Comparative analysis of dosimetric and radiobiological models of IPSA and HIPO algorithms in combined intra-cavitary/interstitial brachytherapy for cervical cancer.

Purpose: To compare inverse planning simulated annealing (IPSA) and hybrid inverse planning optimization (HIPO) using dosimetric and radiobiological models, and provide a basis for selecting the optimization method for cervical cancer. Material and methods: This was a retrospective study including 32 patients with radical cervical cancer. Brachytherapy treatment plans were re-optimized using IPSA, HIPO1 (with a locked uterine tube), and HIPO2 (with an unlocked uterine tube). Dosimetric data, including isodose lines, HR-CTV (D100, V150%, V200%, HI, and CI), and (bladder, rectum, and intestines) D1cc, D2cc for organs at risk (OARs) were also collected. Additionally, TCP, NTCP, BED, and EUBED were calculated, and differences were analyzed using matched samples t-test and Friedman test. Results: Compared with IPSA and HIPO2, HIPO1 had better V150% and V200% (p < 0.05). Compared with IPSA and HIPO1, HIPO2 had better D100 and CI (p < 0.05). The doses to the bladder D1cc (4.72 ±0.33 Gy)/D2cc (4.47 ±0.29 Gy) and rectum D1cc (4.50 ±0.61 Gy)/D2cc (4.11 ±0.63 Gy) were lower in HIPO2 than in IPSA and HIPO1. EUBEDs for HR-CTV were higher in HIPO1 and HIPO2 than in IPSA by 1.39-1.63%. However, TCPs were not remarkably different among the three plans (p > 0.05). Also, the NTCP for the bladder was lower in HIPO2 than in IPSA and HIPO1 by 13.04% and 16.67%, respectively. Conclusions: Although the dosimetric parameters of IPSA, HIPO1, and HIPO2 are comparable, HIPO2 provides better dose conformability and lower NTCP. Therefore, HIPO2 is recommended as an optimization algorithm in IC/ISBT for cervical cancer.

Radiobiological and dosimetric comparison of 60Co versus 192Ir high-dose-rate intracavitary-interstitial brachytherapy for cervical cancer.

BACKGROUND: High-dose-rate (HDR) intracavitary-interstitial brachytherapy (IC-ISBT) is an effective treatment for bulky, middle, and advanced cervical cancer. In this study, we compared the differences between 60Co and 192Ir HDR IC-ISBT plans in terms of radiobiological and dosimetric parameters, providing a reference for clinical workers in brachytherapy. METHODS: A total of 30 patients with cervical cancer receiving HDR IC-ISBT were included in this study, and IC-ISBT plans for each individual were designed with both 60Co and 192Ir at a prescribed dose of CTV D90 = 6 Gy while keeping the dose to OARs as low as possible. Physical dose and dose-volume parameters of CTV and OARs were extracted from TPS. The EQD2, EUBED, EUD, TCP, and NTCP were calculated using corresponding formulas. The differences between the 60Co and 192Ir IC-ISBT plans were compared using the paired t-test. RESULTS: In each patient's 60Co and 192Ir IC-ISBT plan, the average physical dose and EQD2 of 60Co were lower than those of 192Ir, and there were statistically significant differences in D2cc and D1cc for the OARs (p < 0.05); there were statistically significant differences in D0.1 cc for the bladder (p < 0.05) and no significant differences in D0.1 cc for the rectum or intestines (p > 0.05). The EUBED ratio (60Co/192Ir) at the CTV was mostly close to 1 when neither 60Co or 192Ir passed their half-lives or when both passed two half-lives, and the difference between them was not significant; at the OARs, the mean value of 60Co was lower than that of 192Ir. There was no statistical difference between 60Co and 192Ir in the EUD (93.93 versus 93.92 Gy, p > 0.05) and TCP (97.07% versus 97.08%, p > 0.05) of the tumors. The mean NTCP value of 60Co was lower than that of 192Ir. CONCLUSIONS: Considering the CTV and OARs, the dosimetric parameters of 60Co and 192Ir are comparable. Compared with 192Ir, the use of 60Co for HDR IC-ISBT can ensure a similar tumor control probability while providing better protection to the OARs. In addition, 60Co has obvious economic advantages and can be promoted as a good alternative to 192Ir.

Comparative Analysis of 60Co and 192Ir Sources in High Dose Rate Brachytherapy for Cervical Cancer.

High-dose-rate (HDR) brachytherapy (BT) is an essential treatment for cervical cancer, one of the most prevalent gynecological malignant tumors. In HDR BT, high radiation doses can be delivered to the tumor target with the minimum radiation doses to organs at risk. Despite the wide use of the small HDR 192Ir source, as the technique has improved, the HDR 60Co source, which has the same miniaturized geometry, has also been produced and put into clinical practice. Compared with 192Ir (74 days), 60Co has a longer half-life (5.3 years), which gives it a great economic advantage for developing nations. The aim of the study was to compare 60Co and 192Ir sources for HDR BT in terms of both dosimetry and clinical treatment. The results of reports published on the use of HDR BT for cervical cancer over the past few years as well as our own research show that this treatment is safe and it is feasible to use 60Co as an alternative source.

Tumor specificity of WNT ligands and receptors reveals universal squamous cell carcinoma oncogenes.

BACKGROUND: The WNT signal pathway has myriad family members, which are broadly involved in embryonic development and human cancer. Over-activation of WNT-ß-Catenin signaling promotes cancer cell proliferation and survival. However, how diverse components of WNT signaling specifically engaged in distinct tumor types remains incompletely understood. METHODS: We analyzed the transcriptomic profiling of WNT ligands and receptors/co-receptors among 26 different tumor types to identify their expression pattern, and further verified these results using clinical oral squamous cell carcinoma (OSCC) and lung squamous cell carcinoma (LUSC) samples. At the same time, we also detected WNT7B expression in oral inflammation and carcinoma, and constructed stable WNT7B knockdown OSCC cell lines to study the effects of WNT7B on the cell migration and invasion ability. RESULTS: We found a group of tumor-specific WNT members, including a panel of squamous cell carcinomas (SCCs) specific upregulated WNT ligands and receptors, WNT5A, WNT7B, FZD7 and GPC1. We further revealed a significant correlation between these protein expression characteristics and clinical outcomes of OSCC and LUSC patients. Moreover, WNT7B was demonstrated to contribute to the development of oral chronic inflammation and OSCC, partly due to promoting the invasion ability of tumor cells. CONCLUSIONS: These results demonstrate that the function of WNT ligands and receptors in specific tumors depends on the origination of tumor tissue type. Collectively, they support the use of WNT components as a highly specific target for pan-tissue-type originated tumors.

Sinomenine Attenuated Capsaicin-Induced Increase in Cough Sensitivity in Guinea Pigs by Inhibiting SOX5/TRPV1 Axis and Inflammatory Response.

BACKGROUND: Chronic cough is a common complaint which affects a large number of patients worldwide. Increased cough sensitivity is a very important cause of chronic persistent cough. However, there are limited clinical diagnosis and treatment for increased cough sensitivity. Transient receptor potential vanilloid-1 (TRPVl) is a member of the transient receptor potential (TRP) family of channels which is very closely associated with respiratory diseases. However, the mechanism through which TRPV1 that influences downstream events is still poorly understood. RESULTS: Capsaicin induced increase in cough sensitivity by upregulating the protein level of TRPV1, leading to the secretions of Substance P and neurokinin A which stimulated neurogenic inflammation. However, sinomenine, a component of traditional Chinese medicine, significantly attenuated the capsaicin-induced cough by inhibiting the expression of TRPV1 in guinea pigs. In addition, capsaicin increased the expression of SOX5 which mediated the transcriptional upregulation of TRPV1. However, pretreatment with sinomenine reduced the expression of SOX5. CONCLUSION: These results indicate that capsaicin induced increase in cough sensitivity by activating neurogenic inflammation, while sinomenine attenuated the increase in cough sensitivity by inhibiting the expressions of SOX5 and TRPV1 in guinea pigs. This finding may provide a novel target for the treatment of aggravated cough sensitivity.