Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

BACKGROUND: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. METHODS: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. RESULTS: A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. CONCLUSIONS: In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than among those who received ipilimumab. (Funded by the Dutch Cancer Society and others; ClinicalTrials.gov number, NCT02278887.).

Colorectal cancer in the family: psychosocial distress and social issues in the years following genetic counselling.

BACKGROUND: This study examined: (1) levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC); (2) associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3) the impact of genetic counselling on family relationships, and (4) social consequences of genetic counselling. METHODS: In this cross-sectional study, individuals who had received genetic counselling for HNPCC during 1986-1998 completed a self-report questionnaire by mail. RESULTS: 116 individuals (81% response rate) completed the questionnaire, on average 4 years after the last counselling session. Of all respondents, 6% had clinically significant levels of cancer-specific distress (Impact of Event Scale, IES). Having had contact with a professional psychosocial worker for cancer risk in the past 10 years was significantly associated with higher levels of current cancer specific distress. Only a minority of the counselees reported any adverse effects of genetic counselling on: communication about genetic counselling with their children (9%), family relationships (5%), obtaining life insurance (8%), choice or change of jobs (2%), and obtaining a mortgage (2%). CONCLUSION: On average, four years after genetic counselling for HNPCC, only a small minority of counselled individuals reports clinically significant levels of distress, or significant family or social problems.

Screening behavior of individuals at high risk for colorectal cancer.

BACKGROUND AND AIMS: Periodic colonoscopy is an effective means of reducing the incidence and mortality of colorectal cancer in individuals with a family history of the disease. The aims of this study were to determine the degree of compliance and to identify the factors related significantly to noncompliance with periodic screening in this high-risk population. METHODS: A total of 178 individuals who had undergone genetic counseling for colorectal cancer between 1986 and 1998 and who had been advised to undergo periodic screening because of familial colorectal cancer (FCRC) or hereditary nonpolyposis colorectal cancer (HNPCC) were invited to complete a self-report questionnaire on psychosocial issues and screening experiences. Compliance data were derived from medical records and via self-report. RESULTS: A total of 149 individuals (84%) participated in the study. Noncompliance with screening advice was rare (in 3% of cases), but significant delays (more than 1 year) in undergoing screening were observed in approximately 25% of the cases. The number of perceived barriers to screening (eg, discomfort, embarrassment) was the only variable related significantly to noncompliance/screening delay (odds ratio, 1.2; 95% confidence interval, 1.1-1.3). Use of sedatives during the procedure and receipt of a reminder letter seemed to facilitate better compliance. CONCLUSIONS: Although few high-risk individuals abstain from screening entirely, approximately one in 4 deviates significantly from the recommended frequency of screening. Increased compliance may be achieved by reducing the discomfort and embarrassment associated with the procedure and by the use of reminder letters.

Health-related quality-of-life assessments and patient-physician communication: a randomized controlled trial.

CONTEXT: There has been increasing interest in the use of health-related quality-of-life (HRQL) assessments in daily clinical practice, yet few empirical studies have been conducted to evaluate the usefulness of such assessments. OBJECTIVE: To evaluate the efficacy of standardized HRQL assessments in facilitating patient-physician communication and increasing physicians' awareness of their patients' HRQL-related problems. DESIGN: Prospective, randomized crossover trial. SETTING: Outpatient clinic of a cancer hospital in the Netherlands. PARTICIPANTS: Ten physicians and 214 patients (76% women; mean age, 57 years) undergoing palliative chemotherapy who were invited to participate between June 1996 and June 1998. INTERVENTION: At 3 successive outpatient visits, patients completed an HRQL questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30). The responses were computer scored and transformed into a graphic summary. Physicians and patients received a copy of the summary before the consultation. MAIN OUTCOME MEASURES: Audiotapes of the consultations were content analyzed to evaluate patient-physician communication. Physicians' awareness of their patients' health problems was assessed by comparing physicians' and patients' ratings on the Dartmouth Primary Care Cooperative Information Functional Health Assessment (COOP) and the World Organisation Project of National Colleges and Academics (WONCA) charts. RESULTS: The HRQL-related issues were discussed significantly more frequently in the intervention than in the control group (mean [SD] communication composite scores: 4.5 [2.3] vs 3.7 [1.9], respectively (P =.01). Physicians in the intervention group identified a greater percentage of patients with moderate-to-severe health problems in several HRQL domains than did those in the control group. All physicians and 87% of the patients believed that the intervention facilitated communication and expressed interest in its continued use. CONCLUSION: Incorporating standardized HRQL assessments in daily clinical oncology practice facilitates the discussion of HRQL issues and can heighten physicians' awareness of their patients' HRQL.