Long-Term Results from the IDEAL-CRT Phase 1/2 Trial of Isotoxically Dose-Escalated Radiation Therapy and Concurrent Chemotherapy for Stage II/III Non-small Cell Lung Cancer.

PURPOSE: The IDEAL-CRT phase 1/2 multicenter trial of isotoxically dose-escalated concurrent chemoradiation for stage II/III non-small cell lung cancer investigated two 30-fraction schedules of 5 and 6 weeks' duration. We report toxicity, tumor response, progression-free survival (PFS), and overall survival (OS) for both schedules, with long-term follow-up for the 6-week schedule. METHODS AND MATERIALS: Patients received isotoxically individualized tumor radiation doses of 63 to 71 Gy in 5 weeks or 63 to 73 Gy in 6 weeks, delivered concurrently with 2 cycles of cisplatin and vinorelbine. Eligibility criteria were the same for both schedules. RESULTS: One-hundred twenty patients (6% stage IIB, 68% IIIA, 26% IIIB, 1% IV) were recruited from 9 UK centers, 118 starting treatment. Median prescribed doses were 64.5 and 67.6 Gy for the 36 and 82 patients treated using the 5- and 6-week schedules. Grade ≥3 pneumonitis and early esophagitis rates were 3.4% and 5.9% overall and similar for each schedule individually. Late grade 2 esophageal toxicity occurred in 11.1% and 17.1% of 5- and 6-week patients. Grade ≥4 adverse events occurred in 17 (20.7%) 6-week patients but no 5-week patients. Four adverse events were grade 5, with 2 considered radiation therapy related. After median follow-up of 51.8 and 26.4 months for the 6- and 5-week schedules, median OS was 41.2 and 22.1 months, respectively, and median PFS was 21.1 and 8.0 months. In exploratory analyses, OS was significantly associated with schedule (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.32-0.98; P = .04) and fractional clinical/internal target volume receiving ≥95% of the prescribed dose (HR, 0.88; 95% CI, 0.77-1.00; P = .05). PFS was also significantly associated with schedule (HR, 0.53; 95% CI, 0.33-0.86; P = .01). CONCLUSIONS: Toxicity in IDEAL-CRT was acceptable. Survival was promising for 6-week patients and significantly longer than for 5-week patients. Survival might be further lengthened by following the 6-week schedule with an immune agent, motivating further study of such combined optimized treatments.

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.

Tuberculosis en las localidades del municipio Majibacoa: 1995-2001: avances hacia la eliminación / Tuberculosis at the towns of Majibacoa municipality: 1995-2001: progress towards elimination

Marco de referencia: La Vigilancia y Control de la Tuberculosis (TB) en el Municipio Majibacoa ha sido intensificada. Objetivo: Valorar los resultados de una intervención integral en grupos de riesgo asistidos por médicos y enfermeras de la familia. Método: Se realizó un estudio de intervención en el que se describió la incidencia de la TB por áreas de salud en 1995-1997, comparándola con las del periodo 1998 al 2001 después de una intervención consistente en la aplicación de un cuestionario a los médicos y enfermeras de la familia sobre el programa de TB, con un debate grupal inmediato sobre cada pregunta; se utilizaron técnicas informativo-educativas con los dirigentes administrativos-políticos y los líderes comunitarios. Resultados: la incidencia subió desde 13.1 por 105 habitantes en 1995 hasta 23.1 en 1997 y disminuyó a 2.5 en 2001. Las tasas subtotales de los períodos 1995-97 y 1998-01 fueron 19.1 y 5.7 por 105 hab, respectivamente; la tendencia fue similar en ambas áreas, Calixto y Omaja pero el 76% de los casos pertenecían a Calixto. El porcentaje de casos de TB detectados mediante pesquisa activa y pasivo fueron 2.0 y 0.4% respectivamente (RR=4.49) IC95,1.46-13.8 (p=0.04). Conclusiones: La reducción de la incidencia muy posiblemente ha estado relacionada con el proceso integrado de intervención que incluye mejoras de la vigilancia y control así como de las condiciones de vida de territorios críticos del municipio.

Breathlessness clinics within specialist palliative care settings can improve the quality of life and functional capacity of patients with lung cancer.

This paper is a development on recent research that proved the value of non-pharmacological techniques and strategies in the management of breathlessness in lung cancer. It evaluates the intervention in a specialist palliative care setting using an outpatient clinic at Lewis-Manning House. Referrals were made by the patients' physician or specialist nurse. Patients (n = 30) were assessed and treated by the senior physiotherapist in charge of the clinic over three sessions. A number of outcomes were measured at various stages of the patients' treatment. The results have confirmed and strengthened the previous published results. Highly significant improvements in patients' breathlessness, functional capacity, activity levels and distress levels have been shown. For example, the percentage of patients experiencing breathlessness several times or more per day was reduced from 73% to 27% four weeks later. In addition, this project has been able to demonstrate significant improvements in quality of life and high levels of satisfaction with the interventions. Qualitative data enhanced the findings of objective measurements.