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Abstract Intraoperative radiation therapy (IORT) is a radiation technique applying a single fraction with a high dose during surgery. We report the first abdomino-pelvic application of an image-guided intraoperative electron radiation therapy with intraoperative real time dose calculation based on the individual intraoperative patient anatomy. A patient suffering from locoregionally recurrent rectal cancer after treatment with neoadjuvant re-chemoradiation was chosen for this approach. After surgical removal of the recurrence, an adequate IORT applicator was placed as usual. A novel mobile imaging device (ImagingRing, MedPhoton) was positioned around the patient covering the region to be treated with the IORT-applicator in place. It allowed the acquisition of three-dimensional intraoperative cone-beam computed tomography images suitable for dose calculation using an automated scaling (heuristic object and head scatter as well as hardening corrections) of Hounsfield units. After image acquisition confirmed the correct applicator position, the images were transferred to our treatment planning system for intraoperative dose calculation. Treatment could be accomplished using the calculated dose distribution. We herein describe the details of the procedure including necessary adjustments in the typically used IORT equipment and work flow. We further discuss the pros and cons of this new approach generally overcoming a decade long limitation of IORT procedures as well as future perspectives regarding IORT treatments.

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 < 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 >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.

Abstract 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

Abstract 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.

Abstract Concomitant chemo‐radiotherapy (cCRT) with 60 Gy in 30 fractions is the standard of care for stage 111 non‐small cell lung cancer (NSCLC). With a median overall survival of 28.7 months at best and maximum locoregional control rates of 70% at two years, the prognosis for these patients is still dismal. This systematic review summarizes data on dose escalation by alternative fractionation, which has been explored as a primary strategy to improve both local control and overall survival over the past three decades. A Pubmed literature search was performed according to the PRISMA guidelines. Because of the large variety of radiation regimens total doses were converted to EQD2,T. Only studies using an EQD2,T of at least 49.5 Gy, which corresponds to the conventional 60 Gy in six weeks, were included. In a total of 3256 patients, the median OS was 17 months (range 7.4–30 months). While OS was better for patients treated after the year 2000 (P = 0.003) or with a mandatory 18F‐FDG‐PET‐CT in the diagnostic work‐up (P = 0.001), treatment sequence did not make a difference (P = 0.106). The most commonly reported toxicity was acute esophagitis (AE) with a median rate of 24% (range 0%–84%). AE increased at a rate of 0.5% per Gy increment in EQD2,T (P = 0.016). Dose escalation above the conventional 60 Gy using modified radiation fractionation schedules and shortened OTT yield similar mOS and LRC regardless of treatment sequence with a significant EQD2,T dependent increase in AE. Key points Significant findings Modified radiation dose escalation sequentially combined with chemotherapy yields similar outcome as concomitant treatment. OS is better with the mandatory inclusion of FDG‐PET‐CT in the diagnostic work‐up. The risk of acute esophagitis increases with higher EQD2,T. What this study adds Chemo‐radiotherapy (CRT) with modified dose escalation regimens yields OS and LC rates in the range of standard therapy regardless of treatment sequence. This broadens the database of curative options in patients who are not eligible concomitant CRT.

Abstract 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

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.

Introduction: Curatively intended chemo-radio-immunotherapy for non-small cell lung cancer (NSCLC) stage III may lead to post-therapeutic pulmonary function (PF) impairment. We hypothesized that the decrease in global PF corresponds to the increase in tissue density in follow-up CTs. Hence, the study aim was to correlate the dynamics in radiographic alterations to carbon monoxide diffusing capacity (DLCO) and FEV1, which may contribute to a better understanding of radiation-induced lung disease. Methods: Eighty-five patients with NSCLC III were included. All of them received two cycles of platinum-based induction chemotherapy followed by high dose radiation. Thereafter, durvalumab was administered for one year in 63/85 patients (74%). Pulmonary function tests (PFTs) were performed three months and six months after completion of radiotherapy (RT) and compared to baseline. At the same time points, patients underwent diagnostic CT (dCT). These dCTs were matched to the planning CT (pCT) using RayStation® Model Based Segmentation and deformable image registration. Differential volumes defined by specific isodoses were generated to correlate them with the PFTs. Results: In general, significant correlations between PFTs and differential volumes were found in the mid-dose range, especially for the volume of the lungs receiving between 65% and 45% of the dose prescribed (V65−45%) and DLCO (p<0.01). This volume range predicted DLCO after RT (p-value 0.03) as well. In multivariate analysis, DLCO (p-value 0.040) and FEV1 (p-value 0.014) predicted pneumonitis. Conclusions: The current analysis revealed a strong relation between the dynamics of DLCO and CT morphology changes in the mid-dose range, which convincingly indicates the importance of routinely used PFTs in the context of a curative treatment approach.

The term IORT (intraoperative radiotherapy) is currently used for various techniques that show decisive differences in dose delivery. The largest evidence for boost IORT preceding whole breast irradiation (WBI) originates from intraoperative electron treatments with single doses around 10 Gy, providing outstandingly low local recurrence rates in any risk constellation also at long term analyses. Compared to other boost methods, an intraoperative treatment has evident advantages as follows. Precision. Direct visualisation of the tumour bed during surgery guarantees an accurate dose delivery. This fact has additionally gained importance in times of primary reconstruction techniques after lumpectomy to optimise cosmetic outcome. IORT is performed before breast tissue is mobilised for plastic purposes. Cosmesis. As a consequence of direct tissue exposure without distension by hematoma/seroma, IORT allows for small treatment volumes and complete skin sparing, both having a positive effect on late tissue tolerance and, hence, cosmetic appearance. Patient Comfort. Boost IORT marginally prolongs the surgical procedure, while significantly shortening postoperative radiotherapy. Its combination with a 3-week hypofractionated external beam radiotherapy to the whole breast (WBI) is presently tested in the HIOB trial (hypofractionated WBI preceded by IORT electron boost), a prospective multicenter trial of the International Society of Intraoperative Radiotherapy (ISIORT).