Clinically Significant Dermatitis During Adjuvant Radiotherapy for Invasive Breast Cancer.

BACKGROUND/AIM: Patients with breast cancer receiving adjuvant radiotherapy may experience grade ≥2 dermatitis. In the Interreg-project HeAT, a mobile application (app) reminding patients to perform skin care will be prospectively tested with the goal of decreasing clinically significant radiation dermatitis. This study aimed to identify the prevalence of grade ≥2 dermatitis and risk factors, required for designing the prospective trial. PATIENTS AND METHODS: In a retrospective study of 327 patients with breast cancer irradiated during 2022-2023, the prevalence of grade ≥2 dermatitis and 23 potential risk factors were investigated. RESULTS: The prevalence of grade ≥2 dermatitis was 31.2%. On multivariate analysis, it was significantly associated with chronic inflammatory disease (p=0.001), significant cardiovascular disease (p<0.001), smoking history >10 pack years (p<0.001), advanced T-stage (p=0.017), normo-fractionation (p<0.001), and radiation boost (p<0.001). CONCLUSION: The prevalence of grade ≥2 dermatitis and independent risk factors during adjuvant radiotherapy for invasive breast cancer were identified that contribute to improved patient care and the design of a prospective trial.

Robustness of cancer microbiome signals over a broad range of methodological variation.

In 2020, we identified cancer-specific microbial signals in The Cancer Genome Atlas (TCGA) [1]. Multiple peer-reviewed papers independently verified or extended our findings [2-12]. Given this impact, we carefully considered concerns by Gihawi et al. [13] that batch correction and database contamination with host sequences artificially created the appearance of cancer type-specific microbiomes. (1) We tested batch correction by comparing raw and Voom-SNM-corrected data per-batch, finding predictive equivalence and significantly similar features. We found consistent results with a modern microbiome-specific method (ConQuR [14]), and when restricting to taxa found in an independent, highly-decontaminated cohort. (2) Using Conterminator [15], we found low levels of human contamination in our original databases (~1% of genomes). We demonstrated that the increased detection of human reads in Gihawi et al. [13] was due to using a newer human genome reference. (3) We developed Exhaustive, a method twice as sensitive as Conterminator, to clean RefSeq. We comprehensively host-deplete TCGA with many human (pan)genome references. We repeated all analyses with this and the Gihawi et al. [13] pipeline, and found cancer type-specific microbiomes. These extensive re-analyses and updated methods validate our original conclusion that cancer type-specific microbial signatures exist in TCGA, and show they are robust to methodology.

Distress Scores in Elderly Cancer Patients During Radiotherapy.

BACKGROUND/AIM: When assigned to radiotherapy (RT), elderly patients may experience distress. We investigated distress during RT and potential risk factors in these patients. PATIENTS AND METHODS: Six-hundred-and-nineteen patients completed pre-RT and post-RT distress thermometers. Seven characteristics were investigated including age, sex, Karnofsky performance score (KPS), grouped KPS, tumor type, intent of RT, and previous RT. Additional analyses were performed in 358 patients with pre-RT scores ≤5. RESULTS: Mean change of distress was -0.5 (±2.7) points and associated with KPS (p=0.005) and grouped KPS (p<0.001). Male sex (p=0.035), KPS 90-100 (p=0.001), and curative intent (p=0.037) were associated with increased distress on univariable analyses, and KPS 90-100 (odds ratio=1.92, p=0.004) on multivariable analysis. In patients with baseline scores ≤5, mean change was +0.5 (±2.5) points and associated with KPS (p=0.040) and grouped KPS (p=0.025). CONCLUSION: Psychological assistance should be considered for all patients including those with baseline scores ≤5 and KPS 90-100. Patients with risk factors for increased distress would especially benefit.

Survey in radiation oncology departments in Germany, Austria, and Switzerland: state of digitalization by 2023.

PURPOSE: The aim of this work was to assess the current state of digitalization in radiation oncology departments in Germany, Austria, and Switzerland. METHODS: A comprehensive survey was conducted in a digital format, consisting of 53 questions that covered various aspects of digitalization including patient workflow, departmental organization, radiotherapy planning, and employee-related aspects. RESULTS: Overall, 120 forms were eligible for evaluation. Participants were mainly physicians or medical physicists responsible for digitalization aspects in their departments. Nearly 70% of the institutions used electronic patient records, with 50% being completely paperless. However, the use of smartphone apps for electronic patient reported outcomes (ePROMs) and digital health applications (DIGA) was limited (9% and 4.9%, respectively). In total, 70.8% of the radio-oncology departments had interfaces with diagnostic departments, and 36% had digital interchanges with other clinics. Communication with external partners was realized mainly through fax (72%), e­mails (55%), postal letters (63%), or other digital exchange formats (28%). Almost half of the institutions (49%) had dedicated IT staff for their operations. CONCLUSION: To the best of our knowledge, this survey is the first of its kind conducted in German-speaking radiation oncology departments within the medical field. The findings suggest that there is a varied level of digitalization implementation within these departments, with certain areas exhibiting lower rates of digitalization that could benefit from targeted improvement initiatives.

Exploring the Frequency and Distribution of Ecological Non-monotonicity in Associations among Ecosystem Constituents.

Complex links between biotic and abiotic constituents are fundamental for the functioning of ecosystems. Although non-monotonic interactions and associations are known to increase the stability, diversity, and productivity of ecosystems, they are frequently ignored by community-level standard statistical approaches. Using the copula-based dependence measure qad, capable of quantifying the directed and asymmetric dependence between variables for all forms of (functional) relationships, we determined the proportion of non-monotonic associations between different constituents of an ecosystem (plants, bacteria, fungi, and environmental parameters). Here, we show that up to 59% of all statistically significant associations are non-monotonic. Further, we show that pairwise associations between plants, bacteria, fungi, and environmental parameters are specifically characterized by their strength and degree of monotonicity, for example, microbe-microbe associations are on average stronger than and differ in degree of non-monotonicity from plant-microbe associations. Considering directed and non-monotonic associations, we extended the concept of ecosystem coupling providing more complete insights into the internal order of ecosystems. Our results emphasize the importance of ecological non-monotonicity in characterizing and understanding ecosystem patterns and processes. Supplementary Information: The online version contains supplementary material available at 10.1007/s10021-023-00867-9.

Development of Distress During a Radiotherapy Course in Patients Irradiated for Breast Cancer.

BACKGROUND/AIM: Breast cancer patients receiving radiation therapy (RT) may experience considerable distress. We investigated the course of distress during an RT-course for breast cancer. PATIENTS AND METHODS: Three-hundred-and-thirty breast cancer patients completed Distress Thermometers before and directly after RT. Distress was evaluated in the entire cohort and different groups of age, sex, Karnofsky performance score (KPS), intent of RT, and previous RT. RESULTS: Mean change of distress scores was - 0.4 points, which was significantly associated with KPS. Decrease of distress was more pronounced in patients with KPS ≤80 or age <64 years. Deterioration (yes vs. no) was non-significantly associated with no previous RT. In patients with pre-RT distress scores ≤5 points, mean score increased by +0.5 points; no significant associations between characteristics and investigated endpoints were found. CONCLUSION: Psychological assistance should be offered to all patients irradiated for breast cancer, particularly to those with risk factors, regardless of the pre-RT distress score.

Whole-breast Radiotherapy With Boost for Node-negative Breast Cancer: Conventional vs. Hypo-fractionation.

BACKGROUND/AIM: Many breast cancer patients receive adjuvant radiotherapy. Tumor bed boost may reduce risk of local failure in high risk patients. We compared hypofractionated whole-breast irradiation (WBI) plus boost (HF+boost) and conventionally fractionated WBI plus boost (CF+boost). PATIENTS AND METHODS: One-hundred-and-twenty-eight patients receiving HF-WBI (40 Gy in 15 fractions) plus boost (group A) were matched to 127 patients receiving CF-WBI (50.4 Gy in 28 fractions) plus boost (group B), utilizing 10 characteristics. RESULTS: Grade ≥2 dermatitis rates were 16.4% in group A vs. 44.1% in group B (p<0.0001), and grade ≥2 pneumonitis rates were 1.6% vs. 2.4% (p=0.68). Four-year rates of local control, metastases-free survival, and overall survival were 100% vs. 99% (p=0.81), 98% vs. 100% (p=0.29), and 98% vs. 100% (p=0.17), respectively. CONCLUSION: HF+boost was associated with significantly less grade ≥2 dermatitis with similar disease control and survival.

Simultaneous vs. Sequential Boost for Adjuvant Breast Radiotherapy.

BACKGROUND/AIM: During the last 10-15 years, alternative regimens for adjuvant radiotherapy (RT) of breast cancer have become more popular, including simultaneous integrated (SIB) instead of sequential boosts (SEB). We present long-term outcomes after conventional fractionation (CF) plus SIB vs. CF+SEB. PATIENTS AND METHODS: Forty-eight patients receiving CF+SIB (treatment time=5.5 weeks) were matched to 72 patients (control group) receiving CF+SEB (6.5 weeks) considering twelve characteristics. Both groups were compared for radiation dermatitis, pneumonitis, local control (LC), metastases-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Rates of grade ≥2 dermatitis were 35.4% (CF+SIB) and 45.8% (CF+SEB), respectively (p=0.26), and rates of grade ≥2 pneumonitis 0% and 4.2%, respectively (p=0.27). Six-year LC, MFS, CSS, and OS rates were 100% vs. 93% (p=0.11), 97% vs. 100% (p=0.29), 100% vs. 100% (p=1.00), and 98% vs. 100% (p=0.23), respectively. CONCLUSION: CF+SIB was similar to CF+SEB in terms of toxicities and outcomes but reduces total treatment time by one week.

Distress Scores During Radiotherapy for Lung Cancer: Course and Prognostic Factors.

Background/Aim: Cancer treatment can lead to significant distress. We investigated the course of distress during radiotherapy (RT) for lung cancer. Patients and Methods: Data of 159 patients receiving RT for lung cancer were investigated for change of distress scores during RT. Five characteristics were analyzed including age, sex, Karnofsky performance score, intent of RT, and receipt of previous RT. Additional analyses were performed in patients with pre-RT scores ≤5 points. Results: Mean pre-RT and post-RT distress scores were 5.5 (±2.6) and 4.7 (±2.6), respectively. No characteristic was significantly associated with mean change or increase of distress. In patients with pre-RT scores ≤5 points, non-significantly higher rates of increased distress were found for age ≤64 years, female sex, and Karnofsky performance score 90-100. Conclusion: Distress is reduced during a course of RT for lung cancer. This may reflect a reduction in anticipatory distress after first-hand experience.

Comparison of Distress Scores Before and After Radiotherapy for Prostate Cancer.

BACKGROUND/AIM: Prostate cancer patients undergoing radiotherapy (RT) may experience distress. This study evaluated the course of distress during RT. PATIENTS AND METHODS: Four distress characteristics were analyzed for change of distress in 136 patients irradiated for prostate cancer, including age, Karnofsky performance score, intent of RT, and previous RT. RESULTS: Mean distress scores were 4.3 (±2.9) at baseline and 4.2 (±2.7) at the end of RT. Associations with increased distress were found for KPS >80 (p<0.001) and curative intent RT (p=0.072). When evaluating increased distress as binary variable (yes vs. no), KPS >80 was significant on univariable (p<0.001) and multivariable (p=0.016) analyses. In patients with baseline scores ≤5 points, KPS >80 was associated with mean change of distress (p=0.009) and increased distress (p=0.029). CONCLUSION: Many patients receiving RT for prostate cancer do not experience increased distress during their treatment course. Patients at higher risk of increased distress may require early psychological assistance.

Final Results of a Study Evaluating the Course of Distress Scores During Radiotherapy for Malignant Diseases.

BACKGROUND/AIM: Patients who receive radiotherapy (RT) may experience significant distress. This study investigated distress scores during RT for a variety of malignancies. PATIENTS AND METHODS: Distress thermometers (scores of 0-10 points) were completed by 927 patients at baseline and end of RT. Six characteristics were evaluated for changes of distress scores including age, sex, Karnofsky performance score (KPS), tumor type, intent of treatment, and previous RT. RESULTS: Mean distress scores were 4.9 (±2.7) at baseline and 4.6 (±2.7) at the end of RT; mean change was -0.3 (±2.8) points. On univariable analysis, increased distress (≥2 points) was significantly associated with KPS 90-100 (p<0.001) and curative intent (p=0.040). Trends were found for age ≤64 years (p=0.062), head-and-neck cancer (p=0.076), and no prior RT (p=0.055). In patients with baseline scores ≤5 points, deterioration rates were 30-47%. CONCLUSION: Psychological support should be offered to all patients undergoing RT. This would benefit particularly patients with risk factors for increased distress.

Development of Distress During a Radiotherapy Course for Head-and-neck Cancer.

BACKGROUND/AIM: Radiotherapy (RT) is a standard treatment for head-and-neck cancer, which can be associated with patient distress. This study provides data investigating distress during head-and-neck RT. PATIENTS AND METHODS: Fifty-six patients completed the Distress Thermometer before and on the last day of their RT-course. Mean changes of distress scores and increase of distress were evaluated. Age, sex, Karnofsky performance score (KPS), tumor type, intent of RT, and previous RT were analyzed for associations with course of distress. RESULTS: Mean pre-RT and post-RT distress scores were 5.1 (±2.6) and 5.0 (±2.7) points, respectively (mean change: ±0.0 points). Mean change of distress scores was significantly associated with age (p=0.042) and KPS (p<0.001). On multivariable analysis, increased distress (by ≥2 points) was associated with KPS 90-100 (p=0.011) and palliative intent of RT (p=0.036). CONCLUSION: Mean pre-RT and post-RT distress scores were almost identical. Patients with risk factors for increased distress during their RT-course should be offered immediate psychological support.

Treatment Outcomes After Higher-dose Fractionated Stereotactic Radiotherapy (FSRT) Alone for 1-4 Brain Metastases.

BACKGROUND/AIM: Fractionated stereotactic radiotherapy (FSRT) is increasingly used for brain metastases. We investigated higher-dose FSRT with biologically effective doses (BED) of 49.6-66.7 Gy12 Patients and Methods: Eleven characteristics were evaluated for local control (LC), overall survival (OS), and freedom from radiation necrosis (RN) in 69 patients with 1-4 brain metastases. Fifty-seven patients (83%) had extracranial metastases, 23 (33%) Karnofsky performance scores (KPS) ≤70, and 21 (30%) brain metastases ≥21 mm. RESULTS: At 1 and 2 years, LC-rates were 81% and 63%, OS-rates 66% and 43%, and freedom from RN-rates 98% and 87%, respectively. Median time to local progression was 35 months, median survival 19 months. KPS ≥90 was associated with better OS (p=0.048). BED of 49.6-57 Gy12 (vs. 63-66.7 Gy12) was associated with higher rates of freedom from RN (p=0.046), not with LC (p=0.78) or OS (p=0.55). CONCLUSION: Higher-dose FSRT appears feasible and effective in patients with 1-4 brain metastases. BED 63-66.7 Gy12 may not improve LC and OS but may increase RN risk.

Radiation Necrosis Following Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy with High Biologically Effective Doses for Large Brain Metastases.

In Radiation Therapy Oncology Group 90-05, the maximum tolerated dose of single-fraction radiosurgery (SRS) for brain metastases of 21-30 mm was 18 Gy (biologically effective dose (BED) 45 Gy12). Since the patients in this study received prior brain irradiation, tolerable BED may be >45 Gy12 for de novo lesions. We investigated SRS and fractionated stereotactic radiotherapy (FSRT) with a higher BED for radiotherapy-naive lesions. Patients receiving SRS (19-20 Gy) and patients treated with FSRT (30-48 Gy in 3-12 fractions) with BED > 49 Gy12 for up to 4 brain metastases were compared for grade ≥ 2 radiation necrosis (RN). In the entire cohort (169 patients with 218 lesions), 1-year and 2-year RN rates were 8% after SRS vs. 2% and 13% after FSRT (p = 0.73) in per-patient analyses, and 7% after SRS vs. 7% and 10% after FSRT (p = 0.59) in per-lesion analyses. For lesions ≤ 20 mm (137 patients with 185 lesions), the RN rates were 4% (SRS) vs. 0% and 15%, respectively, (FSRT) (p = 0.60) in per-patient analyses, and 3% (SRS) vs. 0% and 11%, respectively, (FSRT) (p = 0.80) in per-lesion analyses. For lesions > 20 mm (32 patients with 33 lesions), the RN rates were 50% (SRS) vs. 9% (FSRT) (p = 0.012) in both per-patient and per-lesion analyses. In the SRS group, a lesion size > 20 mm was significantly associated with RN; in the FSRT group, lesion size had no impact on RN. Given the limitations of this study, FSRT with BED > 49 Gy12 was associated with low RN risk and may be safer than SRS for brain metastases > 20 mm.

Sequence-structure-function relationships in the microbial protein universe.

For the past half-century, structural biologists relied on the notion that similar protein sequences give rise to similar structures and functions. While this assumption has driven research to explore certain parts of the protein universe, it disregards spaces that don't rely on this assumption. Here we explore areas of the protein universe where similar protein functions can be achieved by different sequences and different structures. We predict ~200,000 structures for diverse protein sequences from 1,003 representative genomes across the microbial tree of life and annotate them functionally on a per-residue basis. Structure prediction is accomplished using the World Community Grid, a large-scale citizen science initiative. The resulting database of structural models is complementary to the AlphaFold database, with regards to domains of life as well as sequence diversity and sequence length. We identify 148 novel folds and describe examples where we map specific functions to structural motifs. We also show that the structural space is continuous and largely saturated, highlighting the need for a shift in focus across all branches of biology, from obtaining structures to putting them into context and from sequence-based to sequence-structure-function based meta-omics analyses.

Short Communication: Results of a Consensus Conference on Radiotherapy for Brain and Bone Metastases Within the Interreg-Project TreaT.

BACKGROUND/AIM: Differences between radiotherapy for metastases in Northern Germany and Southern Denmark were previously identified, which led to a consensus conference. PATIENTS AND METHODS: A consensus conference was held between three centers to harmonize radiotherapy regimens for bone and brain metastases. RESULTS: Centers agreed on 1×8 Gy for painful bone metastases in patients with poor or intermediate survival prognoses and 10×3 Gy for favorable-prognosis patients. For complicated bone metastases, 5-6×4 Gy was preferred for poor-prognosis, 10×3 Gy for intermediate-prognosis, and longer-course radiotherapy for favorable-prognosis patients. For ≥5 brain metastases, centers agreed on whole-brain irradiation (WBI) with 5×4 Gy in poor-prognosis and longer-course regimens in other patients. For single brain lesions and patients with 2-4 lesions and intermediate/favorable prognoses, fractionated stereotactic radiotherapy (FSRT) or radiosurgery were recommended. No consensus was reached for 2-4 lesions in poor-prognosis patients; two centers preferred FSRT, one center WBI. Preferred radiotherapy regimens were similar for different age groups including elderly and very elderly patients, but age-specific survival scores were recommended. CONCLUSION: The consensus conference was successful, since harmonization of radiotherapy regimens was achieved for 32 of 33 possible situations.

Mobile applications in radiation oncology-current choices and future potentials.

PURPOSE: To review existing scientific literature on mobile applications (apps) in the field of radiation oncology and to evaluate characteristics of commercially available apps across different platforms. METHODS: A systematic review of the literature for publications presenting apps in the field of radiation oncology was carried out using the PubMed database, Cochrane library, Google Scholar, and annual meetings of major radiation oncology societies. Additionally, the two major marketplaces for apps, App Store and Play Store, were searched for available radiation oncology apps for patients and health care professionals (HCP). RESULTS: A total of 38 original publications which met the inclusion criteria were identified. Within those publications, 32 apps were developed for patients and 6 for HCP. The vast majority of patient apps focused on documenting electronic patient-reported outcomes (ePROs). In the two major marketplaces, 26 apps were found, mainly supporting HCP with dose calculations. CONCLUSION: Apps used in (and for) scientific research in radiation oncology are rarely available for patients and HCP in common marketplaces.

Early Identification of Pneumonitis in Patients Irradiated for Lung Cancer-Final Results of the PARALUC Trial.

Radiotherapy of lung cancer may cause pneumonitis that generally occurs weeks or months following therapy and can be missed. This prospective trial aimed to pave the way for a mobile application (app) allowing early diagnosis of pneumonitis. The primary goal was the identification of the optimal cut-off of a score to detect pneumonitis of grade ≥2 after radiotherapy for lung cancer. Based on the severity of symptoms (cough, dyspnea, fever), scoring points were 0−9. Receiver operating characteristic (ROC)-curves were used to describe the sensitivity and specificity. The area under the ROC-curve (AUC) was calculated to judge the accuracy of the score, Youden-index was employed to define the optimal cut-off. Until trial termination, 57 of 98 patients were included. Eight of 42 patients evaluable for the primary endpoint (presence or absence of radiation pneumonitis) experienced pneumonitis. AUC was 0.987 (0.961−1.000). The highest sensitivity was achieved with 0−4 points (100%), followed by 5 points (87.5%), highest specificity with 5−6 points (100%). The highest Youden-index was found for 5 points (87.5%). The rate of patient satisfaction with the symptom-based scoring system was 93.5%. A cut-off of 5 points was identified as optimal to differentiate between pneumonitis and no pneumonitis. Moreover, pneumonitis was significantly associated with an increase of ≥3 points from baseline (p < 0.0001). The scoring system provided excellent accuracy and high patient satisfaction. Important foundations for the development of a mobile application were laid.