Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited.
We analysed clinical ...data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions.
Median age at diagnosis of BMs was 56 years (22–90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)–positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000–2009 with 2010–2015 (51%–44%), whereas the percentage of patients with luminal-like tumours increased (28%–34%; p = 0.0331). Patients with BMs in the posterior fossa were more often HER2 positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n = 65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p < 0.0001). Median overall survival (OS) time after development of BMs for the overall cohort was 7.4 months (95% confidence interval CI: 6.7–8.0 months). One-year survival rate was 37.7% (95% CI: 35.2–40.1). Patients with HER2-positive tumours had the longest median OS of 11.6 months (95% CI: 10.0–13.4) compared with 5.9 months (95% CI: 5.0–7.2) for patients with luminal-like and 4.6 months (95% CI: 3.9–5.4) for patients with triple-negative tumours. Patients with HER2-positive tumours who received anti-HER2 treatment had longer median OS than those without (17.1 months versus 7.2 months, p < 0.0001).
Prognosis of patients after developing BMs varies significantly according to the subtype. The outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2-negative patients. Our results underline the high medical need for improvement of treatment and prevention strategies for BMs in breast cancer patients.
•The first analysis of 1712 patients of breast cancer patients with brain metastases (BMs) is presented.•Localisation of BMs was different depending on tumour subtypes.•Survival times differ depending on the subtype and localisation of BMs.•A change in the incidence of BMs over time was observed.
In radiotherapy the normal tissue reaction is often a limiting factor for radiation treatment. Still there is no
screening method, which predicts normal tissue reaction on radiotherapy, especially in ...comparison to tumor tissue, and
therefore allows tailoring of the radiation dose to each patient. Here, we present a case of severe radiation-related side effects.
We applied classical cytogenetic techniques (Giemsa-banding and staining of centromeric regions), the comet assay
as well as multicolor fluorescence in situ hybridization on peripheral blood lymphocytes of this patient in order to determine
the radio-sensitivity on the DNA level and to correlate these findings with the clinical outcome. Our investigations
revealed abnormalities on chromosome 9, deficiencies in the DNA-repair capacity after radiation exposure and a high
number of radiation induced chromosomal aberrations. A detected high amount of residual damage two or three hours after
radiation exposure and repair as well as the high number of chromosomal aberrations (ChAs) suggests a correlation between
repair capacity and radiation induced ChAs. We concluded that the detected abnormalities might serve as a genetic
basis for the radio-sensitive phenotype of this patient. Taken together this report strengthens the idea that intensive DNA
genomic analysis of individual patients can serve as the basis for more favourable treatment of cancer patients.
Purpose: Tumor hypoxia is regarded as an important factor influencing radiation response, disease-free, and overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN). ...This study was performed to reevaluate the prognostic significance of the “classical oxygenation parameters” hypoxic fraction (percentage of pO
2 values < 5 mmHg or < 2.5 mmHg, respectively) and median pO
2, and to determine the influence of a new radiobiological factor. This factor was termed the “hypoxic subvolume” (HSV) and was defined as percentage of pO
2-values below 5 mmHg multiplied by the total tumor volume. The rationale of this parameter was to quantify approximately the amount of hypoxic tissue which should be correlated to the number of hypoxic cells in the tumor. It is obvious that a tumor of 100 cm
3 with a hypoxic fraction of 20% (HSV = 20 cm
3) contains more hypoxic cells than a tumor of 1 cm
3 with a hypoxic fraction of 50% (HSV = 0.5 cm
3).
Methods and Materials: Pretreatment pO
2 was assessed in 59 patients with SCCHN with the Eppendorf histograph, and pretreatment volume was determined by ultrasonography (lymphnode metastases) and computer tomography (primaries). All patients were referred to our departments for radiotherapy (
n = 27, median dose 70 Gy) or radiochemotherapy (
n = 32; 5-FU, mitomycin C, median dose 70 Gy), respectively. All parameters were evaluated using the Kaplan-Meier analysis, and significance was assumed at a
p-value of < 0.05 (log-rank test, Cox-Mantel). A multivariate analysis was performed to control for confounding factors. The median follow-up was 233 days. At the time of the evaluation, 34 of the 59 patients were dead.
Results: In univariate analyses, the hypoxic fraction (pO
2 < 5 mmHg, pO
2 < 2.5 mmHg
p < 0.05), the hemoglobin concentration (
p < 0.05), and the hypoxic subvolume (
p< 0.01) were of prognostic significance for overall survival. In multivariate analysis, the hemoglobin concentration and the hypoxic subvolume (
p = 0.01) were significant prognosticators. We found no significant correlation between tumor volume or median pO
2 and overall survival. No clear correlation was found between tumor volume and hypoxic fraction.
Conclusion: These data suggest that the total amount of hypoxic tissue, as determined by the hypoxic subvolume, influences the prognosis of patients suffering from SCCHN. In addition, our data confirm the statements of previous studies that low pretherapy pO
2-values indicate a worse prognosis.
Fragestellung:
Die publizierten Daten zeigen, dass ein Boost mittels IORT eine effektive Alternative zur konventionellen Tumorbettbestrahlung ist, die eine Verkürzung der postoperativen Radiatio um 7 ...– 10 Tage ermöglicht. In einer retrospektive Studie wurden die Ergebnisse der IORT hinsichtlich Toxizität, Kosmetik und Patientenzufriedenheit ausgewertet.
Patienten und Methodik:
Zwischen November 2010 und Januar 2014 wurden 120 Patientinnen, medianes Alter 65 Jahre (43 – 86 Jahre), mit einem IORT-Boost (20 Gy; Intrabeam System) im Rahmen einer brusterhaltenden Operation eines invasiven Mammakarzinoms (cT1 – 2 N0 – 1 M0) behandelt. 91 Frauen (76%) erhielten zusätzlich nach abgeschlossener Wundheilung und ggf. adjuvanter Chemotherapie die perkutane Ganzbrustbestrahlung (46 – 50 Gy), bei 29 Frauen (24%) wurde hierauf im Rahmen der Targit E Studie verzichtet.
Ergebnisse:
Der Nachuntersuchungszeitraum betrug im Median 24 Monate. Lokalrezidive sowie kontralaterale Mammakarzinome wurden bisher nicht beobachtet. Bei zwei Patientinnen (1,6%) wurde eine chronische Wundheilungsstörung diagnostiziert, so dass eine Mastektomie erforderlich war. Weitere Nebenwirkungen waren: entzündliche Reaktionen (5,8%), Schmerzen (16%), Serome (12%), Fibrose (17%), Erythem (6%), Hautretraktion (10%). Das kosmetische Ergebnis wurde von 90% der Patientinnen als sehr gut oder gut beurteilt. Die Auswertung des ZUF-8-Bogens zeigte eine hohe Therapiezufriedenheit.
Schlussfolgerung:
Die IORT ist zur Zeit eine etablierte Methodik, die zusätzliche Boost-Bestrahlung zu ersetzen. In unserem Patientenkollektiv traten relevante Nebenwirkungen auf, die sich auf die Patientengruppe beschränkten, bei denen eine konventionelle homogene Nachbestrahlung erfolgte. Der Verzicht hierauf, d.h. eine ausschließliche IORT, bei Patientinnen mit günstigen tumorbiologischen Kriterien, erscheint als zukünftige Perspektive, wenn entsprechend valide Studiendaten vorliegen.
Schlüsselwörter: intraoperative Radiotherapie – IORT – Mammakarzinom
Patients with small cell lung cancer (SCLC) and superior vena cava syndrome (SVCS) are widely believed to have a grave prognosis. The purpose of this study was to determine the prognosis of patients ...with SCLC and SVCS as compared to SCLC without SVCS.
A retrospective analysis of 408 cases of SCLC +/- SVCS was performed. Three- hundred and sixty showed no clinical signs of SVCS and 43 (11%) had SVCS; in 5 patients no adequate information was available about clinical signs of SVCS. All patients were classified as limited disease cases. About 98% received chemotherapy usually as the first treatment followed by radiotherapy. A median total dose of 46 Gy (range 30 to 70 Gy) was given at 2.0 Gy per fraction five times weekly. A prophylactic cranial irradiation was applied if a complete remission was achieved after chemotherapy or after 30 Gy of irradiation. Kaplan-Meier survival curves are shown and comparisons were made by the log-rank and the Gehan/Wilcoxon test. To adjust for prognostic factors, a proportional hazards analysis was done.
Patients without SVCS had 5-year survival rates ( +/- SE) and a median survival time (MST; 95% confidence intervals) of 11% +/- 2% and 13.7 months (12.7-14.5) in UICC Stage I to III; in Stage III the figures were 9% +/- 2% and 12.6 months (11.2-13.7). In comparison, SCLC with SVCS had 5-year survival rates of 15% +/- 7% and MST of 16.1 months (13.8-20.5). The difference was significant in univariate analysis (Stage II disease: p = 0.008 by the log-rank test). In a multivariate analysis of all patients, Stage (Stage I + II > III; p = 0.0003), SVCS (yes > no; p = 0.005), and Karnofsky performance status ( < or = 70 < 80-100%; p = 0.008) were of significant importance.
SVCS is a favorable prognostic sign in SCLC. The treatment should be curatively intended.
Die zeitliche Integration von Operation, Chemotherapie und Strahlentherapie bei der brusterhaltenden Behandlung des Mammakarzinoms ist in den letzten Jahren zunehmend in den Blickpunkt des Interesses ...gerückt. Die Grundlage dieser Studie bilden 74 Patientinnen, die im Zeitraum 1985 bis 1992 an unserem Institut eine postoperative Strahlentherapie erhielten. Die mediane Nachbeobachtungszeit betrug fünf Jahre. In 73% der Fälle waren die Patientinnen prä- oder perimenopausal. Fast alle Patientinnen (91%) befanden sich im UICC-Stadium II. Axilläre Lymphknoten waren dabei in 95% befallen. Eine makroskopisch vollständige Tumorresektion wurde bei allen Patientinnen erreicht, und in 65% der Fälle waren die Resektionsränder frei von invasivem oder intraduktalem Karzinom. Postoperativ wurden in 70% der Fälle sechs Zyklen Polychemotherapie (hauptsächlich CMF) vor Bestrahlungsbeginn appliziert. Die Strahlendosis betrug fast ausschließlich 60 Gy inklusive 10 Gy Boost. Fünf Jahre nach Behandlungsbeginn betrug die Überlebensrate 86% (95%-Vertrauensbereich 76 bis 93%), die krankheitsfreie Überlebensrate 73% (61 bis 83%) und die Lokalrezidivrate 8% (3 bis 16%). Der einzige signifikante prognostische Faktor für das krankheitsfreie Überleben war die Anzahl befallener Lymphknoten: 0 bis 3=86%, ≥4=40% (p<0,0001). Das Intervall zwischen Operation und Bestrahlungsbeginn (≤ oder >20 Wochen) hatte keinen signifikanten Einfluß auf das krankheitsfreie Überleben oder die lokale Tumorkontrolle. Dagegen fand sich ein Hinweis auf eine vermehrte lymphogene und hämatogene Metastasierung bei Verkürzung des Intervalls, bedingt durch die Applizierung von weniger als sechs Zyklen Chemotherapie vor Beginn der Strahlentherapie. In unserer Erfahrung hat die Verzögerung der Strahlentherapie, um die volle Anzahl von Chemotherapiezyklen vor Bestrahlungsbeginn applizieren zu können, keinen negativen Einfluß auf die lokale Tumorkontrolle. Dabei muß allerdings die niedrige statistische Power dieser Auswertung aufgrund der kleinen Patientenzahl beachtet werden. Es erscheint möglich, daß eine weniger intensive Chemotherapie vor Beginn der Bestrahlung mit einer Erhöhung der Fernmetastasierungsrate und einer entsprechenden Verschlechterung der krankheitsfreien Überlebensrate korreliert. Für Patientinnen mit erhöhtem Metastasierungsrisiko befürworten wir daher sechs Zyklen Polychemotherapie vor der Strahlenbehandlung. The timing of breast conserving surgery, chemotherapy, and radiotherapy in breast cancer treatment has become the subject of increasing interest over the last years. Seventy-four patients who underwent postoperative radiotherapy at our institution between 1985 and 1992 form the basis of this study. Median follow-up time was 5 years. Seventy-three percent of patients were pre- or perimenopausal. Almost all patients (91%) were UICC-stage II. Axillary lymph nodes were positive in 95% of cases. Complete gross tumor resection was achieved in all patients, and in 65% final pathological margins were free of invasive or intraductal carcinoma. Postoperatively, 70% of patients received 6 cycles of polychemotherapy (predominantly CMF) before onset of irradiation. The radiation dose was in almost all cases 60 Gy including 10 Gy boost. Five years after start of treatment overall survival, disease-free survival, and local recurrence rates were 86% (95%-confidence limits, 76 to 93%), 73% (61 to 83%), and 8% (3 to 16%), respectively. For disease-free survival, the only significant prognostic factor was the number of involved lymph nodes: 0 to 3=86%, ≥4=40% (p<0,0001). The interval between surgery and radiation (≤versus >20 weeks) had no significant influence on disease-free survival or local tumor control. In contrast, there was a trend of increased regional and distant failure with shortening of the interval due to the delivery of less than 6 cycles chemotherapy before the onset of radiotherapy. In our experience, there was no negative impact of a delay of radiotherapy in order to deliver full course chemotherapy before initiation of radiotherapy. However, the low statistical power of this analysis due to the small number of patients must be considered. It appears possible that a less intense chemotherapy before starting radiation treatment correlates with enhanced distant failure and subsequently decreased disease-free survival rates. Therefore, for patients at increased risk for distant metastasis, we prefer to give 6 cycles polychemotherapy before irradiation.PUBLICATION ABSTRACT
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