Search

Introduction: Durvalumab following chemoradiotherapy (CRT) for non-small cell lung cancer stage III has become the standard of care (SoC) in the past few years. With this regimen, 5-year overall survival (OS) has risen to 43%. Therefore, adequate pulmonary function (PF) after treatment is paramount in long-term survivors. In this respect, carbon monoxide diffusing capacity (DLCO), which represents the alveolar compartment, seems to be a suitable measure for residual lung capacity. The aim of the current analysis was to correlate DLCO with pneumonitis and radiation dose. Patients and methods: One hundred and twelve patients with histologically confirmed NSCLC III treated between 2015/10 and 2022/03 were eligible for this study. Patients received two cycles of platinum-based induction chemotherapy followed by high-dose radiotherapy (RT). As of 2017/09, durvalumab maintenance therapy was administered for one year. The clinical endpoints were based on the thresholds jointly published by the European Respiratory Society (ERS) and the American Thoracic Society (ATS). Pre-treatment DLCO of 60% was correlated to the incidence of pneumonitis, whereas the post-treatment DLCO decline of 10% was related to radiation dose. Results: Patients with a pre-treatment DLCO < 60% had a higher probability of pneumonitis (n = 98; r = 0.175; p-value 0.042), which could be reproduced in the subgroup of patients who did not receive durvalumab (n = 40; r = 0.288; p-value 0.036). In these individuals, the decline in DLCO ≥ 10% depended significantly on the size of the lung volume receiving between 45% and 65% (V65–45%) of the total radiation dose (r = 0.354; p-value = 0.020) and V20 Total Lung (r = 0.466; corrected p-value = 0.042). Conclusions: The current analysis revealed that DLCO is a predictor for clinically relevant pneumonitis and a monitoring tool for post-treatment lung function as it correlates with radiation dose. This underlines the importance of peri-treatment lung function testing.

Background MicroRNAs are small non-coding RNAs with pivotal regulatory functions in multiple cellular processes. Their significance as molecular predictors for breast cancer was demonstrated in the past 15 years. The aim of this study was to elucidate the role of hsa-miR-3651 for predicting of local control (LC) in early breast cancer. Results By means of high-throughput technology, hsa-miR-3651 was found to be differentially expressed between patients who experienced local relapse compared to those without (N = 23; p = 0.0035). This result could be validated in an independent cohort of 87 patients using RT-qPCR (p < 0.0005). In a second analysis step with a chip-based microarray containing 70,523 probes of potential target molecules, FERM domain protein 3 (FRMD3) was found to be the most down-regulated protein (N = 21; p = 0.0016). Computational analysis employing different prediction algorithms revealed FRMD3 as a likely downstream target of hsa-miR-3651 with an 8mer binding site between the two molecules. This could be validated in an independent patient set (N = 20, p = 0.134). Conclusion The current study revealed that hsa-miR-3651 is a predictor of LC in early breast cancer via its putative target protein FRMD3. Since microRNAs interfere in multiple pathways, the results of this hypothesis generating study may contribute to the development of tailored therapies for breast cancer in the future.

The treatment of locally recurrent lung cancer is a major challenge for radiation-oncologists, especially with data on high-dose reirradiation being limited to small retrospective studies. The aim of the present study is to assess overall survival (OS) for patients with locally recurrent lung cancer after high-dose thoracic reirradiation. Thirty-nine patients who were re-irradiated for lung cancer relapse between October 2013 and February 2019 were eligible for the current retrospective analysis. All patients were re-irradiated with curative intent for in-field tumor recurrence. The diagnostic work-up included a mandatory 18F-FDG-PET-CT scan and—if possible—histological verification. The ECOG was ≤2, and the interval between initial and second radiation was at least nine months. Thirty patients (77%) had non-small cell lung cancer (NSCLC), eight (20%) had small cell lung cancer (SCLC), and in one patient (3%) histological confirmation could not be obtained. More than half of the patients (20/39, 51%) received re-treatment with dose differentiated accelerated re-irradiation (DART) at a median interval of 20.5 months (range: 6–145.3 months) after the initial radiation course. A cumulative EQD2 of 131 Gy (range: 77–211 Gy) in a median PTV of 46 mL (range: 4–541 mL) was delivered. Patients with SCLC had a 3 mL larger median re-irradiation volume (48 mL, range: 9–541) compared to NSCLC patients (45 mL, range: 4–239). The median cumulative EQD2 delivered in SCLC patients was 84 Gy (range: 77–193 Gy), while NSCLC patients received a median cumulative EQD2 of 135 Gy (range: 98–211 Gy). The median OS was 18.4 months (range: 0.6–64 months), with tumor volume being the only predictor (p &lt, 0.000, HR 1.007, 95%-CI: 1.003–1.012). In terms of toxicity, 17.9% acute and 2.6% late side effects were observed, with a toxicity grade &gt, 3 occurring in only one patient. Thoracic high dose reirradiation plays a significant role in prolonging survival, especially in patients with small tumor volume at recurrence.

Background: During the last decade, partial breast irradiation (PBI) has gained traction as a relevant treatment option for patients with early-stage low-risk breast cancer after breast-conserving surgery. The TARGIT-A prospective randomized trial compared a “risk-adapted” intraoperative radiotherapy (IORT) approach with 50-kv X-rays (INTRABEAM®) as the PBI followed by optional whole-breast irradiation (WBI) and conventional adjuvant WBI in terms of observed 5-year in-breast recurrence rates. Recently, long-term data were published. Since the first publication of the TARGIT-A trial, a broad debate has been emerged regarding several uncertainties and limitations associated with data analysis and interpretation. Our main objective was to summarize the data, with an emphasis on the updated report and the resulting implications. Summary: From our point of view, the previously unresolved questions still remain and more have been added, especially with regard to the study design, a change in the primary outcome measure, the significant number of patients lost to follow-up, and the lack of a subgroup analysis according to risk factors and treatment specifications. Key Message: Taking into account the abovementioned limitations of the recently published long-term results of the TARGIT-A trial, the German Society of Radiation Oncology (DEGRO) Breast Cancer Expert Panel adheres to its recently published recommendations on PBI: “the 50-kV system (INTRABEAM) cannot be recommended for routine adjuvant PBI treatment after breast-conserving surgery.”

Background Given the limited curative treatment options for recurrent lung cancer patients, the aim of our retrospective study was to investigate whether these patients would benefit in terms of overall survival (OS) by adding immunotherapy to high‐dose reirradiation. Materials and methods Between 2013 and 2019, 47 consecutive patients with in‐field tumor recurrence underwent high‐dose thoracic reirradiation at our institute. Twenty patients (43%) received high‐dose reirradiation only, while 27/47 (57%) additionally had systemic therapy (immunotherapy and/or chemotherapy). With the exception of one patent, the interval between first and second radiation was at least 9 months. All patients had an Eastern cooperative oncology group ≤2. The diagnostic work‐up included a mandatory fluorodeoxyglucose‐positron emission tomography‐computed tomography scan and histological verification. The primary endpoint was OS after completion of the second course of irradiation. Results In the whole cohort of 47 patients, the median overall survival (mOS) after reirradiation was 18.9 months (95% confidence interval [CI] 16.5–21.3 months), while in the subgroup of 27 patients who received additional systemic treatment after reirradiation, mOS amounted to 21.8 months (95% CI 17.8–25.8 months). Within this group the comparison between reirradiation combined with either immunotherapy (n = 21) or chemotherapy (n = 6) revealed a difference in OS, which was in favor of the first (log‐rank p value = 0.063). Three patients (11%) experienced acute side effects and one (4%) showed a late hemorrhage grade 3. Conclusion Patients who received immunotherapy and reirradiation lived longer than those who did not receive immunotherapy., The aim of our retrospective study was to investigate whether reccurrent lung patients would benefit in terms of overall survival by adding immunotherapy to high‐dose reirradiation. Between 2013 and 2019, 47 consecutive patients with in‐field tumor recurrence underwent high‐dose thoracic reirradiation at our institute. Twenty patients (43%) received high dose reirradiation only, while 27/47 (57%) additionally had systemic therapy (immunotherapy and/or chemotherapy). Patients who received immunotherapy and reirradiation lived longer than those who did not receive immunotherapy.

Evidence from a few small randomized trials and retrospective cohorts mostly including various tumor entities indicates a prolongation of disease free survival (DFS) and overall survival (OS) from local ablative therapies in oligometastatic disease (OMD). However, it is still unclear which patients benefit most from this approach. We give an overview of the several aspects of stereotactic body radiotherapy (SBRT) in extracranial OMD in breast cancer from a radiation oncology perspective. A PubMed search referring to this was conducted. An attempt was made to relate the therapeutic efficacy of SBRT to various prognostic factors. Data from approximately 500 breast cancer patients treated with SBRT for OMD in mostly in small cohort studies have been published, consistently indicating high local tumor control rates and favorable progression-free (PFS) and overall survival (OS). Predictors for a good prognosis after SBRT are favorable biological subtype (hormone receptor positive, HER2 negative), solitary metastasis, bone-only metastasis, and long metastasis-free interval. However, definitive proof that SBRT in OMD breast cancer prolongs DFS or OS is lacking, since, with the exception of one small randomized trial (n = 22 in the SBRT arm), none of the cohort studies had an adequate control group. Further studies are needed to prove the benefit of SBRT in OMD breast cancer and to define adequate selection criteria. Currently, the use of local ablative SBRT should always be discussed in a multidisciplinary tumor board.

To investigate long-term results of patients with hormonal receptor-positive breast cancer treated with breast-conserving surgery (BCS) and consecutive endocrine therapy (ET) with or without whole breast irradiation (WBI).Within the 8 A trial of the Austrian Breast and Colorectal Cancer Study Group, a total of 869 patients received ET after BCS which was randomly followed by WBI (n = 439, group 1) or observation (n = 430, group 2). WBI was applied up to a mean total dosage of 50 Gy (+/- 10 Gy boost) in conventional fractionation.After a median follow-up of 9.89 years, 10 in-breast recurrences (IBRs) were observed in group 1 and 31 in group 2, resulting in a 10-year local recurrence-free survival (LRFS) of 97.5% and 92.4%, respectively (p = 0.004). This translated into significantly higher rates for disease-free survival (DFS): 94.5% group 1 vs 88.4% group 2, p = 0.0156. For distant metastases-free survival (DMFS) and overall survival (OS), respective 10-year rates amounted 96.7% and 86.6% for group 1 versus 96.4% and 87.6%, for group 2 (ns). WBI (hazard ratio [HR]: 0.27, p 0.01) and tumour grading (HR: 3.76, p = 0.03) were found as significant predictors for IBR in multiple cox regression analysis.After a median follow-up of 10 years, WBI resulted in a better local control and DFS compared with ET alone. The omission of WBI and tumour grading, respectively, were the only negative predictors for LRFS.

Introduction: Thoracic re-irradiation for recurrent lung cancer dates back four decades, when the first small series on 29 patients receiving palliative doses was published. With 5-year overall survival rates of 57% in PDL-1 positive patients after primary chemo-radio-immunotherapy, the number of patients who experience loco-regional relapse will increase in the near future. In this context, centrally recurring lung tumors pose a major treatment challenge. Hence, the aim of the current review is to compile the available evidence on curatively intended thoracic re-irradiation for this special clinical situation. Methods: A systematic literature search according to the PRISMA guidelines was performed. A study was included when the following criteria were met: (1) 66% of the patients had NSCLC, (2) a total dose of 50 Gy in the second course and/or a biologically effective dose of at least 100 Gy in both treatment courses was administered, (3) re-irradiation was administered with modern radiation techniques, (4) 50% or more of the patients had a centrally located relapse, (5) the minimum cohort size was 30 patients. Results: Of the initial 227 studies, 11 were analyzed, 1 of which was prospective. Median overall survival (OS) was 18.1 months (range 9.3–25.1), median progression free survival (PFS) was nine months (range 4.5–16), and median loco-regional control (LRC) was 12.1 months (range 6.5–20). Treatment-related mortality rates ranged from 2% to 14%. The total dose at re-irradiation correlated with both LRC (p-value = 0.012) and OS (p-value = 0.007) with a close relation between these two clinical endpoints (p-value = 0.006). The occurrence of acute toxicity grade 1 to 4 depended on the PTV size at re-irradiation (p-value = 0.033). Conclusion: The evidence regarding curative re-irradiation for centrally recurrent NSCLC is primarily based on scarce retrospective data, which are characterized by a high degree of heterogeneity. The OS in this clinically challenging situation is expected to be around 1.5 years after re-treatment. Patients with a good performance score, younger age, small tumors, and a longer interval to recurrence potentially benefit most from re-irradiation. In this context, prospective trials are warranted to achieve substantial advances in the field.

Objective To assess the prognostic profile, clinical outcome, treatment-associated morbidity, and treatment burden of elderly patients with glioblastoma (GBM) undergoing microsurgical tumor resection as part of contemporary treatment algorithms. Methods We retrospectively identified patients with GBM ≥65 years of age who were treated by resection at 2 neuro-oncology centers. Survival was assessed by Kaplan-Meier analyses; log-rank tests identified prognostic factors. Results The study population included 160 patients (mean age, 73.1 ± 5.1 years), and the median contrast-enhancing tumor volume was 31.0 cm3. Biomarker analyses revealed O(6)-methylguanine-DNA methyltransferase–promoter methylation in 62.7% and wild-type isocitrate dehydrogenase in 97.5% of tumors. The median extent of resection (EOR) was 92.3%, surgical complications were noted in 10.0% of patients, and the median postoperative hospitalization period was 8 days. Most patients (60.0%) received adjuvant radio-/chemotherapy. The overall treatment-associated morbidity was 30.6%. The median progression-free and overall survival were 5.4 months (95% confidence interval [CI], 4.6–6.4 months) and 10.0 months (95% CI, 7.9–11.7 months). The strongest predictors for favorable outcome were patient age ≤73.0 years (P = 0.0083), preoperative Karnofsky Performance Status Scale score ≥80% (P = 0.0179), postoperative modified Rankin Scale score ≤1 (P Conclusions Clinical outcome for elderly patients with GBM remains limited. Nonetheless, the observed treatment-associated morbidity and treatment burden were moderate in the patients, and patient age and performance status remained the strongest predictors for survival. The risks and benefits of tumor resection in the age of biomarker-adjusted treatment concepts require further prospective evaluation.

Background Chemoradiotherapy (CRT) is the standard treatment for patients with inoperable stage III non‐small cell lung cancer (NSCLC) stage III. With a median OS beyond 30 months, adequate pulmonary function (PF) is essential to ensure acceptable quality of life after treatment. Forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) are the most widely used parameters to assess lung function. The aim of the current study was to evaluate dose‐volume effects of accelerated high‐dose radiation on PF. Methods A total of 72 patients were eligible for the current analysis. After induction chemotherapy, all patients received dose‐differentiated accelerated radiotherapy with intensity‐modulated radiotherapy (IMRT‐DART). PF tests were performed six weeks, three and six months after the end of radiotherapy. Results The median total dose to the tumor was 73.8 Gy (1.8 Gy bid) with a size dependent range between 61.2 and 90 Gy. In the whole cohort, 321 pulmonary function tests were performed. At six months, the median FEV1 relative to baseline was 0.95 (range: 0.56–1.36), and the relative median DLCO decreased to 0.98 (range: 0.64–1.50). The correlation between V20total lung and FEV1 decline was statistically significant (P = 0.023). A total of 13 of 34 (38%) COPD patients had a 4%–21% FEV1 decrease. Conclusion Patients with a V20total lung

Purpose This study investigated whether hypofractionated adjuvant radiotherapy (RT) increased breast-related complication(s) compared to conventional fractionated RT in reconstructed breast cancer patients. Methods We conducted a retrospective review including 349 breast cancer patients who underwent immediate breast reconstruction following mastectomy or breast-conserving surgery (BCS) between 2009 and 2018 at two institutions. All patients were treated with adjuvant RT via either a conventional fractionated or hypofractionated regimen. We defined a major breast complication as a breast-related toxic event requiring re-operation or re-hospitalization during the follow-up period after the end of RT. Results The median follow-up was 32.3 months (4.8–118.5 months); 126 patients had conventional fractionated RT, and 223 patients received hypofractionated RT. In patients with mastectomy, there was no significant difference in the occurrence of any or major breast-related complications between the two fractionation regimens. In patients undergoing BCS, incidence of any breast complication showed no difference between two RT groups and no major breast complication was reported as well. Hypofractionated RT did not increase major wound problem (infection and dehiscence) compared to conventional RT. Incidence of major contracture was significantly lower in hypofractionated RT. Conclusions There was no significant difference in the occurrence of any or major breast-related complications between the two different fractionation regimens, even in patients with mastectomy. Hypofractionated RT may be used comparable to conventional fractionated RT in terms of breast-related complications in reconstructed breast cancer patients. The prospective randomized trial would be necessary to clarify this issue., Highlights • There was no significant difference in the occurrence of breast complications between the two fractionation regimens. • Hypofractionated RT may be used comparable to conventional fractionated RT in reconstructed breast cancer patients. • The prospective randomized trial would be necessary to clarify this issue.

Background Intraoperative radiotherapy with electrons (IOERT) boost could be not inferior to external beam radiotherapy (EBRT) boost in terms of local control and tissue tolerance. The aim of the study is to present the long-term follow-up results on local control, esthetic evaluation, and toxicity of a prospective study on early-stage breast cancer patients treated with breast-conserving surgery with an IOERT boost of 10 Gy (experimental group) versus 5 × 2 Gy EBRT boost (standard arm). Both arms received whole-breast irradiation (WBI) with 50 Gy (2 Gy single dose). Methods A single-institution phase III randomized study to compare IOERT versus EBRT boost in early-stage breast cancer was conducted as a non-inferiority trial. Primary endpoints were the evaluation of in-breast true recurrences (IBTR) and out-field local recurrences (LR) as well as toxicity and cosmetic results. Secondary endpoints were overall survival (OS), disease-free survival (DFS), and patient’s grade of satisfaction with cosmetic outcomes. Results Between 1999 and 2004, 245 patients were randomized: 133 for IOERT and 112 for EBRT. The median follow-up was 12 years (range 10–16 years). The cumulative risk of IBTR at 5–10 years was 0.8% and 4.3% after IOERT, compared to 4.2% and 5.3% after EBRT boost (p = 0.709). The cumulative risk of out-field LR at 5–10 years was 4.7% and 7.9% for IOERT versus 5.2% and 10.3% for EBRT (p = 0.762). All of the IOERT arm recurrences were observed at > 100 months’ follow-up, whereas the mean time to recurrence in the EBRT group was earlier (55.2 months) (p p = 0.006 objective and p = 0.0004 subjective) and most narrow difference at 12 months after the end of EBRT (p = 0.08 objective and p = 0.04 subjective analysis). Conclusion A 10-Gy IOERT boost during breast-conserving surgery provides high local control rates without significant morbidity. Although not significantly superior to external beam boosts, the median time to local recurrences after IOERT is prolonged by more than 4 years.

Background Breast intraoperative electron radiation therapy (B-IOERT) can be used in clinical practice both as elective irradiation (partial breast irradiation – APBI) in low risk breast cancer patients, and as an anticipated boost. The procedure generally includes the use of a shielding disk between the residual breast and the pectoralis fascia for the protection of the tissues underneath the target volume. The aim of the study was to evaluate the role of intraoperative ultrasound (IOUS) in improving the quality of B-IOERT. Patients and methods B-IOERT was introduced in Trieste in 2012 and its technique was improved in 2014 with IOUS. Both, needle and IOUS were used to measure target thickness and the latter was used even to check the correct position of the shielding disk. The primary endpoint of the study was the evaluation of the effectiveness of IOUS in reducing the risk of a disk misalignment related to B-IOERT and the secondary endpoint was the analysis of acute and late toxicity, by comparing two groups of patients treated with IOERT as a boost, either measured with IOUS and needle (Group 1) or with needle alone (Group 2). Acute and late toxicity were evaluated by validated scoring systems. Results From the institutional patients who were treated between June 2012 and October 2019, 109 were eligible for this study (corresponding to 110 cases, as one patients underwent bilateral conservative surgery and bilateral B-IOERT). Of these, 38 were allocated to group 1 and 72 to group 2. The target thickness measured with the IOUS probe and with the needle were similar (mean difference of 0.1 mm, p = 0.38). The percentage of patients in which the shield was perfectly aligned after IOUS introduction increased from 23% to more than 70%. Moreover, patients treated after IOUS guidance had less acute toxicity (36.8% vs. 48.6%, p = 0.33) from radiation therapy, which reached no statistical significance. Late toxicity turned out to be similar regardless of the use of IOUS guidance: 39.5% vs. 37.5% (p = 0.99). Conclusions IOUS showed to be accurate in measuring the target depth and decrease the misalignment between collimator and disk. Furthermore there was an absolute decrease in acute toxicity, even though not statistically significant, in the group of women who underwent B-IOERT with IOUS guidance.

Background: In order to characterize the various subtypes of breast cancer more precisely and improve patients selection for breast conserving therapy (BCT), molecular profiling has gained importance over the past two decades. MicroRNAs, which are small non-coding RNAs, can potentially regulate numerous downstream target molecules and thereby interfere in carcinogenesis and treatment response via multiple pathways. The aim of the current two-phase study was to investigate whether hsa-miR-375-signaling through RASD1 could predict local control (LC) in early breast cancer. Results: The patient and treatment characteristics of 81 individuals were similarly distributed between relapse (n = 27) and control groups (n = 54). In the pilot phase, the primary tumors of 28 patients were analyzed with microarray technology. Of the more than 70,000 genes on the chip, 104 potential hsa-miR-375 target molecules were found to have a lower expression level in relapse patients compared to controls (p-value &lt, 0.2). For RASD1, a hsa-miR-375 binding site was predicted by an in silico search in five mRNA-miRNA databases and mechanistically proven in previous pre-clinical studies. Its expression levels were markedly lower in relapse patients than in controls (p-value of 0.058). In a second phase, this finding could be validated in an independent set of 53 patients using ddPCR. Patients with enhanced levels of hsa-miR-375 compared to RASD1 had a higher probability of local relapse than those with the inverse expression pattern of the two markers (log-rank test, p-value = 0.069). Conclusion: This two-phase study demonstrates that hsa-miR-375/RASD1 signaling is able to predict local control in early breast cancer patients, which&mdash, to our knowledge&mdash, is the first clinical report on a miR combined with one of its downstream target proteins predicting LC in breast cancer.

Background Approximately 15% of lung cancer patients are diagnosed in early stages. Microscopic proof of disease cannot always be obtained because of comorbidity or reluctance to undergo invasive diagnostic procedures. In the current study, survival data of patients with and without pathology are compared. Methods One hundred and sixty three patients with NSCLC I-IIb (T3 N0) treated between 2002 and 2016 were eligible: 123 (75%) had pathological confirmation of disease, whereas 40 (25%) did not. In accordance with international guidelines, both groups received radiotherapy. Comorbidity was assessed with the Charlson Comorbidity Index (CCI). Results The median follow-up was 28.6 months (range: 0.3-162): 66 (40%) patients are still alive, while 97 (59%) patients died: 48 (29%) cancer-related deaths and 49 (30%) from causes other than cancer. Median overall survival (OS) in patients without pathological confirmation was 58.6 months (range: 0.5-162), which did not differ from those with microscopic proof of disease (39.4 months, range: 0.3-147.5; logrank P = 0.481). Median cancer-specific survival (CSS) also did not differ at 113.4 months (range: 0.5-162) in the non-confirmation group (logrank P = 0.763) versus 51.5 months (range: 3.7-129.5) in patients with pathology. In Cox regression, a CCI of ≥ 3 was associated with poor OS (hazard ratio 2.0; range 1.2-3.4; P = 0.010) and CSS (hazard ratio 2.0; 1.0-4.0; P = 0.043). Conclusion OS and CSS in early lung cancer patients depend on comorbidity rather than on pathological confirmation of disease.

Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35–40 y and 41–50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7–104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41–50 and >50 y, respectively. For the youngest group (35–40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41–50 when compared to best published evidence until 2010.

Background Glioblastoma multiforme (GBM) is usually characterized by diffuse, infiltrative growth and local tumor progression. Extensive leptomeningeal metastases are rarely observed. It is unclear which GBMs are prone to this specific growth pattern and progression, and standardized salvage treatment protocols are unavailable. Case Description In a 45-year-old man without focal neurologic deficit, a right temporal GBM, IDH-wildtype (biomarkers MGMT promoter methylation negative, Ki-67 proliferation rate 70%) was diagnosed. Gross tumor resection followed by concomitant and adjuvant radiotherapy and chemotherapy with temozolomide was performed. Routine follow-up imaging 8 months later showed a right parietal meningeal tumor. Resection confirmed a distant GBM, and next-generation sequencing revealed high tumor mutational burden, high-frequency microsatellite instability, and a pharmacologically targetable KIT mutation. Complete neuraxis imaging revealed multiple contrast-enhancing tumors in the craniocervical junction and levels C7, Th8-Th11, and S1. The craniocervical tumors and the cervical spine from C1-C2 were irradiated as palliative care, and second-line combined chemotherapy and antiangiogenic therapy with irinotecan and bevacizumab was initiated, which was later changed to an immune-checkpoint blockade with pembrolizumab in combination with bevacizumab owing to tumor progression. Tumor growth was slowed, but the patient eventually developed a progressive paraparesis. Subsequent KIT-targeting tyrosine kinase inhibitor therapy with imatinib was administered for a short time. The patient died 13.8 months after initial diagnosis. Conclusions High-risk genetic profiles for GBMs prone to develop extensive leptomeningeal metastases need to be identified. Guidelines on preemptive, complete neuraxis imaging in certain patients with GBM as well as treatment guidelines need to be developed.

Background: The international standard of care for the treatment of high-risk breast cancer (BC) consists of neoadjuvant chemotherapy (NACT) and surgery followed by adjuvant whole breast/chest wall irradiation. In this setting, the time interval from the start of NACT to the end of radiotherapy (RT) is usually postponed to 6 months or longer. In addition to this, a high percentage of capsular fibrosis may occur when breast implants are irradiated. Most of these disadvantages could be avoided by using preoperative RT (PRT). PRT is already the standard of care in several other tumor entities (rectal cancer, esophagus carcinoma, lung cancer, and soft tissue sarcoma). Nevertheless, PRT in BC has been tested in several trials, but randomized prospective trials using modern radiation technology and systemic therapies are lacking. The available evidence summarized in this review indicates that PRT may improve survival and reduce long-term toxicity in patients with a higher risk of recurrence and should be consequently tested in a randomized trial. Summary: Prospective, randomized trials concerning PRT in high-risk BC are needed. We plan to conduct a NeoRad trial (NACT followed by PRT in high-risk BC). Key Messages: Prospective, randomized studies concerning PRT in high-risk BC are needed.

Background and purpose To assess the role of intraoperative radiation with electrons (IOERT) as tumor bed boost followed by hypofractionated whole breast irradiation (HWBI) after breast conserving surgery (BCS) of patients with low to intermediate risk breast cancer focusing on acute/late toxicity and cosmetic outcome. Material and methods In 2011, a prospective multicenter trial (NCT01343459) was started. Treatment consisted of BCS, IOERT (11.1 Gy) and HWBI (40.5 Gy in 15 fractions). In a single-arm design, 5-year IBR-rates are benchmarked by a sequential ratio test (SQRT) against best published evidences in 3 age groups (35–40 y, 41–50 y, >50 y). Acute/late toxicity and cosmesis were evaluated by validated scorings systems. Results Of 627 eligible patients, 44 were excluded, leaving 583 to analyze. After a median follow-up (FUP) of 45 months (range 0–74), for acute effects CTCAE-score 0/1 was noted in 91% (end of HWBI) and 92% (4 weeks later), respectively. Late toxicity Grading 0/1 (mean values, ranges) by LENT-SOMA criteria were observed in 92.7% (89–97.3) at 4/5 months, rising to 96.5% (91–100) at 6 years post HWBI. Baseline cosmesis after wound healing prior to HWBI was scored as excellent/good in 86% of cases by subjective (patient) and in 74% by objective (doctor) assessment with no impairment thereafter. Conclusions Acute and late treatment tolerance of a combined Boost-IOERT/HWBI regimen is excellent in short/mid-term assessment. Postoperative cosmetic appearance is not impaired after 3 years FUP.

IOERT (intraoperative electron radiotherapy) in breast cancer is used either as a boost (10-12 Gy) followed by whole breast irradiation (WBI) or as full-dose partial breast irradiation (PBI, 20-24 Gy) during breast-conserving surgery. IOERT has the longest evidence of all IORT techniques. When administered as a boost, excellent low local recurrence rates were observed in long-term follow-up >5 years. Even in high-risk groups like triple-negative or locally advanced breast cancers, IOERT contributes to long-term local control rates of more than 90%. For selected low-risk groups, IOERT as PBI with 21 Gy seems to be a viable treatment alternative to standard WBI. IOERT has been shown to be advantageous for several reasons: Geographic misses are avoided due to direct visualization of the tumor bed; thus, a high single dose is delivered with utmost precision to small volumes, completely sparing the skin and ensuring good long-term cosmetic outcome. Furthermore, high single doses seem to induce biological mechanisms with verifiable antitumor capability in in-vitro cell-line studies. In addition, IOERT markedly shortens the overall treatment time both in combination with (now mostly hypofractionated) WBI or as a PBI in selected low-risk constellations.

The purpose of this work was to retrospectively evaluate survival and local control rates of triple-negative breast cancer subtypes classified as five marker negative (5NP) and core basal (CB), respectively, after breast-conserving surgery and intraoperative boost radiotherapy with electrons (IOERT) followed by whole breast irradiation. A total of 71 patients with triple-negative breast cancer were enrolled, who were treated with lumpectomy, axillary lymph node dissection, and IOERT with 9.6 Gy (median Dmax) followed by normofractionated whole breast irradiation to median total doses of 54 Gy. Chemotherapy was applied in a neoadjuvant (12 %), adjuvant (75 %), or combinational setting (7 %). After a median follow-up of 97 months (range 4–170 months), 5 in-breast recurrences were detected (7.0 %). For all patients, 8-year actuarial rates for local control, metastases-free survival, disease-specific survival, and overall survival amounted to 89, 75, 80, and 69 %, respectively. All local recurrences occurred in grade 3 (G3) tumors irrespective of their specific immunohistochemical phenotype; thus, the local control rate for grades 1/2 (G1/2) was 100 % for both 5NP and CB, while for G3 it was 88 % for 5NP and 90 % for CB (p = 0.65 and 0.82, respectively, n.s.). For disease-specific survival, only the difference of the best-prognosis group 5-NP/G3 vs. the worst-prognosis cohort CB/G1/2 was statistically significant: 90 % vs. 54 % (p = 0.03). Boost-IOERT provides acceptable long-term in-breast control in triple negative breast cancer. The best subgroup in terms of disease-specific survival was represented by 5NP in combination with tumor grading G3.

Low Karnofsky performance status (KPS) and elevated lactate dehydrogenases (LDHs) as a surrogate marker for tumor load and cell turnover may depict patients with a very short life expectancy. To validate this finding and compare it to other indices, namely, the recursive partitioning analysis (RPA) and diagnosis-specific graded prognostic assessment (DS-GPA), a multicenter analysis was undertaken. A retrospective analysis of 234 metastatic melanoma patients uniformly treated with palliative whole brain radiotherapy (WBRT) was done. Univariate and multivariate analyses were used to determine the impact of patient-, tumor-, and treatment-related parameters on overall survival (OS). KPS and LDH emerged as independent factors predicting OS. By combining KPS and LDH values (KPS/LDH index), groups of patients with statistically significant differences in median OS (days; 95 % CI) after onset of WBRT were identified: group 1 (KPS ≥70/normal LDH) 234 (96–372), group 2 (KPS ≥70/elevated LDH) 112 (69–155), group 3 (KPS

ClinicalTrials.gov Identifier: NCT01343459 Brief background discussion: The commonly accepted standard fractionation schedule for whole breast irradiation (WBI) consists of 25fractionations with single fractional doses of 2 Gy, resulting in cumulative doses of 50 Gy to the whole breast. Hypofractionation trials from UK and Canada demonstrated a similar outcome in local control and cosmesis compared to conventional fractionation. The combination of IOERT boost and hypofractionation was not yet evaluated. Trial design: Prospective one-armed multi-center trial - ISIORT 01 Eligible patients are treated with hypofractionated whole breast irradiation (WBI) of 40.5 Gy in 2.7 Gy per fraction for 15 days, preceded by an intraoperative electron boost (IOERT) to the tumor bed of 10 Gy (90% isodose) during breast conserving surgery. Eligibility criteria: Inclusion criteria: Invasive breast cancer Age 35 years and older T1/T2, N1/N2, G1 - G3 Hormone receptor and Her 2 status: no limitations Exclusion criteria: Non-invasive breast cancer Age less than 35 years T3/T4, N2/N3 Neoadjuvant chemotherapy Aim of the study: To assess the effectiveness of IOERT in combination with hypofractionated WBI in terms of in-breast tumor control and cosmetic outcome, by matching or exceeding the best published results for annual LR rates in 3 different age groups in reference to an upper limit (exceeding = inferiority) and a lower limit (undershooting = superiority) which were estimated on the basis of the existing literature as follows: Age 35 – 40 years: Upper limit (best published evidence): 1.2 % (EORTC 22881- Boost trial) Lower limit (commonly expected dimension): 0.72 % (CONSORT trial) Age 41 – 50 years: Upper limit (best published evidence): 1.2 % (EORTC 22881- Boost trial) Lower limit (commonly expected dimension): 0.72 % (CONSORT trial) Age over 50 years: Upper limit (best published evidence): 0.7 % (EORTC 22881- Boost trial) Lower limit (commonly expected dimension): 0.4 % (START B trial) Primary endpoint: Proof of superiority or iso-effectiveness. Secondary endpoints: Acute toxicity (CTC- toxicity scoring system) and late toxicity (LENT SOMA scoring system), cosmetic results (Van Limbergen - Score), DFS, OS. Statistical methods: Sequential Probability Ratio Test (SPRT): As a consequence of best published analyses for this patient selection, stopping rules for annual local recurrence rates are defined as follows: Age group 35-40: H0: p1 0.72% with p2 = 4.0% Age group 41-50: H0: p1 0.72% with p2 = 2.4% Age group 51+: H0: p1 0.4% with p2 = 1.4% H0-Hypothesis means no superiority to standard regimen. H1-Hypothesis means superiority of HIOB against best published evidence. Present accrual and target accrual: Start date: January 2011 Estimated enrollment: 1500 patients 542 patients recruited by March 2014 10 international institutions recruiting. Citation Format: Roland Reitsamer, Gerd Fastner, Michael Kopp, Felix Sedlmayer. HIOB trial - Hypofractionated whole-breast irradiation preceded by intraoperative radiotherapy with electrons as anticipated boost [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-4-01.

To assess retrospectively the role of an anticipated intraoperative tumor electron radiation therapy (IOERT) as a bed boost during breast-conserving surgery followed by conventional whole breast irradiation (WBI).An unselected cohort of 770 breast cancer patients of all risk types was analyzed in terms of local control (LC) and survival outcome. Patients were treated by breast-conserving surgery, IOERT of 10 Gy, and WBI to total median doses of 54 Gy (range, 1.6-2). Patients were retrospectively analyzed for LC, locoregional control, metastasis-free survival (MFS), overall survival (OS), and breast cancer-specific survival (BCSS).After a median follow-up of 121 months (range, 4-200), 21 (2.7%) in-breast recurrences (IBRs) were observed, 107 patients (14%) died and 106 (14%) developed metastases. Ten-year rates of LC, locoregional control, MFS, OS, and BCSS amounted to 97.2%, 96.5%, 86%, 85.7%, and 93.2 %, respectively. In multivariate analysis, HER2+ and triple-negative breast cancer subtype (TN) turned out to be significant negative predictors for IBRs (hazard ratios, 15.02 and 12.87, respectively; P.05). Sorted by subtypes, 10-year LC rates were observed in 98.7% (range, 96.7%-99.5%) (luminal A), 98% (range, 94%-99.3%) (luminal B), 87.9% (range, 66.2%-96%) (HER2+), and 89% (range, 76.9%-94.9%) (TN), respectively.After 10 years, boost IOERT maintains high LC rates in any risk setting.

Purpose The role of radiotherapy (RT) for nonmetastatic pancreatic cancer is still a matter of debate since randomized control trials have shown inconsistent results. The current retrospective single-institution study includes both resected and unresected patients with nonmetastasized pancreatic cancer. The aim is to analyze overall survival (OS) after irradiation combined with induction chemotherapy. Patients and methods Of the 73 patients with nonmetastatic pancreatic cancer eligible for the present analysis, 42 (58%) patients had adjuvant chemoradiotherapy (CRT), while 31 (42%) received CRT as primary treatment. In all, 65 (89%) had chemotherapy at any time before, during, or after RT, and 39 (53%) received concomitant CRT. The median total dose was 50 Gy (range 12–77 Gy), while 61 (84%) patients received >40 Gy. Results With a median follow-up of 22 months (range 1.2–179.8 months), 14 (19%) are still alive and 59 (81%) of the patients have died, whereby 51 (70%) were cancer-related deaths. Median OS and the 2‑year survival rate were 22.9 months (1.2–179.8 months) and 44%, respectively. In addition, 61 (84%) patients treated with >40 Gy had a survival advantage (median OS 23.7 vs. 17.3 months, p = 0.026), as had patients with 4 months minimum of systemic treatment (median OS 27.5 vs. 14.3 months, p = 0.0004). Conclusion CRT with total doses >40 Gy after induction chemotherapy leads to improved OS in patients with nonmetastatic pancreatic cancer. Electronic supplementary material The online version of this article (10.1007/s00066-018-1281-7) contains supplementary material, which is available to authorized users.

Introduction Two randomized intraoperative radiation therapy trials for early-stage breast cancer were recently published. The ELIOT Trial used electrons (IOERT), and the TARGIT-A Trial Update used 50-kV X-rays (IORT). These studies were compared for similarities and differences. The results were analyzed and used to determine which patients might be suitable for single-dose treatment. Method The primary sources of data were the ELIOT Trial and TARGIT-A Trial, as well as a comprehensive analysis of the peer-reviewed literature of accelerated partial breast irradiation (APBI) using 50-kV X-rays or electrons. Studies published or presented prior to March 2014 were analyzed for efficacy, patient restrictions, complications, and outcome. Results With a median follow-up of 5.8 years, the 5-year recurrence rates for ELIOT versus external beam radiation therapy (EBRT) patients were 4.4 % and 0.4 %, respectively, p = .0001. A low-risk ELIOT group was identified with a 5-year recurrence rate of 1.5 %. With a median follow-up of 29 months, the 5-year recurrence rates for the TARGIT-A versus EBRT patients were 3.3 % and 1.3 %, respectively, p = .042. Conclusion With 5.8 years of median follow-up, IOERT appears to have a subset of low-risk women for whom IOERT is acceptable. With 29 months of median follow-up the results of IORT with 50-kV devices are promising, but longer follow-up data are required. At the current time, single-fraction IOERT or IORT patients should be treated under strict institutional protocols.

To evaluate retrospectively rates of local (LCR) and locoregional tumor control (LRCR) in patients with locally advanced breast cancer (LABC) who were treated with preoperative chemotherapy (primary systemic treatment, PST) followed by breast-conserving surgery (BCS) and either intraoperative radiotherapy with electrons (IOERT) preceding whole-breast irradiation (WBI) (Group 1) or with WBI followed by an external tumor bed boost (electrons or photons) instead of IOERT (Group 2). From 2002 to 2007, 83 patients with clinical Stage II or III breast cancer were enrolled in Group 1 and 26 in Group 2. All patients received PST followed by BCS and axillary lymph node dissection. IOERT boosts were applied by single doses of 9 Gy (90% reference isodose) versus external boosts of 12 Gy (median dose range, 6-16) in 2 Gy/fraction (ICRU). WBI in both groups was performed up to total doses of 51-57 Gy (1.7-1.8 Gy/fraction). The respective median follow-up times for Groups 1 and 2 amount 59 months (range, 3-115) and 67.5 months (range, 13-120). Corresponding 6-year rates for LCR, LRCR, metastasis-free survival, disease-specific survival and overall survival were 98.5, 97.2, 84.7, 89.2 and 86.4% for Group 1 and 88.1, 88.1, 74, 92 and 92% for Group 2, respectively, without any statistical significances. IOERT as boost modality during BCS in LABC after PST shows a trend to be superior in terms of LCR and LRCR in comparison with conventional boosts.