Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by sensitivity to sunlight and predisposition to cutaneous malignancies. There are various types, including the Variant type, which does not manifest with acute sunburn reactions. This results to the development of multiple malignancies that are often discovered at late stages, making management more challenging. This is a case of a 54-year-old Filipino female presenting with multiple basal cell carcinomas (BCCs) on several areas of the face and advanced cutaneous squamous cell carcinoma (cSCC) on the right zygomatic area, treated with imiquimod 5% cream and external beam radiation therapy, respectively. There was an excellent response of the BCCs to imiquimod 5% cream and good tumoral response of the SCC to radiation therapy, with tolerable side effects, highlighting the use of these palliative treatment modalities for XP patients with multiple, unresectable, or difficult-to-treat cutaneous malignancies.

OBJECTIVE: To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R. METHODS: Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label. RESULTS: The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results. CONCLUSIONS SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.
Animals ; Humans ; Nasopharyngeal Carcinoma/genetics* ; Epithelial-Mesenchymal Transition ; Zebrafish ; Cell Proliferation ; Cell Line, Tumor ; Nasopharyngeal Neoplasms/radiotherapy* ; Cell Movement ; Gene Expression Regulation, Neoplastic

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.
Humans ; Small Cell Lung Carcinoma/pathology* ; Lung Neoplasms/pathology* ; Radiotherapy, Intensity-Modulated/methods* ; Retrospective Studies ; Lung Injury ; Radiotherapy Dosage ; Radiation Injuries/epidemiology* ; Esophagitis/epidemiology* ; Risk Factors ; Pulmonary Disease, Chronic Obstructive/complications*

Humans ; Pulmonary Alveolar Proteinosis/radiotherapy* ; Small Cell Lung Carcinoma/radiotherapy* ; Lung ; Bronchoalveolar Lavage ; Lung Neoplasms/radiotherapy*

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.
Humans ; Radiotherapy, Intensity-Modulated ; Immune Tolerance ; Nasopharyngeal Carcinoma ; ROC Curve ; Nasopharyngeal Neoplasms/radiotherapy*

Objective: To explore whether the survival benefit of the third-line extensive small-cell lung cancer (ES-SCLC) will be obtained by the combination of anlotinib and radiotherapy, and evaluate the safety of this treatment regimen. Methods: Twenty-seven patients with ES-SCLC who received third-line treatment with less than three metastatic organs at the Cancer Hospital of Xinjiang Medical University from November 2018 to July 2021 were collected and treated with radiotherapy based on anlotinib. Kaplan-Meier curve was used to estimate the overall survival (OS) and progression-free survival (PFS), descriptive statistical analysis was used to evaluate the safety, and European organisation for research and treatment of cancer quality of life questionnaire-core 30 (EORTC QLQ-C30) was used to evaluate the quality of life. Results: The follow-up cut-off date was July 1, 2021, and the follow-up time ranged from 4.8 to 31.0 months, with a median follow-up time of 10.2 months for the entire group. Among the 27 patients, 4 achieved partial remission, 17 had stable disease and 6 had progression of disease. The objective remission rate (ORR) was 14.8%, and the disease control rate (DCR) was 77.8%. Median PFS and the median OS were 5 months and 11 months, respectively. The most common adverse reactions included fatigue (33.3%, 9/27), anorexia (14.8%, 4/27), bleeding (14.8%, 4/27) and hand-foot syndrome (11.1%, 3/27). Most of them were grade 1 to grade 2, 3 cases were more than grade 3, and there was no grade 5 toxicity recorded. After radiotherapy combined with amlotinib treatment, patients showed improvement in general health, somatic functioning, social functioning, and emotional functioning (all P<0.05). Conclusion: For the third-line ES-SCLC patients, radiotherapy based on the anlotinib can significantly prolong their PFS and OS, and the adverse reactions can be tolerated.
Humans ; Small Cell Lung Carcinoma/radiotherapy* ; Lung Neoplasms/radiotherapy* ; Quality of Life ; Treatment Outcome ; Progression-Free Survival

Objective: To explore whether the survival benefit of the third-line extensive small-cell lung cancer (ES-SCLC) will be obtained by the combination of anlotinib and radiotherapy, and evaluate the safety of this treatment regimen. Methods: Twenty-seven patients with ES-SCLC who received third-line treatment with less than three metastatic organs at the Cancer Hospital of Xinjiang Medical University from November 2018 to July 2021 were collected and treated with radiotherapy based on anlotinib. Kaplan-Meier curve was used to estimate the overall survival (OS) and progression-free survival (PFS), descriptive statistical analysis was used to evaluate the safety, and European organisation for research and treatment of cancer quality of life questionnaire-core 30 (EORTC QLQ-C30) was used to evaluate the quality of life. Results: The follow-up cut-off date was July 1, 2021, and the follow-up time ranged from 4.8 to 31.0 months, with a median follow-up time of 10.2 months for the entire group. Among the 27 patients, 4 achieved partial remission, 17 had stable disease and 6 had progression of disease. The objective remission rate (ORR) was 14.8%, and the disease control rate (DCR) was 77.8%. Median PFS and the median OS were 5 months and 11 months, respectively. The most common adverse reactions included fatigue (33.3%, 9/27), anorexia (14.8%, 4/27), bleeding (14.8%, 4/27) and hand-foot syndrome (11.1%, 3/27). Most of them were grade 1 to grade 2, 3 cases were more than grade 3, and there was no grade 5 toxicity recorded. After radiotherapy combined with amlotinib treatment, patients showed improvement in general health, somatic functioning, social functioning, and emotional functioning (all P<0.05). Conclusion: For the third-line ES-SCLC patients, radiotherapy based on the anlotinib can significantly prolong their PFS and OS, and the adverse reactions can be tolerated.
Humans ; Small Cell Lung Carcinoma/radiotherapy* ; Lung Neoplasms/radiotherapy* ; Quality of Life ; Treatment Outcome ; Progression-Free Survival

Objective: SET8 is a member of the SET domain-containing family and the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20me1). SET8 has been implicated in many essential cellular processes, including cell cycle regulation, DNA replication, DNA damage response, and carcinogenesis. There is no conclusive evidence, however, regarding the effect of SET8 on radiotherapy. In the current study we determined the efficacy of SET8 inhibition on radiotherapy of tumors and the underlying mechanism. Methods: First, we explored the radiotherapy benefit of the SET8 expression signature by analyzing clinical data. Then, we measured a series of biological endpoints, including the xenograft tumor growth in mice and apoptosis, frequency of micronuclei, and foci of 53BP1 and γ-H2AX in cells to detect the SET8 effects on radiosensitivity. RNA sequencing and subsequent experiments were exploited to verify the mechanism underlying the SET8 effects on radiotherapy. Results: Low expression of SET8 predicted a better benefit to radiotherapy in lung adenocarcinoma (LUAD) and invasive breast carcinoma (BRCA) patients. Furthermore, genetic deletion of SET8 significantly enhanced radiation treatment efficacy in a murine tumor model, and A549 and MCF7 cells; SET8 overexpression decreased the radiosensitivity. SET8 inhibition induced more apoptosis, the frequency of micronuclei, and blocked the kinetics process of DNA damage repair as 53BP1 and γ-H2AX foci remained in cells. Moreover, RNF8 was positively correlated with the SET8 impact on DNA damage repair. Conclusion Our results demonstrated that SET8 inhibition enhanced radiosensitivity by suppressing DNA damage repair, thus suggesting that SET8 potentiated radiotherapy of carcinomas. As new inhibitors of SET8 are synthesized and tested in preclinical and clinical settings, combining SET8 inhibitors with radiation warrants consideration for precise radiotherapy.
Animals ; Apoptosis ; Carcinogenesis ; Carcinoma/radiotherapy* ; Cell Cycle ; Cell Line, Tumor ; DNA Damage ; DNA Replication ; HeLa Cells ; Histone-Lysine N-Methyltransferase ; Humans ; Mice ; Radiotherapy

BACKGROUND: Immunotherapy (IT) is recommended for the treatment of advanced non-small cell lung cancer (NSCLC), while brain radiotherapy (RT) is the mainstream treatment for patients with brain metastases (BM). This study aimed to investigate the efficacy and safety of combined use of RT and IT. METHODS: The date was limited to May 1, 2022, and literature searches were carried out in CNKI, Wanfang, PubMed, EMBASE and Cochrane databases. Heterogeneity was judged using the I2 test and P value. Publication bias was assessed using a funnel plot. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Statistical analysis was performed using Stata 16.0 software. RESULTS: A total of 17 articles involving 2,636 patients were included. In the comparison of RT+IT group and RT group, no significant difference was found in overall survival (OS) (HR=0.85, 95%CI: 0.52-1.38, I2=73.9%, Pheterogeneity=0.001) and intracranial distance control (DBC) (HR=1.04, 95%CI: 0.55-1.05, I2=80.5%, Pheterogeneity<0.001), but the intracranial control (LC) in the RT+IT group was better than the RT group (HR=0.46, 95%CI: 0.22-0.94, I2=22.2%, Pheterogeneity=0.276), and the risk of radiation necrosis/treatment-related imaging changes (RN/TRIC) was higher than RT (HR=1.72, 95%CI: 1.12-2.65, I2=40.2%, Pheterogeneity=0.153). In the comparison between the RT+IT concurrent group and the sequential group, no significant difference was found in OS (HR=0.62, 95%CI: 0.27-1.43, I2=74.7%, Pheterogeneity=0.003) and RN/TRIC (HR=1.72, 95%CI: 0.85-3.47, I2=0%, Pheterogeneity=0.388) was different between the two groups. However, DBC in the concurrent treatment group was better than that in the sequential treatment group (HR=0.77, 95%CI: 0.62-0.96, I2=80.5%, Pheterogeneity<0.001). CONCLUSIONS RT combined with IT does not improve the OS of NSCLC patients with BM, but also increases the risk of RN/TRIC. In addition, compared with sequential RT and IT, concurrent RT and IT improved the efficacy of DBC.
Humans ; Lung Neoplasms/radiotherapy* ; Carcinoma, Non-Small-Cell Lung/radiotherapy* ; Brain Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Radiation Injuries

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage