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.

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.

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.

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.

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.

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).

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).

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.

Development of a Short Instrument for Measuring Health-Related Quality of Life in Oncological Patients for Clinical Use: Protocol for an Observational Study.

BACKGROUND: Cancer patients often suffer from the physical and psychological burden of their disease and its treatment. This is frequently insufficiently identified and addressed in clinical practice. In the context of improving patient-centered care in oncological patients, patient-reported outcomes (PROs) represent an important addition to current routine care. So far, available PRO questionnaires for cancer patients are unsuitable for routine procedures due to their length and complexity. OBJECTIVE: This study aimed to develop and psychometrically test a short questionnaire to measure health-related quality of life (HrQoL) in cancer patients for use in routine care. METHODS: This observational study consists of two parts: (1) a qualitative study to develop a short questionnaire measuring HrQoL and (2) a quantitative study to psychometrically test this questionnaire in five oncological departments of a comprehensive cancer center. In part 1 of the study, semistructured interviews with 28 cancer patients, as well as five focus groups with 22 clinicians and nurses, were conducted to identify clinically relevant dimensions of HrQoL. The identified dimensions were complemented with related dimensions from empirical studies and reviewed via expert discussion. Based on this, a short instrument was developed. In part 2 of the study, the developed questionnaire was tested in cancer in- and outpatients at five participating oncological clinics using additional standardized questionnaires assessing HrQoL and other important PROs. The questionnaire was presented to more than 770 patients twice during treatment. RESULTS: The project started in May 2017 with recruitment for study phase I beginning in December 2017. Recruitment for study phases I and II ended in April 2018 and February 2019, respectively. After study phase II and psychometrical analyses, the newly developed questionnaire measuring the HrQoL of all cancer entities in routine care was finalized. CONCLUSIONS: With five to six dimensions and one item per dimension, the developed questionnaire is short enough to not disrupt routine procedures during treatment and is profound enough to inform clinicians about the patient's HrQoL impairments and status. TRIAL REGISTRATION: Open Science Framework Registries 10.17605/OSF.IO/Y7XCE; https://osf.io/y7xce/. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/17854.

Prognostic factors for lymphedema in patients with locally advanced head and neck cancer after combined radio(chemo)therapy- results of a longitudinal study.

AIM: Treatment-associated lymphedema is a common side effect after multimodal therapy for locally advanced head and neck cancer (LAHNC). This study aims to evaluate potential prognostic factors for head and neck lymphedema (HNL) and its potential impact on clinical outcome. METHODS: This is a prospective data registry analysis on 280 patients treated for locally advanced head and neck cancer (LAHNC). All patients received surgery and risk-adapted platinum-based adjuvant intensity modulated radio(chemo)therapy (R(C)T, IMRT). Treatment- related toxicity was prospectively registered in a data base in regular intervals (baseline 3 months after R(C)T, every 3 months for 3 years, and every 6 months thereafter) and documented according to RTOG/EORTC toxicity criteria. RESULTS: Predictive for any grade HNL 3 months after R(C)T were age, BMI, number of removed nodes and RT modality. Multivariable logistic regression analysis showed that in the acute toxicity phase (3 months after R(C)T) higher body mass index (BMI), extracapsular spread (ECE), linac-based IMRT, bilateral treatment to the neck (surgery and RT), and the addition of chemotherapy increase the risk for grade 2 HNL. For chronic HNL, higher BMI, linac-based IMRT and ECE were predictive for grade 2 HNL. Higher BMI is associated with better local control rates. Advanced age and ECE had a negative impact on OS. CONCLUSION: HNL is a common acute and late side effect after multimodal therapy for LAHNC. Knowing risk factors for HNL prior to therapy enables caregivers and patients to take measures prior to treatment to prevent or limit the effects of HNL.

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.

Locally Ablative Radiation Therapy of a Primary Human Small Cell Lung Cancer Tumor Decreases the Number of Spontaneous Metastases in Two Xenograft Models.

PURPOSE: To investigated the influence of radiation therapy (RT), surgery (OP), radio-chemotherapy (RChT), or chemotherapy (ChT) on small cell lung cancer metastases in 2 xenograft models. METHODS AND MATERIALS: A total of 1 × 106 human small cell lung cancer cells (OH1, H69) were subcutaneously injected into severe combined immunodeficiency mice to form a local primary tumor node at the lower trunk. Radiation therapy, OP, RChT, or ChT were started after development of palpable tumors. Chemotherapy was given as a single intraperitoneal injection of cisplatin. Radiation therapy was 5 × 10 Gy on the local tumor node. Two additional groups were implemented to assess primary tumors and distant metastases in untreated mice at the beginning (control group A) and at the end of the experiment (control group B). Proapoptotic, antiproliferative, antiangiogenic, and hypoxic effects were assessed by Feulgen, Ki67, S1P1 receptor, and hypoxia-inducible factor 1α staining, respectively. Quantitative Alu-polymerase chain reaction was used to determine circulating tumor cells in the blood, and disseminated tumor cells in the lungs, bone marrow, liver, and brain. RESULTS: In both xenograft models, RT and RChT abrogated local tumor growth, indicated by increased apoptosis, decreased cell proliferation, and reduced microvessel density (equally affecting vessels of all diameters). Regarding metastases, RT and RChT not only counteracted the time-dependent increase of dissemination but also decreased the metastatic load pre-existing at therapy induction in the blood, lungs, and liver. Only in the case of relapse-free surgery could similar effects be achieved by OP. CONCLUSIONS: Our models provide evidence that RT and RChT ablate the primary tumor and inhibit metastasis development over time. Upon local recurrence, RT showed beneficial effects compared with OP with regard to suppression of circulating tumor cells and disseminated tumor cells.

Magnetic resonance imaging for precise radiotherapy of small laboratory animals.

AIMS: Radiotherapy of small laboratory animals (SLA) is often not as precisely applied as in humans. Here we describe the use of a dedicated SLA magnetic resonance imaging (MRI) scanner for precise tumor volumetry, radiotherapy treatment planning, and diagnostic imaging in order to make the experiments more accurate. METHODS AND MATERIALS: Different human cancer cells were injected at the lower trunk of pfp/rag2 and SCID mice to allow for local tumor growth. Data from cross sectional MRI scans were transferred to a clinical treatment planning system (TPS) for humans. Manual palpation of the tumor size was compared with calculated tumor size of the TPS and with tumor weight at necropsy. As a feasibility study MRI based treatment plans were calculated for a clinical 6MV linear accelerator using a micro multileaf collimator (µMLC). In addition, diagnostic MRI scans were used to investigate animals which did clinical poorly during the study. RESULTS: MRI is superior in precise tumor volume definition whereas manual palpation underestimates their size. Cross sectional MRI allow for treatment planning so that conformal irradiation of mice with a clinical linear accelerator using a µMLC is in principle feasible. Several internal pathologies were detected during the experiment using the dedicated scanner. CONCLUSION: MRI is a key technology for precise radiotherapy of SLA. The scanning protocols provided are suited for tumor volumetry, treatment planning, and diagnostic imaging.

Survival and overall treatment time after postoperative radio(chemo)therapy in patients with head and neck cancer.

BACKGROUND: Generally, overall treatment time for patients with locally advanced head and neck cancer should be as short as reasonably possible. This analysis was undertaken to determine at what overall treatment time additional survival/locoregional control benefits could be achieved compared to a 100-day cutoff. METHODS: Clinical impact of overall treatment time was assessed in 272 patients by multivariable Cox regression and Kaplan-Meier analyses using the historical 100-day cutoff and the optimal overall treatment time, determined using recursive partitioning analysis. Survival endpoints were determined for the 100-day and optimal overall treatment times validated using bootstrap resampling. RESULTS: Recursive partitioning determined the optimal overall treatment time as 87 days. In the 87-day multivariable analysis, adverse factors for overall survival (OS) and disease-free survival (DFS) were overall treatment time ≥87 days and extracapsular spread, and overall treatment time and R1 status, respectively. CONCLUSION: Overall treatment time is important for survival in patients with head and neck cancer. Completing treatment within as short a timeframe as possible may be associated with longer OS and DFS. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1058-1065, 2016.

Five-year biochemical recurrence-free and overall survival following high-dose-rate brachytherapy with additional external beam or radical prostatectomy in patients with clinically localized prostate cancer.

INTRODUCTION: High-dose-rate brachytherapy (HDR-BT) with external-beam radiation therapy and radical prostatectomy (RP) are common treatment options for clinically localized prostate cancer. The aim was to describe risk factors for biochemical recurrence (BCR) and death, as well as BCR rates and overall survival (OS) rates in both treatment groups. PATIENTS AND METHODS: Overall, 5,619 patients with localized prostate cancer underwent either RP (n = 5,200) or HDR-BT (n = 419) between 1999 and 2009. Median follow-up time was 72.4 months. Kaplan-Meier analyses and multivariable Cox regression analyses were performed for the overall cohort and for a propensity score-matched cohort to predict BCR and OS rates. Within the matched cohort, stratified analyses were repeated for HDR-BT alone (n = 206) and HDR-BT plus androgen deprivation therapy (ADT) (n = 213). Sensitivity analyses were performed to adjust for prostate-specific antigen rebound. RESULTS: The 5-year BCR-free survival rates were 82.1% vs. 80.3% (P<0.01) for RP and HDR-BT, respectively. Corresponding 5-year OS rates were 97.1% vs. 92.4% (P<0.01). In the propensity score-matched cohort, 5-year BCR-free survival rates were 80.3% vs. 77.1%; P = 0.06 and 5-year OS rates were 95.7% vs. 92.4%; P = 0.5. In multivariable models, the overall HDR-BT exerted no significant effect on BCR, and the same results were recorded in the matched cohort. In stratified analyses, HDR-BT alone vs. RP increased BCR risk (1.45; P<0.01); conversely, HDR-BT plus ADT vs. RP decreased BCR risk (hazard ratio = 0.66; P = 0.02). CONCLUSIONS: First, RP offers equivalent oncological control without the need for concurrent hormone therapy and its morbidity. Second, patients who have RP avoid ADT (2%) and the need for salvage and adjuvant external-beam radiation therapy is low at 11% and 3%, respectively.