Kerstin Siebenlist

Performance of an atlas-based autosegmentation software for delineation of target volumes for radiotherapy of breast and anorectal cancer

BACKGROUND AND PURPOSE To validate atlas-based autosegmentation for contouring breast/anorectal targets. METHODS AND MATERIALS ABAS uses atlases with defined CTVs as template cases to automatically delineate target volumes in other patient CT-datasets. Results are compared with manually contoured CTVs of breast/anorectal cancer according to RTOG-guidelines. The impact of using specific atlases matched to individual patient geometry was evaluated. Results were quantified by analyzing Dice Similarity Coefficient (DSC), logit(DSC) and Percent Overlap (PO). DSC >0.700 and logit(DSC) >0.847 are acceptable. In addition a new algorithm (STAPLE) was evaluated. RESULTS ABAS produced good results for the CTV of breast/anorectal cancer targets. Delineation of inguinal lymphatic drainage, however, was insufficient. Results for breast CTV were (DSC: 0.86-0.91 ([0,1]), logit(DSC): 1.82-2.36 ([-∞,∞]), PO: 75.5-82.89%) and for anorectal CTVA (DSC: 0.79-0.85, logit(DSC): 1.40-1.77, PO: 68-73.67%). CONCLUSIONS ABAS produced satisfactory results for these clinical target volumes that are defined by more complex tissue interface geometry, thus streamlining and facilitating the radiotherapy workflow which is essential to face increasing demand and limited resources. STAPLE improved contouring outcome. Small target volumes not clearly defined are still to be delineated manually. Based on these results, ABAS has been clinically introduced for precontouring of CTVs/OARs.

Flattening-filter-free intensity modulated breath-hold image-guided SABR (Stereotactic ABlative Radiotherapy) can be applied in a 15-min treatment slot

Hypofractionated image-guided stereotactic ablative radiotherapy (igSABR) is effective in small lung/liver lesions. Computer-assisted breath-hold reduces intrafraction motion but, as every gating/triggering strategy, reduces the duty cycle, resulting in long fraction times if combined with intensity-modulated radiotherapy (IMRT). 10 MV flattening-filter-free IMRT reduces daily fraction duration to <10 min for single doses of 5-20 Gy.

Hypofractionated image-guided breath-hold SABR (Stereotactic Ablative Body Radiotherapy) of liver metastases – clinical results

PurposeStereotactic Ablative Body Radiotherapy (SABR) is a non-invasive therapy option for inoperable liver oligometastases. Outcome and toxicity were retrospectively evaluated in a single-institution patient cohort who had undergone ultrasound-guided breath-hold SABR.Patients and methods19 patients with liver metastases of various primary tumors consecutively treated with SABR (image-guidance with stereotactic ultrasound in combination with computer-controlled breath-hold) were analysed regarding overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC), acute and late toxicity.ResultsPTV (planning target volume)-size was 108 ± 109cm3 (median 67.4 cm3). BED2 (Biologically effective dose in 2 Gy fraction) was 83.3 ± 26.2 Gy (median 78 Gy). Median follow-up and median OS were 12 months. Actuarial 2-year-OS-rate was 31%. Median PFS was 4 months, actuarial 1-year-PFS-rate was 20%. Site of first progression was predominantly distant. Regression of irradiated lesions was observed in 84% (median time to detection of regression was 2 months). Actuarial 6-month-LC-rate was 92%, 1- and 2-years-LC-rate 57%, respectively. BED2 influenced LC. When a cut-off of BED2 = 78 Gy was used, the higher BED2 values resulted in improved local control with a statistical trend to significance (p = 0.0999). Larger PTV-sizes, inversely correlated with applied dose, resulted in lower local control, also with a trend to significance (p-value = 0.08) when a volume cut-off of 67 cm3 was used.No local relapse was observed at PTV-sizes < 67 cm3 and BED2 > 78 Gy. No acute clinical toxicity > °2 was observed. Late toxicity was also ≤ °2 with the exception of one gastrointestinal bleeding-episode 1 year post-SABR. A statistically significant elevation in the acute phase was observed for alkaline-phosphatase; in the chronic phase for alkaline-phosphatase, bilirubine, cholinesterase and C-reactive protein.ConclusionsA trend to statistically significant correlation of local progression was observed for BED2 and PTV-size. Dose-levels BED2 > 78 Gy cannot be reached in large lesions constituting a significant fraction of this series. Image-guided SABR (igSABR) is therefore an effective non-invasive treatment modality with low toxicity in patients with small inoperable liver metastases.

Estimation of intracranial failure risk following hippocampal-sparing whole brain radiotherapy

PURPOSE To estimate the risk of undertreatment in hippocampal-sparing whole brain radiotherapy (HS-WBRT). METHODS Eight hundred and fifty six metastases were contoured together with the hippocampi in cranial MRIs of 100 patients. For each metastasis, the distance to the closest hippocampus was calculated. Treatment plans for 10 patients were calculated and linear dose profiles were established. For SCLC and NSCLC, dose-response curves were created based on data from studies on prophylactic cranial irradiation, allowing estimating the risk for intracranial failure. RESULTS Only 0.4% of metastases were located inside a hippocampus in 3% of all patients. SCLC showed a relatively high rate of hippocampal metastasis (18.2% of all SCLC patients) and HS-WBRT in a commonly applied fractionation scheme would increase the risk for brain relapse by ∼4% compared to conventional WBRT. NSCLC showed a lower rate of brain metastasis in the hippocampi (2.8%) and HS-WBRT would account for a slightly increased absolute risk of 0.2%. CONCLUSIONS Prophylactic or therapeutic HS-WBRT is expected to be associated with a low risk of undertreatment. For SCLC, it bears a minimally elevated risk of failure compared to standard WBRT. In NSCLC, HS-WBRT is most likely not associated with a clinically relevant increase in risk of failure.

Factors of influence on acute skin toxicity of breast cancer patients treated with standard three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery (BCS)

Purpose/ObjectivesStandard 3D-CRT after BCS may cause skin toxicity with a wide range of intensity including acute effects like erythema or late effects. In order to reduce these side effects it is mandatory to identify potential factors of influence in breast cancer patients undergoing standard three-dimensional conformal radiation therapy (3D-CRT) of the breast and modern systemic therapy.Materials/MethodsBetween 2006 and 2010 a total of 211 breast cancer patients (median age 52,4 years, range 24–77) after BCS consecutively treated in our institution with 3D-CRT (50 Gy whole breast photon radiotherapy followed by 16 Gy electron boost to the tumorbed) were evaluated with special focus on documented skin toxicity at the end of the 50 Gy-course. Standardized photodocumentation of the treated breast was done in each patient lying on the linac table with arms elevated. Skin toxicity was documented according to the common toxicity criteria (CTC)-score. Potential influencing factors were classified in three groups: patient-specific (smoking, age, breast size, body mass index = BMI, allergies), tumor-specific (tumorsize) and treatment-specific factors (antihormonal therapy with tamoxifen or aromatase inhibitors, chemotherapy). Uni- and multivariate statistical analyses were done using IBM SPSS version 19.ResultsAfter 50 Gy 3D-CRT to the whole breast 28.9% of all 211 patients had no erythema, 62.2% showed erythema grade 1 (G1) and 8.5% erythema grade 2. None of the patients had grade 3/4 (G3/4) erythema.In univariate analyses a significant influence or trend on the development of acute skin toxicities (erythema G0 versus G1 versus G2) was observed for larger breast volumes (p=0,004), smoking during radiation therapy (p=0,064) and absence of allergies (p=0,014) as well as larger tumorsize (p=0,009) and antihormonal therapy (p=0.005).Neither patient age, BMI nor choice of chemotherapy showed any significant effect on higher grade toxicity. In the multivariate analysis, factors associated with higher grade skin toxicity were larger breast target volume (p=0,003), smoking (p=0,034) and absence of allergies (p=0,002).ConclusionPatients treated in this study showed less objectively documented skin toxicity after 50 Gy 3D-CRT compared to similar patient cohorts. Factors associated with higher grade skin toxicity were smoking during 3D-CRT, absence of allergies and larger breast volumes.

Postoperative Seroma Formation After Intraoperative Radiotherapy Using Low-Kilovoltage X-Rays Given During Breast-Conserving Surgery

PURPOSE To determine the frequency and volume of seroma after breast-conserving surgery (BCS) with or without intraoperative radiotherapy (IORT). METHODS AND MATERIALS Seventy-one patients with 73 breast cancers (IORT group) treated with IORT (20 Gy Intrabeam) as a boost during BCS were compared with 86 patients with 88 breast tumors (NO-IORT group) treated without IORT. Clinical examination and measurement of seroma volume on treatment-planning CT (CT-seroma) was done at median interval of 35 days after BCS. RESULTS Seroma were found on palpation in 37 patients (23%) and on CT in 105 patients (65%; median volume, 26.3 mL). Interval between BCS and CT was significantly shorter in patients with palpable seroma (median, 33 days) or CT-seroma (33 days) compared with those with no palpable seroma (36.5 days; p = 0.027) or CT-seroma (52 days, p < 0.001). The rate of palpable seroma was not different (IORT n = 17, 23%; NO-IORT n = 20, 23%; p = 0.933), whereas fewer patients required puncture in the IORT group [3 (4%) vs. 10 (11%)]. In contrast, more patients showed CT-seroma after IORT (IORT n = 59, 81%; NO-IORT n = 46, 52%; p < 0.001). The interval between BCS and CT was significantly shorter in patients with IORT as compared with the NO-IORT patients (median, 33 days vs. 41.5 days; p = 0.036). CONCLUSION Intraoperative radiotherapy with low-kilovoltage X-rays during BCS is not associated with an increased rate of palpable seroma or seroma requiring treatment. The rate of seroma formation on CT was higher after IORT compared with the NO-IORT group, which might be because of the shorter interval between BCS and CT.

Radiotherapy for tumors of the stomach and gastroesophageal junction – a review of its role in multimodal therapy

There is broad consensus on surgical resection being the backbone of curative therapy of gastric- and gastroesophageal junction carcinoma. Nevertheless, details on therapeutic approaches in addition to surgery, such as chemotherapy, radiotherapy or radiochemotherapy are discussed controversially; especially whether external beam radiotherapy should be applied in addition to chemotherapy and surgery is debated in both entities and differs widely between regions and centers. Early landmark trials such as the Intergroup-0116 and the MAGIC trial must be interpreted in the context of potentially insufficient lymph node resection. Despite shortcomings of both trials, benefits on overall survival by radiochemotherapy and adjuvant chemotherapy were confirmed in populations of D2-resected gastric cancer patients by Asian trials.Recent results on junctional carcinoma patients strongly suggest a survival benefit of neoadjuvant radiochemotherapy in curatively resectable patients. An effect of chemotherapy in the perioperative setting as given in the MAGIC study has been confirmed by the ACCORD07 trial for junctional carcinomas; however both the studies by Stahl et al. and the excellent outcome in the CROSS trial as compared to all other therapeutic approaches indicate a superiority of neoadjuvant radiochemotherapy as compared to perioperative chemotherapy in junctional carcinoma patients. Surgery alone without neoadjuvant or perioperative therapy is considered suboptimal in patients with locally advanced disease.In gastric carcinoma patients, perioperative chemotherapy has not been compared to adjuvant radiochemotherapy in a randomized setting. Nevertheless, the results of the recently published ARTIST trial and the Chinese data by Zhu and coworkers, indicate a superiority of adjuvant radiochemotherapy as compared to adjuvant chemotherapy in terms of disease free survival in Asian patients with advanced gastric carcinoma. The ongoing CRITICS trial is supposed to provide reliable conclusions about which therapy should be preferred in Western patients with gastric carcinoma. If radiotherapy is performed, modern approaches such as intensity-modulated radiotherapy and image guidance should be applied, as these methods reduce dose to organs at risk and provide a more homogenous coverage of planning target volumes.

Clinical outcome of hypofractionated breath-hold image-guided SABR of primary lung tumors and lung metastases.

BackgroundStereotactic Ablative RadioTherapy (SABR) of lung tumors/metastases has been shown to be an effective treatment modality with low toxicity. Outcome and toxicity were retrospectively evaluated in a unique single-institution cohort treated with intensity-modulated image-guided breath-hold SABR (igSABR) without external immobilization. The dose–response relationship is analyzed based on Biologically Equivalent Dose (BED).Patients and methods50 lesions in 43 patients with primary NSCLC (n = 27) or lung-metastases of various primaries (n = 16) were consecutively treated with igSABR with Active-Breathing-Coordinator (ABC®) and repeat-breath-hold cone-beam-CT. After an initial dose-finding/-escalation period, 5x12 Gy for peripheral lesions and single doses of 5 Gy to varying dose levels for central lesions were applied. Overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC) and toxicity were analyzed.ResultsThe median BED2 was 83 Gy. 12 lesions were treated with a BED2 of <80 Gy, and 38 lesions with a BED2 of >80 Gy. Median follow-up was 15 months. Actuarial 1- and 2-year OS were 67% and 43%; respectively. Cause of death was non-disease-related in 27%. Actuarial 1- and 2-year PFS was 42% and 28%. Progression site was predominantly distant. Actuarial 1- and 2 year LC was 90% and 85%. LC showed a trend for a correlation to BED2 (p = 0.1167). Pneumonitis requiring conservative treatment occurred in 23%.ConclusionIntensity-modulated breath-hold igSABR results in high LC-rates and low toxicity in this unfavorable patient cohort with inoperable lung tumors or metastases. A BED2 of <80 Gy was associated with reduced local control.

Treatment of Adrenal Metastases with Conventional or Hypofractionated Image-guided Radiation Therapy – Patterns and Outcomes

Background/Aim: Metastases involving the adrenal glands can be treated surgically or with radiation therapy. Retrospective studies indicate that radiotherapy for this indication is safe, well-tolerated and associated with symptom palliation and good local control. We conducted this analysis to report on patterns and outcomes of patients with adrenal metastases treated with hypo- or conventionally fractionated image-guided radiotherapy. Patients and Methods: Patients with adrenal metastases from solid tumors treated at our department between 01/2010-12/2017 were reviewed. A total of 22 lesions were treated in 18 patients with a median dose of 35 Gy (20-60 Gy) in a median number of 7 (4-25) fractions. Results: No grade ≥3 toxicity occurred. Median overall survival was 11.9 months. Five local failures occurred (22.7%). Lesion sizes or radiation dose were not correlated with local control. Patients treated for oligometastatic and oligoprogressive disease had a median overall survival of 33 and 6.5 months, respectively (palliative/polymetastatic: 1.6 months). Symptoms improved in all patients treated for clinically apparent lesions. Conclusion: Stereotactic radiotherapy of adrenal metastases was safe and effective in patients with oligometastases or oligoprogression. In palliative patients, short-course radiotherapy complemented with supportive care should be preferred.