Search

• One-third of pediatric tumor patients require radiotherapy. • High pediatric radiotherapy utilization rate in a middle-income country. • Pediatric soft tissue sarcoma requires the highest radiotherapy utilization rate. • Palliative radiotherapy is frequently used for brainstem glioma patients. • Palliative radiotherapy is underutilized in childhood cancers. Although the radiotherapy utilization rate (RUR) is determined for most adult cancers, it is seldom reported in childhood tumors, particularly in low- and middle-income countries (LMIC) where the majority of pediatric cancer patients reside. This study aims to investigate the real-life RUR for pediatric tumors in a large LMIC center. The electronic files of patients treated at a single institution during 2010–2017 were reviewed and the RUR was defined as the percentage of patients who received at least one radiotherapy (RT) course from the total number of patients. A total of 4390 out of 13,305 pediatric cancer patients received at least one RT course with a RUR of 33%. The curative, salvage, and palliative RURs were 27.8%, 2%, and 5.7%, respectively. There was a considerable variation in the RUR between various tumors, ranging from 0% in choroid plexus papilloma and other rare tumors to 100% in intracranial germinoma. Moreover, the RUR varied among different stages within each tumor type. Overall, 753 patients received 920 palliative RT courses (range 1–9) at a median dose of 30 Gy. The most commonly irradiated metastatic sites were the bone (34%) and the brain (9.8%). This is the first analysis to provide valuable insights into the RUR for childhood tumors. Together with population-based pediatric cancer registries, this will help decipher pediatric RT needs and deficits. Additionally, the underutilization of palliative RT calls for multidisciplinary palliative care provision for pediatric cancer patients. [ABSTRACT FROM AUTHOR]

• The cancer burden, radiotherapy availability and mortality-incidence ratio in Arabic countries showed a shortage of radiotherapy service especially in low income and politically unstable countries. Arab countries share a common location, history, language and culture with different economic characteristics. In this study, we analyze the availability and factors influencing radiotherapy services and cancer mortality incidence ratio (MIR) in Arabic countries. Data were collected from GLOBOCAN report, World Health Organization, World Bank, United Nation and Directory of Radiotherapy Centre databases. The average number of megavoltage machines (MVM) in Arab countries is 0.84 machine per 1000 cancer patients. The number of MVM per 1000 cancer patients was found to be significantly correlated with gross domestic product (GDP) per capita ( r = 0.583, P = 0.006). In addition, it was found to be significantly more in politically stable countries compared to unstable ones ( P = 0.004) and more in high and upper-middle income countries (median 0.94 ± 1.0) compared to lower-middle and low income countries (median 0.3 ± 0.51) ( P = 0.013). MIR was found to be significantly correlated with GDP per capita, physicians per 1000 population, MVM per 1000 cancer patients and absolute MVM deficit ( r = −0.555, −0.625, −0.42, −0.436 and P = 0.009, 0.006, 0.047, 0.043, respectively). On multivariate regression analysis, the number of physicians per 1000 population had the strongest prediction of MIR in Arabic countries ( P = 0.01). Although the economic status is of paramount importance, it is not the only factor determining the quantity and quality of radiotherapy services in the Arab world. More efforts are urgently needed to improve the status of radiation oncology and fill its gap in the Arab countries. [ABSTRACT FROM AUTHOR]

Access to radiation facilities in low- and middle-income countries (LMIC) is far from optimal. Latin America and Africa represent 55% of LMIC, and radiation therapy facilities are available in only 70% and 46% of the countries, respectively. Only 3 countries in both regions meet the International Atomic Energy Agency's recommendation of 250,000 population per megavoltage machine (MVM). In Africa, the mean population served by 1 MVM is 3.56 million, compared with 0.65 million in Latin America. The distribution of radiation facilities in both regions varies according to income group. In Latin America, lower-middle-income countries have a distribution of 1.64 million inhabitants per MVM, as opposed to 0.64 and 0.49 million inhabitants per MVM in upper-middle- and high-income countries, respectively. In Africa, a distribution of 39.8, 2.47, and 0.8 million people per MVM is present in low-, lower-middle-, and upper-middle-income countries, respectively. Significant correlations were clearly demonstrated between population per MVM and gross domestic product (GDP) per capita (r = -0.3, P = .014), percentage of current health expenditure from GDP (r = -0.4, P = .014), life expectancy (r = -0.5, P = .0007), and cancer mortality incidence ratio (r = 0.4, P = .003). Stepwise multivariate regression showed that life expectancy was the only statistically significant factor (P = .001). These findings may indicate the detrimental impact of low radiation therapy coverage on life expectancy and cancer mortality incidence ratio in LMIC. It is noteworthy that in Latin America, a significant negative correlation was noted between population per MVM and GDP per capita (r = -0.6, P = .0004), as opposed to Africa (r = -0.4, P = .075). This indicates that African countries face challenges other than income level in addressing radiation therapy needs. More international efforts are urgently required to address the crisis of unmet radiation therapy needs in LMIC. [ABSTRACT FROM AUTHOR]

In the rapidly expanding era of cancer target therapy, regulators of apoptosis are emerging as attractive therapeutic targets. X-linked inhibitor of apoptosis (XIAP) is of specific interest owing to its characteristic overexpression in a wide variety of neoplasms, with a resultant survival advantage for tumor cells and treatment resistance. In this study, we examined three pyrazolo [3,4- d ] pyridazine derivatives (PPDs) through molecular modeling and studied their modes of interaction with XIAP-BIR3 domain. PPD-1, which possessed the highest binding affinity with XIAP, was tested on A549 (lung cancer cell line); HCT-116 (colorectal carcinoma cell line); HEPG2 (liver carcinoma cell line), HFB4 (normal human skin melanocyte cell line) and WI-38 (human embryonic lung fibroblasts). In comparison to cisplatin as a positive control, PPD-1 yielded remarkable cytotoxicity on all cancer cell lines, with the highest anti-tumor activity on A549 and a favorable therapeutic ratio. Flow cytometry studies concluded that PPD-1 treatment induces Sub G1 and G2/M cell cycle arrest and apoptosis. The percentage of apoptotic cells in PPD-1 treated A549 cells was considerably higher than that in untreated cells (10.06% vs 0.57%, respectively). To further investigate the mechanism of induction of apoptosis by PPD-1, Real time-PCR was used to quantify the expression levels of key apoptotic regulators. Significant overexpression of the effector capsase-3 , pro-apoptotic bax and tumor suppressor gene p53 were noted as compared to untreated cells (7.19 folds, 7.28 folds, and 5.08 folds, respectively). Moreover, PPD-1 inhibited the expression of the anti-apoptotic bcl-2 gene to 0.22 folds. These findings demonstrate that PPD-1 treatment disrupts the Bcl-2/BAX balance in lung cancer cell lines, leading to apoptosis induction possibly through intrinsic mitochondria-dependent pathway. These novel insights elucidate the mechanism of PPD-1 cytotoxicity in lung cancer cell lines and offer a promising therapeutic approach that needs further study. [ABSTRACT FROM AUTHOR]