Incorporating patient-reported outcome measures (PROMs) into a clinical quality registry (CQR) for ovarian cancer: considerations and challenges.

As medical treatment increasingly focuses on improving health-related quality of life, patient-reported outcome measures (PROMs) are an essential component of clinical research. The National Gynae-Oncology Registry (NGOR) is an Australian clinical quality registry. A suitable PROM was required for the NGOR ovarian cancer module to complement clinical outcomes and provide insights into outcomes important to patients. Our narrative review aimed to identify existing ovarian cancer-specific PROMs and ascertain which tool would be most appropriate for implementation into the NGOR ovarian cancer module.A literature review of Cochrane Library, Embase, MEDLINE and PubMed databases was performed to identify existing ovarian cancer-specific PROM tools. A steering committee was convened to (1) determine the purpose of, and criteria for our required PROM; and (2) to review the available tools against the criteria and recommend the most appropriate one for implementation within the NGOR.The literature review yielded five tools: MOST, EORTC QLQ-OV28, FACIT-O, NFOSI-18 and QOL-OVCA. All were developed and validated for use in clinical trials, but none had been validated for use in clinical quality registry. Our expert steering committee pre-determined purpose of a PROM tool for use within the NGOR was to enable cross-service comparison and benchmarking to drive quality improvements. They identified that while there was no ideal, pre-existing, ovarian cancer-specific PROM tool for implementation into the NGOR, on the basis of its psychometric properties, its available translations, its length and its ability to be adapted, the EORTC tool is most fit-for-purpose for integration into the NGOR.This process enabled identification of the tool most appropriate to provide insights into how ovarian cancer treatments impact patients' quality of life and permit benchmarking across health services.

Rates of paclitaxel hypersensitivity reactions using a modified Markman's infusion protocol as primary prophylaxis.

PURPOSE: Markman's desensitisation protocol allows successful retreatment of patients who have had significant paclitaxel hypersensitivity reactions. We aimed to reduce the risk and severity of paclitaxel hypersensitivity reactions by introducing this protocol as primary prophylaxis. METHODS: We evaluated all patients with a gynaecological malignancy receiving paclitaxel before (December 2018 to September 2019) and after (October 2019 to July 2020) the implementation of a modified Markman's desensitisation protocol. The pre-implementation group received paclitaxel over a gradually up-titrated rate from 60 to 180 ml/h. The post-implementation group received paclitaxel via 3 fixed-dose infusion bags in the first 2 cycles. Rates and severity of paclitaxel hypersensitivity reactions were compared. RESULTS: A total of 426 paclitaxel infusions were administered to 78 patients. The median age was 64 years (range 34-81), and the most common diagnosis was ovarian, fallopian tube and primary peritoneal cancer (67%, n = 52/78). Paclitaxel hypersensitivity reaction rates were similar in the pre-implementation (8%, n = 16/195) and post-implementation groups (9%, n = 20/231; p = 0.87). Most paclitaxel hypersensitivity reactions occurred within 30 min (pre- vs. post-implementation, 88% [n = 14/16] vs. 75% [n = 15/20]; p = 0.45) and were grade 2 in severity (pre- vs. post-implementation, 81% [n = 13/16] vs. 75% [n = 15/20]; p = 0.37). There was one grade 3 paclitaxel hypersensitivity reaction in the pre-implementation group. All patients were successfully rechallenged in the post-implementation group compared to 81% (n = 13/16) in the pre-implementation group (p = 0.43). CONCLUSION: The modified Markman's desensitisation protocol as primary prophylaxis did not reduce the rate or severity of paclitaxel hypersensitivity reactions, although all patients could be successfully rechallenged.

Hidden in plain sight - Survival consequences of baseline symptom burden in women with recurrent ovarian cancer.

OBJECTIVE: To describe the baseline symptom burden(SB) experienced by patients(pts) with recurrent ovarian cancer(ROC) prior and associations with progression free survival (PFS) and overall survival (OS). METHODS: We analysed baseline SB reported by pts. with platinum resistant/refractory ROC (PRR-ROC) or potentially­platinum sensitive ROC receiving their third or greater line of chemotherapy (PPS-ROC≥3) enrolled in the Gynecologic Cancer InterGroup - Symptom Benefit Study (GCIG-SBS) using the Measure of Ovarian Symptoms and Treatment concerns (MOST). The severity of baseline symptoms was correlated with PFS and OS. RESULTS: The 948 pts. reported substantial baseline SB. Almost 80% reported mild to severe pain, and 75% abdominal symptoms. Shortness of breath was reported by 60% and 90% reported fatigue. About 50% reported moderate to severe anxiety, and 35% moderate to severe depression. Most (89%) reported 1 or more symptoms as moderate or severe, 59% scored 6 or more symptoms moderate or severe, and 46% scored 9 or more symptoms as moderate or severe. Higher SB was associated with significantly shortened PFS and OS; five symptoms had OS hazard ratios larger than 2 for both moderate and severe symptom cut-offs (trouble eating, vomiting, indigestion, loss of appetite, and nausea; p < 0.001). CONCLUSION: Pts with ROC reported high SB prior to starting palliative chemotherapy, similar among PRR-ROC and PPS-ROC≥3. High SB was strongly associated with early progression and death. SB should be actively managed and used to stratify patients in clinical trials. Clinical trials should measure and report symptom burden and the impact of treatment on symptom control.

Mucinous ovarian carcinoma: A survey of practice in Australia and New Zealand.

BACKGROUND: Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer with limited evidence to support clinical care. AIMS: We undertook a clinician survey to better understand current practice in treating MOC in Australia and New Zealand, and to determine any features associated with variation in care. In addition, we aimed to understand future research priorities. METHODS: A RedCap survey was distributed to clinician members of the Australia New Zealand Gynaecological Oncology Group (ANZGOG). Questions included respondent demographics, three case studies and future research priorities. Clinicians were asked questions specific to their speciality. RESULTS: Respondents (n = 47) were commonly experienced gynae-oncology specialists, most often surgical (38%) or medical (30%) oncologists. There was good consensus for surgical approaches for stage I disease; however, variation in practice was noted for advanced or recurrent MOC. Variation was also observed for medical oncologists; in early-stage disease there was no clear consensus on whether to offer chemotherapy, or which regimen to recommend. For advanced and recurrent disease a wide range of chemotherapy options was considered, with a trend away from an ovarian-type toward gastrointestinal (GI)-type regimens in advanced MOC. This practice was reflected in future research priorities, with 'Is a GI chemotherapy regimen better than an ovarian regimen?' the most highly ranked option, followed by 'Should stage 1C patients receive chemotherapy?' CONCLUSIONS: Although the number of respondents limited the analyses, it was clear that chemotherapy selection was a key point of divergence for medical oncologists. Future research is needed to establish well-evidenced guidelines for clinical care of MOC.

Effect of storage temperature on the dimensional stability of DLP printed casts.

STATEMENT OF PROBLEM: Despite studies focusing on the accuracy and dimensional stability of additive manufacturing, research on the impact of storage conditions on these properties of 3-dimensional (3D) printed objects is lacking. PURPOSE: The purpose of this in vitro study was to investigate the influence of storage temperature on the dimensional stability of digital light processing (DLP) printed casts and to determine how different locations in printed casts react differently. MATERIAL AND METHODS: A completely dentate maxillary typodont model was digitized with a desktop laser scanner. The typodont was subsequently modified with a software program by adding cuboids with a side length of 3 mm on both maxillary central incisors, first molars, and second molars. The file was saved in the standard tessellation language (STL) format. The modified digitized typodont was then processed through the DLP technology printing process with a desktop DLP printer and photopolymerizing resin. The casts were printed 32 times and stored in sealed plastic bags, shielded from light, and subjected to 4 different temperature conditions (-20 °C, 4 °C, 20 °C, and 37 °C, n=8 each). The cuboids on the central incisors were labeled as the P1 group, first molars as the P2 group, and second molars as the P3 group. The distance between the cuboids was measured 5 times, with results recorded immediately after cast production and at 1, 2, 3, 5, 7, 14, and 28 days after. Repeated analysis of variance (ANOVA) and the Tukey honestly significant difference (HSD) test were used to compare the recorded values among the groups (α=.05). RESULTS: In the P1 group, the casts stored at -20 °C exhibited the smallest overall size change, with a mean ±standard deviation volume of 99.42 ±0.04% compared with the original casts after 28 days of storage. This was followed by the casts stored at 4 °C, 20 °C, and 37 °C, with remaining volumes of 99.39 ±0.06% (P=.139), 99.14 ±0.08% (P<.001), and 98.96 ±0.03% (P<.001), respectively. For the P2 and P3 groups, casts stored at 4 °C retained the most volume at 99.82 ±0.01%, whereas those stored at -20 °C, 20 °C, and 37 °C underwent greater changes, with remaining volumes of 99.66 ±0.03%, 100.32 ±0.02%, and 100.44 ±0.02%, respectively (P<.001). The P3 group exhibited a similar trend to that of the P2 group, with the casts stored at 4 °C remaining closest to the original dimensions at 99.86 ±0.02%, while casts stored at -20 °C showed 99.73 ±0.03% of the original volume and those stored at 20 °C and 37 °C expanded with volumes of 100.37 ±0.03% and 100.48 ±0.03%, respectively (P<.001). CONCLUSIONS: DLP printed casts stored at 4 °C exhibited the greatest overall dimensional stability, followed sequentially by those stored at -20 °C, 20 °C, and 37 °C. Additionally, the study confirmed that the posterior and anterior teeth regions of DLP printed casts respond differently to different storage temperatures.

Association of chemotherapy dose intensity and age with outcomes in patients with Ewing's family sarcoma.

BACKGROUND: Ewing's family sarcoma (EFS) is an aggressive malignancy with a peak incidence in adolescents. Multimodal treatment involves surgery and/or radiotherapy, and chemotherapy typically with VDC/IE (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide). There is a paucity of data for the treatment of adults, with protocols extrapolated from the pediatric setting. This study aimed to assess patterns of care, chemotherapy tolerability across age groups, and outcomes from four Australian sarcoma centers. METHODS: ANZSA ACCORD sarcoma database and medical records were used to identify and collect data of patients aged ≥ 10 years with EFS who received VDC/IE between 2010 and 2020. Survival outcomes were analyzed based on chemotherapy received dose intensity (RDI). Clinical predictors of RDI were explored using logistic regression. RESULTS: Of 146 patients with EFS, 76 received VDC/IE. The majority had localized disease (65%). Seventy-one percent completed scheduled chemotherapy, with some requiring dose reduction (29%), delay > 7 days (65%), or cycle omission (4%). Hematological toxicity was the main reason for dose reduction/delay. Fifty-seven percent patients achieved an acceptable RDI ≥85%. Compared to those aged 10-19, the odds ratio for acceptable RDI aged 40-59 was 0.20 (95% CI 0.04-0.86, p = 0.04). RDI was an independent prognostic factor for overall survival, after accounting for age, gender, Ewing's type, primary site, and stage (adjusted HR 0.25 [95% CI 0.10-0.63], p = 0.004). CONCLUSION: Survival outcomes in EFS were associated with chemotherapy RDI. Older adults more commonly required dose reduction or early cessation of treatment due to toxicity. VDC/IE chemotherapy should be carefully tailored in adults > 40 years.

A phase I study of the Wee1 kinase inhibitor adavosertib (AZD1775) in combination with chemoradiation in cervical, upper vaginal, and uterine cancers.

OBJECTIVE: Wee1 kinase is a crucial regulator of the G2/M checkpoint which prevents entry of damaged DNA into mitosis. Adavosertib (AZD1775), a selective inhibitor of Wee1, induces G2 escape and increases cytotoxicity when combined with DNA damaging agents. We aimed to evaluate the safety and efficacy of adavosertib in combination with definitive pelvic radiotherapy and concurrent cisplatin in patients with gynecological cancers. METHODS: A multi-institutional, open-label phase I trial was designed to assess dose escalation (3+3 design) of adavosertib in combination with standard chemoradiation. Eligible patients with locally advanced cervical, endometrial or vaginal tumors were treated with a 5-week course of pelvic external beam radiation 45-50 Gy in 1.8-2 Gy daily fractions plus concurrent weekly cisplatin 40 mg/m2 and adavosertib 100 mg/m2 on days 1, 3 and 5 of each week during chemoradiation. The primary endpoint was to determine the recommended phase II dose of adavosertib. Secondary endpoints included toxicity profile and preliminary efficacy. RESULTS: Ten patients were enrolled (nine locally advanced cervical and one endometrial cancer). Two patients experienced a dose-limiting toxicity at dose level 1 (adavosertib 100 mg by mouth daily on days 1, 3 and 5), including one patient with grade 4 thrombocytopenia, and one with treatment hold >1 week due to grade 1 creatinine elevation and grade 1 thrombocytopenia. At dose level -1 (adavosertib 100 mg by mouth daily on days 3 and 5), one out of five patients enrolled had a dose-limiting toxicity in the form of persistent grade 3 diarrhea. The overall response rate at 4 months was 71.4%, including four complete responses. At 2 years follow-up, 86% of patients were alive and progression-free. CONCLUSION: The recommended phase II dose could not be determined due to clinical toxicity and early trial closure. Preliminary efficacy appears promising, yet selecting the adequate dose/schedule in combination chemoradiation warrants further investigation to limit overlapping toxicities.

Managing Adverse Effects Associated With Poly (ADP-ribose) Polymerase Inhibitors in Ovarian Cancer: A Synthesis of Clinical Trial and Real-World Data.

The use of poly (ADP-ribose) polymerase (PARP) inhibitor therapy is standard care in the management of patients with various malignancies including ovarian, breast, prostate, and pancreatic cancers. PARP inhibitors have been approved in different settings for patients with specific hereditary pathogenic variants, most notably homologous recombination repair pathways such as BRCA1 and BRCA2 genes. The vast experience with PARP inhibitors (olaparib, niraparib, rucaparib) has been in the management of epithelial ovarian cancer. There have not been any head-to-head comparisons of PARP inhibitors in randomized trials, and we can only perform cross-comparison on the basis of the reported literature. The three approved PARP inhibitors share several common adverse effects because of a class effect including nausea, fatigue, and anemia, but there are notable differences likely because of variations in their poly-pharmacology and off-target effects. Finally, patients included in clinical trials are often younger with a good performance status and less comorbidities than the real-world population, and hence, the potential benefits and adverse effects may not be superimposable. In this review, we describe these differences and discuss strategies to mitigate and manage adverse side effects effectively.

Patient-Reported Outcomes in Ovarian Cancer: Facilitating and Enhancing the Reporting of Symptoms, Adverse Events, and Subjective Benefit of Treatment in Clinical Trials and Clinical Practice.

Patient-reported outcomes (PROs) provide a valid, standardized way of assessing symptoms, adverse events and the subjective benefit of treatment from the patient's perspective. Assessment of PROs is critical in ovarian cancer due to the high morbidity of the disease and its treatments. Several well-validated PRO measures are available to assess PROs in ovarian cancer. Their inclusion in clinical trials can provide evidence on the benefits and harms of new treatments based on patients' experiences to guide improvements in clinical practice and health policy. Aggregate PRO data collected in clinical trials can be used to inform patients about likely treatment impacts and assist them to make informed treatment decisions. In clinical practice, PRO assessments can facilitate monitoring of a patient's symptoms throughout treatment and follow-up to guide their clinical management; in this context, an individual patient's responses can facilitate communication with their treating clinician about troublesome symptoms and their impact on their quality of life. This literature review aimed to provide clinicians and researchers with a better understanding of why and how PROs can be incorporated into ovarian cancer clinical trials and routine clinical practice. We discuss the importance of assessing PROs throughout the ovarian cancer disease and treatment trajectory in both clinical trials and clinical practice, and provide examples from existing literature to illustrate the uses of PROs as the goals of treatment change in each setting.

Adjuvant chemotherapy following chemoradiotherapy as primary treatment for locally advanced cervical cancer versus chemoradiotherapy alone (OUTBACK): an international, open-label, randomised, phase 3 trial.

BACKGROUND: Standard treatment for locally advanced cervical cancer is chemoradiotherapy, but many patients relapse and die of metastatic disease. We aimed to determine the effects on survival of adjuvant chemotherapy after chemoradiotherapy. METHODS: The OUTBACK trial was a multicentre, open-label, randomised, phase 3 trial done in 157 hospitals in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the USA. Eligible participants were aged 18 year or older with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, II, IIIB, or IVA disease), Eastern Cooperative Oncology Group performance status 0-2, and adequate bone marrow and organ function. Participants were randomly assigned centrally (1:1) using a minimisation approach and stratified by pelvic or common iliac nodal involvement, requirement for extended-field radiotherapy, FIGO 2008 stage, age, and site to receive standard cisplatin-based chemoradiotherapy (40 mg/m2 cisplatin intravenously once-a-week for 5 weeks, during radiotherapy with 45·0-50·4 Gy external beam radiotherapy delivered in fractions of 1·8 Gy to the whole pelvis plus brachytherapy; chemoradiotherapy only group) or standard cisplatin-based chemoradiotherapy followed by adjuvant chemotherapy with four cycles of carboplatin (area under the receiver operator curve 5) and paclitaxel (155 mg/m2) given intravenously on day 1 of a 21 day cycle (adjuvant chemotherapy group). The primary endpoint was overall survival at 5 years, analysed in the intention-to-treat population (ie, all eligible patients who were randomly assigned). Safety was assessed in all patients in the chemoradiotherapy only group who started chemoradiotherapy and all patients in the adjuvant chemotherapy group who received at least one dose of adjuvant chemotherapy. The OUTBACK trial is registered with ClinicalTrials.gov, NCT01414608, and the Australia New Zealand Clinical Trial Registry, ACTRN12610000732088. FINDINGS: Between April 15, 2011, and June 26, 2017, 926 patients were enrolled and randomly assigned to the chemoradiotherapy only group (n=461) or the adjuvant chemotherapy group (n=465), of whom 919 were eligible (456 in the chemoradiotherapy only group and 463 in the adjuvant chemotherapy group; median age 46 years [IQR 37 to 55]; 663 [72%] were White, 121 [13%] were Black or African American, 53 [6%] were Asian, 24 [3%] were Aboriginal or Pacific islander, and 57 [6%] were other races) and included in the analysis. As of data cutoff (April 12, 2021), median follow-up was 60 months (IQR 45 to 65). 5-year overall survival was 72% (95% CI 67 to 76) in the adjuvant chemotherapy group (105 deaths) and 71% (66 to 75) in the chemoradiotherapy only group (116 deaths; difference 1% [95% CI -6 to 7]; hazard ratio 0·90 [95% CI 0·70 to 1·17]; p=0·81). In the safety population, the most common clinically significant grade 3-4 adverse events were decreased neutrophils (71 [20%] in the adjuvant chemotherapy group vs 34 [8%] in the chemoradiotherapy only group), and anaemia (66 [18%] vs 34 [8%]). Serious adverse events occurred in 107 (30%) in the adjuvant chemotherapy group versus 98 (22%) in the chemoradiotherapy only group, most commonly due to infectious complications. There were no treatment-related deaths. INTERPRETATION: Adjuvant carboplatin and paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer increased short-term toxicity and did not improve overall survival; therefore, it should not be given in this setting. FUNDING: National Health and Medical Research Council and National Cancer Institute.

Exercise during CHemotherapy for Ovarian cancer (ECHO) trial: design and implementation of a randomised controlled trial.

INTRODUCTION: Epidemiological evidence supports an association between higher levels of physical activity and improved cancer survival. Trial evidence is now needed to demonstrate the effect of exercise in a clinical setting. The Exercise during CHemotherapy for Ovarian cancer (ECHO) trial is a phase III, randomised controlled trial, designed to determine the effect of exercise on progression-free survival and physical well-being for patients receiving first-line chemotherapy for ovarian cancer. METHODS AND ANALYSIS: Participants (target sample size: n=500) include women with newly diagnosed primary ovarian cancer, scheduled to receive first-line chemotherapy. Consenting participants are randomly allocated (1:1) to either the exercise intervention (plus usual care) or usual care alone, with stratification for recruitment site, age, stage of disease and chemotherapy delivery (neoadjuvant vs adjuvant). The exercise intervention involves individualised exercise prescription with a weekly target of 150 minutes of moderate-intensity, mixed-mode exercise (equivalent to 450 metabolic equivalent minutes per week), delivered for the duration of first-line chemotherapy through weekly telephone sessions with a trial-trained exercise professional. The primary outcomes are progression-free survival and physical well-being. Secondary outcomes include overall survival, physical function, body composition, quality of life, fatigue, sleep, lymphoedema, anxiety, depression, chemotherapy completion rate, chemotherapy-related adverse events, physical activity levels and healthcare usage. ETHICS AND DISSEMINATION: Ethics approval for the ECHO trial (2019/ETH08923) was granted by the Sydney Local Health District Ethics Review Committee (Royal Prince Alfred Zone) on 21 November 2014. Subsequent approvals were granted for an additional 11 sites across Queensland, New South Wales, Victoria and the Australian Capital Territory. Findings from the ECHO trial are planned to be disseminated via peer-reviewed publications and international exercise and oncology conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ANZCTRN12614001311640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367123&isReview=true).

Older age should not be a barrier to testing for somatic variants in homologous recombination DNA repair-related genes in patients with high-grade serous ovarian carcinoma.

BACKGROUND: Somatic pathogenic variants (PVs) in homologous recombination DNA repair (HR)-related genes found in high-grade serous ovarian carcinomas (HGSC) are not well-characterised in older patients (≥70 years). This may reflect low testing rates in older patients. METHODS: Data from 1210 HGSC patients in AACR Project GENIE and 324 patients in an independent dataset INOVATe were analysed. Cases where somatic variants could be distinguished from germline variants were included, and analysis was restricted to those with a somatic TP53 variant, to ensure cases were HGSC. RESULTS: Of 1210 patients in GENIE, 27% (n = 325) were aged ≥70 years at testing. Patients with somatic-only PVs in BRCA2 were older compared with BRCA1 (median 71 vs 60 years, p = 0.002). Median age for 21 patients with somatic-only PVs in 11 other HR-related genes ranged from 40 to 67 years. In older patients, 7% (n = 22) had somatic BRCA1/2 PVs, and 1% (n = 2) had PVs other HR-related genes; this rate was not significantly different to younger patients (<70 years), 7% (n = 62) BRCA1/2 and 2% (n = 19) other HR-related genes (p = 0.36). The overall frequency of somatic BRCA1/2 PVs was similar in INOVATe (n = 25; 7.7%) and somatic-only BRCA2 PVs were again found in older patients compared with BRCA1 (median age: at testing, 70 vs 63 years; at diagnosis, 68 vs 60 years). CONCLUSIONS: The overall frequency of somatic-only PVs in HR-related genes was similar in older and younger patients with HGSC, highlighting the importance of somatic testing irrespective of age. Limiting somatic testing by age may exclude patients who could benefit from maintenance poly(ADP-ribose) polymerase (PARP) inhibitors.

Management of Malignant Bowel Obstruction: An Innovative Proactive Outpatient Nurse-Led Model of Care for Patients With Advanced Gynecologic Cancer.

BACKGROUND: Malignant bowel obstruction (MBO) in patients with advanced gynecologic cancer (GyCa) can negatively impact clinical outcomes and quality of life. Oncology nurses can support these patients with adequate tools/processes. PROBLEM: Patients with GyCa with/at risk of MBO endure frequent emergency or hospital admissions, impacting patient care. APPROACH: Optimizing oncology nurses' role to improve care for patients with GyCa with/at risk of MBO, the gynecology oncology interprofessional team collaborated to develop a proactive outpatient nurse-led MBO model of care (MOC). OUTCOMES: The MBO MOC involves a risk-based algorithm engaging interdisciplinary care, utilizing standardized tools, risk-based assessment, management, and education for patients and nurses. The MOC has improved patient-reported confidence level of bowel self-management and decreased hospitalization. Following education, nurses demonstrated increased knowledge in MBO management. CONCLUSIONS: An outpatient nurse-led MBO MOC can improve patient care and may be extended to other cancer centers, fostering collaboration and best practice.

Evaluation of the marginal adaptation and gingival status of full-crown restorations using an intraoral camera.

OBJECTIVE: The purpose of this study was to compare the usefulness of intraoral photographs, acquired with a household intraoral camera operating in conventional, calibrated, and polarized modes, with clinical examinations for assessing the marginal adaptation and gingival status of full-crown restorations. METHODS: Clinical examinations were performed by a prosthodontist who classified the marginal adaptation of full-crown restorations according to FDI World Dental Federation criteria, and a periodontal expert who classified gingival status according to the Modified Gingival Index (MGI). The margins and gingival status of the conventional, calibration, and polarization groups of full-crown restorations were independently assessed by three evaluators who obtained photographs using an intraoral camera. Cases where at least two of three assessors were in agreement were analyzed using Cohen's kappa coefficient and the chi-square test, and the sensitivity and specificity were calculated. RESULTS: The conventional, calibration, and polarization groups differed significantly in marginal and gingival status of full-crown restorations. In the calibration group, there was good agreement between the camera-based and oral clinical examinations in terms of the gingival status of full-crown restorations (kappa = 0.945), with 100% sensitivity and 91.67% specificity; this was also the case in the polarization group with respect to the margins of full-crown restorations (kappa = 0.917, sensitivity = 97.22%, specificity = 94.44%). CONCLUSIONS: An intraoral camera with black and white calibrated images is useful to assess the gingival status of full-crown restorations. Polarization mode can be used to assess the marginal adaptation of full-crown restorations. The camera is a feasible and valid diagnostic aid.

Measure of Ovarian Symptoms and Treatment concerns (MOST) indexes and their associations with health-related quality of life in recurrent ovarian cancer.

PURPOSE: The Measure of Ovarian Symptoms and Treatment (MOST) concerns is a validated patient-reported symptom assessment tool for assessing symptom benefit and adverse effects of palliative chemotherapy in women with recurrent ovarian cancer (ROC). We aimed to examine (i) how symptoms within MOST symptom indexes track together (i.e. co-occur) and (ii) the association between MOST symptom indexes and key aspects of health-related quality of life (HRQL). METHOD: A prospective cohort of women with ROC completed the MOST-T35, EORTC QLQ-C30 and EORTC QLQ-OV28 at baseline and before each cycle of chemotherapy. Analyses were conducted on baseline and end-of-treatment data. Exploratory factor analysis and hierarchical cluster analysis identified groups of co-occurring symptoms. Path models examined associations between MOST symptom indexes and HRQL. RESULTS: Data from 762 women at baseline and 681 at treatment-end who completed all 22 symptom-specific MOST items and at least one HRQL measure were analysed. Four symptom clusters emerged at baseline and treatment-end: abdominal symptoms, symptoms associated with peripheral neuropathy, nausea and vomiting, and psychological symptoms. Psychological symptoms (MOST-Psych) and symptoms due to disease (ovarian cancer) or treatment (MOST-DorT) were associated with poorer scores on QLQ-C30 and OV28 functioning domains and worse overall health at both time points. CONCLUSION: Four MOST symptom clusters were consistent across statistical methods and time points. These findings suggest that routine standardized assessment of psychological and physical symptoms in clinical practice with MOST plus appropriate symptom management referral pathways is an intervention for improving HRQL that warrants further research.

Interobserver and intraobserver variability of RECIST assessment in ovarian cancer.

OBJECTIVES: Measurement of Response Evaluation Criteria In Solid Tumors (RECIST) relies on reproducible unidimensional tumor measurements. This study assessed intraobserver and interobserver variability of target lesion selection and measurement, according to RECIST version 1.1 in patients with ovarian cancer. METHODS: Eight international radiologists independently viewed 47 images demonstrating malignant lesions in patients with ovarian cancer and selected and measured lesions according to RECIST V.1.1 criteria. Thirteen images were viewed twice. Interobserver variability of selection and measurement were calculated for all images. Intraobserver variability of selection and measurement were calculated for images viewed twice. Lesions were classified according to their anatomical site as pulmonary, hepatic, pelvic mass, peritoneal, lymph nodal, or other. Lesion selection variability was assessed by calculating the reproducibility rate. Lesion measurement variability was assessed with the intra-class correlation coefficient. RESULTS: From 47 images, 82 distinct lesions were identified. For lesion selection, the interobserver and intraobserver reproducibility rates were high, at 0.91 and 0.93, respectively. Interobserver selection reproducibility was highest (reproducibility rate 1) for pelvic mass and other lesions. Intraobserver selection reproducibility was highest (reproducibility rate 1) for pelvic mass, hepatic, nodal, and other lesions. Selection reproducibility was lowest for peritoneal lesions (interobserver reproducibility rate 0.76 and intraobserver reproducibility rate 0.69). For lesion measurement, the overall interobserver and intraobserver intraclass correlation coefficients showed very good concordance of 0.84 and 0.94, respectively. Interobserver intraclass correlation coefficient showed very good concordance for hepatic, pulmonary, peritoneal, and other lesions, and ranged from 0.84 to 0.97, but only moderate concordance for lymph node lesions (0.58). Intraobserver intraclass correlation coefficient showed very good concordance for all lesions, ranging from 0.82 to 0.99. In total, 85% of total measurement variability resulted from interobserver measurement difference. CONCLUSIONS: Our study showed that while selection and measurement concordance were high, there was significant interobserver and intraobserver variability. Most resulted from interobserver variability. Compared with other lesions, peritoneal lesions had the lowest selection reproducibility, and lymph node lesions had the lowest measurement concordance. These factors need consideration to improve response assessment, especially as progression free survival remains the most common endpoint in phase III trials.

TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members.

PURPOSE: Tubo-ovarian cancer (TOC) is a sentinel cancer for BRCA1 and BRCA2 pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed. We assessed the feasibility of detecting PVs in this population to enable genetic risk reduction in relatives. PATIENTS AND METHODS: In this pilot study, deceased probands were ascertained from research cohort studies, identification by a relative, and gynecologic oncology clinics. DNA was extracted from archival tissue or stored blood for panel sequencing of 10 risk-associated genes. Testing of deceased probands ascertained through clinic records was performed with a consent waiver. RESULTS: We identified 85 PVs in 84 of 787 (11%) probands. Familial contacts of 39 of 60 (65%) deceased probands with an identified recipient (60 of 84; 71%) have received a written notification of results, with follow-up verbal contact made in 85% (33 of 39). A minority of families (n = 4) were already aware of the PV. For many (29 of 33; 88%), the genetic result provided new information and referral to a genetic service was accepted in most cases (66%; 19 of 29). Those who declined referral (4 of 29) were all male next of kin whose family member had died more than 10 years before. CONCLUSION: We overcame ethical and logistic challenges to demonstrate that retrospective genetic testing to identify PVs in previously untested deceased probands with TOC is feasible. Understanding reasons for a family member's decision to accept or decline a referral will be important for guiding future TRACEBACK projects.

Treatment patterns after poly-ADP ribose polymerase (PARP) inhibitors in epithelial ovarian cancer patients.

OBJECTIVES: The primary objective of this study was to describe treatment patterns after poly-ADP ribose polymerase (PARP) inhibitor in patients with epithelial ovarian cancer. Secondary objectives were to evaluate duration of response, time to first subsequent therapy, progression-free survival and overall survival. METHODS: This was a retrospective analysis of patients with epithelial ovarian cancer treated with PARP inhibitor therapy at six Australian gynecological oncology centers. Eligible patients were identified via clinics, trial databases and pharmacy dispensing logs between January 2005 and September 2019. Information regarding clinico-pathological characteristics and treatment outcomes were collated from medical records. RESULTS: A total of 85 patients with epithelial ovarian cancer were identified. Of these, 61% had germline BRCA1/2 mutations, 9% had somatic BRCA1/2 mutations, 5% had confirmed homologous recombination deficiency and 25% were BRCA1/2 wildtype mutations. A total of seventy-seven (91%) patients received chemotherapy after PARP inhibitor, with fifty-six (72.7%) of these patients receiving platinum-based chemotherapy. Four patients (5%) had a complete response, 15 (20%) a partial response, 15 (20%) stable disease and 41 (55%) progressive disease. Median duration of response to chemotherapy was 7.0 months (range 0.2-20.4). Median time to first subsequent therapy was 17.6 and 15.1 months in patients who received a PARP inhibitor as maintenance therapy and treatment, respectively. Median progression-free survival of first line treatment after PARP inhibitor was 9.6, 3.5 and 4.6 months for platinum doublet, single agent platinum and non-platinum chemotherapy, respectively. Adjusting for age and FIGO (Federation of Gynecological Oncologists classification) stage progression-free survival did not differ between treatment groups (p=0.14). Median overall survival for the cohort was 69 months, and patients with platinum sensitive ovarian cancer had improved survival compared with those with platinum refractory or resistant disease. CONCLUSION: Platinum doublet chemotherapy resulted in non-significant improved progression-free survival compared with other regimens, suggesting potential independent mechanisms of resistance between PARP inhibitor and platinum compounds.

Symptom burden and quality of life with chemotherapy for recurrent ovarian cancer: the Gynecologic Cancer InterGroup-Symptom Benefit Study.

OBJECTIVE: The Gynecologic Cancer InterGroup (GCIG)-Symptom Benefit Study was designed to evaluate the effects of chemotherapy on symptoms and health-related quality of life (HRQL) in women having chemotherapy for platinum resistant/refractory recurrent ovarian cancer (PRR-ROC) and potentially platinum sensitive with ≥3 lines of chemotherapy (PPS-ROC ≥3). METHODS: Participants completed the Measure of Ovarian Cancer Symptoms and Treatment (MOST) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 questionnaires at baseline and every 3-4 weeks until progression. Participants were classified symptomatic if they rated ≥4 of 10 in at least one-third of symptoms in the MOST index. Improvement in MOST was defined as two consecutive scores of ≤3 in at least half of the symptomatic items at baseline. Improvement in HRQL was defined as two consecutive scores ≥10 points above baseline in the QLQ-C30 summary score scale (range 0-100). RESULTS: Of 948 participants enrolled, 910 (96%) completed baseline questionnaires: 546 with PRR-ROC and 364 with PPS-ROC ≥3. The proportions of participants symptomatic at baseline as per MOST indexes were: abdominal 54%, psychological 53%, and disease- or treatment-related 35%. Improvement was reported in MOST indexes: abdominal 40%, psychological 35%, and disease- or treatment-related 38%. Median time to improvement in abdominal symptoms occurred earlier for PRR-ROC than for PPS-ROC ≥3 (4 vs 6 weeks, p=0.044); median duration of improvement was also similar (9.0 vs 11.7 weeks, p=0.65). Progression-free survival was longer among those with improvement in abdominal symptoms than in those without (median 7.2 vs 2.5 months, p<0.0001). Improvements in HRQL were reported by 77/448 (17%) with PRR-ROC and 61/301 (20%) with PPS-ROC ≥3 (p=0.29), and 102/481 (21%) of those with abdominal symptoms at baseline. CONCLUSION: Over 50% of participants reported abdominal and psychological symptoms at baseline. Of those, 40% reported an improvement within 2 months of starting chemotherapy. Approximately one in six participants reported an improvement in HRQL. Symptom monitoring and supportive care is important as chemotherapy palliated less than half of symptomatic participants.