfunction by reducing parasympathetic activity and enhancing sympathetic activity. Importantly, the study found that the concurrent use of systemic therapies did not significantly amplify or contribute to the alterations in autonomic function in the short-term following thoracic radiotherapy. DC, AC and HRV are promising and feasible biomarkers for evaluating autonomic dysfunction caused by thoracic radiotherapy.

Preoperative neoadjuvant chemoradiotherapy provides borderline resectable thoracic esophageal cancer with equivalent treatment results as clinically T3 thoracic esophageal cancer.

Because the optimal treatment strategy for borderline resectable (cT3br) thoracic esophageal cancer patients remains unclear, it is of great interest whether preoperative neoadjuvant therapy for cT3br could achieve results comparable to those seen with resectable T3 cancer (cT3r). We speculated that preoperative neoadjuvant chemoradiotherapy (NACRT) would be particularly effective in cT3br thoracic esophageal cancer patients and compared to cT3br and cT3r. Of 186 cT3 thoracic esophageal cancer patients treated with intended NACRT, 162 received radical esophagectomy. More than 97% were squamous cell carcinomas. Patients were partitioned into two groups according to whether invasion of adjacent organs was suspected (cT3br and cT3r). Treatment outcomes and survival were analyzed. Sixty-eight patients (36.6%) were classified as cT3br and 118 (63.4%) as cT3r. The cT3br group had significantly more tumors in the upper and middle mediastinum (p < 0.0001) and more cases with cM1 (lymph node) (p = 0.0104) than the cT3r group. In addition, the cT3br patients receiving esophagectomy exhibited a significantly lower pathological complete response rate than the cT3r patients (p = 0.0374). However, the R0 resection rate did not differ between the cT3br and cT3r patients (p = 0.0978), and the two groups treated with intended NACRT had similar 5-year overall (OS) and disease-specific survival (DSS) (p = 0.3831 and p = 0.9020). In addition, the incidence and patterns of recurrence did not differ between the cT3br and cT3r patients receiving esophagectomy (p = 0.8109 and p = 0.3128). Preoperative neoadjuvant chemoradiotherapy appears to be a promising treatment for patients with borderline resectable thoracic esophageal squamous cell carcinoma.

Individualized treatment estimates to inform on personalized cancer care decisions for treatment selection and treatment management.

e13571 Background: Clinical trials report average effects of treatments at a population level. However, clinicians must balance treatment benefits against risks to personalize therapy. Here, we present a statistical framework which incorporates real-world data to estimate efficacy and symptom burden for an individual patient. We then assess the potential impact of continuing immunotherapy beyond progression in patients with metastatic solid malignancies on immune-related adverse events, progression, and survival. Methods: We corrected for sampling biases with inverse propensity score weighting (IPTW), and used the IPTW-transformed data to train predictive models of patient outcomes under each option. The models utilize a peer-based similarity based on 222 routinely-collected patient characteristics, such as cancer and treatment specific factors, laboratory tests, demographics, vitals, stage, comorbidities and symptoms, which are extracted from the electronic health record or natural language processing of clinician narratives, and Social Determinants of Health from Census data. We developed our methods on “Dataset A”: 5,919 breast and genitourinary (GU) cancer patients at a tertiary cancer center. We computed individualized treatment effect (ITE) estimates on “Dataset B”: 5,486 breast, GU, and thoracic cancer patients who received immunotherapy. Results: Our approach eliminated biases in Dataset A: the IPTW-transformation reduced the between-group standardized mean difference across identified confounders from an average of 0.225 to an average of 0.022. The similarity model exhibited strong discrimination (ROC-AUC &gt; 0.75), and identified associations between patient characteristics and outcomes that matched clinicians’ expectations. Validations are ongoing to assess the ITE estimates on a held-out subset of Dataset B. These include subgroup analyses for metastatic triple-negative breast cancer and non-small cell lung cancer. Conclusions: We introduce a method to estimate the efficacy and toxicity of interventions, actions, or treatment decisions, which replicates the statistical robustness of a clinical trial while obtaining individualized insights. This framework provides causal estimates of symptom burden and risks of progression and survival to inform clinical decisions, including continuation of immunotherapy beyond progression. After IPTW, confounders in Dataset A were balanced between the treatment groups, with weighted standardized mean differences &lt;0.1. [Table: see text]

P21 facilitates macrophage chemotaxis by promoting CCL7 in the lung epithelial cell lines treated with radiation and bleomycin

BackgroundInterstitial lung diseases (ILDs) can be induced and even exacerbated by radiotherapy in thoracic cancer patients. The roles of immune responses underlying the development of these severe lung injuries are still obscure and need to be investigated.MethodsA severe lung damage murine model was established by delivering 16 Gy X-rays to the chest of mice that had been pre-treated with bleomycin (BLM) and thus hold ILDs. Bioinformatic analyses were performed on the GEO datasets of radiation-induced lung injury (RILI) and BLM-induced pulmonary fibrosis (BIPF), and RNA-sequencing data of the severely damaged lung tissues. The screened differentially expressed genes (DEGs) were verified in lung epithelial cell lines by qRT-PCR assay. The injured lung tissue pathology was analyzed with H&E and Masson’s staining, and immunohistochemistry staining. The macrophage chemotaxis and activity promoted by the stressed epithelial cells were determined by using a cell co-culture system. The expressions of p21 in MLE-12 and Beas-2B cells were detected by qRT-PCR, western blot, and immunofluorescence. The concentration of CCL7 in cell supernatant was measured by ELISA assay. In some experiments, Beas-2B cells were transfected with p21-siRNA or CCL7-siRNA before irradiation and/or BLM treatment.ResultsAfter the treatment of irradiation and/or BLM, the inflammatory and immune responses, chemokine-mediated signaling pathways were steadily activated in the severely injured lung, and p21 was screened out by the bioinformatic analysis and further verified to be upregulated in both mouse and human lung epithelial cell lines. The expression of P21 was positively correlated with macrophage infiltration in the injured lung tissues. Co-culturing with stressed Beas-2B cells or its conditioned medium containing CCL7 protein, U937 macrophages were actively polarized to M1-phase and their migration ability was obviously increased along with the damage degree of Beas-2B cells. Furthermore, knockdown p21 reduced CCL7 expression in Beas-2B cells and then decreased the chemotaxis of co-cultured macrophages.ConclusionsP21 promoted CCL7 release from the severely injured lung epithelial cell lines and contributed to the macrophage chemotaxis in vitro, which provides new insights for better understanding the inflammatory responses in lung injury.

On the correction of respiratory motion-induced image reconstruction errors in positron-emission tomography-guided radiation therapy

Free breathing (FB) positron emission tomography (PET) images are routinely used in radiotherapy for lung cancer patients. Respiration-induced artifacts in these images compromise treatment response assessment and obstruct clinical implementation of dose painting and PET-guided radiotherapy. The purpose of this study is to develop a blurry image decomposition (BID) method to correct motion-induced image-reconstruction errors in FB-PETs. Assuming a blurry PET is represented as an average of multi-phase PETs. A four-dimensional computed-tomography image is deformably registered from the end-inhalation (EI) phase to other phases. With the registration-derived deformation maps, PETs at other phases can be deformed from a PET at the EI phase. To reconstruct the EI-PET, the difference between the blurry PET and the average of the deformed EI-PETs is minimized using a maximum-likelihood expectation-maximization algorithm. The developed method was evaluated with computational and physical phantoms as well as PET/CT images acquired from three patients. The BID method increased the signal-to-noise ratio from 1.88±1.05 to 10.5±3.3 and universal-quality index from 0.72±0.11 to 1.0 for the computational phantoms, and reduced the motion-induced error from 69.9% to 10.9% in the maximum of activity concentration and from 317.5% to 8.7% in the full width at half maximum of the physical PET-phantom. The BID-based corrections increased the maximum standardized-uptake values by 17.7±15.4% and reduced tumor volumes by 12.5±10.4% on average for the three patients. The proposed image-decomposition method reduces respiration-induced errors in PET images and holds potential to improve the quality of radiotherapy for thoracic and abdominal cancer patients.

Comparisons of minimally invasive esophagectomy and open esophagectomy in lymph node metastasis/dissection for thoracic esophageal cancer.

The study aimed to clarify the characteristics of lymph node metastasis (LNM) and to compare the oncologic outcomes of minimally invasive esophagectomy (MIE) with open esophagectomy (OE) in terms of lymph node dissection (LND) in thoracic esophageal cancer patients. The data from esophageal cancer patients who underwent MIE or OE from January 2016 to January 2019 were retrospectively reviewed. The characteristics of LNM in thoracic esophageal cancer were discussed, and the differences in numbers of LND, LND rate, and LNM rate/degree of upper mediastinum between MIE and OE were compared. For overall characteristics of LNM in 249 included patients, the highest rate of LNM was found in upper mediastinum, while LNM rate in middle and lower mediastinum, and abdomen increased with the tumor site moving down. The patients were divided into MIE ( n = 204) and OE groups ( n = 45). In terms of number of LND, there were significant differences in upper mediastinum between MIE and OE groups (8 [5, 11] vs. 5 [3, 8], P < 0.001). The comparative analysis of regional lymph node showed there was no significant difference except the subgroup of upper mediastinal 2L and 4L group (3 [1, 5] vs. 0 [0, 2], P < 0.001 and 0 [0, 2] vs. 0, P = 0.012, respectively). Meanwhile, there was no significant difference in terms of LND rate except 2L (89.7% [183/204] vs. 71.1% [32/45], P = 0.001) and 4L (41.2% [84/204] vs . 22.2% [10/45], P = 0.018) groups. For LNM rate of T3 stage, there was no significant difference between MIE and OE groups, and the comparative analysis of regional lymph node showed that there was no significant difference except 2L group (11.1% [5/45] vs . 38.1% [8/21], P = 0.025). The LNM degree of OE group was significantly higher than that of MIE group (27.2% [47/173] vs . 7.6% [32/419], P < 0.001), and the comparative analysis of regional LNM degree showed that there was no significant difference except 2L (34.7% [17/49] vs . 7.7% [13/169], P < 0.001) and 4L (23.8% [5/21] vs . 3.9% [2/51], P = 0.031) subgroups. MIE may have an advantage in LND of upper mediastinum 2L and 4L groups, while it was similar to OE in other stations of LND.