Efficient Creation of Ultracold Ground State

We report the creation of ultracold ground state ^{6}Li^{40}K polar molecules with high efficiency. Starting from weakly bound molecules, stimulated Raman adiabatic passage is adopted to coherently transfer the molecules to their singlet rovibrational ground state |X^{1}Σ^{+},v=0,J=0⟩. By employing a singlet stimulated Raman adiabatic passage pathway and low-phase-noise narrow-linewidth lasers, we observed a one-way transfer efficiency of 96(4)%. Held in an optical dipole trap, the lifetime of the ground state molecules is measured to be 5.0(3) ms. The large permanent dipole moment of LiK is confirmed by applying a dc electric field on the molecules and performing Stark shift spectroscopy of the ground state. With recent advances in the quantum control of collisions, our work paves the way for exploring quantum many-body physics with strongly interacting ^{6}Li^{40}K molecules.

Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities.

PURPOSE: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS: For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA.

Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer.

PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

Singlet Pathway to the Ground State of Ultracold Polar Molecules.

Starting from weakly bound Feshbach molecules, we demonstrate a two-photon pathway to the dipolar ground state of bi-alkali molecules that involves only singlet-to-singlet optical transitions. This pathway eliminates the search for a suitable intermediate state with sufficient singlet-triplet mixing and the exploration of its hyperfine structure, as is typical for pathways starting from triplet dominated Feshbach molecules. By selecting a Feshbach state with a stretched singlet hyperfine component and controlling the laser polarizations, we assure coupling to only single hyperfine components of the A^{1}Σ^{+} excited potential and the X^{1}Σ^{+} rovibrational ground state. In this way an ideal three level system is established, even if the hyperfine structure is not resolved. We demonstrate this pathway with ^{6}Li^{40}K molecules, and discuss its application to other important molecular species.

Testicular epidermoid cysts: a reevaluation.

BACKGROUND: Testicular epidermoid cysts (TECs) are rare benign testicular neoplasms. As TECs are rarely associated with germ cell tumours (GCTs), the understanding of biological behaviour and clinical management of TEC is unresolved. METHODS: We retrospectively searched the files of patients treated for testicular neoplasms and germ cell cancer in the time from 2000 to 2017. Those with TEC were subjected to closer review looking to clinical and histological features, and to results from imaging with ultrasonography (US), contrast enhanced sonography (CEUS) and magnetic resonance imaging (MRI). RESULTS: Among 589 patients undergoing surgery for testicular tumour, nine simple TECs were identified (1.5, 95% confidence intervals 0.53-2.50%). Median age was 26 years. Imaging revealed sharply demarcated roundish lesions with avascular central areas. Eight patients underwent testis-sparing excision with no recurrence ensuing. One had orchiectomy because of large size of the mass. Histologically, TECs consisted of cornifying squamous cell epithelium and no accompanying germ cell neoplasia in situ. Two additional cases (0.3% of all) required orchiectomy because these TECs were associated with ipsilateral GCT. CONCLUSIONS: TEC is usually a benign lesion that can safely be diagnosed with US, CEUS and MRI due to its roundish shape and its avascular centre. Histologically, this TEC corresponds to the prepubertal-type teratoma unrelated to germ cell neoplasia in situ of the 2016 WHO classification. The other subtype of TEC that is associated with invasive GCT represents a teratoma of postpubertal-type. From a clinical point of view it could be easier to differentiate between a "simple TEC" which is benign (prepubertal type) and a "complex TEC" which is malignant because of its association with invasive GCT.

ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up.

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

Is there still a place for retroperitoneal lymph node dissection in clinical stage 1 nonseminomatous testicular germ-cell tumours? A retrospective clinical study.

BACKGROUND: Primary retroperitoneal lymph node dissection (RPLND) ultimately lost its role as the standard management of clinical stage (CS) 1 nonseminomatous (NS) testicular germ cell tumours (GCTs) in Europe when the European Germ Cell Cancer Consensus Group released their recommendations in 2008. Current guide-lines recommend surgery only for selected patients but reasons for selection remain rather ill-defined. We evaluated the practice patterns of the management of CS1 patients and looked specifically to the role of RPLND among other standard treatment options. METHODS: We retrospectively evaluated the treatment modalities of 75 consecutive patients treated for CS1 NS at one centre during 2008-2017. The patients undergoing RPLND were selected for a closer review. Particular reasons for surgery, clinical features of patients, and therapeutic outcome were analyzed using descriptive statistical methods. RESULTS: Twelve patients (16%) underwent nerve-sparing RPLND, nine surveillance, 54 had various regimens of adjuvant chemotherapy. Particular reasons for surgery involved illnesses precluding chemotherapy (n = 2), patients´ choice (n = 4), and teratomatous histology of the primary associated with equivocal radiologic findings (n = 6). Five patients had lymph node metastases, two received additional chemotherapy. Antegrade ejaculation was preserved in all cases. One patient had a grade 2 complication that was managed conservatively. All RPLND-patients remained disease-free. CONCLUSIONS: Primary RPLND is a useful option in distinct CS1 patients, notably those with concurrent health problems precluding chemotherapy, and those with high proportions of teratoma in the primary associated with equivocal radiological findings. Informed patient's preference represents another acceptable reason for the procedure. RPLND properly suits the needs of well-selected patients with CS1 nonseminoma and deserves consideration upon clinical decision-making.

Interobserver variability in target volume delineation of hepatocellular carcinoma : An analysis of the working group "Stereotactic Radiotherapy" of the German Society for Radiation Oncology (DEGRO).

BACKGROUND: Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel. METHODS: The analysis was performed within the "Stereotactic Radiotherapy" working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch. RESULTS: The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT. CONCLUSION: The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.

Stability of a frequency-comb-based transfer-lock using a passive Fabry-Perot resonator.

We report on a transfer-lock laser frequency stabilization that utilizes a frequency comb (FC) and a radio frequency counter referenced to a GPS frequency standard to compensate for the frequency drifts of two lasers, which are locked to a single passive Fabry-Perot resonator (FPR). The method requires only one optical phase lock with the FC and allows transfer locking of lasers at wavelengths beyond the usable range of the FC. To attain a large frequency tuning range for the lasers, we implement optical serrodyning. We further demonstrate an efficient scheme to suppress residual amplitude modulation, thereby improving the stability of the Pound-Drever-Hall lock used in this case. The absolute frequency stability was found to be better than 2×10-13 on timescales up to 300 s. Hence, together with the frequency stability on short timescales provided by the FPR, this scheme facilitates coherent Raman spectroscopy as needed for an example for the production of ultracold dipolar heteronuclear molecules.

Relative survival of patients with non-malignant central nervous system tumours: a descriptive study by the Austrian Brain Tumour Registry.

BACKGROUND: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. METHODS: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. RESULTS: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). CONCLUSION: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases.

BACKGROUND: Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. METHODS: Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. RESULTS: NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0%) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5%) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. CONCLUSION: Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies.

Contrast-enhanced ultrasound and real-time elastography for the diagnosis of benign Leydig cell tumors of the testis - a single center report on 13 cases.

PURPOSE: To describe sonomorphological features in testicular Leydig cell tumors (LCTs) with a special focus on contrast-enhanced ultrasonography (CEUS) and real-time elastography (RTE). PATIENTS AND METHODS: In a series of 186 patients with testicular surgery for neoplastic disease, 13 benign LCTs (in 12 patients) were histopathologically diagnosed. Preoperatively, all patients had been examined with a standardized protocol (high-resolution grayscale and color-coded ultrasonography, CEUS). 5 patients underwent RTE. In CEUS, the filling time of the lesion was compared to that of 14 size-matched germ cell tumors (GCT). RESULTS: 10/13 LCTs had a size of < 10 mm, and a sharply demarcated hypoechoic appearance was typical (10/13). Color-coded ultrasonography detected signals in 8 lesions, while CEUS showed clear hypervascularization in all. LCTs had a significantly shorter filling time than GCTs (p < 0.0005), with 9/13 LCTs being completely filled within 4 s. In RTE, all 5 examined lesions were clearly "harder" than the surrounding testicular tissue. CONCLUSION: Contrary to some earlier reports, we could demonstrate marked hypervascularization in LCTs. This feature clearly allows for the differentiation of a small LCT from focal scars. However, it may only be visible on CEUS. In CEUS, LCT is suggested by the findings of a short filling time or by a circumferential vessel with a rapid centripetal filling, combined with a "harder" appearance in RTE. These features along with the findings of a small and peripherally situated hypoechoic tumor would justify an operative strategy with frozen section examination and possibly organ sparing surgery instead of orchiectomy.

Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group.

BACKGROUND: The treatment of testicular intraepithelial neoplasia (TIN), the progenitor of testicular germ cell tumours (GCTs), is based on little data. PATIENTS AND METHODS: Two hundred and twenty-eight GCT patients with contralateral TIN were retrospectively enrolled. Ten had surveillance, 122 radiotherapy to testis with 18-20 Gy, 30 cisplatin-based chemotherapy (two cycles), 51 chemotherapy (three cycles), and 15 carboplatin. The study end point was a malignant event (ME), defined as detection of TIN upon control biopsy or occurrence of a second GCT. The Secondary end point was hypogonadism during follow-up. RESULTS: Numbers, proportions of ME, and median event-free survival (EFS) times were: radiotherapy N = 3, 2.5%, 11.08 years; chemotherapy (two cycles) N = 15, 50%, 3.0 years; chemotherapy (three cycles) N = 12, 23.5%, 9.83 years; carboplatin N = 10, 66%, 0.9 years; surveillance N = 5, 50%, 7.08 years. EFS is significantly different among the groups. Hypogonadism rates were in radiotherapy patients 30.8%, chemotherapy (two cycles) 13%, chemotherapy (three cycles) 17.8%, carboplatin 40%, surveillance 40%. CONCLUSIONS: Local radiotherapy is highly efficacious in curing TIN. Chemotherapy is significantly less effective and the cure rates are dose-dependent. Though hypogonadism occurs in one-third of patients, radiotherapy with 20 Gy remains the standard management of TIN.

Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer.

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

Can treatment of pediatric Hodgkin's lymphoma be improved by PET imaging and proton therapy?

BACKGROUND AND PURPOSE: To explore a new positron emission tomography (PET)-based target concept for pediatric Hodgkin's lymphoma (PHL). PATIENTS AND METHODS: For 10 patients, the planning target volume PTV1 was based on initial CT tumor extension and PTV2 on anatomy-related PET-positive lymph node levels after chemotherapy. The treatment techniques investigated (prescribed dose 19.8 Gy) comprised opposed-field (2F), intensity-modulated photon (IMXT), and single-field (PS) proton techniques. Treatment concepts were compared concerning dose-volume histogram (DVH) parameters and organ-equivalent doses (OED). RESULTS: The median PTV1 and PTV2 were 902 ± 555 cm(3) and 281 ± 228 cm(3). When using PTV2 instead of PTV1 for all techniques, the D(2%) of the heart was reduced from 14 to 9 Gy and the D(mean) of the thyroid from 16.6 to 2.7 Gy. Low- (20%), median- (50%), and high-dose volumes (80%) were reduced by 60% for the heart and bones using PTV2. PS reduced the high-dose volume of the lungs and the heart by up to 60%. IMXT increased the low-dose volumes and OED. PTV2 reduced OED by 54 ± 10% for all organs at risk. CONCLUSION: PTV2 has a high impact on the treated volume and on sparing of organs at risk. The combination of an adaptive target volume definition with protons could contribute to future PHL treatment concepts.

MicroRNAs miR-371-3 in serum as diagnostic tools in the management of testicular germ cell tumours.

BACKGROUND: miRNAs are small noncoding RNA molecules that can be released into body fluids. Germ cell tumours (GCTs) overexpress miRNAs of the miR-371-3 cluster. Thus, serum levels of these miRNAs may correlate with tumour load. METHODS: miRNAs of the miR-371-3 cluster were quantified in cubital vein blood samples of 20 GCT patients with clinical stage 1, and of 4 patients with advanced stages before and after treatment. In six patients testicular vein blood (TVB) was examined additionally. Seventeen healthy males served as controls. Likewise, expression of miRNAs in 15 matching tumour specimens was measured. RESULTS: In all patients, serum levels of miRNAs 371-3 were much higher than in controls. In stage 1, levels decreased postoperatively 336.7-fold, 7.4-fold, and 7.7-fold for miRNAs 371a-3p, 372, and 373-3p, respectively (P<0.01). Also, in those cases with advanced disease levels dropped to the normal range after completion of treatment. miR-371-3 levels in TVB exceeded those in peripheral blood in all cases. Expression of miR-371a-3p was also documented in tumour tissue. However, no correlation was found regarding the extent of miRNA expression in tissue and the values measured in matching serum. CONCLUSION: Thus, miR-371a-3p serum level appears to be a useful biomarker in GCTs.

Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases.

BACKGROUND: Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit. METHODS: Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy. RESULTS: Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012). INTERPRETATION: This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ≥70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.

Brain-only metastatic breast cancer is a distinct clinical entity characterised by favourable median overall survival time and a high rate of long-term survivors.

BACKGROUND: The clinical course of breast cancer patients with brain metastases (BM) as only metastatic site (brain-only metastatic breast cancer (BO-MBC)) has been insufficiently explored. METHODS: All breast cancer patients with BM treated at our institution between 1990 and 2011 were identified. For each patient, full information on follow-up and administered therapies was mandatory for inclusion. Oestrogen receptor, progesterone receptor and Her2 status were determined according to standard protocols. Statistical analyses including computation of survival probabilities was performed. RESULTS: In total, 222 female patients (26% luminal; 47% Her2; 27% triple negative) with BM of MBC were included in this study. In all, 38/222 (17%) BM patients did not develop extracranial metastases (ECM) during their disease course and were classified as BO-MBC. Brain-only-MBC was not associated with breast cancer subtype or number of BM. The median overall survival of BO-MBC patients was 11 months (range 0-69) and was significantly longer than in patients with BM and ECM (6 months, range 0-104; P=0.007). In all, 7/38 (18%) BO-MBC patients had long-term survival of >3 years after diagnosis of BM and long-term survival was significantly more common in BO-MBC patients as compared with BM patients with ECM (P<0.001). CONCLUSIONS: Brain-only metastatic behaviour occurs in around 17% of breast cancer with BM and is not associated with breast cancer subtype. Exploitation of all multimodal treatment options is warranted in BO-MBC patients, as these patients have favourable prognosis and long-term survival is not uncommon.

Brain metastases free survival differs between breast cancer subtypes.

BACKGROUND: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. METHODS: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34-16.66) compared with 18 months (95% CI: 14.46-21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71-44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). CONCLUSION: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.

Multicenter evaluation of different target volume delineation concepts in pediatric Hodgkin's lymphoma. A case study.

BACKGROUND AND PURPOSE: In pediatric Hodgkin's lymphoma (PHL) improvements in imaging and multiagent chemotherapy have allowed for a reduction in target volume. The involved-node (IN) concept is being tested in several treatment regimens for adult Hodgkin's lymphoma. So far there is no consensus on the definition of the IN. To improve the reproducibility of the IN, we tested a new involved-node-level (INL) concept, using defined anatomical boundaries as basis for target delineation. The aim was to evaluate the feasibility of IN and INL concepts for PHL in terms of interobserver variability. PATIENTS AND METHODS: The INL concept was defined for the neck and mediastinum by the PHL Radiotherapy Group based on accepted concepts for solid tumors. Seven radiation oncologists from six European centers contoured neck and mediastinal clinical target volumes (CTVs) of 2 patients according to the IN and the new INL concepts. The median CTVs, coefficient of variation (COV), and general conformity index (CI) were assessed. The intraclass correlation coefficient (ICC) for reliability of delineations was calculated. RESULTS: All observers agreed that INL is a feasible and practicable delineation concept resulting in stronger interobserver concordance than the IN (mediastinum CI(INL) = 0.39 vs. CI(IN) = 0.28, neck left CI(INL) = 0.33; CI(IN) = 0.18; neck right CI(INL) = 0.24, CI(IN) = 0.14). The COV showed less dispersion and the ICC indicated higher reliability of contouring for INL (ICC(INL) = 0.62, p < 0.05) as for IN (ICC(IN) = 0.40, p < 0.05). CONCLUSION: INL is a practical and feasible alternative to IN resulting in more homogeneous target delineation, and it should be therefore considered as a future target volume concept in PHL.