Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy.

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.

Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation.

The CD39-CD73-adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I-IV COAD. Our data demonstrated that CD73 staining strongly marked malignant epithelial cells and CD39 was highly expressed in stromal cells. Attractively, tumor CD73 expression was significantly associated with tumor stage and the risk of distant metastasis, which suggested CD73 was as an independent factor for colon adenocarcinoma patients in univariate COX analysis [HR = 1.465, 95%CI = 1.084-1.978, p = 0.013]; however, high stromal CD39 in COAD patients was more likely to have favorable survival outcome [HR = 1.458, p = 1.103-1.927, p = 0.008]. Notably, high CD73 expression in COAD patients showed poor response to adjuvant chemotherapy and high risk of distant metastasis. High CD73 expression was inversely associated with less infiltration of CD45+ and CD8+ immune cells. However, administration with anti-CD73 antibodies significantly increased the response to oxaliplatin (OXP). Blockade of CD73 signaling synergistically enhanced OXP-induced ATP release, which is a marker of immunogenic cell death (ICD), promotes dendritic cell maturation and immune cell infiltration. Moreover, the risk of colorectal cancer lung metastasis was also decreased. Taken together, the present study revealed tumor CD73 expression inhibited the recruitment of immune cells and correlated with a poor prognosis in COAD patients, especially patients received adjuvant chemotherapy. Targeting CD73 to markedly increased the therapeutic response to chemotherapy and inhibited lung metastasis. Therefore, tumor CD73 may be an independent prognostic factor as well as the potential of therapeutic target for immunotherapy to benefit colon adenocarcinoma patients.

BM3D-based denoising method for color polarization filter array.

Color split-focal plane polarization imaging systems are composed of image sensors with a color polarization filter array (CPFA). The noise generated during image acquisition leads to incorrect estimation of the color polarization information. Therefore, it is necessary to denoise CPFA image data. In this study, we propose a CPFA block-matching and 3D filtering (CPFA-BM3D) algorithm for CPFA image data. The algorithm makes full use of the correlation between different polarization channels and different color channels, restricts the grouping of similar 2D image blocks to form 3D blocks, and attenuates Gaussian noise in the transform domain. We evaluate the denoising performance of the proposed algorithm using simulated and real CPFA images. Experimental results show that the proposed method significantly suppresses noise while preserving the image details and polarization information. Its peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) indicators are superior to those of the other existing methods. The mean values of the PSNR and SSIM of the degree of linear polarization (DoLP) color images calculated through CPFA image interpolation can be increased to 200% and 400%, respectively, by denoising with the proposed method.

Risk Management for Radiation-Induced Cardiovascular Disease (RICVD): The 2022 Consensus Statement of the Taiwan Society for Therapeutic Radiology and Oncology (TASTRO) and Taiwan Society of Cardiology (TSOC).

Advances in cancer management have significantly improved survival in patients with cancers. Cardiovascular complications of cancer treatment are becoming significant competing causes of death in these patients. Radiotherapy is an indispensable component of cancer treatment, and irradiation of the heart and vasculature during cancer radiotherapy is now recognized as a new risk factor for cardiovascular diseases. It is important to involve multidisciplinary expertise and provide practical recommendations to promote awareness, recognize risks, and provide adequate interventions without jeopardizing cancer control. In this consensus paper, experts from the Taiwan Society for Therapeutic Radiology and Oncology and Taiwan Society of Cardiology provide a focused update on the clinical practice for risk stratification and management of radiation-induced cardiovascular disease (RICVD). We believe that implementing RICVD care under a collaborative cardio-oncology program will significantly improve cancer treatment outcomes and will facilitate high quality clinical investigations.

Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-α H score.

Sea surface clutter suppression method based on time-domain polarization characteristics of sun glint.

A method for suppressing sea surface clutter, based on the characteristics of sun glint, is proposed. The proposed method is built on an infrared polarization radiation model of the dynamic sea surface. Based on the time-domain polarization characteristics of sun glint in a dynamic sea scene, a method for taking linearly polarized images at different analyzer angles over fixed intervals is used to suppress sea clutter by using the minimum operation. Experimental results show that the proposed method can effectively improve the contrast between a target and its background. Following simplification, this method can also provide a streamlined sea clutter suppression method with obvious results.

Prediction of local relapse and distant metastasis in patients with definitive chemoradiotherapy-treated cervical cancer by deep learning from [18F]-fluorodeoxyglucose positron emission tomography/computed tomography.

BACKGROUND: We designed a deep learning model for assessing 18F-FDG PET/CT for early prediction of local and distant failures for patients with locally advanced cervical cancer. METHODS: All 142 patients with cervical cancer underwent 18F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. In each round of k-fold cross-validation, a well-trained proposed model and a slice-based optimal threshold were derived from a training set and used to classify each slice set in the test set into the categories of with or without local or distant failure. The classification results of each tumor were aggregated to summarize a tumor-based prediction result. RESULTS: In total, 21 and 26 patients experienced local and distant failures, respectively. Regarding local recurrence, the tumor-based prediction result summarized from all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively. CONCLUSION: This is the first study to use deep learning model for assessing 18F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. KEY POINTS: • This is the first study to use deep learning model for assessing 18 F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. • All 142 patients with cervical cancer underwent 18 F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. • For local recurrence, all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively.

The irregular breathing effect on target volume and coverage for lung stereotactic body radiotherapy.

The major challenge in treating a mobile target is obtaining the temporal and spatial information imaging and treatment details. This phantom study quantitatively evaluates the geometric and dosimetric effects of various treatment techniques under different respiratory patterns. The regular motion model was a sinusoidal waveform with a longitudinal range of ±1.5 cm and a period of 4 sec, while irregular motion models were generated by extracting signals from clinical cases. Helical CT for a static target and 4D CT with retrospective sorting were acquired. Phase bin, maximum, and average intensity projection (MIP and AIP) CT datasets were reconstructed. RapidArc and IMRT plans were generated on static and moving target CT datasets with different motion patterns using the phase-based gating and nongating treatment. Dose measurements were performed using EBT3 films. Dose profile and gamma analysis (±3%/1 mm criteria) were used for dose comparisons. For the irregular motions, internal target volume variations between AIP and MIP datasets (AIP/MIP) had slight differences (-6.2% to -7.7%) for gated plans, and larger differences (-12.3% to -15.2%) for nongated plans. Dosimetric measurements showed a high gamma passing rate (>98.5%) for the static plan in the target region, while the AIP and MIP gated plans had average passing rates of 92.2% ± 5.7% and 85.8% ± 9.5%, respectively. Nongated plans had significantly lower and deviated passing rates, while the AIP and MIP plans had passing rates of 43.6% ± 22.2% and 66.7% ± 28.2%, respectively (p < 0.05). Lung stereotactic body radiotherapy treatment delivered with the gated technique did not compromise the gross tumor volumes coverage, and was insensitive to the breathing irregularities and plan techniques. Adequate margins should be accounted to cover the mis-gating effect when using the phase-based gating under irregular motion.

Total body irradiation tremendously impair the proliferation, differentiation and chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells.

Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control. The irradiated and non-irradiated MSCs shared similar morphology, phenotype, and hematopoiesis-supporting function. However, irradiated MSCs showed much lower proliferative and differentiative potential. Irradiation also induced clonal cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo irradiation experiments, decreased proliferative and differentiative abilities and clonal cytogenetic abnormalities can also be found in MSCs isolated from transplant recipients who had received TBI-based conditioning previously. Thus, TBI used in HSCT drastically injury MSCs and may contribute to the development of some long-term complications associated with clonal cytogenetic abnormality and poor adipogenesis and osteogenesis after TBI.

Polarimetric infrared imaging simulation of a synthetic sea surface with Mie scattering.

A novel method to simulate the polarimetric infrared imaging of a synthetic sea surface with atmospheric Mie scattering effects is presented. The infrared emission, multiple reflections, and infrared polarization of the sea surface and the Mie scattering of aerosols are all included for the first time. At first, a new approach to retrieving the radiative characteristics of a wind-roughened sea surface is introduced. A two-scale method of sea surface realization and the inverse ray tracing of light transfer calculation are combined and executed simultaneously, decreasing the consumption of time and memory dramatically. Then the scattering process that the infrared light emits from the sea surface and propagates in the aerosol particles is simulated with a polarized light Monte Carlo model. Transformations of the polarization state of the light are calculated with the Mie theory. Finally, the polarimetric infrared images of the sea surface of different environmental conditions and detection parameters are generated based on the scattered light detected by the infrared imaging polarimeter. The results of simulation examples show that our polarimetric infrared imaging simulation can be applied to predict the infrared polarization characteristics of the sea surface, model the oceanic scene, and guide the detection in the oceanic environment.

Water surface-clutter suppression method based on infrared polarization information.

Targeting star-like water surface clutter, a clutter suppression method based on infrared polarization information is proposed. First, the clutter is suppressed from a global perspective using infrared polarization imaging technology, and a basic clutter-suppressed image is obtained. Then, using the Reed-Xiaoli anomaly detection algorithm, the remaining clutter positions in the basic image are determined from the polarization intensity image and basic image. Finally, an image filtering algorithm is utilized to further suppress the remaining clutter in the basic image. In experiments, the proposed method can not only improve the signal-to-clutter ratio as much as 152%, but also preserve the target information and background texture features effectively, indicating clear superiority of our method over existing clutter suppression algorithms. Clutter suppression and target detail preservation can enhance observer understanding of a scene significantly, so this method is applied to the detection and recognition of targets on the water surface.

A Population-based Study of the Effectiveness of Stereotactic Ablative Radiotherapy Versus Conventional Fractionated Radiotherapy for Clinical Stage I Non-small Cell Lung Cancer Patients.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is a promising option for non-operated early-stage non-small cell lung cancer (NSCLC) compared to conventional fractionated radiotherapy (CFRT). However, results from conclusive randomized controlled trials are not yet available. The aim of our study was to explore the effectiveness of SABR vs. CFRT for non-operated early-stage NSCLC. PATIENTS AND METHODS: We used a comprehensive population-based database to identify clinical stage I non-operated NSCLC patients in Taiwan diagnosed from 2007 to 2013 who were treated with either SABR or CFRT. We used inverse probability weighting and the propensity score as the primary form of analysis to address the nonrandomization of treatment. In the supplementary analyses, we constructed subgroups based on propensity score matching to compare survival between patients treated with SABR vs. CFRT. RESULTS: We identified 238 patients in our primary analysis. A good balance of covariates was achieved using the propensity score weighting. Overall survival (OS) was not significantly different between those treated with SABR vs. CFRT (SABR vs. CFRT: probability weighting adjusted hazard ratio [HR] 0.586, 95% confidence interval 0.264-1.101, p = 0.102). However, SABR was significantly favored in supplementary analyses. CONCLUSIONS: In this population-based propensity-score adjusted analysis, we found that OS was not significantly different between those treated with SABR vs. CFRT in the primary analysis, although significance was observed in the supplementary analyses. Our results should be interpreted with caution given the database (i.e., nonrandomized) approach used in our study. Overall, further studies are required to explore these issues.

[18]Fluorodeoxyglucose Positron Emission Tomography for the Textural Features of Cervical Cancer Associated with Lymph Node Metastasis and Histological Type.

BACKGROUND: In this study, we investigated the correlation between the lymph node (LN) status or histological types and textural features of cervical cancers on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. METHODS: We retrospectively reviewed the imaging records of 170 patients with International Federation of Gynecology and Obstetrics stage IB-IVA cervical cancer. Four groups of textural features were studied in addition to the maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis (TLG). Moreover, we studied the associations between the indices and clinical parameters, including the LN status, clinical stage, and histology. Receiver operating characteristic curves were constructed to evaluate the optimal predictive performance among the various textural indices. Quantitative differences were determined using the Mann-Whitney U test. Multivariate logistic regression analysis was performed to determine the independent factors, among all the variables, for predicting LN metastasis. RESULTS: Among all the significant indices related to pelvic LN metastasis, homogeneity derived from the gray-level co-occurrence matrix (GLCM) was the sole independent predictor. By combining SUVmax, the risk of pelvic LN metastasis can be scored accordingly. The TLGmean was the independent feature of positive para-aortic LNs. Quantitative differences between squamous and nonsquamous histology can be determined using short-zone emphasis (SZE) from the gray-level size zone matrix (GLSZM). CONCLUSION: This study revealed that in patients with cervical cancer, pelvic or para-aortic LN metastases can be predicted by using textural feature of homogeneity from the GLCM and TLGmean, respectively. SZE from the GLSZM is the sole feature associated with quantitative differences between squamous and nonsquamous histology.

Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in 18fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer.

BACKGROUND: This study examined genomic factors associated with a reduction in 18fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography-computed tomography (PET-CT) for definitive chemoradiotherapy (CRT) in patients with pharyngeal cancer. METHODS: The pretreatment and interim PET-CT images of 25 patients with advanced pharyngeal cancers receiving definitive CRT were prospectively evaluated. The maximum standardized uptake value (SUVmax) of the interim PET-CT and the reduction ratio of the SUVmax (SRR) between the two images were measured. Genomic data from pretreatment incisional biopsy specimens (SLC2A1, CAIX, VEGF, HIF1A, BCL2, Claudin-4, YAP1, MET, MKI67, and EGFR) were analyzed using tissue microarrays. Differences in FDG uptake and SRRs between tumors with low and high gene expression were examined using the Mann-Whitney test. Cox regression analysis was performed to examine the effects of variables on local control. RESULTS: The SRR of the primary tumors (SRR-P) was 0.59 ± 0.31, whereas the SRR of metastatic lymph nodes (SRR-N) was 0.54 ± 0.32. Overexpression of HIF1A was associated with a high iSUVmax of the primary tumor (P < 0.001) and neck lymph node (P = 0.04) and a low SRR-P (P = 0.02). Multivariate analysis revealed that patients who had tumors with low SRR-P or high HIF1A expression levels showed inferior local control. CONCLUSION: In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUVmax or a slow reduction in FDG uptake. Prospective trials are needed to determine whether the local control rate can be stratified using the HIF1A level as a biomarker and SRR-P.

Radiotherapy did not increase thyroid cancer risk among women with breast cancer: A nationwide population-based cohort study.

The aim of this study was to evaluate whether an increased risk of thyroid cancer exists among women with breast cancer in Taiwan, particularly among those receiving RT. We used data from the National Health Insurance system of Taiwan for the investigation. The breast cancer cohort contained 55,318 women (including 28,187 who received RT and 27,131 who received no RT), each of whom was randomly frequency matched according to age and index year with three women without breast cancer from the general population. Cox's proportion hazards regression analysis was conducted to estimate the effects of breast cancer with or without RT treatment on subsequent thyroid cancer risk. We found that women with breast cancer exhibited a significantly higher risk of subsequent thyroid cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.60-2.44). The two groups (with or without RT) in the breast cancer cohort exhibited significantly increased risks. However, in the breast cancer cohort, the risk of thyroid cancer among women who received RT was not significantly higher than that of women who received no RT (aHR = 1.28, 95% CI = 0.90-1.83). Stratified analysis according to age revealed that only younger women with breast cancer (20-54 y) had a significantly higher risk of developing thyroid cancer. This study determined that Taiwanese women with breast cancer had a higher risk of developing thyroid cancer; however, RT seems to not play a crucial role in this possible relationship.

Depression and risk of venous thromboembolism: a population-based retrospective cohort study.

OBJECTIVE: This study investigated the relationship between depression and the risk of subsequent venous thromboembolism (VTE) development. METHODS: We conducted a population-based retrospective cohort analysis by using data for the period of 2000 to 2011 from the Longitudinal Health Insurance Database 2000 of Taiwan. A depression cohort comprising 35,274 patients and a nondepression cohort comprising 70,548 patients matched according to sex, age, and index year with no history of VTE were evaluated. Cox proportional hazard regression analysis was used to assess the effects of depression and comorbidities, and the Kaplan-Meier method was applied to estimate the cumulative VTE incidence curves. RESULTS: Compared with individuals without depression, depressed patients had a 1.38-fold greater risk (95% confidence interval = 1.09-1.73) of developing VTE. This risk was significantly higher in male and younger (≤49 years) patients. In addition, patients with comorbidities such as hypertension, diabetes, heart failure, and cancer had a higher risk of depression-associated VTE that was attenuated, although nonsignificantly, by antidepressant use. CONCLUSIONS: The incidence of VTE in Taiwan is higher in depressed patients than in nondepressed patients. Moreover, men, people 49 years or younger, and patients with comorbidities have a significantly greater risk of VTE after depression.

Association between colonic diverticular disease and colorectal cancer: a nationwide population-based study.

BACKGROUND & AIMS: We investigated whether a diagnosis of colonic diverticular disease is associated with an increased risk for subsequent development of colorectal cancer (CRC) in a nationwide population-based retrospective study. METHODS: We identified 41,359 individuals diagnosed with colonic diverticular disease as inpatients from 2000 through 2009 from the Taiwan National Health Insurance Research Database (study cohort) and collected data for 165,436 randomly selected additional subjects, matched by sex, age, and baseline year (comparison cohort). Data were collected until individuals developed CRC or withdrew from the National Health Insurance system, or until December 31, 2010. Cumulative incidences and hazard ratios (HRs) of CRC development were determined. To assess for ascertainment bias, we conducted an analysis excluding the first 12 months of follow-up evaluation. RESULTS: The risk of CRC was significantly higher in the study cohort than in the comparison cohort (HR adjusted for age, sex, and comorbidities, 4.54; 95% confidence interval, 4.19-4.91; P < .0001). In a sensitivity analysis, we excluded the first 12 months of follow-up evaluation after a diagnosis of colonic diverticular disease; subsequent incidence rates for CRC in the study and comparison cohorts were 15.13 and 15.74 per 10,000 person-years, respectively (adjusted HR, 0.96; 95% confidence interval, 0.83-1.11). CONCLUSIONS: Colonic diverticular disease is not associated with an increased risk of subsequent CRC after the first year of diagnosis of colonic diverticular disease. An increased risk was observed in the first year, possibly owing to misclassification and screening effects.

Low-dose, prophylactic, extended-field, intensity-modulated radiotherapy plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes, and negative para-aortic lymph nodes.

OBJECTIVE: The objective of this study was to assess prospectively the clinical outcomes of low-dose prophylactic extended-field, intensity-modulated radiotherapy (IMRT) plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes (PLNs), and negative para-aortic lymph nodes (PALNs). METHODS: Thirty-two patients with stage IB2-IIIB cervical cancer with positive PLN and negative PALN were included prospectively. All lymph nodes were assessed with positron emission tomography. The PALN field, including lymphatics from the superior border of L1 to the L4-L5 interphase, was irradiated concurrently with pelvic IMRT with a prescribed dose of 40 Gy in 25 fractions. Chemotherapy consisted of cisplatin delivered weekly at a dose of 40 mg/m. Using historical controls treated with pelvic radiotherapy, the survival curves were compared to assess the difference between the 2 treatment periods. RESULTS: Thirty-one patients completed the allocated extended-field IMRT, and all finished the planned pelvic IMRT and brachytherapy. Acute ≥ grade 3 gastrointestinal, genitourinary, and hematologic toxicities were seen in 2, 1, and 18 patients, respectively. During a median follow-up of 33 months, 5 patients developed out-field distant recurrences. One patient had a late grade 3 gastrointestinal complication, and 1 patient had genitourinary toxicity. The 3-year actuarial overall survival, disease-free survival, and distant metastasis-free survival for the study cohort and historic controls were 87% versus 62% (P = 0.02), 82% versus 54% (P = 0.02), and 79% versus 57% (P = 0.01), respectively. CONCLUSIONS: Extended-field IMRT of 40 Gy to the PALN plus concurrent cisplatin can effectively eradicate subclinical disease at the PALN and improve the outcome for patients with PLN-positive stage IB2-IIIB cervical cancer.

Subdural haemorrhage is associated with recent morphine treatment in patients with cancer: a retrospective population-based nested case-control study.

BACKGROUND: This study investigated the relationship between recent morphine use and risk of subdural haemorrhage (SDH) in patients with cancer. METHODS: This study identified a malignancy cohort of 25,322 patients who had never received morphine treatment. In this malignancy cohort, 200 patients who subsequently developed SDH were designated as the SDH group. Control-group patients without SDH were selected from the malignancy cohort and were matched ∼4:1 to each SDH case for age, sex, year of cancer diagnosis and index year. Morphine use was designated as 'recent' if the prescription duration covered the index date or ended within 6 months before the index date. Logistic regression was used to estimate odds ratios and 95% confidence intervals and a multivariable model was applied to control for age, sex and cerebrovascular disease. RESULTS: Compared with non-morphine users, patients with cancer who received morphine within 6 months of the index date exhibited a 2.58-fold (95% CI = 1.23-5.39) increase in the risk of developing SDH. The risk of SDH development increased as the duration of morphine treatment increased. CONCLUSION: The incidence of SDH in patients with cancer in Taiwan is associated with recent morphine treatment (≤6 months) and is dependent on the duration of morphine use.

Efficacy of Definitive Radiotherapy for Patients with Clinical Stage IIIB or IIIC Lung Adenocarcinoma and Epidermal Growth Factor Receptor (EGFR) Mutations Treated Using First- or Second-Generation EGFR Tyrosine Kinase Inhibitors.

Background: The effectiveness of definitive radiotherapy (RT) for patients with clinical stage IIIB or IIIC lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutations who received first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) is unclear. Methods: Taiwan Cancer Registry data were used in this retrospective cohort study to identify adult patients diagnosed with EGFR-mutated stage IIIB or IIIC lung adenocarcinoma between 2011 and 2020. Patients treated with first- or second-generation EGFR TKIs were classified into RT and non-RT groups. Propensity score (PS) weighting was applied to balance covariates between groups. The primary outcome was overall survival (OS), and the incidence of lung cancer mortality (ILCM) was considered as a supplementary outcome. Additional supplementary analyses were conducted to assess the robustness of the findings. Results: Among 270 eligible patients, 41 received RT and 229 did not. After a median follow-up of 46 months, PS-weighted analysis showed the PS-weighted hazard ratio of death for the RT group compared to the non-RT group was 0.94 (95% CI: 0.61-1.45, p = 0.78). ILCM rates did not differ significantly between the two groups. Supplementary analyses yielded consistent results. Conclusion: The addition of definitive RT to first- or second-generation EGFR TKI treatment does not significantly improve OS of patients with EGFR-mutated stage IIIB or IIIC lung adenocarcinoma. NCT03521154NCT05167851.