Quality of life in patients with limited (1-3) brain metastases undergoing stereotactic or whole brain radiotherapy : A prospective study of the DEGRO QoL working group.

PURPOSE: Published results of quality of life (QoL) studies mostly concern whole brain radiotherapy for limited or multiple brain metastases. This prospective multicentre study was designed to compare the QoL of patients with limited (1-3) brain metastases treated with either whole brain (WBRT) or stereotactic radiotherapy (SRT). METHODS: From 01/2007-03/2011, 90 limited brain metastases patients who were previously untreated (n = 77) or had undergone primary surgery (n = 13) were recruited at 14 centres in Germany and Austria. QoL was measured with the EORTC-QLQ-C15-PAL and BN20 brain modules before the start of radiotherapy and after 3 months. RESULTS: Fifty-two patients (58%) received WBRT and 38 (42%) received SRT. At 3 months, 67 patients (74%) were still living, and 92.6% of the 3­month survivors completed the second set of questionnaires. Analysis of the QLQ-C15-PAL and BN20 scales revealed significant deterioration in patients treated with WBRT and SRT in physical function (p < 0.001 and p = 0.007), fatigue (p < 0.001 and p = 0.036), nausea (p = 0.003 and p = 0.002), appetite loss (p < 0.001 and p = 0.025), drowsiness (p < 0.001 and p = 0.011), hair loss (p = 0.019 and p = 0.023) and itchy skin (p = 0.030 and p = 0.018). Motor dysfunction (p < 0.001), communication deficits (p = 0.002) and leg weakness (p < 0.001) declined significantly only in patients treated with WBRT. Comparing the two radiotherapy techniques over time, the results showed significant differences in symptom scores for future uncertainty, fatigue and appetite loss. CONCLUSIONS: QoL data as an outcome of the paper should be considered in decision making on the irradiation technique in patients with small number of brain metastases. Larger studies are required to verify the results according to subgroups.

Predictors of overall satisfaction of cancer patients undergoing radiation therapy.

BACKGROUND: Reporting the experiences and satisfaction of patients, as well as their quality of care scores is an emerging recommendation in health care systems. Many aspects of patients' experience determine their overall satisfaction. The aim of this evaluation was to define the main factors contributing to the satisfaction of patients undergoing radiotherapy in an outpatient setting. PATIENTS AND METHODS: A total of 1,710 patients with a histologically proven cancer, who were treated in our department between 2012 and 2014, were recruited for this prospective evaluation. At the end of therapy, each patient was asked to grade the skills and the care provided by radiation therapists, physicians, and physician's assistants, as well as the overall satisfaction during therapy. Statistical analysis was performed to determine which parameters had the greatest influence on overall satisfaction. RESULTS: Overall satisfaction with the provided care was high with a mean satisfaction score of 1.4. Significant correlations were found between overall satisfaction and each of the following survey items: courtesy, protection of privacy, professional skills and care provided by the radiation therapists and physicians, accuracy of provided information, and cleanliness. Linear regression analysis demonstrated that courteous behavior and the protection of privacy were the strongest predictors for overall satisfaction (P<0.001), followed by care and skills of physicians and radiation therapists. Patients suffering from head and neck cancer expressed lower overall satisfaction. CONCLUSION: Based on our prospectively acquired data, we were able to identify and confirm key factors for patient satisfaction in an outpatient radiooncological cancer center. From these results, we conclude that patients want most importantly to be treated with courtesy, protection of privacy and care.

Serpentine channels: micro-rheometers for fluid relaxation times.

We propose a novel device capable of measuring relaxation times of viscoelastic fluids as small as 1 ms. In contrast to most rheometers, which by their very nature are concerned with producing viscometric or nearly-viscometric flows, here we make use of an elastic instability that occurs in the flow of viscoelastic fluids with curved streamlines. To calibrate the rheometer we combine simple scaling arguments with relaxation times obtained from first normal-stress difference data measured in a classical shear rheometer. As an additional check we also compare these relaxation times to those obtained from Zimm theory and good agreement is observed. Once calibrated, we show how the serpentine rheometer can be used to access smaller polymer concentrations and lower solvent viscosities where classical measurements become difficult or impossible to use due to inertial and/or resolution limitations. In the absence of calibration, the serpentine channel can still be a very useful comparative or index device.

Elasto-inertial turbulence.

Turbulence is ubiquitous in nature, yet even for the case of ordinary Newtonian fluids like water, our understanding of this phenomenon is limited. Many liquids of practical importance are more complicated (e.g., blood, polymer melts, paints), however; they exhibit elastic as well as viscous characteristics, and the relation between stress and strain is nonlinear. We demonstrate here for a model system of such complex fluids that at high shear rates, turbulence is not simply modified as previously believed but is suppressed and replaced by a different type of disordered motion, elasto-inertial turbulence. Elasto-inertial turbulence is found to occur at much lower Reynolds numbers than Newtonian turbulence, and the dynamical properties differ significantly. The friction scaling observed coincides with the so-called "maximum drag reduction" asymptote, which is exhibited by a wide range of viscoelastic fluids.

Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases.

BACKGROUND: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. METHODS: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. RESULTS: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. CONCLUSIONS: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information.

Dysphagia. Impact on quality of life after radio(chemo)therapy of head and neck cancer.

BACKGROUND: In the past, xerostomia was considered one of the most important determining factors of quality of life (QoL) after radiotherapy (RT) of the head and neck region. In addition, more recent studies have shown that RT-induced dysphagia has an essential influence on the QoL. PATIENTS AND METHODS: Between September 2005 and August 2007, 35 patients with locally advanced squamous cell carcinoma of the head and neck region were included in the prospective study. Patients were treated by IMAT (intensity-modulated arc therapy) or IMRT (intensity-modulated radiotherapy) planned on 3D imaging. A total of 28 patients (80%) received concomitant chemotherapy. The evaluation of QoL (EORTC QLQ-C30, H&N C-35) and toxicities (CTC 2.0) were assessed at the beginning of, during, and after RT as well as up to 12 months after the end of therapy. RESULTS: At the end of therapy, 86% of the patients experienced difficulties in swallowing (62% CTC II-III°). Twelve months after the end of treatment, 15% still suffered from dysphagia CTC II-III°. Concomitant chemotherapy exacerbated the incidence and gravity of dysphagia, resulting in increasing dietary problems. QoL (EORTC) was significantly affected by dysphagia. In particular, the global state of health and QoL were influenced at the end of treatment (p=0.033) and at a later stage (p=0.050). CONCLUSION: The findings of this study suggest that more emphasis should be placed on structured clinical diagnostics, therapy, and rehabilitation of deglutition problems. This means in particular to not only spare the parotids while planning the irradiation, but also to take into consideration the important structures for deglutition, like the retropharyngeal muscles.

Effects of radiotherapy for brain metastases on quality of life (QoL). Prospective pilot study of the DEGRO QoL working party.

BACKGROUND: Prospective data on quality-of-life (QoL) effects of radiotherapy for brain metastases are currently lacking, but would be of great interest to guide therapeutic decisions. PATIENTS AND METHODS: From 01/2007 to 08/2007, 46 patients with previously untreated brain metastases were recruited at eight centers. QoL was measured at start of treatment (T(0)) and at 3 months (T(3mo)). In the pilot study, two combinations of QoL instruments could be used at the discretion of the centers (A: EORTC QLQ-C30 and B: EORTC QLQ-C15-PAL both with brain module BN20, assessment by proxies with A: Palliative Care Outcome Scale, B: self-constructed brain-specific instrument). RESULTS: All patients received whole-brain radiotherapy, four with an additional boost irradiation. At T(3mo), 26/46 patients (56.5%) had died. 17/20 survivors (85%) completed the questionnaires. In 3-month survivors, QoL deteriorated in most domains, significant in drowsiness, hair loss and weakness of legs. The scores for headaches and seizures were slightly better after 3 months. Assessment by proxies also suggested worsening of QoL. Initial QoL at T(0) was better in those alive than in those deceased at T(3mo), significant for physical function and for the symptom scales of fatigue and pain, motor dysfunction, communication deficit and weakness of legs. CONCLUSION: Practicability and compliance appeared better with the (shorter) version B. This version is now used in the ongoing main phase of the study with additional centers. First results indicate a moderate worsening of QoL during the first 3 months after start of palliative radiotherapy for brain metastases. QoL at initiation of radiotherapy may be prognostic for survival.

Job stress and job satisfaction of physicians, radiographers, nurses and physicists working in radiotherapy: a multicenter analysis by the DEGRO Quality of Life Work Group.

BACKGROUND: Ongoing changes in cancer care cause an increase in the complexity of cases which is characterized by modern treatment techniques and a higher demand for patient information about the underlying disease and therapeutic options. At the same time, the restructuring of health services and reduced funding have led to the downsizing of hospital care services. These trends strongly influence the workplace environment and are a potential source of stress and burnout among professionals working in radiotherapy. METHODS AND PATIENTS: A postal survey was sent to members of the workgroup "Quality of Life" which is part of DEGRO (German Society for Radiooncology). Thus far, 11 departments have answered the survey. 406 (76.1%) out of 534 cancer care workers (23% physicians, 35% radiographers, 31% nurses, 11% physicists) from 8 university hospitals and 3 general hospitals completed the FBAS form (Stress Questionnaire of Physicians and Nurses; 42 items, 7 scales), and a self-designed questionnaire regarding work situation and one question on global job satisfaction. Furthermore, the participants could make voluntary suggestions about how to improve their situation. RESULTS: Nurses and physicians showed the highest level of job stress (total score 2.2 and 2.1). The greatest source of job stress (physicians, nurses and radiographers) stemmed from structural conditions (e.g. underpayment, ringing of the telephone) a "stress by compassion" (e.g. "long suffering of patients", "patients will be kept alive using all available resources against the conviction of staff"). In multivariate analyses professional group (p < 0.001), working night shifts (p = 0.001), age group (p = 0.012) and free time compensation (p = 0.024) gained significance for total FBAS score. Global job satisfaction was 4.1 on a 9-point scale (from 1 - very satisfied to 9 - not satisfied). Comparing the total stress scores of the hospitals and job groups we found significant differences in nurses (p = 0.005) and physicists (p = 0.042) and a borderline significance in physicians (p = 0.052).In multivariate analyses "professional group" (p = 0.006) and "vocational experience" (p = 0.036) were associated with job satisfaction (cancer care workers with < 2 years of vocational experience having a higher global job satisfaction). The total FBAS score correlated with job satisfaction (Spearman-Rho = 0.40; p < 0.001). CONCLUSION: Current workplace environments have a negative impact on stress levels and the satisfaction of radiotherapy staff. Identification and removal of the above-mentioned critical points requires various changes which should lead to the reduction of stress.

Split course hyperfractionated accelerated radio-chemotherapy (SCHARC) for patients with advanced head and neck cancer: influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis.

BACKGROUND: The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. METHODS: From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1-5: 20 mg/m2/d DDP + 750-1000 mg/m2/d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69-70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. RESULTS: Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2-3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient < 1.0 g/nl) and the mean hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. CONCLUSION: The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in about 50 % of the patients with significant but acceptable toxicity. Most patients were not anemic at beginning of therapy. Therefore, we could assess the influence of pre-treatment hemoglobin on survival. However, a low hemoglobin nadir was associated with poor outcome. This result suggests an influence of anemia during therapy on prognosis.

Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy -- case report and review of literature.

BACKGROUND: Modern radiotherapy (RT) reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a "recall phenomenon" imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of "radiation recall dermatitis" (RRD) one year after RT as a result of taking hypericin (St. John's wort). CASE REPORT: A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward. CONCLUSION: Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially for complementary or alternative drugs because patients tend to conceal such medication as harmless.

Clinical results of intracoronary brachytherapy (ICBT) for multiple in-stent restenosis.

BACKGROUND AND PURPOSE: Treatment of in-stent restenosis (ISR) with percutaneous coronary intervention (PCI) alone is often followed by early re-restenosis. The present study focused on the effect of intracoronary brachytherapy (ICBT) on multiple in-stent restenosis (MISR) after repeated PCI. PATIENTS AND METHODS: 40 patients (27 male, 13 female, age: 66 +/- 9 years) with MISR (two to six ISRs, median three ISRs) were retrospectively analyzed. All patients were treated by using the Novoste((R)) Beta-Cathtrade mark 3.5F System after PCI. The target vessel received 18.4-25.3 Gy of radiation at a depth of 2 mm from the center of the source. The restenosis-free survival and overall survival were calculated by Kaplan-Meier analysis (log-rank). The time interval between last PCI without ICBT and the consecutive recurrence was compared with the follow-up time after PCI with ICBT. RESULTS: The 3-year overall survival rate after ICBT was 93%. The 0.5-, 1-, 2-, and 3-year ISR-free survival rates after PCI + ICBT were 81%, 72%, 52%, and 38%, respectively. After PCI alone, the 0.5-, 1-, and 2-year ISR-free survival rates were 30%, 13%, and 0%, respectively. This difference was highly significant (p < 0.0001). Patients with more than three ISRs before ICBT had a better outcome (3-year ISR-free survival: 80%) than patients with only two or three ISRs before ICBT (3-year ISR-free survival: 25%; p < 0.05). CONCLUSION: ICBT is highly effective and safe in patients with ISR. The results of this study are in accordance with the WRIST and BETA-WRIST data. After 6 months both studies revealed an ISR-free survival rate of 86% (WRIST) and 66% (BETA-WRIST), respectively. The ISR rates in the own control group (70%) were comparable to the placebo groups in WRIST (68%) and BETA-WRIST (72%). Interestingly, patients with more than three ISRs before ICBT had the lowest ISR rate after ICBT.

Medical decision-making of the patient in the context of the family: results of a survey.

GOALS OF THE STUDY: From the perspective of patient autonomy, the family is often looked upon as a troublemaker in medical decision-making. The question remains open as to whether it is possible to do justice to the autonomy of the individual patient and to the claims of his family at the same time. PATIENTS AND METHODS: A clinical study was undertaken when both patients and dependents were interviewed. One hundred people (50 pairs) participated in this study and could be analyzed. A questionnaire consisting of 15 items was used and was evaluated to see if and how the attitudes concerning medical decision-making differ between patient and dependent. RESULTS: The majority of the interviewees (89%) agreed with the opinion that medical decisions should be made jointly by the patient, the family, and the doctor. Ninety-three percent approved of the claim to inform not only the patient, but also the family. Seventy percent of the patients and 54% of the dependents think that the family is entitled to have a say in matters concerning medical decision-making, only 30% of the patients, but 42% of the dependents argued against this view. Eighty-four percent of the patients argued against a change in this right at the end of life, which was approved by 32% of the family members. CONCLUSIONS: The family plays a central role in medical decision-making. This could be shown by a survey among patients with malignant diseases and their dependents. These initial findings must be verified in a larger population. The increased inclusion of the family in the process of medical decision-making corresponds in general to the expressed will of the patients. The model of shared decision-making is favored by values which both the family and the patient have in common. Thus, a family-based decision-making theory needs to be formulated in the future.

[The prognostic value of time parameters in adjuvant radiotherapy of head and neck cancer. A retrospective analysis of 138 patients]. / Prognostische Wertigkeit der Zeitparameter in der adjuvanten Radiotherapie von HNO-Tumoren Eine retrospektive Untersuchung an 138 Patienten.

PURPOSE: To answer the question, how the parameters waiting time, radiation treatment time and overall treatment time (OTT) influenced the endpoints overall (OS), event-free (EFS) and local recurrence-free survival (LRFS) in patients with locally advanced head-and-neck cancer, who had received postoperative radiotherapy. PATIENTS AND METHODS: 138 patients were included into a retrospective analysis from 10/1993 to 05/2000. Besides the time parameters waiting time, radiation treatment time and OTT, tumor- and therapy-related parameters (T-, N-, R-status, grading, tumor site, surgical technique, and postoperative hemoglobin < 12 g/dl) with potential impact on the endpoints were investigated in the univariate analysis (Kaplan-Meier log-rank test). Individual parameters with a significant impact (p = 0.05) were subjected to a multivariate Cox regression analysis. RESULTS: Besides a postoperative hemoglobin value < 12 g/dl, in the univariate analysis an OTT >/= 105 days negatively influenced all endpoints, as well as a radiation treatment time >/= 60 days. On multivariate Cox regression analysis, postoperative hemoglobin < 12 g/dl and an OTT >/= 105 days were identified as independent negative prognostic factors for all endpoints. CONCLUSION: The waiting time should be managed according to the ASARA (as short as reasonably achievable) recommendation, radiation treatment should not be protracted exceeding an overall treatment of 105 days. Generally, time parameters should be routinely included in the standard tumor documentation, thus facilitating further evaluation of these prognostically relevant factors.

[Spinal and cerebral leptomeningeal seeding from a melanocytoma of the cerebello-pontine angle]. / Spinale und zerebrale Meningeosis eines sekundär malignisierten Melanozytoms des Kleinhirnbrückenwinkels.

Meningeal melanocytoma refers to the uncommon clinical appearance of a generally benign tumour deriving from leptomeningeal melanocytes. Meningeal spread of this tumour is very rarely observed. We present the case of a 38-year-old man with meningeal melanocytoma of the cerebello-pontine angle, who showed a biphasic course of this disease, with a stable period followed by a steady progress within few months. After surgical resection of the melancytoma in the left skull base and of a first local recurrence five years later, a second local recurrence occurred 6 years after diagnosis, with intracerebral and spinal meningeal seeding. This tumor did not respond to a combined radiochemotherapy including oral temozolomide, and the patient died 5 months after starting treatment for this relapse. Secondary malignisation of the melancytoma is suggested.