DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.

PURPOSE: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis. MATERIALS AND METHODS: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation). CONCLUSION AND RECOMMENDATIONS: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.

An easy way to determine bone mineral density and predict pelvic insufficiency fractures in patients treated with radiotherapy for cervical cancer.

PURPOSE: The aim of this study was to investigate whether bone mineral density (BMD) as measured in planning computed tomographies (CTs) by a new method is a risk factor for pelvic insufficiency fractures (PIF) after radio(chemo)therapy (R(C)T) for cervical cancer. METHODS: 62 patients with cervical cancer who received definitive or adjuvant radio(chemo)therapy between 2013 and 2017 were reviewed. The PIF were detected on follow-up magntic resonance imaging (MRI). The MRI of the PIF patients was registered to the planning CT and the PIF contoured. On the contralateral side of the fracture, a mirrored structure of the fracture was generated (mPIF). For the whole sacral bone, three lumbar vertebrae, the first and second sacral vertebrae, and the PIF, we analyzed the BMD (mg/cm3), V50Gy, Dmean, and Dmax. RESULTS: Out of 62 patients, 6 (9.7%) had a fracture. Two out of the 6 patients had a bilateral fracture with only one of them being symptomatic. PIF patients showed a significantly lower BMD in the sacral and the lumbar vertebrae (p < 0.05). The BMD of the contoured PIF, however, when comparing to the mPIF, did not reach significance (p < 0.49). The difference of the V50Gy of the sacrum in the PIF group compared to the other (OTH) patients, i.e. those without PIF, did not reach significance. CONCLUSION: The dose does not seem to have a relevant impact on the incidence of PIF in our patients. One of the predisposing factors for developing PIF after radiotherapy seems to be the low BMD. We presented an easy method to assess the BMD in planning CTs.

Dosimetric comparison of organs at risk using different contouring guidelines for definition of the clinical target volume in anal cancer.

BACKGROUND: There are different contouring guidelines for definition of the clinical target volume (CTV) for intensity-modulated radiation therapy (IMRT) of anal cancer (AC). We conducted a planning comparison study to evaluate and compare the dose to relevant organs at risk (OARs) while using different CTV definitions. METHODS: Twelve patients with a primary diagnosis of anal cancer, who were treated with primary chemoradiation (CRT), were selected. We generated four guideline-specific CTVs and subsequently planned target volumes (PTVs) on the planning CT scan of each patient. An IMRT plan for volumetric arc therapy (VMAT) was set up for each PTV. Dose parameters of the planned target volume (PTV) and OARs were evaluated and compared, too. RESULTS: The mean volume of the four PTVs ranged from 2138 cc to 2433 cc. The target volumes contoured by the authors based on the recommendations of each group were similar in the pelvis, while they differed significantly in the inguinal region. There were no significant differences between the four target volumes with regard to the dose parameters of the cranially located OARs. Conversely, some dose parameters concerning the genitals and the skin varied significantly among the different guidelines. CONCLUSION: The four contouring guidelines differ significantly concerning the inguinal region. In order to avoid inguinal recurrence and to protect relevant OARs, further investigations are needed to generate uniform standards for definition of the elective clinical target volume in the inguinal region.

Effect of hypofractionation on the incidental axilla dose during tangential field radiotherapy in breast cancer.

OBJECTIVE: Tangential field irradiation in breast cancer potentially treats residual tumor cells in the axilla after sentinel lymph node biopsy (SLNB). In recent years, hypofractionated radiotherapy has gained importance and currently represents the recommended standard in adjuvant breast cancer treatment for many patients. So far, the impact of hypofractionation on the effect of incidental lymph node irradiation has not be addressed. MATERIALS AND METHODS: Biological effective dose (BED) and tumor control probability (TCP) were estimated for four different hypofractionated radiation schemes (42.50 Gy in 16 fractions [Fx]; 40.05 Gy in 15 Fx; 27 Gy in 5 Fx; and 26 in 5 Fx) and compared to conventional fractionation (50 Gy in 25 Fx). For calculation of BED and TCP, a previously published radiobiological model with an α/ß ratio of 4 Gy was used. The theoretical BED and TCP for incidental irradiation between 0 and 100% of the prescribed dose were evaluated. Subsequently, we assessed BED and TCP in 431 axillary lymph node metastases. RESULTS: The extent of incidental lymph node irradiation and the fractionation scheme have a direct impact on BED and TCP. The estimated mean TCP in the axillary nodes ranged from 1.5 ± 6.4% to 57.5 ± 22.9%, depending on the patient's anatomy and the fractionation scheme. Hypofractionation led to a significant reduction of mean TCP of lymph node metastases for all schedules. CONCLUSION: Our data indicate that hypofractionation might affect the effectiveness of incidental radiotherapy in the axilla. This is particularly relevant for patients with positive sentinel lymph nodes who receive SLNB only.

Craniospinal irradiation(CSI) in patients with leptomeningeal metastases: risk-benefit-profile and development of a prognostic score for decision making in the palliative setting.

BACKGROUND: The aim of our study was to assess the feasibility and oncologic outcomes in patients treated with spinal (SI) or craniospinal irradiation (CSI) in patients with leptomeningeal metastases (LM) and to suggest a prognostic score as to which patients are most likely to benefit from this treatment. METHODS: Nineteen patients treated with CSI at our institution were eligible for the study. Demographic data, primary tumor characteristics, outcome and toxicity were assessed retrospectively. The extent of extra-CNS disease was defined by staging CT-scans before the initiation of CSI. Based on outcome parameters a prognostic score was developed for stratification based on patient performance status and tumor staging. RESULTS: Median follow-up and overall survival (OS) for the whole group was 3.4 months (range 0.5-61.5 months). The median overall survival (OS) for patients with LM from breast cancer was 4.7 months and from NSCLC 3.3 months. The median OS was 7.3 months, 3.3 months and 1.5 months for patients with 0, 1 and 2 risk factors according to the proposed prognostic score (KPS < 70 and the presence of extra-CNS disease) respectively. Nonhematologic toxicities were mild. CONCLUSION: CSI demonstrated clinically meaningful survival that is comparable to the reported outcome of intrathecal chemotherapy. A simple scoring system could be used to better select patients for treatment with CSI in this palliative setting. In our opinion, the feasibility of performing CSI with modern radiotherapy techniques with better sparing of healthy tissue gives a further rationale for its use also in the palliative setting.

Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?

BACKGROUND: The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. MATERIAL AND METHODS: Treatment plans (n = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. RESULTS: IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2-3.4 Gy (median: 1.9 Gy) in FB and 0.0-1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2-2.4% in FB and 0.0-1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0-1.5% and 0-2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0-2.2%). CONCLUSION: According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.

CT-based dose recalculations in head and neck cancer radiotherapy: comparison of daily dose recalculations to less time-consuming approaches.

BACKGROUND: The goal of this study was to investigate if daily dose recalculations are necessary or if less time-consuming approaches can be used to identify dose differences to the planned dose in patients with head and neck cancers (H&N). METHODS: For 12 H&N patients treated with helical tomotherapy, daily dose calculations were performed retrospectively. Four different summation doses (SuDo) were calculated: DayDo (daily dose calculation), MVCTx2, MVCTx5, and MVCTx10 (dose calculations every second, fifth, and tenth fraction). Dose recalculations were depicted on the last contoured mega voltage CT (MVCT). The DayDo was compared to the planned dose and to the less time-consuming SuDo scenarios. The doses were assessed for the planning target volume (PTV) and the organs at risk (OARs): mandible (mand), spinal cord (SC), spinal cord +5 mm (SC+5 mm), parotid glands (PG). RESULTS: The ipsilateral PG, contralateral PG, and PTV volume decreased by -22.5% (range: -34.8 to 5.2%), -19.5% (-31.5 to 15.8%), and -2.6% (-16.7 to 0.2%), respectively. There was a significant median mean dose (Dmean) dose difference for DayDo compared to the planned dose for PG total of 1.9 Gy (-3.3 to 7.3 Gy). But less time-consuming SuDo compared to DayDo showed statistically significant but not clinically relevant (<2%) dose differences for several organs. Hence the small dose difference to the gold standard (DayDo), we recommend dose recalculations every fifth MVCT in order to identify the occurrence of dose differences compared to the planned dose. CONCLUSION: Daily dose calculations are the most precise to assess dose differences between actual and planned dose. Dose recalculations on every fifth MVCT (i. e., weekly control CTs) are an applicable and time-saving way of identifying patients with significant dose differences compared to the planned dose.

Outcomes of immediate oncoplastic surgery and adjuvant radiotherapy in breast cancer patients.

BACKGROUND: Oncoplastic surgery techniques lead to a rearrangement of the breast tissue and impede target definition during adjuvant radiotherapy (RT). The aim of this study was to assess local control rates after immediate oncoplastic surgery and adjuvant RT. METHODS: This study comprises 965 patients who underwent breast-conserving therapy and adjuvant RT between 01/2000 and 12/2005. 288 patients received immediate oncoplastic surgery (ONC) and 677 patients breast-conserving surgery only (NONC). All patients were treated with adjuvant external tangential-beam RT (total dose: 50/50.4 Gy; fraction dose 1.8/2.0 Gy). An additional boost dose of 10-16 Gy to the primary tumor bed was given in 900 cases (93.3%). Local control rates (LCR), Progression free survival (PFS) and overall survival (OS) were assessed retrospectively after a median follow-up period of 67 (Q25-Q75: 51-84) months. RESULTS: No significant difference was found between ONC and NONC in regard to LCR (5-yr: ONC 96.8% vs. NONC 95.3%; p = 0.25). This held also true for PFS (5-yr: ONC 92.1% vs. NONC 89.3%; p = 0.09) and OS (5-yr: ONC 96.0% vs. NONC 94.8%; p = 0.53). On univariate analyses G2-3 (p = 0.04), a younger age (p = 0.01), T-stage (p < 0.01) lymph node involvement (p < 0.01) as well as triple negative tumors (p < 0.01) were identified as risk factors for local recurrence. In a propensity score stratified Cox-regression model no significant impact of oncoplastic surgery on local control rate was found (HR: 2.05, 95% CI [0.93; 4.51], p = 0.08). CONCLUSION: Immediate oncoplastic surgery seems not to affect the effectiveness of adjuvant whole breast RT on local control rates in breast cancer patients.

Have we achieved adequate recommendations for target volume definitions in anal cancer? A PET imaging based patterns of failure analysis in the context of established contouring guidelines.

BACKGROUND: There are different contouring guidelines for the clinical target volume (CTV) in anal cancer (AC) which vary concerning recommendations for radiation margins in different anatomical regions, especially on inguinal site. PET imaging has become more important in primary staging of AC as a very sensitive method to detect lymph node (LN) metastases. Using PET imaging, we evaluated patterns of LN spread, and examined the differences of the respective contouring guidelines on the basis of our results. METHODS: We carried out a retrospective study of thirty-seven AC patients treated with chemoradiation (CRT) who underwent FDG-PET imaging for primary staging in our department between 2011 and 2018. Patients showing PET positive LN were included in this analysis. Using a color code, LN metastases of all patients were delineated on a template with "standard anatomy" and were divided indicating whether their location was in- or out-field of the standard CTV as recommended by the Radiation Therapy Oncology Group (RTOG), the Australasian Gastrointestinal Trials Group (AGITG) or the British National Guidance (BNG). Furthermore, a detailed analysis of the location of LN of the inguinal region was performed. RESULTS: Twenty-two out of thirty-seven AC patients with pre-treatment PET imaging had PET positive LN metastases, accumulating to a total of 154 LN. The most commonly affected anatomical region was inguinal (49 LN, 32%). All para-rectal, external/internal iliac, and pre-sacral LN were covered by the recommended CTVs of the three different guidelines. Of forty-nine involved inguinal LN, fourteen (29%), seven (14%) and five (10%) were situated outside of the recommended CTVs by RTOG, AGITG and BNG. Inguinal LN could be located up to 5.7 cm inferiorly to the femoral saphenous junction and 2.8 cm medial or laterally to the big femoral vessels. CONCLUSION: Pelvis-related, various recommendations are largely consistent, and all LN are covered by the recommended CTVs. LN "misses" appear generally cranially (common iliac or para-aortic) or caudally (inguinal) to the recommended CTVs. The established guidelines differ significantly, particular regarding the inguinal region. Based on our results, we presented our suggestions for CTV definition of the inguinal region. LN involvement of a larger number of patients should be investigated to enable final recommendations.

Moving targets in 4D-CTs versus MIP and AIP: comparison of patients data to phantom data.

PURPOSE: Maximum (MIP) and average intensity projection (AIP) CTs allow rapid definition of internal target volumes in a 4D-CT. The purpose of this study was to assess the accuracy of these techniques in a large patient cohort in combination with simulations on a lung phantom. METHODS: 4DCT data from a self-developed 3D lung phantom and from 50 patients with lung tumors were analyzed. ITVs were contoured in maximum (ITVMIP) and average intensity projection (ITVAIP) and subsequently compared to ITVs contoured in 10 phases of a 4D-CT (ITV10). In the phantom study additionally a theoretical target volume was calculated for each motion and compared to the contoured volumes. RESULTS: ITV10 overestimated the actual target volume by 9.5% whereas ITVMIP and ITVAIP lead to an underestimation of - 1.8% and - 11.4% in the phantom study. The ITVMIP (ITVAIP) was in average - 10.0% (- 18.7%) smaller compared to the ITV10. In the patient CTs deviations between ITV10 and MIP/AIP were significantly larger (MIP: - 20.2% AIP: -33.7%) compared to this. Tumors adjacent to the chestwall, the mediastinum or the diaphragm showed lower conformity between ITV10 and ITVMIP (ITVAIP) compared to tumors solely surrounded by lung tissue. Large tumor diameters (> 3.5 cm) and large motion amplitudes (> 1 cm) were associated with lower conformity between intensity projection CTs and ITV10-. CONCLUSION: The application of MIP and AIP in the clinical practice should not be a standard procedure for every patient, since relevant underestimation of tumor volumes may occur. This is especially true if the tumor borders the mediastinum, the chest wall or the diaphragm and if tumors show a large motion amplitude.

The importance of surrounding tissues and window settings for contouring of moving targets.

AIM: The aim of the study was to assess the importance of surrounding tissues for the delineation of moving targets in tissue-specific phantoms and to find optimal settings for lung, soft tissue, and liver tumors. MATERIALS AND METHODS: Tumor movement was simulated by a water-filled table tennis ball (target volume, TV). Three phantoms were created: corkboards to simulate lung tissue (lung phantom, LunPh), animal fat as fatty soft tissue (fatty tissue phantom, FatPh), and water enhanced with contrast medium as the liver tissue (liver phantom, LivPh). Slow planning three-dimensional compute tomography images (3D-CTs) were acquired with and without phantom movements. One-dimensional tumor movement (1D), three-dimensional tumor movement (3D), as well as a real patient's tumor trajectories were simulated. The TV was contoured using two lung window settings, two soft-tissue window settings, and one liver window setting. The volumes were compared to mathematical calculated values. RESULTS: TVs were underestimated in all phantoms due to movement. The use of soft-tissue windows in the LivPh led to a significant underestimation of the TV (70.8% of calculated TV). When common window settings [LunPh + 200 HU/-1,000 HU (upper window/lower window threshold); FatPh: + 240 HU/-120 HU; LivPh: + 175 HU/+ 50 HU] were used, the contoured TVs were: LivPh, 84.0%; LunPh, 93.2%, and FatPh, 92.8%. The lower window threshold had a significant impact on the size of the delineated TV, whereas changes of the upper threshold led only to small differences. CONCLUSION: The decisive factor for window settings is the lower window threshold (for adequate TV delineation in the lung and fatty-soft tissue it should be lower than density values of surrounding tissue). The use of a liver window should be considered.

A survey of cancer patients' interest in undertaking exercise to promote relaxation during radiotherapy for breast cancer and metastatic cancer.

BACKGROUND: Approximately 25-50% of patients undergoing radiotherapy (RT) experience psychological distress and anxiety, which can detrimentally affect both their quality of life and treatment outcomes. While previous research has demonstrated that relaxation exercises can enhance the tolerability of RT and alleviate associated stress and anxiety, the specific needs for such therapies in radiation oncology remain under-explored. This study aims to investigate the demand for and preferences toward relaxation exercises among radiotherapy patients, addressing a critical gap in patient-centered care. METHODS: A prospective pseudonymized survey study using a one-time paper-based questionnaire was conducted from 2022 to 2023 among patients undergoing curative-intent RT for breast cancer or patients undergoing palliative RT for bone metastases. Patients were asked in a 11-item questionnaire about their anxiety, pre-existing practice of relaxation exercises/interventions, their interest in relaxation exercises, and preferences on the type and format of instruction. Data were analyzed descriptively. RESULTS: 100 patients (74 female and 26 male) responded, of whom 68 received curative-intent adjuvant RT and 32 palliative RT. Median age was 62 years. 78% of patients indicated a desire to be actively involved in their radiotherapy, but only 27% had used relaxation exercises prior to RT. 44.8% of both curatively and palliatively treated patients who wanted to be actively involved in their therapy desired to learn how to best relax. 56.4% of respondents were willing to spend extra time learning offered exercises. CONCLUSION: The survey indicates that patients undergoing RT, both for curative or palliative intent, desire relaxation exercises to relieve stress and anxiety from RT. It is therefore important to assess the need for relaxation interventions in individual patients and to develop suitable programs or collaborate with other healthcare professionals to meet these needs.

Detecting Metastatic Patterns of Oligometastatic Breast Cancer: A Comparative Analysis of 18F-FDG PET/CT and Conventional CT Imaging.

Metastasis-directed therapy has the potential to improve progression-free and overall survival in oligometastatic disease (OMD). For breast cancer, however, randomized trials have failed so far to confirm this finding. Because the concept of metastasis-directed therapy in OMD is highly dependent on the accuracy of the imaging modality, we aimed to assess the impact of 18F-FDG PET/CT on the definition of OMD in breast cancer patients. Methods: Eighty patients with a total of 150 18F-FDG PET/CT images (between October 2006 and January 2022) were enrolled in this retrospective study at the Technical University of Munich. The inclusion criteria were OMD, defined as 1-5 distant metastases, at the time of 18F-FDG PET/CT. For the current study, we systemically compared the metastatic pattern on 18F-FDG PET/CT with conventional CT. Results: At the time of 18F-FDG PET/CT, 21.3% of patients (n = 32) had a first-time diagnosis of metastatic disease, 40.7% (n = 61) had a previous history of OMD, and 38% (n = 57) had a previous history of polymetastatic disease. In 45.3% of cases, the imaging modality (18F-FDG PET/CT vs. conventional CT) had an impact on the assessment of whether OMD was present. An identical metastatic pattern was observed in only 32% of cases.18F-FDG PET/CT detected additional metastases in 33.3% of cases, mostly in the nonregional lymph node system. Conclusion: The use of 18F-FDG PET/CT had a substantial impact on the definition of OMD and detection of metastatic pattern in breast cancer. Our results emphasize the importance of establishing a standardized definition for imaging modalities in future trials and clinical practices related to metastasis-directed therapy in breast cancer patients.

Tumor Contact With Internal Mammary Perforator Vessels as Risk Factor for Gross Internal Mammary Lymph Node Involvement in Patients With Breast Cancer.

PURPOSE: The identification of internal mammary lymph node metastases and the assessment of associated risk factors are crucial for adjuvant regional lymph node irradiation in patients with breast cancer. The current study aims to investigate whether tumor contact with internal mammary perforator vessels is associated with gross internal mammary lymph node involvement. METHODS AND MATERIALS: We included 297 patients with primary breast cancer and gross internal mammary (IMN+) and/or axillary metastases as well as 230 patients without lymph node metastases. Based on pretreatment dynamic contrast-enhanced magnetic resonance imaging, we assessed contact of the tumor with the internal mammary perforating vessels (IMPV). RESULTS: A total of 59 patients had ipsilateral IMN+ (iIMN+), 10 patients had contralateral IMN+ (cIMN+), and 228 patients had ipsilateral axillary metastases without IMN; 230 patients had node-negative breast cancer. In patients with iIMN+, 100% of tumors had contact with ipsilateral IMPV, with 94.9% (n = 56) classified as major contact. In iIMN- patients, major IMPV contact was observed in only 25.3% (n = 116), and 36.2% (n = 166) had no IMPV contact at all. Receiver operating characteristic analysis revealed that "major IMPV contact" was more accurate in predicting iIMN+ (area under the curve, 0.85) compared with a multivariate model combining grade of differentiation, tumor site, size, and molecular subtype (area under the curve, 0.65). Strikingly, among patients with cIMN+, 100% of tumors had contact with a crossing contralateral IMPV, whereas in cIMN- patients, IMPVs to the contralateral side were observed in only 53.4% (iIMN+) and 24.8% (iIMN-), respectively. CONCLUSIONS: Tumor contact with the IMPV is highly associated with risk of gross IMN involvement. Further studies are warranted to investigate whether this identified risk factor is also associated with microscopic IMN involvement and whether it can assist in the selection of patients with breast cancer for irradiation of the internal mammary lymph nodes.

Association of Skin Microbiome Dynamics With Radiodermatitis in Patients With Breast Cancer.

Importance: The interindividual differences in severity of acute radiation dermatitis are not well understood. To date, the pathomechanism and interplay of microbiome and radiodermatitis before and during treatment remain largely unknown. Objective: To assess the association of skin microbiome baseline composition and dynamics with severity of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer. Design, Setting, and Participants: A longitudinal prospective pilot observational study was conducted between January 2017 and January 2019. Sequencing results were received in March 2021, and the data were analyzed from August 2021 to March 2023. This study was performed at an urban academic university cancer center. A total of 21 female patients with breast cancer after surgery were consecutively approached, of which 1 patient withdrew consent before the study started. Exposure: Adjuvant radiotherapy for breast cancer for 7 weeks. Main Outcomes and Measures: The main outcome was the association of baseline skin microbiome composition and its dynamics with the severity of radiodermatitis. A total of 360 skin microbiome samples from patients were analyzed, taken before, during, and after radiotherapy, from both the treated and contralateral healthy sides. The skin microbiome samples were analyzed using 16S (V1-V3) amplicon sequencing and quantitative polymerase chain reaction bacterial enumeration. Results: Twenty female patients with breast cancer after surgery who underwent radiotherapy enrolled in the study had a median (range) age of 61 (37-81) years. The median (range) body mass index of the patients was 24.2 (17.6-38.4). The 16S sequencing revealed that low (<5%) relative abundance of commensal skin bacteria (Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes) at baseline composition was associated with the development of severe radiodermatitis with an accuracy of 100% (sensitivity and specificity of 100%, P < .001). Furthermore, in patients with severe radiodermatitis, quantitative polymerase chain reaction bacterial enumeration revealed a general non-species-specific overgrowth of skin bacterial load before the onset of severe symptoms. Subsequently, the abundance of commensal bacteria increased in severe radiodermatitis, coinciding with a decline in total bacterial load. Conclusions and Relevance: The findings of this observational study indicated a potential mechanism associated with the skin microbiome for the pathogenesis of severe radiodermatitis, which may be a useful biomarker for personalized prevention of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer.

Regional nodal irradiation in breast cancer patients: Effects of deep inspiration breath hold on the internal mammary chain location.

The purpose of this study was to investigate the impact of deep inspiration breath hold (DIBH) on the positioning of thoracic structures and provide treatment planning recommendations for internal mammary chain (IMC) irradiation in breast cancer patients. Thirty-two breast cancer patients from our database underwent both DIBH and free breathing (FB) treatment planning. Contouring of the axillary lymph node clinical target volumes (CTVs: level I, II, III, IV, and IMC according to ESTRO), the internal mammary artery (IMA), the heart, and the left anterior descending artery (LAD) was performed. The following were then analyzed: the distance between the IMA and the heart, the craniocaudal distance in which IMC-CTV and heart coexist, the craniocaudal distance between the lower end of the of level III and IV and the upper end of the heart. Several significant geometric differences were observed between DIBH and FB that explain the efficacy of the DIBH for regional nodal irradiation. In >80% of patients the cranial origin of the LAD lies below the lower edge of the IMC-CTV in DIBH. In addition the slices in which the heart/LAD and IMC-CTV coexist decrease during DIBH. The IMA-heart distance is significantly larger in DIBH. Also the craniocaudal distance between the lower border of the CTV level III and IV and the upper border of the heart is larger in DIBH. The observed mechanisms during DIBH contribute significantly to the dose reduction in regional nodal irradiation. To further enhance the benefits of DIBH for the irradiation of the IMC-CTV, it is recommended to implement steep dose gradients in the caudal plane.

Outcome of patients with soft tissue sarcomas of the extremities and trunk treated by (neo)adjuvant intensity modulated radiation therapy with curative intent.

BACKGROUND: Soft tissue sarcomas (STS) are a relatively rare group of malignant tumors. Currently, there is very little published clinical data, especially in the context of curative multimodal therapy with image-guided, conformal, intensity-modulated radiotherapy. METHODS: Patients who received preoperative or postoperative intensity-modulated radiotherapy for STS of the extremities or trunk with curative intent were included in this single centre retrospective analysis. A Kaplan-Meier analysis was performed to evaluate survival endpoints. Multivariable proportional hazard models were used to investigate the association between survival endpoints and tumour-, patient-, and treatment-specific characteristics. RESULTS: 86 patients were included in the analysis. The most common histological subtypes were undifferentiated pleomorphic high-grade sarcoma (UPS) (27) and liposarcoma (22). More than two third of the patients received preoperative radiation therapy (72%). During the follow-up period, 39 patients (45%) suffered from some type of relapse, mainly remote (31%). The two-years overall survival rate was 88%. The median DFS was 48 months and the median DMFS was 51 months. Female gender (HR 0.460 (0.217; 0.973)) and histology of liposarcomas compared to UPS proved to be significantly more favorable in terms of DFS (HR 0.327 (0.126; 0.852)). CONCLUSION: Conformal, intensity-modulated radiotherapy is an effective treatment modality in the preoperative or postoperative management of STS. Especially for the prevention of distant metastases, the establishment of modern systemic therapies or multimodal therapy approaches is necessary.

Simultaneous integrated boost within the lymphatic drainage system in breast cancer: A single center study on toxicity and oncologic outcome.

Background and purpose: In breast cancer patients, the increasing de-escalation of axillary surgery and the improving resolution of diagnostic imaging results in a more frequent detection of residual, radiographically suspect lymph nodes (sLN) after surgery. If resection of the remaining suspect lymph nodes is not feasible, a simultaneous boost to the lymph node metastases (LN-SIB) can be applied. However, literature lacks data regarding the outcome and safety of this technique. Materials and methods: We included 48 patients with breast cancer and sLN in this retrospective study. All patients received a LN-SIB. The median dose to the breast or chest wall and the lymph node system was 50.4 Gy in 28 fractions. The median dose of the LN-SIB was 58.8 Gy / 2.1 Gy (56-63 Gy / 2-2.25 Gy). The brachial plexus was contoured in every case and the dose within the plexus PRV (+0.3-0.5mm) was limited to an EQD2 of 59 Gy. All patients received structured radiooncological and gynecological follow-up by clinically experienced physicians. Radiooncological follow-ups were at baseline, 6 weeks, 3 months, 6 months and subsequent annually after irradiation. Results: The median follow-up time was 557 days and ranged from 41 to 3373 days. Overall, 28 patients developed I°, 18 patients II° and 2 patients III° acute toxicity. There were no severe late side effects (≥ III°) observed during the follow-up period. The most frequent chronic side effect was fatigue. One patient (2.1 %) developed pain and mild paresthesia in the ipsilateral arm after radiotherapy. After a follow-up of 557 days (41 to 3373 days), in 8 patients a recurrence was observed (16.7%). In 4 patients the recurrence involved the regional lymph node system. Hence, local control in the lymph node drainage system after a median follow-up of 557 days was 91.6 %. Conclusion: If surgical re-dissection of residual lymph nodes is not feasible or refused by the patient, LN-SIB-irradiation can be considered as a potential treatment option. However, patients need to be informed about a higher risk of regional recurrence compared to surgery and an additional risk of acute and late toxicity compared to adjuvant radiotherapy without regional dose escalation.

The importance of planning CT-based imaging features for machine learning-based prediction of pain response.

Patients suffering from painful spinal bone metastases (PSBMs) often undergo palliative radiation therapy (RT), with an efficacy of approximately two thirds of patients. In this exploratory investigation, we assessed the effectiveness of machine learning (ML) models trained on radiomics, semantic and clinical features to estimate complete pain response. Gross tumour volumes (GTV) and clinical target volumes (CTV) of 261 PSBMs were segmented on planning computed tomography (CT) scans. Radiomics, semantic and clinical features were collected for all patients. Random forest (RFC) and support vector machine (SVM) classifiers were compared using repeated nested cross-validation. The best radiomics classifier was trained on CTV with an area under the receiver-operator curve (AUROC) of 0.62 ± 0.01 (RFC; 95% confidence interval). The semantic model achieved a comparable AUROC of 0.63 ± 0.01 (RFC), significantly below the clinical model (SVM, AUROC: 0.80 ± 0.01); and slightly lower than the spinal instability neoplastic score (SINS; LR, AUROC: 0.65 ± 0.01). A combined model did not improve performance (AUROC: 0,74 ± 0,01). We could demonstrate that radiomics and semantic analyses of planning CTs allowed for limited prediction of therapy response to palliative RT. ML predictions based on established clinical parameters achieved the best results.