Classification of painful bone metastases as mild, moderate, or severe using both EORTC QLQ-C15-PAL and EORTC QLQ-BM22.

PURPOSE: Previous studies have determined optimal cut points (CPs) for the classification of pain severity as mild, moderate, or severe using only the Brief Pain Inventory (BPI) or the BPI in conjunction with a quality of life (QOL) tool. The purpose of our study was to determine the optimal CPs based on correlation with only QOL outcomes. METHODS: We conducted an analysis of 298 patients treated with radiation therapy for painful bone metastases on a phase III randomized trial. Prior to treatment, patients provided their worst pain score on a scale of 0 (no pain) to 10 (worst possible pain), as well as completed the European Organization of Cancer Research and Treatment (EORTC) QOL Questionnaire Bone Metastases module (QLQ-BM22) and the EORTC QOL Questionnaire Core-15 Palliative (QLQ-C15-PAL). Optimal CPs were determined to be those that yielded the largest F ratio for the between category effect on each subscale of the QLQ-BM22 and QLQ-C15-PAL using the multivariate analysis of variance (MANOVA). RESULTS: The two largest F ratios for Wilk's λ, Pillai's Trace, and Hotelling's Trace were for CPs 5,6 and 5,7. Combining both, the optimal CPs to differentiate between mild, moderate, and severe pain were 5 and 7. Pain scores of 1-5, 6, and 7-10 were classified as mild, moderate, and severe, respectively. Patients with severe pain experienced greater functional interference and poorer QOL when compared to those with mild pain. CONCLUSION: Our results suggest that, based on the impact of pain on QOL measures, pain scores should be classified as follows: 1-5 as mild pain, 6 as moderate pain, and 7-10 as severe pain. Optimal CPs vary depending on the type of outcome measurement used.

A novel homozygous nonsense mutation in the PVRL4 gene and expansion of clinical spectrum of EDSS1.

Ectodermal dysplasias (EDs) belong to a group of genetic diseases which result from alterations in ectoderm-derived appendages including hair, nail, teeth and sweat glands. Ectodermal dysplasia syndactyly syndrome (EDSS1) is one of the rare forms of ED caused by mutations in nectin-4, encoded by the PVRL4 gene. The present study described clinical investigation of the EDSS1 identified in a large consanguineous family. Furthermore, DNA sequence analysis revealed a novel homozygous nonsense mutation (181C>T, p.Asp61*) in the PVRL4 gene.

Analysis of a novel protocol of combined induction chemotherapy and concurrent chemoradiation in unresected non-small-cell lung cancer: a ten-year experience with vinblastine, Cisplatin, and radiation therapy.

BACKGROUND: The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. PATIENTS AND METHODS: We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. RESULTS: A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation therapy, and cisplatin dose. Similarly, Univariate Cox regression showed that completion surgery, use of radiation therapy, cisplatin dose, and vinblastine dose were associated with increased survival. CONCLUSION: This retrospective analysis of a large cohort of patients reveals an OS for VCRT comparable to that reported in the literature for other current combined chemoradiation protocols. The success of this protocol seems to be dose dependent and the outcomes in those who underwent completion surgery suggests that pathologic complete remission is possible for IIIA and IIIB NSCLC.

Is extended volume external beam radiation therapy covering the anastomotic site beneficial in post-esophagectomy high risk patients?

BACKGROUND AND PURPOSE: To assess the impact of extended volume radiation therapy (RT) with anastomotic coverage on local control in high risk post-operative esophageal cancer patients. PATIENTS AND METHODS: This is a retrospective study of high risk (T(3), T(4), nodes positive, with or without margin involvement) post-operative esophageal cancer patients treated at London Regional Cancer Centre from 1989 to 1999. After esophagectomy, all patients received adjuvant combined modality therapy consisting of four cycles of fluorouracil-based chemotherapy, and loco-regional RT with or without coverage of the anastomotic site. RT dose ranged from 45 to 60 Gy at 1.8-2.0 Gy/fraction with treatment fields tailored to the pathologic findings and location of the anastomosis. CT planning was used in all patients to design spinal cord sparing beam arrangements. First relapse rate (first incidence of an event), disease specific survival and overall survival were calculated by Chi-Square, Log-Rank, and Kaplan-Meier (K-M) methods. RESULTS: During the study period, 72 patients had underwent esophagectomy and were considered for adjuvant chemoradiation therapy. Three patients were excluded due to disease progression prior to therapy. The 69 remaining patients formed the study cohort for the present analysis. The median age of the study group was 60 years (range 35-82 years). Pathologic stage distribution (AJCC 1997 staging) was T(2,3) N(1) in 94% patients, 65% of the cases were adenocarcinoma and had undergone transhiatal esophagectomy (86%) with positive/close margins in 34 (49%) patients. Median follow-up was 30.5 months (range 3.4-116.3 months). Two- and 5-year actuarial overall survivals rates were 50 and 31%, respectively. First relapse rate after adjuvant therapy was 63.7% (n = 44) and median time to relapse was 27.2 months. Anastomosis recurrence rates were 29% with small volume and 0% with extended volume RT (P = 0.041). Local and regional relapse occurred in 74.2% of patients treated with small volume RT compared to 15.4% in patients treated with extended volume RT (P < 0.001). After adjusting for resection margin status, the local control benefit of extended volume RT remained significant (P = 0.003). Treatment interruptions and late gastrointestinal toxicity were not significantly increased with the use of extended volume RT. CONCLUSIONS: A significant decrease in local and regional relapse without added late toxicity was achieved with the use of extended volume RT encompassing the anastomotic site post-operatively in high risk esophageal cancer patients.

Improving the consistency in cervical esophageal target volume definition by special training.

PURPOSE: Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions. METHODS AND MATERIALS: A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 protocol to 12 radiation oncologists. Target volumes were redrawn immediately and at 1-2 months later. Post-training vs. pre-training target volumes were compared. RESULTS: There was less variability in the longitudinal positions of the target volumes post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case had more variability due to the lack of a visible gross tumor on CT scans. Transverse contours of target volumes did not show any significant difference pre- or post-training. CONCLUSION: For cervical esophageal cancer, this study suggests that special training on protocol guidelines may improve consistency in target volume definition. Explicit protocol directions are required for situations where the gross tumor is not easily visible on CT scans. This may be particularly important for multicenter clinical trials, to reduce the occurrences of protocol violations.