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Brachytherapy and survival in small cell cancer of the cervix and uterus.

ABSTRACT: PURPOSE:Small cell cancer involving the cervix and uterus is considered the same rare disease, but management is controversial and disparate. Patterns of care and outcomes in the United States are unclear. METHODS AND MATERIALS:Clinical data from patients with small cell cancer of the cervix and uterus were abstracted from the National Cancer Database from 2004 to 2014. Patients with missing clinical stage, incomplete followup, or receiving treatment >90 days from diagnosis were excluded. RESULTS:There were 621 cervical and 95 uterine patients with cancer treated from 2004 to 2014. Compared to patients with a cervix primary site, patients with a uterine primary site were older (median age 64 years vs. 47 years), more likely to present with distant metastatic disease (47% vs. 33%), less likely to receive any pelvic radiation (31% vs. 64%), less likely to receive brachytherapy (3% vs. 27%), more likely to have at least a total hysterectomy (58% vs. 28%), and less likely to receive chemotherapy (74% vs. 88%), all p < 0.05. Brachytherapy was associated with improved overall survival (OS) for patients with locally advanced cervical small cell carcinoma (II-IVA, p = 0.03), but only 38% of patients with Stage II-IVA disease received brachytherapy. For the uterine site, hysterectomy (p = 0.001) and external irradiation (p = 0.03) were associated with improved OS in unadjusted Kaplan-Meier analysis, but only chemotherapy and stage were significantly associated with higher OS in multivariable analysis. CONCLUSIONS:Brachytherapy may improve OS for Stage II-IVA small cell cancer of the cervix but appears underutilized. Brachytherapy was not commonly delivered for uterine primaries.

SUBMITTER: Lin AJ

PROVIDER: S-EPMC7008011 | biostudies-literature | 2019 Mar - Apr

REPOSITORIES: biostudies-literature

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Brachytherapy and survival in small cell cancer of the cervix and uterus.

Lin Alexander J AJ Hassanzadeh Comron C Markovina Stephanie S Schwarz Julie J Grigsby Perry P

Brachytherapy 20181215 2

<h4>Purpose</h4>Small cell cancer involving the cervix and uterus is considered the same rare disease, but management is controversial and disparate. Patterns of care and outcomes in the United States are unclear.<h4>Methods and materials</h4>Clinical data from patients with small cell cancer of the cervix and uterus were abstracted from the National Cancer Database from 2004 to 2014. Patients with missing clinical stage, incomplete followup, or receiving treatment >90 days from diagnosis were e ...[more]

PMID: 30563743

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Project description:PURPOSE:This study reported long-term outcomes of patients with cervical cancer who were treated with intensity modulated radiation therapy and 3-dimensional (3D) image-guided adapted brachytherapy (IMRT/3D-IGABT) compared with those treated with 2-dimensional (2D) external irradiation and 2D brachytherapy (2D EBRT/BT). METHODS AND MATERIALS:This study included patients with newly diagnosed cervical cancer and pretreatment fluorodeoxyglucose positron emission tomography scans who were treated with curative-intent irradiation from 1997 to 2013. The treatment policy changed from using 2D EBRT/BT to IMRT/3D-IGABT in 2005. Patterns of recurrence, cancer-specific survival (CSS), and overall survival (OS) were evaluated. Late gastrointestinal and genitourinary toxicity were scored with National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS:The median follow-up for patients alive at the time of last follow-up in the 2D EBRT/BT group (n = 300) was 15.3 years (range, 10.8-20.5 years). In the IMRT/3D-IGABT group (n = 300), it was 7 years (range, 5-12.4 years). According to the International Federation of Gynecology and Obstetrics, 33% of tumors were stage IB1 to IB2, 41% were stage IIA to IIB, and 26% were stage IIIA to IVA. The results after 5 years for patients treated with 2D EBRT/BT showed that freedom from relapse (FFR) was 57%, CSS was 62%, and OS was 57%. For the IMRT/3D-IGABT group, the 5-year results showed that FFR was 65% (P = .04), CSS was 69% (P = .01), and OS was 61% (P = .04). When stratified by lymph node status according to positron emission tomography scan results, disease control was most improved with IMRT/3D-IGABT versus 2D EBRT/BT in patients with positive pelvic lymph nodes only (P = .02). Cumulatively, 88 of 600 patients (15%) had grade ?3 late bowel/bladder toxicity. The 2D EBRT/BT group had 55 patients (18%), and the IMRT/3D-IGABT group had 33 patients (11%; P = .02). CONCLUSIONS:IMRT/3D-IGABT was associated with improved survival and decreased gastrointestinal and genitourinary toxicity in patients with cervical cancer compared with those who received 2D EBRT/BT.

Project description:KEY POINTS:Older pregnant women have a greater risk of operative delivery, still birth and post-term induction. This suggests that maternal age can influence the timing of birth and processes of parturition. We have found that increasing maternal age in C57BL/6J mice is associated with prolongation of gestation and length of labour. Older pregnant mice also had delayed progesterone withdrawal and impaired myometrial function. Uterine ageing and labour dysfunction should be investigated further in older primigravid women. ABSTRACT:Advanced maternal age (?35 years) is associated with increased rates of operative delivery, stillbirth and post-term labour induction. The physiological causes remain uncertain, although impaired myometrial function has been implicated. To investigate the hypothesis that maternal age directly influences successful parturition, we assessed the timing of birth and fetal outcome in pregnant C57BL/6J mice at 3 months (young) and 5 months (intermediate) vs. 8 months (older) of age using infrared video recording. Serum progesterone profiles, myometrium and cervix function, and mitochondrial electron transport chain complex enzymatic activities were also examined. Older pregnant mice had a longer mean gestation and labour duration (P < 0.001), as well as reduced litter size (P < 0.01) vs. 3-month-old mice. Older mice did not exhibit the same decline in serum progesterone concentrations as younger mice. Cervical tissues from older mice were more distensible than younger mice (P < 0.05). Oxytocin receptor and connexin-43 mRNA expression were reduced in the myometrium from 8-month-old vs. 3-month-old mice (P < 0.05 and P < 0.01 respectively) in tandem with more frequent but shorter duration spontaneous myometrial contractions (P < 0.05) and an attenuated contractile response to oxytocin. Myometrial mitochondrial copy number was reduced in older mice, although there were no age-induced changes to the enzymatic activities of the mitochondrial electron transport chain complexes. In conclusion, 8-month-old mice provide a useful model of reproductive ageing. The present study has identified potential causes of labour dysfunction amenable to investigation in older primigravid women.

Project description:A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions. (NIHR01CA122276).

Project description:PurposeTo establish a dose volume-effect relationship for predicting late rectal complication (LRC) in locally advanced cervical cancer patients treated with external beam radiotherapy (EBRT) followed by combined intracavitary/interstitial brachytherapy (IC/IS-BT).Materials and methodsA retrospective analysis was performed in 110 patients with locally advanced cervical cancer who underwent definitive radiotherapy combined with IC/IS-BT from July 2010 to September 2018. We report the 90% of the target volume receiving the minimum dose for high risk clinical target volume (HR-CTV D90) and intermediate risk clinical target volume (IR-CTV D90), and the minimum doses to the most exposed 0.1, 1, and 2 cm³ D0.1cm3,D1cm3,D2cm3 doses at the International Commission on Radiation Units and Measurements (DICRU) for organs at risk (OARs). The total dose of EBRT plus brachytherapy was transformed to the biologically equivalent dose in 2 Gy fractions (EQD2) with α/β value of 10 Gy for target, 3 Gy for organs at risk using the linear quadratic model. The morbidity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria. The Probit model was used to establish a prediction model on rectum between the organs at risk for dose and LRC. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of dose volume parameters for LRC.ResultsThe median follow-up time was 72.3 months. The mean ( ± standard deviation) D2cm3,D1cm3,D0.1cm3 , and DICRU values of rectum were 64.72 ± 7.47 GyEQD2, 70.18 ± 5.92 GyEQD2, 79.32 ± 7.86 GyEQD2, and 67.22 ± 7.87 GyEQD2, respectively. The Probit model showed significant relationships between D1cm3 or D0.1cm3 , and the probability of grade1-4, grade 2-4 rectal events at 1 year, and between D1cm3 and the probability of grade2-4 rectal events at 3 and 5 years. The dose values for 10% complication rates (ED10) of D1cm3 were 74.18 (70.42-76.71) GyEQD2, 67.80 (59.91, 71.08) GyEQD2, 66.37 (52.00, 70.27) GyEQD2 for grade 2-4 with rectal morbidity at 1, 3, and 5 years, respectively.ConclusionOur study proved that D1cm3 andD0.1cm3 were considered as useful dosimetric parameters for predicting the risk of grade1-4 and grade2-4 LRC at 1-year, and D1cm3 might be an indicator for predicting grade2-4 LRC at 3/5years. The patients with rectal D1cm3 >66.37-74.18 GyEQD2 should be closely observed for grade2-4 LRC.

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Brachytherapy and survival in small cell cancer of the cervix and uterus.

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Brachytherapy and survival in small cell cancer of the cervix and uterus.

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