Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours.

BACKGROUND: Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. Here, we assess whether modified treatments for these patients have increased survival and identify new prognostic factors. METHODS: The United Kingdom GTD database was screened to identify all PSTT/ETT cases diagnosed between 1973 and 2014. Data and survival outcomes from our prior patient cohort (1976-2006) were compared to our new modern cohort (2007-2014), when intensified treatments were introduced. RESULTS: Of 54,743 GTD patients, 125 (0.23%) were diagnosed with PSTT and/or ETT. Probability of survival at 5 and 10 years following treatment was 80% (95% CI 72.8-87.6%) and 75% (95% CI 66.3-84.3%), respectively. Univariate analysis identified five prognostic factors for reduced overall survival (age, FIGO stage, time since antecedent pregnancy, hCG level, mitotic index) of which stage IV disease (HR 6.18, 95% CI 1.61-23.81, p = 0.008) and interval ≥48 months since antecedent pregnancy (HR 14.57, 95% CI 4.17-50.96, p < 0.001) were most significant on multivariable analysis. No significant differences in prognostic factors were seen between the old and new patient cohort. However, the new cohort received significantly more cisplatin-based and high-dose chemotherapy, and patients with an interval ≥48 months demonstrated an improved median overall survival (8.3 years, 95% CI 1.53-15.1, versus 2.6 years, 95% CI 0.73-4.44, p = 0.·005). CONCLUSION: PSTT/ETT with advanced FIGO stage or an interval ≥48 months from their last known pregnancy have poorer outcomes. Platinum-based and high-dose chemotherapy may help to improve survival in poor-prognosis patients.

The relationship between smoking and quality of life in advanced lung cancer patients: a prospective longitudinal study.

PURPOSE: Smoking is a major cause of lung cancer, and continued smoking may compromise treatment efficacy and quality of life (health-related quality of life (HRQoL)) in patients with advanced lung cancer. Our aims were to determine (i) preference for treatments which promote quality over length of life depending on smoking status, (ii) the relationship between HRQoL and smoking status at diagnosis (T1), after controlling for demographic and clinical variables, and (iii) changes in HRQoL 6 months after diagnosis (T2) depending on smoking status. METHODS: Two hundred ninety-six patients with advanced lung cancer were given questionnaires to assess HRQoL (EORTC QLQ-C30), time-trade-off for life quality versus quantity (QQQ) and smoking history (current, former or never smoker) at diagnosis (T1) and 6 months later (T2). Medical data were extracted from case records. RESULTS: Questionnaires were returned by 202 (68.2 %) patients at T1 and 114 (53.3 %) at T2. Patients favoured treatments that would enhance quality of life over increased longevity. Those who continued smoking after diagnosis reported worse HRQoL than former smokers or those who never smoked. Smoking status was a significant independent predictor of coughing in T1 (worse in smokers) and cognitive functioning in T2 (better in never smokers). CONCLUSIONS: Smoking by patients with advanced lung cancer is associated with worse symptoms on diagnosis and poorer HRQoL for those who continue smoking. The results have implications to help staff explain the consequences of smoking to patients.

Prevention of anastrozole-induced bone loss with monthly oral ibandronate during adjuvant aromatase inhibitor therapy for breast cancer.

PURPOSE: The aromatase inhibitor anastrozole is a highly effective well-tolerated treatment for postmenopausal endocrine-responsive breast cancer. However, its use is associated with accelerated bone loss and an increase in fracture risk. The ARIBON trial is a double-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in women taking anastrozole. EXPERIMENTAL DESIGN: BMD was assessed in 131 postmenopausal, surgically treated women with early breast cancer at two U.K. centers. Of these, 50 patients had osteopenia (T score -1.0 to -2.5) at either the hip or lumbar spine. All patients were treated with anastrozole 1 mg once a day and calcium and vitamin D supplementation. In addition, osteopenic patients were randomized to receive either treatment with ibandronate 150 mg orally every month or placebo. RESULTS: After 2 years, osteopenic patients treated with ibandronate gained +2.98% (range -8.9, +19.9) and +0.60% (range -9.0, +6.9) at the lumbar spine and hip, respectively. Patients treated with placebo, however, lost -3.22% (range -16.0, +4.3) at the lumbar spine and -3.90% (range -12.3, +7.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (P < 0.01). At 12 months, urinary n-telopeptide, serum c-telopeptide, and serum bone-specific alkaline phosphatase levels declined in patients receiving ibandronate (30.9%, 26.3%, and 22.8%, respectively) and increased in those taking placebo (40.3%, 34.9%, and 37.0%, respectively). CONCLUSIONS: Monthly oral ibandronate improves bone density and normalizes bone turnover in patients treated with anastrozole.

The use of a point of care device for monitoring the bone resorption biomarker urinary N-telopeptide in cancer patients with bone metastases.

Type I collagen is the major constituent of bone and its breakdown products are increasingly used as sensitive markers of bone resorption. The N-terminal peptide-bound crosslinks of type I collagen (NTX) can be measured in urine and is useful for the monitoring of patients with metastatic bone disease. Studies have shown that raised NTX levels in metastatic bone disease correlate with an increased risk of complications and pathological fracture. The development of accurate and instantaneous point of care devices (POCD) would facilitate patient treatment and avoid delays in awaiting results from specialist laboratories. This study assesses the clinical performance of a single use POCD (OSTEOMARK NTx Point of Care Rx Home Use) to monitor NTX levels in patients with metastatic bone disease. NTX was measured in duplicate in 136 urine samples from patients attending clinic with metastatic bone disease using the POCDs. In our centre the frequency of bisphosphonate treatment is dependent on the NTX level, which is categorised into three groups (0-50, 50-100 and >100 nmol BCE/mmol creatinine). We used these categories to compare the clinical performance of the POCDs to that of a laboratory immunoassay. From a total of 272 devices, 231 (84.9%) successfully recorded a value in nM BCE/mM creatinine. Statistical analysis of the measure of agreement between POCD and laboratory assay found moderate agreement between the two assays (kappa 0.508). Out of the 72 samples with a laboratory assay value of <50, 53 (73.6%) were found to be within the same group recorded by POCD. From the 20 samples with a laboratory assay value of >100, 19 (95.0%) were found to be within the same category using POCDs. The measurement of urinary NTX by POCD appears to be a viable option for the monitoring of metastatic cancer patients. Whilst POCDs appear to record higher values than laboratory assays, the correlation between devices is good and with further research the NTX categories could be modified to accommodate this variation.

Risk-adjusted prognostic models for Hodgkin's disease (HD) and grade II non-Hodgkin's lymphoma (NHL II): validation on 6728 British National Lymphoma Investigation patients.

Using significant factors from multivariate analyses, based on 20 putative markers from a consecutive series of 1198 Sheffield Lymphoma Group patients, risk-adjusted prognostic models had been previously derived for Hodgkin's disease (HD) (using age, albumin and lymphocyte count) and non-Hodgkin's lymphoma (NHL) grade II (based on albumin, age, erythrocyte sedimentation rate, lactate dehydrogenase and stage). Data from 6728 patients on the British National Lymphoma Investigation database were used for validation: thus the models were applied to 4411 patients with HD and 2317 patients with NHL grade II. Survival curves derived from these validation groups confirmed our risk models.