Patterns of clinicopathological features and outcome in epithelial ovarian cancer patients: 35 years of prospectively collected data.

OBJECTIVE: Investigate the clinical landscape of ovarian carcinoma (OC) over time. DESIGN: Register-based prospectively collected data. SETTING: South East Scotland. SAMPLE: A total of 2805 OC patients diagnosed in 1981-2015. METHODS: Survival times were visualised using the Kaplan-Meier method; median survival, 5-year survival probabilities and associated restricted mean survival time analyses were used to quantify survival differences. MAIN OUTCOME MEASURES: Disease-specific survival. RESULTS: A significant increase in disease-specific survival (DSS) from 1981-1985 to 2011-2015 was observed (median 1.73 versus 4.23 years, P < 0.0001). Corresponding increase in progression-free survival (PFS) was not statistically significant (median 1.22 versus 1.58 years, P = 0.2568). An increase in the proportion of cases with low residual disease volume (RD) (<2 cm RD) following debulking was observed (54.0% versus 87.7%, P < 0.0001). The proportion of high grade serous (HGS) cases increased (P < 0.0001), whereas endometrioid and mucinous cases decreased (P = 0.0005 and P = 0.0002). Increases in stage IV HGS OC incidence (P = 0.0009) and stage IV HGS OC DSS (P = 0.0122) were observed. Increasing median age at diagnosis correlated with increasing Eastern Cooperative Oncology Group Performance Status (ECOG PS) over time (r = 0.86). CONCLUSIONS: OC DSS has improved over the last 35 years. PFS has not significantly increased, highlighting that improvement in outcome has been limited to extending post-relapse survival. Distribution of stage at diagnosis, histological subtype and RD following debulking has changed over time, reflecting evolution in tumour classification, staging and optimal debulking definitions (from low RD to minimal or zero RD). Histology, stage, RD and ECOG PS remain reliable outcome predictors. Increasing median age at diagnosis and ECOG PS indicates demographic shifts in the clinical population. TWEETABLE ABSTRACT: Significant improvement in ovarian carcinoma survival has been seen over time. Most of this improvement is due to an extension of survival following disease relapse.

Diurnal profile of interstitial glucose following dexamethasone prophylaxis for chemotherapy treatment of gynaecological cancer.

AIMS: Hyperglycaemia, a side-effect of acute glucocorticoid exposure, is associated with poor outcome in those undergoing chemotherapy. The incidence, risk factors and diurnal profile of glucocorticoid-induced glucose dysregulation in the context of chemotherapy treatment remain incompletely understood. METHODS: Blinded continuous interstitial glucose monitoring was performed on 16 women without diabetes for 24 h prior to and 5 days following carboplatin/paclitaxel chemotherapy combined with dexamethasone treatment for gynaecological cancer. At the end of the treatment period, glucose data were analysed and integrated with baseline metabolic and anthropomorphic variables. RESULTS: 15/16 (94%) women exhibited elevated glucose levels (> 11.1 mmol/l). Peak glucose levels were highest on the day of treatment (median 14.45 mmol/l, range 10.2-22.2 mmol/l) and total time spent with an elevated interstitial glucose level was highly variable (median 3.6 h, range 0.0-55.1 h). Peak interstitial glucose levels occurred predominantly, but not exclusively, in the afternoon (13.00-15.00) and evening (19.00-22.00); however elevated levels were noted throughout the 24-h period. Baseline HbA1c was independently associated with severity and duration of elevated glucose levels in a regression adjusted for baseline BMI. CONCLUSIONS: These data report for the first time that high glucose levels are encountered by nearly all women following this regimen, the severity and duration of which are independently associated with HbA1c . Further work is required to determine if controlling glucose levels during treatment influences outcome.

Routine germline BRCA1 and BRCA2 testing in patients with ovarian carcinoma: analysis of the Scottish real-life experience.

OBJECTIVE: To determine the rates of germline BRCA1 and BRCA2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy. DESIGN: Retrospective cohort study. SETTING: Four cancer/genetics centres in Scotland. POPULATION: Patients with ovarian cancer undergoing germline BRCA1 and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with selection based solely on family history), after 2013 (under the 'new criteria', with sequencing offered to newly presenting patients with non-mucinous ovarian cancer), and in the 'prevalent population' (who presented before 2013, but were not eligible for sequencing under the old criteria but were sequenced under the new criteria). METHODS: Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria. MAIN OUTCOME MEASURES: Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations. RESULTS: Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria', 'new criteria', and 'prevalent' populations, respectively. The frequency of gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%. CONCLUSIONS: Sequencing all patients with non-mucinous ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history-based models operate. TWEETABLE ABSTRACT: BRCA sequencing all non-mucinous cancer patients increases mutation detection five fold.

Impact of neutropenia on delivering planned adjuvant chemotherapy: UK audit of primary breast cancer patients.

The UK audit was undertaken in primary breast cancer patients receiving adjuvant chemotherapy to: (1) record the incidence of neutropenic events (hospitalisation due to febrile neutropenia, dose delay of > or =1 week or dose reduction of > or =15% due to neutropenia); (2) evaluate the impact of neutropenic events on overall dose intensity (DI) received and (3) review the use of granulocyte colony-stimulating factor (G-CSF) in clinical practice. Data from 422 patients with Stage I-III breast cancer were collected from 15 centres. Cyclophosphamide, methotrexate and 5-fluorouracil(CMF)- or anthracycline-based regimens were the most commonly used. Only 5.2% of patients received G-CSF. Overall, 29% of patients experienced a neutropenic event, most frequently dose delay. Neutropenic events had a significant impact on the ability to deliver planned DI. Out of 422 patients, 17% did not achieve 85% of their planned DI; due to neutropenia in 11% of patients. Of the neutropenic patients receiving CMF- or anthracycline-based regimens, around 40 and 32% of patients, respectively, did not achieve 85% of their planned DI. Patients who experienced one neutropenic event had a higher risk of a second event. During adjuvant chemotherapy of primary breast cancer, neutropenic events are common, likely to occur in subsequent chemotherapy cycles, and have a significant impact on receiving planned DI.

Osteonecrosis of the femoral head following adjuvant chemotherapy for breast cancer.

We report a case of osteonecrosis in a patient treated with adjuvant chemotherapy for breast cancer. A 68-year-old woman presented with severe right hip pain. Seven months after completing a course of 6 cycles of adjuvant Cyclophosphamide, Methotrexate and 5-Fluorouracil with standard anti-emetic prophylaxis of Dexamethasone and Domperidone for a T2N0M0 breast cancer. Investigations revealed evidence of osteonecrosis of the right femoral head. Due to ongoing hip pain, she underwent an elective total hip replacement and her mobility has returned almost to normal. Osteonecrosis has been associated with corticosteroids and cytotoxic regimens which omit these agents. Osteonecrosis is a rare complication of cytotoxic therapy but with the increasing use of chemotherapy it should be considered in the differential diagnosis of joint pain in patients who have received anti-tumour therapies.