[Stereotactic radiosurgery of brain tumors]. / Agyi daganatos elváltozások sztereotaxiás besugárzása.

Stereotactic radiosurgery is today a well-established treatment modality for various intracranial pathologies. The principle of high dose focused intracranial radiation guided by stereotactic technique ("Gamma Knife") was introduced by the Swedish neurosurgeon Prof. Lars Leksell in 1968. After the advent of CT and later MR imaging, stereotactic radiosurgery evolved rapidly regarding indications, and new technical solutions made it possible for linear accelerator systems to perform radiosurgery. A huge number of patients are treated yearly worldwide with this technology. In this article we overview the major indications, advantages and possible complications of stereotactic radiosurgery.

Interval From Simulation Imaging to Treatment Delivery in SABR of Lung Lesions: How Long is Too Long for the Lung?

Purpose: The purpose of this study was to evaluate the effect of delay between planning computed tomography (CT) used as a basis for treatment planning and the start of treatment (delay planning treatment [DPT]), on local control (LC) for lung lesions treated by SABR. Methods and Materials: We pooled 2 databases from 2 monocentric retrospective analysis previously published and added planning CT and positron emission tomography (PET)-CT dates. We analyzed LC outcomes based on DPT and reviewed all available cofounding factors among demographic data and treatment parameters. Results: A total of 210 patients with 257 lung lesions treated with SABR were evaluated. The median DPT was 14 days. Initial analysis revealed a discrepancy in LC as a function of DPT and a cutoff delay of 24 days (21 days for PET-CT almost systematically done 3 days after planning CT) was determined according to the Youden method. Cox model was applied to several predictors of local recurrence-free survival (LRFS). Univariate analysis showed LRFS decreasing significantly related to DPT ≥24 days (P = .0063), gross tumor volume, and clinical target volume (P = .0001 and P = .0022), but also with the presence of >1 lesion treated with the same planning CT (P = .024). LRFS increased significantly with higher biological effective dose (P < .0001). On multivariate analysis, LRFS remained significantly lower for lesions with DPT ≥24 days (hazard ratio, 2.113; 95% confidence interval, 1.097-4.795; P = .027). Conclusions: DPT to SABR treatment delivery for lung lesions appears to reduce local control. Timing from imaging acquisition to treatment delivery should be systematically reported and tested in future studies. Our experience suggests that the time from planning imaging to treatment should be <21 days.

The Role of Stereotactic Radiotherapy in the Management of Melanoma, A Retrospective Single Institute Preliminary Study of 30 Patients.

Cutaneous melanoma is the third most common type of skin cancer in the world. The incidence of melanoma is increasing in most countries, however, mortality seems to be slowly decreasing. The treatment of advanced cutaneous melanoma changed radically since 2011. The new therapeutic modalities, such as immuno- and targeted therapies give a chance to successfully reach more prolonged progression-free survival (PFS) and overall survival (OS) in patients with metastatic melanoma. Despite the great therapeutic benefit, most patients eventually develop resistance to these therapies, and the disease will progress. In some cases oligoprogression develops. In those cases local therapy, such as stereotactic radiotherapy can make it possible to continue the previously applied effective medical treatment for the benefit of patients. In our study of a total of 30 patients-20 of them received pre-treatment with systemic medical therapy-received stereotactic radiotherapy using various systems, in the National Institute of Oncology, Hungary, Budapest. We managed to prolong the systemic therapy for 12.5 months median period with the assistance of CyberKnife technique. Therapy related adverse events were mostly tolerable with only 3% of Grade 3 toxicity. We concluded that stereotactic radiotherapy and stereotactic radiosurgery, are safe, and effective therapeutic modalities for regional tumor control in cases of oligoprogression.

[Stereotactic radiotherapy with CyberKnife and linear accelerator in the management of malignant melanoma]. / CyberKnife és lineáris gyorsító alapú sztereotaxiás sugárkezelés alkalmazása melanómában.

Stereotactic radiotherapy gains more and more importance in the management of malignant melanoma, owing to technical developments of recent years. This approach might be applied with success in solitary or oligometastatic cases, since the deliverable biological dose is far higher than that of conventional radiotherapy. Beyond chemotherapy of decreasing importance, there is a widening range of new targeted and immunotherapy agents, leading to longer survival times even in disseminated stages. This latter underlines that it is worth to treat metastatic lesions locally, making this strategy part of present clinical routine. The authors summarize relevant literature of strereotactic radiotherapy in malignant melanoma, and describe related concepts such as oligometastases, abscopal effect or the combination of radiosurgery with modern systemic therapies.

[Radiotherapy of pancreatic cancer]. / A hasnyálmirigyrák sugárterápiája.

The therapy of pancreatic cancer is fundamentally based on surgical removal and chemotherapy. The available evidence and results of publications concerning the application of radiotherapy are controversial. Accordingly, the international guidelines formulated by radiation oncology organizations have paramount interest in this particular pathology. Answers are eagerly awaited in several unclear questions from ongoing, or recently closed, yet unpublished trials. Modern radiotherapy techniques, like stereotactic radiotherapy, or actually less available modalities, like particle therapy or magnetic resonance imaging guided radiotherapy show promising results, as well as combination of radiation with immunotherapy.

Accelerated partial breast irradiation with 3-dimensional conformal and image-guided intensity-modulated radiotherapy following breast conserving surgery - 7-Year results of a phase II trial.

PURPOSE: To present the 7-year results of accelerated partial breast irradiation (APBI) using three-dimensional conformal (3D-CRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) following breast-conserving surgery (BCS). PATIENTS AND METHODS: Between 2006 and 2014, 104 patients were treated with APBI given by means of 3D-CRT using 3-5 non-coplanar, isocentric wedged fields, or IG-IMRT using kV-CBCT. The total dose of APBI was 36.9 Gy (9 × 4.1 Gy) using twice-a-day fractionation. Survival results, side effects and cosmetic results were assessed. RESULTS: At a median follow-up of 90 months three (2.9%) local recurrences, one (0.9%) regional recurrence and two (1.9%) distant metastases were observed. The 7-year local (LRFS), recurrence free survival was 98.9%. The 7-year disease-free (DFS), metastases free (MFS) and overall survival (OS) was 94.8%, 97.9% and 94.8%, respectively. Late side effects included G1 skin toxicity in 15 (14.4%), G1, G2, and G3 fibrosis in 26 (25%), 3 (2.9%) and 1 (0.9%) patients respectively. Asymptomatic (G1) fat necrosis occurred in 10 (9.6%) patients. No ≥ G2 or higher late side effects occurred with IMRT. The rate of excellent/good and fair/poor cosmetic results was 93.2% and 6.8%, respectively. CONCLUSION: 7-year results of APBI with 3D-CRT and IG-IMRT are encouraging. Toxicity profile and local tumor control are comparable to other series using multicatheter interstitial brachytherapy. Therefore, these external beam APBI techniques are valid alternatives to whole breast irradiation and brachytherapy based APBI.

[Application of modern radiotherapy in lung cancer]. / A tüdorák modern sugárterápiája.

Lung cancer is known for its outstanding incidence and mortality rates. One of the cornerstones of the treatment of this disease is radiation therapy. A remarkable development was observed in this field through the latest decades. Intensity-modulated and image-guided radiotherapy (IMRT and IGRT) are now widely accessible in Hungarian centers, and should be increasingly applied in case of thoracic irradiations as well. Application of modern radiotherapy techniques in the treatment of lung cancer allows better clinical results and lower rates of side effects. In this work the authors give an overview of this above mentioned development regarding different clinical stages.

Implementation of Stereotactic Accelerated Partial Breast Irradiation Using Cyber-Knife - Technical Considerations and Early Experiences of a Phase II Clinical Study.

To report the implementation, dosimetric results of and early experiences with stereotactic accelerated partial breast irradiation (SAPBI) following breast conserving surgery (BCS) for postmenopausal low-risk St I-II invasive breast cancer (IBC) patients. Between November 2018 and August 2019, 27 patients were registered in our phase II prospective study. SAPBI was performed with Cyber-Knife (CK) M6 machine, in 4 daily fractions of 6.25 Gy to a total dose of 25 Gy. Respiratory movements were followed with implanted gold markers and Synchrony system. Corrections for patient displacement and respiratory movement during treatment were performed with the robotic arm. Early side effects, cosmetic results, and dosimetric parameters were assessed. The average volume of the surgical cavity, clinical target volume (CTV), and planning target volume (PTV_EVAL) were 8.1 cm3 (range: 1.75-27.3 cm3), 55.3 cm3 (range: 26.2-103.5 cm3), and 75.7 cm3 (range: 40-135.4 cm3), respectively. The mean value of the PTV_eval/whole breast volume ratio was 0.09 (range: 0.04-0.19). No grade 2 or worst acute side-effect was detected. Grade 1 (G1) erythema occurred in 6 (22.2%) patients, while G1 oedema was reported by 3 (11.1%) cases. G1 pain was observed in 1 (3.4%) patient. Cosmetic result were excellent in 17 (62.9%) and good in 10 (37.1%) patients. SAPBI with CK is a suitable and practicable technique for the delivery of APBI after BCS for low-risk, St. I-II. IBC. Our early findings are encouraging, CK-SAPBI performed with four daily fractions is convenient and perfectly tolerated by the patients.

Stereotactic robotic body radiotherapy for patients with oligorecurrent pulmonary metastases.

BACKGROUND: Our aim is to report treatment efficacy and toxicity of patients treated by robotic (Cyberknife®) stereotactic body radiotherapy (SBRT) for oligorecurrent lung metastases (ORLM). Additionally we wanted to evaluate influence of tumor, patient and treatment related parameters on local control (LC), lung and distant progression free- (lung PFS/Di-PFS) and overall survival (OS). METHODS: Consecutive patients with up to 5 ORLM (confirmed by FDG PET/CT) were included in this study. Intended dose was 60Gy in 3 fractions (prescribed to the 80% isodose volume). Patients were followed at regular intervals and tumor control and toxicity was prospectively scored. Tumor, patient and treatment data were analysed using competing risk- and Cox regression. RESULTS: Between May 2010 and March 2016, 104 patients with 132 lesions were irradiated from primary lung carcinoma (47%), gastro-intestinal (34%) and mixed primary histologies (19%). The mean tumor volume was 7.9 cc. After a median follow up of 22 months, the 1, 2 and 3 year LC rate (per lesion) was 89.3, 80.0 and 77.8% respectively. The corresponding (per patient) 1, 2 and 3 years lung PFS were 66.3, 50.0, 42.6%, Di-PFS were 80.5, 64.4, 60.6% and OS rates were 92.2, 80.9 and 72.0% respectively. On univariable analysis, gastro-intestinal (GI) as primary tumor site showed a significant superior local control versus the other primary tumor sites. For OS, significant variables were primary histology and primary tumor site with a superior OS for patients with metastases of primary GI origin. LC was significantly affected by the tumor volume, physical and biologically effective dose coverage. Significant variables in multivariable analysis were BED prescription dose for LC and GI as primary site for OS. The vast majority of patients developed no toxicity or grade 1 acute and late toxicity. Acute and late grade 3 radiation pneumonitis (RP) was observed in 1 and 2 patients respectively. One patient with a centrally located lesion developed grade 4 RP and died due to possible RT-induced pulmonary hemorrhage. CONCLUSIONS: SBRT is a highly effective local therapy for oligorecurrent lung metastases and could achieve long term survival in patients with favourable prognostic features.

[Early experience with CyberKnife treatment in case of intra-, suprasellar hypernephroma metastasis]. / Korai tapasztalataink CyberKnife-kezeléssel suprasellarisan is terjedo hypernephroma-áttét esetén.

Among tumours found in the suprasellar region metastases are very rare and the most frequent primary tumours are lung and breast cancer. Data of a patient with clear cell renal carcinoma with intra-suprasellar metastasis will be discussed. As in most of the tumours in the sellar region, the first symptom was visual deterioration with visual field defect. A transsphenoidal debulking of the tumour was performed and the residual tumor was treated by CyberKnife hypofractionated stereotactic radiotherapy. Both our patient's visual acuity and visual field impairment improved after the surgery and CyberKnife treatment. At 6-month after irradiation, MR of the sella showed a complete remission of the tumour. This was the first treatment with CyberKnife in our country in case of a tumour close to the optic chiasm. According to our best knowledge, there are 21 cases in the literature with renal cell carcinoma metastasis in the suprasellar region.

[Stereotactic body radiation therapy with CyberKnife accelerator for low- and intermediate risk prostate cancer]. / Kis és közepes kockázatú prosztatarákos betegek sztereotaxiás sugárkezelése CyberKnife gyorsítóval: korai radiogén mellékhatások.

We report implementation of stereotactic body radiotherapy (SBRT) for the treatment of early, localized prostate cancer patients, and acute side effects caused by radiation therapy. Between February 2018 and July 2018, 36 prostate cancer patients were treated with SBRT. Treatments were performed with "CyberKnife M6" linear accelerator. In low-risk patients 8 Gy was delivered to the prostate in each fraction. For intermediate risk, 8 Gy to the prostate and 6.5 Gy to the seminal vesicles were delivered by each fraction with a simultaneous integrated boost technique. A total of 5 fractions (total dose 40 Gy) were given every second working days. Acute radiogenic genitourinary (GU) and gastrointestinal (GI) side effects were assessed using the Radiation Therapy Oncology Group (RTOG) score. The duration of radiotherapy was 1 week and 3 days. The frequency of acute radiogenic side effects was as follows: GU grade 0: 13.9%, grade I: 30.6%, grade II: 52.8%, grade III: 2.7%. GI grade 0: 55.5%, grade I: 30.6%, grade II: 13.9%, grade III: 0%. Grade IV-V side effects were not observed. SBRT appears to be a safe and well tolerated treatment in patients with early stage, localized prostate cancer.

[Application of CyberKnife stereotactic radiosurgery in the treatment of head and neck cancer]. / A CyberKnife sztereotaxiás sugárterápia alkalmazásának lehetõsége fej-nyaki daganatok kezelésében.

The treatment of squamous cell carcinoma of the head and neck is multimodal, including surgery, chemotherapy, and radiotherapy, or the combination of those. Though aggressive treatment results in complete tumor remission in many patients even in locally advanced stages, unfortunately local relapse is not uncommon. For patients not candidate for salvage surgery, chemotherapy and conventional fractionated external beam irradiation can be applied. However, for patients previously treated with full-dose radiotherapy, the deliverable reirradiation dose is limited, considering the elevated risk of toxicity caused by cumulative doses. CyberKnife is a highly conformal radiosurgical technology which can successfully treat this subset of patients. In addition, it can be applied for hardly resectable rare tumors of the skull base and the head and neck region like chordoma, chondrosarcoma and paragangliomas. The CyberKnife stereotacic radiosurgery technology is now available in Hungary, in the National Institute of Oncology.

Combined dabrafenib and trametinib treatment in a case of chemotherapy-refractory extrahepatic BRAF V600E mutant cholangiocarcinoma: dramatic clinical and radiological response with a confusing synchronic new liver lesion.

Since the prognosis of advanced cholangiocarcinoma (CCA) remains poor with traditional chemotherapy, attention has shifted to molecularly targeted agents. Results of available clinical studies reveal little or no benefit of using targeted agents in advanced CCA. Limitations of these trials could be the lack of comprehensive molecular and genetic characterization of CCA samples in order to identify potential drug targets. Here we report a case of a 59-year-old female with chemotherapy-refractor, metastatic extrahepatic cholangiocarcinoma (EHCCA). After failure of first-line chemotherapy with cisplatin plus gemcitabine, next generation sequencing (NGS) based tumor molecular profiling was performed on aspiration cytological sample, that revealed BRAF V600E mutation. Multidisciplinary team decided on the initiation of combined treatment with BRAF and MEK inhibitors. Dabrafenib was started orally 150 mg twice a day, adding trametinib 2 mg once a day. Right from the initiation of targeted therapy, significant clinical improvement had been observed. Even though the first restaging computed tomography (CT) scan at 8 weeks revealed spectacular decrease in all metastatic sites, a new hepatic mass of 67 mm × 40 mm was identified and interpreted as new metastatic lesion. As the clinical and radiological response was contradictory, CT-guided biopsy was taken from the hepatic lesion while the therapy was continued on. Histopathologic evaluation excluded the hepatic lesion from being a metastasis, instead described it as a fibrotic, inflammatory lesion. At 12 week, PET CT confirmed further tumor regression with complete regression of the multiple cerebral metastases. The therapy has been extremely well tolerated by the patient. According to our knowledge, this is the first reported case on a successful treatment of EHCCA with the combination of dabrafenib and trametinib. Our case highlights the importance of molecular profiling in CCA, in order to find potential actionable driver mutations for personalised treatment.

Stereotactic Robotic Body Radiotherapy for Patients With Unresectable Hepatic Oligorecurrence.

BACKGROUND: The purpose of this study was to analyze local control (LC), liver progression-free survival (PFS), and distant PFS (DFS), overall survival (OS), and toxicity in a cohort of patients treated with stereotactic body radiotherapy (SBRT) with fiducial tracking for oligorecurrent liver lesions; and to evaluate the potential influence of lesion size, systemic treatment, physical and biologically effective dose (BED), treatment calculation algorithms and other parameters on the obtained results. PATIENTS AND METHODS: Unoperable patients with sufficient liver function had [18F]-fluorodeoxyglucose-positron emission tomography-computed tomography and liver magnetic resonance imaging to confirm the oligorecurrent nature of the disease and to further delineate the gross tumor volume (GTV). An intended dose of 45 Gy in 3 fractions was prescribed on the 80% isodose and adapted if risk-related. Treatment was executed with the CyberKnife system (Accuray Inc) platform using fiducials tracking. Initial plans were recalculated using the Monte Carlo algorithm. Patient and treatment data were processed using the Kaplan-Meier method and log rank test for survival analysis. RESULTS: Between 2010 and 2015, 42 patients (55 lesions) were irradiated. The mean GTV and planning target volume (PTV) were 30.5 cc and 96.8 cc, respectively. Treatments were delivered 3 times per week in a median of 3 fractions to a PTV median dose of 54.6 Gy. The mean GTV and PTV D98% were 51.6 Gy and 51.2 Gy, respectively. Heterogeneity corrections did not influence dose parameters. After a median follow-up of 18.9 months, the 1- and 2-year LC/liver PFS/DFS/OS were 81.3%/55%/62.4%/86.9%, and 76.3%/42.3%/52%/78.3%, respectively. Performance status and histology had a significant effect on LC, whereas age (older than 65 years) marginally influenced liver PFS. Clinical target volume physical dose V45 Gy > 95%, generalized equivalent uniform dose (a = -30) > 45 Gy and a BED (α/ß = 10) V105 Gy > 96% showed statistically significant effect on the LC. Acute Grade 3 gastrointestinal (GI) and late Grade 2 GI and fatigue toxicity were found in 5% and 11% patients, respectively. CONCLUSION: Favorable survival and toxicity results support the potential paradigm shift in which the use of SBRT in oligorecurrent liver disease could benefit patients with unresectable or resectable liver metastases.

The Influence of Treatment Position (Prone vs. Supine) on Clip Displacement, Seroma, Tumor Bed and Partial Breast Target Volumes: Comparative Study.

To analyse the displacement of surgical clips in prone (Pr) position and assess the consequences on target volumes and integral dose of partial breast irradiation (PBI). 30 post-lumpectomy breast cancer patients underwent CT imaging in supine (Su) and Pr. Clip displacements were measured by the distances from the clips to a common fix bony reference point. On each dataset, the tumour bed (TB = clips ± seroma), clinical target volume (CTV = TB + 1.5 cm) and planning target volumes (PTV = CTV + 1 cm) for PBI were determined and the volume pairs were compared. Furthermore estimation of integral dose ratio (IDR) within the breast from tangential treatment was performed as the ratio of the irradiated breast volume and the volume encompassing all clips. Clips close to the chest wall (CW) in Su showed significantly less displacement in Pr. The mean volumes of seroma, CTV and PTV were significantly higher in Pr than in Su. The PTV volume difference (Pr-Su) was significantly higher in patients with presence of seroma, deep clips and TB location in the superior-internal-quadrant (SIQ) and at the junction of superior quadrants (jSQ). In a multivariate analysis two factors remained significant: seroma and TB localization in SIQ-jSQ. The IDR was significantly larger in Su than in Pr (7.6 vs. 4.1 p < 0.01). Clip displacements varied considerably with respect to their relative position to the CW. In selected patients Pr position potentially leads to a significant increase in target volumes of PBI. Tangential beam arrangement for PBI should be avoided, not only in Su but in Pr as well in case of clip-based target volume definition.

[Implementation of cone beam CT-guided volumetric modulated arc therapy and establishment of related institutional quality assurance protocols]. / CT-képvezérelt, intenzitásmodulált ívterápiás sugárterápiás program klinikai rutinba való bevezetése és a megfelelõ rendszeres fizikusi minõségbiztosítás protokollizálása.

We intend to present the process of implementation of kilovoltage CT-guided volumetric modulated arc therapy (VMAT), and related quality assurance (QA). An Elekta Synergy™ linear accelerator has been installed recently in our institution, equipped with Agility© head, kilovoltage cone-beam CT image guidance and ability of arc therapy. The major steps of the implementation of these techniques and the background of physics QA will be described. Specific dynamic tests have been performed to verify intensity-modulated radiation delivery and the accuracy of on board imaging. Systematic daily, weekly and monthly physics QA protocols have been worked out and applied in the clinical practice. As a result, cone beam CT based image-guided radiotherapy (IGRT) and volumetric modulated arc therapy was introduced in our institution.

Respiratory Motion, Anterior Heart Displacement and Heart Dosimetry: Comparison Between Prone (Pr) and Supine (Su) Whole Breast Irradiation.

To analyze respiratory motion of surgical clips, chest wall (CW) and the anterior displacement of the heart and its impact on heart dosimetry between prone (Pr) and supine (Su) positions during whole breast radiotherapy after breast conserving surgery. Sixteen patients underwent 4D-CT for radiotherapy planning in Pr and Su positions. Maximum inhale and maximum exhale phases were analyzed. Mean 3D vectorial displacements ± standard deviations (SD) of the surgical clips were measured. Volumetric changes of the CW were recorded and compared. Cardiac displacement was assessed by a volume between the inner surface of CW and the myocardium of the heart (CW/H-V). For left-sided cases, comparative dosimetry was performed in each position simulating no- (Pr-noC, Su-noC) versus daily correction protocols (Pr-C, Su-C). The movements of 81 surgical clips were analyzed. Prone positioning significantly reduced both the mean 3D vectorial displacements (1.1 ± 0.6 (Pr) vs. 2.0 ± 0.9 mm (Su), p < 0.01) and their variability (0.3 ± 0.2 vs. 0.5 ± 0.3 mm, p = 0.01). Respiration-induced volumetric changes of CW were also significantly lower in Pr (2.3 ± 4.9 vs. 9.6 ± 7.1 cm(3), p < 0.01). The CW/H-V was significantly smaller in Pr than in Su (39.9 ± 14.6 vs. 64.3 ± 28.2 cm(3), p < 0.01). Besides identical target coverage heart, left-anterior-descending coronary artery (LADCA) and ipsilateral lung dose parameters were lowered with Pr-C compared to Pr-noC, Su-C and Su-noC. Prone position significantly reduced respiration-related surgical clip movements, their variability as well as CW movements. Significant anterior heart displacement was observed in Pr. Prone position with daily online correction could maximize the heart and LADCA protection.

[Accelerated partial breast irradiation with three-dimensional conformal external beam radiotherapy following breast-conserving surgery -- preliminary results of a phase II clinical study]. / Akcelerált parciális konformális külso emlobesugárzás emlomegtartó mûtét után - fázis II prospektív klinikai vizsgálat elozetes eredményei.

The aim of the study was to implement accelerated partial breast irradiation (APBI) by means of three-dimensional conformal radiotherapy (3D-CRT) following breast-conserving surgery (BCS) for early-stage breast cancer. Between December 2006 and February 2011, in 45 cases of low-risk, stage I-II breast cancer the tumour bed was marked with titanium clips during BCS. Postoperative APBI was given by means of 3D-CRT using 3 to 5 non-coplanar fields. The total dose of APBI was 36.9 Gy (9 x 4.1 Gy) using a twice-a-day fractionation over 5 consecutive days. Early and late radiation side effects and cosmetic results were analysed for the first 30 patients with a minimum follow-up of 1 year. At a mean follow-up of 25.2 months neither loco-regional nor distant failure was observed. Excellent, good, fair, and poor cosmetic outcome was detected in 10 (33.3%), 16 (53.4%), 4 (13.3%), and 0 (0%) patients, respectively. Grade 2 or worse acute side effect was not observed. Grade 1 fibrosis, grade 2 teleangiectasia and asymptomatic fat necrosis occurred in 4 (13.3%), 1 (3.3%) and 5 (16.7%) patients, respectively. No grade 3-4 late side effects were detected. 3D-CRT is a reproducible and feasible technique for the delivery of APBI following conservative surgery for the treatment of low-risk, early-stage invasive breast carcinoma. The preliminary results are promising, early- and mid-term radiation side effects are rare, and cosmetic results are excellent.

The role of high-dose-rate brachytherapy boost in breast-conserving therapy: Long-term results of the Hungarian National Institute of Oncology.

AIM: To report the long-term results of high-dose-rate (HDR) brachytherapy (BT) boost for breast cancer patients treated with conservative surgery and radiotherapy. MATERIALS AND METHODS: Between 1995 and 2007, 100 early-stage breast cancer patients received an HDR BT boost after conservative surgery and whole breast irradiation. Ten patients (10%) received a single-fraction HDR boost of 8-10.35 Gy using rigid needles, while 90 (90%) were treated with a fractionated multi-catheter HDR BT boost. The latter consisted of 3 × 4 Gy (n = 19), 3 × 4.75 Gy (n = 70), and 2 × 6.4 Gy (n = 1). Breast cancer related events, cosmetic results and side effects were assessed. RESULTS: At a median follow-up time of 94 months (range: 8-152) only 7 (7%) ipsilateral breast failures were observed for a 5- and 8-year actuarial rate of 4.5 and 7.0%, respectively. The 8-year disease-free, cancer-specific, and overall survival was 76.1, 82.8, and 80.4%, respectively. Cosmetic outcome was rated excellent in 17%, good in 39%, fair in 33%, and poor in 11%. Data on late radiation side effects were available for 91 patients (91%). Grade 3 fibrosis and grade 3 telangiectasia occurred in 6 (6.6%) and 2 (2.2%) patients, respectively. In univariate analysis only positive margin status had a significant negative effect on local control. CONCLUSIONS: HDR BT boost using multi-catheter implants produce excellent long-term local tumour control with acceptable cosmetic outcome and low rate of grade 3 late radiation side effects.

Fat necrosis after partial-breast irradiation with brachytherapy or electron irradiation versus standard whole-breast radiotherapy--4-year results of a randomized trial.

PURPOSE: To examine the incidence and clinical relevance of fat necrosis after accelerated partial-breast irradiation (PBI) using interstitial high-dose-rate brachytherapy (HDR-BT) in comparison with partial-breast electron irradiation (ELE) and whole-breast irradiation (WBI). METHODS AND MATERIALS: Between 1998 and 2004, 258 early-stage breast cancer patients were randomized to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 x 5.2 Gy HDR-BT (n = 88) or 50 Gy ELE (n = 40). The incidence of fat necrosis, its impact on cosmetic outcome, accompanying radiologic features, and clinical symptoms were evaluated. RESULTS: The 4-year actuarial rate of fat necrosis was 31.1% for all patients, and 31.9%, 36.5%, and 17.7% after WBI, HDR-BT and ELE, respectively (p(WBI/HDR-BT) = 0.26; p(WBI/ELE) = 0.11; p(ELE/HDR-BT) = 0.025). The respective rate of asymptomatic fat necrosis was 20.2%, 25.3%, and 10% of patients. The incidence of symptomatic fat necrosis was not significantly different after WBI (8.5%), HDR-BT (11.4%), and ELE (7.5%). Symptomatic fat necrosis was significantly associated with a worse cosmetic outcome, whereas asymptomatic fat necrosis was not. Fat necrosis was detectable with mammography and/or ultrasound in each case. Additional imaging examinations were required in 21% of cases and aspiration cytology in 42%. CONCLUSIONS: Asymptomatic fat necrosis is a common adverse event of breast-conserving therapy, having no significant clinical relevance in the majority of the cases. The incidence of both symptomatic and asymptomatic fat necrosis is similar after conventional WBI and accelerated partial-breast HDR-BT.