Systemic therapy

Abstract: Until recently, there was a dearth of effective systemic therapies for kidney cancer. The incidence of the disease steadily increased from 1975 through 2008 and leveled off after 2008.1-3 Currently, it is among the 10 most frequently diagnosed cancers in men and women in the United States, with more than an estimated 62,000 new cases in 2016.4 The prognosis has historically been poor, with current 5-year survival rates of 74% overall, decreasing to 53% among patients with locoregional (stage III) disease and 8% among patients with metastatic disease.1,3 Kidney cancer is a disease of the middle-aged and elderly: 91% of patients receive a diagnosis at 45 years of age or older, and 48% receive a diagnosis at 65 years of age or older.1 Renal-cell carcinoma, the most common form of kidney cancer, occurs in 90% of cases and is nearly twice as common in men as in women.3 The 5-year survival rate among patients with kidney cancer increased from 57% in 1987−1989 to 74% in 2006−20121; this increase was attributable in part to a higher proportion of indolent and low-stage tumors identified using improved early-detection techniques.5 Still, one third of patients with kidney cancer present with regional or distant metastases,1 and of patients with localized renal-cell carcinoma treated with nephrectomy with curative intent, approximately one quarter have relapses in distant sites.6-8 Distant metastases occur most often in the lungs, lymph nodes, liver, bone, and brain.9 Although more than 14,000 patients die from kidney cancer each year,4 we have seen considerable progress in the systemic treatment of metastatic renal-cell carcinoma in the past 20 years.10 Researchers have achieved a better understanding of the pathogenesis of the most common type of renal-cell carcinoma, clear-cell renal-cell carcinoma. This understanding has led to new agents, expanded treatment options, and increased rates of survival.

Abstract: This classic volume deals with the strategies of both psychotherapists and clients as they maneuver each other in the process of treatment. How a therapist induces a client to change is described within a framework of interpersonal theory and directive family therapy. This work represents a step from the study of therapy in terms of the individual to therapy as communication between at least two people. In this volume, Jay Haley acknowledges his debt to the Gregory Bateson research project exploring the nature of communication as well as to Dr. Milton H. Erickson, M.D. for the many hours of conversations and a new perspective on the nature of therapy. The reactions to this different view continue to be controversial today in the therapy field.

Abstract: Summary Background Evidence from retrospective studies suggests that disease progression after first-line chemotherapy for metastatic non-small-cell lung cancer (NSCLC) occurs most often at sites of disease known to exist at baseline. However, the potential effect of aggressive local consolidative therapy for patients with oligometastatic NSCLC is unknown. We aimed to assess the effect of local consolidative therapy on progression-free survival. Methods In this multicentre, randomised, controlled, phase 2 study, eligible patients from three hospitals had histological confirmation of stage IV NSCLC, three or fewer metastatic disease lesions after first-line systemic therapy, an Eastern Cooperative Oncology Group performance status score of 2 or less, had received standard first-line systemic therapy, and had no disease progression before randomisation. First-line therapy was four or more cycles of platinum doublet therapy or 3 or more months of EGFR or ALK inhibitors for patients with EGFR mutations or ALK rearrangements, respectively. Patients were randomly assigned (1:1) to either local consolidative therapy ([chemo]radiotherapy or resection of all lesions) with or without subsequent maintenance treatment or to maintenance treatment alone, which could be observation only. Maintenance treatment was recommended based on a list of approved regimens, and observation was defined as close surveillance without cytotoxic treatment. Randomisation was not masked and was balanced dynamically on five factors: number of metastases, response to initial therapy, CNS metastases, intrathoracic nodal status, and EGFR and ALK status. The primary endpoint was progression-free survival analysed in all patients who were treated and had at least one post-baseline imaging assessment. The study is ongoing but not recruiting participants. This study is registered with ClinicalTrials.gov, number NCT01725165. Findings Between Nov 28, 2012, and Jan 19, 2016, 74 patients were enrolled either during or at the completion of first-line systemic therapy. The study was terminated early after randomisation of 49 patients (25 in the local consolidative therapy group and 24 in the maintenance treatment group) as part of the annual analyses done by the Data Safety Monitoring Committee of all randomised trials at MD Anderson Cancer Center, and before a planned interim analysis of 44 events. At a median follow-up time for all randomised patients of 12·39 months (IQR 5·52–20·30), the median progression-free survival in the local consolidative therapy group was 11·9 months (90% CI 5·7–20·9) versus 3·9 months (2·3–6·6) in the maintenance treatment group (hazard ratio 0·35 [90% CI 0·18–0·66], log-rank p=0·0054). Adverse events were similar between groups, with no grade 4 adverse events or deaths due to treatment. Grade 3 adverse events in the maintenance therapy group were fatigue (n=1) and anaemia (n=1) and in the local consolidative therapy group were oesophagitis (n=2), anaemia (n=1), pneumothorax (n=1), and abdominal pain (n=1, unlikely related). Interpretation Local consolidative therapy with or without maintenance therapy for patients with three or fewer metastases from NSCLC that did not progress after initial systemic therapy improved progression-free survival compared with maintenance therapy alone. These findings suggest that aggressive local therapy should be further explored in phase 3 trials as a standard treatment option in this clinical scenario. Funding MD Anderson Lung Cancer Priority Fund, MD Anderson Cancer Center Moon Shot Initiative, and Cancer Center Support (Core), National Cancer Institute, National Institutes of Health.

Abstract: The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology and risk stratification of patients is important in therapy selection. The NCCN Guidelines for Kidney Cancer stratify treatment recommendations by histology; recommendations for first-line treatment of ccRCC are also stratified by risk group. To further guide management of advanced RCC, the NCCN Kidney Cancer Panel has categorized all systemic kidney cancer therapy regimens as "Preferred," "Other Recommended Regimens," or "Useful in Certain Circumstances." This categorization provides guidance on treatment selection by considering the efficacy, safety, evidence, and other factors that play a role in treatment selection. These factors include pre-existing comorbidities, nature of the disease, and in some cases consideration of access to agents. This article summarizes surgical and systemic therapy recommendations for patients with relapsed or stage IV RCC.