Prospective evaluation of multitarget treatment of pediatric patients with helical intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy (RT) is persistently gaining significance in the treatment of pediatric tumors. However, individual features of a growing body and multifocal stages complicate this approach. Tomotherapy offers advantages in the treatment of anatomically complex tumors with low risks of side effects. Here we report on toxicity incidence and outcome of tomotherapy with a focus on multitarget RT (mtRT). MATERIALS AND METHODS: From 2008 to 2017, 38 children diagnosed with sarcoma were treated with tomotherapy. The median age was 15 years (6-19 years). Toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03 and classified into symptoms during RT, acutely (0-6 months) and late (>6 months) after RT, and long-term sideeffects (>24 months). RESULTS: The main histologies were Ewing sarcoma (n = 23 [61%]) and alveolar rhabdomyosarcoma (n = 5 [13%]). RT was performed with a median total dose of 54 Gy (40.5-66.0 Gy) and a single dose of 2 Gy (1.80-2.27 Gy). Twenty patients (53%) received mtRT. Median follow-up was 29.7 months (95% confidence interval 15.3-48.2 months) with a 5-year survival of 55.2% (±9.5%). The 5­year survival rate of patients with mtRT (n = 20) was 37.1 ± 13.2%, while patients who received single-target RT (n = 18) had a 5-year survival rate of 75 ± 10.8%. Severe toxicities (grade 3 and 4) emerged in 14 patients (70%) with mtRT and 7 patients (39%) with single-target RT. Two non-hematological grade 4 toxicities occurred during RT: one mucositis and one radiodermatitis. After mtRT 5 patients had grade 3 toxicities acute and after single-target RT 4 patients. One patient had acute non-hematological grade 4 toxicities (gastritis, pericarditis, and pericardial effusion) after mtRT. Severe late effects of RT occurred in 2 patients after mtRT and in none of the single-target RT patients. No severe long-term side effects appeared. CONCLUSION: Our results showed acceptable levels of acute and late toxicities, considering the highly advanced diseases and multimodal treatment. Hence, tomotherapy is a feasible treatment method for young patients with anatomically complex tumors or multiple targets. Especially mtRT is a promising and innovative treatment approach for pediatric sarcomas, delivering unexpectedly high survival rates for patients with multifocal Ewing sarcomas in this study, whereby the limited number of patients should invariably be considered in the interpretation.

Integration of PET-imaging into radiotherapy treatment planning for low-grade meningiomas improves outcome.

PURPOSE: Meningiomas have an excellent survival prognosis, and radiotherapy (RT) is a central component of interdisciplinary treatment. During treatment planning, the definition of the target volume remains challenging using MR and CT imaging alone. This is the first study to analyze the impact of additional PET-imaging on local control (LC) and overall survival (OS) after high-precision RT. METHODS: We analyzed 339 meningiomas treated between 2000 and 2018. For analyses, we divided the patients in low-grade (n = 276) and high-grade (n = 63) cases. We performed RT in an adjuvant setting due to subtotal resection or later due to recurrent tumor growth. The target volumes were delineated based on diagnostic CT and MRI and, if available, additional PET-imaging (low-grade: n = 164, 59.4%; high-grade: n = 39, 61.9%) with either 68Ga-Dotanoc/Dotatoc, 18F-fluoroethyltyrosine or 11C-methionine tracer. Patients were treated with fractionated stereotactic RT with a median total dose and dose per fraction of 54 Gy and 1.8 Gy, respectively. RESULTS: Median follow-up was 5.6 years. For low-grade meningiomas, mean OS was 15.6 years and mean LC was 16.9 years; for high-grade cases mean OS was 11.6 years, and mean LC was 11.1 years. In univariate analyses, PET-imaging had a significant impact on OS (p = 0.035) and LC (p = 0.041) for low-grade meningiomas and remained significant (p = 0.015) for LC in the multivariate analysis. For high-grade cases, PET did not influence both OS and LC. Further prognostic factors could be identified. CONCLUSIONS: For low-grade meningiomas, we showed that the addition of PET-imaging for target volume definition led to a significantly enhanced LC. Thus, PET improves the detection of tumor cells and helps distinguish between healthy tissue and meningioma tissue, especially during the treatment planning process.

Stereotactic body radiotherapy (SBRT) in patients with lung metastases - prognostic factors and long-term survival using patient self-reported outcome (PRO).

OBJECTIVES: The present study aims to evaluate long-term side-effects and outcomes and confirm prognostic factors after stereotactic body radiotherapy (SBRT) of pulmonary lesions. This is the first work that combines the investigated data from patient charts and patient-reported outcome (PRO) up to 14 years after therapy. MATERIALS AND METHODS: We analyzed 219 patients and 316 lung metastases treated between 2004 and 2019. The pulmonary lesions received a median dose and dose per fraction of 35 Gy (range: 14-60.5 Gy) and 8 Gy (range: 3-20 Gy) to the surrounding isodose. During the last 1.5 years of monitoring, we added PRO assessment to our follow-up routine. We sent an invitation to a web-based survey questionnaire to all living patients whose last visit was more than 6 months ago. RESULTS: Median OS was 27.6 months. Univariate analysis showed a significant influence on OS for KPS ≥90%, small gross tumor volume (GTV) and planning target volume (PTV), the absence of external metastases, ≤3 pulmonary metastases, and controlled primary tumor. The number of pulmonary metastases and age influenced local control (LC) significantly. During follow-up, physicians reported severe side-effects ≥ grade 3 in only 2.9% within the first 6 months and in 2.5% after 1 year. Acute symptomatic pneumonitis grade 2 was observed in 9.7%, as grade 3 in 0.5%. During PRO assessment, 39 patients were contacted, 38 patients participated, 14 participated twice during follow-up. Patients reported 15 cases of severe side effects (grade ≥ 3) according to PROCTCAE classification. Severe dyspnea (n = 6) was reported mostly. CONCLUSION: We could confirm excellent local control and low toxicity rates. PROs improve and complement follow-up care. They are an essential measure in addition to the physician-reported outcomes. Future research must be conducted regarding the correct interpretation of PRO data.

Single-institutional outcome-analysis of low-dose stereotactic body radiation therapy (SBRT) of adrenal gland metastases.

BACKGROUND: Adrenal gland metastases are a common diagnostic finding in various tumor diseases. Due to the increased use of imaging methods, they are diagnosed more frequently, especially in asymptomatic patients. SBRT has emerged as a new, alternative treatment option in the field of radiation oncology. In the past, it was often used for treating inoperable lung, liver, prostate, and brain tumors. Meanwhile, it is also an established keystone in the treatment of oligometastatic diseases. This retrospective study aims to evaluate the effect of low-dose SBRT in patients with adrenal metastases. METHODS: We analyzed a group of 31 patients with 34 adrenal gland lesions treated with low-dose SBRT between July 2006 and July 2019. Treatment-planning was performed through contrast-enhanced CT, followed by image-guided stereotactic radiotherapy using cone-beam CT. The applied cumulative median dose was 35 Gy; the median single dose was 7 Gy. We focused on local control (LC), progression-free survival (PFS), overall survival (OS), as well as acute and late toxicity. RESULTS: Seven adrenal gland metastases (20.6%) experienced local failure, 80.6% of the patients faced a distant progression. Fourteen patients were still alive. Median follow-up for all patients was 9.8 months and for patients alive 14.4 months. No treatment-related side-effects >grade 2 occurred. Of all, 48.4% suffered from acute gastrointestinal disorders; 32.3% reported acute fatigue, throbbing pain in the renal area, and mild adrenal insufficiency. Altogether, 19.4% of the patients faced late-toxicities, which were as follows: Grade 1: 12.9% gastrointestinal disorders, 3.2% fatigue, Grade 2: 9.7% fatigue, 6.5% headache, 3.2% loss of weight. The 1-year OS and probability of LF were 64 and 25.9%, respectively. CONCLUSION: Low-dose SBRT has proven as an effective and safe method with promising outcomes for treating adrenal metastases. There appeared no high-grade toxicities >grade 2, and 79.4% of treated metastases were progression-free. Thus, SBRT should be considered as a therapy option for adrenal metastases as an individual therapeutic concept in the interdisciplinary discussion as an alternative to surgical or systemic treatment.

Early and late toxicity profiles of patients receiving immediate postoperative radiotherapy versus salvage radiotherapy for prostate cancer after prostatectomy.

PURPOSE: The present study aims to evaluate both early and late toxicity profiles of patients receiving immediate postoperative radiotherapy (RT; adjuvant RT or additive RT) compared to salvage RT. METHODS: We evaluated 253 patients with prostate cancer treated with either immediate postoperative (adjuvant RT, n = 42; additive RT, n = 39) or salvage RT (n = 137). Thirty-five patients received salvage treatment but did not achieve a postoperative prostate specific antigen (PSA) level <0.1 ng/ml and thus were excluded from analysis. RESULTS: A significantly higher rate of early grade 1/2 proctitis in the immediate postoperative RT group without additional pelvic RT was observed (p = 0.02). Patients in the immediate postoperative RT group without additional pelvic RT showed significantly more early urinary tract obstructions (p = 0.003). Toxicity rates of early (<3 months) and late (3-6 months) postoperative RT were similar (p > 0.05). Baseline recovery rate of erectile dysfunction was better in patients with immediate postoperative RT without additional pelvic RT (p = 0.02; hazard ratio (HR) = 2.22, 95%-confidence interval, 95%-CI: 1.12-4.37). Recovery rate of urinary incontinence showed no significant difference in all groups (p > 0.05). CONCLUSION: Patients receiving immediate postoperative RT (adjuvant or additive RT) without additional pelvic RT experience early gastrointestinal (GI) side effect proctitis and, as well as early genitourinary (GU) toxicity urinary tract obstruction more frequently than patients treated with salvage RT. Therefore, complete recovery after surgery is essential. However, we suggest basing the treatment decision on the patient's postoperative clinical condition and evaluation of any adverse risk factors, since many studies demonstrate a clear benefit for immediate postoperative RT (adjuvant or additive RT) in terms of oncological outcome.

Cavity volume changes after surgery of a brain metastasis-consequences for stereotactic radiation therapy.

PURPOSE: For a large or symptomatic brain metastasis, resection and adjuvant radiotherapy are recommended. Hypofractionated stereotactic radiotherapy (HFSRT) is increasingly applied in patients with a limited number of lesions. Exact target volume definition is critical given the small safety margins. Whilst technical advances have minimized inaccuracy due to patient positioning and radiation targeting, little is known about changes in target volume. This study sought to evaluate potential changes in the resection cavity of a brain metastasis. METHODS: In all, 57 patients treated with HFSRT after surgical resection of one brain metastasis between 2008 and 2015 in our institution were included in this study. Gross tumor volume (GTV) of the initial metastasis and the volume of the resection cavity in the post-operative, planning, and follow-up MRIs were measured and compared. RESULTS: The mean cavity size decreased after surgery with the greatest change of -23.4% (±41.5%) occurring between post-operative MRI and planning MRI (p < 0.01). During this time period, the cavity volume decreased, remained stable, and increased in 79.1, 3.5, and 17.4%, respectively. A further decrease of -20.7% (±58.1%) was perceived between planning MRI and first follow-up (p < 0.01). No significant difference in pattern of change could be observed depending on the volume of initial GTV, size of the post-operative resection cavity, initial or post-resection FLAIR (fluid-attenuated inversion recovery) hyper-intensity, postsurgical ischemia, or primary tumor. The resection cavities of patients with post-operative ischemia were significantly larger than resection cavities of patients without ischemia. CONCLUSION: The resection cavity seems to be very dynamic after surgery. Hence, it remains necessary to use very recent scans for treatment planning.

Stereotactic irradiation of the resection cavity after surgical resection of brain metastases - when is the right timing?

Purpose: This study aimed to evaluate whether an early beginning of the adjuvant stereotactic radiotherapy after macroscopic complete resection of 1-3 brain metastases is essential or whether longer intervals between surgery and radiotherapy are feasible.Material and methods: Sixty-six patients with 69 resection cavities treated with HFSRT after macroscopic complete resection of 1-3 brain metastases between 2009 and 2016 in our institution were included in this study. Overall survival, local recurrence and locoregional recurrence were evaluated depending on the time interval from surgery to the start of radiation therapy.Results: Patients that started radiotherapy within 21 days from surgery had a significantly decreased OS compared to patients treated after a longer interval from surgery (p < .01). There was no significant difference between patients treated ≥ 34 and 22-33 days from surgery (p = .210). In the univariate analysis, local control was superior for patients starting treatment 22-33 days from surgery compared to a later start (p = .049). This effect did not prevail in a multivariate model. There was no significant difference between patients treated within 21 days and patients treated more than 33 days after surgery (p = .203). Locoregional control was not influenced by RT timing (p = .508).Conclusion: A short delay in the start of radiotherapy does not seem to negatively impact the outcome in patients with resected brain metastases. We even observed an unexpected reduction in OS in patients treated within 21 days from surgery. Further studies are needed to define the optimal timing of postoperative radiotherapy to the resection cavity.

A Second Course of Radiotherapy in Patients with Recurrent Malignant Gliomas: Clinical Data on Re-irradiation, Prognostic Factors, and Usefulness of Digital Biomarkers.

OPINION STATEMENT: The treatment of malignant gliomas has undergone a significant intensification during the past decade, and the interdisciplinary treatment team has learned that all treatment opportunities, including surgery and radiotherapy (RT), also have a central role in recurrent gliomas. Throughout the decades, re-irradiation (re-RT) has achieved a prominent place in the treatment of recurrent gliomas. A solid body of evidence supports the safety and efficacy of re-RT, especially when modern techniques are used, and justifies the early use of this regimen, especially in the case when macroscopic disease is present. Additionally, a second adjuvant re-RT to the resection cavity is currently being investigated by several investigators and seems to offer promising results. Although advanced RT technologies, such as stereotactic radiosurgery (SRS), fractionated stereotactic radiotherapy (FSRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT) have become available in many centers, re-RT should continue to be kept in experienced hands so that they can select the optimal regimen, the ideal treatment volume, and the appropriate techniques from their tool-boxes. Concomitant or adjuvant use of systemic treatment options should also strongly be taken into consideration, especially because temozolomide (TMZ), cyclohexyl-nitroso-urea (CCNU), and bevacizumab have shown a good safety profile; they should be considered, if available. Nonetheless, the selection of patients for re-RT remains crucial. Single factors, such as patient age or the progression-free interval (PFI), fall too short. Therefore, powerful prognostic scores have been generated and validated, and these scores should be used for patient selection and counseling.

Complementary medicine in radiation oncology : German health care professionals' current qualifications and therapeutic methods.

INTRODUCTION: Recently, complementary and alternative medicine (CAM) has moved more into the focus, and cancer societies such as the German Cancer Society (Deutsche Krebsgesellschaft, DKG) have established working groups to develop a guideline for CAM. The present work aims to evaluate the acceptance of CAM in the whole radiation oncology community. METHODS: We conducted an online survey on CAM and sent the modified questionnaire that was successfully distributed to all members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynakologische Onkologie, AGO) of the DKG in 2014 to the members of the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie und Strahlentherapie, DEGRO). The survey consisted of 17 questions regarding personal information and current CAM guidelines within the workplace/clinic. RESULTS: A total of 143 members participated. Of these, 12% had some CAM qualification. For hematological cancer in 35% and in up to 76% for breast cancer, CAM treatment is offered in German radiation oncology facilities, mainly due to fatigue symptoms. CAM is part of routine treatment in 32.2%, 22.0% are planning to incorporate it. Most physicians advise patients to partake in sports activities and recommend dietary supplements and nutritional counseling. The cost of CAM treatment is fully covered in 9.8% of all participating facilities. CONCLUSION: Today, CAM is integrated into cancer care; however, skepticism regarding its effect still exists. Evidence-based results must be generated to convince physicians of the effectiveness of CAM methods. CAM qualifications must be included in physicians' training to improve their understanding and counseling regarding CAM options in cancer care.

Semantic imaging features predict disease progression and survival in glioblastoma multiforme patients.

BACKGROUND: For glioblastoma (GBM), multiple prognostic factors have been identified. Semantic imaging features were shown to be predictive for survival prediction. No similar data have been generated for the prediction of progression. The aim of this study was to assess the predictive value of the semantic visually accessable REMBRANDT [repository for molecular brain neoplasia data] images (VASARI) imaging feature set for progression and survival, and the creation of joint prognostic models in combination with clinical and pathological information. METHODS: 189 patients were retrospectively analyzed. Age, Karnofsky performance status, gender, and MGMT promoter methylation and IDH mutation status were assessed. VASARI features were determined on pre- and postoperative MRIs. Predictive potential was assessed with univariate analyses and Kaplan-Meier survival curves. Following variable selection and resampling, multivariate Cox regression models were created. Predictive performance was tested on patient test sets and compared between groups. The frequency of selection for single variables and variable pairs was determined. RESULTS: For progression free survival (PFS) and overall survival (OS), univariate significant associations were shown for 9 and 10 VASARI features, respectively. Multivariate models yielded concordance indices significantly different from random for the clinical, imaging, combined, and combined + MGMT models of 0.657, 0.636, 0.694, and 0.716 for OS, and 0.602, 0.604, 0.633, and 0.643 for PFS. "Multilocality," "deep white-matter invasion," "satellites," and "ependymal invasion" were over proportionally selected for multivariate model generation, underlining their importance. CONCLUSIONS: We demonstrated a predictive value of several qualitative imaging features for progression and survival. The performance of prognostic models was increased by combining clinical, pathological, and imaging features.

Treatment-related features improve machine learning prediction of prognosis in soft tissue sarcoma patients.

BACKGROUND AND PURPOSE: Current prognostic models for soft tissue sarcoma (STS) patients are solely based on staging information. Treatment-related data have not been included to date. Including such information, however, could help to improve these models. MATERIALS AND METHODS: A single-center retrospective cohort of 136 STS patients treated with radiotherapy (RT) was analyzed for patients' characteristics, staging information, and treatment-related data. Therapeutic imaging studies and pathology reports of neoadjuvantly treated patients were analyzed for signs of response. Random forest machine learning-based models were used to predict patients' death and disease progression at 2 years. Pre-treatment and treatment models were compared. RESULTS: The prognostic models achieved high performances. Using treatment features improved the overall performance for all three classification types: prediction of death, and of local and systemic progression (area under the receiver operatoring characteristic curve (AUC) of 0.87, 0.88, and 0.84, respectively). Overall, RT-related features, such as the planning target volume and total dose, had preeminent importance for prognostic performance. Therapy response features were selected for prediction of disease progression. CONCLUSIONS: A machine learning-based prognostic model combining known prognostic factors with treatment- and response-related information showed high accuracy for individualized risk assessment. This model could be used for adjustments of follow-up procedures.

A trend towards a more intense adjuvant treatment of low-grade-gliomas in tertiary centers in Germany after RTOG 9802 - results from a multi-center survey.

BACKGROUND: The treatment recommendations for Low-grade Gliomas (LGG) underwent profound changes due to results from RTOG 9802 published in April 2016. This work aims to investigate whether the results from the trial were already incorporated into the treatment recommendations at German oncology centers before an update of the official guidelines. METHODS: An online based questionnaire with questions covering all aspects of adjuvant treatments of LGGs was generated, including three cases with distinct clinical situations. We contacted all members of the neuro-oncologic working group (NOA) of the German Cancer Society (DKG) as well as all German-speaking members of the European Low-Grade Glioma Network via E-mail. RESULTS: We collected 38 responses. All responders were at least specialists; they predominantly worked at tertiary hospitals with a high volume of LGGs treated annually (75% with more than 10 cases per year). All responders stated to consent treatment recommendation for LGGs within interdisciplinary oncologic boards. The treatment recommendations for LGGs changed profoundly between 2015 and 12/2016. There is a trend towards PCV-based multimodal treatments, especially for oligodendroglial LGGs, as well as a trend away from watchful-waiting-policies for astrocytic LGGs. CONCLUSION: Neurooncologists do adapt results from clinical trials quickly. None the less, there is still an immense heterogeneity within the treatment recommendations, predominantly for astrocytic LGGs. Well planned clinical trials and concise treatment recommendations are warranted; additionally, individual counseling of patients is essential.

Complementary and alternative medicine in radiation oncology : Survey of patients' attitudes.

BACKGROUND: Complementary and alternative medicine (CAM) are gaining in importance, but objective data are mostly missing. However, in previous trials, methods such as acupuncture showed significant advantages compared to standard therapies. Thus, the aim was to evaluate most frequently used methods, their significance and the general acceptance amongst cancer patients undergoing radiotherapy (RT). METHODS: A questionnaire of 18 questions based on the categorical classification released by the National Centre for Complementary and Integrative Health was developed. From April to September 2015, all patients undergoing RT at the Department of Radiation Oncology, Technical University of Munich, completed the survey. Changes in attitude towards CAM were evaluated using the questionnaire after RT during the first follow-up visit (n = 31). RESULTS: Of 634 patients, 333 answered the questionnaire (52.5%). Of all participants, 26.4% used CAM parallel to RT. Before RT, a total of 39.3% had already used complementary medicine. The most frequently applied methods during therapy were vitamins/minerals, food supplements, physiotherapy/manual medicine, and homeopathy. The majority (71.5%) did not use any complementary treatment, mostly stating that CAM was not offered to them (73.5%). The most common reasons for use were to improve the immune system (48%), to reduce side effects (43.8%), and to not miss an opportunity (37.8%). Treatment integrated into the individual therapy concept, e.g. regular acupuncture, would be used by 63.7% of RT patients. CONCLUSION: In comparison to other studies, usage of CAM parallel to RT in our department is considered to be low. Acceptance amongst patients is present, as treatment integrated into the individual oncology therapy would be used by about two-third of patients.

High-precision radiotherapy for meningiomas : Long-term results and patient-reported outcome (PRO).

OBJECTIVE: To evaluate long-term outcome after high-precision radiotherapy (RT) of meningioma patients in terms of survival and side effects. METHODS: We analyzed 275 meningioma cases: 147 low-grade and 43 high-grade meningiomas (WHO II: n = 40, III: n = 3). In all, 85 patients had no pathologically confirmed histology but were determined as low-grade based on multimodal imaging. Surgery was performed in 183 cases. RT was delivered as either radiosurgery (RS, n = 16), fractionated stereotactic radiotherapy (FSRT, n = 241), or intensity-modulated radiation therapy (IMRT, n = 18). Of 218 patients contacted for patient-reported-outcome (PRO), 207 responded (95%). RESULTS: Median follow-up was 7.2 years. For low-grade meningioma the survival rate (OS) was 97% at 3 years, 85% at 10 years, and 64% at 15 years, for atypical meningioma 91% at 3 years, 62% at 10 years, and 50% at 15 years. Local control rate (PFS) for low-grade meningioma was 91% at 3 years, 87% at 5 years, and 86% at 10 years, for atypical cases 67% at 3 years and 55% at 5 years. Of all, 3.0% of patients reported worsened or new symptoms grade ≥3 during RT and the first 6 months thereafter; 17.5% reported a deterioration after more than 2 years. We found the prognostic factors tumor volume and age significantly influencing OS and PFS. CONCLUSION: Complemented by PRO, we found long-term low toxicity rates in addition to excellent local control. Thus, due to the beneficial risk-benefit profile of benign and high-risk meningiomas, RT should be performed as adjuvant treatment and should not be postponed until tumor progression.

Fractionated vs. single-fraction stereotactic radiotherapy in patients with vestibular schwannoma : Hearing preservation and patients' self-reported outcome based on an established questionnaire.

BACKGROUND: Stereotactic radiotherapy (RT) has been established as a valid treatment alternative in patients with vestibular schwannoma (VS). There is ongoing controversy regarding the optimal fractionation. Hearing preservation may be the primary goal for patients with VS, followed by maintenance of quality of life (QoL). METHODS: From 2002 to 2015, 184 patients with VS were treated with radiosurgery (RS) or fractionated stereotactic radiotherapy (FSRT). A survey on current symptoms and QoL was conducted between February and June 2016. RESULTS: Median follow-up after RT was 7.5 years (range 0-14.4 years). Mean overall survival (OS) after RT was 31.1 years, with 94 and 87% survival at 5 and 10 years, respectively [corrected]. Mean progression-free survival (PFS) was 13.3 years, with 5­ and 10-year PFS of 92%. Hearing could be preserved in RS patients for a median of 36.3 months (range 2.3-13.7 years). Hearing worsened in 17 (30%) cases. Median hearing preservation for FSRT was 48.7 months (range 0.0-13.8 years); 29 (23%) showed hearing deterioration. The difference in hearing preservation was not significant between RS and FSRT (p = 0.3). A total of 123/162 patients participated in the patient survey (return rate 76%). The results correlate well with the information documented in the patient files for tinnitus and facial and trigeminal nerve toxicity. Significant differences appeared regarding hearing impairment, gait uncertainty, and imbalance. CONCLUSION: These data confirm that RS and FSRT are comparable in terms of local control for VS. RS should be reserved for smaller lesions, while FSRT can be offered independently of tumor size. Patient self-reported outcome during follow-up is of high value. The established questionnaire could be validated in the independent cohort.

Oligometastases from prostate cancer: local treatment with stereotactic body radiotherapy (SBRT).

BACKGROUND: The impact of local tumor ablative therapy in oligometastasized prostate cancer (PC) is still under debate. To gain data for this approach, we evaluated oligometastasized PC patients receiving stereotactic body radiotherapy (SBRT) to bone metastases. METHODS: In this retrospective study, 15 oligometastasized PC patients with a total of 20 bone metastases were evaluated regarding biochemical progression-free survival (PSA-PFS), time to initiation of ADT, and local control rate (LCR). Three patients received concomitant androgen deprivation therapy (ADT). RESULTS: The median follow-up after RT was 22.5 months (range 7.0-53.7 months). The median PSA-PFS was 6.9 months (range 1.1-28.4 months). All patients showing a decrease of PSA level after RT of at least factor 10 reveal a PSA-PFS of >12 months. Median PSA-PFS of this sub-group was 23.1 months (range 12.1-28.4 months). Local PFS (LPFS) after 2 years was 100%. One patient developed a local failure after 28.4 months. Median distant PFS (DPFS) was 7.36 months (range 1.74-54.34 months). The time to initiation of ADT in patients treated without ADT was 9.3 months (range 2.6-36.1 months). In all patients, the time to intensification of systemic therapy or the time to initiation of ADT increased from 9.3 to 12.3 months (range 2.6-36.1 months). Gleason-Score, ADT or the localization of metastasis had no impact on PFS or time to intensification of systemic therapy. No SBRT related acute or late toxicities were observed. CONCLUSION: Our study shows that SBRT of bone metastases is a highly effective therapy with an excellent risk-benefit profile. However, PFS was limited due to a high distant failure rate implying the difficulty for patient selection for this oligometastatic concept. SBRT offers high local cancer control rates in bone oligometastases of PC and should be evaluated with the aim of curation or to delay modification of systemic treatment.

Validation of an established prognostic score after re-irradiation of recurrent glioma.

BACKGROUND: Re-irradiation (Re-RT) is offered widely in clinical routine, and has been established as a key element in the treatment of recurrent gliomas. At our center, generally re-resection is performed widely by an experienced neurosurgical team. Thus, Re-RT mostly offered to patients with macroscopic residuals or irresectable lesions, is applied later compared to other centers. Therefore, we sought to validate the Combs Prognostic Score developed in 2012 using our independent patient cohort. PATIENTS AND METHODS: We included 199 patients treated from 2002 until April 2016 for recurrent glioma at the Department of Radiation Oncology at the Klinikum Rechts der Isar, Munich. Different concepts of Re-RT were applied. RESULTS: Median follow-up after Re-RT was 2.5 months. Median overall survival (OS) after Re-RT was 7.9 months for WHO IV gliomas, 11.3 months for WHO III gliomas, and 13.6 months for low-grade gliomas (WHO I/II). Univariate analyses confirmed the prognostic factors primary histology (p = 0.001), age (p = 0.002), and time between primary radiotherapy and Re-RT (p < 0.001). We also tested Karnofsky Performance Score (KPS), gender, and neurological symptoms before Re-RT as well as planning target volume and found only KPS also significant at p < 0.001. Comparing the prognostic score groups, the outcome was highly statistically significant at p < 0.001. CONCLUSION: In our analysis, we validated the Combs Prognostic Score. Validation in this independent large patient cohort confirms the significance of the score for glioma recurrences. Thus, the role of the Combs Prognostic Score might be an essential component of future clinical decision making and patient stratification.

HFSRT of the resection cavity in patients with brain metastases.

PURPOSE: Aim of this single center, retrospective study was to assess the efficacy and safety of linear accelerator-based hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavity of brain metastases after surgical resection. Local control (LC), locoregional control (LRC = new brain metastases outside of the treatment volume), overall survival (OS) as well as acute and late toxicity were evaluated. PATIENTS AND METHODS: 46 patients with large (> 3 cm) or symptomatic brain metastases were treated with HFSRT. Median resection cavity volume was 14.16 cm(3) (range 1.44-38.68 cm(3)) and median planning target volume (PTV) was 26.19 cm(3) (range 3.45-63.97 cm(3)). Patients were treated with 35 Gy in 7 fractions prescribed to the 95-100 % isodose line in a stereotactic treatment setup. LC and LRC were assessed by follow-up magnetic resonance imaging. RESULTS: The 1-year LC rate was 88 % and LRC was 48 %; 57% of all patients showed cranial progression after HFSRT (4% local, 44% locoregional, 9% local and locoregional). The median follow-up was 19 months; median OS for the whole cohort was 25 months. Tumor histology and recursive partitioning analysis score were significant predictors for OS. HFSRT was tolerated well without any severe acute side effects > grade 2 according to CTCAE criteria. CONCLUSION: HFSRT after surgical resection of brain metastases was tolerated well without any severe acute side effects and led to excellent LC and a favorable OS. Since more than half of the patients showed cranial progression after local irradiation of the resection cavity, close patient follow-up is warranted. A prospective evaluation in clinical trials is currently being performed.

Mobile Apps in Oncology: A Survey on Health Care Professionals' Attitude Toward Telemedicine, mHealth, and Oncological Apps.

BACKGROUND: Mobile apps are an evolving trend in the medical field. To date, few apps in an oncological context exist. OBJECTIVE: The aim was to analyze the attitude of health care professionals (HCPs) toward telemedicine, mHealth, and mobile apps in the field of oncology. METHODS: We developed and conducted an online survey with 24 questions evaluating HCPs' general attitude toward telemedicine and patients using medical mobile apps. Specific questions on the possible functionality for patients and the resulting advantages and disadvantages for both the patients' and HCPs' daily clinical routine were evaluated. RESULTS: A total of 108 HCPs completed the survey. In all, 88.9% (96/108) considered telemedicine useful and 84.3% (91/108) supported the idea of an oncological app complementing classical treatment. Automatic reminders, timetables, and assessment of side effects and quality of life during therapy were rated as the most important functions. In contrast, uncertainty regarding medical responsibility and data privacy were reasons mostly named by critics. Most (64.8%, 70/108) were in favor of an alert function due to data input needing further clarification, and 94% (66/70) were willing to contact the patient after a critical alert. In all, 93.5% (101/108) supported the idea of using the collected data for scientific research. Moreover, 75.0% (81/108) believed establishing a mobile app could be beneficial for the providing hospital. CONCLUSIONS: A majority of HCPs are in favor of telemedicine and the use of oncological apps by patients. Assessing side effects can lead to quicker response and thus lower inconvenience for patients. Clinical data, such as life quality and treatment satisfaction, could be used to evaluate and improve the therapy workflow. Eventually, a mobile app would enhance the patients' relationship to their treating department because they are in permanent contact.

Helical intensity-modulated radiotherapy of the pelvic lymph nodes with a simultaneous integrated boost to the prostate--first results of the PLATIN 1 trial.

BACKGROUND: Definitive, percutaneous irradiation of the prostate and the pelvic lymph nodes in high-risk prostate cancer is the alternative to prostatectomy plus lymphadenectomy. To date, the role of whole pelvis radiotherapy (WPRT) has not been clarified especially taking into consideration the benefits of high conformal IMRT (intensity modulated radiotherapy) of complex-shaped target volumes. METHODS: From 2009 to 2012, 40 patients of high-risk prostate cancer with an increased risk of microscopic lymph node involvement were enrolled into this prospective phase II trial. Patients received at least two months of antihormonal treatment (AT) before radiotherapy continuing for at least 2 years. Helical IMRT (tomotherapy) of the pelvic lymph nodes (51.0 Gy) with a simultaneous integrated, moderate hypofractionated boost (single dose of 2.25 Gy) to the prostate (76.5 Gy) was performed in 34 fractions. PSA levels, prostate-related symptoms and quality of life were assessed at regular intervals for 24 months. RESULTS: Of the 40 patients enrolled, 38 finished the treatment as planned. Overall acute toxicity rates were low and no acute grade 3 or 4 gastrointestinal (GI) and genitourinary (GU) toxicity occurred. 21.6% of patients experienced acute grade 2 but no late grade ≥ 2 GI toxicity. Regarding GU side effects, results showed 48.6% acute grade 2 and 6.4% late grade 2 toxicity. After a median observation time of 23.4 months the PLATIN 1 trial can be considered as sufficiently safe meeting the prospectively defined aims of the trial. With 34/37 patients free of a PSA recurrence it shows promising efficacy. CONCLUSION: Tomotherapy of the pelvic lymph nodes with a simultaneous integrated boost to the prostate can be performed safely and without excessive toxicity. The combined irradiation of both prostate and pelvic lymph nodes seems to be as well tolerated as the irradiation of the prostate alone. TRIAL REGISTRATION: Trial Numbers: ARO 2009-05, ClinicalTrials.gov: NCT01903408.