Targeted therapies and radiotherapy

Targeted therapies are at this moment the subject of an intensive research program. Their action is, however, for most of them, cytostatic, and their combination with classical cytotoxic approaches, as radiotherapy, is logical. A lot of experimental data are now available, regarding interactions between radiations and EGF-receptor inhibitors, antiangiogenic therapies, farneysltransferase inhibitors and cell cycle inhibitors. These experimental results are reviewed, and possible mechanisms of interactions are discussed. Preliminary clinical results are reported and criticized. In conclusion, the combination of radiotherapy and targeted therapies seems a promising approach, particularly with the inhibitors of the EGFR pathway and anti-vascular treatments, and require the continuation and intensification of the clinical trials.     

Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline concentration: a comparison with sugar permeability tests

BACKGROUND: Intestinal mucositis is an important cause of cancer treatment-related morbidity and mortality, carrying a serious economic burden. Currently, objective parameters are lacking that would enable the monitoring of gut damage in routine clinical practice, thus hindering the development of clinical studies designed to investigate potential new strategies aimed at reducing or preventing this side effect. The authors investigated the characteristics of serum citrulline concentration compared with sugar permeability tests with respect to its use as a marker for cancer treatment-induced small bowel injury. METHODS: In this prospective study, 10 patients with hematologic malignancies who were receiving myeloablative therapy had gut toxicity assessed with sugar permeability tests. Serum citrulline concentrations also were determined using archival serum samples. The association between both parameters and their respective characteristics were analyzed and compared with data from the literature. RESULTS: Sensitivity and specificity were better for the citrulline assay compared with sugar permeability tests. Maximum gut damage assessed with the citrulline assay was observed 1-2 weeks earlier compared with the sugar permeability test. Similarly, citrulline indicated recovery of gut damage at 3 weeks after transplantation, whereas most sugar permeability tests remained abnormal. CONCLUSIONS: The simplicity of the method, the low costs, and the lack of drawbacks to the method make the citrulline assay the first choice for measuring and monitoring treatment-related gut damage and provides an objective parameter for cancer treatment-related gut toxicity.     

Undetectable prostate specific antigen at 6-12 months: a new marker for early success in hormonally treated patients after prostate brachytherapy

BACKGROUND: The concept of a prostate-specific antigen (PSA) "nadir" has been used as a predictive marker for treatment success in patients treated with radiotherapy for localized prostate carcinoma. However, this approach is not applicable in patients who are concomitantly treated with short-term hormonal therapies. To address this, the authors sought to develop a new predictive marker in such patients after prostate brachytherapy (BT). METHODS: Between March 1997 and November 2002, 194 men with clinical Stage T1A-T3N0M0 prostate carcinoma (according to the 1992 International Union Against Cancer/American Joint Committee on Cancer TNM classification system) were treated with interstitial palladium (103Pd3) BT and androgen ablation therapy with or without external beam radiotherapy (EBRT). Based on tumor characteristics, 127 patients received an antiandrogen, finasteride, and BT whereas 67 received an antiandrogen, leuprolide, and EBRT followed by a BT boost. Hormonal therapy was initiated 2-3 months before any radiotherapy for a total duration of 8-9 months. Follow-up included physical examination and determining the PSA level at 3-month intervals. Postoperative serum testosterone was evaluated in preoperatively potent patients with erectile dysfunction > 6 months after therapy. A PSA level < or = 0.06 ng/mL or < or = 0.20 ng/mL detected during a 6-12-month window after the implant were evaluated as predictors of biochemically disease-free survival (DFS), defined as the time to a PSA level > or = 1.0 ng/mL. RESULTS: Of the 194 patients, 163 were available for analysis. The median length of follow-up was 48 months. In those patients with a PSA level < or = 0.20 ng/mL at 6-12 months, the DFS at 48 months after the implant was 96% (95% confidence interval [95% CI], 91-99%) compared with the remainder of the patients, whose DFS decreased to 80% (95% CI, 65-89%) (P < 0.001). When a PSA level < or = 0.06 ng/mL was used as an indicator, the 48-month DFS was 99% (95% CI, 91-100%) compared with that for patients with a PSA level > 0.06 ng/mL, in whom the DFS was 85% (95% CI, 74-92%) (P = 0.004). Furthermore, because testosterone levels may occasionally remain low after the cessation of luteinizing hormone-releasing hormone agonist therapy and result in erectile dysfunction and an artificially low PSA level, the authors reviewed the serum testosterone levels in 23 patients who were so treated and were experiencing erectile dysfunction. None had PSA values below the lower limit of normal. CONCLUSIONS: A PSA level < or = 0.20 ng/mL or < or = 0.06 ng/mL measured at 6-12 months after BT appears to be a useful predictive marker for detecting early success in patients with prostate carcinoma who are treated with neoadjuvant androgen ablation and BT. These markers may be used to identify those patients who are at an increased risk of biochemical failure and may be useful in stratifying patients for closer follow-up, long-term adjuvant therapies, or clinical trials. A longer follow-up period will be needed to verify whether these are predictive of long-term cancer control.     

Physicians' communication with a cancer patient and a relative: a randomized study assessing the efficacy of consolidation workshops

BACKGROUND: Although patients with cancer are often accompanied by a relative during medical interviews, to the authors' knowledge little is known regarding the efficacy of communication skills training programs on physicians' communication skills in this context. The objective of the current study was to assess the efficacy of 6 consolidation workshops, 3 hours in length, that were conducted after a 2.5-day basic training program. METHODS: After attending the basic training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual interviews that were recorded on an audio tape at baseline, after consolidation workshops for the consolidation-workshops group, and 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' and relatives' perceptions of and satisfaction with physicians' communication performance were assessed using a 15-item questionnaire. RESULTS: Sixty-two physicians completed the training program. Compared with physicians who participated to the basic training program, when addressing the patient, physicians who were randomized to the consolidation workshops used more open, open directive, and screening questions (P = 0.011 in simulated patient interviews and P = 0.005 in actual patient interviews) and elicited and clarified psychologic concerns more often (P = 0.006 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the relative, physicians who were randomized to the consolidation workshops gave less premature information (P = 0.032 in simulated patient interviews and P < 0.001 in actual patient interviews). When they addressed the patient and the relative simultaneously, physicians who were randomized to the consolidation workshops used more empathy, educated guesses, alerting to reality, confronting, negotiating, and summarizing (P = 0.003 in simulated patient interviews and P = 0.024 in actual patient interviews). Patients, but not relatives, who interacted with physicians in the consolidation-workshops group were more satisfied globally with the interviews (P = 0.022). CONCLUSIONS: Six 3-hour consolidation workshops resulted in improved communication skills addressed to patients and to relatives. The current results showed that the transfer of skills addressing relatives' concerns remained limited and that consolidation workshops should focus even more systematically on the practice of three-person interviews.     

Factors that influence physicians' detection of distress in patients with cancer: can a communication skills training program improve physicians' detection?

BACKGROUND: No study to date has assessed the impact of skills acquisition after a communication skills training program on physicians' ability to detect distress in patients with cancer. METHODS: First, the authors used a randomized design to assess the impact, on physicians' ability to detect patients' distress, of a 1-hour theoretical information course followed by 2 communication skills training programs: a 2.5-day basic training program and the same training program consolidated by 6 3-hour consolidation workshops. Then, contextual, patient, and communication variables or factors associated with physicians' detection of patients' distress were investigated. After they attended the basic communication skills training program, physicians were assigned randomly to consolidation workshops or to a waiting list. Interviews with a cancer patient were recorded before training, after consolidation workshops for the group that attended consolidation workshops, and approximately 5 months after basic training for the group that attended basic training without the consolidation workshops. Patient distress was recorded with the Hospital Anxiety and Depression Scale before the interviews. Physicians rated their patients' distress on a visual analog scale after the interviews. Physicians' ability to detect patients' distress was measured through computing differences between physicians' ratings of patients' distress and patients' self-reported distress. Communication skills were analyzed according to the Cancer Research Campaign Workshop Evaluation Manual. RESULTS: Fifty-eight physicians were evaluable. Repeated-measures analysis of variance showed no statistically significant changes over time and between groups in physicians' ability to assess patient distress. Mixed-effects modeling showed that physicians' detection of patients' distress was associated negatively with patients' educational level (P = 0.042) and with patients' self-reported distress (P < 0.000). Mixed-effects modeling also showed that physicians' detection of patient distress was associated positively with physicians breaking bad news (P = 0.022) and using assessment skills (P = 0.015) and supportive skills (P = 0.045). CONCLUSIONS: Contrary to what was expected, no change was observed in physicians' ability to detect distress in patients with cancer after a communication skills training programs, regardless of whether physicians attended the basic training program or the basic training program followed by the consolidation workshops. The results indicated a need for further improvements in physicians' detection skills through specific training modules, including theoretical information about factors that interfere with physicians' detection and through role-playing exercises that focus on assessment and supportive skills that facilitate detection.     

Physical activity in physical education: teacher or technology effects

This study assessed if wearing a heart rate monitor influenced student activity levels in elementary physical education. Data were analyzed for 4 students using an alternating treatment design to assess differential effects between accelerometer activity counts obtained from students when wearing the heart rate monitor and when they were not wearing the monitor. Results show that (a) there was no difference in activity counts between the 2 conditions, (b) boys had higher means than girls, and (c) the variance between more and less active boys was greater than the variance among the girls.     

Follow-up of the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA 2) 1991-2003: methods and characterization of participants

Summary. Objectives: The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) was designed to investigate the health effects from long-term exposure to air pollution.Methods: The health assessment at recruitment (1991) and at the first reassessment (2001–3) consisted of an interview about respiratory health, occupational and other exposures, spirometry, a methacholine bronchial challenge test, end-expiratory carbon monoxide (CO) measurement and measurement for atopy. A bio bank for DNA and blood markers was established. Heart rate variability was measured using a 24-hour ECG (Holter) in a random sample of participants aged 50 years and older. Concentrations of nitrogen dioxide (NO₂), sulphur dioxide (SO₂), ozone (O₃) and particulates in ambient air have been monitored in all study areas since 1991. Residential histories collected over the 11 year follow-up period coupled with GIS modelling will provide individual long-term air pollutant exposure estimates.Results: Of 9651 participants examined in 1991, 8715 could be traced for the cohort study and 283 died. Basic information about health status was obtained for 8047 individuals (86% of alive persons), 6528 individuals (70%) agreed to the health examination and 5973 subjects (62%) completed the entire protocol. Non-participants in the reassessment were on average younger than participants and more likely to have been smokers and to have reported respiratory symptoms in the first assessment. Average weight had increased by 5.5 kg in 11 years and 28% of smokers in 1991 had quit by the time of the reassessment.Ursula Ackermann-Liebrich and Birgit Kuna-Dibbert contributed equally     

The value of basic science in clinical diagnosis: creating coherence among signs and symptoms

BACKGROUND: We investigated whether learning basic science mechanisms may have mnemonic value in helping students remember signs and symptoms, in comparison with learning the relation between symptoms and diagnoses directly. PURPOSE: To compare 2 approaches to learning diagnosis: learning how features of various conditions relate to underlying pathophysiological mechanisms and learning the conditional probabilities of features and diseases. METHODS: Undergraduate students (n = 36) were taught 4 disorders (upper motor neuron lesion, lower motor neuron lesion, neuromuscular junction disease and muscular disease), either using basic science explanations or (symptom x disease) probabilities. They were tested with diagnostic cases immediately after learning and 1 week later. RESULTS: On the immediate test, there was no difference in the results. One week later, the accuracy of the mechanism group remained at 0.52, but the performance of the probability group had dropped to 0.43. CONCLUSIONS: Knowledge of basic science may have value in clinical diagnosis by helping students recall or reconstruct the relationships between features and diagnoses.