The aim of this review is to give an overview of the results of prospective and retrospective studies using allogenic reconstruction and postmastectomy radiotherapy (PMRT) in breast cancer and to make recommendations regarding this interdisciplinary approach. A PubMed search was conducted to extract relevant articles from 2000 to 2024. The search was performed using the following terms: (breast cancer) AND (reconstruction OR implant OR expander) AND (radiotherapy OR radiation). Data from the literature on allogenic breast reconstruction and radiation are presented and discussed in relation to toxicity and cosmesis. Breast reconstruction is also feasible if PMRT is necessary. Patients need to be informed about the relevant risk of capsular fibrosis and implant failure. A planned reconstruction is no reason to forgo PMRT nor is an indication for PMRT a reason to forego implant-based breast reconstruction if desired by the patient. It is important to provide detailed information here to enable shared decision-making. There is still no clear consensus regarding implant-based reconstruction (IBR) and PMRT. However, in clinical practice, both a one-stage (immediate “implant-direct” IBR) procedure with PMRT up to the final implant and a two-stage (immediate-delayed IBR) procedure with PMRT up to the tissue expander (TE) and later exchange of the TE are used; both approaches have their specific advantages and disadvantages. Depending on patient-specific factors and the surgeon’s experience and estimates, both IBR procedures are also possible in combination with PMRT. When using a TE/implant approach, completing skin stretching by adequately filling the expander before PMRT may be favorable. This approach is particularly practical when adjuvant chemotherapy is planned but may lead to postponement of radiotherapy when primary systemic therapy is given. According to the latest data, moderate hypofractionation also appears to be safe in the context of the IBR approach. It is important to have a closely coordinated interdisciplinary approach and to fully inform patients about the increased rate of potential side effects.

Abstract BACKGROUND Primary CNS lymphoma (PCNSL) is a rare but deadly disease. Treatment primarily comprises high-dose chemotherapy involving methotrexate. Regarding the use of radiotherapy (RT) as consolidation or primary treatment, or in the setting of recurrent disease, comprehensive multicentric data are sparse. Particularly, comparative data concerning different RT concepts like focal- (FRT) or whole brain radiotherapy (WBRT) are missing. MATERIAL AND METHODS Within a multi-center registry of the German Society for Radiation Oncology − Working Group Neuro-Radio-Oncology (DEGRO AG-NRO), patients that were treated between 2007-2023 for PCNSL and received RT at any time during their disease were included. Among these, a comparative survival analysis was performed on patients who were treated with FRT compared to those who were treated with WBRT. RESULTS 153 patients from 8 German large tertiary centres were included. The median age at the time of diagnosis was 66.5 years (range: 27-89 years), median ECOG was 2 (range: 0-4). 18% (n=27) of patients received primary RT, 33% (n=49) consolidation treatment after initial chemotherapy and 49% (n=79) were treated with RT at recurrent disease. WBRT was most frequently used (primary/consolidating treatment: n=76, 77.6%; recurrent disease: n=62, 83.3%), FRT was less frequently applied (primary/consolidating treatment: n=17, 22.3%; recurrent disease: n=11, 14.9%). Median overall survival (OS) in the entire cohort was 24.1 months (95% CI 14.7-33.4 months), and median survival from the start of radiotherapy was 7.2 months (95% CI 4.5-10.00 months). In patients treated with FRT, the median OS was 67.6 months (95% CI 35.7-99.6 months) compared to patients with WBRT (median OS: 20.1 months, 95% CI 10.5-29.8 months; p=0.016). Likewise, survival from the start of RT was longer after FRT (median: 44.0 months, 95% CI 5.9-82.1 months) than with WBRT (median: 5.8 months, 95% CI 3.2-8.4 months); p=0.017. Differences in survival from RT were discernible in the setting of recurrent disease (FRT: median 8.2 months, 95% CI 0.0-30 months; WBRT: median 3.6 months, 95% CI 1.5-5.6 months; p=0.045) and in primary treatments (FRT: median 44.0 months, 95% CI 0.0-97.2 months; WBRT: median 11.5 months, 95% CI 0.0-33.9 months; p=0.19). In the Cox multiple regression analysis, non-DLBCL histology (HR=0.345; 95% CI, 0.162-0.733; p<0.01) and FRT (HR=0.518; 95%CI, 0.270-0.993; p<0.05) were associated with an improved OS. Size of target volume appeared not associated with OS (Cox regression, p=0.43). CONCLUSION RT for treating PCNSL is mainly used in elderly and frail patients. Treatment concepts are heterogeneous. The use of FRT compared to WBRT during the course of the disease appeared associated with longer survival.

Abstract BACKGROUND This trial aimed to investigate whether re-irradiation based on (O-(2-Fluoroethyl)-L-tyrosine, FET)-positron emission tomography (PET) leads to an improvement in progression-free survival (PFS) in patients with recurrent glioblastoma (rGBM), compared to a target volume delineation based on contrast-enhanced T1-weighted MRI (T1Gd-MRI). MATERIAL AND METHODS GLIAA was a prospective, multicenter, randomized clinical trial (NOA 10/ARO 2013-1, DKTK-a., NCT01252459). Patients with rGBM of 1-6 cm were randomized 1:1 at 14 centers in Germany between a FET-PET- and a T1Gd-MRI-based target volume delineation. The RT was performed with 3 Gy/d, 5x/week, to a total dose of 39 Gy. All patients had been previously irradiated with 59.4-60Gy at least 6 months before study treatment and had a histologically confirmed rGBM with a diameter of 1 - 6 cm on both FET-PET and T1Gd-MRI. The primary end point was PFS. Secondary end points included overall survival (OS), locally controlled survival, assessment of delineated volumes, topography of progression, rate of radiation necrosis after re-irradiation, and safety of FET-application in PET imaging. RESULTS Between November 2013 and September 2021, 200 patients were randomized between FET-PET-based (n=100) and GdT1-MRI-based (n=100) target volume delineation. A total of n=98 and n=97 patients, respectively, were treated per protocol. Median PFS was 4.0 months (95% confidence interval [CI] 3.7-5.2) in the FET-PET arm and 4.9 months (95% CI 3.7-6.0) in the GdT1-MRI arm (one-sided stratified log-rank test p=0.98; adjusted HR for the experimental versus the control arm 1.14 [95% CI 0.85-1.52], p=0.39;). Median OS was 9.4 months (95% CI 7.8-11.1) in the FET-PET arm and 9.0 months (95% CI 7.6-10.5) in the GdT1-MRI arm (HR 1.01 [95% CI 0.75-1.37], p=0.92). Median LCS was 6.3 months (95% CI 5.1-7.2) in the FET-PET arm and 6.8 months (95% CI 6.2-7.3) in the GdT1-MRI arm (HR 1.20 [95% CI 0.88-1.62], p=0.25). At 12 months, the local control rate was 22% in the FET-PET arm (95% CI 14%-31%) and 20% in the GdT1-MRI arm (95% CI 12%-29%). In the PET arm, 45.0% of recurrences were in field, 28.3% out of field, and 21.7% marginal. In the MRI arm, 47.4% relapsed in field, 31.6% out of field, and 14.0% marginal. 25.5% of patients in the FET-PET arm and 21.6% in the GdT1-MRI arm had a documented radiation necrosis. There were no adverse events related to the application of the FET tracer. CONCLUSION This is the first randomized trial to investigate the relevance of FET-PET in the irradiation treatment planning of rGBM. There was no survival benefit identified for patients treated with FET-PET- versus GdT1-MRI-based re-irradiation. Both imaging modalities led to similar outcomes and can be therefore used for radiation treatment planning for rGBM. The FET-PET investigation and the re-irradiation were well-tolerated, supporting the safety of this treatment.

Radiodermatits is commonly observed during radiotherapy in post-surgery breast cancer patients, reducing their quality of life. To date, neither the inter-indivdual differences nor the pathomechanism are sufficiently understood. To investigate the role of the skin microbiome in the development of severe radiodermatitis, we conducted a longitudinal pilot study with 20 female breast cancer patients undergoing radiotherapy. At 9 visits, the skin physiology was assessed and skin swabs for next-generation sequencing of the V1-V3 region of the 16S rRNA and quantitative PCR on both the affected and non-affected bodysides were taken on a weekly basis before, during and after radiotherapy (360 samples). All patients developed mild (n=7), moderate (n=9) or severe (n=4) radiodermatitis. Strikingly, low (<5%) relative abundance of skin commensals (Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes) before radiotherapy was significantly predictive for the development of severe radiodermatitis with an accuracy of 100%. Instead, severe patients were characterized by higher Corynebacteriaceae relative abundance which was correlated with increased skin pH. Interestingly, severe patients only showed an increase in total bacterial load before the onset of severe radiodermatitis symptoms estimated by qPCR of the 16S rRNA copies in contrast to stable bacterial load in mild and moderate radiodermatitis patients. Summarizing, we observed a link between low commensals relative abundance before radiotherapy with an increase in total bacterial load in the early phase of radiation leading to severe radiodermatitis symptoms in the late phase of radiation. Our results hint towards a direct influence of microbes in the pathogenesis of severe radiodermatitis.

BACKGROUND:Rectal cancer treatment has improved considerably due to the introduction of total meso-rectal excision, radio-chemotherapy, and high-resolution imaging. The aim of this observational cohort study was to quantify the effectiveness of these advances using high-quality data from a representative cohort of patients. METHODS:20 281 non-metastasized cases retrieved from the Munich Cancer Registry database were divided into three time periods corresponding to before (1988-1997), partial (1998-2007), and full implementation (2008-2019) of clinical advances. Early-onset (<50 yrs.), middle-aged, elderly patient subgroups (> 70 yrs.) were compared. The overall effectiveness of evidence-based guideline adherence was also examined. RESULTS:Median survival improved by 1.5 yrs. from the first to the last time period. Relative survival increased from 74.9% (5-yr 95%CI[73.3 - 76.6]) to 79.2% (95%CI[77.8 - 80.5]). The incidence of locoregional recurrences was reduced dramatically by more than half (5-yr 17.7% (95%CI[16.5 - 18.8]); 6.7% (95%CI[6.1 - 7.3])). Gains in 5-yr relative survival were limited to early-onset and middle-aged patients with no significant improvement seen in elderly patients (Female 68.6% [63.9 - 73.3] to 67.6% [64.0 - 71.2]; Male 71.7% [65.9 - 77.4] to 74.0% [70.8 - 77.2]). CONCLUSIONS:Real-world evidence suggests that recent treatment advances have lead to an increase in prognosis for rectal cancer patients. However, more effort should be made to improve the implementation of new developments in elderly patients. Especially considering, that these cases represent a growing majority of diagnosed patients.

Abstract Background Given the young age of patients with CNS WHO grade 2 and 3 oligodendrogliomas and the relevant risk of neurocognitive, functional, and quality-of-life impairment with the current aggressive standard of care treatment, chemoradiation with PCV, of the tumour located in the brain optimizing care is the major challenge. Methods NOA-18 aims at improving qualified overall survival (qOS) for adult patients with CNS WHO grade 2 and 3 oligodendrogliomas by randomizing between standard chemoradiation with up to six six-weekly cycles with PCV and six six-weekly cycles with lomustine and temozolomide (CETEG) (n = 182 patients per group accrued over 4 years) thereby delaying radiotherapy and adding the chemoradiotherapy concept at progression after initial radiation-free chemotherapy, allowing for effective salvage treatment and delaying potentially deleterious side effects. QOS represents a new concept and is defined as OS without functional and/or cognitive and/or quality of life deterioration regardless of whether tumour progression or toxicity is the main cause. The primary objective is to show superiority of an initial CETEG treatment followed by partial brain radiotherapy (RT) plus PCV (RT-PCV) at progression over partial brain radiotherapy (RT) followed by procarbazine, lomustine, and vincristine (PCV) chemotherapy (RT-PCV) and best investigators choice (BIC) at progression for sustained qOS. An event concerning a sustained qOS is then defined as a functional and/or cognitive and/or quality of life deterioration after completion of primary therapy on two consecutive study visits with an interval of 3 months, tolerating a deviation of at most 1 month. Assessments are done with a 3-monthly MRI, assessment of the NANO scale, HRQoL, and KPS, and annual cognitive testing. Secondary objectives are evaluation and comparison of the two groups regarding secondary endpoints (short-term qOS, PFS, OS, complete and partial response rate). The trial is planned to be conducted at a minimum of 18 NOA study sites in Germany. Discussion qOS represents a new concept. The present NOA trial aims at showing the superiority of CETEG plus RT-PCV over RT-PCV plus BIC as determined at the level of OS without sustained functional deterioration for all patients with oligodendroglioma diagnosed according to the most recent WHO classification. Trial registration Clinicaltrials.govNCT05331521. EudraCT 2018–005027-16.

Preoperative stereotactic radiosurgery (SRS) of brain metastases may achieve similar local control and better leptomeningeal control rates than postoperative fractionated stereotactic radiotherapy (FSRT) in patients treated with elective metastasectomy. To plan a multicentre trial of preoperative SRS compared with postoperative FSRT, a survey of experts was conducted to determine current practice. A survey with 15 questions was distributed to the DEGRO Radiosurgery and Stereotactic Radiotherapy Working Group. Participants were asked under what circumstances they offered SRS, FSRT, partial and/or whole brain radiotherapy before or after resection of a brain metastasis, as well as the feasibility of preoperative stereotactic radiosurgery and neurosurgical resection within 6 days. Of 25 participants from 24 centres, 22 completed 100% of the questions. 24 respondents were radiation oncologists and 1 was a neurosurgeon. All 24 centres have one or more dedicated radiosurgery platform and all offer postoperative FSRT. Preoperative SRS is offered by 4/24 (16.7%) centres, and 9/24 (37.5%) sometimes recommend single-fraction postoperative SRS. Partial brain irradiation is offered by 8/24 (33.3%) centres and 12/24 (50%) occasionally recommend whole-brain irradiation. Two centres are participating in clinical trials of preoperative SRS. SRS techniques and fractionation varied between centres. All responding centres currently offer postoperative FSRT after brain metastasectomy. Approximately one third offer single-fraction postoperative SRS and four already perform preoperative SRS. With regard to potential co-investigators, 18 were identified for the PREOP‑2 multicentre trial, which will randomise between preoperative SRS and postoperative FSRT.

Human papillomavirus (HPV)-driven head and neck squamous cell carcinomas (HNSCC) generally have a more favourable prognosis. We hypothesized that HPV-associated HNSCC may be identified by an miRNA-signature according to their specific molecular pathogenesis, and be characterized by a unique transcriptome compared to HPV-negative HNSCC. We performed miRNA expression profiling of two p16/HPV DNA characterized HNSCC cohorts of patients treated by adjuvant radio(chemo)therapy (multicentre DKTK-ROG n = 128, single-centre LMU-KKG n = 101). A linear model predicting HPV status built in DKTK-ROG using lasso-regression was tested in LMU-KKG. LMU-KKG tumours (n = 30) were transcriptome profiled for differential gene expression and miRNA-integration. A 24-miRNA signature predicted HPV-status with 94.53% accuracy (AUC: 0.99) in DKTK-ROG, and 86.14% (AUC: 0.86) in LMU-KKG. The prognostic values of 24-miRNA- and p16/HPV DNA status were comparable. Combining p16/HPV DNA and 24-miRNA status allowed patient sub-stratification and identification of an HPV-associated patient subgroup with impaired overall survival. HPV-positive tumours showed downregulated MAPK, Estrogen, EGFR, TGFbeta, WNT signaling activity. miRNA-mRNA integration revealed HPV-specific signaling pathway regulation, including PD−L1 expression/PD−1 checkpoint pathway in cancer in HPV-associated HNSCC. Integration of clinically established p16/HPV DNA with 24-miRNA signature status improved clinically relevant risk stratification, which might be considered for future clinical decision-making with respect to treatment de-escalation in HPV-associated HNSCC.