A Method for Assessing the Risks of Complications in Chemoradiation Treatment of Squamous Cell Carcinoma of the Head and Neck

Background: More than 500,000 new cases of squamous cell carcinoma of the head and neck (SCCHN) are registered annually in the world. 7,036 new cases of the disease were registered in Ukraine during 2018, about 35% of patients did not live even a year from the date of diagnosis as a modern standard for the treatment of patients with inoperable locally advanced SCCHN, chemoradiation treatment in the classical dose fractionation mode with chemo modification with cisplatin is used by specialists. Objective: The objective of this study is to analyze the effectiveness of chemoradiation treatment with cisplatin and 5-fluorouracil in the treatment of patients with SCCHN using modern mathematical models. Methods: During the investigation we assessed the effectiveness of treatment in 108 patients with locally advanced SCCHN (stages III, IVa, IVb). The results of calculating the probabilities of complications were obtained using the method of multivariate classification based on the radial basis ANN. Results: Analyzing the groups with different methods of chemo modification, we can conclude that the method of chrono-modulated radiochemotherapy with 5-fluorouracil and the chemoradiation therapy with cisplatin were almost equal in efficiency, namely 77% and 73.5%, respectively (p=0.35). Conclusion: Using the chemoradiation therapy with 5-fluorouracil in the treatment of patients with low somatic status and elderly patients is more expedient in contrast to the methods using cisplatin. The advantage of selection of mentioned treatment method is also confirmed by the results of calculating the average complication risks using the method of multivariate classification based on a radial-basis neural network.

Stat1 confers sensitivity to radiation in cervical cancer cells by controlling Parp1 levels: a new perspective for Parp1 inhibition

Cervical cancer (CC) is the fourth most common cause of cancer-related death in women. According to international guidelines, a standard treatment for locally advanced cervical cancer (LACC) consists of exclusive concurrent chemoradiation treatment (CRT). However, chemoradioresistance and subsequent relapse and metastasis of cancer occur in many patients, and survival for these women has generally remained poor. Therefore, strategies to overcome resistance are urgently needed. We have recently reported a radiosensitizing effect of the signal transducer and activator of transcription 1 (STAT1) in CC, associated with the control of [Poly(ADP-ribose) polymerase −1] PARP1 levels, a key factor in cell response to DNA damage induced by radiation. Here, we sought to decipher the underlying mechanism of STAT1-mediated control of PARP1, elucidating its role as a radiosensitizer in CC. Functional and molecular biology studies demonstrated that STAT1 may act at both transcriptional and posttranscriptional levels to modulate PARP1 expression in CC cells. In light of these results, we tested the effect of Olaparib in sensitizing CC cells to radiation and investigated signaling pathways involved in the activity observed. Results showed that PARP1 inhibition, at clinically achievable doses, may indeed selectively improve the sensitivity of resistant CC cells to DNA-damaging treatment. The translational relevance of our findings was supported by preliminary results in a limited patient cohort, confirming that higher PARP1 levels are significantly associated with a radioresistant phenotype. Finally, bioinformatics analysis of GEPIA and TCGA databases, demonstrated that PARP1 mRNA is higher in CC than in normal tissues and that increased PARP1 mRNA expression levels are associated with poor prognosis of LACC patients. Overall, our data open new opportunities for the development of personalized treatments in women diagnosed with CC.

Combination ozone therapy as an effective method of radiomodification in chemoradiation treatment of patients with cervical cancer.

e17515 Background: The purpose of the study was to evaluate advantages of combination ozone therapy as an effective factor of radiomodification and radioprotection in the treatment of patients with cervical cancer. Methods: The study included 20 patients with stage IIIb cervical cancer T3бNхM0, the mean age 52 years. Controls (n = 10) received standard chemoradiation therapy; the main group (n = 10) received combination ozone therapy in addition to chemoradiation therapy. Systemic ozone therapy involved intravenous administration of 250 ml ozonized solution of 0.9% sodium chloride, 15 sessions during external beam radiotherapy. Local ozone therapy involved 15-minute instillations into the vagina during brachytherapy. All patients received standard chemoradiation therapy, total irradiation dose to the primary focus 80 Gy, plus weekly cisplatin 40 mg/m2. Results: In the main group, pain and discomfort in the lower abdomen were managed in 20% patients by the 5th session of ozone therapy; 30% - on the 10th day; in 50% - on the 14th day. In the control group, such symptoms in 40% of patients were reduced after 20 days. The main group showed a more rapid regression of tumor infiltration, disappearance of purulent discharge, relief of intoxication syndrome. Manifestations of gastrointestinal toxicity were observed in 10% of the main group and in 100% controls; leukopenia developed in 7 patients in the control group and was not registered in the main group. MRI showed complete clinical regression in 90% in the main group and in 65% in the control group. The treatment was completed within 7 weeks in the main group and 8.5 weeks in the control group. Conclusions: Combination ozone therapy causes a more pronounced antitumor effect, and its radioprotective effects significantly reduce the severity of chemotherapy-induced disorders. It does not aggravate concomitant pathology and shortens the treatment period.

Tactics of managing patients with primarily detected nasopharyngeal neoplasm. Case reports

In 5% of cases in the nasopharynx of an adult can be found a neoplasm with benign or malignant nature. Clinical manifestations of such pathology are next: persistent dysfunction of the auditory tubes, nasalness and postnasal drip syndrome. Endoscopy of the nasopharynx, computed tomography of the sinuses and magnetic resonance imaging of the head are the main diagnostic criteria for detecting neoplasms in this area. The tactics of treatment depends on the dysplasia type of the pathological process and varies from endoscopic one-stage resection to chemoradiation treatment. Using the example of two clinical cases, we will consider an algorithm for diagnosis and treatment the patients.

Nonbacterial Thrombotic Endocarditis Related to Adenocarcinoma of the Uterine Cervix

We report a 66-year-old female patient who presented with acute onset of visual loss with relative afferent pupillary defect, hemineglect, hemihypesthesia, and apraxia. Magnetic resonance imaging of the brain demonstrated different stages of ischemic stroke in different vascular territories, suggesting cardiogenic embolism. Past history was significant for advanced-stage adenocarcinoma of the uterine cervix under chemoradiation treatment. On echocardiogram, vegetation at the aortic valve was observed. With the absence of evidence of infectious endocarditis, diagnosis of nonbacterial thrombotic endocarditis was made, and the patient was treated by long-term anticoagulant. This case is unique in terms of the adenocarcinoma cell type of cervical cancer, which is uncommon and has been rarely reported to be related to nonbacterial thrombotic endocarditis.

Inclusion of economic outcomes in NCI grants: A portfolio analysis.

7047 Background: While new interventions have improved cancer screening, treatment, and survivorship, the costs and other economic impacts of interventions may affect their uptake and availability. It is unknown what proportion of recently-funded National Cancer Institute (NCI) grants include economic outcomes. Methods: We used the NIH Query/View/Report (QVR) System to determine the number of competitive grants funded by NCI 2015-2020 that included economic outcomes. Grants were identified using the NIH Research, Condition, and Disease Categorization (RCDC) category “Cost Effectiveness Research”; 19 RCDC terms/concepts related to economic analyses; and 18 economic phrases searched for in grant titles, abstracts, and specific aims. The specific aims and abstracts of all grants meeting any of these search criteria were reviewed by an NCI scientist to ensure the presence of economic study outcomes. Results: Among over 13,700 competitive grants awarded by NCI 2015-2020, the search identified 149 grants; following abstract/specific aims review, 102 of these grants (0.74% of all grants) included an economic outcome. Most (69 of 102, 67.6%) included cost-effectiveness analysis; 24 included other cost analyses, 7 assessed financial hardship or similar outcomes, and 2 focused on developing economic methods. Among RCDC terms, more than half (53) listed modeling (9 listing Cancer Intervention and Surveillance Modeling Network), 24 randomized controlled trials, 15 QALYs, 11 implementation science, 3 willingness to pay. The most common cancer sites listed were breast (28), lung (23), cervical (19), and colorectal (17) cancer. Almost half (48) mentioned screening and 24 cancer prevention. Risk factors listed included 28 for smoking, 18 HPV, 8 HIV, 8 physical activity, 6 obesity, 4 nutrition. Ten listed treatment efficacy, 6 chemotherapy, 4 radiation therapy, 3 hormone therapy, and 1 chemoradiation. “Treatment as usual” was listed by 16, symptom management 4, and telehealth 4. Survivors were listed for 15, caregivers 3, health disparity 18, rural 15, young adult 4. The majority of grant mechanisms were R01 (76, 74.5%); 3 were R21/R03, 4 other R mechanisms, 7 K awards, 6 U grants, 6 P, F, or L grants. Conclusions: While this search may not have identified all funded NCI grants over the past 5 years involving economic analyses, we found that less than 1% included economic outcomes. Recommendations to assist NCI in supporting health economics research focused on cancer across the entire care spectrum should be considered.