Pelvic Bone Marrow Sparing Intensity Modulated Radiation Therapy Reduces the Bone Mineral Density Loss of Patients With Cervical Cancer.

PURPOSE: To test the efficacy and feasibility of pelvic bone marrow sparing intensity modulated radiation therapy (PBMS-IMRT) in reducing bone density loss for patients with cervical cancer undergoing pelvic radiation therapy (RT). METHODS AND MATERIALS: Patients with nonsurgical cervical cancer with stage Ib2-IIIc cancer were randomly allocated into the PBMS group or the control group. The PBMS group additionally received pelvic bone marrow dose constraint. Computed tomography (CT) imaging sets were acquired at baseline and at 1, 3, 6, 9, and 12 months after treatment. Radiation dose and Hounsfield unit were registered. Bone density loss rates and fracture events at different follow-up time points were recorded. RESULTS: Data from 90 patients in the PBMS group and 86 patients in the control group were used for statistical analysis, which included 30 and 26 patients with extended-field radiation therapy (EFR), respectively. The median follow-up for all patients was 12 months. Compared with baseline, the bone density of all bones at the last follow-up decreased by 43% and 53% in the PBMS and control groups, respectively, with the most significant decline at 1 month after treatment. Although patients without EFR received minimal irradiation in the upper lumbar spine, a 22.33% decrease in bone density was detected. In the group of patients with EFR, the decrease was 51.18% (P < .01). Lumbar or pelvic fracture incidence rates of patients in the PBMS and control groups were 7.8% and 12.79%, respectively. Among the dosimetric parameters, mean dose had the strongest correlation with bone density loss. CONCLUSIONS: In patients undergoing pelvic RT, the loss of bone density can begin to appear early after RT, and it can occur either inside or outside of the irradiation field. Results of this study showed that PBMS-IMRT reduced bone mineral density loss compared with IMRT alone.

Comparison of post-chemoradiotherapy pneumonitis between Asian and non-Asian patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis.

Background: Pneumonitis is a common complication for patients with locally advanced non-small cell lung cancer undergoing definitive chemoradiotherapy (CRT). It remains unclear whether there is ethnic difference in the incidence of post-CRT pneumonitis. Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched for eligible studies from January 1, 2000 to April 30, 2023. The outcomes of interest were incidence rates of pneumonitis. The random-effect model was used for statistical analysis. This meta-analysis was registered with PROSPERO (CRD42023416490). Findings: A total of 248 studies involving 28,267 patients were included. Among studies of CRT without immunotherapy, the pooled rates of pneumonitis for Asian patients were significantly higher than that for non-Asian patients (all grade: 66.8%, 95% CI: 59.2%-73.9% vs. 28.1%, 95% CI: 20.4%-36.4%; P < 0.0001; grade ≥2: 25.1%, 95% CI: 22.9%-27.3% vs. 14.9%, 95% CI: 12.0%-18.0%; P < 0.0001; grade ≥3: 6.5%, 95% CI: 5.6%-7.3% vs. 4.6%, 95% CI: 3.4%-5.9%; P = 0.015; grade 5: 0.6%, 95% CI: 0.3%-0.9% vs. 0.1%, 95% CI: 0.0%-0.2%; P < 0.0001). Regarding studies of CRT plus immunotherapy, Asian patients had higher rates of all-grade (74.8%, 95% CI: 63.7%-84.5% vs. 34.3%, 95% CI: 28.7%-40.2%; P < 0.0001) and grade ≥2 (34.0%, 95% CI: 30.7%-37.3% vs. 24.6%, 95% CI: 19.9%-29.3%; P = 0.001) pneumonitis than non-Asian patients, but with no significant differences in the rates of grade ≥3 and grade 5 pneumonitis. Results from subgroup analyses were generally similar to that from the all studies. In addition, the pooled median/mean of lung volume receiving ≥20 Gy and mean lung dose were relatively low in Asian studies compared to that in non-Asian studies. Interpretation: Asian patients are likely to have a higher incidence of pneumonitis than non-Asian patients, which appears to be due to the poor tolerance of lung to radiation. Nevertheless, these findings are based on observational studies and with significant heterogeneity, and need to be validated in future large prospective studies focusing on the subject. Funding: None.

UNC5A, an epigenetically silenced gene, functions as a tumor suppressor in non-small cell lung cancer.

UNC5A has been reported to be related with human cancers. However, the function and mechanism in non-small cell lung carcinoma (NSCLC) remains unknown. We analyzed two NSCLC cell lines (A549 and H157), one normal human bronchial epithelial cell line (BEAS-2B) and the tissues of NSCLC. We used quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical (IHC) staining to examine the expression of UNC5A. Methylation status of the UNC5A promoter was analyzed using methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). We used western blot to analyzed protein levels of PI3K/Akt pathway. We found that the mRNA expression of UNCA5 was significantly downregulated in NSCLC cells and tissues. The promoter of UNC5A was hypermethylated in NSCLC cells compared to normal control cells. The expression of UNC5A could be reversed by demethylation agent in NSCLC cells. The expression of UNC5A was decreased in NSCLC samples and significantly associated with the advanced types of NSCLC. Functionally, knockdown of UNC5A promoted cell proliferation, migration, invasion and induced apoptosis in NSCLC, overexpression of UNC5A yielded the opposite result. Moreover, we found that UNC5A negatively regulated PI3K/Akt signaling pathway in NSCLC. UNC5A is a novel epigenetically silenced gene in NSCLC and consequent under-expression of UNC5A may contribute to NSCLC tumorigenesis through regulating PI3K/Akt pathway.

CCAE: Cross-field categorical attributes embedding for cancer clinical endpoint prediction.

Patients with advanced cancer are burdened physically and psychologically, so there is an urgent need to pay more attention to their health-related quality of life (HRQOL). With an expected clinical endpoint prediction, over-treatment can be effectively eliminated by the means of palliative care at the right time. This paper develops a deep learning based approach for cancer clinical endpoint prediction based on patient's electronic health records (EHR). Due to the pervasive existence of categorical information in EHR, it brings unavoidably obstacles to the effective numerical learning algorithms. To address this issue, we propose a novel cross-field categorical attributes embedding (CCAE) model to learn a vectorized representation for cancer patients in attribute-level by orders, in which the strong semantic coupling among categorical variables are well exploited. By transforming the order-dependency modeling into a sequence learning task in an ingenious way, recurrent neural network is adopted to capture the semantic relevance among multi-order representations. Experimental results from the SEER-Medicare EHR dataset have illustrated that the proposed model can achieve competitive prediction performance compared with other baselines.

Elective nodal irradiation versus involved-field irradiation in patients with esophageal cancer receiving neoadjuvant chemoradiotherapy: a network meta-analysis.

BACKGROUND: To assess the comparative efficacy and safety of elective nodal irradiation (ENI) and involved-field irradiation (IFI) in patients with esophageal cancer (EC) receiving neoadjuvant chemoradiotherapy plus surgery (nCRTS). MATERIAL AND METHODS: PubMed, Embase, Cochrane Library, Web of Science and major meetings were searched for randomized controlled trials (RCTs) that compared at least two of the following treatment regimens: nCRTS, neoadjuvant chemotherapy plus surgery (nCTS), and surgery (S) alone. Overall survival (OS) was the primary outcomes of interest, reported as hazard ratio (HR) and 95% confidence intervals (CIs). A Bayesian network meta-analysis was performed to compare all regimens simultaneously. RESULTS: Twenty-nine RCTs with a total of 5212 patients were included in the meta-analysis. Both nCRTS adopting ENI (nCRTS-ENI) (HR = 0.63, 95% CI: 0.48-0.83) and nCRTS adopting IFI (nCRTS-IFI) (HR = 0.75, 95% CI: 0.66-0.86) significantly improved OS compared to S alone. No significant differences in OS, locoregional recurrence, distant metastases, R0 resection and postoperative mortality were observed between nCRTS-ENI and nCRTS-IFI. In subgroup analyses, nCRTS-IFI showed a significant OS advantage over nCTS (HR = 0.78, 95% CI: 0.63-0.96) and S alone (HR = 0.50, 95% CI: 0.38-0.68) for esophagus squamous cell carcinoma (ESCC), but nCRTS-ENI did not; nCRTS-ENI using three-dimensional radiotherapy (3D-RT) resulted in an improved OS compared to that with 2D-RT (HR = 0.58, 95% CI: 0.34-0.99). Based on treatment ranking in term of OS, nCRTS-IFI (0.90) and nCRTS-ENI (0.96) was ranked the most effective treatment for ESCC and esophagus adenocarcinoma (EAC), respectively. CONCLUSION: Either adopting ENI or IFI, nCRTS is likely to be the optimal treatment for resectable EC, and nCRTS-IFI and nCRTS-ENI seem to be more effective for patients with ESCC and EAC, respectively. Future head to head comparison trials are needed to confirm these findings.

First-line immune checkpoint inhibitors for advanced non-small cell lung cancer with wild-type epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK): a systematic review and network meta-analysis.

BACKGROUND: To assess the comparative efficacy and safety of first-line immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK). METHODS: PubMed, Embase, Cochrane Library, Web of Science, and major international scientific meetings were searched for relevant randomized controlled trials. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes and serious adverse events (SAEs) were the secondary outcome of interests and were reported as hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: Fourteen trials with 9,570 patients randomized to receive ten ICI-based treatments (including PD-1/PD-L1 and CTLA-4 antibodies and PD-1/PD-L1 with CTLA-4 combination therapies) were included in the meta-analysis. Pembrolizumab combined with chemotherapy (Pem + CT) (HR =0.56, 95% CI: 0.42-0.74) and Pem (HR =0.75, 95% CI: 0.62-0.91) were more effective than CT in terms of OS; Pem + CT was also superior to Pem (HR =0.74, 95% CI: 0.56-0.98), atezolizumab + CT (HR =0.65, 95% CI: 0.50-0.85), ipilimumab + CT (HR =0.65, 95% CI: 0.47-0.89), and nivolumab (HR =0.52, 95% CI: 0.31-0.87). In subgroup analyses, Pem + CT was more effective than CT regardless of PD-L1 expression, while Pem was superior to CT only for PD-L1 with expression ≥50%; Pem + CT showed significant OS advantage over other treatments in patients with non-squamous cell carcinoma (NSCC); ICIs had a comparable efficacy in younger vs. older patients. Based on treatment ranking in terms of OS, Pem + CT had the highest probability (98%) of being the most effective treatment, followed by Pem (70%), with acceptable toxicity limit. CONCLUSIONS: Pem + CT seemed to be more effective first-line regimen for advanced NSCLC with wild-type EGFR or ALK, especially for patients with NSCC. However, limitations of the study including methodological quality and immature OS data need to be considered.

The association of UNC5A expression with the clinicopathologic features and prognosis of radiotherapy in patients with non-small-cell lung cancer.

UNC5A is widely known as a neuronal axonal guide factor and was found to have a low expression in a variety of tumors. In our study, we investigated the expression of UNC5A in non-small cell lung cancer (NSCLC) and analyzed its association with the clinical features and prognosis of NSCLC radiotheray patients. METHODS: We collected 169 NSCLC patients' clinical and pathological data for the study. Immunohistochemical staining was evaluated to analyze the expression of UNC5A in NSCLC tissues. The expressions of UNC5A in normal and NSCLC tissues were analyzed using the Oncomine database. We investigated the overall prognostic value of UNC5A in NSCLC patients through the Kaplan-Meier plotter database. RESULTS: The low expression rate of UNC5A was 55.0% (93/169) in NSCLC by immunohistochemical analysis. The overall survival (OS) of NSCLC radiotheray patients with a low expression of UNC5A was shorter than that in patients with a high expression (P = 0.000). The expression of UNC5A was strongly and significantly associated with the TNM stage (P = 0.013) but not associcated with other clinicopathologic features. The results of COX regression showed that the expression of UNC5A, general condition and TNM stage were independent prognositic factors of NSCLC patients. ROC analysis showed a high area under the curve for UNC5A expression in NSCLC (AUC = 0.746). At a cut-off level of > 1027, the UNC5A expression, general condition and TNM stages, could be used for the prognosis of NSCLC with high sensitivity and specificity. The Oncomine database showed that UNC5A expression was found to significantly decline in NSCLC tissues compared to normal tissues (P = 0.029). We used the Kaplan-Meier plotter database to analyze NSCLC patients with a high expression of UNC5A and found they had better OS than patients with a low expression (P = 0.0492). CONCLUSION: The expression of UNC5A may be a potential prognostic biomarker of NSCLC.

Synchronous of gastric adenocarcinoma and schwannoma: report of a case and review of literatures.

We presented a case of 80-year-old male with long term stomachache, marasmus and anaemia. Endoscopic evaluation suggested the malignant ulcerative tumor on the Gastric antrum, and biopsy confirmed the diagnosis of gastric adenocarcinoma. Surprisingly, in resected specimen the pathologist found a nodule just below the ulcer with clear boundary and gray-yellow section. Histologically, the whole lesion was composed with adenocarcinoma area and spindle tumor cells area. In the spindle tumor cells area, the cells with round or oval nuclei, eosinophilic cytoplasm, and these cells showed bundle or fence-like arrangement. Immunohistochemistry study presented positive expression of vimentin, S-100 and GFAP, negative expression of SMA, desmin, CD34, CD117 and Dog-1, which suggested the diagnosis of co-occurrence of gastric adenocarcinoma and schwannoma. To our knowledge, it is an extremely rare case that only two cases have been reported.

Mesothelioma of the tunica vaginalis testis with prominent adenomatoid features: a case report.

Malignant mesotheliomas of the testis arise from the tunica vaginalis, formed from the evagination of the abdominal peritoneum into the scrotum. It is an extremely rare tumor representing 0.3% to 5% of all malignant mesotheliomas. We presented an interesting case of 68-year-old male with swelling and slightly painful in the right scrotum. Histologically, the lesion were composed of small tubular, microcystic, gland lined by flattened epithelioid cells and vague signet ring cells set in a myxofibrous stroma, which is resemblance to adenomatoid tumor. But the tumor cells showed significant atypical cytologic morphology and invaded into spermatic cord tissue, which indicated the diagnosis of malignant tumor. Immunohistochemistry study showed positive expression of CK, CK5/6, CK7, Calretinin, D2-40 and Vimentin which indicated the diagnosis of malignant mesothelioma. This case of mesothelioma should be classified as epithelial in type. To our knowledge, the mesothelioma of the tunica vaginalis testis with adenomatoid tumor-like microscopic features is very rare.