Red blood cell transfusion practices for patients with cervical cancer undergoing radiotherapy

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005

Improved disease control with adjuvant therapy for stage IA serous and clear cell uterine cancer: A pooled multi-institutional analysis

Purpose/Objective(s): The optimal adjuvant management of Stage IA endometrial cancer with serous or clear cell histology is not well defined. The objective of this study is to explore the role of adjuvant radiotherapy in this population. Purpose/Objective(s): In this ethics board approved study, retrospective review of consecutive patients at six academic centers who underwent hysterectomy for 2009 FIGO Stage IA endometrial cancer with serous or clear cell histology between 2004 and 2015 was conducted. After excluding patients who were upstaged following surgery, descriptive statistics were generated. Time-to event outcomes were calculated using the Kaplan-Meier method, with prognostic factors identified through univariable and multivariable Cox-proportional hazard modeling. Statistical comparisons were calculated in the SAS environment, with significance defined at the 2-sided 0.05 level. Results: A total of 414 patients with a median age of 67 years (range 41-90) met the inclusion criteria. The most common histology was pure serous (64%) followed by mixed (27%) and pure clear cell (9%). Myometrial invasion was identified in 54%. Adjuvant RT was delivered to 47% of patients (pelvic external beam radiotherapy (EBRT) alone 16%; vaginal vault brachytherapy alone 56%; both 28%). One hundred and fourteen patients (34%) received adjuvant chemotherapy with carboplatin/paclitaxel most commonly used (77%). The median follow-up was 2.7 years (range 0-12). The 5-year local control (LC) was as follows: EBRT + brachytherapy 96%, brachytherapy alone 98%, EBRT alone 86% and no radiation 83%. Adjuvant brachytherapy (both alone and in association with EBRT) was associated with improved LC (5-year 96% vs. 84%, log-rank P = 0.0073, adjusted HR 0.36) and disease free survival (DFS) (5-year 79% vs. 71%, log-rank P = 0.0033, adjusted HR 0.70, P = 0.23) but not cancer specific survival (CSS) or overall survival (OS). The 5-year RC was 93% and was not improved by EBRT. Improved regional control was observed when brachytherapy was delivered but not in EBRT subgroup in multivariate analysis (HR 0.16, P = 0.02). Myometrial invasion, lymphovascular invasion, histological subtypes, and the proportion of type II component were not found to be significant prognostic factors for LC. No differential LC benefits with adjuvant RT were observed in subgroups. Adjuvant chemotherapy was associated with improved LC (5-year 94% vs. 84%, HR 0.29, log-rank P = 0.0079) and DFS (5-year 79% vs. 71%, HR 0.47, log-rank P = 0.033), but did not impact RC, DF or CSS. Conclusion: Adjuvant vaginal vault brachytherapy and chemotherapy were independently associated with improved LC and DFS without an observed OS benefit for stage IA serous and clear cell uterine cancer. Prospective study is warranted to clarify the role of adjuvant pelvic EBRT in this setting

The role of adjuvant therapy in stage IA serous and clear cell uterine cancer: A pooled analysis.

Purpose or Objective The optimal adjuvant management of Stage IA endometrial cancer with serous or clear cell histology is controversial. The objective of this study is to explore the role of adjuvant therapy in this population and identify patient characteristics of those suitable for observation. Material and Methods Retrospective chart reviews for consecutive patients who underwent hysterectomy for FIGO Stage IA endometrial cancer with serous or clear cell histology between 2004- 2015 were conducted in 6 academic centres. After excluding patients who were upstaged following surgery, a pooled analysis was performed for relevant endpoints. Results A total of 414 patients with a median age of 67 years(range 41-90) met the inclusion criteria. The most common histology were pure serous (64%,n=266) followed by mixed (27%,n=112) and pure clear cell (9%,n=36). Myometrial invasion was identified in 54%(n=222). Most patients underwent some surgical staging including sampling of pelvic lymph node (LN) (81%,n=335), para-aortic LN (45%,n=146), omentum (58%,n=239) and peritoneal washing (62%,n=219). Only 23% of patients (n=95) were considered to have adequate staging (pre-defined as ≥10 pelvic LN, sampled para-aortic LN and omentum). Thirtyfour percent of patients (n=140) received adjuvant chemotherapy and carboplatin/paclitaxel was most commonly used (77%, n=108). Adjuvant RT was delivered to 47%(n=178) of patients (external beam alone 16%,n=29; brachytherapy alone 56%, n=99; both 28%,n=50). The median follow-up was 2.7 years (range 0-12). Among patients who did not received any adjuvant treatment, 5- year actuarial estimates were as follows: local control(LC) 88%, regional control(RC) 93%, distant failure(DF) 15%, disease free survival(DFS) 74%, cancer specific survival(CSS) 91% and overall survival(OS) 82%. Adequate staging was associated with better CSS in patients who did not have adjuvant treatment (100% vs. 87%, logrank p=0.0035). Adjuvant RT was associated with better LC(5- year 96% vs. 84%, HR 0.32,logrank p=0.014). The 5-year RC was 93%, which was not found to be significantly improved by external beam RT. Adjuvant chemotherapy was associated with better LC(5-year 94% vs. 84%,HR 0.29, logrank p=0.0079), DFS(5-year 79% vs. 71%, HR 0.47, logrank p=0.033), but not for RC, DF or CSS. The delivery of at least 5 cycles of chemotherapy, was associated with a trend towards better LC (4-year 98% vs. 88%, HR 0.18,logrank p=0.090). Myometrial invasion, lymphovascular invasion, histological subtypes and the proportion of type II component were not found to be significant prognostic factors for LC, RR, DF or CSS. Conclusion Adjuvant radiotherapy and chemotherapy were associated with better LC and DFS but not for RC, DF or CSS for stage IA serous and clear cell uterine cancer. Observation may be an acceptable strategy in patients who have had adequate surgical staging

The Role of Adjuvant Therapy in Stage IA Serous and Clear Cell Uterine Cancer: A Pooled Analysis

Purpose or Objective The optimal adjuvant management of Stage IA endometrial cancer with serous or clear cell histology is controversial. The objective of this study is to explore the role of adjuvant therapy in this population and identify patient characteristics of those suitable for observation. Material and Methods Retrospective chart reviews for consecutive patients who underwent hysterectomy for FIGO Stage IA endometrial cancer with serous or clear cell histology between 2004- 2015 were conducted in 6 academic centres. After excluding patients who were upstaged following surgery, a pooled analysis was performed for relevant endpoints. Results A total of 414 patients with a median age of 67 years(range 41-90) met the inclusion criteria. The most common histology were pure serous (64%,n=266) followed by mixed (27%,n=112) and pure clear cell (9%,n=36). Myometrial invasion was identified in 54%(n=222). Most patients underwent some surgical staging including sampling of pelvic lymph node (LN) (81%,n=335), para-aortic LN (45%,n=146), omentum (58%,n=239) and peritoneal washing (62%,n=219). Only 23% of patients (n=95) were considered to have adequate staging (pre-defined as ≥10 pelvic LN, sampled para-aortic LN and omentum). Thirtyfour percent of patients (n=140) received adjuvant chemotherapy and carboplatin/paclitaxel was most commonly used (77%, n=108). Adjuvant RT was delivered to 47%(n=178) of patients (external beam alone 16%,n=29; brachytherapy alone 56%, n=99; both 28%,n=50). The median follow-up was 2.7 years (range 0-12). Among patients who did not received any adjuvant treatment, 5- year actuarial estimates were as follows: local control(LC) 88%, regional control(RC) 93%, distant failure(DF) 15%, disease free survival(DFS) 74%, cancer specific survival(CSS) 91% and overall survival(OS) 82%. Adequate staging was associated with better CSS in patients who did not have adjuvant treatment (100% vs. 87%, logrank p=0.0035). Adjuvant RT was associated with better LC(5- year 96% vs. 84%, HR 0.32,logrank p=0.014). The 5-year RC was 93%, which was not found to be significantly improved by external beam RT. Adjuvant chemotherapy was associated with better LC(5-year 94% vs. 84%,HR 0.29, logrank p=0.0079), DFS(5-year 79% vs. 71%, HR 0.47, logrank p=0.033), but not for RC, DF or CSS. The delivery of at least 5 cycles of chemotherapy, was associated with a trend towards better LC (4-year 98% vs. 88%, HR 0.18,logrank p=0.090). Myometrial invasion, lymphovascular invasion, histological subtypes and the proportion of type II component were not found to be significant prognostic factors for LC, RR, DF or CSS. Conclusion Adjuvant radiotherapy and chemotherapy were associated with better LC and DFS but not for RC, DF or CSS for stage IA serous and clear cell uterine cancer. Observation may be an acceptable strategy in patients who have had adequate surgical staging

Is prostate brachytherapy a dying art? Trends and variation in the definitive management of prostate cancer in Ontario, Canada

Background and purpose: Declining prostate brachytherapy utilization has been reported in several studies, despite strong evidence for efficacy and safety compared to alternatives. We sought to evaluate contemporary trends in brachytherapy, external beam radiotherapy (EBRT) and prostatectomy utilization in a publicly funded healthcare system. Materials and methods: Men with localized prostate cancer diagnosed and treated between 2006 and 2017 in Ontario, Canada were identified using administrative data. Men received EBRT, brachytherapy (monotherapy or boost) or prostatectomy as initial definitive management. Multivariable logistic regression evaluated patient-, tumour-, and provider-factors on treatment utilization. Results: 61,288 men were included. On multivariable regression, the odds of receiving brachytherapy boost increased 24% per year (odds ratio [OR]:1.24, 95% CI 1.22–1.26, p \u3c 0.01), brachytherapy monotherapy increased 3% per year (OR:1.03, 95% CI:1.02–1.04, p \u3c 0.01), and prostatectomy declined by 6% per year (OR:0.94, 95% CI 0.93–0.95, p \u3c 0.01). Treatment year was not significant on multivariable modelling of EBRT. In a separate multivariable model limited to those who received radiotherapy, if the first radiation oncologist seen performed brachytherapy, the OR of receiving brachytherapy monotherapy over EBRT was 5.66 (95% CI: 5.11–6.26, p \u3c 0.01) and 2.88 (95% CI: 2.60–3.19, p \u3c 0.01) for brachytherapy boost over EBRT alone. Substantial geographic, provider and patient variation in treatment receipt was observed. Conclusion: We found increasing brachytherapy utilization, largely driven by increasing utilization of brachytherapy boost. To our knowledge, this is the first report of increasing brachytherapy use in the era of dose escalated EBRT

Improved disease control with adjuvant therapy for stage IA serous and clear cell uterine cancer: A pooled multi-institutional analysis.

Purpose/Objective(s): The optimal adjuvant management of Stage IA endometrial cancer with serous or clear cell histology is not well defined. The objective of this study is to explore the role of adjuvant radiotherapy in this population. Purpose/Objective(s): In this ethics board approved study, retrospective review of consecutive patients at six academic centers who underwent hysterectomy for 2009 FIGO Stage IA endometrial cancer with serous or clear cell histology between 2004 and 2015 was conducted. After excluding patients who were upstaged following surgery, descriptive statistics were generated. Time-to event outcomes were calculated using the Kaplan-Meier method, with prognostic factors identified through univariable and multivariable Cox-proportional hazard modeling. Statistical comparisons were calculated in the SAS environment, with significance defined at the 2-sided 0.05 level. Results: A total of 414 patients with a median age of 67 years (range 41-90) met the inclusion criteria. The most common histology was pure serous (64%) followed by mixed (27%) and pure clear cell (9%). Myometrial invasion was identified in 54%. Adjuvant RT was delivered to 47% of patients (pelvic external beam radiotherapy (EBRT) alone 16%; vaginal vault brachytherapy alone 56%; both 28%). One hundred and fourteen patients (34%) received adjuvant chemotherapy with carboplatin/paclitaxel most commonly used (77%). The median follow-up was 2.7 years (range 0-12). The 5-year local control (LC) was as follows: EBRT + brachytherapy 96%, brachytherapy alone 98%, EBRT alone 86% and no radiation 83%. Adjuvant brachytherapy (both alone and in association with EBRT) was associated with improved LC (5-year 96% vs. 84%, log-rank P = 0.0073, adjusted HR 0.36) and disease free survival (DFS) (5-year 79% vs. 71%, log-rank P = 0.0033, adjusted HR 0.70, P = 0.23) but not cancer specific survival (CSS) or overall survival (OS). The 5-year RC was 93% and was not improved by EBRT. Improved regional control was observed when brachytherapy was delivered but not in EBRT subgroup in multivariate analysis (HR 0.16, P = 0.02). Myometrial invasion, lymphovascular invasion, histological subtypes, and the proportion of type II component were not found to be significant prognostic factors for LC. No differential LC benefits with adjuvant RT were observed in subgroups. Adjuvant chemotherapy was associated with improved LC (5-year 94% vs. 84%, HR 0.29, log-rank P = 0.0079) and DFS (5-year 79% vs. 71%, HR 0.47, log-rank P = 0.033), but did not impact RC, DF or CSS. Conclusion: Adjuvant vaginal vault brachytherapy and chemotherapy were independently associated with improved LC and DFS without an observed OS benefit for stage IA serous and clear cell uterine cancer. Prospective study is warranted to clarify the role of adjuvant pelvic EBRT in this setting

Dose Escalated Radiotherapy (RT) Alone or in Combination With Short-Term Total Androgen Suppression (TAS) for Intermediate Risk Prostate Cancer: Patient Reported Outcomes (PROs) From the NRG Oncology/RTOG 0815 Randomized Trial

Purpose/Objective(s): To report the PROs of a phase III randomized trial evaluating TAS combined with dose-escalated RT for patients with intermediate risk prostate cancer. Materials/Methods: Eligible patients had intermediate risk prostate cancer defined as harboring ≥ 1 of these risk factors: clinical stage T2b-T2c, Gleason score 7, or PSA \u3e 10 to ≤ 20 ng/mL. Patients were randomized to dose-escalated RT alone (Arm 1) or RT plus TAS (Arm 2) consisting of LHRH agonist/antagonist with oral antiandrogen for 6 months. Validated PROs included the Expanded Prostate Cancer Index Composite (EPIC-50) and Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue short form. PRO change scores, calculated for each patient as the follow-up score minus baseline score (at end of RT, 6, 12, and 60 months from start of RT) were compared between treatment arms using a two-sample t test. An effect size (ES) of 0.50 SD (standard deviation) of the baseline measure was considered clinically meaningful. For the PRO sample size, 200 patients per arm would provide 90% statistical power to detect an ES \u3c 0.50 if the completion rate was only 60%. Mixed effect regression models were also utilized. Clinical outcomes are reported in a separate abstract. Results: Of the 402 initial planned subset of trial patients who completed baseline PROs, PRO compliance was approximately 96%, 89%, 86% and 87% at end of RT, 6, 12 and 60 months, respectively. There were no significant differences between these 402 patients and the remaining patients on this trial with respect to age, race, performance status, # risk factors, or comorbidity score. While EPIC urinary and bowel scores decreased significantly by the end of RT in both arms, no clinically meaningful differences between arms were detected over time. For the EPIC hormonal and sexual domains, however, there were clinically meaningful differences between the two arms with greater (P \u3c 0.0001) deficits in the RT + TAS arm. These differences improved over time, with ∼50% resolution by one year after treatment and no clinically meaningful differences by 5 years between arms. PROMIS-fatigue scores increased from baseline in both arms and were significantly higher in arm 2 at the end of RT (P = 0.016), though slightly lower at 12 and 60 months. Conclusion: The addition of TAS to dose-escalated RT demonstrated significant clinically meaningful declines in the EPIC hormonal and sexual domains, and increases in the PROMIS-fatigue scores, compared to RT alone. These scores gradually improved over time, with no clinically meaningful differences between arms in fatigue by one year, or in hormonal and sexual domains by 5 years. Beyond the clinical outcomes, these PRO results directly from patients provide added value to help patients make informed decisions among treatment options