Design and performance validation of a novel 3d printed thin-walled and transparent electron beam applicators for intraoperative radiation therapy with beam energy up to 12 MeV.

A high-energy electron accelerator is used in the treatment of patients in the so-called intraoperative electron radiotherapy (IOERT). The work aimed to present the results of the validation of a new design of an electron beam applicator for use in IOERT. A novel solution was described along with the design optimization method based on Monte Carlo simulations. In this solution, the applicator consists of two parts. The lower exchangeable part collimates the therapeutic field. Measurements were made based on the International Electrotechnical Commission (IEC) standard recommendations. The measurement described in the standard has been adapted to the specificity of the intraoperative accelerator Source to Skin Distance - of 60 cm and applicators with a circular cross-sectional area. Measurements were performed for nominal beam energies of 6, 10, and 12 MeV and two therapeutic field diameters of 6 and 10 cm. The dose due to stray X-ray radiation in all energies is less than 0.3% and increases for energies from 6 to 12 MeV by 2.9 times from 0.1 for 6MeV to 0.29 for 12 MeV. The average dose due to leakage radiation also shows an increasing trend and is higher for a 6 cm diameter applicator. Validation confirmed the usefulness of the novel applicator design for clinical applications. Thanks to the use of 3D printing, it was possible to make applicators that are transparent, biocompatible and, at the same time, light and form a beam field with therapeutically useful accuracy, and the leakage radiation does not exceed normative recommendations.

The paradox of autoimmunity and autoinflammation in inherited neutrophil disorders - in search of common patterns.

Congenital defects of neutrophil number or function are associated with a severe infectious phenotype that may require intensive medical attention and interventions to be controlled. While the infectious complications in inherited neutrophil disorders are easily understood much less clear and explained are autoimmune and autoinflammatory phenomena. We survey the clinical burden of autoimmunity/autoinflammation in this setting, search for common patterns, discuss potential mechanisms and emerging treatments.

Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey.

Venetoclax, the best established BH3-mimetic, is a practice-changing proapoptotic drug in blood cancers in adults. In paediatrics the data are fewer but exciting results were recently presented in relapsed or refractory leukaemias demonstrating significant clinical activity. Importantly, the in-terventions could be potentially molecularly guided as vulnerabilities to BH3-mimetics were re-ported. Currently venetoclax is not incorporated into paediatric treatment schedules in Poland but it has been already used in patients that failed conventional therapy in Polish paediatric haemato-oncology departments. The aim of the study was to gather clinical data and correlates of all paediatric patients treated so far with venetoclax in Poland. We set out to gather this experience to help choose the right clinical context for the drug and stimulate further research. The questionnaire regarding the use of venetoclax was sent to all 18 Polish paediatric haemato-oncology centres. The data as available in November 2022 were gathered and analysed for the diagnoses, triggers for the intervention, treatment schedules, outcomes and molecular associations. We received response from 11 centres, 5 of which administered venetoclax to their patients. Clinical benefit, in most cases consistent with hematologic complete remission (CR), was reported in 5 patients out of ten, whereas 5 patient did not show clinical benefit from the intervention. Importantly, patients with CR included subtypes expected to show venetoclax vulnerability, such as poor-prognosis ALL with TCF::HLF fusion. We believe BH3-mimetics have clinical activity in children and should be available to pae-diatric haemato-oncology practitioners in well-selected applications.

What challenges does the humanitarian crisis and large number of refugees from Ukraine pose for Polish oncology?

The war in Ukraine has led to a massive influx of refugees into Poland, posing a major challenge for the health care system. The large number of refugees will undoubtedly lead to a substantial increase in the number of patients requiring treatment for a wide range of conditions, including cancer. In the present article, we describe and discuss the many difficulties faced by cancer treatment centres in Poland due to these circumstances. Key issues include the lack of proper diagnostic testing in this population and differences in oncological practices between Poland and Ukraine. Other problems include difficulties in obtaining patients' medical records and communication issues caused by the language barrier. In addition, in the context of the ongoing COVID-19 pandemic, the low vaccination rate among Ukrainian refugees is also a significant risk factor. Addressing these challenges will require a comprehensive approach involving the national health care agency and individual cancer centres. This is especially important in oncology due to the interdisciplinary nature of the field, which requires the contribution of specialists from many different fields as well as appropriate funding.

Hypofractionated Whole Breast Irradiation and Boost-IOERT in Early Stage Breast Cancer (HIOB): First Clinical Results of a Prospective Multicenter Trial (NCT01343459).

Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35−40 y and 41−50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7−104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41−50 and >50 y, respectively. For the youngest group (35−40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41−50 when compared to best published evidence until 2010.

Toxicity and cosmetic outcome after hypofractionated whole breast irradiation and boost-IOERT in early stage breast cancer (HIOB): First results of a prospective multicenter trial (NCT01343459).

BACKGROUND AND PURPOSE: To assess the role of intraoperative radiation with electrons (IOERT) as tumor bed boost followed by hypofractionated whole breast irradiation (HWBI) after breast conserving surgery (BCS) of patients with low to intermediate risk breast cancer focusing on acute/late toxicity and cosmetic outcome. MATERIAL AND METHODS: In 2011, a prospective multicenter trial (NCT01343459) was started. Treatment consisted of BCS, IOERT (11.1 Gy) and HWBI (40.5 Gy in 15 fractions). In a single-arm design, 5-year IBR-rates are benchmarked by a sequential ratio test (SQRT) against best published evidences in 3 age groups (35-40 y, 41-50 y, >50 y). Acute/late toxicity and cosmesis were evaluated by validated scorings systems. RESULTS: Of 627 eligible patients, 44 were excluded, leaving 583 to analyze. After a median follow-up (FUP) of 45 months (range 0-74), for acute effects CTCAE-score 0/1 was noted in 91% (end of HWBI) and 92% (4 weeks later), respectively. Late toxicity Grading 0/1 (mean values, ranges) by LENT-SOMA criteria were observed in 92.7% (89-97.3) at 4/5 months, rising to 96.5% (91-100) at 6 years post HWBI. Baseline cosmesis after wound healing prior to HWBI was scored as excellent/good in 86% of cases by subjective (patient) and in 74% by objective (doctor) assessment with no impairment thereafter. CONCLUSIONS: Acute and late treatment tolerance of a combined Boost-IOERT/HWBI regimen is excellent in short/mid-term assessment. Postoperative cosmetic appearance is not impaired after 3 years FUP.

The incidence of inflammation among patients suffering from cervix cancer with positive beta haemolytic streptococci cultures from genital tract.

AIM: The main goal of this investigation was to evaluate the influence of positive beta haemolytic streptococci culture from the genital tract on patients receiving radiation therapy who suffer from cervical cancer. The other aim was to observe radiation therapy complications. BACKGROUND: Group B streptococci (GBS), group C streptococci (GCS) and group G streptococci (GGS) have been described as frequent invasive pathogens in elderly patients, often in association with underlying medical conditions including immunodeficiency and cancer. MATERIALS AND METHODS: In the years 2006-2015, vaginal swabs from 452 patients were examined. A total of 118 women with positive beta haemolytic streptococci (BHS) groups A, B, C, F, G cultures were analysed, of whom 111 were diagnosed with cervix cancer of IB to IVA degree according to the FIGO 1988 clinical classification. RESULTS: Of the 452 patients suffering from cervix cancer 26.1% were positive for A, B, C, F or G group BHS isolated from the genital tract. All of the 114 examined strains were sensitive to beta-lactam antibiotics. The antimicrobials for which resistance was noted were erythromycin, clindamycin, ciprofloxacin and tetracycline. CONCLUSIONS: Positive cultures of BHS from the genital tract were demonstrated to occur in patients with cervix cancer. Complications were found during radiotherapy in 30 (27%) of these patients, including 20 (18%) patients suffering from clinical symptoms of inflammation. When beta-lactam antibiotics are not recommended because of allergy, sensitivity tests to other drugs are necessary.

Relations between dose cumulated in organs at risk and treatment based on different image-guidance strategies of cervical cancer.

PURPOSE: In this study, relations between dose cumulated in organs at risk and treatment based on different image guidance strategies (IG) of cervical cancer were analyzed. MATERIAL/METHODS: Thirty patients with cervical cancer were subjected to analysis. The first phase of the study involved analysis of shifts resulting from the registration process and calculations of margins based on shifts data. The margin was calculated for two imaging scenarios - based on the analysis of bones and soft tissues. The margins thus obtained were used in the second phase of the study where the VMAT and IMRT treatment plans were prepared and, in consequence, analyzed in the light of the dose distribution. RESULTS: Using different IG implicates different margins for specified parts of the CTV. IG based on bones allows to establish margins for lymph nodes (CTV2) that are smaller than margins for the vagina/paravaginal tissues (CTV1). The opposite applies to the IG based on soft tissues, for which margins for CTV1 are smaller than for CTV2. While decreasing the margins for CTV1 reduces the doses in the bladder and rectum, doses cumulated in the bone marrow are independent of the size of the margin resulting from the type of IG used. Nevertheless, the average doses and the values of normal tissue complication probability in the bone marrow were smaller for VMAT than for IMRT. CONCLUSION: The VMAT plan and image guidance based on soft tissue registration for the vagina/paravaginal tissues are recommended for radiotherapy of cervical cancer patients.

Influence of 18F-FDG-PET/CT on staging of cervical cancer.

AIM: Cervical cancer is one of the most common cancers of the female reproductive system. The aim of the study was to assess the usefulness of the 18F-FDG-PET/CT study in staging of cervical cancer, with focus on the primary tumor parameters. MATERIAL & METHODS: 105 patients (mean age 56 ±â€…11y) with newly diagnosed cervical cancer underwent PET/CT examination which was performed 60 min after IV injection of 18F-FDG with a mean activity of 364 ±â€…75MBq. 68 patients were diagnosed with stage IIIA/IIIB, 19 patients with IIB, 10 patients with IB, 8 patients with stage IVA/IVB. Wilcoxon-Mann-Whitney test and ROC curves were used for statistical analysis. RESULTS: In 35 cases 18F-FDG-PET/CT did not show active proliferative process outside the cervix. In 38 cases metastases were found in iliac lymph nodes and in 32 patients scans showed metastases above the aortic bifurcation including lymph nodes and other organs. The largest volumes of primary tumor occurred in patients with distant metastases, while the lowest in patients with disease limited only to cervix. In 63 % of the patients PET/CT result was compatible with FIGO classification, in 20 % patients PET/CT result showed less advanced disease and in 17 % of the patients PET/CT results were higher than FIGO classification. CONCLUSION: PET/CT using 18F-FDG has an important impact on the assessment of the stage of cervical cancer. In over 30 % of patients, this study resulted in a radical change in the treatment plan.

Strategy and early results of treatment of advanced cervical cancer patients with synchronous cancers observed in PET-CT imaging.

OBJECTIVES: The aim of this study was to present strategy and early results of treatment of advanced cervical cancer patients with synchronous cancers observed in PET-CT imaging, treated at the Greater Poland Cancer Center. MATERIAL AND METHODS: The study included a group of 200 patients with diagnosed stage IIB-IIIB cervical cancer who received PET-CT for the purpose of radiotherapy treatment planning. RESULTS: Among our study group, four patients (2%) were found to have a synchronous cancer. Two of the cases were diagnosed as breast cancer. However, cancers diagnosed in the other two patients were head and neck malignancies - hypopharyngeal and laryngeal cancer. The choice of an optimal therapeutic approach requires taking into account characteristics of particular malignancies, their stage and histopathology. The whole therapy included radiotherapy of cervical cancer with various combinations of systemic treatment, radiotherapy or surgery of synchronous cancer. According to treatment results, patients diagnosed with breast cancer and hypopharyngeal cancer achieved complete remission of both primary and secondary tumour. Patient diagnosed with laryngeal malignancy, despite achieving complete remission of cervical cancer, finished radiotherapy of the synchronous cancer at a palliative dose. CONCLUSIONS: The growing availability of PET-CT and other imaging methods in cancer diagnosis will increase the number of diagnosed synchronous cancers. Second primary cancers are often detected at an early stage, where radical treatment can be performed for both primary and secondary tumour. However, treatment of such complicated clinical cases as synchronous cancers should be carried out by multidisciplinary teams.

Relations between doses cumulated in bone marrow and dose delivery techniques during radiation therapy of cervical and endometrial cancer.

PURPOSE: To compare normal tissue complication probability (NTCP) and average doses in the bone marrow (BM), obtained for five different radiotherapy delivery and planning strategies of cervical and endometrial cancer. MATERIAL/METHODS: 50 patients were taken to analysis. For each case, 3 different dose delivery techniques were used: 4-field, X15MV, 3DCRT; 7-field, X6MV, IMRT; and 2-arc, X6MV, VMAT. Two optimization scenarios were used for the IMRT and VMAT plans generation: with (+) and without (-) the inclusion of the BM as an optimized structure. Average doses and dose-volume histogram parameters for the PTV, BM, bladder, rectum, bowels and femoral heads were compared. In addition, the BM doses were analyzed with respect to the PTV and/or volume of the BM, and NTCP for the BM were computed. RESULTS: The dose in PTV for evaluated plans was similar. The worst doses in organs at risk were obtained for 3DCRT. Using the BM during the optimization of IMRT and VMAT reduces an average dose in BM without increasing the doses in the bladder, rectum and bowels. Differences between doses in BM for IMRT(+) and VMAT(+) plans were similar while NTCP was lower for VMAT(+). A correlation between average dose in BM and the volume ratio of BM and PTV was found for each technique. CONCLUSION: Using the BM during the optimization of the IMRT and VMAT plans effectively reduces the dose in BM without increasing the dose in the bladder, rectum and bowels. The VMAT(+) plans were characterized by the lowest NTCP.

Combination of microbiological culture and multiplex PCR increases the range of vaginal microorganisms identified in cervical cancer patients at high risk for bacterial vaginosis and vaginitis.

BACKGROUND: Bacterial vaginosis (BV) and vaginitis in cervical cancer patients might becaused by mixed aerobic, anaerobic, and atypical bacteria. Since genital tract infections can be complicated, early and accurate identification of causal pathogens is vital. OBJECTIVES: The purpose of this study was i) to determinate if currently used aerobic culture methods are sufficiently sensitive to identify pathogens that can appear in the cervix of women after cancer treatment; ii) to investigate if molecular methods can improve the diagnostic process of BV and vaginitis, as well as broaden the range of detectable pathogens that would otherwise be difficult to cultivate. METHODS: A one-year hospital-based study was conducted in 2011/2012. Cervical swabs from 130 patients were examined by microbiological culture and multiplex PCR. RESULTS: Swab samples were positive for 107 and 93 women by microbiological culture and multiplex PCR, respectively The most common bacteria isolated from culture were: Escherichia coli, Enterococcus faecalis, Streptococcus agalactiae, and Staphylococcus aureus, and using the molecular technique were: Gardnerella vaginalis, Bacteroides fragilis, Ureoplasma ureoliticum/parvum, Mobiluncus curtisii and Atopobium vaginae. CONCLUSIONS: Multiplex PCR might contribute to the diagnosis of genital tract infections and it broadens the number of detectable microorganisms responsible for BV. Combination of these two methods may become the basis for standardized diagnosis of BV and vaginitis.

The future of Radiation Oncology: Considerations of Young Medical Doctor.

Radiation therapy plays an increasingly important role in the management of cancer. Currently, more than 50% of all cancer patients can expect to receive radiotherapy during the course of their disease, either in a primary management (radical or adjuvant radiotherapy) or for symptom control (palliative radiotherapy). Radiation oncology is a very unique branch of medicine connected with clinical knowledge and also with medical physics. In recent years, this approach has become increasingly absorbed with technological advances. This increasing emphasis on technology, together with other important changes in the health-care economic environment, now place the specialty of radiation oncology in a precarious position. New treatment technologies are evolving at a rate unprecedented in radiation therapy, paralleled by improvements in computer hardware and software. These techniques allow assessment of changes in the tumour volume and its location during the course of therapy (interfraction motion) so that re-planning can adjust for such changes in an adaptive radiotherapy process. If radiation oncologists become simply the guardians of a single therapeutic modality they may find that time marches by and, while the techniques will live on, the specialty may not. This article discusses these threats to the field and examines strategies by which we may evolve, diversify, and thrive.

Clinical and morphological aspects of thin glomerular basement membrane disease.

The report presents the results of investigations carried out in 63 patients (49 children and 14 adults) with thin glomerular basement membrane disease. Of 49 children, 13 came from nine families with family members suffering from kidney diseases (mostly manifested by haematuria). In the group of children, the most frequent initial clinical symptom (noted in 29 cases) was isolated haematuria, more rarely (in eight cases) haematuria and proteinuria, and (in seven cases) nephrotic syndrome. Isolated proteinuria was observed in another three children. In the adults, only in five patients was isolated haematuria the initial symptom of the disease; more frequently (in seven cases), they presented with isolated proteinuria. In two patients, proteinuria and haematuria were noted. In the two groups of patients, in addition to markers of thin glomerular basement membrane disease, the authors also observed markers indicative of other glomerulopathies: in seven children and four adults focal segmental glomerulosclerosis (FSGS) without any other glomerular pathologies (with the exception of thin glomerular basement membrane disease). Also in cases in which in addition to thin glomerular basement membrane disease other glomerular pathologies were present (mesangial hypercellularity, mesangial glomerulonephritis), matrix expansion was detected; this phenomenon might be considered a harbinger of glomerular sclerosis. In general, although not in each and every case, these pathologies were associated with duration of the disease.