Simon Hughes

The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people

Background:Although comorbidities are identified in routine oncology practice, intervention plans for the coexisting needs of older people receiving chemotherapy are rarely made. This study evaluates the impact of geriatrician-delivered comprehensive geriatric assessment (CGA) interventions on chemotherapy toxicity and tolerance for older people with cancer.Methods:Comparative study of two cohorts of older patients (aged 70+ years) undergoing chemotherapy in a London Hospital. The observational control group (N=70, October 2010–July 2012) received standard oncology care. The intervention group (N=65, September 2011–February 2013) underwent risk stratification using a patient-completed screening questionnaire and high-risk patients received CGA. Impact of CGA interventions on chemotherapy tolerance outcomes and grade 3+ toxicity rate were evaluated. Outcomes were adjusted for age, comorbidity, metastatic disease and initial dose reductions.Results:Intervention participants undergoing CGA received mean of 6.2±2.6 (range 0–15) CGA intervention plans each. They were more likely to complete cancer treatment as planned (odds ratio (OR) 4.14 (95% CI: 1.50–11.42), P=0.006) and fewer required treatment modifications (OR 0.34 (95% CI: 0.16–0.73), P=0.006). Overall grade 3+ toxicity rate was 43.8% in the intervention group and 52.9% in the control (P=0.292).Conclusions:Geriatrician-led CGA interventions were associated with improved chemotherapy tolerance. Standard oncology care should shift towards modifying coexisting conditions to optimise chemotherapy outcomes for older people.

Role of fluorodeoxyglucose positron emission tomography (FDG PET)-computed tomography (CT) in the staging of bladder cancer

To determine whether to use 18F‐fluorodeoxyglucose positron emission tomography (FDG PET) scans in the preoperative staging of bladder cancer (BC).

Inter-fraction variations in respiratory motion models

Respiratory motion can vary dramatically between the planning stage and the different fractions of radiotherapy treatment. Motion predictions used when constructing the radiotherapy plan may be unsuitable for later fractions of treatment. This paper presents a methodology for constructing patient-specific respiratory motion models and uses these models to evaluate and analyse the inter-fraction variations in the respiratory motion. The internal respiratory motion is determined from the deformable registration of Cine CT data and related to a respiratory surrogate signal derived from 3D skin surface data. Three different models for relating the internal motion to the surrogate signal have been investigated in this work. Data were acquired from six lung cancer patients. Two full datasets were acquired for each patient, one before the course of radiotherapy treatment and one at the end (approximately 6 weeks later). Separate models were built for each dataset. All models could accurately predict the respiratory motion in the same dataset, but had large errors when predicting the motion in the other dataset. Analysis of the inter-fraction variations revealed that most variations were spatially varying base-line shifts, but changes to the anatomy and the motion trajectories were also observed.

Phase III, Double-Blind, Randomized Trial That Compared Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 1/2–Positive Metastatic Bladder Cancer

Purpose To establish whether maintenance lapatinib after first-line chemotherapy is beneficial in human epidermal growth factor receptor (HER) 1/HER2-positive metastatic urothelial bladder cancer (UBC). Methods Patients with metastatic UBC were screened centrally for HER1/HER2 overexpression. Patients who screened positive for HER1/2 and who did not have progressive disease during chemotherapy (four to eight cycles) were randomly assigned one to one to lapatinib or placebo after completion of first-line/initial chemotherapy for metastatic disease. The primary end point was progression-free survival (PFS). Results Between 2007 and 2013, 446 patients with UBC were screened, and 232 with HER1- or HER2-positive disease were randomly assigned. The median PFS for lapatinib and placebo was 4.5 (95% CI, 2.8 to 5.4) and 5.1 (95% CI, 3.0 to 5.8) months, respectively (hazard ratio, 1.07; 95% CI, 0.81 to 1.43; P = .63). The overall survival for lapatinib and placebo was 12.6 (95% CI, 9.0 to 16.2) and 12.0 (95% CI, 10.5 to 14.9) months, respectively (hazard ratio, 0.96; 95% CI, 0.70 to 1.31; P = .80). Discontinuation due to adverse events were similar in both arms (6% lapatinib and 5% placebo). The rate of grade 3 to 4 adverse events for lapatinib and placebo was 8.6% versus 8.1% ( P = .82). Preplanned subset analysis of patients strongly positive for HER1/HER2 (3+ on immunohistochemistry; n = 111), patients positive for only HER1 (n = 102), and patients positive for only HER2 (n = 42) showed no significant benefit with lapatinib in terms of PFS and overall survival ( P > .05 for each). Conclusion This trial did not find significant improvements in outcome by the addition of maintenance lapatinib to standard of care.

Management of Prostate Cancer in Elderly Patients: Recommendations of a Task Force of the International Society of Geriatric Oncology

CONTEXT Prostate cancer is the most frequent male cancer. Since the median age of diagnosis is 66 yr, many patients require both geriatric and urologic evaluation if treatment is to be tailored to individual circumstances including comorbidities and frailty. OBJECTIVE To update the 2014 International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer in men aged >70 yr. The update includes new material on health status evaluation and the treatment of localised, advanced, and castrate-resistant disease. DATA ACQUISITION A multidisciplinary SIOG task force reviewed pertinent articles published during 2013-2016 using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments, and castration-refractory/resistant disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus. DATA SYNTHESIS Elderly patients should be managed according to their individual health status and not according to age. Fit elderly patients should receive the same treatment as younger patients on the basis of international recommendations. At the initial evaluation, screening for cognitive impairment is mandatory to establish patient competence in making decisions. Initial evaluation of health status should use the validated G8 screening tool. Abnormal scores on the G8 should lead to a simplified geriatric assessment that evaluates comorbid conditions (using the Cumulative Illness Score Rating-Geriatrics scale), dependence (Activities of Daily Living) and nutritional status (via estimation of weight loss). When patients are frail or disabled or have severe comorbidities, a comprehensive geriatric assessment is needed. This may suggest additional geriatric interventions. CONCLUSIONS Advances in geriatric evaluation and treatments for localised and advanced disease are contributing to more appropriate management of elderly patients with prostate cancer. A better understanding of the role of active surveillance for less aggressive disease is also contributing to the individualisation of care. PATIENT SUMMARY Many men with prostate cancer are elderly. In the physically fit, treatment should be the same as in younger patients. However, some elderly prostate cancer patients are frail and have other medical problems. Treatment in the individual patient should be based on health status and patient preference.

Is there an antiandrogen withdrawal syndrome with enzalutamide

To examine prostate‐specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.

Is there an anti-androgen withdrawal syndrome with enzalutamide?

To examine prostate‐specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

Purpose To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.

Should testosterone replacement be offered to hypogonadal men treated previously for prostatic carcinoma

Androgen administration can cause prostate cancer progression, and androgen deprivation therapy is a commonly used therapeutic modality in the treatment of prostate cancer. In trying to answer the posed clinical question, this article reviews the risks and benefits of testosterone replacement therapy in this setting and the published data from clinical series. Recommendations are made based on the available evidence.

Evolution of the Treatment Paradigm for Patients with Metastatic Castration-Resistant Prostate Cancer

As recently as 2004, treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) were limited, with docetaxel the only approved agent conferring a survival benefit. The therapeutic landscape is now very different, with several agents demonstrating prolonged survival since 2010. New agents for the treatment of mCRPC include sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide and radium-223. All are now approved for use in this patient group, although the specific licensing terms vary between agents. In addition, denosumab may have utility in patients with bone metastases. A number of novel agents are also in development with promising initial results. However, because these treatment options have proliferated rapidly, there is currently a paucity of clinical evidence regarding their optimal sequencing. Selection of an appropriate treatment option should take into consideration disease characteristics, drug availability and patient choice. In summary, we discuss several new treatment options available for mCRPC and their integration into the current treatment paradigm.