Cost-Effectiveness Modeling of Surgery Plus Adjuvant Endocrine Therapy Versus Primary Endocrine Therapy Alone in UK Women Aged 70 and Over With Early Breast Cancer

ObjectivesApproximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective.MethodsSurvival outcomes from a statistical model, and published data on recurrence, were combined with data from a large, multicenter, prospective cohort study of over 3400 UK women aged 70+ with early breast cancer and median 52-month follow-up, to populate a probabilistic economic model. This model evaluated the cost-effectiveness of surgery plus adjuvant therapies relative to PET for 24 illustrative subgroups: Age {70, 80, 90} × Nodal status {FALSE (F), TRUE (T)} × Comorbidity score {0, 1, 2, 3+}.ResultsFor a 70-year-old with no lymph node involvement and no comorbidities (70, F, 0), surgery plus adjuvant therapies was cheaper and more effective than PET. For other subgroups, surgery plus adjuvant therapies was more effective but more expensive. Surgery plus adjuvant therapies was not cost-effective for 4 of the 24 subgroups: (90, F, 2), (90, F, 3), (90, T, 2), (90, T, 3).ConclusionFrom a UK perspective, surgery plus adjuvant therapies is clinically effective and cost-effective for most women aged 70+ with early breast cancer. Cost-effectiveness reduces with age and comorbidities, and for women over 90 with multiple comorbidities, there is little cost benefit and a negative impact on quality of life.     

THE PROGNOSIS OF BREAST CANCER BASED ON HISTOLOGICAL ASSESSMENT

Histopathology data from 298 patients with breast cancer have been stored in a computer, and features influencing survival have been analysed by the life table method and presented in survival curves. Prognostic features assessed were the size, type, and grade of neoplasm, the amount of stromal elastosis and lymphocytic infiltrate, and the presence and number of axillary metastases. The most reliable indications of short survival are the presence of axillary metastases and a high tumour grade. These two features are correlated, as highgrade tumours are much more likely to have metastases at presentation. No statistical difference is found in the survival of patients with metastases in one or two axillary nodes compared with those with larger numbers involved. There are differences in survival in different types of carcinoma; the well-differentiated infiltrating duct carcinoma with tubular pattern has the best prognosis, followed by the medullary carcinoma. The size of the tumour has some prognostic significance, but this is outweighed by its grade.     

Case report: gastroduodenal intussusception of a gastrointestinal stromal tumour

Gastrointestinal stromal tumours (GISTs), previously termed leiomyomas and leiomyosarcomas are relatively common tumours of the gastrointestinal tract, most commonly found in the stomach. Most GISTs are asymptomatic but may cause abdominal pain or bleeding from ulceration of the overlying mucosa. A rare case of gastroduodenal intussusception of a large gastric stromal tumour, which presented with intermittent abdominal pain and gastric outlet obstruction, is reported. Pre-operative diagnosis was made on abdominal CT and confirmed at laparotomy. Pre-operative diagnostic difficulties and management are discussed.     

Aminolaevulinic acid-induced photodynamic therapy: cellular responses to glucose starvation

Photodynamic therapy is a cancer treatment based on the interaction of light, oxygen and a photosensitiser. Protoporphyrin. IX is an endogenous photosensitiser derived from the pro-drug aminolaevulinic acid. Tumours contain areas of hypoxia and hypoglycaemia. Tumour cells adapt to these conditions by stress protein induction which may induce resistance to cancer therapies. The effect of chronic hypoglycaemia on sensitivity to aminolaevulinic acid-induced photodynamic therapy in vitro was studied in MCF-7, human breast cancer cells. Following chronic exposure to 0, 1 or 25 mM, glucose, cells were treated with aminolaevulinic acid and the generation of intracellular protoporphyrin. IX measured by spectrofluorimetry. Aminolaevulinic acid-induced photodynamic therapy sensitivity was compared between cells following chronic exposure to 0, 1 or 25 mM glucose. Percentage cell survival was determined by clonogenic assay. Cells cultured in low glucose generated higher levels of protoporphyrin IX compared to standard glucose medium (0 mM glucose: 0.88 x 10(-5) ng cell(-1), 1 mM: 0.86 x 10(-5) ng cell(-1), 25 mM: 0.60 5x 10(-5) ng cell(-1), P<0.05). However, photodynamic therapy sensitivity was reduced in glucose deprived cells (0 mM glucose: 61% survival, 1 mM: 80.5% and 25 mM: 39.6%, P<0.05). Chronic exposure to low glucose induces photodynamic therapy resistance despite increased intracellular concentrations of protoporphyrin IX and may reflect cellular adaptation to chronic glucose deprivation.     

The decision-making process for senior cancer patients: treatment allocation of older women with operable breast cancer in the UK

Objective

Up to 40% of women over 70 years with primary operable breast cancer in the UK are treated with primary endocrine therapy (PET) as an alternative to surgery. A variety of factors are important in determining treatment for older breast cancer patients. This study aimed to identify the patient and tumor factors associated with treatment allocation in this population.

Methods

Prospectively collected data on treatment received (surgery vs. PET) were analysed with multivariable logistic regression using the variables age, modified Charlson Comorbidity Index (CCI), activities of daily living (ADL) score, Mini-Mental State Examination (MMSE) score, HER2 status, tumour size, grade and nodal status.

Results

Data were available for 1,122 cancers in 1,098 patients recruited between February 2013 and June 2015 from 51 UK hospitals. About 78% of the population were treated surgically, with the remainder being treated with PET. Increasing patient age at diagnosis, increasing CCI score, large tumor size (5 cm or more) and dependence in one or more ADL categories were all strongly associated with non-surgical treatment (P<0.05).

Conclusion

Increasing comorbidity, large tumor size and reduced functional ability are associated with reduced likelihood of surgical treatment of breast cancer in older patients. However, age itself remains a significant factor for non-surgical treatment; reinforcing the need for evidence-based guidelines.KEYWORDS : Frail elderly, breast neoplasms, decision-making     

Phase I trial of CYT997, a novel cytotoxic and vascular-disrupting agent

Background:

CYT997 is a novel microtubule inhibitor and vascular-disrupting agent with marked preclinical anti-tumour activity.

Methods:

This phase I dose-escalation study assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of CYT997 administered by continuous intravenous infusion over 24 h every 3 weeks to patients with advanced solid tumours.

Results:

Thirty-one patients received CYT997 over 12 dose levels (7–358 mg m⁻²). Doses up to 202 mg m⁻² were well tolerated. Dose-limiting toxicities were observed at 269 and 358 mg m⁻², consisting of grade 3 prolonged corrected QT interval in two patients and grade 3 hypoxia and grade 4 dyspnea in one patient. All toxicities were reversible. The pharmacokinetics of CYT997 were linear over the entire dose range. Dynamic contrast-enhanced magnetic resonance imaging scans showed significant changes in tumour K^trans values consistent with vascular disruption in 7 out of 11 evaluable patients treated at CYT997 doses of ⩾65 mg m⁻². Moreover, plasma levels of von Willebrand factor and caspase-cleaved cytokeratin-18 increased post-treatment at higher dose levels. Among 22 patients evaluable for response, 18 achieved stable disease for >2 cycles.

Conclusions:

CYT997 was well tolerated at doses that were associated with pharmacodynamic evidence of vascular disruption in tumours.     

Pregnancy Outcomes for Kidney Transplant Recipients

Pregnancy outcomes in a transplant population have not been well documented. Data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and the National Perinatal Epidemiology and Statistics Unit (NPESU) were analyzed. We described pregnancy outcomes within the transplant population and compared these to outcomes for the general population. Six hundred ninety‐two pregnancies in 447 transplant recipients were reported between 1971 and 2010 (ANZDATA); a corresponding 5 269 645 pregnancies were reported nationally in Australia between 1991 and 2010 (NPESU). At pregnancy transplant mothers had a median age of 31 years (interquartile range [IQR]: 27, 34), a median creatinine of 106 µmol/L (IQR: 88, 1103 µmol/L) and a functioning transplant for a median of 5 years (IQR: 3, 9). The mean gestational age at birth was 35 ± 5 weeks in transplant recipients, significantly shorter than the national average of 39 weeks (p < 0.0001). Mean live birth weight for transplant recipients was 873 g lower than the national average (2485 ± 783 g vs. 3358 ± 2 g); a significant difference remained after controlling for gestational age. There was lower perinatal survival rate in babies born to transplant recipients, 94% compared with 99% nationally (p < 0.001). Although transplant pregnancies are generally successful, outcomes differ from the general population, indicating these remain high‐risk pregnancies despite good allograft function.