"Like one part of a puzzle" - individualized aromatherapy for women with gynecological cancers in aftercare: results from a qualitative-focused mixed-methods study.

BACKGROUND: Gynecological cancer(s), including breast cancer patients in aftercare and survivors, need supportive strategies to cope with symptoms that are adapted to their individual needs and circumstances. Aromatherapy has potential to be such strategy, but (qualitative) empirical research taking users' own views into consideration about the potential and challenge of aromatherapy is lacking. PURPOSE: The purpose of the study is to gain insights from individualized aromatherapy as a supportive care treatment, regarding their use and evaluation by women with gynecological cancers in aftercare. METHODS: We conducted a study with a mixed-methods design, focused on qualitative research. Five essential oil products were given to 18 participants to apply individually over a 4-week period. After the intervention, qualitative semi-structured interviews were conducted. Further, we documented and assessed symptomatic burdens of the women (MYMOP2) before and after intervention quantitatively. RESULTS: Aromatherapy was customized by the participants according to their needs. It showed potential for relief of symptomatic burdens - especially nausea, peripheral neuropathy, pain, and sleep. Additionally, opportunities emerged to indirectly affect symptomatic burdens. These developed out of new coping strategies (e.g., sleep routines) or by combining with existing strategies (e.g., meditation). Furthermore, aromatherapy was successfully used to promote well-being and encourage mindfulness. CONCLUSION: Our findings demonstrated the potential of aromatherapy as a supportive treatment modality that can be used as a kind of toolbox. Challenges, such as individual odor aversions and intolerances, and limitations due to medication or illness should be considered in future aromatherapy research.

Lymphovascular space invasion and Ki67 as predictors of lymph node metastasis in primary low grade serous ovarian cancer.

OBJECTIVE: Low grade serous ovarian cancers characterize a unique clinical pattern and likely less frequent incidence of lymphatic metastasis. The expression level of Ki67 is associated with differences in prognosis and therapy outcome. However, its expression in combination with lymphovascular space invasion has not been evaluated in the prediction of lymphatic metastasis. METHODS: Patients with low grade serous ovarian cancer were identified in an institutional database. Patients with primary low grade serous ovarian cancer diagnosed and/or treated at our center between September 2000 and December 2018 were identified. Receiver operator characteristics curve analysis was performed to find the cut-off values of per cent Ki67 to discriminate patients with lymph node metastasis. The association between the presence of lymphovascular space invasion and lymph node involvement was analyzed. RESULTS: A total of 109 patients with primary low grade serous ovarian cancer were identified in our institution's database. Of these, 72 (66.1%) patients underwent primary surgery with pelvic and para-aortic lymph node dissection. Complete data for Ki67 expression and lymphovascular space invasion were obtained for 61 (84.7%) of these patients. Among them, 37 (60.7%) patients had lymph node metastasis. The presence of lymphovascular space invasion was associated with an increased risk of lymph node metastases (odds ratio (OR)=12.78, 95% confidence interval (CI) 3.15 to 51.81; p<0.001). In multivariate analysis including age >65 years, peritoneal carcinomatosis, and ascites>500 mL, lymphovascular space invasion remained a significant risk factor for lymphatic metastases (OR=35.11, 95% CI 2.38 to 517.69; p=0.010). Ki67 ≥6% was associated with a higher risk of lymphovascular space invasion (OR=3.67, 95% CI 1.26 to 10.64; p=0.017). No significant correlation between Ki67 expression level and nodal metastases was found (OR=2.19, 95% CI 0.76 to 6.26; p=0.14). Neither presence of lymphovascular space invasion or nodal metastases was associated with a statistically poorer prognosis. CONCLUSIONS: We showed an association between lymphovascular space invasion, Ki67 expression, and risk of lymph node metastasis in primary low grade ovarian cancer. Further prospective trials evaluating lymphovascular space invasion and Ki-67 as predictors of lymph node metastasis are needed.

Recurrent Treatment in Ovarian Cancer Patients: What Are the Best Regimens and the Order They Should Be Given?

OPINION STATEMENT: The choice of the right treatment regimen for recurrent ovarian cancer (rOC) remains a case-by-case decision. It is based on multiple factors that involve patient characteristics and biological factors at the same time. The prioritization of factors is still subject to changes with a trend towards a more personalized medicine. Therefore, participation and engagement in clinical studies constitutes a substantial need for the future development of the treatment algorithm of rOC.

Ki67 expression as a predictor of chemotherapy outcome in low-grade serous ovarian cancer.

OBJECTIVE: Low-grade serous ovarian cancers characterize a unique clinical pattern and lower chemotherapy responsiveness. The expression level of Ki67 is associated with differences in prognosis; however, this has not yet been evaluated in regard to predicting the outcome of therapy. METHODS: Patients with low-grade serous ovarian cancers were identified in an institutional database. Receiver-operator characteristics (ROC) curve analysis was performed to find cut-off values of Ki67 to discriminate patients with residual tumor mass after surgery from maximal debulked patients: therapy response and therapy-free interval (TFI). RESULTS: A total of 68 patients with low-grade serous ovarian cancer were identified. All patients underwent surgery. 61 (89.7%) patients received platinum-based first-line chemotherapy; of these 61 patients, 13 (21.3%) had residual mass (>0 mm) after primary cytoreduction and 11 (18%) received neo-adjuvant chemotherapy. Ki67 ≥3.6% was associated with higher risk of residual mass after surgery (OR 8.1, 95% CI 1.45 to 45.18; p=0.017). Patients with Ki67 <3.6% showed a therapy-free interval of ≥6 months more often (OR 13.9, 95% CI 1.62 to 118.40; p=0.016). In the multivariate analysis of TFI <6 months, including CA125, age at diagnosis, peritoneal carcinomatosis, and ascites, Ki67 <3.6% remained a significant prognostic factor (OR 18.8, 95% CI 1.77 to 199.09; p=0.015). Chemotherapy responsiveness was evaluated in 21 patients who had residual disease and/or received neo-adjuvant chemotherapy. Ki67 ≥4.0% (OR 44.1, 95%CI 2.36-825.17, p = 0.011) was related to a significantly higher response rate (complete and partial response). CONCLUSIONS: This is the first study to show an association between Ki67 expression and chemotherapy response, duration of TFI to platinum-based chemotherapy as well as outcome of surgery in low-grade serous ovarian cancers. Further prospective trials should use Ki-67 as a stratification factor to explore the effect of chemotherapy and endocrine strategies.

Surgery in recurrent ovarian cancer.

Ovarian cancer is one of the most challenging diseases in gynecologic oncology. The presentation of frequent recurrences requires the establishment and further development of therapy standards for this patient group. Surgery is crucial in the therapy of patients with primary ovarian cancer, and the postoperative residual tumor mass is the most relevant clinical prognostic factor. The surgical management of recurrent disease is still subject to an emotional international discussion. Only a few prospective clinical trials focused on the effects of surgery in relapsed ovarian cancer have been published. The available data show improvements in the prognosis due to complete cytoreduction in the setting of recurrence. However, the selection of eligible patients is the essential issue. Therefore, the establishment of reliable predictive factors for complete tumor resection as well as a definition of the group of patients who might profit from this approach remains a field for research. Further randomized trials designed to develop and incorporate operative standards for recurrent ovarian cancer should follow.

Lack of Survival Benefit of Para-Aortic Lymphadenectomy in Advanced Cervical Cancer.

INTRODUCTION: The presence of positive para-aortic lymph nodes in advanced cervical cancer remains the most important prognostic factor for survival and also defines the treatment. Our aim was to define the influence of staging para-aortic lymphadenectomy in patients' survival. MATERIAL AND METHODS: The medical records of 74 patients with advanced cervical cancer (FIGO IIB-IVA) were reviewed. In 31 patients (41.9%), the assessment of lymph nodes was performed with imaging test (group 1) and in 43 (58.1%) within a surgical staging para-aortic lymphadenectomy (group 2). We compared both groups according to stage of disease, treatment, progression-free survival (PFS), and overall survival (OS). RESULTS: The extended-field radiotherapy was performed in 44.2 and 19.4% of patients in surgical and imaging staging group, respectively (p = 0.045). The disease-free survival rate was 17.4 ± 17.4 months in group 1 and 14.4 ± 12.6 months in group 2 (p = 0.456). No differences in OS were found between these 2 groups (p = 0.676). CONCLUSIONS: Despite the higher diagnostic accuracy of surgical staging and the higher number of patient who received extended field radiotherapy, we did not find differences between the overall and PFS rates in both the studied groups. Further prospective study on a higher number of patients would be necessary.

Clinical Outcome After Completion Surgery in Patients With Ovarian Cancer: The Charite Experience.

OBJECTIVE: The aim of this study was to estimate surgical outcome and survival benefit after completion surgery. METHODS: We evaluated 164 patients with epithelial ovarian cancer who underwent incomplete primary cytoreductive surgery or rather received only staging procedures from January 2000 to December 2014 in outside institutions. Patient-related data were registered in prospective database of Tumor Bank Ovarian Cancer. The outcome analyses were performed for early and advanced stages of ovarian cancer separately. RESULTS: The majority of patients were at the time of completion surgery in advanced stages of disease. From overall 111 advanced epithelial ovarian cancer patients, 74 (66.6%) could be operated macroscopically tumor free, minimal residual disease 1 cm or less was achieved in 15.3% of the cases. Mean overall survival for patients without versus those with any tumor residual was 70 months (95% confidence interval, 61.3-81.5) versus 24.7 months (95% confidence interval, 7.1-42.4; P ≤ 0.0001). After applying completion surgery, 47 (28.6%) and 12 (6.7%) patients were upstaged in FIGO (International Federation of Gynecology and Obstetrics) IIIC and IV stages, respectively. Upstaging resulted in therapy changes in 10 patients (19%) with assumed FIGO IA stages. Major operative complications were registered in 28.8% of advanced cases, and 30-day mortality reached 1.8%. CONCLUSIONS: Recent research has shown that the most profound impact on survivorship occurs when women get proper care from surgeons trained in the latest techniques for treating ovarian cancer. Completion surgery maintained that even after initial incomplete cytoreduction outside of the high specialized units, after applying appropriate surgery techniques macroscopically, disease-free situation is achievable and outcomes are comparable with the results of primary debulking surgery.

Robotic and Advanced Laparoscopic Surgical Training in European Gynecological Oncology Trainees.

INTRODUCTION: Advanced minimal access surgical training is an important component of training in gynecological oncology (GO). Europe-wide data on this topic are lacking. We present data on availability and trainee experience of advanced laparoscopic surgical (ALS) and robotic surgical (RS) training in GO across Europe. METHOD: A prospective web-based anonymized survey of European GO trainees was sent to the European Network of Young Gynaecological Oncologists members/trainees. It included sociodemographic information and specific questions pertaining to training experience or satisfaction in laparoscopic and robotic surgery. χ test was used for evaluating categorical variables and Mann-Whitney/Kruskal-Wallis (nonparametric) tests for continuous variables between 2 and more independent groups. RESULTS: A total of 113 GO trainees from 29 countries responded. The mean (standard deviation) age was 35.2 (6.1) years, 59.3% were men, 40.7% were women, and 46% were in accredited training posts. The ALS and RS training was offered in only 43% and 23% of institutes respectively, and 54% and 23% of trainees had undergone some form of formal or informal training in ALS and RS respectively. A total of 62.4% felt that RS should be a formal component of GO training programs. A total of 61% and 35% planned to go outside their institute for ALS or RS training respectively. Trainees rating (1-5 scale) of their open surgery and ALS or RS skills (3.3/2.6/1.9) and training experience (3.5/2.8/2.1), respectively, were higher for open surgery than ALS or RS (P < 0.0005). Accredited posts were more likely than nonaccredited posts to offer ALS training (60%/31%, P = 0.002), formal training schedules (27.9%/4.4%, P = 0.003), and use of logbooks (46%/23%, P = 0.035). CONCLUSIONS: Training and experience in ALS and RS are poorly rated by GO trainees across Europe, and only few centers offer this. There is an urgent need to expand and harmonize training opportunities for ALS and RS. Most trainees want RS included as a formal component of their training.

Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer. An analysis of the AGO Study Group metadatabase.

OBJECTIVE: Since almost two decades standard 1st-line chemotherapy for advanced ovarian cancer (AOC) has been a platinum/taxane combination. More recently, this general strategy has been challenged because different types of AOC may not benefit homogenously. Low-grade serous ovarian cancer (LGSOC) is one of the candidates in whom efficacy of standard chemotherapy should be revised. METHODS: This study is an exploratory case control study of the AGO-metadatabase of 4 randomized phase III trials with first-line platinum combination chemotherapy without any targeted therapy. Patients with advanced FIGO IIIBIV low-grade serous ovarian cancer were included and compared with control cases having high-grade serous AOC. RESULTS: Out of 5114 patients in this AGO database 145 (2.8%) had LGSOC and of those thirty-nine (24.1%) had suboptimal debulking with post-operative residual tumor >1cm, thus being eligible for response evaluation. An objective response was observed in only 10 patients and this 23.1% response rate (RR) was significantly lower compared to 90.1% RR in the control cohort of high-grade serous ovarian cancer (HGSOC) (p<0.001). Both, LGSOC and HGSOC patients who underwent complete cytoreduction had significantly better progression free survival (PFS) and overall survival (OS) in comparison to those with residuals after primary surgery, accordingly (p<0.001). CONCLUSIONS: Our observation indicates that low-grade serous cancer is not as responsive to platinum-taxane-based chemotherapy as high-grade serous AOC. In contrast, surgical debulking showed a similar impact on outcome in both types of AOC thus indicating different roles for both standard treatment modalities. Systemic treatment of low grade serous AOC urgently warrants further investigations.

The work place educational climate in gynecological oncology fellowships across Europe: the impact of accreditation.

BACKGROUND: A good educational climate/environment in the workplace is essential for developing high-quality medical (sub)specialists. These data are lacking for gynecological oncology training. OBJECTIVE: This study aims to evaluate the educational climate in gynecological oncology training throughout Europe and the factors affecting it. METHODS: A Web-based anonymous survey sent to ENYGO (European Network of Young Gynecological Oncologists) members/trainees to assess gynecological oncology training. This included sociodemographic information, details regarding training posts, and a 50-item validated Dutch Residency Educational Climate Test (D-RECT) questionnaire with 11 subscales (1-5 Likert scale) to assess the educational climate. The χ test was used for evaluating categorical variables, and the Mann-Whitney U (nonparametric) test was used for continuous variables between 2 independent groups. Cronbach α assessed the questionnaire reliability. Multivariable linear regression assessed the effect of variables on D-RECT outcome subscales. RESULTS: One hundred nineteen gynecological oncological fellows responded. The D-RECT questionnaire was extremely reliable for assessing the educational environment in gynecological oncology (subscales' Cronbach α, 0.82-0.96). Overall, trainees do not seem to receive adequate/effective constructive feedback during training. The overall educational climate (supervision, coaching/assessment, feedback, teamwork, interconsultant relationships, formal education, role of the tutor, patient handover, and overall consultant's attitude) was significantly better (P = 0.001) in centers providing accredited training in comparison with centers without such accreditation. Multivariable regression indicated the main factors independently associated with a better educational climate were presence of an accredited training post and total years of training. CONCLUSIONS: This study emphasizes the need for better feedback mechanisms and the importance of accreditation of centers for training in gynecological oncology to ensure training within higher quality clinical learning climates.

Usefulness of diagnostic indices comprising clinical, sonographic, and biomarker data for discriminating benign from malignant ovarian masses.

The objective of this study was to review the accuracy of indices combining several diagnostic variables, in comparison to other models, sonography alone, and biomarker assays, for predicting benign or malignant ovarian lesions. Different single modalities were reviewed. The most useful complex models were International Ovarian Tumor Analysis (IOTA) sonographic logistic regression model 2 (area under the curve, 0.949), risk of malignancy index-cancer antigen 125-human epididymis protein 4 (0.950), risk of malignancy algorithm (0.953), pelvic mass score (0.960), non-IOTA logistic regression model (0.970), and histoscanning score logistic regression model (0.970). None of the indices was superior to an expert subjective sonographic assessment (0.968). For women with adnexal tumors, indices with high accuracy are available that are applicable in clinical practice and comparable to an expert subjective sonographic assessment for discriminating benign from malignant masses.

Evaluation of leptin serum concentrations during surgery and first-line chemotherapy in primary epithelial ovarian cancer patients.

AIM OF THE STUDY: The available data on serum leptin levels in ovarian cancer present contradictory results. The majority of authors report lower leptin levels in those patients in comparison to healthy individuals. However, there is no data regarding leptin concentrations during therapy in women with primary epithelial ovarian cancer. MATERIAL AND METHODS: Blood samples were collected at the time of diagnosis, after initial surgery, and after first-line chemotherapy. Leptin serum concentrations were analysed using ELISA technique. Additionally, parallel measurements of CA125 levels were performed. RESULTS: Fifty-three patients with primary epithelial ovarian cancer met the inclusion criteria and were included in our study. Our analysis revealed a significant difference in mean preoperative serum leptin concentrations between early and advanced ovarian cancer patients (p < 0.0001). We identified statistically significant elevation of mean serum leptin levels (p < 0.001) after complete macroscopic cytoreduction and after first-line chemotherapy in advanced ovarian cancer cases. DISCUSSION: In this cohort, a significant elevation of postoperative serum leptin levels after complete macroscopic cytoreduction were shown. Moreover, elevation of leptin levels corresponded with remission after chemotherapy. Further studies are needed to determine if leptin can be a potential marker of surgery completeness as well as a marker in chemotherapy response evaluation.

Creation of the Polish version and adaptation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Endometrial Cancer Module (QLQ-EN24).

AIM OF THE STUDY: The purpose of this study was to create and introduce a Polish version of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Endometrial Cancer (QLQ-EN24). MATERIAL AND METHODS: The translation procedure described by the EORTC was adopted; this comprised two independent forward translations of the original English questionnaire into Polish, two independent backward translations from Polish to English and pilot testing conducted on 12 patients with diagnosed endometrial cancer. They were asked whether there was any difficulty in answering, confusion while answering, or difficulty in understanding the questions, and if the patients themselves would have framed the questions in a different way. RESULTS: During the process of translation, discussions and text corrections were performed by medical experts and native English speakers. Some sentences or phrasing were adopted from other EORTC questionnaires for different diseases. After pilot testing, further text corrections were adopted according to patients' comments. These involved wording, sentence structure, and text editing (font size, bolding). CONCLUSIONS: The final version of the Polish EN24 questionnaire has been approved by the EORTC Translational Office. It is available on the EORTC web page now.

Pre-Operative Malnutrition in Patients with Ovarian Cancer: What Are the Clinical Implications? Results of a Prospective Study.

BACKGROUND: Malnutrition was associated with worse survival outcomes, impaired quality of life, and deteriorated performance status across various cancer types. We aimed to identify risk factors for malnutrition in patients with epithelial ovarian cancer (EOC) and impact on survival. METHODS: In our prospective observational monocentric study, we included the patients with primary and recurrent EOC, tubal or peritoneal cancer conducted. We assessed serum laboratory parameters, body mass index, nutritional risk index, nutritional risk screening score (NRS-2002), and bio-electrical impedance analysis. RESULTS: We recruited a total of 152 patients. Patients > 65 years-old, with ascites of >500 mL, or with platinum-resistant EOC showed statistically significant increased risk of malnutrition when evaluated using NRS-2002 (p-values= 0.014, 0.001, and 0.007, respectively). NRS-2002 < 3 was an independent predictive factor for complete tumor resectability (p = 0.009). The patients with NRS-2002 ≥ 3 had a median overall survival (OS) of seven months (95% CI = 0-24 months), as compared to the patients with NRS-2002 < 3, where median OS was forty-six months (p = 0.001). A phase angle (PhAα) ≤ 4.5 was the strongest predictor of OS. CONCLUSIONS: In our study, we found malnutrition to be an independent predictor of incomplete cytoreduction and independent prognostic factor for poor OS. Preoperative nutritional assessment is an effective tool in the identification of high-risk EOC groups characterized by poor clinical outcome.

The need for more workshops in laparoscopic surgery and surgical anatomy for European gynaecological oncology trainees: a survey by the European Network of Young Gynaecological Oncologists.

OBJECTIVE: The objective of this study was to highlight the relative preference of European gynecologic oncology trainees for workshops that could support and supplement their training needs. METHODS: A Web-based survey was sent to 900 trainees on the European Network of Young Gynaecological Oncologists database in November 2011. Respondents were asked to rate a 13-item questionnaire (using a 1- to 5-point Likert scale) on workshop topics they felt would most benefit their training requirements. Free text space for additional topics was also provided. Descriptive analysis was used to describe the mean scores reported for different items. A complete linkage hierarchical cluster analysis with Dendron plot was used to assess any clustering of data, and Cronbach α was used to assess the internal reliability of the questionnaire. RESULTS: One hundred ninety trainees from 37 countries responded to the survey, giving a 21% response rate. The 3 most important topics reported were laparoscopic surgery; surgical anatomy, and imaging techniques in gynecologic oncology. The Dendron plot indicated 4 different clusters of workshops (research related skills, supportive ancillary skills, related nonsurgical subspecialties, and core surgical skills) reflecting different competencies trainees need to meet. There was no significant association between individual country of training and workshop preference. The mean duration of the workshop preferred by 71% of respondents was 2 days. Cronbach α of the 13-item questionnaire was 0.78, which suggests good internal consistency/reliability. CONCLUSIONS: This report for the first time highlights the relative importance and significance European trainees attach to some of their training needs in gynecologic oncology. Laparoscopic surgery, surgical anatomy, and imaging appear to be the 3 areas of greatest need. The European Society of Gynaecological Oncology, other national specialist societies, and institutions should direct additional training efforts at these areas.

Surgical outcome of extraperitoneal paraaortic lymph node dissections compared with transperitoneal approach in gynecologic cancer patients.

STUDY OBJECTIVE: To evaluate the surgical outcome of extraperitoneal paraaortic lymph node dissection compared with the traditional transperitoneal approach. DESIGN: Retrospective review (Canadian Task Force classification III). SETTING: University hospital. PATIENTS: Women with gynecologic malignancies admitted to our hospital between 2007 and 2011 who underwent laparoscopic paraaortic lymphadenectomy. INTERVENTIONS: Indication, diagnosis, and outcome according to type of surgery were evaluated. MEASUREMENTS AND MAIN RESULTS: Of 47 patients who underwent laparoscopic paraaortic lymphadenectomy because of gynecologic indications, 28 patients underwent extraperitoneal paraaortic lymph node dissection and 19 underwent the same procedure via the classic transperitoneal technique. The most frequent indication for extraperitoneal lymph node dissection was cervical cancer (71.4%), and for the transperitoneal technique was endometrial cancer (47.4%). The mean (SD) duration of surgery was 211 (38) minutes in the transperitoneal approach group, and 173 (51) minutes in the extraperitoneal lymphadenectomy group (p = .009). No significant differences between groups were found in the number of lymph nodes removed (15 [5.9] nodes in the extraperitoneal group vs 17.4 [8.6] in the transperitoneal group; p = .25). However, a higher rate of positive nodes was observed in the extraperitoneal group than in the transperitoneal group (42.8% vs 36.2%, respectively [p = .001]), and a significantly shorter stay in the intensive care unit in the extraperitoneal group (0.59 [0.5] vs 1.1 [0.5] days, respectively; p = .02). No significant differences in complication rate were found between groups. CONCLUSIONS: Extraperitoneal paraaortic lymph node dissection is a minimally invasive procedure that is an excellent and safe approach to the paraaortic area, with a low complication rate, sufficient number of lymph nodes, and short hospital stay. It seems to be a good alternative to the classic transperitoneal approach.

Improving community-based COPD care in general practice in Poland - a cluster randomized controlled trial.

INTRODUCTION AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. The aim of the study was to evaluate the impact of intervention on exacerbations of COPD in elderly patients compared to those receiving usual care. MATERIAL AND METHODS: A 12 month, multicentre, three-arm, pragmatic, cluster randomized controlled trial was performed (CRCT). The 97 largest PHC clinics with at least 46 COPD registered patients in the Lódz Province, in central Poland. In total, 27,534 COPD patients aged 65 and over were identified from the National Health Fund (NFZ) electronic health records. A checklist of selected, recommended COPD interventions sent to GPs once or twice by post and shown on their desk in their clinics, in the intervention arms. RESULTS: A primary outcome was the difference in exacerbations or deaths between the 3 arms at 12 months. The amounts of specific short- and long-acting drugs purchased by patients were also assessed as secondary outcomes. Only 0.44% (122 of 27 534) COPD patients demonstrated exacerbations after the one-year study period. No statistically significant associations were found between interventions and exacerbations (p=0.1568, Chi-Square) or deaths (p=0.8128, Chi-Square) at 12 months. CONCLUSIONS: As this study coincided with the pandemic period, the results should be interpreted with care. The intervention had no association with exacerbations. Future research on interventions aimed at improving chronic illness care are needed.

Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis.

PURPOSE: For patients with severe renal impairment (CrCl ≤ 30 ml/min) or end-stage renal disease (ESRD), olaparib intake is not recommended as the pharmacokinetics and safety of olaparib have not been evaluated in this patient group. Therefore, this valuable patient group is generally excluded from poly(ADP-ribose) polymerase inhibitor (PARPi) therapy. Here we report the pharmacokinetics (PK), efficacy, safety and tolerability of olaparib capsules 200 mg BID in a patient with recurrent epithelial ovarian cancer (EOC) and ESRD requiring hemodialysis. METHODS: Blood and dialysate samples of the patient were collected on a dialysis and non-dialysis day. Olaparib total plasma concentrations were determined through high-performance liquid chromatography with tandem mass spectrometric detection. Actual scheduled sample times were used in the PK analysis to determine multiple dose PK parameters at steady state. RESULTS: Maximum concentration was achieved 1.5 h after drug administration on non- dialysis and after 1 h on dialysis day. The steady-state trough concentration and the maximal plasma concentration were similar on dialysis and non- dialysis day. On non-dialysis day, the AUCss was 30% higher (24.0 µg.h/mL vs. 16.9 µg.h/ml) than on dialysis day. The plasma clearance CLss/F was lower on non-dialysis day. Olaparib was not detectable in the dialysate samples. CONCLUSION: A total dose of olaparib 200 mg BID capsule formulation was well tolerated by our patient with ESRD and hemodialysis. Moreover, this maintenance therapy led to 16 months of progression free survival. Further trials on PARPi therapy in patients with hemodialysis are warranted.