We report our experience of using helical tomotherapy (HT) to treat large and irregular shaped loco-regional advanced breast cancer target volumes embracing various organs at risk.
We retrospectively ...analyzed 26 patients treated for very large, irregular shaped breast cancers. Patients were treated either with the intent to achieve local control in a primary setting (n = 14) or in a reirradiation setting (n = 12). The recurrence group was heavily pretreated with systemic therapy. Tumors were characterized by wide infiltration of the skin, encompassing mostly a complete hemithorax. The primary group underwent irradiation of supraclavicular, infraclavicular, axillary and parasternal lymphonodal region. Radiotherapy was combined with chemotherapy (n = 11). We assessed the PTV volume and its craniocaudal extension, the dose to the organs at risk, acute toxicity and survival.
Median PTV was 2276 cm
(1476-6837 cm
) with a median cranio-caudal extension of 28 cm (15-52 cm). The median dose to PTV was 40 Gy (32-60Gy). HT could be carried out in all patients without interruption. The acute toxicities were mild to moderate. The median LRFS and OS after radiotherapy was 21 and 57 months for the primary group versus 10 and 11 months for the recurrence group. Median PFS was 18 months (primary group) and 7 months (recurrence group).
HT is feasible for advanced thorax embracing target volumes with acceptable acute toxicity. Both curative and palliative indications can be considered good indications based on treatment volume and anatomical constellation.
Abstract
BACKGROUND
Tumor Treating Fields (TTFields) are low intensity (1–3 V/cm) alternating electric fields with an intermediate frequency of 100–300 kHz. TTFields in addition to temozolomide (TMZ) ...after radiochemotherapy according to Stupp significantly increased progression-free survival (PFS), overall survival (OS) and long-term survival rates in patients with newly diagnosed glioblastoma (GBM) in the multicenter phase 3, EF-14 trial. Post-hoc analysis of the trial revealed that TTFields in combination with second-line therapy after first recurrence significantly prolonged OS compared to second-line therapy alone. We here report on a GBM patient with partial resection showing regressive volume of unresected, previously progressive tumor under combination therapy of TTFields and second-line CCNU chemotherapy.
MATERIAL AND METHODS
In November 2018, MRI of a 59-year-old female patient revealed a large heterogeneous space-occupying lesion in the left occipital region with clearly contrast-enhanced margin, perifocal edema and two smaller contrast-enhancing lesions in the splenium corporis callosi and right of the trigonum suboccipitale. While the tumor in the left occipital region was completely resected, lesions in the right hemisphere remained unresected. Histopathology identified MGMT-promoter methylated GBM. The patient received concomitant radiochemotherapy followed by adjuvant TMZ. However, after three cycles, the unresected tumor progressed, TMZ was exchanged by procarbazine/CCNU and TTFields therapy was initiated. After two cycles, chemotherapy was changed to only CCNU due to further progression while TTFields therapy was continued.
RESULTS
One year after diagnosis, MRI showed no contrast-enhancing tissue in the resection cavity and regressive perifocal edema while lesions in the right hemisphere remained stable. Under tolerable hematotoxicity CCNU was continued together with TTFields, to which the patient showed high adherence far beyond the suggested threshold of 75%. Control examination in February 2020 reported regressive tumor volume in the right hemisphere under CCNU/TTFields therapy. Until January 2021, the tumor regressed even further without the detection of new lesions. The patient is currently continuing CCNU together with TTFields, achieving an average usage of 84% over the last twelve months.
CONCLUSION
In the presented case, the combination of TTFields and CCNU was feasible and safe in progressive GBM. The patient showed radiological response and local tumor regression under the combination therapy, whereas the tumor had previously progressed under chemotherapy alone. In conclusion, the addition of TTFields to chemotherapy is a valuable treatment option to improve clinical and radiological outcome of patients with progressive GBM. This example of TTFields use in clinical practice encourages its use beyond tumor progression.
Tumor but not normal cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface (mHsp70) from where it can be actively released. Therefore, membrane (mHsp70) and ...soluble Hsp70 (sHsp70) were investigated as potential tumor biomarkers and for monitoring the outcome of radiation therapy.
Biopsies and blood were collected from patients with squamous cell carcinoma of the head and neck (SCCHN) at different time points (before, during therapy and in the follow-up period). Hsp70 membrane expression was determined on single cell suspensions of tumor biopsies and reference tissues by flow cytometry, sHsp70 protein and antibody levels were determined in the serum of patients and healthy donors by ELISA and NK cell markers that are related to the presence of sHsp70 were analyzed in the patient's peripheral blood lymphocytes (PBL).
Tumor biopsies exhibited significantly increased mHsp70 expression levels compared to the reference tissue. Soluble Hsp70 levels were significantly higher in SCCHN patients compared to healthy human volunteers and high mHsp70 expression levels on tumor cells were associated with high sHsp70 levels in the serum of patients. Following surgery and radiotherapy sHsp70 levels in patients dropped in patients without tumor relapse in the follow-up period. In contrast to sHsp70 protein, anti-Hsp70 antibody levels remained nearly unaltered in the serum of SCCHN patients before and after therapy. Furthermore, sHsp70 protein but not anti-Hsp70 antibody levels were found to be associated with the tumor volume in SCCHN patients before start of therapy. The expression densities of the activatory NK cell markers CD56, CD94, NKG2D, NKp30, Nkp44, and NKp46 differed in patients following therapeutic intervention. A significant increase in the density of NKG2D was observed in SCCHN patients in the follow-up period after surgery and radiotherapy.
We suggest sHsp70 as a potential biomarker for detecting tumors and for monitoring the clinical outcome of radiotherapy in SCCHN patients.
The theme of homelands is not only topical but also highly charged. An intensive and above all ongoing reflection on this changing concept is essential - not only in the light of current migration ...movements. In this discursively structured volume, historians, humanities scholars, social scientists and scientists come together to discuss the problematic nature of homelands. Their perspectives do not limit themselves to the contemporary concepts of homelands, but rather reach all the way back to antiquity. The contributors to this volume, all of whom were involved in a workshop at the Laboratory of the Enlightenment at the Friedrich Schiller University in Jena include Friedemann Schmoll, Martina Haedrich, Frank W, Hellwig and Meinolf Vielberg.
This study describes the antibiotic resistance of 1961 staphylococcal strains that were isolated at the University Hospital of Vienna from July to December 1991. Staphylococcus aureus (SA) ...represented 43.2%; coagulase-negative (CNS) staphylococci 56.8%, three quarters of which were Staphylococcus epidermidis. Excepting netilmicin, the proportion of resistant strains to all antibiotics was higher with CNS than SA. Methicillin resistance (M(r)) was found in 11.8% of SA and 30.3% of CNS. Borderline oxacillin resistance (BOR) was noted in 7.4% of SA and 32.5% of CNS. It is important to note that severe or generalized infections due to M(r) staphylococci should be treated with glycopeptide antibiotics such as vancomycin or teicoplanin from the very beginning, whereas chemotherapy of those with BOR strains may also be carried out with beta lactamase-stable beta lactam antibiotics. Comparing the results of this study with those of the first half of 1991, the respective proportion of M(r) staphylococci was significantly lower than 23.6% for SA and 47.6% for CNS recorded then. As compared with the foregoing period, however, these strains demonstrated increased resistance frequencies to gentamicin (from 81.3 to 90%), amikacin (from 35.4 to 69%), netilmicin (35.4 to 55%), and ciprofloxacin (56.2 to 64%). This is taken as an indication for the epidemic spread of a clone of resistant strains.
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