Physical and Psychosocial Correlates of Rehabilitation, Survival and Relapse in Head and Neck Cancer Patients

The number of new patients in the Netherlands each year diagnosed with head and neck cancer is about 21 00.1 This number will increase in the coming years because of progessive aging of the population and the particularly high birthrate post second world war, producing a cohort of children who are now at risk for developing head and neck cancer. Moreover, patients are currently 'in medical hands' for a longer time than before because of the introduction of treatment techniques for more advanced tumors and better palliative care. In 1995 the estimated number of patients alive with carcinoma of the most common sites of head and neck cancer was 9125.2 Traditionally, the medical treatment of head and neck tumors has been directed at irradicating the disease and aiming for a longer survival of the patient. Therefore, the main focus has been on clinical data such as localization, type and staging of the tumor and the effect of treatment, demonstrated by loco-regional control and survival. As Bailar and Gornick stated recently, the effect on mortality of new treatments, in the period 1970 through 1994, has been disappointing for most cancer sites.3 Also, the survival rate for head and neck cancer in 1994 was found largely unchanged since 1973. In the Netherlands, the 5-year overall relative survival for oral cavity cancer improved from 52 to 58%, for oropharynx cancer decreased from 38 to 30% and remained unchanged (70%) in laryngeal cancer.2 For the patients both quantity and quality of life are important. Today head and neck cancer patients and their healthcare providers are confronted with the effects of more aggressive treatment modalities introduced since the 70's. Fundamental life functions, like breathing, eating and speaking, and the bodily appearance of the patient, are often largely affected by tumor and treatment, often with severe consequences for daily life and social interaction

Possible lack of full cross-resistance of 5HT3 antagonists; a pilot study

We investigated the potential of cross-over to the serotonin receptor (5HT3) antagonist ondansetron after protection failure with tropisetron. Several cases of complete protection were observed. These limited data suggest that there is an indication for retreatment with a different 5HT3 antagonist after an initial failure to another and also stress the need and relevance for comparative studies between 5HT3 antagonists

Communication of prognosis in head and neck cancer patients

Objectives: In shared decision making it is important to adequately, timely and actively involve patients in treatment decisions. Sharing prognostic information can be of key importance. This study describes whether and how prognostic information on life expectancy is included during communication on diagnosis and treatment plans between physicians and head and neck (H&N) oncologic patients in different phases of disease. Methods: A descriptive, qualitative study was performed of n = 23 audiotaped physician-patient conversations in which both palliative and curative treatment options were discussed and questions on prognosis were expected. Verbatim transcribed consultations were systematically analyzed. A distinction was made between prognostic information that was provided (a) quantitatively: by giving numerical probability estimates, such as percentages or years or (b) qualitatively: through the use of words such as ‘most likely’ or ‘highly improbable’. Results: In all consultations, H&N surgeons provided some prognostic inform

Involving the patient: A prospective study on use, appreciation and effectiveness of an information system in head and neck cancer care

Objective: To determine use, appreciation and effectiveness of an electronic health information support system in head and neck (H&N) cancer care. Design: A prospective evaluation study. The evaluated system has four different functions: (1) communication amongst health care providers and between health care providers and patients, (2) information for health care providers and patients, (3) contact with fellow sufferers and (4) monitoring of discharged patients by means of electronic questionnaires. Evaluation of the system was done both objectively using automatically created log files and stored messages, and subjectively by using paper questionnaires from patients and general practitioners (GPs). Setting: Department of Otorhinolaryngology and Head and Neck Surgery of a tertiary health care centre in the Netherlands. The system was put at patients' disposal for a period of 6 weeks following discharge from the hospital after surgery for H&N cancer, and was additional to standard care. Participants: Head and neck cancer patients, hospital physicians, members of a hospital-based support team, GPs, district nurses and speech therapists. Main outcome measures: Actual use of the system by patients and health care providers. Patients' appreciation for each of the system's four different functions. GPs' appreciation for the system. Capability to detect potential patient problems with the system. Results: The system was used by 36 H&N cancer patients, 10 hospital physicians, 2 members of the support team, 8 GPs, 2 district nurses and 2 speech therapists. The total number of patient-sessions was 982: an average of 27.3 sessions per patient during the 6 weeks study period. In total, 456 monitoring questionnaires were completed. The support team in hospital responded with 231 actions. In 16 cases, an extra appointment was made for a patient with the hospital physician. Out of these cases, immediate action was considered necessary eight times. Patients appreciated the system highly, rating it with an average score of 8.0 on a 10-point scale. All patients used the monitoring function, and rated 'monitoring' with a mean score of 8.0 on a 10-point scale. Least used and appreciated was the 'contact with fellow sufferers' function. Only 8 out of possible 36 GPs used the system, rating it with an average of 5.6 on a 10-point scale. Conclusions: The electronic health information support system was used intensively and highly appreciated by H&N cancer patients. The system enabled the early detection of occurring health problems that required direct intervention. ICT can play an additional role in the management of patients, also in a relatively elderly and computer illiterate patient population

Physiological interaction of heart and lung in thoracic irradiation

INTRODUCTION: The risk of early radiation-induced lung toxicity (RILT) limits the dose and efficacy of radiation therapy of thoracic tumors. In addition to lung dose, coirradiation of the heart is a known risk factor in the development RILT. The aim of this study was to identify the underlying physiology of the interaction between lung and heart in thoracic irradiation. METHODS AND MATERIALS: Rat hearts, lungs, or both were irradiated to 20 Gy using high-precision proton beams. Cardiopulmonary performance was assessed using breathing rate measurements and F(18)-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) scans biweekly and left- and right-sided cardiac hemodynamic measurements and histopathology analysis at 8 weeks postirradiation. RESULTS: Two to 12 weeks after heart irradiation, a pronounced defect in the uptake of (18)F-FDG in the left ventricle (LV) was observed. At 8 weeks postirradiation, this coincided with LV perivascular fibrosis, an increase in LV end-diastolic pressure, and pulmonary edema in the shielded lungs. Lung irradiation alone not only increased pulmonary artery pressure and perivascular edema but also induced an increased LV relaxation time. Combined irradiation of lung and heart induced pronounced increases in LV end-diastolic pressure and relaxation time, in addition to an increase in right ventricle end-diastolic pressure, indicative of biventricular diastolic dysfunction. Moreover, enhanced pulmonary edema, inflammation and fibrosis were also observed. CONCLUSIONS: Both lung and heart irradiation cause cardiac and pulmonary toxicity via different mechanisms. Thus, when combined, the loss of cardiopulmonary performance is intensified further, explaining the deleterious effects of heart and lung coirradiation. Our findings show for the first time the physiological mechanism underlying the development of a multiorgan complication, RILT. Reduction of dose to either of these organs offers new opportunities to improve radiation therapy treatment of thoracic tumors, potentially facilitating increased treatment doses and tumor control

A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y 12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y 12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y 12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.)

A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y 12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y 12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y 12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.)

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Abstract: Background & Aims Patients with autoimmune hepatitis (AIH) almost inevitably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy. Methods In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and immunoglobulin G after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Results Seventy patients (mean 57.9 years (standard deviation (SD) 14.0); 72.9% female) were randomly assigned to the MMF plus prednisolone (n=39) or azathioprine plus prednisolone (n=31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% confidence interval (CI), 4.0 to 46.7; p=0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p=0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p=0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p=0.018). Conclusions In patients with treatment-naive AIH, MMF with prednisolone achieved a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. Impact and implications This randomised controlled trial directly compares azathioprine and mycophenolate mofetil (MMF), both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis (AIH). Achieving complete remission is desirable to prevent disease progression. Patients assigned to the MMF group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with AIH