Rafal Tarnawski | Jagiellonian University (original) (raw)

Papers by Rafal Tarnawski

International Journal of Radiation Oncology Biology Physics, Nov 1, 2020

Current Radiopharmaceuticals, May 20, 2015

Due to somatostatin receptor expression in meningiomas, PET with somatostatin analogs appears to ... more Due to somatostatin receptor expression in meningiomas, PET with somatostatin analogs appears to be useful in radiotherapy treatment planning. We report the case of a 63-year-old man diagnosed with meningioma of the left frontal lobe in 2011. He underwent total tumor excision (pathology was atypical meningioma WHO 2) and radiotherapy, but one year after the completion of treatment, he complained about diplopia and left upper eyelid ptosis. The MRI showed a new parasagittal lesion and the patient received stereotactic radiotherapy. Few weeks later, two new lesions were found-one in the sella turcica region and the other adjacent to the greater wing of the right sphenoid bone. The patient underwent transsphenoidal biopsy, but was not qualified for neurosurgery due to high risk of bleeding. In the radiotherapy treatment planning, we used a fusion of MRI and 68Ga-DOTA-(Tyr3)-octreotate PET/CT images. The patient received stereotactic radiotherapy, first to the parasellar lesion and then to the progressing tumor adjoining the sphenoid bone. In both cases, PET/CT scans helped to define the target, its volume being bigger on PET/CT than on MRI images. In patients with meningiomas, 68-Ga-DOTA-(Tyr3)-octreotate PET/CT can be considered as a useful imaging modality in radiotherapy treatment planning, which helps to visualize the tumor extension and to define the target.

Folia Histochemica Et Cytobiologica, Jan 12, 2017

Introduction. Prediction of response to preoperative breast cancer chemotherapy may offer a subst... more Introduction. Prediction of response to preoperative breast cancer chemotherapy may offer a substantial optimization of medical management of this disease. The most efficient prediction would be done a priori, before the start of chemotherapy and based on the biological features of patient and tumor. Numerous markers have been proposed but none of them has been applied as a routine. The role of MKI67 and HSP90 expression has been recently suggested to predict treatment sensitivity in HER2-positive breast cancer. The aim of this study was to validate the utility of proliferation based markers (MKI67 and CDK1) and heat shock proteins (namely HSP90) to predict response to chemotherapy in cohort of breast cancer patients treated preoperatively. Material and methods. Ninety-three patients with breast cancer, all females, mean age 42.2 years, among them 32% T1-T2 patients, 49% T3 patients and 13% with T4 tumor stage, 27% N0, 42% N1, 16% N2, 15% N3 were subjected to initial chemotherapy. The majority of patients (86%) received anthracycline and taxane chemotherapy. Among the patients there were 9 individuals with metastatic disease (M1) at initial presentation, and 11 patients were not treated surgically after initial chemotherapy (no sufficient disease response). From 82 patients operated on, 20 patients (24%) showed pathological complete response (pCR), while in 62 patients there was 203 Proliferation genes and HSP90 in breast cancer chemotherapy ©Polish Society for Histochemistry and Cytochemistry Folia Histochem Cytobiol. 2016 10.5603/FHC.a2016.0026 www.fhc.viamedica.pl no pCR. 42% of patients were hormone-sensitive HER2-negative, 20% hormone-sensitive HER2-positive, 9% only HER-positive and 29% with triple negative breast cancer. Four gene transcripts (MKI67, cyclin-dependent kinase 1 [CDK1], heat shock proteins HSP90AA1 and HSP-90AB1) were analyzed in total RNA isolated from single core obtained during preoperative core needle biopsy by quantitative real-time PCR with fluorescent probes (Universal Probe Library, Roche). Results were normalized to the panel of reference genes. Results. There were no statistically significant differences in MKI67 and CDK1 expression between pCR and no pCR groups (p = 0.099 and 0.35, respectively), although the median expression of both genes was slightly higher in pCR group. In contrast, both HSP90AA1 and HSP90AB1 transcripts showed decreased expression in pCR group (medians 0.77 and 0.55) when compared to no pCR group (median 0.86 and 0.73), statistically significant for HSP90AA1 (p = 0.031) and of borderline significance for HSP90AB1 (p = 0.054). The most significant predictor of pCR was the ratio of CDK1 transcript to HSP90AA transcript. This ratio was significantly higher in CR group (median 0.99) than in no CR group (median 0.68, p = 0.0023), and showed a potential diagnostic utility (area under receiver operating characteristic [ROC] curve 0.72). Conclusions. HSP90AA1 and AB1 genes exhibit low expression in breast cancers highly sensitive to chemotherapy and may indicate the patients with higher probability of pathological complete response. The ratio of HSP90AA1 to proliferation-related markers (CDK1 or MKI67) may be even better predictor of pCR chance, with higher expression of proliferation genes and lower stress response in patients sensitive to chemotherapy.

Cancers, May 17, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Journal of Clinical Medicine, Jan 4, 2023

Introduction/Background Expected median survival for patients with cervical carcinoma stage IV B ... more Introduction/Background Expected median survival for patients with cervical carcinoma stage IV B is 17–26 months. Methodology This is a case report of 6 years survival for patients with metastatic cervical cancer. Results 59 years old women was diagnosed with squamous cell cervical cancer in 2012. MRI- revealed cervical tumor 7 cm involving anterior fornix, vaginal wall, parametrium and metastases to iliac lymph nodes. FDG/PET confirmed disease in pelvis and show metastases to III and X segment of the right lung. The patient was treated with palliative radiotherapy directed to pelvis (20 Gy, 4 Gy/fx). Completed response was achieved. After RT 4 cycles of chemotherapy (Carboplatin and Paclitaxel) stabilization was observed but the treatment had to be ceased because of toxicity. Three months after the chemotherapy, CT show progression of the lung metastases. Stereotactic radiation therapy (SRT) was applied: 40 Gy, 20Gy/fx to the tumors. Complete regression on CT was observed but after 5 months a new lesion in the apex of the right lung was diagnosed. It was treated with SRT (45 Gy, 15Gy/fx) - three months after the treatment a complete response was observed but a new nodules was seen in the right hilum. This one was treated with SRT (30 Gy, 10 Gy/fx). A complete regression was observed. The patient was well until the February of 2018 when local recurrence was diagnosed. The patient was reirradiated (30 Gy, 10 Gy/fx). Near complete regression was seen. After one months a second local progression was observed. The patients underwent palliative chemotherapy, but it was discontinued due to lack of effectiveness. The treatment described above allowed sixed year survival for patients with metastases to lung. Conclusion Agressive treatment is warrant in radiosensitive cervical cancer, even in case of multiple metastases. Disclosure Nothing to disclose.

Journal of Clinical Neuroscience, Aug 1, 2021

The optimal timing of adjuvant radiochemotherapy (RCT) in glioblastoma (GBM) patients remains unk... more The optimal timing of adjuvant radiochemotherapy (RCT) in glioblastoma (GBM) patients remains unknown and the paradigm of 'the sooner, the better' has been challenged by many recent publications. In this study, we present unique data on the outcomes of patients with significant treatment delays. The study group consisted of 346 GBM patients (median age 56.8 years) who received surgical treatment (total or subtotal resection) and then underwent adjuvant concurrent RCT at one institution. The main endpoint was overall survival (OS). The Univariate and multivariate Cox Proportional-Hazard Model, log-rank test, and Kaplan-Meier method were used for the analysis. The median OS was 18.7 months and the 5-year overall survival was 8.5%. The median time interval from surgery to RCT was 9.8 weeks. The Cox regression showed that the time interval had no statistically significant impact on OS both in uni- and multivariate analysis. The explorative analysis suggested a positive trend for improved survival for patients in the 1st quartile of the time interval, especially for patients with residual disease or local recurrence prior to RCT, However, considering the 6.9 weeks median interval in the 1st quartile, this subgroup should still be regarded as 'moderate delay' compared with other literature data. The results indicate that the time interval is not a clear prognostic factor in the treatment of GBM. Prospective trials are highly warranted, as data suggest that moderate delays in the initiation of adjuvant treatment might be associated with survival benefit.

Upsala Journal of Medical Sciences, 1993

NMR investigations of model protein of elastic fibre is presented. Detailed conformation of alpha... more NMR investigations of model protein of elastic fibre is presented. Detailed conformation of alpha-elastin polypeptide chain is discussed by comparison with the conformation of synthetic repeat peptides of elastin. Amino acid composition of alpha-elastin obtained from C-13 NMR spectra correlates with the results of sequencing of tropoelastin.

International Journal of Gynecological Cancer, Mar 1, 2022

Cervical cancer represents a significant portion of the global cancer burden for women, with low-... more Cervical cancer represents a significant portion of the global cancer burden for women, with low-and middleincome countries carrying the bulk of this burden. Additionally, underserved populations in countries with sufficient resources may have a higher incidence of cervical cancer and poorer outcomes. Concurrent chemoradiotherapy is the standard-of-care treatment for locally advanced cervical cancer, which includes patients with stage IB3 to IVA disease, and it is effective for many patients; however, cervical cancer-related mortality remains high. The critical nature of cervical cancer treatment is underscored by the recent launch of the World Health Organization global initiative to accelerate the elimination of cervical cancer using a tripleintervention strategy of increased vaccination, screening, and treatment. The initiative calls for 90% of all patients diagnosed with cervical cancer to receive the appropriate treatment, but to reach this global goal there are significant barriers related to radiotherapy that must be addressed. We discuss and review evidence of the lack of adherence to guideline-recommended treatment, brachytherapy underutilization, limited access to radiotherapy in low-and middle-income countries, as well as regional limitations within high-income countries, as the major barriers to radiotherapy treatment for locally advanced cervical cancer. We further review ways these barriers are currently being addressed and, in some cases, make additional recommendations to address these issues. Finally, despite receiving recommended treatments, many patients with locally advanced cervical cancer have a poor prognosis. With effective administration of current standards of care, the global community will be able to shift focus to advancing treatment efficacy for these patients. We review several types of therapies under clinical investigation that are additions to concurrent chemoradiotherapy, including immune checkpoint inhibitors, antiangiogenic agents, DNA repair inhibitors, human papillomavirus vaccines, and radiosensitizing nanoparticles.

Radiotherapy and Oncology, Aug 1, 2021

Frontiers in Oncology, Jul 21, 2020

Conclusions: Cervical cancer patients had faster decreases in ANC, lymphocyte, and platelet count... more Conclusions: Cervical cancer patients had faster decreases in ANC, lymphocyte, and platelet counts, and lower ANC nadirs, indicating a significant effect of pelvic irradiation on acute peripheral blood cell counts. Both cohorts exhibited a compensatory response with increased out-of-field bone marrow activity.

Polish Journal of Pathology, 2019

Currently, breast cancer chemotherapy response can be predicted based on various parameters, with... more Currently, breast cancer chemotherapy response can be predicted based on various parameters, with common reporting of tumour grade and Ki67 proliferation index. We analysed their association with pathological complete response (pCR) in a multivariate approach. The study was carried out in a group of 353 patients, treated by preoperative chemotherapy and prospectively observed. In selected patients, parallel to routing core needle biopsy assessment, gene expression profile of tumour was analysed by oligonucleotide microarrays. Tumour parameters associated with pCR in univariate analysis were: tumour grade, nuclear grade, mitotic index, Ki67, oestrogen and progesterone receptor (all p < 0.0001), and triple-negative status (p = 0.0032). The highest increase of pCR chance was observed in patients with high-grade tumours and with Ki67 ≥ 20%. In multivariate analysis, only tumour grade and oestrogen receptor status were predictive for pCR independently of other variables, with high grade increasing the odds of pCR 2.42 fold, and high ER decreasing the chance of pCR 0.41 fold. Tumour grading reflects important biological features of breast cancer and is not inferior to proliferation markers, including Ki67. It should be taken into account in decision-making for preoperative chemotherapy in parallel to breast cancer biologic subtypes, because grade 3 tumours exhibit a higher proportion of pCR.

Information Sciences, Apr 1, 2017

Abstract Although there are several data analysis frameworks, both commercial and open source, su... more Abstract Although there are several data analysis frameworks, both commercial and open source, supporting the detection of tumours on nuclear magnetic resonance (NMR) sequences, none of them gives satisfactory results in the case of low volume tumors. The majority of the frameworks require the detailed analysis of at least two sequences of the examined sample, or give sample specific thresholds distinguishing between the tumor and subtypes of healthy tissue. In this paper, we present a novel algorithm for the automated estimation of tumor specific cut-off values in the domain of the apparent diffusion coefficient (ADC). Once the cut-off characteristics for a particular type of tumor is estimated, their further usage on other independent samples does not require any calculations except for an easy thresholding. The proposed methodology is a combination of classical decomposition of ADC distribution into a Gaussian mixture model (GMM) with k-means clustering subsequently performed on the parameters of mixture model components, leading to the identification of ADC distributions for every tissue type. The maximum conditional probability criterion gives the final threshold estimate. The developed signal analysis pipeline was applied to the problem of Glioblastoma Multiforme grade IV brain tumor segmentation, with a dataset of 119 randomly chosen ADC maps and Leave-One-Out cross-validation procedure for population error estimate. Additionally, a comparison to standard GMM based tumor segmentation algorithms as well as to three other automated segmentation methods was performed and the obtained tumor regions were referenced to the segmentation done by a human expert. The results demonstrate the average MiMSeg similarity to the expert-curated decision measured by the Dice coefficient as equal to 89.2% (with 95% confidence interval 87.7 ÷ 90.6). The MiMSeg algorithm significantly outperforms other techniques in the case of small tumors (of volume less than 10%), obtaining similarity to the expert-curated decision at the level 86.7%, with 44.9% obtained by standard GMM, 79.0% by Self-Organising-Maps algorithm, 68.7% by Murakami’s algorithm, and 78.2% by Kang’s method.

Radiotherapy and Oncology, Feb 1, 1998

To measure changes in spontaneous growth rate and radiation response in the progeny of irradiated... more To measure changes in spontaneous growth rate and radiation response in the progeny of irradiated squamous cell carcinoma cells. Murine SCC cells of the line AT478 were grown as epithelial megacolonies in vitro, using both the original line and two subsequent passages derived from a clone that had recurred after a high radiation dose. Radiosensitivity was evaluated in terms of local control following single dose irradiation of standard size megacolonies (0.8 cm2). In addition, original megacolonies were given a priming dose of 20 Gy and the recurrent clones arising in situ were retreated at three dose levels for analysis of curability. A marked increase in radiosensitivity was observed in the megacolonies grown from irradiated progeny as compared to original megacolonies, reflected in a shift of the TCD50 from 24.5 to 16.5 Gy. Direct parameter estimation from the cure data suggested that the underlying change was a lowered number of clonogenic 'stem' cells rather than increased cellular sensitivity. A similar decrease in clonogen density was also apparent for the recurrent clones in situ. The change in megacolony curability was paralleled by a substantial growth retardation. The data demonstrate persistent changes in the progeny of irradiated SCC tumour cells that affect both growth and radiosensitivity and are compatible with the expression of delayed reproductive death.

International Journal of Radiation Oncology Biology Physics, Mar 1, 2017

We performed an international phase II trial to test the Purpose: To test the hypothesis that int... more We performed an international phase II trial to test the Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer.

International Journal of Radiation Oncology Biology Physics, Nov 1, 2018

than TSR applicators (left mean 8.1 vs. 13.3 Gy, p<0.01; right mean 7.67 vs. 12.5 Gy, p<0.01). TO... more than TSR applicators (left mean 8.1 vs. 13.3 Gy, p<0.01; right mean 7.67 vs. 12.5 Gy, p<0.01). TO applicators also yielded a larger maximum craniocaudal dimension of the 100% isodose distribution (mean 8.2 vs. 6.8cm, p<0.01). TSR applicators, however, yielded a wider horizontal max dimension of the 100% isodose distribution (mean 7.8 vs. 6.7cm, p<0.01) and a correspondingly wider horizontal colpostat separation (mean 5.4 vs. 3.7 cm, p<0.01). Conclusion: Because this analysis evaluates both TO and TSR applicators in the same patients, it provides the unique advantage of contrasting dosimetry and target coverage while controlling for tumor and pelvic anatomy. Our study demonstrates that TO applicators consistently yield lower vaginal mucosal doses compared to TSR, likely reflective of the generally larger ovoid caps, without significantly different dose to the rectum or bladder. Although tumor coverage was equivalent, differences in dose distribution persist, such as greater horizontal width with TSR and improved craniocaudal coverage with TO, which may guide selection between the two devices.

Radiotherapy and Oncology, May 1, 2017

Purpose or Objective Stereotactic radiosurgery (SRS) has been increasingly advocated for 1-3 smal... more Purpose or Objective Stereotactic radiosurgery (SRS) has been increasingly advocated for 1-3 small brain metastases. Goal of this study was to evaluate the clinical results in patients with brain metastases treated with SRS using a thermoplastic mask non-invasive fixation system and image-guided treatment. Material and Methods In this single-institution study 48 patients with 77 brain metastases were treated between February 2012 and January 2014. The head fixation was realized using a BrainLAB thermoplastic mask. The prescribed dose was 20 Gy or 18 Gy as a single dose. The SRS were performed with a True Beam STX Novalis Radiosurgery LINAC (Varian Medical Systems). The verification of positioning was done using the BrainLAB ExacTrac ® X-ray 6D system and conebeam CT. Results In 69 of 77 (89.6%) treated brain metastases the follow-up was documented on MR imaging performed every 3 months. In 7/69 (10.1%) brain metastases local failure was diagnosed with a mean follow-up time of 10.7 months (range 1-43 months). Estimated 1-year local control was 83.1%. Median progression free survival (PFS) was 3.7 months, largely due to distant brain relapse. Breast cancer was significantly associated with a worse progression free survival. A GTV of ≤ 2.0 cm³ was significantly associated with a better PFS than a GTV > 2.0 cm³. We observed 2 cases of radiation necrosis diagnosed by histology after surgical resection. No other cases of severe side effects (CTACE≥3) were observed. Conclusion In our experience local control after frameless (ringless) LINAC based SRS with mean follow-up of 10.7 months is 89.9%. Without the invasive head fixation radiotherapy is more comfortable for the patients. EP-1107 Treatment Strategies for local and distant recurrence after HFSRT of the Resection Cavity

Radiotherapy and Oncology, May 1, 2017

Background: To test the hypothesis that atlas-based active bone marrow (ABM)-sparing intensity mo... more Background: To test the hypothesis that atlas-based active bone marrow (ABM)-sparing intensity modulated radiation therapy (IMRT) yields similar dosimetric results compared to custom ABM-sparing IMRT for cervical cancer patients. Methods: We sampled 62 cervical cancer patients with pre-treatment FDG-PET/CT in training (n = 32) or test (n = 30) sets. ABM was defined as the subvolume of the pelvic bone marrow (PBM) with standardized uptake value (SUV) above the mean on the average FDG-PET image (ABM Atlas) vs. the individual's PET (ABM Custom). Both were deformed to the planning CT. Overlap between the two subvolumes was measured using the Dice coefficient. Three IMRT plans designed to spare PBM, ABM Atlas , or ABM Custom were compared for 30 test patients. Dosimetric parameters were used to evaluate plan quality. Results: ABM Atlas and ABM Custom volumes were not significantly different (p = 0.90), with a mean Dice coefficient of 0.75, indicating good agreement. Compared to IMRT plans designed to spare PBM and ABM Custom , ABM Atlas-sparing IMRT plans achieved excellent target coverage and normal tissue sparing, without reducing dose to ABM Custom (mean ABM Custom dose 29.4 Gy vs. 27.1 Gy vs. 26.9 Gy, respectively; p = 0.10); however, PTV coverage and bowel sparing were slightly reduced. Conclusions: Atlas-based ABM sparing IMRT is clinically feasible and may obviate the need for customized ABM-sparing as a strategy to reduce hematologic toxicity.

Informatik aktuell, 2015

In der Bestrahlungsplanung bei Hirntumoren wird typischerweise ein Sicherheitsabstand von 2 − 2, ... more In der Bestrahlungsplanung bei Hirntumoren wird typischerweise ein Sicherheitsabstand von 2 − 2, 5 cm um das im T2-Flair MR-Bild hyperintense Gebiet eingeplant. Verlasliche Vorhersagen des Tumorwachstums konnen dazu beitragen, die Strahlendosis noch besser auf gefahrdete Regionen zu konzentrieren und gleichzeitig gesundes Gewebe zu schonen. Aktuelle Verfahren aus der Forschung nahern sich diesem Problem mit einer expliziten, generativen Modellierung des Wachstumsprozesses. Wir prasentieren ein alternatives, diskriminatives Verfahren. Mit Hilfe einer annotierten Datenbasis und uberwachtem Lernen wird ein Wachstumsmodell trainiert und im nachsten Schritt auf ungesehene Daten angewendet. In allen 6 Testpatienten lieferte der Ansatz genauere Vorhersagen (DICE 0, 80±0, 09) als die bisherige Herangehensweise (DICE 0, 56 ± 0, 07).

International Journal of Radiation Oncology Biology Physics, Nov 1, 2020

Current Radiopharmaceuticals, May 20, 2015

Folia Histochemica Et Cytobiologica, Jan 12, 2017

Cancers, May 17, 2023

Journal of Clinical Medicine, Jan 4, 2023

Journal of Clinical Neuroscience, Aug 1, 2021

Upsala Journal of Medical Sciences, 1993

International Journal of Gynecological Cancer, Mar 1, 2022

Radiotherapy and Oncology, Aug 1, 2021

Frontiers in Oncology, Jul 21, 2020

Polish Journal of Pathology, 2019

Information Sciences, Apr 1, 2017

Radiotherapy and Oncology, Feb 1, 1998

International Journal of Radiation Oncology Biology Physics, Mar 1, 2017

International Journal of Radiation Oncology Biology Physics, Nov 1, 2018

Radiotherapy and Oncology, May 1, 2017

Informatik aktuell, 2015