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Simple Summary: Proton therapy is a highly effective type of radiotherapy that is used to treat cancer while minimizing damage to healthy tissue. In Switzerland, health insurance typically covers the cost of proton therapy. However, patients may still need to pay for their lodging and travel expenses during the treatment's 5–7 week duration. This can lead to financial stress, also known as financial toxicity. The present study is the first to measure patient-reported financial toxicity in a group of patients receiving proton therapy, including both patients and caregivers of pediatric cancer patients. It shows that many patients receiving proton therapy experience financial toxicity, which is measured by the COST score. Low income, long travel distances, and marriage can contribute to this financial burden. Patients often had to save money by cutting back on expenses in different areas. The study emphasizes the importance of considering financial aspects as part of cancer patients' overall care during proton therapy. Background: Proton therapy is indicated for cancers that would be difficult to treat with conventional radiotherapy. Compulsory healthcare insurance covers the costs of this therapy in Switzerland, but this does not mean that proton therapy is cost-neutral for every cancer patient. Significant out-of-pocket (OOP) costs may arise due to expenses associated with proton therapy, and patients may experience treatment-related financial distress—an effect known as "financial toxicity." This study investigates the financial toxicity of patients undergoing proton therapy in a high-income country with a compulsory health insurance policy. Methods: Between September 2019 and November 2021, 146 Swiss cancer patients treated with proton therapy participated in this study, of whom 90 (62%) were adults and 56 (38%) were caregivers of child cancer patients. Financial toxicity was assessed using the FACIT Comprehensive Score for Financial Toxicity (COST). OOP costs during proton therapy were recorded weekly, and financial coping strategies were captured at the end of treatment. Findings: The median COST score, indicating financial toxicity, was 29.9 (IQR 21.0; 36.0) for all patients, 30.0 (IQR 21.3; 37.9) for adults, and 28.0 (IQR 20.5; 34.0) for children's caregivers. Higher income (estimate 8.1, 95% CI 3.7 to 12.4, p ≤ 0.001) was significantly associated with higher COST scores, indicating less financial toxicity. Further distance from home to the treatment centre per 100 km (estimate −3.7, 95% CI −5.7 to −1.9, p ≤ 0.001) was significantly associated with lower COST scores, indicating increased financial toxicity. Married adult patients had substantially lower COST scores than single patients (estimate: −9.1, 95% CI −14.8 to −3.4, p ≤ 0.001). The median OOP cost was 2050 Swiss francs (CHF) and was spent mainly on travel, accommodation, and eating out. Sixty-three (43%) patients used their savings; 54 (37%) cut spending on leisure activities; 21 (14.4%) cut living expenses; 14 (9.6%) borrowed money; nine (6.2%) worked more; and four (2.7%) sold property. Patients with high COST scores used significantly fewer coping strategies such as saving on leisure activities (estimate −9.5, 95% CI −12.4 to −6.6, p ≤ 0.001), spending savings (estimate −3.9, 95% CI −6.3 to −1.4, p = 0.002), borrowing money (estimate −6.3, 95% CI −10.4 to −2.2, p = 0.003), and increasing workload (estimate −5.5, 95% CI −10.5 to −0.4, p = 0.035). Interpretation: A substantial number of cancer patients treated with proton therapy experience financial toxicity in Switzerland. Long travel distances to the proton therapy centre and low income negatively affect the financial well-being of these patients during proton therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Most patients with skull base tumors require radiation therapy as part of their overall treatment, preferably with protons. However, vital and healthy organs, such as the cochlea, are often located in the immediate anatomical vicinity of the tumor. Despite the high precision of the proton beam, irradiating the cochlea is often unavoidable, resulting in an increased risk of hearing loss. To assess the frequency and severity of changes in hearing after proton therapy, we performed a retrospective study in a cohort of 51 patients undergoing proton therapy for skull base tumors. We observed that a hearing threshold shift correlates to the applied radiation dose intensity to the cochlea. In addition, advancing age, hearing sensitivity before proton therapy, and the time elapsed after the end of proton therapy are independently associated with the deterioration of the hearing threshold after proton therapy. These results are essential to adequately inform patients about the treatment's impact and side effects. To assess the incidence and severity of changes in hearing threshold in patients undergoing high-dose pencil-beam-scanning proton therapy (PBS-PT). This retrospective cohort study included fifty-one patients (median 50 years (range, 13–68)) treated with PBS-PT for skull base tumors. No chemotherapy was delivered. Pure tone averages (PTAs)were determined before (baseline) and after PBS-PT as the average hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz. Hearing changes were calculated as PTA differences between pre-and post-PBS-PT. A linear mixed-effects model was used to assess the relationship between the PTA at the follow-up and the baseline, the cochlea radiation dose intensity, the increased age, and the years after PBS-PT. Included patients were treated for chordoma (n = 24), chondrosarcoma (n = 9), head and neck tumors (n = 9), or meningioma (n = 3), with a mean tumor dose of 71.1 Gy (RBE) (range, 52.0–77.8), and a mean dose of 37 Gy (RBE) (range, 0.0–72.7) was delivered to the cochleas. The median time to the first follow-up was 11 months (IQR, 5.5–33.7). The PTA increased from a median of 15 dB (IQR 10.0–25) at the baseline to 23.8 (IQR 11.3–46.3) at the first follow-up. In the linear mixed-effect model, the baseline PTA (estimate 0.80, 95%CI 0.64 to 0.96, p ≤ 0.001), patient's age (0.30, 0.03 to 0.57, p = 0.029), follow-up time (2.07, 0.92 to 3.23, p ≤ 0.001), and mean cochlear dose in Gy (RBE) (0.34, 0.21 to 0.46, p ≤ 0.001) were all significantly associated with an increase in PTA at follow-up. The applied cochlear dose and baseline PTA, age, and time after treatment were significantly associated with hearing loss after proton therapy. [ABSTRACT FROM AUTHOR]

Purpose: To compare survival and severe late radiation toxicity between patients who received continuous low-dose-rate (LDR) brachytherapy (BT) and pulsed-dose-rate (PDR) BT for cervical cancer. Methods and Materials: A retrospective review of cervical cancer patients who underwent primary radiotherapy with or without concurrent cisplatin was performed. Late Grade 3 or worse toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. The study endpoints were overall and disease-free survival and the probability of severe late toxicity. Results: A total of 109 patients (65.7%) received LDR BT and 57 (34.3%) received PDR BT. Seventy patients received concurrent chemotherapy with cisplatin. The 3-year overall survival and disease-free survival rate was 70% and 57% for the LDR group and 82% and 70% for the PDR group, respectively (p = 0.25 and p = 0.19). The 3-year probability rate for late Grade 3 or worse toxicity was 7.4% for LDR BT patients and 7.6% for PDR BT patients, respectively (p = 0.69) and 6.9% and 7.6%, respectively, for concurrent chemotherapy vs. none (p = 0.69). Conclusion: No difference was found in severe late toxicity, overall survival, or disease-free survival between the LDR and PDR groups. [Copyright &y& Elsevier]

Vascular endothelial growth factor (VEGF) plays an important role in the regulation of tumour growth and metastasis. It was the aim of this study to examine the impact of serum VEGF levels on the likelihood of response to radiotherapy and on the disease-free survival in patients with cervical cancer. Blood was taken before commencing treatment and serum VEGF was assessed by quantitative ELISA in 23 patients with cervical cancer stage IB–IVA undergoing primary radiotherapy. Serum VEGF levels were correlated with clinical and histopathologic factors as well as with response to radiotherapy and time to progression. Nineteen of the 23 patients had a complete response and four patients had persistent disease at 3 months. The median follow-up was 25 months (95% confidence interval: 23.5–26.5 months). At the time of analysis, eight patients were tumour-free and 15 patients had tumour progression; 12 of these 15 patients died of disease. Overall, the median serum VEGF level was 244 pg/ml (range 31.9–817.6 pg/ml). All four patients with local failure had VEGF levels >244 pg/ml, whereas 11 of the 19 patients with complete response had serum VEGF of ≤244 pg/ml (P=0.035). The median time to progression was 5 months in patients with VEGF of >244 pg/ml compared to 19 months in patients with VEGF of ≤244 pg/ml (log rank, P=0.003). In multivariate analysis, serum VEGF, tumour size and histological type, but not the patient's age, stage and grade of histological differentiation influenced the progression-free survival. Elevated pre-therapeutic serum VEGF levels are associated with poor response and a shorter time to progression in patients with cervical cancer undergoing primary radiotherapy. [Copyright &y& Elsevier]

Background and purpose: Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at unusually low dose levels and are thus difficult to understand considering dose metrics only. When transitioning from double scattering to pencil beam scanning, little consideration was given to increased dose rates observed with the latter delivery paradigm. We explored if dose rate related metrics could provide additional predicting factors for the development of late visual toxicities. Materials and methods: Radiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated. Results: For the index cases, which developed toxicities at low dose levels (mean, 50 GyRBE), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 GyRBE/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 GyRBE/s. LET-related metrics were not substantially different between the index and non-toxicity cases. Conclusions: Our observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury. [ABSTRACT FROM AUTHOR]

• Combined proton–photon therapy (CPPT) increases treatment plan quality vs. IMRT & IMPT. • Increased proton beam flexibility in CPPT increases treatment plan quality further. • Substantial decrease of photon contributions to CPPT with increasing proton beam flexibility. • Probabilities for Xerostomia and Dysphagia reduce with CPPT compared to IMPT, even in the case of an arc-like proton beam flexibility. • CPPT needs adaption for head and neck cancer treatments. This study investigates whether combined proton–photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments. Five HNC patients with a planning CT and multiple (4–7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared. The target coverage for CPPT without adaptation is insufficient (average V95%=88.4 %), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5 %) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are −2.7 %/-3.4 %/-5.0 % for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are + 0.8 %/-0.9 %/-4.3 %. CPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To assess feasibility, safety and effectiveness of CT–based 3D conformal external beam radiotherapy (EBRT) plus concurrent cisplatin and MRI–based 3D conformal HDR-brachytherapy (HDR-BT) in the treatment of advanced cervical cancer. Patients and methods: A total of 48 patients with advanced cervical cancer, treated with CT–based EBRT plus simultaneous cisplatin chemotherapy (40mg/m2 of body surface per week for 5 weeks) and MRI–based HDR-BT, were included for analysis. Results: All patients completed radiotherapy as planned and 90% received at least four cycles chemotherapy. Frequencies of CTC grade 3 anaemia, grade 3–4 leucopenia and grade 3 thrombocytopenia were 4, 23 and 10%, respectively. Two patients developed deep vein thrombosis and one non-fatal pulmonary embolism. Grade 4 genitourinary late side effects (bladder) occurred in 2 patients. No grade 3–4 gastrointestinal side effects were observed. Complete response (CR) was obtained in 45 patients (94%). After a median follow-up of 33 months, 27 patients were disease free. Actuarial overall survival at 3 years was 61%, progression free survival 51% and continuous complete remission for true pelvis 85%. Conclusions: MRI–based 3D HDR-BT and 3D EBRT plus cisplatin appears to be safe and effective, although acute haematological toxicity is increased. Gastrointestinal morbidity is minimal when prospectively applying 3D dose volume constraints and MRI–based 3D dose volume adaptation. [Copyright &y& Elsevier]

• High-quality sCT generation from MR images with 3D uncertainty prediction. • Improved plan robustness against network prediction error by uncertainty-aware optimisation. • Clinically acceptable accuracy (+/-3%) for proton therapy planning of 64 brain tumour patients. • Powerful tools for determining the clinical usefulness of synthetic CTs for individual patients. Deep learning techniques excel in MR-based CT synthesis, but missing uncertainty prediction limits its clinical use in proton therapy. We developed an uncertainty-aware framework and evaluated its efficiency in robust proton planning. A conditional generative-adversarial network was trained on 64 brain tumour patients with paired MR-CT images to generate synthetic CTs (sCT) from combined T1-T2 MRs of three orthogonal planes. A Bayesian neural network predicts Laplacian distributions for all voxels with parameters (μ , b). A robust proton plan was optimized using three sCTs of μ and μ ± b. The dosimetric differences between the plan from sCT (sPlan) and the recalculated plan (rPlan) on planning CT (pCT) were quantified for each patient. The uncertainty-aware robust plan was compared to conventional robust (global ± 3 %) and non-robust plans. In 8-fold cross-validation, sCT-pCT image differences (Mean-Absolute-Error) were 80.84 ± 9.84HU (body), 35.78 ± 6.07HU (soft tissues) and 221.88 ± 31.69HU (bones), with Dice scores of 90.33 ± 2.43 %, 95.13 ± 0.80 %, and 85.53 ± 4.16 %, respectively. The uncertainty distribution positively correlated with absolute prediction error (Correlation Coefficient: 0.62 ± 0.01). The uncertainty-conditioned robust optimisation improved the rPlan-sPlan agreement, e.g., D95 absolute difference (CTV) was 1.10 ± 1.24 % compared to conventional (1.64 ± 2.71 %) and non-robust (2.08 ± 2.96 %) optimisation. This trend was consistent across all target and organs-at-risk indexes. The enhanced framework incorporates 3D uncertainty prediction and generates high-quality sCTs from MR images. The framework also facilitates conditioned robust optimisation, bolstering proton plan robustness against network prediction errors. The innovative feature of uncertainty visualisation and robust analyses contribute to evaluating sCT clinical utility for individual patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the outcome of patients with head and neck adenoid cystic carcinoma (ACC) treated using pencil beam scanning proton therapy (PBS PT) at our institution.Materials and Methods: Thirty-five patients who underwent treatment with PBS PT for ACC between 2001 and 2017 were included. Local control (LC), distant control (DC), progression-free survival (PFS), overall survival (OS) and their prognostic factors were evaluated. Adverse effects were prospectively assessed.Results: The median patient follow-up was 30 months. Prior to PT, 26 patients (74.3%) underwent surgery with R0/R1/R2 outcome in 5, 13 and 8 cases, respectively. Nine patients (25.7%) presented with inoperable disease. The 2-year LC, DC, PFS and OS was 92.2%, 77.8%, 74.3% and 88.8%, respectively. LC was influenced by patient age (p = 0.002) with a significant difference between local and distant failure (median 61.3 vs. 42.3 years, p = 0.005). Tumor T stage was a significant risk factor for PFS (p = 0.045) and tumor prognostic group affected OS (p = 0.049). No significant survival advantage for operable vs. inoperable disease could be identified. The acute and late grade 3 toxicity rates were 14.3% and 6.1%, respectively. No acute or late grade 4/5 toxicities were observed.Conclusions: PBS PT is an effective and safe treatment for patients with head & neck ACC in both definitive and adjuvant setting. Distant metastases are the main pattern of failure. Age, tumor stage and clinical stage had a significant negative impact on LC, OS and PFS. [ABSTRACT FROM AUTHOR]

Background: Skull base chordomas are rare and heterogeneously behaving tumors. Though still classified as benign they can grow rapidly, are locally aggressive, and have the potential to metastasize. To adapt the treatment to the specific needs of patients at higher risk of recurrence, a pre-proton therapy prognostic grading system would be useful. The aim of this retrospective analysis is to assess prognostic factors and the "Sekhar Grading System for Cranial Chordomas" (SGSCC) by evaluating the larger cohort of patients treated at our institution as to determine its reproducibility and ultimately to ensure more risk adapted local treatments for these challenging tumors.Methods: We analyzed 142 patients treated for skull base chordomas between 2004 and 2016. We focused the analysis on the 5 criteria proposed for the SGSCC (tumor size, number of anatomic regions and vessels involved, intradural invasion, as well as recurrence after prior treatment) and classified our patients according to their score (based on the above mentioned criteria) into three prognostic groups, low-risk, intermediate-risk and high-risk. The three groups were then analyzed in regards of local control, local recurrence-free survival and overall survival.Results: The median follow up was 52 months (range, 3-152). We observed 34 (24%) patients with a local recurrence, resulting in a local control of 75% at 5 years. Overall survival was 83% at 5 years, 12 (9%) patients had died due to local progression. When split into the three prognostic groups according to the SGSCC the observed local control was 90, 72 and 64% (p = 0.07) in the low-, intermediate- and high-risk group, respectively. A similar correlation was observed for local recurrence-free survival with 93, 89 and 66% (p = 0.05) and for overall survival with 89, 83 and 76% (p = 0.65) for the same prognostic groups.Conclusions: After splitting our patient cohort into the three SGSCC risk groups, we found a trend towards better outcome for those patients with lower as opposed to higher scores. These results suggest that this prognostic grading system published by Sekhar et al. could be integrated in the management decision-tree for patients with skull base chordoma. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose Skull-base chondrosarcoma (ChSa) is a rare bone tumor and the outcome of patients with this malignancy has been documented only in a limited number of series with a restricted number of patients. Objective This study was conducted to assess the outcome and prognostic factors of a large cohort of ChSa patients treated with radiotherapy in two proton therapy centers. Materials and methods From 1996 to 2015, 251 (male, 43.4%) patients (mean age, 42.0 ± 16.2 years) were treated with protons with (n = 135; 53.8%) or without photons (n = 116; 46.2%). Median delivered dose was 70.2 Gy RBE. Failure-free survival (FFS), overall survival (OS) and CTCAE grade ≥3 toxicity free survival (TFS) were calculated using the Kaplan–Meier method. Results After a median follow-up of 88.0 months for surviving patients, local and distant failures were observed in 12 (4.8%) and 4 (1.6%) patients, respectively. Late failures >6 years were observed in 4 (33.3%) patients. The estimated 7-year FFS was 93.1%. Twenty-five (10%) patients died. The estimated 7-year OS was 93.6%. Tumor volume (p = 0.006) and optic pathway compression (p = 0.027) were significantly associated with the risk of treatment failure on univariate analysis. Treatment failure was significantly associated with a higher risk of death (hazard ratio = 126). The estimated 7-year TFS was 84.2%. Conclusions The outcome of skull-base ChSa patients treated with high-dose protons with or without photons is excellent, particularly for patients with small tumors with no optic pathway compression. Treatment failure was however associated with a significantly increased risk of death. [ABSTRACT FROM AUTHOR]

Background We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe. Material and methods The modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015. Results The average number of patients treated per year and per particle center was 221 (range, 40–557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets. Conclusions As the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To determine the efficacy and feasibility of induction chemotherapy (ICT) with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy and cetuximab (C) in patients with locally advanced head and neck cancer. Patients and methods: Forty-nine previously untreated patients with local advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) received three courses of ICT consisting of docetaxel 75mg/m2 day 1, cisplatin 75mg/m2 day 1 and infusional 5-fluorouracil 750mg/m2/day on days 1–5 followed by radiotherapy plus C at 250mg/m2/week (after an initial loading dose of 400mg/m2). Results: After completion of ICT 44 of 49 patients received radiotherapy plus C. Three months after therapy completion tumour response was observed in 33 patients and after two years, 25 patients were in complete remission (CR). The most common grade 4 toxicity during the whole treatment period was dermatitis (30%), followed by mucositis (27%) and neutropenia (17%) without fever. One toxic related death was observed during ICT. Two-year progression-free survival (PFS) rate was 59% and two-year overall survival (OS) rate was 63%, respectively. Conclusion: Concurrent radiotherapy plus C after three courses of ICT was feasible and was associated with promising CR, PFS and OS rates. Further optimisation of dose and sequence is warranted. [Copyright &y& Elsevier]

Abstract: The study aimed to determine whether post-radiation vaginal side effects in cervical cancer patients can be correlated with DVH parameter D2cc. The result was negative in that no correlation could be demonstrated between D2cc and the presence and grade of side effects in this patients’ subset treated with high brachytherapy doses. [ABSTRACT FROM AUTHOR]

Background. The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer 18F-fluoroazomycin-arabinoside (18FAZA ). Material and methods. Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm3 (+/− 67, SD). Dynamic and static 18FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/− concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk. Results. Five patients had visually identifiable tumours on 18FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five 18FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten 18FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/−12, SD). Conclusion. PET imaging with 18FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of 18FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with complex brain tumors are regularly treated with proton therapy (PT) to obtain an optimal curative treatment with limited toxicity. Value-based oncological medicine is increasingly important, particularly when long-term survival is to be expected. The aim of our prospective study was to evaluate health-related quality of life (HRQOL) and patient reported outcomes (PROs) in patients treated with PT for brain tumors. PT only temporarily influences PROs and QoL directly following PT and lower QoL and PROs were mostly reported by patients who were already in a worse condition with symptoms related to the tumor and previous treatment, before the start of PT. This study assists in improving patient support in patients with brain tumors receiving PT. Proton therapy (PT) is delivered to complex brain tumors to obtain an optimal curative treatment with limited toxicity. Value-based oncological medicine is increasingly important, particularly when long-term survival is to be expected. This study aims to evaluate health-related quality of life (HRQOL) and patient reported outcomes (PROs) in patients treated with PT for brain tumors. Adult patients with brain tumors treated with PT filled out the EORTC-QLQ-C30 and BN20 questionnaires up to three years following PT. Toxicity was scored using the CTCAE v4.03. QoL and PRO were correlated to clinical factors. Three-year overall survival, distant brain control and local control rates were 98%, 97% and 84%, respectively. No ≥G3 acute toxicity was observed. Late PT-related ≥G3 severe toxicity occurred in seven patients (5.7%). Lower global QoL scores after PT were significantly correlated to low Karnofsky performance status (KPS) before PT (p = 0.001), surgical complications before PT (p = 0.04) and progressive disease (p = 0.017). A low QLQ-30 summary score at one year follow-up was correlated to sex (p = 0.015), low KPS before PT (p < 0.001), and central nervous system symptoms before PT (p = 0.018). Reported QLQ-BN20 neurological symptoms were correlated to lower KPS at baseline (p < 0.001) and surgical complications before PT (p = 0.03). PT-related toxicity only influenced reported symptoms directly following PT, but not QoL. Although global QoL temporarily decreased after treatment, it improved again from one year onwards. Global QoL and reported symptoms over time were not correlated with the proton therapy and were more related to preexisting symptoms and progressive disease. This study assists in improving patient support in patients with brain tumors receiving PT. [ABSTRACT FROM AUTHOR]

Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369–1142). All patients completed PT and received a median of 5 HT sessions (range, 2–6). Median follow-up was 18 months (range, 9–26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9–72). All patients experienced acute Grade 2–3 local pain. One patient presented with a late Grade 3 iliac fracture. Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma. [ABSTRACT FROM AUTHOR]

Proton therapy (PT) has been administered for many years to a number of cancers, including brain tumours. Due to their remarkable physical properties, delivering their radiation to a very precise brain volume with no exit dose, protons are particularly appropriate for these tumours. The decrease of the brain integral dose may translate with a diminution of neuro-cognitive toxicity and increase of quality of life, particularly so in children. The brain tumour patient's access to PT will be substantially increased in the future, with many new facilities being planned or currently constructed in Europe, Asia and the United States. Although approximately 150'000 patients have been treated with PT, no level I evidence has been demonstrated for this treatment. As such, it is this necessary to generate high-quality data and some new prospective trials will include protons or will be activated to compare photons to protons in a randomized design. PT comes however with an additional cost factor that may contribute to the ever-growing health's expenditure allocated to cancer management. These additional costs and financial toxicity will have to be analysed in the light of a more conformal radiation delivery, non-target brain irradiation and lack of potential for dose escalation when compared to photons. The latter is due to the radiosensitivity of organs at risk in vicinity of the brain tumour, that photons cannot spare optimally. Consequentially, radiation-induced toxicities and tumour recurrences, which are cost-intensive, may decrease with PT resulting in an optimized photon/proton financial ratio in the end. This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors. [ABSTRACT FROM AUTHOR]