First prospective clinical evaluation of feasibility and patient acceptance of magnetic resonance-guided radiotherapy in Germany.

PURPOSE: Magnetic resonance-guided radiotherapy (MRgRT) has recently been introduced in our institution. As MRgRT requires high patient compliance compared to conventional techniques and can be associated with prolonged treatment times, feasibility and patient tolerance were prospectively assessed using patient-reported outcome questionnaires (PRO-Q). MATERIALS AND METHODS: Forty-three patients were enrolled in a prospective observational study and treated with MRgRT on a low-field hybrid Magnetic Resonance Linear Accelerator system (MR-Linac) between April 2018 and April 2019. For assistance in gated breath-hold delivery using cine-MRI, a video feedback system was installed. PRO-Qs consisted of questions on MR-related complaints and also assessed aspects of active patient participation. RESULTS: The most commonly treated anatomic sites were nodal metastases and liver lesions. The mean treatment time was 34 min with a mean beam-on time of 2:17 min. Gated stereotactic body radiotherapy (SBRT) was applied in 47% of all patients. Overall, patients scored MRgRT as positive or at least tolerable in the PRO­Q. Almost two thirds of patients (65%) complained about at least one item of the PRO­Q (score ≥4), mainly concerning coldness, paresthesia, and uncomfortable positioning. All patients reported high levels of satisfaction with their active role using the video feedback system in breath-hold delivery. CONCLUSION: MRgRT was successfully implemented in our clinic and well tolerated by all patients, despite MR-related complaints and complaints about uncomfortable immobilization. Prospective clinical studies are in development for further evaluation of MRgRT and for quantification of the benefit of MR-guided on-table adaptive radiotherapy.

Potential of quantitative susceptibility mapping for detection of prostatic calcifications.

PURPOSE: To evaluate whether quantitative susceptibility (QSM) may be used as an alternative to computed tomography (CT) to detect calcification in prostate cancer patients. MATERIALS AND METHODS: Susceptibility map calculation was performed using 3D gradient echo magnetic resonance imaging (MRI) data from 26 patients measured at 3T who previously received a planning CT of the prostate. Phase images were unwrapped using Laplacian-based phase unwrapping, the background field was removed with the V-SHARP method, and susceptibility maps were calculated with the iLSQR method. Two blinded readers were asked to identify peri- and intraprostatic calcifications. RESULTS: Average mean and minimum susceptibility values (referenced to iliopsoas muscle) of calcifications were -0.249 ± 0.179 ppm and -0.551 ± 0.323 ppm, and average mean and maximum intensities in CT images were 319 ± 164 HU and 679 ± 392 HU. Twenty-one and 17 out of 22 prostatic calcifications were identified using susceptibility maps and magnitude images, respectively, as well as more than half of periprostatic phleboliths depicted by CT. Calcifications in the prostate and its periphery were quantitatively differentiable from noncalcified prostate tissue in CT (mean values for calcifications / for noncalcified tissue: 71 to 649 / -1 to 83 HU) and in QSM (mean values for calcifications / for noncalcified tissue: -0.641 to 0.063 / -0.046 to 0.181 ppm). Moreover, there was a significant correlation between susceptibility values and CT image intensities for calcifications (P < 0.004). CONCLUSION: Prostatic calcifications could be well identified with QSM. Susceptibility maps can be easily obtained from clinical prostate MR protocols that include a 3D gradient echo sequence, rendering it a promising technique for detection and quantification of intraprostatic calcifications. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:889-898.

Malignant pleural mesothelioma - Pleural cavity irradiation after decortication with helical tomotherapy.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive disease that poses a treatment challenge in spite of recent technical developments. The aim of this retrospective analysis is to assess the feasibility of administering intensity-modulated radiotherapy (IMRT) to the pleural cavity using helical tomotherapy in patients who had undergone pleurectomy/decortication (P/D) and also the resulting toxicity levels. PATIENTS AND METHODS: Ten patients who had MPM and had undergone P/D were treated with pleural cavity irradiation that included a median dose of 52.2 Gy using helical tomotherapy. The median age of the patients was 53 years (31-74). In addition to clinical and diagnostic findings from regular follow-up examinations, we evaluated the dose distribution for other organs at risk to assess treatment in relation to toxicity, with special regard for the underlying intact lung. RESULTS: The mean lung dose on the treatment site was 32.8 Gy (±6.8). The V20 Gy was 71.7% (±17.2). No treatment-related toxicity that exceeded grade III according to common toxicity criteria (CTC) was observed. Median progression-free survival (PFS) was 13 months with a median overall survival (OAS) of 19 months. CONCLUSION: The findings of this analysis provide data indicating that sparing the underlying lung in patients with MPM after P/D is not only feasible with helical tomotherapy, but that this treatment also causes reasonably few side effects.

(68)Ga-PSMA-11 PET/CT: a new technique with high potential for the radiotherapeutic management of prostate cancer patients.

PURPOSE: Radiotherapy is the main therapeutic approach besides surgery of localized prostate cancer. It relies on risk stratification and exact staging. This report analyses the potential of [(68)Ga]Glu-urea-Lys(Ahx)-HBED-CC ((68)Ga-PSMA-11), a new positron emission tomography (PET) tracer targeting prostate-specific membrane antigen (PSMA) for prostate cancer staging and individualized radiotherapy planning. METHODS: A cohort of 57 patients with prostate cancer scanned with (68)Ga-PSMA-11 PET/CT for radiotherapy planning was retrospectively reviewed; 15 patients were at initial diagnosis and 42 patients at time of biochemical recurrence. Staging results of conventional imaging, including bone scintigraphy, CT or MRI, were compared with (68)Ga-PSMA ligand PET/CT results and the influence on radiotherapeutic management was quantified. RESULTS: (68)Ga-PSMA ligand PET/CT had a dramatic impact on radiotherapy application in the presented cohort. In 50.8 % of the cases therapy was changed. CONCLUSION: The presented imaging technique of (68)Ga-PSMA PET/CT could be a key technology for individualized radiotherapy management in prostate cancer.

Intensity-modulated whole abdomen irradiation following adjuvant carboplatin/taxane chemotherapy for FIGO stage III ovarian cancer : four-year outcomes.

INTRODUCTION: A prospective study to assess toxicity and survival outcomes after intensity-modulated whole-abdominal irradiation (IM-WAI) following surgery and adjuvant intravenous carboplatin/taxane chemotherapy in advanced FIGO stage III ovarian cancer. PATIENTS AND METHODS: Between 2006 and 2009, 16 patients with optimally resected FIGO stage III ovarian cancer, who had received six cycles of adjuvant carboplatin/taxane chemotherapy were treated with consolidation IM-WAI. Radiotherapy was delivered to a total dose of 30 Gy in 1.5-Gy fractions, using step-and-shoot (n = 3) or helical tomotherapy (n = 13). The first 10 patients were treated within a phase I trial; the following patients received the same treatment modality. The target volume included the entire peritoneal cavity, the diaphragm, the liver capsule, and the pelvic and para-aortic node regions. Organs at risk were kidneys, liver, heart, and bone marrow. RESULTS: Median follow-up was 44 months (range 19.2-67.2 months). No grade 4 toxicities occurred during IM-WAI. Common Toxicity Criteria for Adverse Events (CTCAE) grade 3 toxicities were: diarrhea (25 %), leucopenia (19 %), nausea/vomiting (6 %), and thrombocytopenia (6 %). No toxicity-related treatment break was necessary. Small bowel obstruction occurred in a total of 6 patients: in 3 cases (19 %) due to postsurgical adhesions and in 3 cases due to local tumor recurrence (19 %). Median recurrence-free survival (RFS) was 27.6 months (95 % confidence interval, CI = 24-44 months) and median overall survival (OS) was 42.1 months (95 %CI = 17-68 months). The peritoneal cavity was the most frequent site of initial failure. CONCLUSION: Consolidation IM-WAI following surgery and adjuvant chemotherapy is feasible and can be performed with manageable acute and late toxicity. The favorable RFS outcome is promising and justifies further clinical trials.

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.

Accelerated tomotherapy delivery with TomoEdge technique.

TomoEDGE is an advanced delivery form of tomotherapy which uses a dynamic secondary collimator. This plan comparison study describes the new features, their clinical applicability, and their effect on plan quality and treatment speed. For the first 45 patients worldwide that were scheduled for a treatment with TomoEdge, at least two plans were created: one with the previous "standard"mode with static jaws and 2.5 cm field width (Reg 2.5) and one with TomoEdge technique and 5 cm field width (Edge 5). If, after analysis in terms of beam on time, integral dose, dose conformity, and organ at risk sparing the treating physician decided that the Edge 5 plan was not suitable for clinical treatment, a plan with TomoEdge and 2.5 cm field width was created (Edge 2.5) and used for the treatment. Among the 45 cases, 30 were suitable for Edge 5 treatment, including treatments of the head and neck, rectal cancer, anal cancer, malignancies of the chest, breast cancer, and palliative treatments. In these cases, the use of a 5 cm field width reduced beam on time by more than 30% without compromising plan quality. The 5 cm beam could not be clinically applied to treatments of the pelvic lymph nodes for prostate cancer and to head and neck irradiations with extensive involvement of the skull, as dose to critical organs at risk such as bladder (average dose 28 Gy vs. 29 Gy, Reg 2.5 vs. Edge 5), small bowel (29% vs. 31%, Reg 2.5 vs. Edge 5) and brain (average dose partial brain 19 Gy vs. 21 Gy, Reg 2.5 vs. Edge 5) increased to a clinically relevant, yet not statistically significant, amount. TomoEdge is an advantageous extension of the tomotherapy technique that can speed up treatments and thus increase patient comfort and safety in the majority of clinical settings.

Helical intensity-modulated radiotherapy of the pelvic lymph nodes with integrated boost to the prostate bed - initial results of the PLATIN 3 Trial.

BACKGROUND: Adjuvant and salvage radiotherapy of the prostate bed are established treatment options for prostate cancer. While the benefit of an additional radiotherapy of the pelvic lymph nodes is still under debate, the PLATIN 3 prospective phase II clinical trial was initiated to substantiate toxicity data on postoperative IMRT of the pelvic lymph nodes and the prostate bed. METHODS: From 2009 to 2011, 40 patients with high-risk prostate cancer after prostatectomy with pT3 R0/1 M0 or pT2 R1 M0 or a PSA recurrence and either > 20% risk of lymph node involvement and inadequate lymphadenectomy or pN + were enrolled. Patients received two months of antihormonal treatment (AT) before radiotherapy. AT continuation was mandatory during radiotherapy and was recommended for another two years. IMRT of the pelvic lymph nodes (51.0 Gy) with a simultaneous integrated boost to the prostate bed (68.0 Gy) was performed in 34 fractions. PSA level, prostate-related symptoms and quality of life were assessed at regular intervals for 24 months. RESULTS: Of the 40 patients enrolled, 39 finished treatment as planned. Overall acute toxicity rates were low and no acute grade 3/4 toxicity occurred. Only 22.5% of patients experienced acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity. During follow-up, 10.0% late grade 2 GI and 5.0% late grade 2 GU toxicity occurred, and one patient developed late grade 3 proctitis and enteritis. After a median observation time of 24 months the PLATIN 3 trial has shown in 97.5% of all patients sufficient safety and thus met its prospectively defined aims. After a median of 24 months, 34/38 patients were free of a PSA recurrence. CONCLUSIONS: Postoperative whole-pelvis IMRT with an integrated boost to the prostate bed can be performed safely and without excessive toxicity.

Stereotactic body radiotherapy (SBRT) for adrenal metastases of oligometastatic or oligoprogressive tumor patients.

INTRODUCTION: Local ablative treatment strategies are frequently offered to patients diagnosed with oligometastatic disease. Stereotactic body radiotherapy (SBRT), as ablative treatment option, is well established for lung and liver metastases, whereas for isolated adrenal gland metastases the level of evidence is scarce. MATERIAL AND METHODS: This single-institution analysis of oligometastatic or oligoprogressive disease was limited to patients who received SBRT to adrenal metastasis between 2012 and 2019. Patient, tumor, treatment characteristics, and dosimetric parameters were analyzed for evaluation of their effect on survival outcomes. RESULTS: During the period of review 28 patients received ablative SBRT to their adrenal gland metastases. Most common primary tumors were non-small cell lung cancers (46%) with most patients diagnosed with a single adrenal gland metastasis (61%), which occurred after a median time of 14 months. SBRT was delivered to a median biological effective dose at α/ß of 10 (BED10) of 75 Gy (range: 58-151 Gy). Median gross tumor volume (GTV) and median planning target volume (PTV) were 42 and 111 mL, respectively. The homogeneity and conformity indices were 1.17 (range: 1.04-1.64) and 0.5 (range: 0.4.0.99), respectively, with the conformity index being affected by dose restrictions to organs at risk (OARs) in 50% of the patients. Overall response rate based on RECIST criteria was 86% (CR = 29%, PR = 57%) with 2-year local control (LC) of 84.8%, 2-year progression-free survival (PFS) of 26.3%, and 1-and 2-year overall survival (OS) of 46.6 and 32.0%, respectively. During follow up, only two local recurrences occurred. A trend for superior LC was seen if BED10 was ≥75Gy (p = 0.101) or if the PTV was < 100 ml (p = 0.072). SBRT was tolerated well with only mild toxicity. CONCLUSION: SBRT for adrenal metastases resulted in promising LC with low toxicity. Treatment response appeared to be superior, if SBRT was applied with higher BED. As the close proximity of OARs often limits the application of sufficiently high doses, further dose escalations strategies and techniques should be investigated in future.

Helical tomotherapy in patients with leptomeningeal metastases.

PURPOSE: Leptomeningeal metastasis (LM) is an increasingly common complication of late-stage systemic cancer, for which there is no standard treatment. We analyzed outcome and toxicity in patients with LM undergoing craniospinal irradiation via helical tomotherapy (HT-CSI) at our institution. PATIENTS AND METHODS: The charts of 15 patients diagnosed with LM and undergoing HT-CSI between 2006 and 2014 were retrospectively assessed. Main neoplasms included breast cancer, lung cancer, and lymphoma. All patients presented with cranial neuropathy due to LM. Follow-up was performed regularly. Survival analysis was performed by the Kaplan-Meier method, and prognostic factors were tested using the COX-regression model. RESULTS: Median survival by cancer type was 6 (breast cancer), 1 (lung cancer), and 2 months (lymphoma), respectively. Median overall survival and relapse-free survival were calculated to be between 2 and 3 months. Six- and 12-month survival was 30% (95% CI 0.08-0.5) and 20% (95% CI 0.05-0.4), respectively. Symptom palliation occurred in 53% of patients in general, but in 67% of breast cancer patients, in particular. Patients with lung cancer experienced no improvement. Most common acute treatment-related toxicity at different levels were hematological toxicity, multiple cranial neuropathy, fatigue, infections, nausea, and headache. CONCLUSION: HT-CSI can help meet the challenge of treating patients with LM, especially because it can palliate symptoms and improve neurological functions. One-year survival remains as disappointing as before.

Whole-brain helical tomotherapy with integrated boost for brain metastases in patients with malignant melanoma - final results of the BRAIN-RT trial.

Background: Patients with multiple brain metastases (BMs) from malignant melanoma have a poor prognosis. Recent developments in radiation techniques allow simultaneous integrated boost (SIB) concepts while sparing organs at risk. Data on conventional versus dose-escalated radiation approaches in multiple BMs from malignant melanoma are warranted. Methods: In this prospective, single-center, randomized two-armed study (trial ID: DRKS00005127), patients with multiple BMs from malignant melanoma were treated with either conventional whole-brain radiotherapy (WBRT) applying 30 Gy in 10 fractions (standard arm) or helical tomotherapy applying 30 Gy to the whole brain with an integrated boost to metastases of 50 Gy in 10 fractions and sparing of the hippocampus (HA-WBRT, experimental arm). The primary endpoint was treatment-related toxicity, while secondary endpoints were imaging response, intracerebral progression-free survival (PFS), overall survival (OS) and quality of life. Results: The study was stopped early due to slow patient recruitment. A total number of 7 patients were enrolled (standard arm n=3, experimental arm n=4), and were followed-up for a median time of 5 months between August 2013 and July 2017. All patients were treated according to protocol. The median OS, intracerebral PFS and follow-up time were 5 months, 2 months and 5 months, respectively. The local control in every individual BM was significantly longer in the experimental versus the standard arm. No patient developed radiation-related high-grade toxicities. Conclusion: HA-WBRT with SIB results in improved local control in the individual melanoma BMs without radiation-associated high-grade toxicities. Survival times were comparable to published data.

Prostate bed irradiation with alternative radio-oncological approaches (PAROS) - a prospective, multicenter and randomized phase III trial.

BACKGROUND: For patients with treatment-naïve carcinoma of the prostate, hypofractionated irradiation becomes more and more popular. Due to the low α/ß value of prostate cancer, increased single dose leading to a shortened treatment period seems to be safe and feasible. However, reliable data is lacking for post-prostatectomy patients so far. Further, the role of proton therapy is still under debate. Two prospective phase II trials with both, hypofractionated photon and proton therapy, provided promising results. METHODS/ DESIGN: The PAROS trial is a prospective, multicenter and randomized phase III trial for men with localized prostate carcinoma after surgery. Post-prostatectomy patients will be randomized to either normofractionated radiotherapy (nRT) with photons (70.0/ 2.0 Gy), or hypofractionated radiotherapy (hRT) with photons (57.0/ 3.0 Gy) or hRT with protons (57.0/ 3.0 Gy relative biological effectiveness [RBE]). Block randomization is stratified by Gleason Score (≤ 7 vs. > 7) and treatment indication (adjuvant vs. salvage). The trial is planned to enroll 897 patients. The primary objective is to show an improvement in the bowel-score according to EORTC QLQ-PR25 after proton therapy compared to photon irradiation (week 12 vs. baseline). Secondary aims are non-inferiority of hRT compared to nRT with regard to biochemical progression-free survival (bPFS), overall survival (OS), quality of life and toxicity. DISCUSSION: The present study aims to evaluate the role of hypofractionated radiotherapy to the prostate bed with photons and protons leading to significant impact on future management of operated men with prostate cancer. TRIAL REGISTRATION: Deutsches Register klinischer Studien: DRKS00015231 ; registered 27 September 2018.

Elective Node Irradiation With Integrated Boost to the Prostate Using Helical IMRT-Clinical Outcome of the Prospective PLATIN-1 Trial.

Introduction: This prospective, non-randomized phase II trial aimed to investigate the role of additional irradiation of the pelvic nodes for patients with prostate cancer and a high risk for nodal metastases using helical intensity-modulated radiotherapy with daily image guidance (IMRT/IGRT). Methods and materials: Between 2009 and 2012, 40 men with treatment-naïve prostate cancer and a risk of lymph node involvement of more than 20% were enrolled in the PLATIN-1 trial. All patients received definitive, helical IMRT of the pelvic nodes (total dose of 51.0 Gy) with a simultaneous integrated boost (SIB) to the prostate (total dose of 76.5 Gy) in 34 fractions. Antihormonal therapy (AHT) was administered for a minimum of 2 months before radiotherapy continuing for at least 24 months. Results: After a median follow-up of 71 months (range: 5-95 months), pelvic irradiation was associated with a 5-year overall survival (OS) and biochemical progression-free survival (bPFS) of 94.3% and 83.6%, respectively. For our cohort, no grade 4 gastrointestinal (GI) and genitourinary (GU) toxicity was observed. Quality of life (QoL) assessed by EORTC QLQ-C30 questionnaire was comparable to EORTC reference values without significant changes. Conclusion: The current trial demonstrates that elective IMRT/IGRT of the pelvic nodes with SIB to the prostate for patients with a high-risk of lymphatic spread is safe and shows an excellent clinical outcome without compromising the quality of life. The PLATIN-1 trial delivers eminent baseline data for future studies using modern irradiation techniques.

Treatment Outcome of a Combined Dose-Escalated Treatment Regime With Helical TomoTherapy® and Active Raster-Scanning Carbon Ion Boost for Adenocarcinomas of the Head and Neck.

Introduction: Data regarding treatment and survival outcome of patients with adenocarcinoma of the head and neck are limited to case reports and case series. As a consequence of lacking evidence, treatment guidelines do not exist. We aimed to analyze the effect of a bimodal irradiation regime with intensity modulated radiotherapy (IMRT) and carbon ion boost on local control (LC) and survival in adenocarcinoma patients for a large patient collective. Materials and Methods: Patient records of eighty consecutive patients treated between 2009 and 2018 were analyzed retrospectively and Kaplan-Meier estimates for LC, overall survival (OS) and progression-free survival (PFS) were compared among patients with salivary gland adenocarcinoma (SGAC), salivary duct adenocarcinoma (SDAC), and intestinal-type adenocarcinoma (ITAC) according to the World Health Organization (WHO). Prognostic factors were identified using the log-rank test and cox-regression modeling. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Median follow-up was 41 months. The 3-year and estimated 5-year Kaplan-Meier rates for all patients were 83 and 75% for LC, 74 and 50% for OS and 60 and 53% for PFS, respectively. While bimodal RT for ITAC resulted in a significantly decreased 3-year LC rate of 50 vs. 93% for each SGAC and SDAC (p < 0.01), no statistical significant survival differences could be identified across the three groups regarding OS (p = 0.08) and PFS (p = 0.063). 3-year OS was 88% for SGAC, 78% for SDAC and 67% for ITAC and 3-year PFS was 72% for SGAC, 53% for SDAC and 44% for ITAC, respectively. Nevertheless, in subgroup analysis, OS for ITAC was significantly worse compared to SGAC (p = 0.024). In multivariate analysis, bilateral tumor side (vs. unilateral) solely could be identified as independent negative prognostic factor for LC (p < 0.01). Treatment was well-tolerated with 21% acute (n = 17) and 25% (n = 20) late grade ≥3 toxicities. Conclusion: Radiotherapy including active raster-scanning carbon ion boost for relatively radio resistant adenocarcinomas of the head and neck resulted in favorable survival outcome for salivary gland and salivary duct adenocarcinomas with moderate toxicity. However, local control and prognosis for bilateral intestinal-type adenocarcinomas (ITAC) seem to remain low even after dose-escalation.

The impact of age on the outcome of patients treated with radiotherapy for mucoepidermoid carcinoma (MEC) of the salivary glands in the head and neck: A 15-year single-center experience.

INTRODUCTION: Data regarding treatment and survival outcome of patients with mucoepidermoid carcinoma of the head and neck are limited to case reports and case series. As a consequence of lacking evidence, treatment guidelines do not exist. We aimed to analyze the effect of modern radiotherapy in form of intensity modulated radiotherapy (IMRT) either with simultaneously integrated boost or carbon ion boost on local control and survival for a relatively large patient collective. MATERIALS AND METHODS: Patient records of 62 consecutive patients treated with postoperative (n = 53, 85%) or definitive (n = 9, 15%) radiotherapy between 2004 and 2019 were analyzed retrospectively. Kaplan-Meier estimates for overall survival (OS), distant progression-free survival (PFS), local control (LC) and locoregional control (LRC) were statistically calculated and prognostic factors were identified using the log-rank test. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: The median follow-up was 47 months (range, 4-188 months). The 3-year OS, DPFS, LC and LRC, estimated by Kaplan-Meier curves, were 82%, 87%, 89% and 92%, the estimated 5-year OS, DPFS, LC and LRC were 78%, 87%, 84% and 88%, respectively. In univariate analysis, age >56 years (vs. age ≤56 years) was identified as the only independent negative prognostic factor for decreased OS (HR = 1.078; 95%-CI = 1.029-1.130; p = 0.001), DPFS (HR = 1.055; 95%-CI = 1.000-1.114; p = 0.051) and LC (HR = 1.087; 95%-CI = 1.022-1.157; p = 0.008). Treatment was well tolerated without any grade ≥4 toxicity. Acute and late grade 3 toxicities were rare with 16% acute (n = 10) and 13% late toxicities (n = 8). CONCLUSION: Radiotherapy with intensity modulated radiotherapy including either simultaneously integrated photon boost or active raster-scanning carbon ion boost for mucoepidermoid carcinomas of the head and neck resulted in excellent survival outcome and locoregional control with moderate toxicity. However, patients older than 56 years seem to have a disadvantage in all calculated endpoints (OS, DPFS, LRC) due to frequent local and distant relapses. CONDENSED ABSTRACT: Modern radiotherapy with intensity modulated radiotherapy including either a simultaneously integrated photon boost or carbon ion boost for mucoepidermoid carcinoma results in excellent survival outcome and locoregional control with moderate toxicity. The 5-year OS, DPFS, LC and LRC, estimated by Kaplan-Meier curves, were 89%, 75%, 84% and 80%, respectively. Patients older than 56 years seem to have a disadvantage in all calculated endpoints (OS, DPFS, LRC).

Adjuvant intensity modulated whole-abdominal radiation therapy for high-risk patients with ovarian cancer FIGO stage III: final results of a prospective phase 2 study.

BACKGROUND: To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy). METHODS: The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS). RESULTS: All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status decreased by 18.1 points (95%-CI: 7.1-29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively. CONCLUSIONS: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov ( NCT01180504 ). Registered 12 August 2010 - retrospectively registered.

Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis.

BACKGROUND: Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10-15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC. PATIENTS AND METHODS: Twenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45-59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0-2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival. RESULTS: Twenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3-34.0, 95% CI: 11.0-32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (P=0.001), age ≤55 years at LC diagnosis (P=0.022), cerebrospinal fluid (CSF) protein <100 mg/dL (P=0.018) and no more than mild or moderate neurologic deficits (NFS ≤2; P=0.007) were predictive of longer OS. So were the neurologic response to treatment (P=0.018) and the application of systemic therapy after RT completion (P=0.029). The presence of CSF flow obstruction was predictive of shorter OS (P=0.026). In multivariate analysis, age at LC diagnosis (P=0.018), KPI (P<0.001) and neurologic response (P=0.037) remained as independent prognostic factors for longer OS. Treatment-associated toxicity was manageable and mostly grades I and II according to the Common Terminology Criteria for Adverse Events v4.0. Eight patients (32%) developed grade III myelosuppression. Neurologic symptom stabilization could be achieved in 40.0% and a sizeable improvement in 28.0% of all patients. CONCLUSION: CSI for the treatment of LC is feasible and may have therapeutic value in carefully selected patients, alleviating symptoms or delaying neurologic deterioration. OS after CSI was comparable to the rates described in current literature for patients with LC. The use of modern irradiation techniques such as helical IMRT is warranted to limit toxicity. Patient selection should take into account prognostic factors such as age, clinical performance, neurologic function and the availability of systemic treatment options.

Bimodality treatment of patients with pelvic adenoid cystic carcinoma with photon intensity-modulated radiotherapy plus carbon ion boost: a case series.

BACKGROUND: Treatment of patients with pelvic adenoid cystic carcinoma (ACC) remains a challenge owing to the rarity of the disease, the lack of data, and the relative radioresistance of these tumors. CASE REPORTS: This case series presents the results of three patients with recurrent or inoperable pelvic ACC treated with intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost. Patients received C12 therapy at a dose of 3 Gray equivalents (GyE) (relative biological effectiveness [RBE]) per fraction up to 24 GyE RBE, followed by 50 GyE of photon IMRT in 25 fractions. CONCLUSION: IMRT plus C12 ion boost as a definitive or adjuvant treatment for pelvic ACCs seems to be a promising therapeutic option. No unexpected toxicity was detected and the observed toxicity remained consistently low. The initial treatment response is promising and similar to that experienced for head and neck ACCs.

Palliative Radiotherapy for Leptomeningeal Carcinomatosis-Analysis of Outcome, Prognostic Factors, and Symptom Response.

Introduction: The purpose of this article is to report our institution's 10-year experience on palliative radiotherapy for the treatment of leptomeningeal carcinomatosis (LC), assessing survival, neurologic outcome, and prognostic factors. Patients and methods: We retrospectively analyzed 110 patients who received palliative radiotherapy for LC between 2008 and 2018. The most common histologies were breast cancer (n = 43, 39.1%) and non-small cell lung cancer (NSCLC) (n = 31, 28.2%). Radiotherapy was administered as whole-brain radiotherapy (WBRT) (n = 51, 46.4%), focal spinal RT (n = 11, 10.0%) or both (n = 47, 42.7%). Twenty-five patients (22.7%) were selected for craniospinal irradiation. Clinical performance and neurologic function were quantified on the neurologic function scale (NFS) before and in response to therapy. A Cox Proportional Hazards model with univariate and multivariate analysis was fitted for survival. Results: Ninety-eight patients (89.1%) died and 12 (10.9%) were alive at the time of analysis. Median OS from LC diagnosis and from the beginning of RT was 13.9 weeks (IQR: 7.1-34.0) and 9.9 weeks (IQR: 5.3-26.3), respectively. In univariate analysis, prognostic of longer OS were a Karnofsky performance scale index (KPI) of ≥70% (HR 0.20, 95%-CI: [0.13; 0.32], p < 0.001), initially moderate neurological deficits (NFS ≤2) (HR 0.32, 95% CI: [0.19; 0.52], p < 0.001), symptom response to RT (HR 0.41, 95%-CI: [0.26; 0.67], p < 0.001) and the administration of systemic therapy (HR 0.51, 95%-CI: [0.33; 0.78], p = 0.002). Prognostic of inferior OS were high-grade myelosuppression (HR 1.78, 95% CI: [1.06; 3.00], p = 0.03) and serum LDH levels >500 U/l (HR 3.62, 95% CI: [1.76; 7.44], p < 0.001). Clinical performance, symptom response and serum LDH stayed independently prognostic for survival in multivariate analysis. RT was well-tolerated and except for grade III myelosuppression in 19 cases (17.3%), no high-grade acute toxicities were observed. Neurologic symptom stabilization was achieved in 83 cases (75.5%) and a sizeable improvement in 39 cases (35.5%). Conclusion: Radiotherapy is a well-tolerated and efficacious means of providing symptom palliation for patients with LC, delaying neurologic deterioration while probably not directly influencing survival. Prognostic factors such as clinical performance, neurologic response and serum LDH can be used for patient stratification to facilitate treatment decisions.

Craniospinal irradiation using helical tomotherapy for central nervous system tumors.

The aim of this study was to describe early and late toxicity, survival and local control in 45 patients with primary brain tumors treated with helical tomotherapy craniospinal irradiation (HT-CSI). From 2006 to 2014, 45 patients with central nervous system malignancies were treated with HT-CSI. The most common tumors were medulloblastoma in 20 patients, ependymoma in 10 patients, intracranial germinoma (ICG) in 7 patients, and primitive neuroectodermal tumor in 4 patients. Hematological toxicity during treatment included leukopenia Grades 1-4 (6.7%, 33.3%, 37.8% and 17.8%, respectively), anemia Grades 1-4 (44.4%, 22.2%, 22.2% and 0%, respectively) and thrombocytopenia Grades 1-4 (51.1%, 15.6%, 15.6% and 6.7%, respectively). The most common acute toxicities were nausea, vomiting, fatigue, loss of appetite, alopecia and neurotoxicity. No Grade 3 or higher late toxicity occurred. The overall 3- and 5-year survival rates were 80% and 70%, respectively. Survival for the main tumor entities included 3- and 5-year survival rates of 80% and 70%, respectively, for patients with medulloblastoma, 70% for both in patients with ependymoma, and 100% for both in patients with ICG. Relapse occurred in 11 patients (24.4%): 10 with local and 1 with multifocal relapse. One patient experienced a secondary cancer. M-status and the results of the re-evaluation at the end of treatment were significantly related to survival. Survival after HT-CSI was in line with the existing literature, and acute treatment-induced toxicity resolved quickly. Compared with conventional radiotherapy, HT offers benefits such as avoiding gaps and junctions, sparing organs, and better and more homogeneous dose distribution and coverage of the target volume.