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Table of Contents
Oct-Dec 2019
Volume 15 | Issue 6
Page Nos. 1201-1425
Online since Tuesday, December 24, 2019
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ORIGINAL ARTICLES
Phase I study on pegylated liposomal doxorubicin in combination with docetaxel for patients with platinum-resistant or partially platinum-sensitive epithelial ovarian cancer: The Kansai Clinical Oncology Group study
p. 1201
Kensuke Hori, Kimihiko Ito, Kentaro Kuritani, Shiho Kuji, Naoto Furukawa, Hiroshi Tsubamoto, Atsushi Arakawa
DOI
:10.4103/jcrt.JCRT_742_16
PMID
:31898647
Context:
In platinum-resistant ovarian cancer, single-agent chemotherapy is recommended for the reduction of adverse events. However, in clinical practice, some patients can tolerate drug-specific adverse events.
Aims:
We assessed the safety of pegylated liposomal doxorubicin (PEG-LD) and docetaxel regimen in the first cycle of ovarian cancer.
Settings and Design:
We performed a phase I study to evaluate the combination therapy of PEG-LD and docetaxel.
Materials and Methods:
We recruited five patients with recurrent ovarian cancer within 12 months of first-line platinum-based chemotherapy. All patients had measurable disease severity. PEG-LD and docetaxel were intravenously administered on day 1 and every 21 days using three dose levels: 25 mg/m
2
PEG-LD and 50 mg/m
2
docetaxel; 30 mg/m
2
PEG-LD and 50 mg/m
2
docetaxel; and 30 mg/m
2
PEG-LD and 60 mg/m
2
docetaxel.
Statistical Analysis Used:
We defined the maximum tolerated dose of the combination therapy based on the modified Fibonacci method.
Results:
Five patients were enrolled in this study. The median treatment-free interval was 5.5 months. Two dose-limiting toxicities (Grade 4 neutropenia) were observed in two patients. One complete response, one partial response, one stable disease, and two progressive disease cases were observed. The overall response rate was 2/5, and the disease control rate was 3/5. The median overall survival was 7.4 months.
Conclusions:
We determined that 25 mg/m
2
of PEG-LD and 50 mg/m
2
of docetaxel were safe and effective doses. This preliminary efficacy and safety data should be further investigated in a Phase II trial.
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Implications of bladder volume on target coverage and dose to critical structures during high dose rate intracavitary brachytherapy for cervical cancer: A dosimetric study
p. 1207
Rahil B Patel, Janaki Manur Gururajachar, T Revathy
DOI
:10.4103/jcrt.JCRT_253_19
PMID
:31898648
Background:
The distension of the bladder during intracavitary brachytherapy (ICBT) affects the applicator position and in turn the dose to tumour and normal structures.
Aims and Objectives:
To quantify the changes in the dose to high risk clinical target volume (HRCTV) and organs at risk (OARs) due to bladder filling.
Methods and Materials:
In this prospective study, dosimetric parameters of 40 cervical cancer patients treated with (ICBT) were studied. Two sets of CT images with empty and bladder filled with 100 ml of contrast were used for analysis of doses to HRCTV and organs at risk OARs. The distance between posterior wall of the bladder and reference point on the flange was recorded in X,Y and Z.
Results:
Target coverage between bladder distension and empty bladder was 84.15 vs 84.85 % (P=0.003) respectively. Mean dose to bladder was 1.57vs 2Gy (P=0.000), median dose was 6 vs7.25Gy (P=0.000), D5cc was 3.94 vs 4.17 Gy (P=0.103) and D2cc was 4.5 vs 5 Gy (P=0.01) respectively. The doses to rectum was D2cc - 3.76 vs 4.07Gy (P=0.000), Sigmoid was D2cc - 2.18 vs 2.43Gy (P=0.005), bowel D2cc was 2.81 vs 3.43Gy (P=0.000). The mean distance of the posterior wall of the bladder from reference point was 0.042 vs -0.079cm (P=0.391) in the X-axis, -0.618 vs -0.630cm (P=0.603) in Z-axis and 0.19 vs 0.26cm (P=0.009) in the Y-axis between two status of the bladder.
Conclusions:
Smaller volume of bladder receive higher dose and larger volumes a lower dose with bladder distension, while dose is same for rectum, sigmoid and bowel. The applicators shift posteriorly when the bladder is distended.
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Dosimetric comparison of
60
Co and
192
Ir high dose rate source used in brachytherapy treatment of cervical cancer
p. 1212
Arvind Kumar Shukla, Pawan Kumar Jangid, Vikram Singh Rajpurohit, Atul Verma, Suresh Kumar Dangayach, Vaibhav Gagrani, Narendra Kumar Rathore
DOI
:10.4103/jcrt.JCRT_372_19
PMID
:31898649
Purpose:
The study purpose included dosimetric comparison of cobalt 60 (
60
Co) and iridium 192 (
192
Ir) high dose rate (HDR) source used in brachytherapy treatment of cervical cancer.
Materials and Methods:
Computed tomography (CT) scans for 15 patients of carcinoma of uterine cervix using 3-mm slice thickness were considered for the study The contouring of high-risk clinical target volume (HRCTV), bladder, and rectum on CT images was done as per the GEC ESTRO guidelines with the help of magnetic resonance imaging images in the treatment planning system. All parameters were kept the same for
60
Co (3.5 mm active length, 0.5 mm active dia, Bebig) and
192
Ir (3.5 mm active length, 0.6 mm active dia, Bebig) HDR source with 2.5-mm step size and dose prescription to Point A. As per the International Commission on Radiation Unit (ICRU)-89 guidelines, the dose–volume parameters such as D
50
(Gy), D
90
(Gy), and D
98
(Gy) for HRCTV and D
0.1cc
(Gy), D
1cc
(Gy), D
2cc
(Gy), and D
5cc
(Gy) to the bladder and rectum were calculated for both the HDR sources.
Results:
The difference in dose–volume histogram parameters such as D
50,
D
90,
and D
98
of HRCTV was 3.19%, 1.13%, and 0.50%, respectively, for the two radioisotopes. The difference in dose values of D
0.1cc
, D
1cc
, D
2cc
, D
5cc
, and ICRU reference points of bladder was –0.58%, –0.67%, –0.99%, –0.94%, and –1.75%, respectively. On the other hand, dose difference for D
0.1cc
, D
1cc
, D
2cc
, D
5cc
, and ICRU reference points of rectum was 0.67%, 0.26%, 0.56%, 0.63%, and –0.33%, respectively.
Conclusions:
The present study results show that all the dose parameters of HRCTV, bladder, and rectum with
60
Co were comparable with those of
192
Ir HDR source. The isodose distribution is more bulge out for
60
Co in cranial-caudal direction compared to that of
192
Ir. However, these differences can be reduced by treatment planning optimization techniques. The clinical plan evaluation in each slice and plane is necessary to explore the logistic and financial benefits of miniaturized
60
Co source over
192
Ir HDR source.
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Baicalein suppresses the proliferation of human cervical cancer cells via Notch 1/Hes signaling pathway
p. 1216
Hu Lian, Yuan Hui, Tang Xiaoping, Tang Wei, Xia Jiyi, Yu Xiaolan
DOI
:10.4103/0973-1482.204899
PMID
:31898650
Background:
Baicalein is an active compound extracted from the roots of Scutellaria baicalensis georgi, which is widely and traditionally used in the anticancer therapy. Notch signaling pathway is usually abnormally activated in kinds of human cancers. The aim of the present study is to investigate the antitumor effects of baicalein in human cervical cancer and explore whether baicalein treatment affects notch signaling pathway in human cervical cancers.
Materials and Methods:
Cervical cancer cells were treated with increasing concentrations of baicalein for 24, 48, and 72 h, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine cell viability of cervical cancer cells. The apoptosis rate was determined by FACS assay. Furthermore, the molecular mechanism was investigated. The expression levels of Notch 1, Notch 2, Notch 3, hairy enhancer of split-1 (Hes-1), and Hes-5 were determined by western blotting analysis.
Results:
MTT assay results revealed that baicalein inhibited cell proliferation of HeLa cells and SiHa cells in a time- and dose-dependent manner. The data from FACS assay demonstrated that baicalein-induced cell apoptosis of cervical cancer cells at the final concentration of 100 μM for 24 h. Furthermore, baicalein treatment downregulated Notch 1/Hes-1, Hes-5 signaling pathway, and there was no obvious change on the expression of Notch 2 and Notch 3.
Conclusion:
Baicalein inhibited the proliferation of human cervical cancer cells via Notch 1/Hes signaling Pathway. The study would provide some new clues in the clinical therapy of human cervical cancers.
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Establishment of a drug-resistant human cervical cancer cell line and research on its drug-resistance
p. 1221
Haiyan Wang, Yuanfang Zhu, Chenyuan Hao, Jing Fan, Yun Liu, Yifeng Wang
DOI
:10.4103/0973-1482.204900
PMID
:31898651
Aims:
To investigate the differences and international connections between the human cervical cancer cell line (HeLa cells) and the Taxol-resistant HeLa cell line (HeLa/Taxol).
Materials and Methods:
As parental cells, HeLa cells were cultured in stepwise escalating concentration of Taxol from 0.01 μg/ml (11.7 × 10
−9
mol/L) to 0.5 μg/ml (585 × 10
−9
mol/L). The drug resistance of HeLa/Taxol cells was detected by methyl-thiazolyl-tetrazolium assay. Real time-polymerase chain reaction (RT-PCR) was conducted to detect the messenger RNA levels of drug resistance genes and apoptosis-related genes. The proteins levels were detected through immunofluorescence and Western blot.
Results:
Compared with parental HeLa cells, HeLa/Taxol with Taxol resistance had the following biological characteristics: first, they had a lower growth velocity; second, the expression of P-glycoprotein and glutathione S-transferases was significantly increased; Third, the expression of antiapoptotic protein Bcl-2 and apoptosis inhibitor protein survivin was prominently increased.
Conclusions:
The drug-resistance in HeLa/Taxol is mainly associated with the high expression of multidrug resistance genes, antiapoptotic protein Bcl-2, and apoptosis inhibitor protein survivin as an important reason for the failure of chemotherapy of tumor tissue.
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Neutrophil-to-lymphocyte ratio and platelet count as prognostic factors in ovarian malignancies
p. 1226
Rosekeila Simões Nomelini, Ana Flávia Carrijo Chiovato, Fernanda Beatriz Ferreira Abdulmassih, Rafael de Carvalho da Silva, Beatriz Martins Tavares-Murta, Eddie Fernando Candido Murta
DOI
:10.4103/jcrt.JCRT_304_17
PMID
:31898652
Objective:
The objectives of the present study were to demonstrate the influence of neutrophils, platelets, and neutrophil–lymphocyte ratio (NLR) in the ovarian cancer prognosis and to compare these parameters with benign ovarian neoplasms.
Materials and Methods:
Records of patients underwent surgery for ovarian cysts were evaluated. There were 72 malignant neoplasms and 213 benign neoplasms. Age, parity, histologic type, tumor stage, type of surgery performed, chemotherapy, disease-free survival, serum levels of tumor markers, neutrophils, lymphocytes, platelets, and NRL were recorded. The Mann-Whitney, the Chi-square test and multiple linear regression were used. A P-value < 0.05 was established as the significance level.
Results:
Higher values of platelets, neutrophils, and NLR were found in malignant tumors (
P
= 0.0132,
P
= 0.0208, and
P
< 0.0001, respectively), while lymphocytes values were higher in benign group (
P
< 0.0001). Preoperative platelet count 300,000/mm3 was related to less aggressive histological types (
P
= 0.0148). NLR <3 was related to the initial stages (
P
= 0.0053), and patients with disease-free survival >24 months had most often neutropenia during chemotherapy (
P
= 0.0482). After multivariate analysis, platelets, NLR, and serum levels of CA15.3 were considered independent variables related to tumor staging (
P
= 0.028,
P
= 0.028, and
P
= 0.035, respectively).
Conclusion:
NLR and serum levels of platelets may represent potential prognostic factors in ovarian cancer, and they may also serve as therapeutic targets in the future treatment strategies.
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Preoperative predictors of pelvic and para-aortic lymph node metastases in cervical cancer
p. 1231
Varol Gulseren, Mustafa Kocaer, Ozgu Gungorduk, Isa Aykut Ozdemir, Mehmet Gokcu, Emre Merter Mart, Muzaffer Sanci, Kemal Gungorduk
DOI
:10.4103/jcrt.JCRT_467_17
PMID
:31898653
Aim:
This study investigated potential preoperative predictors of pelvic lymph node (PLN) and para-aortic LN (PaLN) involvement in cervical cancer (CC).
Materials and Methods:
This study retrospectively analyzed 283 patients diagnosed with early (stage IA1–IIA) CC who underwent retroperitoneal LN dissection between January 1992 and February 2015. Several risk factors that are believed to influence PLN and PaLN involvement in CC were analyzed as follows: age >50 years, lymphovascular space invasion (LVSI), tumor size ≥2 cm, hemoglobin <12 g/dL, and nonsquamous cell histologic type.
Results:
LVSI (odds ratio [OR] = 11.3, 95% confidence interval [CI] = 5.2–24.3) and tumor size (OR = 3.2, 95% CI = 1.4–7.2) were independent predictors of PLN involvement. None of the factors predicted PaLN involvement in a regression analysis. However, all nine patients who had PaLN involvement also had PLN involvement.
Conclusion:
LVSI and tumor size independently increase the risk of PLN involvement.
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The determination of the knowledge level and behavior of Turkish women from various occupations about human papillomavirus, cervical cancer, and pap smear test
p. 1235
Vildan Savas Cimke, Gulay Borekci
DOI
:10.4103/jcrt.JCRT_1195_16
PMID
:31898654
Background:
Cervical cancer is one of the most common types of cancer among women. Early diagnosis and effective treatment are possible with Pap smear test. However, women should be informed about human papilloma virus (HPV), cervical cancer, and Pap smear test to protect against cervical cancer.
Aim:
The aim of this study is to identify knowledge level and behavior of women from various occupations, who reside in a city in the south of Turkey, about HPV, cervical cancer, and Pap smear test.
Materials and Methods:
The study was conducted with 753 women consisting of 228 nurses, 28 doctors, 135 teachers, 20 academicians, 21 policewomen, and 321 homemakers. The data were collected with face-to-face interview method using survey form and attitude scale related to early diagnosis of cervical cancer.
Results:
Of the women whose age average is 34.7 ± 7.51, 79% are married, 52.9% have middle income, 62.5% live in towns, and 58.6% are primary school graduates. It was determined that 69.2% of these women had gynecological examination, 27.8% had Pap smear test, and 1.3% had HPV vaccination. About 59.5% of these women stated not having heard of HPV, 61.3% of HPV vaccination, and 41.9% that HPV causes cervical cancer. Those women who have a good education and income level and who live in the city are found to have higher knowledge levels of HPV, HPV vaccination, Pap smear test, and cervical cancer (
P
< 0.05). Among the occupational groups, it was determined that the nurses are the ones who have least gynecological examination had and the doctors are the ones who have the most number of Pap smear tests had. It was found that average point that women got from the attitude scale of early diagnosis of cervical cancer was 101.91 ± 10.77 that the doctors and nurses had the highest points, 105.29 ± 11.65 and 103.15 ± 9.92, respectively, and that police officers had the lowest points by 93.42 ± 16.50.
Conclusion:
It was determined that the knowledge level and attitudes of the participant women about HPV, cervical cancer, and Pap smear test were insufficient.
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Presentation of a matrix-based method to calculate dose distribution in brachytherapy with photon-emitting sources
p. 1245
Mahdi Ghorbani, Azam Mozaffari, Hossein Akbari-Lalimi
DOI
:10.4103/jcrt.JCRT_1274_16
PMID
:31898655
Aim of Study:
The report of the task group number 43(TG-43) of AAPM has been known as the most common method to obtain the dose distribution around brachytherapy sources. The error caused by independent obtaining and rounding and combinational error caused by algebraic operations of each TG-43 dosimetry parameters increase the total error in the calculation of the dose distribution around the brachytherapy sources. The aim of the present study is to present and evaluate a matrix-based approach for simplifying and reducing calculation errors.
Materials and Methods:
In this study, the simulation method with MCNPX code was used to obtain the dose distribution. Four sources were simulated, and the dose matrix around these sources was obtained. Finally, the dose distribution obtained from the matrix-based method was compared with the dose distribution obtained from the method of TG-43 report.
Results:
There is little difference between the values obtained from the two methods in some points. Absolute mean differences between the values obtained by these two methods were 1.4% for the
60
Co, 3.52% for the
137
Cs, 2.67% for the
192
Ir, and 2.42% for the
103
Pd sources. The advantage of the matrix-based method is its simple computing process and less computation time.
Conclusion:
Considering that the comparison of brachytherapy sources is not raised in calculations of treatment planning systems and also considering the more uncertainty in the calculation of the dose distribution in TG-43 method, it is recommended that dose distribution obtained from matrix-based method be used as input for treatment planning systems.
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Interdigitated versus sequential high-dose-rate intracavitary brachytherapy with external beam radiotherapy in locally advanced carcinoma cervix
p. 1254
Nawed Alam, Mohammad Akram, Shahid Ali Siddiqui, M A Bilal Hussain
DOI
:10.4103/jcrt.JCRT_301_17
PMID
:31898656
Aims:
To decrease overall treatment time (OTT) and to compare the clinical outcome of interdigitated high-dose-rate intracavitary brachytherapy (HDRICBT) versus sequential HDRICBT with external beam radiotherapy (EBRT) in the treatment of locally advanced carcinoma cervix.
Methods:
Eighty-two patients with histologically confirmed carcinoma of the cervix, untreated International Federation of Gynecology and Obstetrics Stage IIB–IIIB, were included and randomized into two groups. The study group received EBRT 50 Gy/25 fractions with interdigitated HDRICBT 8 Gy/fraction weekly a total of three fractions. Patients in the control group received EBRT 50 Gy/25 fractions with sequential HDRICBT 8 Gy/fraction weekly a total of three fractions. At the end of the study, results of both groups compared in terms of OTT, acute and late toxicities, and response to therapy clinically.
Results:
A total of 82 patients were enrolled 41 in each arm. Seventy-two patients completed treatment and were analyzed. Mean OTT in study group and control group was 40 and 60 days, respectively. The median follow-up duration was 10 months (3–18). Most of the acute and late toxicities were of Grade 1 and 2 type and comparable in both study and control groups. Treatment interruption due to treatment-related toxicity was slightly higher in the study group than the control group, but it was statistically insignificant. Os negotiability was not found to be a limiting factor for interdigitated HDRICBT.
Conclusion:
Interdigitated HDRICBT has equivalent response and toxicities as sequential HDRICBT with the advantage of significant reduction in OTT.
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Nodal metastasis of cervix carcinoma- As a probable cause of bone erosion
p. 1260
Sonal Sethi, Vidyasagar Ramalingam, Mukesh Yadav, Sanjay Thulkar
DOI
:10.4103/jcrt.JCRT_374_18
PMID
:31898657
Introduction:
Carcinoma of cervix is a common gynaecological malignancy and remains the third most common cancer in developing countries. While nodal metastases are common in cervical cancer, major sites of the less common haematogenous metastases include lung, liver and bones. Bone involvement in cases of carcinoma of cervix is low and the estimates range from 0.8-16 % according to various series.Several patterns of bone involvement are observed in cases of carcinoma of cervix including, (1) direct extension into bone, either from the parametrial extensions of the primary or recurrent pelvic tumor, (2) direct extension into adjacent bone from the pelvic or distant lymph node metastasis (3) regional or systemic haematogenous metastasis to bones.
Aims:
To evaluate the pattern of metastases in patients of carcinoma of uterine cervix, with particular emphasis on the pattern of bone involvement on contrast enhanced CT.
Settings and Design:
Retrospective study.
Materials and Methods:
This was a retrospective study, where we reviewed the hospital records and data of patients of cervical cancer who underwent contrast enhanced CT (CECT) of the chest and abdomen over a period of one year between January and December 2016. A total of 100 patients of carcinoma cervix were included. CT images were reviewed by two experienced radiologists. The bony erosion due to pelvic mass or lymphadenopathy was classified as subtle or gross.
Results:
Bone involvement was seen in 11 out of 100 cases (11% cases). Among 13 cases direct bone involvement by the pelvic mass/recurrence and metastatic lymph nodes (8/11; 72.7%) was slightly more common than thehematogenous bone metastasis (5/11; 45.4% cases). Among the direct bone involvement direct erosion of the underlying bone by the nodal metastasis (6/8; 75%) was twice more common than the direct bone involvement by the pelvic mass/recurrence(2/8; 25%).
Conclusions:
Direct bone involvement by erosion of adjacent bone by nodal metastasis is the most common mechanism of bone involvement in cases of carcinoma of cervix signifying the high propensity of lymph nodal deposits to erode the underlying bone. This finding of direct bone erosion is not seen in any other gynaecological malignancy and should be promptly looked for in all cases of carcinoma of cervix.
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The role of syndecan-1 during endometrial carcinoma progression
p. 1265
Ozgen Arslan Solmaz
DOI
:10.4103/jcrt.JCRT_364_17
PMID
:31898658
Aim:
Syndecan-1 (CD138) has most extensively been studied and correlated with many types of cancers. CD138 is mainly expressed in epithelial cells and plasma cells. Quite a few previous studies have called attention to the expression status of CD138 in EC. We aimed to determine the location of CD138 in the hyperplasia and endometrial carcinoma progression scale, and its relation with proliferation via Ki67, and to identify a new criterion in the differential diagnosis of hyperplasia–carcinoma.
Materials and Methods:
A total of 120 endometrial curettage materials with proliferative and secretory phase endometrium, hyperplasia without atypical, atypical hyperplasia, and endometrium carcinoma examined in the pathology laboratory between 1995 and 2016 were included in the study. Samples were subjected to immunostaining for CD138 and Ki67 using antibody.
Results:
Statistical analysis revealed a significant and negative correlation between histopathological progression and CD138 (
P
< 0.01). Statistical analysis revealed a significant and positive correlation between histopathological progression and Ki67 (
P
< 0.01) and a significant negative correlation between Ki67 and CD138 (
P
< 0.01).
Conclusion:
CD138 may be helpful in diagnostic difficulties, and benign pathologies should be considered due to the increase in staining density. Furthermore, we believe that CD138 will be an important criterion in determining the risk of malignancy in hyperplasia, and the risk of malignancy progression may increase in cases, of which intensity of staining decreases in accordance with the normal endometrium.
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DNA base excision repair genes variants rs25487 (X-ray repair cross-complementing 1) and rs1052133 (human 8-oxoguanine glycosylase 1) with susceptibility to ovarian cancer in the population of the Jammu region, India
p. 1270
Sonali Verma, Varun Sharma, Ashna Nagpal, Amrita Bhat, GR Bhat, Ruchi Shah, Ajay Wakhloo, Jyotsna Suri, Deepak Abrol, Sandeep Kaul, Audesh Bhat, Vijeshwar Verma, Rakesh Kumar
DOI
:10.4103/jcrt.JCRT_65_18
PMID
:31898659
Background:
Ovarian cancer is highly prevalent in the population of Jammu, in India; the ovarian cancer ranks third among other types of cancer prevalent in females. However, association studies on ovarian cancer are lacking in this region. We aimed to investigate the disease susceptible variants rs1052133 (human 8-oxoguanine glycosylase 1 [
hOGG1
]) and rs25487 (X-ray repair cross-complementing 1 [
XRCC1
]) with ovarian cancer in population of Jammu, India.
Materials and Methods:
The study conducted in the Shri Mata Vaishno Devi University is a 3-year study which included a total of 280 well-characterized samples (130 ovarian cancer cases and 150 healthy controls).
hOGG1
and
XRCC1
polymorphisms were determined by polymerase chain reaction-based restriction fragment length polymorphism, and these genotyping results were confirmed by Sanger sequencing. Hardy–Weinberg equilibrium for both single-nucleotide polymorphisms (SNPs) was assessed using the Chi-square test. The allele and genotype-specific risks were estimated by odds ratios with 95% confidence intervals.
Results:
In this preliminary study, SNP rs1052133 showed protection with ovarian cancer (
P
= 0.042). The SNP rs25487 was not found associated with ovarian cancer (
P
= 0.271).
Conclusion:
Our results indicate that the G allele of rs1052133 imparts protection to the population whereas variant rs25487 was not associated with ovarian cancer in population from the Jammu region, indicating that larger sample size is needed for further statistical validation. Further, association of other SNPs in these genes should also be carried out as their role cannot be ruled out.
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Low health literacy, poor knowledge, and practice among Turkish women patients undergoing cervical cancer screening
p. 1276
Gulay Yilmazel
DOI
:10.4103/jcrt.JCRT_1142_16
PMID
:31898660
Objective:
The objective of this study is to evaluate health literacy level, cervical cancer knowledge, and practice among women patients undergoing screening.
Materials and Methods:
A cross-sectional study was conducted among 455 women family health center patients. Health literacy level was evaluated by Rapid Estimate of Adult Literacy in Medicine. Patients characteristics, health behaviors, cervical cancer knowledge, and practice were assessed by a questionnaire form. Chi-square test and logistic regression analyses were applied.
Results:
This study has found that 19.3% women were in adequate health literacy level and 80.7% of were in low (inadequate or marginal) level. Health literacy levels were showed significant differences by age, education status, employment, self-perception of health, health condition and having health profession, smoking status, physical activity, body mass index, taking health care, skills and concern on materials. Inadequate health literacy was significantly higher among women patients with poor cervical cancer knowledge and practice. Based on binary regression analyses, adequate health literacy was significantly associated with younger ages.
Conclusion:
Adequate health literacy was poor among women patients. Health literacy levels were affected by patient characteristics, health behaviors, and cervical cancer knowledge and practice.
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Resistance to bevacizumab in ovarian cancer SKOV3 xenograft due to EphB4 overexpression
p. 1282
Li Li, Fangfang Nan, Qingzhi Guo, Dongdong Guan, Chao Zhou
DOI
:10.4103/0973-1482.204896
PMID
:31898661
Aim of Study:
Bevacizumab (BV) is broadly used to treat a number of cancers; however, BV resistance mechanisms and strategies to overcome this resistance are yet to be determined.
Materials and Methods:
In this study, we used ovarian xenograft model to evaluate the underlying resistance mechanisms of BV in ovarian cancer treatment.
Results:
Our results showed that EphB4 was overexpressed in BV-resistant xenograft models instead of other common receptor tyrosine kinases. In addition, when coadministrated with EphB4 blocker NVP-BHG712, the antitumor effect of BV was significantly enhanced in the resistant model, further confirmed the role of EphB4 in BV-resistant ovarian cancer. These results indicate that NVP-BHG712 reverses EphB4 overexpression-mediated resistance to BV.
Conclusion:
These findings represent a guide for the design of future medication strategy and may be useful in guiding the use of BV in combination with NVP-BHG712 in patients with resistance or intolerance ovarian cancer.
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Upregulation of sulfatase-1 decreases metastatic potential of SKOV3 human ovarian cancer cells
in vitro
and
in vivo
p. 1288
Salma Abdi Mahmoud, Mohammed Ibrahim Mohammed, Muhiddin Abdi Mahmoud, Adam Munkaila, Iddrisu Baba Yabasin
DOI
:10.4103/jcrt.JCRT_194_17
PMID
:31898662
Aim:
Sulfatase-1 (SULF-1) is one of the genes associated with the inhibition of several signaling pathways by desulfating HSPG in cancer cells. The aim of this study is to investigate the effect of SULF-1 upregulation on SKOV3 ovarian cancer cell line and its influence on cell proliferation, migration, invasion
in vitro
, and lymph node metastasis in 615 inbred mice
in vivo
.
Materials and Methods:
In
in vitro
study, we upregulated SULF-1 in SKOV3 cells using SULF-1 expression plasmid. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were used to measure SULF-1 expression levels after stable upregulation. CCK-8, flow cytometry, Boyden Transwell-chamber, and scratch-wound healing assay were performed to explore the effect of SULF-1 on the proliferation, migration, and invasion. In
in vivo
study, immunohistochemistry and eosin stain (H and E) were used to evaluate the expression level of SULF-1 gene and to measure the lymph node metastatic rate of mice inoculated with SULF-1-SKOV3-expressed plasmid, SKOV3, and Nc-SKOV3 cells.
Results:
qRT-PCR and western blot assay confirmed that SULF-1 was upregulated both in mRNA and protein levels. Following SULF-1 stable upregulation, the cell proliferation, migration, and invasion were significantly reduced in the SULF-1 upregulated cells (SULF-1-SKOV3) compared with the nontransfected (SKOV3) and the nonspecific sequence transfected cells (Nc-SKOV3). IHC results showed that SULF-1 was highly expressed after stably upregulation in SKOV3 cells, and H and E stain confirmed that the mice inoculated with SULF-1-SKOV3 cells decreased lymph node metastatic rate compared to the two control groups.
Conclusions:
Our findings showed that overexpression of SULF-1 in SKOV3 results in a decrease in ovarian cancer cell proliferation, migration, and invasion
in vitro
and decreased lymph node metastasis
in vivo
. This finding could have a potential therapeutic window in the management of ovarian cancer.
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A comparison of six fractions per week chemoradiation versus five fractions per week of conventional chemoradiation in carcinoma cervix: A prospective controlled study
p. 1296
Deepak Kumar, Satyajit Pradhan, Sunil Choudhary, Lalit M Aggarwal, Avipsa Das, Sovan Sarangdhar, Prashant Kaser, Satish Dewangan
DOI
:10.4103/jcrt.JCRT_698_19
PMID
:31898663
Aims:
The standard of care for carcinoma cervix stage IB2-IVA is five fractions per week of radiotherapy (RT) with concurrent cisplatin. We compared the standard treatment with six fractions per week of RT with concurrent Cisplatin to see whether the later had improved survival outcomes with comparable toxicities.
Settings and Design:
46 patients of carcinoma cervix with stage IB2-IVAwere randomized into two arms.
Materials and Methods:
Study arm: 46 Gy/23 fractions/26 days, 6 fractions/week with injection CDDP 40 mg/m
2
and Control arm: 46 Gy/23 fractions/31 days, 5 fractions/week with injection Cisplatin 40mg/m
2
. Patients in both the arms received LDR brachytherapy to a dose of 29 Gy at point A.
Statistical Analysis Used:
The primary end points were disease-free survival (DFS) and overall survival (OS). Compliance to treatment and treatment toxicities were the secondary end points. P value ≤0.05 were considered significant.
Results:
The study was carried out during June, 2014–April, 2015. Statistical analysis was done in May, 2019. Of 46 patients, 39 patients completed the treatment. The study and control arms had 17 and 22 patients, respectively. Median follow-up period is 45 months (range: 1–54 months). 3-year DFS rates and OS was 69.5% vs. 72.7% (
P
= 0.73) and 63% vs. 68% (
P
= 0.45) in study and in control arm, respectively. There was no significant difference in acute and late radiation toxicities between two arms.
Conclusion:
Chemoradiotherapy with six fractions per week seems feasible and equally efficacious in terms of survival outcomes and toxicity profile. Further prospective randomized controlled study is required to prove the merit of altered fractionation with concurrent cisplatin.
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Interfraction physical dose variations in high-dose-rate brachytherapy for carcinoma cervix based on computed tomography image dataset to find the compatibility of the first fraction plan to treat successive fractions
p. 1304
Suresh Yadav, OP Singh, S Choudhary, Dinesh Kumar Saroj, Anil Kumar Maurya, Veenita Yogi
DOI
:10.4103/jcrt.JCRT_475_19
PMID
:31898664
Context:
Due to limited resources and/or affordability by majority of the patients, many centers in low- and middle-income countries are still not able to adapt three-dimensional image-based brachytherapy planning in their routine practice.
Aim:
The aim of the study was to see the feasibility of using computed tomography (CT)-based plan of the first fraction to treat successive fractions of intracavitary brachytherapy based on the estimation of the physical dosimetric differences between successive applications.
Materials and Methods:
CT image-based brachytherapy plans of 38 patients who received three insertions of intracavitary application with high-dose-rate brachytherapy have been analyzed. Revised plans for the second and third insertions were generated by adapting dwell time and dwell position of the first insertion plan. The dose to point “A” and maximum doses to 2, 1, and 0.1 cc volumes of the rectum and bladder have been used for dosimetric comparison.
Results:
The statistical differences of mean point “A” doses were observed insignificant except between original and revised plans for the second insertions. The dosimetric differences between consecutive original and revised plans for the bladder and rectum have not shown any significance except minimum dose to 0.1 cc volume of the rectum for the third insertions.
Conclusions:
Dosimetric deviation for tumor and organs at risk is within acceptable limit while using CT image-based brachytherapy plan of the first fraction for treating successive fractions.
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Epithelial–mesenchymal transition in serous and mucinous epithelial tumors of the ovary
p. 1309
Geet Bhuyan, Rashmi Arora, Charanjeet Ahluwalia, Preeti Sharma
DOI
:10.4103/jcrt.JCRT_35_18
PMID
:31898665
Context:
The concept of epithelial–mesenchymal transition (EMT) in cancer origin, progression, and metastasis is of recent origin and not fully understood. So far, many cell culture studies have been done to investigate the role of EMT in epithelial ovarian cancer, but only a few human studies have been conducted.
Aims:
The aim of the study is to study the expression of E-cadherin and vimentin in serous and mucinous tumors of the ovary and to compare their expression in benign and malignant serous and mucinous ovarian tumors.
Methods:
This study was a prospective study done on 60 patients with a histological diagnosis of serous and mucinous ovarian malignancy. The study was conducted in the Department of Pathology and Department of Obstetrics and Gynaecology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi. The expression of epithelial marker E-cadherin and mesenchymal marker vimentin was studied in each of the tumors.
Statistical Analysis:
Unpaired
t
-test/Mann–Whitney test, Chi-Square test/Fisher's exact test, and Kolmogorov–Smirnov test were used.
Results:
Of the total 60 cases included in the study, 30 benign and 30 malignant cases of serous and mucinous tumors were taken. Of the 30 benign cases, 22 cases (73.3%) were that of serous cystadenomas, whereas 8 (26.67%) cases were of mucinous cystadenomas. Among the malignant cases, 21 cases (70%) were serous surface epithelial ovarian carcinoma, whereas 9 (30%) were mucinous surface epithelial ovarian carcinoma. Subsequently, the malignant cases were graded according to their glandular differentiation. Immunohistochemistry was performed in each of the 60 cases.
Conclusion:
In the malignant cases with increasing grade of the tumor, a reduced expression of E-cadherin and an increased expression of vimentin were seen in the epithelial cells.
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Prevalence of human papillomavirus type 16 in Sudanese women diagnosed with cervical carcinoma
p. 1316
Lina Mohamed Elamin Elhasan, Devendra Bansal, Omran Fadol Osman, Khalid Enan, Elmoubasher Abu Baker Abd Farag
DOI
:10.4103/jcrt.JCRT_656_18
PMID
:31898666
Objectives:
Squamous cell carcinoma (SCC) of the cervix is one of the leading causes of death in developing countries. Infection with high-risk human papillomavirus (HR-HPV) is the major risk factor to develop malignant lesions HR types (HPV16 and HPV18) account for about 70% of all invasive cervical cancers worldwide. It is estimated that 833 Sudanese women are diagnosed with cervical cancer and 534 die from the disease every year. The present study aimed to detect HPV 16, and determine the association of HPV16 with age and various grades of cervical carcinoma in patients with clinically confirmed cervical SCC.
Materials and Methods:
A total of 158 formalin fixed paraffin embedded tissues blocks from Sudanese women diagnosed as cervical cancer and benign were collected between 2012 and 2016 at Omdurman Maternity Hospital and National Laboratories, Khartoum, Sudan. HPV DNA detection was done using HPV 16 specific primers in real-time polymerase chain reaction.
Results:
The frequency of HPV 16 was identified among 10.34% (
n
= 6) and 6% (
n
= 6) women with abnormal cytology and normal cytology, respectively. Based on age, high prevalence rate of HPV 16 was observed among age group 61–70 in women with malignant cases. The degree of differentiation, an important classification in SCC cases revealed that 5% (
n
= 3) cases had moderately differentiated SCC and two of them were keratinized SCC. In addition, 3.4% (
n
= 2) SCC cases were keratinized and well differentiated.
Conclusion:
Overall, the prevalence of HPV types 16 was higher but had no significant association with cervical SCC in Sudanese women.
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Regulation of HMGA2 and KRAS genes in epithelial ovarian cancer by miRNA hsa-let-7d-3p
p. 1321
Tuba Gunel, Berkcan Dogan, Ece Gumusoglu, Mohammad Kazem Hosseini, Samet Topuz, Kilic Aydinli
DOI
:10.4103/jcrt.JCRT_866_18
PMID
:31898667
Aim of the Study:
The purpose of this study was to identify specific circulating microRNAs (miRNAs) and investigate expression level of their target genes for evaluation of pathogenesis of epithelial ovarian cancer (EOC).
Materials and Methods:
In this study, we have studied on EOC patients' serum and whole blood, healthy control (HC) serum, and whole blood samples. Sixteen serum samples were collected to compare miRNA expression analysis through microarray. According to microarray results, one of the dysregulated miRNA in serum, hsa-let-7d-3p, was validated by RT-qPCR for discriminate two groups. The hsa-let-7d-3p is one of the tumor suppressive let-7d family members. Let-7d is downregulated in numerous types of cancer, including ovarian cancer and directly targets various oncogenes. We analyzed the let-7d targets, which are
High Mobility Group A2 (HMGA2)
and
(Kirsten Rat Sarcoma Viral Oncogene Homolog),
as the oncogenes that are associated with EOC. The relation between target genes of hsa-let-7d-3p and EOC has been examined by Pathway Studio. Twenty serum and whole blood samples collected to analyze expression level of target genes were analyzed by real-time PCR.
Results:
31 significantly dysregulated miRNAs were identified by microarray in serum. Hsa-let-7d-3p has been selected for the validation, according to P-value and dysregulated level. RT-qPCR results showed that hsa-let-7d-3p could discriminate EOC patients from HC (P = 0.0484, AUC = 0.7). Furthermore, we identified hsa-let-7d-3p's target genes
(HMGA2, KRAS)
by bioinformatic analysis. The expression level of genes could discriminate patients with EOC from HC, with a power area under the ROC curves (AUC) of 62 and 64.2, respectively.
Conclusion:
HMGA2
and
KRAS
could be translationally downregulated by the hsa-let-7d-3p, and the loss of hsa-let-7d-3p expression led to the progression of EOC related to the tumorigenesis, invasion, and metastasis.
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Carcinoma vulva patterns of recurrence and treatment outcomes: A single-institution experience
p. 1328
Rohith Singareddy, Harjot Kaur Bajwa, Krishnam Raju Alluri, K V. V N Raju, T Subramanyeshwar Rao, G Rajeev
DOI
:10.4103/jcrt.JCRT_44_18
PMID
:31898668
Aim:
The aim of this study was to evaluate the patterns of recurrence and outcomes in patients with vulvar cancer treated with surgery, with or without postoperative radiotherapy (RT) or RT alone.
Materials and Methods:
The hospital records were retrospectively analyzed from February 2007 to May 2016. All patients that had biopsy-proven carcinoma vulva were included for analysis. Surgery was done by simple or radical vulvectomy with or without lymph node dissection. Radical RT dose was 60 Gy (photons alone or with electron boost). Adjuvant RT was administered in case of node positivity or positive margins.
Results:
A total of 76 patients were diagnosed as squamous cell carcinoma of vulva. The median age was 59 years. About 59 patients were treated by surgery and 17 patients were treated by radical RT. The most common stage was IB. Adjuvant RT was administered in 10 patients. About 13 patients (22%) underwent inguinal lymphadenectomy. At a median follow-up of 35 months, 49 patients (64.4%) were alive, 27 died, and 6 patients were lost to follow-up. Locoregional recurrence rate was 24.5% in radical surgery group, 12% in surgery plus adjuvant RT group, and 47% in radical RT group. Distant metastasis rate was 4%. The progression-free survival at 3 years was 45.3% and 35.5% in the surgery group and radical RT group, respectively.
Conclusion:
Surgery resulted in favorable local control rates in early-stage carcinoma vulva. Adjuvant RT is indicated in case of nodal positivity or positive margins. Radical RT can be considered as an alternative in patients with comorbidities.
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Comparison of volume doses from conventional two-dimensional brachytherapy with corresponding doses from three-dimensional magnetic resonance imaging-based brachytherapy in carcinoma cervix
p. 1332
Susan Mathews, M Biju Azariah, Seetha Mohandas, Sharika V Menon, Preethi George, PG Jayaprakash
DOI
:10.4103/jcrt.JCRT_992_17
PMID
:31898669
Purpose:
The purpose of this study was to evaluate the doses delivered to the brachytherapy (BT) target volume and organs at risk from two-dimensional X-ray-based plans on magnetic resonance imaging (MRI) and to compare these doses with the corresponding doses from the image-based optimized plans.
Materials and Methods:
Twenty patients with cervical cancer treated with chemoradiation and BT were included in this study. All patients had two sets of treatment plans generated for the first fraction of BT. Volume doses resulting from MRI-based optimized plans were compared with the corresponding doses from standard “Point A” prescription plans.
Results:
There was statistically significant difference between the two planning modalities for the mean high-risk clinical target volume (HRCTV) D90 doses (
P
= 0.0014) although mean D2cc of bladder (
P
= 0.1667) and rectum (
P
= 0.051) was not different. Standard plans with a prescription dose of 7 Gy to Point A delivered a mean HRCTV D90 of 10.07 Gy in patients with no gross residual disease at the time of BT, which was very similar to the mean dose from MR-based plans (MRI 10.02 Gy and standard 10.07 Gy). The only factor seen affecting dose distribution in this group was the applicator geometry. Standard plans failed to deliver HRCTV D90 doses of >8.5 Gy in all patients with gross residual disease. The doses were <7.00 Gy to the HRCTV in three patients who had maximum residual diseases at the time of BT.
Conclusion:
Conventional X-ray-based plans with moderate Point A doses deliver HRCTV D90 comparable to MRI-based plans in patients with no residual disease, and centrally placed residual disease, provided proper applicator placement and ideal geometry can be ensured. Soft-tissue image-based BT dose optimization ought to be considered in all patients with gross residual disease at the time of brachytherapy.
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Factors affecting quality of life of cervical cancer patients: A multivariate analysis
p. 1338
Uma Singh, Manju Lata Verma, Zakia Rahman, Sabuhi Qureshi, Kirti Srivastava
DOI
:10.4103/jcrt.JCRT_1028_17
PMID
:31898670
Objective:
The aim of good management for cancer survivors should not be limited to only clinical care, but rather it should also include best quality of life (QOL). The objective of this study was to find out various factors affecting QOL in cervical cancer patients so that by modifying these factors, the best QOL can be provided to them.
Materials and Methods:
This was a prospective cohort study conducted in the Department of Obstetrics and Gynaecology and Department of Radiotherapy, King George's Medical University (KGMU), Lucknow, from May 2015 to July 2016. The cases were selected from patients visiting the outpatient department or who were admitted to the Department of Obstetrics and Gynaecology and Department of Radiotherapy, KGMU. The data information was collected in the form of face-to-face interview using European Organization for Research and Treatment of Cancer general cancer QOL Score 30 (EORTC QLQ C-30) and EORTC QOL questionnaire cervical cancer module (QLQ CX-24) questionnaire.
Results:
QOL was assessed in 85 patients. Health-related QOL was separately studied in terms of overall general QOL and cancer cervix-specific QOL, and various factors affecting QOL were studied by multivariate analysis.
Conclusion:
Education, tobacco use, degree of differentiation of tumor, and size of tumor were the independent factors found to have statistically significant effect on QOL of cervical cancer survivors.
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Implications of applicators orientations on bladder, and rectal doses in gynecological mHDR brachytherapy: A retrospective analysis of reproducibility in multi-fractionated regimen
p. 1345
Anoop Kumar Srivastava, Madhup Rastogi, SP Mishra
DOI
:10.4103/jcrt.JCRT_1158_16
PMID
:31898671
Introduction:
Variation of doses due to positional uncertainties of applicators based on orthogonal radiograph has been evaluated by several researchers. The present study has analyzed the various possibilities of special alterations of applicator placements in intracavitary brachytherapy (ICBT) and its impact on the dose to target volume, rectum, and bladder. An innovative approach has been suggested to quantify and utilize the special coordinates for reproducibility of applicator based on the pelvic bone landmark.
Materials and Methods:
A total of 27 fractions of 9 (
n
= 9) cancer cervix patients treated with external beam radiotherapy followed by ICBT have been evaluated retrospectively. The first fraction of each patient was planned as per the International Commission on Radiation Units and Measurements report 38 guidelines and was considered reference for consecutive fractions regarding dwell positions, dose to target volume, bladder, and rectum points. For each fraction, positioning of applicators regarding their spatial orientations with respect to pelvic bone landmarks and their correlation with dose to bladder and rectum was recorded and analyzed.
Results:
It was found that mean angulations between (1) the two applicator points with respect to tip of central tandem (α), (2) the two applicator points with junction point situated on the sacrum bone (β) and (3) the angle between the line joining applicator points and a point defined on pelvic bone (γ) is 62.20° ± 5.74°, 37.13° ± 5.64° and 105.51° ± 6.58°, respectively. Bladder dose increased with increment in α but decreased with increase of β and γ. Dose to rectum remained unaffected for γ. Mean distance from couch top to tip of central tandem and two ovoids is, respectively, 11.17 cm and 8.70 cm.
Conclusion:
Optimal plans even with orthogonal radiographs may be generated by verifying the application based on the parameters mentioned in the present study and computed tomography-based plans could be utilized more effectively instead of doing automatic or manual optimization. Whereever orthogonal radiograph based or template based ICBT practices is performed this study may create a dataset to have an optimal treatment plan even without three-dimensional images.
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Application of dextran-coated iron oxide nanoparticles in enhancing the radiosensitivity of cancerous cells in radiotherapy with high-energy electron beams
p. 1352
Masoud Rezaei, Karim Khoshgard, Leila Hosseinzadeh, Abbas Haghparast, Mohammad-Taghi Eivazi
DOI
:10.4103/jcrt.JCRT_19_17
PMID
:31898672
Purpose:
Nowadays, cancer is one of the most important causes of morbidity and mortality in the world. The ideal aim of radiotherapy is delivering a lethal radiation dose to tumor cells while minimizing radiation exposure to healthy tissues around the tumor. One way to increase the dose in the tumor cells is the use of high-atomic number nanoparticles as radiosensitizer agents in these cells. The aim of this
in vitro
study was investigating the radiosensitization enhancement potential of the dextran-coated iron oxide nanoparticles (IONPs) on HeLa and MCF-7 cell lines in irradiations with high-energy electron beams.
Materials and Methods:
In this
in vitro
study, the cytotoxicity level of dextran-coated IONPs at different concentrations (10, 40, and 80 μg/ml) was assessed on HeLa and MCF-7 cell lines. To evaluate the radiosensitivity effect, the nanoparticles were incubated with the cells at different concentrations for 24 h and afterward irradiated with different doses (0, 2, 4, 6, and 8 Gy) of 6 and 12 MeV electron beams. The cells survival fractions were obtained by the methylthiazoletetrazolium assay.
Results:
Toxicity results of the nanoparticles at 10 and 40 μg/ml concentrations showed no significant cytotoxicity effect. The cells survival rates in groups receiving radiation in the absence and presence of IONPs showed a significant difference. The radiosensitivity enhancement induced by the nanoparticles in MCF-7 cell line was more than it in HeLa cell line. The average of radiosensitization enhancement factor at 10, 40, and 80 μg/ml concentrations and under 6 MeV irradiations obtained as 1.13, 1.19, 1.25, and 1.26, 1.28, 1.29 for HeLa, and MCF-7 cells, respectively. When 12 MeV electron beams were carried out, the values of 1.17, 1.26, 1.32, and 1.29, 1.32, 1.35 were obtained for the cells at the mentioned concentrations, respectively. Furthermore, the significant differences were observed in radiosensitization enhancement between 6 and 12 MeV electron beams irradiations.
Conclusion:
Use of dextran-coated IONPs can increase radiosensitivity and consequently at a given absorbed dose more cell killing will occur in cancerous cells. In other words, these nanoparticles can improve the efficiency of electron therapy.
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Locally advanced cervical cancer – neoadjuvant chemotherapy followed by concurrent chemoradiation and targeted therapy as maintenance: A phase II study
p. 1359
Rony Benson, Sushmita Pathy, Lalit Kumar, Sandeep Mathur, Vatsla Dadhwal, Bidhu Kalyan Mohanti
DOI
:10.4103/jcrt.JCRT_39_18
PMID
:31898673
Aim:
The survival in locally advanced cervical cancer remains low. We evaluated the role of neoadjuvant chemotherapy (NACT), chemoradiotherapy (CRT), followed by gefitinib maintenance in locally advanced cervical cancer.
Materials and Methods:
Twenty-five patients with locally advanced carcinoma cervix were enrolled between July 2012 and May 2013. Patients received 6 weekly doses of NACT Paclitaxel (60 mg/m
2
) and carboplatin (AUC 2), followed by CRT and brachytherapy. The analysis of epidermal growth factor receptor (EGFR) expression was carried out by immunohistochemistry. Gefitinib (250 mg daily) was given as maintenance therapy for 1 year after completion of chemoradiation. Comparison of EGFR expression and survival outcomes was done.
Results:
Twenty-four of 25 patients completed the neoadjuvant chemotherapy and concurrent chemoradiotherapy. Post-CRT, all patients were started on gefitinib maintenance, and twenty patients completed the intended 1 year of gefitinib maintenance. Nineteen (76%) patients had a radiological complete response to NACT. EGFR was moderately or strongly expressed in 86.3% of the patients. The 3-year overall survival was 69.8%, and 3-year progression-free survival was 51.4%. Expression of EGFR was not found to be a significant factor affecting overall survival or progression-free survival.
Conclusions:
Weekly neoadjuvant chemotherapy is associated with a good response rate in locally advanced cervical cancer. Neoadjuvant chemotherapy, chemoradiation, followed by gefitinib maintenance gives good survival outcome in patients with locally advanced cervical cancer.
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Effect of different definitions of prescription point “A” in high dose rate brachytherapy for cervical cancer
p. 1365
Shraddha Srivastava, Nirmal Kumar Painuly, Surendra Prasad Mishra, Kirti Srivastava, Navin Singh, Madan Lal Brahma Bhatt
DOI
:10.4103/jcrt.JCRT_480_18
PMID
:31898674
Aim:
This study intended to compare the dosimetric parameters using different definitions of prescription point A in high dose rate (HDR) brachytherapy of cervical cancer patients.
Background:
Manchester point A has been widely used for prescribing dose in brachytherapy. However, due to certain limitations of this point, a new definition of point A has been recommended by the American Brachytherapy Society (ABS).
Materials and Methods:
We retrospectively investigated 55 computed tomography-based plans of 20 cervical cancer patients treated with Ir-192-based intracavitary HDR brachytherapy. The dose of 7 Gy in 3 fractions each was prescribed to point A using revised Manchester definition of point A (A
MAN
) and ABS guideline definition (A
ABS
). The effect of both definitions on various parameters including dose to point A and 90% of tumor volume (D
90
), dose received by 2cc volume of bladder, rectum and small bowel and treatment volume receiving 100% of prescription dose (V
100
) was analyzed.
Results:
Mean percentage difference of point A
MAN
dose and A
ABS
dose with respect to prescription dose was 1.25% ± 1.43% and 1.21% ± 1.01%, respectively. Mean V
100
was 80.4 ± 20.45cc and 88.47 ± 16.78cc for A
MAN
and A
ABS
plans, respectively, while mean percentage difference between prescribed dose and D
90
was found to be –37.90% ± 25.06% and –30.47% ± 25.50% respectively for both the definitions.
Conclusion:
Doses to both Manchester point A and ABS point A may be recorded during the transition period. However, ABS point A can be preferred over the Manchester point A as it conforms better with the desired dosimetric outcome and is found to be more static.
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Study of the effects of dwell time deviation constraints on inverse planning simulated annealing optimized plans of intracavitary brachytherapy of cancer cervix
p. 1370
Saurabh Roy, V Subramani, Kishore Singh, Arun Kumar Rathi, Arora Savita, Aggarwal Aditi
DOI
:10.4103/jcrt.JCRT_246_18
PMID
:31898675
Purpose:
High Dose Rate (HDR) remote afterloading brachytherapy machine and advanced treatment planning system have made it possible to make variations in individual dwell times across a catheter according to tumour density and for sparing normal structures. New inverse planning technique such as Inverse Planning Simulated Annealing (IPSA) has also been introduced. But very few institutions are venturing towards volume based IPSA optimised intracavitary brachytherapy. This study focuses on dwell time deviation constraint (DTDC) feature of IPSA based optimization which restricts the large variation of dwell time across the catheter.
Methods and Material:
For this retrospective study we have generated IPSA optimised intracavitary brachytherapy plans for 20 cancer cervix applications. The initial DTDC value of each IPSA plan was kept 0.0. Later on gradual increment was made in DTDC values in step of 0.2. Plan modulation index (M) defined by Ryan L. Smith et al was used for characterising the variation of dwell time modulation with respect to gradual increase in DTDC parameter.
Results:
Plan modulation index gradually decreases with increasing value of DTDC from 0.0 to 1.0. There was the 83% decrease in M value from IPSA of DTDC 0.0 to fully constrained IPSA of DTDC1.0. There is reduction of 8.26% and 6.95% for D2cc values of rectum and bladder respectively for DTDC 1.0 compared to DTDC 0.0.
Conclusions:
One of the benefits of applying DTDC constrained in IPSA plan is that, it removes local hot spots. It's another advantage is the reduction in rectum and bladder dose.
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Adjuvant radiotherapy for uterine carcinosarcoma: A retrospective assessment of treatment outcomes
p. 1377
Ugur Yilmaz, Senem Alanyali, Arif Bulent Aras, Zeynep Ozsaran
DOI
:10.4103/jcrt.JCRT_531_18
PMID
:31898676
Objectives:
The objective of the study is to understand the impact of adjuvant radiotherapy (RT) and prognostic factors for patients diagnosed with uterine carcinosarcoma.
Materials and Methods:
The records of 31 patients receiving adjuvant RT between the dates of September 2003–January 2013 in our clinic were evaluated retrospectively. Surgery was performed in 27 (87%) patients as staging laparotomy, for 4 patients as total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pelvic external beam radiotherapy (EBRT) was 4500–5040 cGy in 25–28 fractions. In addition, 23 patients received brachytherapy following EBRT, 12 patients received adjuvant, and 1 patient received neoadjuvant chemotherapy (CT).
Results:
The median age was 63 (between 30 and 78). The stage distribution of the patients was as follows: Stage I, 20 (64%); Stage II, 7 (23%), and Stage III, 4 (13%) patients. Five-year locoregional control (LRC) rate was 100%, disease-free survival (DFS) and overall survival (OS) rates were 65.5% and 66.2%, respectively. Stage I or II patients have a tendency for better 5-year OS and DFS rates than Stage III patients (73.1% vs. 42.9% and 72.7% vs. 42.9%;
P
= 0.065 and 0.051). Regarding lymph node dissection was performed or not, 5-year OS (64.7% vs. 75.0%) was not statistically different between groups (
P
= 0.77). Five-year OS and DFS rates were 69.2% and 61.5% for patients receiving CT (adjuvant or neoadjuvant) versus 63.7% and 68.8% for patients not receiving CT;
P
= 0.63 and
P
= 0.89, respectively. Based on the analysis of peritoneal washings, 5-year OS was 0% for patients with malignant or suspicious cytology whereas 89% for patients with benign cytology (
P
= 0.000). A negative correlation was observed between mitotic count of sarcomatous component and DFS time (rs = −0.812 and
P
= 0.05).
Conclusions:
Surgery and adjuvant RT seem beneficial for excellent LRC rate. However, survival rates are low due to distant metastases. Thus, there is a great need for better systemic therapies.
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A phase 2 randomized controlled trial of oral resistant starch supplements in the prevention of acute radiation proctitis in patients treated for cervical cancer
p. 1383
Balu Krishna Sasidharan, Balamurugan Ramadass, PN Viswanathan, Prasanna Samuel, Mahasampath Gowri, Srinivasan Pugazhendhi, Balakrishnan S Ramakrishna
DOI
:10.4103/jcrt.JCRT_152_19
PMID
:31898677
Background:
Radiation induced proctitis is frequently encountered during the radiation therapy of cervical and prostate cancers that causes pain and occasionally with bleeding and may affect the continuity of radiation therapy.
Aims and Objectives:
The purpose of the study is to look at the benefit of administration of an oral prebiotic amylase resistant starch in reducing the incidence of acute radiation proctitis, a distressing symptom in patients receiving radiation therapy for cancer of the cervix.
Material and Methods:
The study was conducted between 2011 and 2014 in 104 patients receiving radical chemo-radiotherapy for carcinoma cervix. Patients were randomized in to two arms, one receiving 30 gm of resistant starch and the other digestible starch on a daily basis throughout the course of the external radiotherapy. All patients received standard 4-field box radiation portals, 50 Gy in 25 fractions with 4 cycles of weekly concurrent Cisplatin. At completion of external beam radiotherapy, all patients underwent LDR/HDR brachytherapy. The study was double blinded and allocation was concealed from the investigators. The investigator recorded the radiotherapy related toxicity of the patients according to CTC V 3.0. The incidence and severity of grade 2-4 diarrhoea and proctitis were documented on a weekly basis and compared across the two groups and analyzed. Stool short chain fatty acid concentrations were measured at baseline at 2
nd
and 4
th
week and after 6 weeks of completion of radiotherapy in both study placebo arms and reported. The pattern of microbiota in the stool were also estimated in all patients at 4 time points. Two patients who progressed during therapy were not included in the analyses and two patients discontinued the intervention. A per protocol analyses was done.
Results:
At analysis there were 50 patients in each arm. The severity of clinical proctitis was found to be similar in both groups of patients with 12.2 % of patients experiencing toxicity of grade 2 and above in digestible starch group versus 14.6% in the resistant starch group. Functional proctitis was similarly graded and it was found that 16.3 % patients in digestible starch group experienced toxicity against 10.2 % patients in the resistant starch group. This difference was seen at 4
th
week and continued in the subsequent weeks till the end of radiation. Both groups had similar reported toxicity at 6 weeks post intervention and similar incidence of grade 2 and above diarrhea. The resistant starch group was found to have 8% incidence as compared to 2% in the other group at the 5
th
and 6
th
week. The short chain fatty acid concentrations were not significantly different in the groups at any point.
Conclusion:
The study did not demonstrate a significant benefit in administering resistant starch over and above normal diet to patients receiving pelvic radiotherapy. The reasons may be attributed to concurrent use of chemotherapy and decrease in intestinal probiotics. The use of digestible starch in the control arm may have contributed to lower incidence of the toxicity endpoints as well.
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CASE REPORTS
Primary vaginal malignant melanoma: A rare entity with review of literature
p. 1392
Shailja Puri, Sarita Asotra
DOI
:10.4103/jcrt.JCRT_893_15
PMID
:31898678
Primary vaginal malignant melanoma (PVMM) is an extremely rare tumor of the female genital tract, accounting for only 3% of melanomas of the female genital tract and 0.3%–0.8% of all melanomas in females. Vaginal melanoma is a very aggressive tumor with a 5-year survival rate of 5%–25%. High incidence of recurrence, spread to regional lymph nodes, and distant metastasis are responsible for poor prognosis of PVMM. Grossly, amelanotic melanoma of the vagina may be mistaken for other primary vaginal malignancies. Differentiation of malignant melanoma from other primary vaginal melanomas is essential because of better prognosis of most of other vaginal malignancies as compared to melanoma. Despite having poor prognosis, early detection and early treatment of PVMM may improve the prognosis.
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A diagnostic dilemma: A rare case of an ovarian carcinoma with signet ring cells hidden behind a substantial dermatomyositis
p. 1395
Asim Armagan Aydin, Hulya Ayik, Arif Hakan Onder, Banu Ozturk, Mustafa Yildiz
DOI
:10.4103/jcrt.JCRT_1012_16
PMID
:31898679
Dermatomyositis (DM) is a malignancy-associated inflammatory connective tissue disease which involves muscles and skin. It accompanies many cancer types. Herein, we aimed to present a 42-year-old patient with primary signet ring cell ovarian carcinoma which has not been seen hitherto. Presentation with DM induces rapid and aggressive progression and emphasizes the importance of more comprehensive malignancy screening in these patients.
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Primary extraneural ependymoma of the broad ligament: A rare entity
p. 1398
Anita Kumari, Preeti Diwaker, Priyanka Gogoi, Vinod K Arora, Pankaj Kumar Garg, Rambha Pandey
DOI
:10.4103/jcrt.JCRT_672_17
PMID
:31898680
Extraneural broad ligament ependymoma is a rare entity. Herein, we present a case of unusually large broad ligament ependymoma in a 32-year-old female with pain and lump in the lower abdomen. Contrast-enhanced computed tomography abdomen revealed multiple heterogeneously enhancing pelvic masses with lobulated surface in bilateral adnexa along with multiple peritoneal nodules. Her relevant serum tumor markers were unremarkable. Core biopsy revealed tumor composed of elongated cells arranged predominantly in true and pseudoperivascular rosettes. The histopathological differentials included ependymoma, primitive neuroectodermal tumor, and teratoma with neural differentiation. Results of immunohistochemistry favored the diagnosis of ependymoma. Surgical exploration and optimal cytoreduction were done, and a final diagnosis of primary broad ligament ependymoma with peritoneal metastasis was made. The patient received six cycles of adjuvant chemotherapy and is doing well after 8-month follow-up. The present case highlights the diagnostic workup and management of a rare and an unusually large broad ligament ependymoma with peritoneal metastasis.
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Isolated acrometastasis: A rare presenting feature of endometrial carcinoma
p. 1402
Irappa V Madabhavi, Apurva Patel, Malay S Sarkar, Mitul G Modi, Suhas Aagre
DOI
:10.4103/jcrt.JCRT_394_15
PMID
:31898681
The most common presenting feature of endometrial carcinoma (EC) is abnormal uterine bleeding. Bone metastasis, as a presenting feature of EC, is very unusual which is usually restricted to pelvis and vertebrae. The occurrence of foot metastasis is exceedingly rare. We report a case of a postmenopausal female presented with pain and swelling involving right foot. Biopsy revealed metastatic adenocarcinoma. The patient denied any history of vaginal bleeding or other gynecological symptoms. Bone scan suggested increased uptake in multiple tarsal bones. Uterine curettage confirmed the diagnosis of endometrial adenocarcinoma. The patient was successfully treated with debulking surgery, palliative radiotherapy to the right foot, bisphosphonates, and systemic chemotherapy with marked improvement in local symptoms and is under follow-up for the last 6 months after completion of the treatment. An extensive review of the literature, to the best of our knowledge, did not reveal many cases of acrometastasis as a presenting feature of EC.
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Carcinoma cervix
de novo
with widespread cutaneous/subcutaneous metastasis: A rare case report
p. 1405
Shraddha Raj, Neha Kakkar, Prachi Agrawal, Satya Dutta, KT Bhowmik
DOI
:10.4103/jcrt.JCRT_774_17
PMID
:31898682
Cancer of the uterine cervix is one of the leading gynecological malignancies of developing nations including India. A 45-year-old female presented with menstrual irregularities and other nonspecific symptoms. After initial workup, she was diagnosed with carcinoma cervix, Stage IV A, while she was being planned to take up radical concomitant chemoradiotherapy, she developed widespread nodules over various sites over the body, which were histopathologically proven as metastatic lesions. She was treated with a palliative intent by radiotherapy and chemotherapy. Only a few such cases have been reported in the literature with variable outcomes. These rare presentations should be thoroughly worked up and studied to know more about their biological behavior.
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Sister Mary Joseph's nodule in endometrial cancer: A case report and review of the literature
p. 1408
Martina De Angeli, Mariantonia Carosi, Enrico Vizza, Giacomo Corrado
DOI
:10.4103/jcrt.JCRT_523_18
PMID
:31898683
Sister Mary Joseph's nodule (SMJN) is an umbilical mass referring to an intraabdominal and/or pelvic tumor's metastasis. SMJN is frequently associated with gynecological malignancies, but only 30 cases of SMJN originated from endometrial cancer have been described in the literature. We reported a case of SMJN detected within the primary diagnosis of endometrial cancer, in which a 1-year vaginal relapse occurs. A robotic single-site total hysterectomy and a bilateral salpingo-oophorectomy were performed to treat the primary tumor, followed by an adjuvant radiotherapy. The SMJN was resected during the surgical procedure. The relapse was treated by a partial colpectomy. No evidence of disease has been observed to date, and an overall survival of 31 months has been achieved. Due to the rare occurrence of an umbilical metastasis from an endometrial carcinoma, SMJN is difficult to recognize in this contest; nevertheless, its diagnosis is becoming increasingly important in relation to the choice of a proper treatment.
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Lobular carcinoma of the breast with metastasis to the uterine cervix
p. 1411
Danilo Rafael Silva Fontinele, Sabas Carlos Vieira, Raimundo Gerônimo da Silva Júnior, Tatyanne Silva Rodrigues
DOI
:10.4103/jcrt.JCRT_469_18
PMID
:31898684
Metastases may occur in early-stage or locally-advanced tumors in diverse locations. Nevertheless, the uterine cervix is an uncommon site for metastasis, since the majority of tumors in this organ is primary carcinomas or result from the direct extension of primary pelvic tumors. The objective of the current study was to report a clinical case considered rare in the literature, as well as discuss its implications and peculiarities. This case report describes a 57-year-old patient with lobular carcinoma metastatic to the uterine cervix, >3 years after the termination of the left breast cancer treatment. A literature analysis confirmed that most cases presented with vaginal bleeding or abdominal discomfort, but many were asymptomatic. Common characteristics between the cases were the patient's age, the time period between primary tumor diagnosis and the emergence of metastatic lesions, treatment, medication, and signs/symptoms. Although rare, metastasis should be considered in women with a history of breast cancer, particularly when the complaint is abnormal vaginal bleeding.
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Peritoneal metastasis in Stage IB1 adenocarcinoma cervix: A rare entity
p. 1415
Seema Singhal, Sunesh Kumar, Dayanand N Sharma, Sandeep Mathur
DOI
:10.4103/jcrt.JCRT_830_18
PMID
:31898685
The presence of ovarian or peritoneal metastasis in early-stage cervical malignancy is a rare entity. It often poses a diagnostic challenge whether it is a synchronous primary tumor or a metastatic lesion. A 63-year-old postmenopausal woman presented with Stage 1B1 carcinoma cervix with ascites, and a 5.8 cm × 4.2 cm × 3.5 cm left solid adnexal mass. She underwent Type III radical hysterectomy, excision of peritoneal mass, with bilateral pelvic and paraaortic lymphadenectomy and infracolic omentectomy. On histopathology, cervix showed features of adenocarcinoma, and the peritoneal mass revealed similar histomorphology as cervical growth with metastatic tumor deposits in omentum. Immunohistochemistry (IHC) was utilized to determine the origin of mass. The early stage disease and histology may not always predict the distant metastasis. Therefore, a thorough pretreatment evaluation, meticulous intraoperative assessment, and IHC are mandatory for optimum management and prognostication.
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BRIEF COMMUNICATION
Synchronous benign Brenner's tumor of ovary with leiomyoma and endometrial adenocarcinoma in a postmenopausal female
p. 1418
Jyotsana Harit Gaur, Mohammad Jaseem Hassan, Arifa Anwar Elahi, Shaan Khetrapal, Sabina Khan, Sujata Jetley
DOI
:10.4103/jcrt.JCRT_109_18
PMID
:31898686
Brenner tumors of ovary are usually an incidental finding. It is an uncommon tumor which is seen affecting women of fifth to sixth decade. It is classified under transitional cell tumors of ovary, which includes benign, borderline, and malignant Brenner tumors and transitional cell carcinoma. These tumors have been associated with synchronous and metachronous neoplasia, most commonly other ovarian epithelial tumors such as mucinous cystadenoma. Occasionally, these tumors may be associated with endometrial hyperplasia or carcinomas which are due to hormones elaborated by the stromal component of Brenner tumor. The hormone produced is estrogen and less commonly androgens, which alters the estrogen and progesterone levels, causing hyperstimulation of endometrium. We present a case of 50-year-old postmenopausal women who presented with coexisting incidental Brenner tumor with leiomyoma and Endometrial adenocarcinoma. Only few authors have reported similar tumor occurrence in the past.
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LETTER TO THE EDITOR
Cost–risk analysis of available cervix cancer vaccine: Situation analysis from Thailand
p. 1421
Somsri Wiwanitkit, Viroj Wiwanitkit
DOI
:10.4103/jcrt.JCRT_415_18
PMID
:31898687
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BOOK REVIEW
Mesenchymal stem cells in cancer therapy
p. 1422
Mohammad Reza Atashzar
DOI
:10.4103/0973-1482.257983
PMID
:31898688
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ERRATUM
Erratum: Anticancer activity of britannin through the downregulation of cyclin D1 and CDK4 in human breast cancer cells
p. 1424
DOI
:10.4103/0973-1482.274081
PMID
:31898689
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Erratum: Primary large cell neuroendocrine carcinoma of the prostate in a hormone naive patient: A case report from Taiwan
p. 1425
DOI
:10.4103/0973-1482.274082
PMID
:31898690
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st
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th
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