Irradiation dose to the swallowing apparatus impacts nutritional status in head and neck cancer patients-results from the prospective randomized HEADNUT trial.

PURPOSE: To investigate the influence of radiation dose to the swallowing muscles on the nutritional status in patients with head and neck cancer undergoing primary or adjuvant (chemo)radiotherapy (C)RT. METHODS: Between 2018 and 2020, 61 patients were prospectively randomized into the so-called HEADNUT trial (head and neck cancer patients undergoing nutritional intervention). Follow-up was continued until 2022. Contouring of the swallowing apparatus included the superior (scm), middle (mcm), and inferior constrictor muscle (icm), the cricopharyngeal muscle (cphm), and the esophageal inlet. Nutritional status was assessed by bioelectrical impedance analysis (BIA) at the beginning and the end of radiotherapy. The posttherapeutic nutritional status was evaluated by the BIA-derived fat-free mass index (FFMI; kg/m2). Malnutrition was assumed at FFMI values of < 15 (women) and < 17 (men) kg/m2. To find differences between dosimetric parameters in well- and malnourished patients, Mann-Whitney U test was used. To model the association between malnutrition and its potentially influencing variables, several logistic regression models were built. RESULTS: The following parameters differed between well- and malnourished patients at the end of therapy: icm Dmean, V40Gy (%), V50Gy (%), and V60Gy (%), and sphm V40Gy (%). After entering these parameters into a multivariable logistic regression model (dosimetric model), icm Dmean (b = -0.12; Exp(b) = 0.88; 95% CI: 0.78-1.0; p = 0.06) and icm V40Gy (%; b = 0.06; Exp(b) = 1.07; 95% CI: 1-1.13; p = 0.04) proved to be independent dosimetric predictors of malnutrition. We only determined the cut-off value for predicting malnutrition for icm V40Gy (%) since it was the only parameter which met p < 0.05. The optimal cut-off value for the predictor V40Gy (%) based on the Youden Index was 85.6%. Another logistic regression model (dosimetric-clinical model) consisted of icm V40 (%) and the clinical parameters tumor localization, malnutrition before RT, gender, and combined chemotherapy. It was confirmed that both icm V40% (b = -1.9; Exp(b) = -2.7; 95% CI: 0.01-0.8; p = 0.03) and malnutrition at baseline (b = -1.9; Exp(b) = 4.4; 95% CI: 8.4-816.6; p = 0.0002) were independent predictors of subsequent malnutrition the end of RT. CONCLUSION: Establishment of a normal nutritional status before the start of RT and adherence to dose constraints for the swallowing apparatus may prevent malnutrition in head and neck cancer patients at the end of therapy. Specifically, we suggest an icm V40Gy (%) of more than 86% to be predictive for nutritional complications.

Risk management patterns in radiation oncology-results of a national survey within the framework of the Patient Safety in German Radiation Oncology (PaSaGeRO) project.

PURPOSE: Risk management (RM) is a key component of patient safety in radiation oncology (RO). We investigated current approaches on RM in German RO within the framework of the Patient Safety in German Radiation Oncology (PaSaGeRO) project. Aim was not only to evaluate a status quo of RM purposes but furthermore to discover challenges for sustainable RM that should be addressed in future research and recommendations. METHODS: An online survey was conducted from June to August 2021, consisting of 18 items on prospective and reactive RM, protagonists of RM, and self-assessment concerning RM. The survey was designed using LimeSurvey and invitations were sent by e­mail. Answers were requested once per institution. RESULTS: In all, 48 completed questionnaires from university hospitals, general and non-academic hospitals, and private practices were received and considered for evaluation. Prospective and reactive RM was commonly conducted within interprofessional teams; 88% of all institutions performed prospective risk analyses. Most institutions (71%) reported incidents or near-events using multiple reporting systems. Results were presented to the team in 71% for prospective analyses and 85% for analyses of incidents. Risk conferences take place in 46% of institutions. 42% nominated a manager/committee for RM. Knowledge concerning RM was mostly rated "satisfying" (44%). However, 65% of all institutions require more information about RM by professional societies. CONCLUSION: Our results revealed heterogeneous patterns of RM in RO departments, although most departments adhered to common recommendations. Identified mismatches between recommendations and implementation of RM provide baseline data for future research and support definition of teaching content.

Impact of dosimetric factors on long-term percutaneous enteral gastrostomy (PEG) tube dependence in head and neck cancer patients after (chemo)radiotherapy-results from a prospective randomized trial.

PURPOSE/OBJECTIVE: To analyze dose-volume histogram (DVH)-derived data on the exposure of organs at risk with impact on long-term percutaneous enteral gastrostomy (PEG) tube dependence in head and neck cancer patients at 6 and 12 months after definitive or adjuvant (chemo)radiotherapy. MATERIALS AND METHODS: Sixty-one patients were prospectively treated with (chemo)radiotherapy. Prophylactic or reactive gastrostomy tube placement was performed in 41 (67.2%) patients. Dose-volume histogram parameters were obtained for the swallowing apparatus. RESULTS: Median follow-up time was 25 (2-34) months. Overall survival was shorter in patients with inlying PEG tubes at 6 and 12 months (log rank p = 0.038 and p = 0.017) after therapy completion. The estimated median time of tube dependency was 6 (95% confidence interval: 2-14) months. After 6 months, 46.5% of patients were tube dependent. After 12 months, this estimated proportion fell to 31.5%. For both time points, the volume to the larynx (in %) receiving at least 50 Gy (larynx V50Gy) exceeding 53% was predictive for long-term tube feeding (6 months: p = 0.041 and 12 months: p = 0.042) being an independent predictor during multivariable analysis. There was no clinical feature influencing tube dependence after 12 months. CONCLUSION: Long-term gastrostomy dependence was found to be strongly associated with an exposure of laryngeal structures (specifically, V50Gy ≥ 53%) during radiotherapy. Consequently, the avoidance of supraglottic as well as glottic structures is warranted.

The impact of nutritional counseling on thyroid disorders in head and neck cancer patients after (chemo)radiotherapy: results from a prospective interventional trial.

OBJECTIVE: To analyze the impact of nutritional counseling on the development of hypothyroidism after (chemo)radiotherapy in head and neck cancer patients to propose a new normal tissue complication probability (NTCP) model. MATERIALS AND METHODS: At baseline, at the end of (chemo)radiotherapy, and during follow-up, thyroid-stimulating hormone (TSH) with free thyroxin (fT3 and fT4), nutritional status, and nutrient intake were prospectively analyzed in 46 out of 220 screened patients. Patients received (chemo)radiotherapy within an intervention (individual nutritional counseling every 2 weeks during therapy) and a control group (no nutritional counseling). RESULTS: Overall median follow-up was 16.5 [IQR: 12; 22] months. Fourteen patients (30.4%) presented with hypothyroidism after 13.5 [8.8; 17] months. During (chemo)radiotherapy, nutritional status worsened in the entire cohort: body mass index (p < 0.001) and fat-free mass index (p < 0.001) decreased, calorie deficit (p = 0.02) increased, and the baseline protein intake dropped (p = 0.028). The baseline selenium intake (p = 0.002) increased until the end of therapy. Application of the NTCP models by Rønjom, Cella, and Boomsma et al. resulted in good performance of all three models, with an AUC ranging from 0.76 to 0.78. Our newly developed NTCP model was based on baseline TSH and baseline ferritin. Model performance was good, receiving an AUC of 0.76 (95% CI: 0.61-0.87), with a sensitivity of 57.1% and specificity of 96.9% calculated for a Youden index of 0.73 (p = 0.004; area = 0.5). CONCLUSION: Baseline TSH and ferritin act as independent predictors for radiotherapy-associated hypothyroidism. The exclusion of such laboratory chemistry parameters in future NTCP models may result in poor model performance.

Nutritional Status Impacts Quality of Life in Head and Neck Cancer Patients Undergoing (Chemo)Radiotherapy: Results from the Prospective HEADNUT Trial.

Malnutrition negatively impacts quality of life (QoL) in patients with head and neck cancer (HNC). This is the first prospective study to assess the impact of malnutrition (defined by the bioelectrical impedance analysis (BIA)-derived fat-free mass index) on QoL in patients with HNC undergoing (chemo)radiotherapy. Between October 2018 and October 2020, 58 HNC patients prospectively completed the QoL-questionnaires EORTC-QLQ-C30 and EORTC-QLQ-H&N35 at the beginning (tb) and at the end of (chemo)radiotherapy (te) as well as during follow-up (tf). At these time points, nutritional risk assessment (MUST, NRS-2002, Nutriscore), BIA measurement and laboratory testing was performed by a permanent study team. Differences between malnourished (n = 14) and well-nourished patients (n = 44) were observed in UICC classification (P < 0.001) and HPV status (P = 0.03). Well-nourished patients showed higher baseline hemoglobin (P = 0.025) and albumin (P = 0.005), but lower c-reactive protein levels (P < 0.001). At tb, mostly malnourished patients presented with worse QoL. Multivariable analysis showed that MUST, NRS-2002, HPV status, and UICC classification were related to QoL. Nutritional status has a crucial impact on QoL. The nutritional screening protocols MUST and NRS-2002 are suitable for identifying patients at risk and predicting QoL in patients with HNC undergoing (chemo)radiotherapy.

Parotid sparing and quality of life in long-term survivors of locally advanced head and neck cancer after intensity-modulated radiation therapy.

PURPOSE: Intensity-modulated radiation therapy (IMRT) enables radiation oncologists to optimally spare organs at risk while achieving homogeneous dose distribution in the target volume. Despite great advances in technology, xerostomia is one of the most detrimental long-term side effects after multimodal therapy in patients with locally advanced head and neck cancer (HNC). This prospective observational study examines the effect of parotid sparing on quality of life in long-term survivors. PATIENTS AND METHODS: A total of 138 patients were grouped into unilateral (n = 75) and bilateral (n = 63) parotid sparing IMRT and questioned at 3, 24, and 60-month follow-up using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires. Treatment-related toxicity was scored according to the RTOG/EORTC toxicity criteria. Patients' QoL 24 and 60 months after IMRT was analyzed by ANCOVA using baseline QoL (3 months after IMRT) as a covariate. RESULTS: Patients with bilateral and unilateral parotid-sparing IMRT surviving 60 months experience similar acute and late side effects and similar changes in QoL. Three months after IMRT, physical and emotional function as well as fatigue, nausea and vomiting, pain, dyspnea, and financial problems are below (function scales) or above (symptom scales) the threshold of clinical importance. In both groups, symptom burden (EORTC H&N35) is high independent of parotid sparing 3 months after IMRT and decreases over time in a similar pattern. Pain and financial function remain burdensome throughout. CONCLUSION: Long-term HNC survivors show a similar treatment-related toxicity profile independent of unilateral vs. bilateral parotid-sparing IMRT. Sparing one or both parotids had no effect on global QoL nor on the magnitude of changes in function and symptom scales over the observation period of 60 months. The financial impact of the disease and its detrimental effect on long-term QoL pose an additional risk to unmet needs in this special patient population. These results suggest that long-term survivors need and most likely will benefit from early medical intervention and support within survivorship programs.

Implementation analysis of patient reported outcomes (PROs) in oncological routine care: an observational study protocol.

BACKGROUND: The successful implementation of patient-reported outcomes (PROs) in clinical routine faces many challenges, first and foremost the lack of consideration thereof in the patient care process. The aim of this study will be to first identify relevant barriers and facilitators and then design suitable implementation strategies which will be evaluated to improve the effectiveness of a PRO measure assessment in inpatient and outpatient cancer routine care. METHODS: During the preparation phase, interviews with oncological patients (N = 28) and medical staff (N = 4) as well as focus groups with medical staff (N = 18) across five different departments caring for cancer patients were conducted. On the basis of these, qualitative content analysis revealed relevant barriers and facilitators for implementation of PROs in cancer care. Subsequently, implementation strategies and a model of implementation were developed. In the study phase, implementation strategies will be evaluated based on nine different implementation outcomes in five different oncological clinics. Evaluation of the implementation process will take place during three months in each clinic and data will be conducted pre, while and post implementation of the PRO measure. Therefore a sample size of 60 participants of whom 30 staff members and 30 participants will be questioned using existing and newly developed implementation outcome evaluation instruments. DISCUSSION: Key to improving the effectiveness of PRO assessment in the time-critical clinical environment is the utilization of easy-to-use, electronic PRO questionnaires directly linked to patients' records thereby improving consideration of PROs in patient care. In order to validate the effectiveness of this implementation process further, an evaluation parallel to implementation following an observational study design with a mixed-methods approach will be conducted. This study could contribute to the development of adequate evaluation processes of implementation of PROs to foster sustainable integration of PRO measures into routine cancer care. TRIAL REGISTRATION: This study was registered at Open Science Framework (https://osf.io/y7xce/).

Results of a multicenter intensity modulated radiation therapy treatment planning comparison study for a sample prostate cancer case.

PURPOSE: To determine the influence of different medical physicists, photon energies, treatment planning systems and treatment machines on the resulting external beam radiotherapy dose distribution for a sample prostate cancer case. METHODS: A pre-contoured computed tomography (CT) dataset containing planning target volume 1 (PTV1) prostate and seminal vesicles (single dose [SD] 1.8 Gy, total dose [TD] 59.4 Gy), PTV2 prostate (simultaneously integrated boost [SIB], SD 2.0 Gy, TD 66 Gy), PTV3 prostate and seminal vesicles approach (SD 1.8 Gy, TD 73.8 Gy/80.4 Gy SIB) as well as organs at risk (OAR: rectum, bladder, femoral heads, bowel, anus) was offered to the members of the task group IMRT (intensity-modulated radiation therapy) of the German Society for Medical Physics. The purpose was to calculate one combined treatment plan (TP) for PTV1 and PTV2, as well as a separate one for PTV3. Dose volume histograms (DVH), different dose values, conformity index (CI), homogeneity index (HI), gradient index (GI) and a new "better than average score" were used to analyse the dose distributions. RESULTS: Altogether 44 institutions took part in this study and submitted acceptable dose distributions for the PTVs. However, there were statistically significant differences, especially for the doses administered to the OAR, such as rectum, bladder and femoral heads. Differences between the treatment plans were not easily detectable by visual inspection of the isodose distribution. Dose maxima may occur outside the PTV. Even though scoring indices are already published, the new "better than average score" was needed to identify a plan that minimises dose to all OAR simultaneously. CONCLUSION: Different medical physicists or dosimetrists, photon energies, treatment planning systems, and treatment machines have an impact on the resulting dose distribution. However, the differences only become apparent when comparing DVH, analysing dose values, comparing CI, HI, GI, as well as reviewing the dose distribution in every single plane. A new score was introduced to identify treatment plans that simultaneously deliver a low dose to all OAR. Such inter- and intra-institutional comparison studies are needed to explore different treatment planning strategies; however, there is still no automatic solution for an "optimal" treatment plan.

Toxicity and risk factors after combined high-dose-rate brachytherapy and external beam radiation therapy in men ≥75 years with localized prostate cancer.

PURPOSE: Combined high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) is a favorable treatment option in non-metastatic prostate cancer. However, reports on toxicity and outcome have mainly focused on younger patients. We aimed to determine toxicity and biochemical control rates after combined HDR-BT and EBRT in men ≥75 years. METHODS: From 1999 to 2015, 134 patients aged ≥75 years (median 76 years; 75-82 years) were identified. Patients received 18 Gy of HDR-BT (9 Gy/fraction on days 1 and 8) with an iridium-192 source. After 1 week, supplemental EBRT with a target dose of 50.4 Gy was started (delivered in 1.8 Gy fractions). RESULTS: Median follow-up time was 25 months (0-127 months). No severe (grade 4) gastrointestinal (GIT) or genitourinary (GUT) toxicities were observed. In 76 patients (56.7%), 3D conformal radiation therapy (CRT) and in 34.3% intensity-modulated radiotherapy (IMRT) was applied. CRT-treated patients were at a 2.17-times higher risk (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.31-3.57, p = 0.002) of experiencing GUT. GIT risks could be reduced by 78% using IMRT (HR: 0.22, 95% CI: 0.07-0.75, p = 0.015). Patients with a higher T stage (T2c-3a/b) were less likely to experience GIT or GUT (HR: 0.49, 95% CI: 0.29-0.85, p = 0.011 and HR: 0.5, 95% CI: 0.3-0.81, p = 0.005, respectively). CONCLUSION: HDR-BT/EBRT is a well-tolerated treatment option for elderly men ≥75 years with a limited number of comorbidities and localized intermediate- or high-risk prostate cancer. IMRT should be favored since side effects were significantly reduced in IMRT-treated patients.

The impact of [68Ga]PSMA I&T PET/CT on radiotherapy planning in patients with prostate cancer.

PURPOSE: To determine the impact of Gallium-68-labled prostate-specific membrane antigen positron-emission tomography/computed tomography ([68Ga]PSMA PET/CT) on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer. METHODS: A total of 106 patients with prostate cancer scheduled for radiation therapy underwent 120 [68Ga]PSMA PET/CT scans prior to radiotherapy treatment. In 20 cases, patients underwent [68Ga]PSMA PET/CT for primary therapy (PT), 75 cases were referred for biochemical relapse after surgery (RL), and 25 cases were intended for palliative treatment of localized metastases (MD). We retrospectively compared the impact of [68Ga]PSMA PET/CT on lesion detection and treatment decision to CT alone. RESULTS: [68Ga]PSMA PET/CT revealed a total of 271 positive lesions, whereas CT detected 86 lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases (46%) based on the higher detection rate of [68Ga]PSMA PET/CT: in 15% of cases with PT, in 43% of cases with RL, and in 44% of cases with MD. CONCLUSION: [68Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate cancer, thereby significantly impacting on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

The use of IMRT in Germany.

BACKGROUND: Intensity modulated radiotherapy (IMRT) is frequently used, but there are no data about current frequency regarding specific tumor sites and equipment used for quality assurance (QA). MATERIALS AND METHODS: An online survey about IMRT was executed from April to October 2014 by the collaborative IMRT working group (AK IMRT) of the German Association of Medical Physicists (DGMP). RESULTS: A total of 23 German institutions took part in the survey. Most reports came from users working with Elekta, Varian, and Siemens treatment machines, but also from TomoTherapy and BrainLab. Most frequent IMRT technology was volumetric modulated arc therapy (58.37 %: VMAT/"rapid arc"), followed by step-and-shoot IMRT (14.66 %), dynamic MLC (dMLC: 14.53 %), TomoTherapy (9.25 %), and 3.2 % other techniques. Different commercial hard- and software solutions are available for QA, whereas many institutes still develop their own phantoms. Data of 26,779 patients were included in the survey; 44 % were treated using IMRT techniques. IMRT was most frequently used for anal cancer, (whole) craniospinal irradiation, head and neck cancer, prostate cancer, other tumors in the pelvic region, gynecological tumors (except for breast cancer), and brain tumors. DISCUSSION: An estimated 10 % of all patients treated in 2014 with radiation in Germany were included in the survey. It is representative for the members of the AK IMRT. CONCLUSION: IMRT may be on the way to replace other treatment techniques. However, many scientific questions are still open. In particular, it is unclear when the IMRT technique should not be used.

Residual deficits in quality of life one year after intensity-modulated radiotherapy for patients with locally advanced head and neck cancer: Results of a prospective study.

PURPOSE: Patients with locally advanced head and neck cancer (LAHNC) undergo life-changing treatments that can seriously affect quality of life (QoL). This prospective study examined the key QoL domains during the first year after intensity-modulated radiotherapy (IMRT) and identified predictors of these changes in order to improve patient outcomes. PATIENTS AND METHODS: A consecutive series of patients with LAHNC completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core module (QLQ-C30) and the HNC-specific QLQ-HN35 before (t0) and at the end (t1) of definitive or adjuvant IMRT, then at 6-8 weeks (t2), 6 months (t3), and 1 year (t4) after IMRT. RESULTS: Patients (n = 111) completing questionnaires at all five time points were included (baseline response rate: 99%; dropout rate between t0 and t4: 5%). QoL deteriorated in all domains during IMRT and improved slowly during the first year thereafter. Many domains recovered to baseline values after 1 year but problems with smelling and tasting, dry mouth, and sticky saliva remained issues at this time. Increases in problems with sticky saliva were greater after 1 year in patients with definitive versus adjuvant IMRT (F = 3.5, P = 0.05). CONCLUSION: QoL in patients with LAHNC receiving IMRT takes approximately 1 year to return to baseline; some domains remain compromised after 1 year. Although IMRT aims to maintain function and QoL, patients experience long-term dry mouth and sticky saliva, particularly following definitive IMRT. Patients should be counseled at the start of therapy to reduce disappointment with the pace of recovery.

Additional androgen deprivation makes the difference: Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy.

BACKGROUND: The role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown. PATIENTS AND METHODS: Consecutive PCa patients classified as D'Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan-Meier analyses. RESULTS: Overall, 392 patients were assessable. Of these, 221 (56.4 %) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6 %) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95 % CI: 0.3-0.7, p < 0.001). D'Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank p < 0.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D'Amico intermediate-risk patients (log-rank p = 0.2). CONCLUSIONS: Additional ADT administration improves biochemical control in D'Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process.

Evaluation of a short instrument for measuring health-related quality of life in oncological patients in routine care (HELP-6): an observational study.

Purpose: Patient-reported outcomes have not been sufficiently implemented into the routine care of cancer patients because the existing instruments are often too long and complex or not cancer-specific. The aim of this study is the determination of psychometric properties and item reduction of a newly developed health-related quality of life (HrQoL) questionnaire for use in oncological clinical routines. Methods: This observational study with a repeated measurements design included oncological inpatients and outpatients. A total of 630 patients participated at the first point of measurement and 404 at the second point of measurement. To evaluate the instrument, we conducted hierarchical confirmative factor analyses and for further validation correlated the resulting factors with standardized and validated HrQoL measurements. Test-retest reliability and responsiveness to change were tested. Results: The developed questionnaire "HELP-6" ("Hamburg Inventory for Measuring Quality of Life in Oncological Patients") has a six-factor structure and has moderate-to-good convergent validity (r= -0.25 --0.68). Test-retest reliability was moderate-to-good (r =0.56-0.81, p < 0.001). Indications for responsiveness to change were found for three dimensions. The final version of the questionnaire HELP-6 has six dimensions with one item each. Conclusion: With the HELP-6 instrument for measuring HrQoL in cancer patients, we provide a short and practical patient-reported outcome instrument. Though responsiveness to change could not be confirmed for all dimensions in this study, the HELP-6 includes time-efficient completion and evaluation and is informative in relevant HrQoL dimensions of cancer patients. Therefore, the HELP-6 poses an important addition to inpatient and outpatient routine cancer care. Trial registration: This study was registered at Open Science Framework (https://osf.io/y7xce/), on 9 June 2018.

Is advanced cancer associated with demoralization and lower global meaning? The role of tumor stage and physical problems in explaining existential distress in cancer patients.

OBJECTIVE: This longitudinal study examines the extent to which global meaning, existential distress in terms of demoralization, and depression are predicted by tumor stage (UICC stages 0-II vs III/IV), palliative treatment, and physical problems in cancer patients. METHODS: N = 270 cancer patients were studied at baseline (T1, response rate: 41%) and after 3 months (T2) (N = 178, 72%). The following standardized self-report measures were used: Demoralization Scale, Life Attitude Profile--Revised, Hospital Anxiety and Depression Scale, NCCN DT (physical problems list). RESULTS: Multivariate regression analyses controlling for sociodemographic variables showed the number of physical problems significantly predicting higher demoralization (ß = 0.42, p<0.001) and depression (ß = 0.34, p<0.001), but not global meaning. While palliative treatment intention was related to higher depression (ß = 0.21, p = 0.03) and higher demoralization (ns), there was no effect of tumor stage on dependent variables. The hypothesized moderating effect of global meaning on the relation between physical problems and depression or demoralization, respectively, was not found. CONCLUSIONS: Results indicate a risk of existential distress in cancer patients across all disease stages, possibly due to confrontation with, albeit different, existential stressors throughout the illness. The general protective effect of global meaning against distress, independent of the number of physical problems, underscores the notion of existential concerns being relevant to cancer patients more generally, rather than just to a subgroup. However, physical problems might play a central role in the process of becoming demoralized through impairing the sense of mastery and competence. Findings finally strengthen the difference between the concepts of demoralization and global meaning.

Quality of life, HPV-status and phase angle predict survival in head and neck cancer patients under (chemo)radiotherapy undergoing nutritional intervention: Results from the prospective randomized HEADNUT-trial.

PURPOSE: To analyze the impact of quality of life (QoL), nutritional and clinical indicators on overall survival in patients with head and neck squamous cell cancer (HNSCC) undergoing (chemo)radiotherapy. MATERIALS AND METHODS: At the beginning, at the end of (chemo)radiotherapy and during follow-up, QoL was prospectively assessed using the EORTC-QLQ-C30 and -QLQ-H&N35 questionnaires. Data were analyzed in 58 out of 220 screened patients, who were randomized into a control and intervention group. All patients received a nutritional assessment including bioelectrical impedance analysis (BIA), laboratory testing, and a screening for malnutrition based on the questionnaires MUST, NRS-2002 and Nutriscore at baseline and at the end of therapy. The intervention consisted of an individualized nutritional counseling every 2 weeks. RESULTS: Except for emotional functioning, dyspnea, financial difficulties, dental problems and weight gain, all other scales from the EORTC-QLQ-C30 and -H&N35 deteriorated during (chemo)radiotherapy. At first follow-up, patients of the control group experienced more nausea and vomiting compared to those of the intervention group (p = 0.02). After performing a multivariable model, dental problems at the end of therapy (HR: 1.03; 95% CI: 1-1.06; p = 0.03), HPV negativity (HR: 18.19, 95% CI: 1.61-204.17; p = 0.02), and baseline phase angle (HR: 0.09; 95% CI: 0.01-0.82; p = 0.03) were identified as predictors for overall survival. CONCLUSIONS: Factors influencing overall survival in patients with HNSCC undergoing (chemo)radiotherapy are complex and multifactorial. We were able to identify QoL-related (dental problems), clinical (HPV status) and nutritional (phase angle) factors as negative predictors for survival. This study was registered within the German Clinical Trials Register (DRKS00016862).

Global meaning and meaning-related life attitudes: exploring their role in predicting depression, anxiety, and demoralization in cancer patients.

GOAL OF WORK: While significance of the concept of meaning in understanding adaptation to cancer is widely accepted, it has been little studied, especially in longitudinal data. This study aims to clarify the role of global meaning and meaning-related life attitudes (death acceptance and goal seeking) in predicting different aspects of psychological and existential distress by reference to a specified research model. PATIENTS AND METHODS: At baseline (T1), a sample of 270 cancer patients was recruited. Data from 178 patients could be obtained after 3 months at T2. Patients completed the Life-Attitude-Profile-Revised assessing global meaning and meaning-related life attitudes, the Hospital Anxiety and Depression Scale, and the Demoralization Scale. Hierarchical regression analyses were carried out in two steps. Sociodemographic and physical factors were controlled. RESULTS: Global meaning emerged as a significant negative predictor of depression (ß = -0.27) (p ≤ 0.001) and demoralization (ß = -0.27) (p ≤ 0.001). Death acceptance was a predictor of anxiety only (ß = -0.21) (p ≤ 0.003), whereas goal seeking was a positive predictor of depression (ß = 0.29) (p ≤ 0.001), anxiety (ß = 0.36) (p ≤ 0.001), and demoralization (ß = 0.35) (p ≤ 0.001). DISCUSSION: Findings confirm a global sense of meaning as an important protecting factor regarding the development of distress symptoms. Results suggest that different dimensions of meaning contribute to different dimensions of psychological well-being, as they refer to different existential problems. The need for and relevance of meaning-focused interventions in cancer patients is strengthened.

Head and neck cancer patients under (chemo-)radiotherapy undergoing nutritional intervention: Results from the prospective randomized HEADNUT-trial.

PURPOSE/OBJECTIVE: Patients with squamous cell carcinoma of the head and neck undergoing (chemo-)radiotherapy are at high risk of malnutrition. Nevertheless, there is still a lack of prospective, randomized trials investigating the influence of nutritional status on therapy-related toxicity and patients' outcome. MATERIALS AND METHODS: Between October 2018 and October 2020, 61 patients were randomized into an intervention and control group. Questionnaires (MUST, NRS-2002, and Nutriscore), clinical examinations, laboratory analyses, and bioelectrical impedance analysis (BIA) were used to assess nutritional status for all patients at the beginning and end of therapy as well as every 2 weeks during therapy. The intervention consisted of an individualized nutritional counseling every 2 weeks during therapy. RESULTS: Median baseline BMI for all participants was 23.8 (14.5-37.2) kg/m2 and dropped to 22.9 (16.8-33) kg/m2 after therapy (p < 0.001). In all patients, median baseline fat-free mass index (FFMI) was 18.1 (14-24.7) kg/m2 and decreased to 17.8 (13.4-21.6) kg/m2 till the end of therapy (p < 0.001). Compliant patients with a BMI < 22 kg/m2 presented with less weight loss in the intervention group compared to the control (p = 0.015, CI: 0.33-2.95). At baseline, MUST was the only screening-test which showed both good sensitivity (86%) and specificity (88%) in detecting malnutrition. Median follow-up was 15 (1-26) months and is still ongoing. 2-year overall survival rate was 70% in the control and 79% in the intervention group (log-rank p = 0.79). Pretherapeutic phase angle, posttherapeutic FFMI and albumin level were prognostic indicators for overall survival (log-rank p = 0.002, p = 0.008 and p = 0.016). CONCLUSIONS: Malnutrition negatively impacts patients' outcome under (chemo-)radiotherapy. Baseline phase angle, posttherapeutic FFMI and albumin level are proposed as reliable indicators for overall survival. This study was registered within the German Clinical Trials Register (DRKS00016862).

Long-term follow-up of an intensified myeloablative conditioning regimen with in vivo T cell depletion followed by allografting in patients with advanced multiple myeloma.

We report long-term results after a median follow-up of 105 months in 18 patients with multiple myeloma who received an intensified myeloablative conditioning regimen regimen consisting of modified total body irradiation, busulfan, cyclophosphamide, and antithymocyte globulin, followed by allogeneic stem cell transplantation (SCT). Grade II-IV acute graft-versus-host disease occurred in 7 patients (44%), and treatment-related mortality was 17%. Complete remission (CR) with negative immunofixation after allogeneic SCT occurred in 53% of the patients. For all patients, the estimated overall survival at 12 years was 50% (95% confidence interval [CI], 26%-74%), and the estimated event-free survival (EFS) was 35% (95% CI, 23%-57%). Those patients who achieved CR after SCT had a 12-year estimated PFS of 60%, whereas none of the patients without CR remained progression-free. Our data indicate that an intensified myeloablative conditioning regimen followed by allogeneic SCT can produce long-term survival and freedom from disease in patients with multiple myeloma who achieve CR.