Cost-benefit ratio of modern medical education using micro-costing: a model calculation using the example of an innovative breast brachytherapy workshop.

BACKGROUND AND PURPOSE: Radiation oncology is an essential component of therapeutic oncology and necessitates well-trained personnel. Multicatheter brachytherapy (MCBT) is one radiotherapeutic option for early-stage breast cancer treatment. However, specialized hands-on training for MCBT is not currently included in the curriculum for residents. A recently developed hands-on brachytherapy workshop has demonstrated promising results in enhancing knowledge and practical skills. Nevertheless, these simulation-based teaching formats necessitate more time and financial resources. Our analyses include computational models for the implementation and delivery of this workshop and can serve as a basis for similar educational initiatives. METHODS: This study aimed to assess the cost-effectiveness of a previously developed and evaluated breast brachytherapy simulation workshop. Using a micro-costing approach, we estimated costs at a detailed level by considering supplies, soft- and hardware, and personnel time for each task. This method also allows for a comprehensive evaluation of the costs associated with implementing new medical techniques. The workshop costs were divided into two categories: development and workshop execution. The cost analysis was conducted on a per-participant basis, and the impact on knowledge improvement was measured using a questionnaire. RESULTS: The total workshop costs were determined by considering the initial workshop setup expenses including the development and conceptualization of the course with all involved collaborators, as well as the costs incurred for each individual course. The workshop was found to be financially efficient, with a per-participant cost of €â€¯39, considering the industrial sponsorship provided for brachytherapy equipment. In addition, we assessed the workshop's efficacy by analyzing participant feedback using Likert scale evaluations. The findings indicated a notable enhancement in both theoretical and practical skills among the participants. Moreover, the cost-to-benefit ratio (CBFR) analysis demonstrated a CBFR of €â€¯13.53 for each Likert point increment. CONCLUSION: The hands-on brachytherapy workshop proved to be a valuable and approximately cost-effective educational program, leading to a significant enhancement in the knowledge and skills of the participants. Without the support of industrial sponsorship, the costs would have been unattainable.

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.

Low doses to the heart in daily practice for treating left-sided breast cancer using accelerated partial-breast irradiation by multicatheter brachytherapy and deep-inspiration breath-hold using a SIB.

PURPOSE: The aim of this study was to analyze the heart dose for left-sided breast cancer that can be achieved during daily practice in patients treated with multicatheter brachytherapy (MCBT) accelerated partial-breast irradiation (APBI) and deep-inspiration breath-hold (DIBH) whole-breast irradiation (WBI) using a simultaneous integrated tumor bed boost (SIB)-two different concepts which nonetheless share some patient overlap. MATERIALS AND METHODS: We analyzed the nominal average dose (Dmean) to the heart as well as the biologically effective dose (BED) and the equivalent dose in 2­Gy fractions (EQD2) for an α/ß of 3 in 30 MCBT-APBI patients and 22 patients treated with DIBH plus SIB. For further dosimetric comparison, we contoured the breast planning target volume (PTV) in each of the brachytherapy planning CTs according to the ESTRO guidelines and computed tangential field plans. Mean dose (Dmean), EQD2 Dmean, and BED Dmean for three dosing schemes were calculated: 50 Gy/25 fractions and two hypofractionated regimens, i.e., 40.05 Gy/15 fractions and 26 Gy/5 fractions. Furthermore, we calculated tangential field plans without a boost for the 22 cases treated with SIB with the standard dosing scheme of 40.05 Gy/15 fractions. RESULTS: MCBT and DIBH radiation therapy both show low-dose exposure of the heart. As expected, hypofractionation leads to sparing of the heart dose. Although MCBT plans were not optimized regarding dose to the heart, Dmean differed significantly between MCBT and DIBH (1.28 Gy vs. 1.91 Gy, p < 0.001) in favor of MCBT, even if the Dmean in each group was very low. In MCBT radiation, the PTV-heart distance is significantly associated with the dose to the heart (p < 0.001), but it is not in DIBH radiotherapy using SIB. CONCLUSION: In daily practice, both DIBH radiation therapy as well as MCBT show a very low heart exposure and may thus reduce long term cardiac morbidity as compared to currently available long-term clinical data of patients treated with conventional tangential field plans in free breathing. Our analysis confirms particularly good cardiac sparing with MCBT-APBI, so that this technique should be offered to patients with left-sided breast cancer if the tumor-associated eligibility criteria are fulfilled.

Breast clinical target volume: HU-based glandular CTVs and ESTRO CTVs in modern and historical radiotherapy treatment planning.

PURPOSE: The current study aimed to compare contouring of glandular tissue only (gCTV) with the clinical target volume (CTV) as defined according to European Society for Radiotherapy and Oncology (ESTRO) guidelines (eCTV) and historically treated volumes (marked by wire and determined by palpation and anatomic landmarks) in breast cancer radiotherapy. METHODS: A total of 56 consecutive breast cancer patients underwent treatment planning based solely on anatomic landmarks/wire markings ("wire based"). From these treatment plans, the 50% and 95% isodoses were transferred as structures and compared to the following CT-based volumes: eCTV; a Hounsfield unit (HU)-based automatic contouring of the gCTV; and standardized planning target volumes (PTVs) generated with 1­cm safety margins (resulting in the ePTVs and gPTVs, respectively). RESULTS: The 95% isodose volume of the wire-based plan was larger than the eCTV by 352.39 ± 176.06 cm3 but smaller than the ePTV by 157.58 ± 189.32 cm3. The 95% isodose was larger than the gCTV by 921.20 ± 419.78 cm3 and larger than the gPTV by 190.91 ± 233.49 cm3. Patients with larger breasts had significantly less glandular tissue than those with small breasts. There was a trend toward a lower percentage of glandular tissue in older patients. CONCLUSION: Historical wire and anatomic landmarks-based treatment planning sufficiently covers the glandular tissue and the theoretical gPTV generated for the glandular tissue. Modern CT-based CTV and PTV definition according to ESTRO results in a larger treated volume than the historical wire-based techniques. HU-standardized glandular tissue contouring results in a significantly smaller CTV and might be an option for reducing the treatment volume and improving reproducibility of contouring between institutions.

Oligometastasis in breast cancer-current status and treatment options from a radiation oncology perspective.

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

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.

Post-neoadjuvant treatment with capecitabine and trastuzumab emtansine in breast cancer patients-sequentially, or better simultaneously?

PURPOSE: Following neoadjuvant chemotherapy for breast cancer, postoperative systemic therapy, also called post-neoadjuvant treatment, has been established in defined risk settings. We reviewed the evidence for sequencing of postoperative radiation and chemotherapy, with a focus on a capecitabine and trastuzumab emtansine (T-DM1)-based regimen. METHODS: A systematic literature search using the PubMed/MEDLINE/Web of Science database was performed. We included prospective and retrospective reports published since 2015 and provided clinical data on toxicity and effectiveness. RESULTS: Six studies were included, five of which investigated capecitabine-containing regimens. Of these, four were prospective investigations and one a retrospective matched comparative analysis. One randomized prospective trial was found for T­DM1 and radiotherapy. In the majority of these reports, radiation-associated toxicities were not specifically addressed. CONCLUSION: Regarding oncologic outcome, the influence of sequencing radiation therapy with maintenance capecitabine chemotherapy in the post-neoadjuvant setting is unclear. Synchronous administration of capecitabine is feasible, but reports on possible excess toxicities are partially conflicting. Dose reduction of capecitabine should be considered, especially if normofractionated radiotherapy is used. In terms of tolerance, hypofractionated schedules seem to be superior in terms of toxicity in concurrent settings. T­DM1 can safely be administered concurrently with radiotherapy.

Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward.

Moderate hypofractionation is the standard of care for adjuvant whole-breast radiotherapy after breast-conserving surgery for breast cancer. Recently, 10-year results from the FAST and 5­year results from the FAST-Forward trial evaluating adjuvant whole-breast radiotherapy in 5 fractions over 5 weeks or 1 week have been published. This article summarizes recent data for moderate hypofractionation and results from the FAST and FAST-Forward trial on ultra-hypofractionation. While the FAST trial was not powered for comparison of local recurrence rates, FAST-Forward demonstrated non-inferiority for two ultra-hypofractionated regimens in terms of local control. In both trials, the higher-dose experimental arms resulted in elevated rates of late toxicity. For the lower dose experimental arms of 28.5 Gy over 5 weeks and 26 Gy over 1 week, moderate or marked late effects were similar in the majority of documented items compared to the respective standard arms, but significantly worse in some subdomains. The difference between the standard arm and the 26 Gy of the FAST-Forward trial concerning moderate or marked late effects increased with longer follow-up in disadvantage of the experimental arm for most items. For now, moderate hypofractionation with 40-42.5 Gy over 15-16 fractions remains the standard of care for the majority of patients with breast cancer who undergo whole-breast radiotherapy without regional nodal irradiation after breast-conserving surgery.

Impact of 18F-FDG-PET/CT on the identification of regional lymph node metastases and delineation of the primary tumor in esophageal squamous cell carcinoma patients.

PURPOSE: In patients undergoing chemoradiation for esophageal squamous cell carcinoma (ESCC), the extent of elective nodal irradiation (ENI) is still discussed controversially. This study aimed to analyze patterns of lymph node metastases and their correlation with the primary tumor using 18F­fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. METHODS: 102 ESCC patients with pre-treatment FDG-PET/CT scans were evaluated retrospectively. After exclusion of patients with low FDG uptake and patients without FDG-PET-positive lymph node metastases (LNM), 76 patients were included in the final analysis. All LNM were assigned to 16 pre-defined anatomical regions and classified according to their position relative to the primary tumor (above, at the same height, or below the primary tumor). In addition, the longitudinal distance to the primary tumor was measured for all LNM above or below the primary tumor. The craniocaudal extent (i.e., length) of the primary tumor was measured using FDG-PET imaging (LPET) and also based on all other available clinical and imaging data (endoscopy, computed tomography, biopsy results) except FDG-PET (LCT/EUS). RESULTS: Significantly more LNM were identified with 18F­FDG-PET/CT (177 LNM) compared to CT alone (131 LNM, p < 0.001). The most common sites of LNM were paraesophageal (63% of patients, 37% of LNM) and paratracheal (33% of patients, 20% of LNM), while less than 5% of patients had supraclavicular, subaortic, diaphragmatic, or hilar LNM. With regard to the primary tumor, 51% of LNM were at the same height, while 25% and 24% of lymph node metastases were above and below the primary tumor, respectively. For thirty-three LNM (19%), the distance to the primary tumor was larger than 4 cm. No significant difference was seen between LCT/EUS (median 6 cm) and LPET (median 6 cm, p = 0.846) CONCLUSION: 18F­FDG-PET can help to identify subclinical lymph node metastases which are located outside of recommended radiation fields. PET-based involved-field irradiation might be the ideal compromise between small treatment volumes and decreasing the risk of undertreatment of subclinical metastatic lymph nodes and should be further evaluated.

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.

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.

Cavity volume changes after surgery of a brain metastasis-consequences for stereotactic radiation therapy.

PURPOSE: For a large or symptomatic brain metastasis, resection and adjuvant radiotherapy are recommended. Hypofractionated stereotactic radiotherapy (HFSRT) is increasingly applied in patients with a limited number of lesions. Exact target volume definition is critical given the small safety margins. Whilst technical advances have minimized inaccuracy due to patient positioning and radiation targeting, little is known about changes in target volume. This study sought to evaluate potential changes in the resection cavity of a brain metastasis. METHODS: In all, 57 patients treated with HFSRT after surgical resection of one brain metastasis between 2008 and 2015 in our institution were included in this study. Gross tumor volume (GTV) of the initial metastasis and the volume of the resection cavity in the post-operative, planning, and follow-up MRIs were measured and compared. RESULTS: The mean cavity size decreased after surgery with the greatest change of -23.4% (±41.5%) occurring between post-operative MRI and planning MRI (p < 0.01). During this time period, the cavity volume decreased, remained stable, and increased in 79.1, 3.5, and 17.4%, respectively. A further decrease of -20.7% (±58.1%) was perceived between planning MRI and first follow-up (p < 0.01). No significant difference in pattern of change could be observed depending on the volume of initial GTV, size of the post-operative resection cavity, initial or post-resection FLAIR (fluid-attenuated inversion recovery) hyper-intensity, postsurgical ischemia, or primary tumor. The resection cavities of patients with post-operative ischemia were significantly larger than resection cavities of patients without ischemia. CONCLUSION: The resection cavity seems to be very dynamic after surgery. Hence, it remains necessary to use very recent scans for treatment planning.

Dose variability in different lymph node levels during locoregional breast cancer irradiation: the impact of deep-inspiration breath hold.

PURPOSE: Aim of the present analysis was to evaluate the movement and dose variability of the different lymph node levels of node-positive breast cancer patients during adjuvant radiotherapy (RT) with regional nodal irradiation (RNI) in deep-inspiration breath hold (DIBH). METHODS: Thirty-five consecutive node-positive breast cancer patients treated from October 2016 to February 2018 receiving postoperative RT of the breast or chest wall including RNI of the supra-/infraclavicular lymph node levels (corresponding to levels IV, III, Rotter LN (interpectoral), and some parts of level II) were analyzed. To evaluate the lymph node level movement, a center of volume (COV) was obtained for each lymph node level for free-breathing (FB) and DIBH plans. Geometric shifts and dose differences between FB and DIBH were analyzed. RESULTS: A significant movement of the COV in anterior (y) and cranial (z) dimensions was observed for lymph node levels I-II and Rotter lymph nodes (p < 0.001) due to DIBH. Only minor changes in the lateral dimension (x axis) were observed, without reaching significance for levels III, IV, and internal mammary. There was a significant difference in the mean dose of level I (DIBH vs. FB: 38.2 Gy/41.3 Gy, p < 0.001) and level II (DIBH vs. FB: 45.9 Gy/47.2 Gy, p < 0.001), while there was no significant difference in level III (p = 0.298), level IV (p = 0.476), or internal mammary nodes (p = 0.471). CONCLUSION: A significant movement of the axillary lymph node levels was observed during DIBH in anterior and cranial directions for node-positive breast cancer patients in comparison to FB. The movement leads to a significant dose reduction in level I and level II.

Heart-sparing radiotherapy techniques in breast cancer patients: a recommendation of the breast cancer expert panel of the German society of radiation oncology (DEGRO).

PURPOSE: The aim of this review was to analyze the respective efficacy of various heart-sparing radiotherapy techniques. MATERIAL AND METHODS: Heart-sparing can be performed in three different ways in breast cancer radiotherapy: by seeking to keep the heart out of treated volumes (i.e. by prone position or specific breathing techniques such as deep inspiration breath-hold [DIBH] and/or gating), by solely irradiating a small volume around the lumpectomy cavity (partial breast irradiation, PBI), or by using modern radiation techniques like intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) or protons. This overview presents the available data on these three approaches. RESULTS: Studies on prone position are heterogeneous and most trials only refer to patients with large breasts; therefore, no definitive conclusion can be drawn for clinical routine. Nonetheless, there seems to be a trend toward better sparing of the left anterior descending artery in supine position even for these selected patients. The data on the use of DIBH for heart-sparing in breast cancer patients is consistent and the benefit compared to free-breathing is supported by several studies. In comparison with whole breast irradiation (WBI), PBI has an advantage in reducing the heart dose. Of note, DIBH and PBI with multicatheter brachytherapy are similar with regard to the dose reduction to heart structures. WBI by IMRT/VMAT techniques without DIBH is not an effective strategy for heart-sparing in breast cancer patients with "standard" anatomy. A combination of DIBH and IMRT may be used for internal mammary radiotherapy. CONCLUSION: Based on the available findings, the DEGRO breast cancer expert panel recommends the use of DIBH as the best heart-sparing technique. Nonetheless, depending on the treatment volume and localization, other techniques may be employed or combined with DIBH when appropriate.

Radiotherapy after skin-sparing mastectomy with immediate breast reconstruction in intermediate-risk breast cancer : Indication and technical considerations.

BACKGROUND: Skin-sparing (SSME) and nipple-sparing mastectomy (NSME) were developed to improve the cosmetic results for breast cancer (BC) patients, both allowing for immediate breast reconstruction. Recommendations for post-mastectomy radiotherapy (PMRT) are primarily derived from trials where patients were treated by standard mastectomies. Due to their more conservative character, SSME and especially NSME potentially leave more glandular tissue at risk for subclinical disease. METHODS: Rates and sites of locoregional failures following SSME and NSME plus/minus reconstruction were analyzed regarding tumor stage and biological risk factors. In particular, the role of PMRT in "intermediate"-risk and early stage high-risk breast cancer patients was revisited. Implications on targeting and dose delivery of PMRT were critically reviewed. RESULTS: The value of PMRT in stage III BC remains undisputed. For node-negative BC patients, the majority of reports classify clinical and biological features such as tumor size, close surgical margins, premenopausal status, multicentricity, lymphangiosis, triple-negativity, HER2-overexpression, and poor tumor grading as associated with higher rates of locoregional relapse, thus, building an "intermediate" risk group. Surveys revealed that the majority of radiation oncologists use risk-adaptive models also considering the number of coinciding factors for the estimation of recurrence probability following SSME and NSME. Constellations with a 10-year locoregional recurrence risk of >10% are usually triggering the indication for PMRT. There was no common belief that the amount of residual tissue, e.g., tissue thickness over flaps, serves as additional decision aid. Modern treatment planning can ensure optimal dose distribution for PMRT in almost all patients with SSME. There are no reliable data supporting a reduction of the treatment volume from the CTV chest wall, e.g., to the nipple-areola complex, to the dorsal aspect behind the implant volume, the pectoralis muscle, nor the regional interpectoral, axillary, or complete regional lymph nodes only. The omission of a skin bolus in intermediate-risk BC does not compromise oncological safety. CONCLUSIONS: For intermediate-risk as well as early stage high-risk BC patients, the DEGRO Breast Cancer Expert Panel recommends the use of PMRT following SSME and NSME when a 10-year locoregional recurrence risk is likely to be greater than 10%, as estimated by clinical and biological risk factors. Subvolume-only radiation is discouraged outside of trials. The impact of adequate systemic treatment and the value of radiotherapy on optimal locoregional tumor control, with the goal of less than 5% LRR at 10-years follow-up, has to be verified in prospective trials.

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.

Definitive, intensity modulated tomotherapy with a simultaneous integrated boost for prostate cancer patients - Long term data on toxicity and biochemical control.

AIM: To report long-term data regarding biochemical control and late toxicity of simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) with tomotherapy in patients with localized prostate cancer. BACKGROUND: Dose escalation improves cancer control after curative intended radiation therapy (RT) to patients with localized prostate cancer, without increasing toxicity, if IMRT is used. MATERIALS AND METHODS: In this retrospective analysis, we evaluated long-term toxicity and biochemical control of the first 40 patients with intermediate risk prostate cancer receiving SIB-IMRT. Primary target volume (PTV) 1 including the prostate and proximal third of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. PTV 2 containing the prostate with smaller safety margins was treated as SIB to a total dose of 76 Gy with 2.17 Gy per fraction. Toxicity was evaluated using an adapted CTCAE-Score (Version 3). RESULTS: Median follow-up of living patients was 66 (20-78) months. No late genitourinary toxicity higher than grade 2 has been reported. Grade 2 genitourinary toxicity rates decreased from 58% at the end of the treatment to 10% at 60 months. Late gastrointestinal (GI) toxicity was also moderate, though the prescribed PTV Dose of 76 Gy was accepted at the anterior rectal wall. 74% of patients reported any GI toxicity during follow up and no toxicity rates higher than grade 2 were observed. Grade 2 side effects were reported by 13% of the patients at 60 months. 5-year freedom from biochemical failure was 95% at our last follow up. CONCLUSION: SIB-IMRT using daily MV-CT guidance showed excellent long-term biochemical control and low toxicity rates.

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.