Pharmacogenetic markers of chemotherapy toxicity in gastrointestinal tumors: a preliminary analysis

Aim. To assess the association between the carriage of minor allelic variants of 8 genes that encode key enzymes involved in the metabolism of anticancer drugs (DPYD, GSTP1, MTHFR, UGT1A1) and cell repair (XPC, ERCC1, TYMP, NQO1) and the severity of adverse drug events in patients with common gastrointestinal tumors. Tasks. To study the frequency of minor allelic variants of the DPYD, GSTP1, MTHFR, UGT1A1, XPC, ERCC1, TYMP, NQO1 genes; to assess the frequency and severity of adverse drug events of chemotherapy treatment in the study population. Materials and methods. For the period from October 2020 to April 2021, 56 patients (women 29, men 27) with verified malignant tumors of the gastrointestinal tract were included in a prospective clinical study as a part of the RSF grant No. 20-75-10158. The mean age was 62.311.4 years. Colon cancer was detected in 24 patients, tumors of the esophagus and stomach in 19 patients, tumors of pancreas and biliary tract in 13 patients. First-line palliative chemotherapy was given to 27 patients, adjuvant 19 patients, neoadjuvant 10 patients. All patients had not previously received cytotoxic or radiation treatment. Point nucleotide variants of genes DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, TYMPS, NQO1 were determined by hybridization analysis on biological microchips. Differences in the tolerance of cytotoxic therapy (5-fluorouracil, platinum preparations, irinotecan) depending on the genotype were assessed using Fishers exact test. Results. The average number of chemotherapy courses received was 4.22.6 (112). There was a statistically significant difference in the tolerability of chemotherapy in patients with minor allelic variants of the GSTP1 rs1695 (p=0.03), ERCC1 rs11615 (p=0.01), and UGT1A1 rs8175347 (p=0.003) genes. Conclusion. The use of hybridization analysis on biological microchips to assess allelic variants responsible for the tolerability of cytotoxic therapy is reasonable and requires further prospective assessment.

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Efficacy and safety of ICIs/ICIs combined with chemotherapy vs chemotherapy in advanced gastrointestinal tract cancer: a systematic review and meta-analysis

10.21203/rs.3.rs-376445/v1 ◽

2021 ◽

Author(s):

Xiuqi Fan ◽

Qilong Gao ◽

Lanwei Guo ◽

Yulong Chen ◽

Yicun Han ◽

...

Keyword(s):

Malignant Tumors ◽

Meta Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Gastrointestinal Tumors ◽

Cochrane Library ◽

Efficacy And Safety ◽

Tract Cancer ◽

Significant Difference ◽

Meta Analyses

Abstract Objective: To systematically access the efficacy and safety of ICIs monotherapy or ICIs combined with chemotherapy versus chemotherapy in advanced gastrointestinal cancers. Methods: Retrieved the randomized controlled trials (RCTs) of ICIs or ICIs combined with chemotherapy and chemotherapy in advanced gastrointestinal tumors included in PubMed, Cochrane Library, Embase, and Web of sciences. Meta-analysis was performed using Review Manager 5.3 software. The primary outcomes are overall survival (OS) and progression-free survival (PFS), and secondary outcomes include objective response rate (ORR) and adverse events (AEs).Results: A total of 13 RCTs including 5166 patients with advanced gastrointestinal tumors were included in this meta-analyses. ICIs or ICIs combined with chemotherapy exhibited superior OS (HR: 0.84, 95% CI: 0.76-0.94, P=0.001) compared with chemotherapy. Subgroup analysis shows that the use of anti-PD-1 antibodies significantly benefits OS (HR:0.80, 95%CI:0.70-0.91, P=0.0009). The second-line application of ICIs or ICIs combined with chemotherapy will have more significant OS benefits than chemotherapy ( HR: 0.85, 95%CI: 0.79-0.97, P=0.01). No significant difference was observed in PFS and ORR. The PFS of squamous cell carcinoma seemed to be better (HR:0.72, 95%CI:0.60-0.87, P=0.0005). No significant difference in AEs and grade≥3 AEs. But the incidence of AEs decreased when ICIs monotherapy (RR:0.81, 95%CI:0.66-0.99, P=0.04).Conclusion: For gastrointestinal malignant tumors, patients who received ICIs or ICIs combined with chemotherapy had a superior OS compared with chemotherapy, not at the cost of increased AEs, the proportion of AEs is reduced than chemotherapy while ICIs monotherapy. PFS and ORR are not significantly improved.

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EPID-22. CHARACTERIZATION OF RADIATION-INDUCED MENINGIOMAS IN A BRAIN TUMOR DATABASE

Neuro-Oncology ◽

10.1093/neuonc/noaa215.340 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii83-ii83

Author(s):

Nilan Vaghjiani ◽

Andrew Schwieder ◽

Sravya Uppalapati ◽

Zachary Kons ◽

Elizabeth Kazarian ◽

...

Keyword(s):

African American ◽

Brain Tumor ◽

Radiation Treatment ◽

Latency Period ◽

Data Set ◽

Who Grade ◽

Significant Difference ◽

Radiation Induced ◽

Grade Ii ◽

The Mean

Abstract PURPOSE Radiation-induced meningiomas (RIMs) are associated with previous exposure to therapeutic irradiation. RIMs are rare and have not been well characterized relative to spontaneous meningiomas (SMs). METHODS 1003 patients with proven or presumed meningiomas were identified from the VCU brain tumor database. Chart review classified RIM patients and their characteristics. RESULTS Of the 1003 total patients, 76.47% were female with a mean ± SD age of 67.55 ± 15.50 years. 15 RIM patients were identified (66.67% female), with a mean ± SD age of 52.67 ± 15.46 years, 5 were African American and 10 were Caucasian. The incidence of RIMs was 1.49% in our data set. The mean age at diagnosis was 43.27 ± 15.06 years. The mean latency was 356.27 ± 116.96 months. The mean initiating dose was 44.28 ± 14.68 Gy. There was a significant difference between mean latency period and ethnicity, 258.3 months for African American population, and 405.2 months for Caucasian population (p = 0.003). There was a significant difference between the mean number of lesions in females (2.8) versus males (1.2; p = 0.046). Of the RIMs with characterized histology, 6 (55%) were WHO grade II and 5 (45%) were WHO grade I, demonstrating a prevalence of grade II tumors approximately double that found with SMs. RIMs were treated with combinations of observation, surgery, radiation, and medical therapy. Of the 8 patients treated with radiation, 4 demonstrated response. 8 of the 15 patients (53%) demonstrated recurrence/progression despite treatment. CONCLUSION RIMs are important because of the associated higher grade histology, gender, and ethnic incidences, and increased recurrence/progression compared to SMs. Despite the presumed contributory role of prior radiation, RIMs demonstrate a significant rate of responsiveness to radiation treatment.

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Differences of US-FNA BSRTC class, postoperative pathology, and mutation landscape of thyroid nodules between China and other countries.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3055 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3055-3055

Author(s):

Yuntao Song ◽

Jie Liu ◽

Weiran Wang ◽

Tonghui Ma

Keyword(s):

United States ◽

Thyroid Cancer ◽

Thyroid Nodules ◽

Malignant Tumors ◽

The United States ◽

Braf V600e ◽

Class V ◽

Ras Mutation ◽

First Choice ◽

Significant Difference

3055 Background: Ultrasound and ultrasound-guided fine needle aspiration (US-FNA) are the first choice for judging benign and malignant thyroid nodules. This study will report on the differences of US-FNA BSRTC class, postoperative pathology and mutation landscape of thyroid nodules between China and other countries. Methods: We conducted a prospective study containing 383 FNA samples of thyroid nodules. For most of these FNA samples, genomic DNA and RNA were extracted and sequenced with FSZ-Thyroid NGS Panel V1, and postoperative pathology were followed up. Moreover, we also compared results of this study with those of West China Hospital in China, Yamashita Thyroid Hospital in Japan, and Cleveland Clinic in the United States. Results: Among the 383 FNA samples, the proportions of BSRTC class I to VI were 10.7%, 6.3%, 18.8%, 3.7%, 12.3%, and 48.3% respectively. Compared with study in other countries, the proportion of class II was significantly lower than that in Japan and the United States. Meanwhile, the proportion of class V and VI were significantly higher than the above two countries. Subsequently, 232 thyroid nodules were surgically removed. Postoperative pathology showed that the proportion of malignant tumors (85.3%) was also significantly higher than reported in Japan and the United States. But compared with other studies in China, there was no significant difference. Most of the malignant tumors were papillary thyroid cancer (PTC, 96%), accompanied with 2 follicular thyroid cancer (FTC), 3 medullary cancer (MTC) and 3 anaplastic thyroid cancer (ATC). Compared with study in the United States, the proportion of PTC and FTC were elevated (96% vs. 85.3%) and reduced (1% vs. 9.3%) respectively. At last, we also analysis the mutation landscape of 180 malignant tumors. Compared with TCGA study, the frequency of BRAF V600E in PTC in our study was significantly higher than that of TCGA (73.3% vs. 58%), and the frequency of RAS mutation was significantly lower (1.2% vs. 12.6%). And compared with an institutional experience of ThyroSeq v3 for Bethesda III and IV at the University of Pittsburgh Medical Center, the frequency of BRAF V600E and RAS mutation in Bethesda III-IV malignant tumors was also significantly higher (45.8% vs. 1.4%) and lower (8.3% vs. 47.1%). Conclusions: There were significant differences in BSRTC class and postoperative pathology between China and other countries, such as Japan and the United States. The possible reasons included that the indications for FNA in China were different. For example, most of patients who underwent FNA in this study had suspicious clinical/ultrasound features. So the proportion of BSRTC class V and VI as well as the malignant rate were elevated. On the other hand, more BRAF V600E and less RAS mutations were detected in malignant tumors in this study which might result from racial differentiation and discrepancy in proportion of PTC and FTC.

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Effect of Surgical Mask on Setup Error in Head and Neck Radiotherapy

Technology in Cancer Research & Treatment ◽

10.1177/1533033820974021 ◽

2020 ◽

Vol 19 ◽

pp. 153303382097402

Author(s):

Yi Ding ◽

Pingping Ma ◽

Wei Li ◽

Xueyan Wei ◽

Xiaoping Qiu ◽

...

Keyword(s):

Head And Neck ◽

Radiation Treatment ◽

Virus Disease ◽

T Test ◽

Setup Error ◽

Setup Errors ◽

Significant Difference ◽

The Mean ◽

Head And Neck Radiotherapy ◽

Head Neck

Purpose: With the widespread prevalence of Corona Virus Disease 2019 (COVID-19), cancer patients are suggested to wear a surgical mask during radiation treatment. In this study, cone beam CT (CBCT) was used to investigate the effect of surgical mask on setup errors in head and neck radiotherapy. Methods: A total of 91 patients with head and neck tumors were selected. CBCT was performed to localize target volume after patient set up. The images obtained by CBCT before treatment were automatically registered with CT images and manually fine-tuned. The setup errors of patients in 6 directions of Vrt, Lng, Lat, Pitch, Roll and Rotation were recorded. The patients were divided into groups according to whether they wore the surgical mask, the type of immobilization mask used and the location of the isocenter. The setup errors of patients were calculated. A t-test was performed to detect whether it was statistically significant. Results: In the 4 groups, the standard deviation in the directions of Lng and Pitch of the with surgical mask group were all higher than that in the without surgical mask group. In the head-neck-shoulder mask group, the mean in the Lng direction of the with surgical mask group was larger than that of the without surgical mask group. In the lateral isocenter group, the mean in the Lng and Pitch directions of the with surgical mask group were larger than that of the without surgical mask group. The t-test results showed that there was significant difference in the setup error between the 2 groups ( p = 0.043 and p = 0.013, respectively) only in the Lng and Pitch directions of the head-neck-shoulder mask group. In addition, the setup error of 6 patients with immobilization open masks exhibited no distinguished difference from that of the patients with regular immobilization masks. Conclusion: In the head and neck radiotherapy patients, the setup error was affected by wearing surgical mask. It is recommended that the immobilization open mask should be used when the patient cannot finish the whole treatment with a surgical mask.

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EFFECT OF MINDFULNESS INTERVENTION ON THE INTENSITY OF PAIN IN NASOPHARINGEAL CANCER PATIENTS UNDERGOING RADIATION TREATMENT

Belitung Nursing Journal ◽

10.33546/bnj.128 ◽

2018 ◽

Vol 4 (2) ◽

pp. 195-201

Author(s):

Anna Jumatul Laely ◽

Awal Prasetyo ◽

Chandra Bagus Ropyanto

Keyword(s):

Cancer Patients ◽

Radiation Treatment ◽

Nasopharyngeal Cancer ◽

Psychological Trauma ◽

Control Group ◽

Intensity Level ◽

Control Group Design ◽

Mindfulness Intervention ◽

Significant Difference ◽

Before And After

Background: Physical responses that occur in patients with nasopharyngeal cancer are the emergence of pain due to the effects of treatment. The problem of pain in these patients at the stage of treatment remains critical to solve because it can cause comorbidity, psychological trauma and mortality. Mindfulness intervention is considered useful in transforming consciousness into the stage of acceptance.Objective: This study aims to determine the effect of mindfulness intervention on the intensity of pain in nasopharyngeal cancer patients undergoing radiation treatment.Methods: This was a quasy-experimental study with pretest posttest control group design. Thirty patients were selected using consecutive sampling, which divided into experiment and control group. Visual Analogue Scale (VAS) was used to measure pain. Each respondent received mindfulness intervention for 6 sessions, divided into 3 meetings. Paired t-test was used for data analysis.Results: The results showed a significant reduction of pain from 4.12 (moderate pain) to 3.06 (mild pain) in the experiment group. There was a significant difference in pain level before and after mindfulness intervention (p= 0.001).Conclusion: Mindfulness is effective in reducing pain intensity level in nasopharyngeal cancer patients undergoing radiation therapy.

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Use of F-18 FDG PET/CT Through Delayed Diuretic Imaging for Preoperative Evaluation of Upper Urinary Tract-Occupying Lesions

Frontiers in Oncology ◽

10.3389/fonc.2021.699801 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jun Wang ◽

Liang Zhang ◽

Jian Guo Wu ◽

Ruohua Chen ◽

Jia lin Shen

Keyword(s):

Urinary Tract ◽

Fdg Pet ◽

Malignant Tumors ◽

Upper Urinary Tract ◽

Characteristic Analysis ◽

Patient Age ◽

Patient Âgé ◽

Pet Ct ◽

Significant Difference ◽

Fdg Pet Ct

PurposeTo evaluate the value of F-18 FDG PET/CT in the differentiation of malignant and benign upper urinary tract-occupying lesions.Patients and Methods64 patients with upper urinary tract-occupying lesions underwent F-18 FDG PET/CT at RenJi Hospital from January 2015 to February 2019 in this retrospective study. Of the 64 patients, 50 patients received nephroureterectomy or partial ureterectomy; 14 patients received ureteroscopy and biopsy. The comparisons of PET/CT parameters and clinical characteristics between malignant and benign upper urinary tract-occupying lesions were investigated.ResultsOf the 64 patients, 49 were found to have malignant tumors. Receiver operating characteristic analysis determined the lesion SUVmax value of 6.75 as the threshold for predicting malignant tumors. There were significant associations between malignant and benign upper urinary tract-occupying lesions and SUVmax of lesion (P<0.001), lesion size (P<0.001), and patient age (P=0.011). Multivariate analysis showed that SUVmax of lesion (P=0.042) and patient age (P=0.009) as independent predictors for differentiation of malignant from benign upper urinary tract-occupying lesions. There was a significant difference in tumor size between the positive (SUVmax >6.75) and negative (SUVmax ≤6.75) PET groups in 38 of the 49 patients with malignant tumors.ConclusionThe SUVmax of lesion and patient age is associated with the nature of upper urinary tract-occupying lesions. F-18 FDG PET/CT may be useful to distinguish between malignant and benign upper urinary tract-occupying lesions and determine a suitable therapeutic strategy.

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The Connection of the Level of Estradiol in Serum and Obesity with the Endometrial Bleeding in Postmenopausal Women

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.079 ◽

2019 ◽

Vol 7 (1) ◽

pp. 88-91 ◽

Cited By ~ 1

Author(s):

Valentina Tofiloska ◽

Maria Krstevska ◽

Ana Daneva-Markova ◽

Viktorija Jovanovska

Keyword(s):

Endometrial Cancer ◽

Statistical Significance ◽

Abnormal Uterine Bleeding ◽

Control Group ◽

Prospective Clinical Study ◽

Study Group ◽

Gynecology And Obstetrics ◽

Increased Risk ◽

Significant Difference ◽

Post Menopausal

BACKGROUND: Postmenopausis is a period that begins one year after the last menstrual period. Abnormal uterine bleeding could be of different origins. AIM: This study aimed to determine the association of serum estrogen hormone levels and obesity with the occurrence of endometrial bleeding in post-menopausal women. MATERIAL AND METHODS: Prospective clinical study involving 120 postmenopausal patients treated at the University Clinic for Gynecology and Obstetrics-Skopje, divided into two groups: control and study. The control group consisted of 40 postmenopausal patients without endometrial bleeding, hospitalised and operated due to urogenital pathology. The study group consisted of 80 patients with endometrial bleeding who were divided into three subgroups according to the thickness of the endometrium: from 5-8 mm, 8-11 mm and above 11 mm. In all subjects, estradiol and BMI was determined. RESULTS: Estradiol levels were statistically higher in the study group compared to control while statistically significant difference among the three subgroups according to the thickness of the endometrium about the levels of estradiol in blood is not found. About BMI, the results showed that there was no statistical significance between the two examined groups. CONCLUSION: Patients with endometrial bleeding have increased levels of estradiol and are at increased risk of endometrial cancer about controls, the likelihood of endometrial cancer significantly increases by 1,108 times.

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Тhe effect of cancer patients’ positioning accuracy during radiation therapy sessions using medical linear electron accelerators on the parameters of their individual 3D dose distribution

Doklady BGUIR ◽

10.35596/1729-7648-2020-18-7-31-39 ◽

2020 ◽

Vol 18 (7) ◽

pp. 31-39

Author(s):

M. N. Piatkevich ◽

E. V. Titovich ◽

G. V. Belkov

Keyword(s):

Radiation Therapy ◽

Radiation Treatment ◽

Malignant Tumors ◽

Rapid Development ◽

Treatment Session ◽

Malignant Neoplasms ◽

Horizontal Position ◽

Individual Dose ◽

Dose Distributions ◽

The Impact

Due to the rapid development and further improvement of radiation treatment technologies oncologists have an opportunity to precisely deliver individual dose distributions to the tumor, minimizing the doses obtained by critical organs and healthy structures. For the correct and successful application of these complex methods of radiation therapy, it was necessary to enforce the requirements for the technical and dosimetric parameters of the radiotherapy equipment. The purpose of the research is to determine the magnitude of the possible error for patients’ positioning during their radiotherapy treatments using medical linear accelerators by modeling the impact of the patient’s body on the treatment couch. To determine the values of a possible error, the authors have considered the design and characteristics of a typical treatment couch, developed a model of the “average” patient’s body (phantom), which allowed changing the load to the treatment couch with a step of 1 kg. The position parameters of treatment couches were determined for the main types of localization of radiation therapy for malignant tumors: head and neck tumors, breast tumors and pelvic tumors. Numerical values of the treatment coach deviations from prescribed horizontal position were experimentally established for a load from 40 to 180 kg for a treatment couch used at the N.N. Alexandrov National Cancer Centre of Belarus. Based on the obtained experimental data, the necessity to correct the patient's treatment conditions at the stage of treatment planning were confirmed in order to ensure the delivery accuracy of individual dose distributions as required by the radiation therapy protocols. Authors stated that an analysis of the dependence of the deviations in the dose delivered to the patients on the deviation of the radiotherapy table from its horizontal position should be carried out for each radiotherapy table used in clinical practice. The development and implementation of a mechanism that will allow considering this information when choosing the parameters of the patient’s treatment session and prescribing the dose for any localization of malignant neoplasms is needed.

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Effects of Clinicopathological Characteristics on the Survival of Patients Treated with PD-1/PD-L1 Inhibitor Monotherapy or Combination Therapy for Advanced Cancer: A Systemic Review and Meta-Analysis

Journal of Immunology Research ◽

10.1155/2020/5269787 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Yuhan Wei ◽

Yongfu Li ◽

Qi Du ◽

Xinyi Peng ◽

Jiangtao Jin ◽

...

Keyword(s):

Liver Metastasis ◽

Combination Therapy ◽

Survival Benefit ◽

Malignant Tumors ◽

Smoking Status ◽

Systemic Review ◽

Wild Type ◽

Risk Of Death ◽

Significant Difference ◽

Ecog Ps

Background. PD-1/PD-L1 inhibitors have made unprecedented progress in the treatment of cancer. Methods. A systemic search was conducted for randomized controlled trials that compared PD-1/PD-L1 inhibitor monotherapy or combination therapy with nonimmunotherapy. Hazard ratios (HRs) of overall survival (OS) according to the sex, age, ECOG PS, smoking status, liver metastasis, PD-L1 expression, EGFR, and KRAS status of patients were analyzed. Results. Totally, 13 studies with monotherapy and 5 with combination regimens were included, and the pooled HRs of OS were 0.74 ( P < 0.001 ) and 0.64 ( P < 0.001 ), respectively. EGFR wild-type patients could benefit from immunotherapy monotherapy (HR, 0.77; P < 0.001 ) while those of the mutant type had no survival benefit (HR, 1.11; P = 0.54 ), and the difference was statistically significant (interaction, P = 0.005 ). KRAS wild-type patients had no survival benefit from monotherapy (HR, 0.89; P = 0.49 ). For combination therapy, both male and female derived benefits but female had a significantly reduced risk of death (HR, 0.45; P < 0.001 ) compared with male (HR, 0.73; P < 0.001 ; interaction, P = 0.004 ). Nonsmokers derived more survival benefits from combination therapy (HR, 0.29; P < 0.001 ) than smokers (HR, 0.63; P = 0.001 ; interaction, P = 0.02 ). No significant difference was found between age, ECOG PS, liver metastasis, PD-L1 expression, and OS of both PD-1/PD-L1 inhibitor monotherapy and combination therapy. Conclusions. Both PD-1/PD-L1 inhibitor monotherapy and combination therapy significantly prolonged the OS of patients with advanced malignant tumors. EGFR status for monotherapy and sex and smoking status for combination therapy were important predictors of survival benefits.

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Number of Nucleoli and Nucleolar Organizer Regions per Nucleus and Nucleolus — Prognostic Value in Canine Mammary Tumors

Veterinary Pathology ◽

10.1177/030098589603300507 ◽

1996 ◽

Vol 33 (5) ◽

pp. 527-532 ◽

Cited By ~ 10

Author(s):

M. BratuliĆ ◽

Ž GrabareviĆ ◽

B. ArtukoviĆ ◽

D. Capak

Keyword(s):

Malignant Tumors ◽

Organizer Region ◽

Nucleolar Organizer Region ◽

Nucleolar Organizer ◽

Staining Technique ◽

Mammary Tumors ◽

World Health ◽

Nucleolar Organizer Regions ◽

Canine Mammary Tumors ◽

Significant Difference

Twenty-eight canine mammary tumors were evaluated for histopathologic classification as recommended by the World Health Organization and silver-binding nucleolar organizer region (AgNOR) and nucleolus counts. Samples of surgically excised tumors and tumors taken at necropsy were fixed in neutral formalin, embedded in paraffin, and cut into 1-3-μm-thick sections. Two sections were taken from each tumor: one was stained with hematoxylin and eosin and the other was treated with the silver staining technique for the demonstration of AgNORs. After histopathologic classification, the number of nucleoli and the number of AgNORs/nucleus and AgNORs/nucleolus were determined. Statistical analysis (Student's t-test) showed a significant difference in the mean number of nucleoli ( P < 0.005), mean number of AgNORs/nucleolus ( P < 0.001), and mean number of AgNORs/nucleus ( P < 0.005) between benign and malignant canine mammary tumors. There was no significant differences between metastatic and nonmetastatic malignant tumors.

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